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Individual responses to behavioral treatment of anxiety disorders vary considerably, which requires a better understanding of underlying processes. In this study, we examined the violation and change of threat beliefs during exposure. From 8,484 standardized exposure records of 605 patients with different anxiety disorders, learning indicators were derived: expectancy violation as mismatch between threat expectancy before exposure and threat occurrence, expectancy change as difference between original and adjusted expectancy after exposure, and prediction-error learning rate as extent to which expectancy violation transferred into change. Throughout sessions, high threat expectancy but low occurrence and adjusted expectancy indicated successful violation and change of threat beliefs by exposure. Expectancy violation, change, and learning rate substantially varied between patients. Not expectancy violation itself, but higher learning rate and expectancy change predicted better treatment outcome. Successful exposure thus requires expectancy violation to induce actual expectancy change, supporting learning from prediction error as transdiagnostic mechanism underlying successful exposure therapy.
Background
Few studies have assessed trajectories of alcohol use in the general population, and even fewer studies have assessed the impact of brief intervention on the trajectories. Especially for low-risk drinkers, it is unclear what trajectories occur, whether they benefit from intervention, and if so, when and how long. The aims were first, to identify alcohol use trajectories among at-risk and among low-risk drinkers, second, to explore potential effects of brief alcohol intervention and, third, to identify predictors of trajectories.
Methods
Adults aged 18-64 years were screened for alcohol use at a municipal registration office. Those with alcohol use in the past 12 months (N = 1646; participation rate: 67%) were randomized to assessment plus computer-generated individualized feedback letters or assessment only. Outcome was drinks/week assessed at months 3, 6, 12, and 36. Alcohol risk group (at-risk/low-risk) was determined using the Alcohol Use Disorders Identification Test–Consumption. Latent class growth models were estimated to identify alcohol use trajectories among each alcohol risk group. Sex, age, school education, employment status, self-reported health, and smoking status were tested as predictors.
Results
For at-risk drinkers, a light-stable class (46%), a medium-stable class (46%), and a high-decreasing class (8%) emerged. The light-stable class tended to benefit from intervention after 3 years (Incidence Rate Ratio, IRR=1.96; 95% Confidence Interval, CI: 1.14–3.37). Male sex, higher age, more years of school, and current smoking decreased the probability of belonging to the light-stable class (p-values<0.05). For low-risk drinkers, a very light-slightly increasing class (72%) and a light-increasing class (28%) emerged. The very light-slightly increasing class tended to benefit from intervention after 6 months (IRR=1.60; 95% CI: 1.12–2.28). Male sex and more years of school increased the probability of belonging to the light-increasing class (p-value < 0.05).
Conclusion
Most at-risk drinkers did not change, whereas the majority of low-risk drinkers increased alcohol use. There may be effects of alcohol feedback, with greater long-term benefits among persons with low drinking amounts. Our findings may help to identify refinements in the development of individualized interventions to reduce alcohol use.
Vielfältig lässt sich die Bedeutung von Vorstrafen zeigen; jenseits ihrer gesellschaftlichen Wirkungen beschäftigen sie Straf-, Arbeits- und Zivilgerichte. Dieser Beitrag untersucht, welche Implikationen die Registrierung einer Verurteilung hat. Dabei soll aus strafrechtlicher wie auch aus grundrechtlicher Perspektive belegt werden, dass der Staat als Autor der Verurteilung alle ihre Folgen bedenken und bestimmten Konsequenzen gegebenenfalls entgegenwirken muss. Zur Einstimmung sollen fünf Fallskizzen Schlaglichter auf den Problemkreis werfen:
Abstract
This brief discussion paper is concerned with the sequence [have NP Vpp] and its distinction into a causative and a passive construction, which hinges on the (non-)agentivity of the subject participant, so that the sequence can be seen as ambiguous in that respect. Instead of analyzing these uses as two different constructions, I propose a unified analysis as instances of the affactive construction. This construction has the functional potential of putting primary focus on secondary participants, so-called afficiary participants. The potential ambiguity with regard to the agentivity of these participants is not an issue in usage, as it is only evoked as part of the conceptual content in the background.
Growth corridors have been an instrument of
economic development for decades but have gained new
attention in regional economic development policies in recent years, e.g., in Sub-Saharan Africa or Southeast Asia.
They are seen by policy makers and private businesses as
catalysts of regional economic integration, pushing traditional businesses into increasingly complex international
value chains. However, the outcomes of such development
initiatives are still barely understood. Critics argue that development policies are based on simplified models that are
unable to sufficiently address the complexity of regional
development. Policies on value-chain development, for
example, can lead to conflicts, external dependencies,
land rush, and a polarization of wealth. Growth corridors
often go hand-in-hand with socio-economic transformations and land-use conflicts. This paper first discusses the
theoretically possible desired and undesired regional socio-economic effects of modern corridors. Second, we illustrate the potential and challenges to realize integrative
(or inclusive) development by contrasting three growth
corridors: the SAGCOT growth corridor in Tanzania, the
Walvis Bay-Ndola-Lubumbashi Development Corridor
(WBNLDC) in Namibia, Zambia and Zimbabwe, and the
growth corridors in the Greater Mekong Subregion (GMS)
AbstractThis paper takes concepts from spatial theory and globalization discourse and uses them in order to analyze the narrative function of descriptions of nature in romantic Icelandic poetry from the beginning of the 19th century and an Icelandic TV-Series from 2015. In Iceland’s romantic poetry of the early 19th century, especially in poems written by Bjarni Thorarensen, sublime nature is described as a form of guardian against foreign influences that threaten the way of living on the peripheral island. This romantic concept of Icelandic nature is closely connected to narrative patterns in the process of the Icelandic Nation-Building, as it characterizes Icelanders as simultaneously defined and protected by the harsh conditions on the island. The paper takes a comparative look at the underlying narrative concepts of nature in two of Bjarni Thorarensen’s poems and a recent Icelandic TV series, Baltasar Kormákur’s Ófærð (2015), that presents a different concept of Icelandic nature in its relation to a (threatening) global influence. The series depicts a globalized world in which crime does not only affect remote communities as an evil from the outside but as a local evil connected to forces on global scale. Nature as a narrative device in the TV series thus does not protect Icelanders from global forces, as it did in Bjarni Thorarensens poems in the early 19th century, but instead functions a catalyst that reveals the evil from the outside and the evil from within.
Background
The COVID-19 pandemic and the imposed lockdowns severely affected routine care in general and specialized physician practices.
Objective
To describe the long-term impact of the COVID-19 pandemic on the physician services provision and disease recognition in German physician practices and perceived causes for the observed changes.
Design
Observational study based on medical record data and survey data of general practitioners and specialists' practices.
Participants
996 general practitioners (GPs) and 798 specialist practices, who documented 6.1 million treatment cases for medical record data analyses and 645 physicians for survey data analyses.
Main measures
Within the medical record data, consultations, specialist referrals, hospital admissions, and documented diagnoses were extracted for the pandemic (March 2020–September 2021) and compared to corresponding pre-pandemic months in 2019. The additional online survey was used to assess changes in practice management during the COVID-19 pandemic and physicians' perceived main causes of affected primary and specialized care provision.
Main results
Hospital admissions (GPs: −22% vs. specialists: −16%), specialist referrals (−6 vs. −3%) and recognized diseases (−9 vs. −8%) significantly decreased over the pandemic. GPs consultations initially decreased (2020: −7%) but compensated at the end of 2021 (+3%), while specialists' consultation did not (−2%). Physicians saw changes in patient behavior, like appointment cancellation, as the main cause of the decrease. Contrary to this, they also mentioned substantial modifications of practice management, like reduced (nursing) home visits (41%) and opening hours (40%), suspended checkups (43%), and delayed consultations for high-risk patients (71%).
Conclusion
The pandemic left its mark on primary and specialized healthcare provision and its utilization. Both patient behavior and organizational changes in practice management may have caused decreased and non-compensation of services. Evaluating the long-term effect on patient outcomes and identifying potential improvements are vital to better prepare for future pandemic waves.
Infective/bacterial endocarditis is a rare but life-threatening disease with a hospital mortality rate of 22.7% and a 1-year mortality rate of 40%. Therefore, continued research efforts to develop efficient anti-infective implant materials are of the utmost importance. Equally important is the development of test systems that allow the performance of new materials to be comprehensively evaluated. In this study, a novel antibacterial coating based on dalbavancin was tested in comparison to rifampicin/minocycline, and the suitability of a recently developed mouse tail vein model for testing the implant coatings was validated. Small polymeric stent grafts coated with a poly-L-lactic acid (PLLA) layer and incorporated antibiotics were colonized with Staphylococcus (S.) aureus before implantation into the tail vein of mice. The main assessment criteria were the hematogenous spread of the bacteria and the local tissue reaction to the contaminated implant. For this purpose, colony-forming units (CFU) in the blood, spleen and kidneys were determined. Tail cross sections were prepared for histological analysis, and plasma cytokine levels and expression values of inflammation-associated genes were examined. Both antibiotic coatings performed excellently, preventing the onset of infection. The present study expands the range of available methods for testing the anti-infectivity of cardiovascular implants, and the spectrum of agents for effective surface coating.
Introduction: To maintain a sufficient donor pool, deferred first-time donors (FTD) should be motivated to return for blood donation. This pilot study investigates how deferral affects momentary mood, satisfaction with the donation process, and subsequent return behavior to examine their potential for motivating (deferred) FTD. Methods: All of the subjects (n = 96) completed a first questionnaire (A1) before pre-donation assessment. Deferred FTD (n = 22) were asked to complete a second questionnaire (A2) immediately after deferral, while non-deferred FTD (n = 74) filled in the second questionnaire (A3) after blood donation. The impact of deferral, momentary mood, and satisfaction with the donation process on return behavior within 12 months was tested by calculating two path analyses, controlling for sex and age. Results: Mood (p < 0.001) and satisfaction with social aspects of the donation process (p = 0.01) were decreased after deferral. Deferred FTD were less likely than non-deferred FTD to return to the blood donation center within 12 months (60.8 vs. 36.4%; p = 0.043). However, path analyses revealed that deferral effects on mood and satisfaction were not connected to return behavior. Instead, age had a significant influence on return behavior (p < 0.05) such that, overall, non-returning FTD were older than returning FTD, regardless of their deferral status. Conclusion: Our findings suggest that mood and satisfaction with the donation process are directly affected by deferral but not clearly responsible for low return rates. It seems promising to embed these variables in established health behavior models in further studies to increase the return rates of deferred FTD.
Introduction: Patients who are overweight or obese have an increased risk of developing type 2 diabetes mellitus (T2DM). Weight loss can have a positive effect on glycemic control. Objective: We aimed to investigate glycemic control in patients with T2DM and overweight or obesity during a structured weight-loss program. Methods: This was a prospective, interventional study. We recruited 36 patients (14 men and 22 women) with a median age of 58.5 years and median body mass index (BMI) of 34.1, to a 15-week structured weight-loss program with a low-calorie (800 kcal) formula diet for 6 weeks. The primary end point, HbA<sub>1c</sub> level, and secondary end points, anthropometric data, medication, and safety, were assessed weekly. Laboratory values and quality of life were assessed at baseline and after 15 weeks. Results: HbA<sub>1c</sub> decreased from 7.3% at baseline to 6.5% at 15 weeks (p < 0.001), median body weight by 11.9 kg (p < 0.001), median BMI by 4.3 (p < 0.001) and median waist circumference by 11.0 cm (p < 0.001). Two participants discontinued insulin therapy, 4 could reduce their dosage of oral antidiabetic agents, and 6 completely discontinued their antidiabetic medication. Insulin dose decreased from 0.63 (0.38–0.89) to 0.39 (0.15–0.70) units/kg body weight (p < 0.001). No patient experienced hypoglycemic episodes or hospital emergency visits. Triglycerides and total cholesterol decreased as well as surrogate markers of liver function. However, the levels of high-density and low-density lipoprotein cholesterol (HDL-C and LDL-C) as well as uric acid remain unchanged. Regarding quality of life, the median physical health score increased from 44.5 (39.7–51.4) at baseline to 48.0 (43.1–55.3; p = 0.007), and the median mental health score decreased from 42.1 (36.1–46.7) to 37.4 (30.3–43.7; p = 0.004). Conclusions: A structured weight-loss program is effective in the short term in reducing HbA<sub>1c</sub>, weight, and antidiabetic medication in patients with T2DM who are overweight or obese. Levels of HDL-C and LDL-C were not affected by short-term weight loss. The decline in mental health and the long-term effects of improved glycemic control require further trials.
Introduction: In the light of the ongoing SARS-CoV-2 pandemic, convalescent plasma is a treatment option for COVID-19. In contrast to usual therapeutic plasma, the therapeutic agents of convalescent plasma do not represent clotting factor activities, but immunoglobulins. Quarantine storage of convalescent plasma as a measure to reduce the risk of pathogen transmission is not feasible. Therefore, pathogen inactivation (e.g., Theraflex®-MB, Macopharma, Mouvaux, France) is an attractive option. Data on the impact of pathogen inactivation by methylene blue (MB) treatment on antibody integrity are sparse. Methods: Antigen-specific binding capacity was tested before and after MB treatment of plasma (n = 10). IgG and IgM isoagglutinin titers were tested by agglutination in increasing dilutions. Furthermore, the binding of anti-EBV and anti-tetanus toxin IgG to their specific antigens was assessed by ELISA, and IgG binding to Fc receptors was assessed by flow cytometry using THP-1 cells expressing FcRI and FcRII. Results: There was no significant difference in the isoagglutinin titers, the antigen binding capacity of anti-EBV and anti-tetanus toxin IgG, as well as the Fc receptor binding capacity before and after MB treatment of plasma. Conclusion: MB treatment of plasma does not inhibit the binding capacity of IgM and IgG to their epitopes, or the Fc receptor interaction of IgG. Based on these results, MB treatment of convalescent plasma is appropriate to reduce the risk of pathogen transmission if quarantine storage is omitted.
Variability of Thyroid Measurements from Ultrasound and Laboratory in a Repeated Measurements Study
(2020)
Background: Variability of measurements in medical research can be due to different sources. Quantification of measurement errors facilitates probabilistic sensitivity analyses in future research to minimize potential bias in epidemiological studies. We aimed to investigate the variation of thyroid-related outcomes derived from ultrasound (US) and laboratory analyses in a repeated measurements study. Subjects and Methods: Twenty-five volunteers (13 females, 12 males) aged 22–70 years were examined once a month over 1 year. US measurements included thyroid volume, goiter, and thyroid nodules. Laboratory measurements included urinary iodine concentrations and serum levels of thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), and thyroglobulin. Variations in continuous thyroid markers were assessed as coefficient of variation (CV) defined as mean of the individual CVs with bootstrapped confidence intervals and as intraclass correlation coefficients (ICCs). Variations in dichotomous thyroid markers were assessed by Cohen’s kappa. Results: CV was highest for urinary iodine concentrations (56.9%), followed by TSH (27.2%), thyroglobulin (18.2%), thyroid volume (10.5%), fT3 (8.1%), and fT4 (6.3%). The ICC was lowest for urinary iodine concentrations (0.42), followed by fT3 (0.55), TSH (0.64), fT4 (0.72), thyroid volume (0.87), and thyroglobulin (0.90). Cohen’s kappa values for the presence of goiter or thyroid nodules were 0.64 and 0.70, respectively. Conclusion: Our study provides measures of variation for thyroid outcomes, which can be used for probabilistic sensitivity analyses of epidemiological data. The low intraindividual variation of serum thyroglobulin in comparison to urinary iodine concentrations emphasizes the potential of thyroglobulin as marker for the iodine status of populations.
Non-carious dental lesions such as developmental defects of enamel (DDE) and erosive tooth wear (ETW) are the subject of intensive research. This paper aims to give perspectives on both DDE, including dental fluorosis and molar incisor hypomineralization (MIH), and ETW, presenting epidemiological data from the Americas and associated diagnostic aspects. Besides, it is important to present evidence to guide the clinical assessment process, supporting the clinicians’ management decisions towards better oral health of their patients. The overall increase in the worldwide prevalence of non-carious lesions discussed in this this paper may reflect the need of perceptual changes. Although the number of publications related to these conditions has been increasing in the last years, there is still a need for clinical diagnostic and management awareness to include these conditions in routine dental practice. Besides, it is important to provide recommendations for standardized clinical assessment criteria, improving the process and helping clinicians’ adherence. In this sense, this paper discusses the most commonly implemented indices for each condition. Thus, despite the wide range of diagnostic indices, BEWE is proposed to be the index recommended for ETW assessment, Dean or Thylstrup & Fejerskov indices for fluorosis and preferably the EAPD criteria (or modified DDE index) for MIH. Overall, non-carious lesions are a growing concern, and it is important to implement preventive measures that control their severity and progression, and accurate diagnosis by the dental clinician.
The triple-trap mass spectrometer ISOLTRAP at ISOLDE/CERN has demonstrated the feasibility of mass spectrometry of in-trap-decay product ions. This novel technique gives access to radionuclides, which are not produced directly at ISOL-type radioactive ion beam facilities. As a proof of principle, the in-trap decay of 37K+ has been investigated in a Penning trap filled with helium buffer gas. The half-life of the mother nuclide was confirmed and the recoiling 37Ar+ daughter ion was contained within the trap. The ions of either the mother or the daughter nuclide were transferred to a precision Penning trap, where their mass was determined.
Colossal magneto-resistance manganites are characterized by a complex interplay of charge, spin, orbital and lattice degrees of freedom. Formulating microscopic models for these compounds aims at meeting two conflicting objectives: sufficient simplification without excessive restrictions on the phase space. We give a detailed introduction to the electronic structure of manganites and derive a microscopic model for their low-energy physics. Focusing on short-range electron–lattice and spin–orbital correlations we supplement the modelling with numerical simulations.
Low-pressure plasmas offer a unique possibility of confinement, control and
fine tailoring of particle properties. Hence, dusty plasmas have grown
into a vast field and new applications of plasma-processed dust particles
are emerging. There is demand for particles with special properties and
for particle-seeded composite materials. For example, the stability of
luminophore particles could be improved by coating with protective Al2O3
films which are deposited by a PECVD process using a metal-organic precursor gas.
Alternatively, the interaction between plasma and injected micro-disperse powder
particles can also be used as a diagnostic tool for the study of plasma surface
processes. Two examples will be provided: the interaction of micro-sized (SiO2)
grains confined in a radiofrequency plasma with an external ion beam as well as
the effect of a dc-magnetron discharge on confined particles during deposition
have been investigated.
The region surrounding the excitonic insulator phase is a three-component plasma composed of electrons, holes, and excitons. Due to the extended nature of the excitons, their presence influences the surrounding electrons and holes. We analyze this correlation. To this end, we calculate the density of bound electrons, the density of electrons in the correlated state, the momentum-resolved exciton density, and the momentum-resolved density of electron-hole pairs that are correlated but unbound. We find qualitative differences in the electron-hole correlations between the weak-coupling and the strong-coupling regime.
Abstract
The increasing global prevalence of dementia demands concrete actions that are aimed strategically at optimizing processes that drive clinical innovation. The first step in this direction requires outlining hurdles in the transition from research to practice. The different parties needed to support translational processes have communication mismatches; methodological gaps hamper evidence‐based decision‐making; and data are insufficient to provide reliable estimates of long‐term health benefits and costs in decisional models. Pilot projects are tackling some of these gaps, but appropriate methods often still need to be devised or adapted to the dementia field. A consistent implementation perspective along the whole translational continuum, explicitly defined and shared among the relevant stakeholders, should overcome the “research‐versus‐adoption” dichotomy, and tackle the implementation cliff early on. Concrete next steps may consist of providing tools that support the effective participation of heterogeneous stakeholders and agreeing on a definition of clinical significance that facilitates the selection of proper outcome measures.
Solar Activity Driven 27‐Day Signatures in Ionospheric Electron and Molecular Oxygen Densities
(2022)
Abstract
The complex interactions in the upper atmosphere, which control the height‐dependent ionospheric response to the 27‐day solar rotation period, are investigated with the superposed epoch analysis technique. 27‐day signatures describing solar activity are calculated from a solar proxy (F10.7) and wavelength‐dependent extreme ultraviolet (EUV) fluxes (Thermosphere Ionosphere Mesosphere Energetics and Dynamics/Solar EUV Experiment), and the corresponding 27‐day signatures describing ionospheric conditions are calculated from electron density profiles (Pruhonice ionosonde station) and O2 density profiles (Global‐scale Observations of the Limb and Disk). The lag analysis of these extracted signatures is applied to characterize the delayed ionospheric response at heights from 100 to 300 km and the impact of major absorption processes in the lower (dominated by O2) and upper ionosphere (dominated by O) is discussed. The observed variations of the delay in these regions are in good agreement with model simulations in preceding studies. Additionally, the estimated significance and the correlation of the delays based on both ionospheric parameters are good. Thus, variations such as the strong shift in 27‐day signatures for the O2 density at low heights are also reliably identified (up to half a cycle). The analysis confirms the importance of ionospheric and thermospheric coupling to understand the variability of the delayed ionospheric response and introduces a method that could be applied to additional ionosonde stations in future studies. This would allow to describe the variability of the delayed ionospheric response spatially, vertically and temporally and therefore may contribute further to the understanding of processes and improve ionospheric modeling.
Separating EEG correlates of stress: Cognitive effort, time pressure, and social‐evaluative threat
(2022)
Abstract
The prefrontal cortex is a key player in stress response regulation. Electroencephalographic (EEG) responses, such as a decrease in frontal alpha and an increase in frontal beta power, have been proposed to reflect stress‐related brain activity. However, the stress response is likely composed of different parts such as cognitive effort, time pressure, and social‐evaluative threat, which have not been distinguished in previous studies. This distinction, however, is crucial if we aim to establish reliable tools for early detection of stress‐related conditions and monitoring of stress responses throughout treatment. This randomized cross‐over study (N = 38) aimed to disentangle EEG correlates of stress. With linear mixed models accounting for missing values in some conditions, we found a decrease in frontal alpha and increase in beta power when performing the Paced Auditory Serial Addition Test (PASAT; cognitive effort; n = 32) compared to resting state (n = 33). No change in EEG power was found when the PASAT was performed under time pressure (n = 29) or when adding social‐evaluative threat (video camera; n = 29). These findings suggest that frontal EEG power can discriminate stress from resting state but not more fine‐grained differences of the stress response.
Abstract
Background
Twenty five‐hydroxy vitamin D (25OHD) levels have been proposed to protect against periodontitis based on in vitro and observational studies but evidence from long‐term randomized controlled trials (RCTs) is lacking. This study tested whether genetically proxied 25OHD is associated with periodontitis using Mendelian randomization (MR).
Methods
Genetic variants strongly associated with 25OHD in a genome‐wide association study (GWAS) of 417,580 participants of European ancestry were used as instrumental variables, and linked to GWAS summary data of 17,353 periodontitis cases and 28,210 controls. In addition to the main analysis using an inverse variance weighted (IVW) model, we applied additional robust methods to control for pleiotropy. We also undertook sensitivity analyses excluding single nucleotide polymorphisms (SNPs) used as instruments with potential pleiotropic effects and used a second 25OHD GWAS for replication. We identified 288 SNPs to be genome‐wide significant for 25OHD, explaining 7.0% of the variance of 25OHD levels and providing ≥90% power to detect an odds ratio (OR) of ≤ 0.97.
Results
MR analysis suggested that a 1 standard deviation increase in natural log‐transformed 25OHD was not associated with periodontitis risk (IVW OR = 1.04; 95% confidence interval (CI): 0.97–1.12; P‐value = 0.297). The robust models, replication, and sensitivity analyses were coherent with the primary analysis.
Conclusions
Collectively, our findings suggest that 25OHD levels are unlikely to have a substantial effect on the risk of periodontitis, but large long‐term RCTs are needed to derive definitive evidence on the causal role of 25OHD in periodontitis.
Abstract
Pikeperch (Sander lucioperca) has become a species of interest in aquaculture. It is a popular and economically valuable food fish and can produce high numbers of offspring. However, during early development, there are transition phases when high mortality rates concur with growth changes, vital organ transformations and a limited energy budget. Up to now, no study focused on the developmental adaption of muscle tissue in pikeperch, regardless of muscle tissue influencing essential traits such as locomotion and thus the competence to hunt prey and avoid predators. In the present study, therefore, the developmental myogenesis of pikeperch was analysed using specimens from early embryonic to larval development. Myogenic and developmental genes were utilized to gain insights into transcriptomic regulation during these stages by applying a nanofluidic qPCR approach. Result, three phases of myogenic gene expression, during somitogenesis, during the late embryonic development and during the larval development were detected. Increased myostatin expression showed an interim arrest of muscle formation between embryonic and larval myogenesis. Expression patterns of satellite cell gene markers indicated an accumulation of stem cells before myogenesis interruption. The here gained data will help to broaden the knowledge on percid myogenesis and can support pikeperch rearing in aquaculture.
Background
Based on learned helplessness theory and conservation of resources theory, the present study explores the role of schools’ social environments (i.e., school belonging, school exclusion, and teacher–student relationships) as potential buffers and amplifiers in students’ development of learned helplessness during adolescence.
Aims
We examine whether school belonging, school exclusion, and teacher–student relationship moderate the longitudinal association of learned helplessness differently for students from low‐track schools and high‐track schools.
Sample
The study uses a sample of N = 1,088 (Mage = 13.70, SD = 0.53; 54% girls) adolescent students who participated in a two‐wave longitudinal study.
Methods
We conducted latent moderated structural equation modelling to examine whether school belonging, school exclusion, and teacher–student relationship moderate the longitudinal association of learned helplessness differently for students from low‐track schools and high‐track schools.
Results
The moderation analyses revealed that students from both school tracks are differently affected by school belonging and school exclusion in their development of learned helplessness. Teacher–student relationship did not moderate the association.
Conclusion
Our findings underline the important role of the social environment in students’ development of learned helplessness. Particularly, the differential effects found for the different educational tracks highlight the necessary awareness of educators to interindividual differences of their students.
Abstract
We investigated four subaerial (paleo)lacustrine landforms at the north‐eastern shoreline of Schweriner See, north‐eastern Germany. These included two beach ridges, one subaerial nearshore bar and a silting up sequence located close to a fossil cliff, which marks the former maximum extent of Schweriner See. We used luminescence profiling with a SUERC portable OSL device (POSL) on all four sediment sequences in combination with sedimentological investigations such as grain size, loss‐on‐ignition and magnetic susceptibility to provide information on the various formations in a lacustrine depositional environment. The POSL reader was used on pre‐treated polymineral samples to gain an insight into luminescence distribution within the individual sediment sequences, but also among the four sequences. POSL proved valuable to understand depositional processes, which were not visible in lithology or sedimentological parameters. With somewhat larger uncertainty this method provides relative chronologies of the sediment sequences. Additionally, we carried out radiocarbon dating and full optical stimulated luminescence (OSL) dating to establish a chronological framework. OSL ages proved to be more reliable to date beach ridges in this setting than radiocarbon samples, which were severely influenced by sediment reworking. This combined approach of sedimentological analyses, luminescence profiling and absolute age determinations revealed details in depositional processes at Schweriner See which otherwise would have remained undetected. Furthermore, it helped to set these subaerial (paleo)lacustrine landforms in a chronological framework.
Background
Postoperative pancreatic fistula (POPF) is the most critical complication after pancreatoduodenectomy (PD). Preoperative identification of high-risk patients and optimal pancreatic reconstruction technique can be a way to reduce postoperative complications.
Methods
A series of 386 patients underwent PD over a 10-year period (2009–2019). On routinely performed preoperative computed tomography (CT) images, the ventro-dorsal diameters of duct (D) and parenchyma (P) were measured in the cutting plane at the superior mesenteric vein. Then, the ratio of both values was calculated (D/P ratio) Double-layer pancreatojejunostomy with alignment of duct and mucosa (ADAM) by two monofilament threads (MFT) was performed in 359 patients and pancreatogastrostomy (PG) in 27 patients. The incidence of POPF was diagnosed according to the International Study Group for Pancreatic Fistula criteria.
Results
The overall rate of POPF was 21% (n = 80), and the rate of clinically relevant type B/C fistulas 6.5% (n = 25). A D/P ratio of <0.2 was significantly associated with type B/C fistula (11%, p < 0.01). In low-risk patients (D/P ratio >0.2), type B/C fistula occurred only in 2%, and in high-risk patients (D/P ratio <0.2) in 9%. ADAM anastomosis was performed safely by two different surgeons. A PG anastomosis had double-digit POPF rates in all groups.
Conclusion
Preoperative CT imaging with D/P measurement may predict the risk of POPF development. A cut off D/P ratio of <0.2 was significantly associated with clinical relevant POPF. ADAM anastomosis may be an option for pancreatojejunostomy. However, preoperative knowledge of the D/P ratio could guide decision-making for primary pancreatectomy when pancreatic reconstruction is critical.
Background
Over the course of the COVID-19 pandemic, previous studies have shown that the physical as well as the mental health of children and adolescents significantly deteriorated. Future anxiety caused by the COVID-19 pandemic and its associations with quality of life has not previously been examined in school children.
Methods
As part of a cross-sectional web-based survey at schools in Mecklenburg-Western Pomerania, Germany, two years after the outbreak of the pandemic, school children were asked about COVID-19-related future anxiety using the German epidemic-related Dark Future Scale for children (eDFS-K). Health-related quality of life (HRQoL) was assessed using the self-reported KIDSCREEN-10. The eDFS-K was psychometrically analyzed (internal consistency and confirmatory factor analysis) and thereafter examined as a predictor of HRQoL in a general linear regression model.
Results
A total of N = 840 8–18-year-old children and adolescents were included in the analysis. The eDFS-K demonstrated adequate internal consistency reliability (Cronbach's α = 0.77), and the confirmatory factor analysis further supported the one-factor structure of the four-item scale with an acceptable model fit. Over 43% of students were found to have low HRQoL. In addition, 47% of the students sometimes to often reported COVID-19-related fears about the future. Children with COVID-19-related future anxiety had significantly lower HRQoL (B = – 0.94, p < 0.001). Other predictors of lower HRQoL were older age (B = – 0.63, p < 0.001), and female (B = – 3.12, p < 0.001) and diverse (B = – 6.82, p < 0.001) gender.
Conclusion
Two years after the outbreak of the pandemic, school-aged children continue to exhibit low HRQoL, which is further exacerbated in the presence of COVID-19-related future anxiety. Intervention programs with an increased focus on mental health also addressing future anxiety should be provided.
ZusammenfassungDer Aufsatz bietet den ersten konsistenten Überblick über den Wandel der politischen Positionen der protestantischen Theologie in der DDR. Mit Hilfe von Anregungen aus der Cambridge School der Ideengeschichte geht der Text der Frage nach, inwieweit die ostdeutsche evangelische Theologie Resistenzpotential gegenüber dem politischen Anpassungsdruck des SED-Regimes aufzubringen vermochte. Dabei widersprechen die Autoren der in der Forschung verbreiteten Auffassung, die Protestanten hätten die Theologie in obrigkeitstreuer Tradition einmal mehr den neuen Verhältnissen angepasst. Vielmehr lässt sich ein deutlicher Bruch nach 1945 erkennen, eine jahrelang anhaltende Kritik an der atheistischen Regierung und ein theologisches Ringen um ein angemessenes Obrigkeitsverständnis. Erst äußere Anlässe brachten die Kirchen dazu, ihre fundamentalkritische Theologie Zug um Zug aufzugeben. Dazu gehört die Zementierung der deutschen Teilung, die den Rückhalt der ostdeutschen Kirchen in der gesamtdeutschen EKD schwächte, oder auch die Ungleichheit in der Verteilung der Machtmittel, die die Kirchen an den Staat auslieferten. Neben diesen strukturellen Gründen benennen die Autoren ideelle Motive wie die Kritik an der Institution EKD, durch die sich die jüngeren Theologen von der älteren Generation ablösen wollten. Einflussreich waren auch internationale ökumenische Diskurse, die seit den siebziger Jahren den Kapitalismus zunehmend kritisch und den Sozialismus entsprechend positiv einordneten. Obwohl die wenigen verbliebenen Christen sich immer wieder unangepasst verhielten, ließ sich die Theologie insgesamt mehr und mehr zur Rechtfertigung des Anpassungsweges einspannen. Nicht sie bestimmte die politische Haltung. Vielmehr gaben äußere Faktoren die theologischen Positionsbestimmungen der Kirche vor.
In order to identify possible experimental signatures of the superfluid to Mott-insulator quantum phase transition we calculate the charge structure factor S(k, ω) for the one-dimensional Bose-Hubbard model using the dynamical density-matrix renormalisation group (DDMRG) technique. Particularly we analyse the behaviour of S(k, ω) by varying – at zero temperature–the Coulomb interaction strength within the first Mott lobe. For strong interactions, in the Mott-insulator phase, we demonstrate that the DDMRG results are well reproduced by a strong-coupling expansion, just as the quasi-particle dispersion. In the super-fluid phase we determine the linear excitation spectrum near k = 0. In one dimension, the amplitude mode is absent which mean-field theory suggests for higher dimensions.
Body dissatisfaction is pervasive among young women in Western countries. Among the many forces that contribute to body dissatisfaction, the overrepresentation of thin bodies in visual media has received notable attention. In this study, we proposed that prevalence-induced concept change may be one of the cognitive mechanisms that explain how beauty standards shift. We conducted a preregistered online experiment with young women (N = 419) and found that when the prevalence of thin bodies in the environment increased, the concept of being overweight expanded to include bodies that would otherwise be judged as “normal.” Exploratory analyses revealed significant individual differences in sensitivity to this effect, in terms of women’s judgments about other bodies as well as their own. These results suggest that women’s judgments about other women’s bodies are biased by an overrepresentation of thinness and lend initial support to policies designed to increase size-inclusive representation in the media.
Background:
Epilepsy development during the course of multiple sclerosis (MS) is considered to be the result of cortical pathology. However, no long-term data exist on whether epilepsy in MS also leads to increasing disability over time.
Objective:
To examine if epilepsy leads to more rapid disease progression.
Methods:
We analyzed the data of 31,052 patients on the German Multiple Sclerosis Register in a case–control study.
Results:
Secondary progressive disease course (odds ratio (OR) = 2.23), age (OR = 1.12 per 10 years), and disability (OR = 1.29 per Expanded Disability Status Scale (EDSS) point) were associated with the 5-year prevalence of epilepsy. Patients who developed epilepsy during the course of the disease had a higher EDSS score at disease onset compared to matched control patients (EDSS 2.0 vs 1.5), progressed faster in each dimension, and consequently showed higher disability (EDSS 4.4 vs 3.4) and lower employment status (40% vs 65%) at final follow-up. After 15 years of MS, 64% of patients without compared to 54% of patients with epilepsy were not severely limited in walking distance.
Conclusion:
This work highlights the association of epilepsy on disability progression in MS, and the need for additional data to further clarify the underlying mechanisms.
The role of large-scale fluctuation structures in electrostatic
drift-wave-type plasma turbulence is highlighted. In particular,
well-defined laboratory experiments allow one to study the
dynamics of drift wave mode structures as well as `eddies' in
drift wave turbulence. In the present paper we discuss the
mutual relationships between observations made in linear
magnetic geometry, purely toroidal geometry and magnetic
confinement. The simplest structure, a saturated, nonlinear
drift mode, is the starting point for a Ruelle-Takens-Newhouse
transition route to chaos and weakly developed turbulence. Both
spectral and phase space analysis are applied to characterize in
detail the transition scenario, which is enforced due to an
increased drive by the plasma equilibrium state. In addition to
direct multi-probe observation, statistical approaches are most
revealing for the systematic study of the spatiotemporal
dynamics in fully developed drift wave turbulence. In
particular, the propagation of large-scale `eddy' structures is
traced by conditional statistics methods. Finally, the control
of drift wave turbulence by spatiotemporal synchronization is
discussed.
Abstract
Body weight loss is frequently regarded as negatively related to outcomes in patients with malignancies. This retrospective analysis of the FIRE‐3 study evaluated the evolution of body weight in patients with metastatic colorectal cancer (mCRC). FIRE‐3 evaluated first‐line FOLFIRI (folinic acid, fluorouracil and irinotecan) plus cetuximab or bevacizumab in mCRC patients with RAS‐WT tumors (ie, wild‐type in KRAS and NRAS exons 2‐4). The prognostic and predictive relevance of early weight loss (EWL) regarding patient outcomes and treatment side effects were evaluated. Retrospective data on body weight during first 6 months of treatment were evaluated (N = 326). To correlate with efficacy endpoints and treatment side effects, patients were grouped according to clinically significant EWL ≥5% and <5% at Month 3. Age constituted the only significant predictor of EWL following a linear relationship with the corresponding log odds ratio (P = .016). EWL was significantly associated with the incident frequencies of diarrhea, edema, fatigue, nausea and vomiting. Further, a multivariate analysis revealed EWL to be an independent negative prognostic factor for overall survival (32.4 vs 21.1 months; hazard ratio [HR]: 1.64; 95% confidence interval [CI] = 1.13‐2.38; P = .0098) and progression‐free survival (11.8 vs 9.0 months; HR: 1.72; 95% CI = 1.18‐2.5; P = .0048). In conclusion, EWL during systemic treatment against mCRC is significantly associated with patient age. Patients exhibiting EWL had worse survival and higher frequencies of adverse events. Early preventative measures targeted at weight maintenance should be evaluated, especially in elderly patients being at highest risk of EWL.
Abstract
We formulate exact generalized nonequilibrium fluctuation relations for the quantum mechanical harmonic oscillator coupled to multiple harmonic baths. Each of the different baths is prepared in its own individual (in general nonthermal) state. Starting from the exact solution for the oscillator dynamics we study fluctuations of the oscillator position as well as of the energy current through the oscillator under general nonequilibrium conditions. In particular, we formulate a fluctuation–dissipation relation for the oscillator position autocorrelation function that generalizes the standard result for the case of a single bath at thermal equilibrium. Moreover, we show that the generating function for the position operator fulfils a generalized Gallavotti–Cohen-like relation. For the energy transfer through the oscillator, we determine the average energy current together with the current fluctuations. Finally, we discuss the generalization of the cumulant generating function for the energy transfer to nonthermal bath preparations.
AbstractGlobal challenges related to land, biodiversity, food and climate interact in diverse ways depending on local conditions and the broader context in which they are embedded. This diversity challenges learning and integrated decision-making to sustainably transform the nexus, that is to say the interactions between these land-based challenges. Providing aggregated insights, archetype analysis has revealed recurrent patterns within the multitude of interactions, i.e. interaction archetypes that are essential to enhance the understanding of nexus relations. This paper synthesises the state of knowledge on interaction or nexus archetypes related to land, biodiversity, food and climate based on a systematic literature review. It focusses on the coverage of thematic aspects, regional distribution, social dimensions and methodologies. The results show that consideration of comprehensive land–biodiversity–food–climate interactions is rare. Furthermore, there are pronounced regional knowledge gaps, social dimensions are inadequately captured, and methodological shortcomings are evident. To enhance the investigation of interaction archetypes, we have framed a future research agenda providing directions to fully capture interactions across space and time, better use the potential of scenario archetypes and up-scale transformative actions. These advances will constructively contribute insights that help to achieve the ambitious objective to sustainably transform the nexus between land, biodiversity, food and climate.
AbstractPlasma medicine refers to the application of nonequilibrium plasmas at approximately body temperature, for therapeutic purposes. Nonequilibrium plasmas are weakly ionized gases which contain charged and neutral species and electric fields, and emit radiation, particularly in the visible and ultraviolet range. Medically-relevant cold atmospheric pressure plasma (CAP) sources and devices are usually dielectric barrier discharges and nonequilibrium atmospheric pressure plasma jets. Plasma diagnostic methods and modelling approaches are used to characterize the densities and fluxes of active plasma species and their interaction with surrounding matter. In addition to the direct application of plasma onto living tissue, the treatment of liquids like water or physiological saline by a CAP source is performed in order to study specific biological activities. A basic understanding of the interaction between plasma and liquids and bio-interfaces is essential to follow biological plasma effects. Charged species, metastable species, and other atomic and molecular reactive species first produced in the main plasma ignition are transported to the discharge afterglow to finally be exposed to the biological targets. Contact with these liquid-dominated bio-interfaces generates other secondary reactive oxygen and nitrogen species (ROS, RNS). Both ROS and RNS possess strong oxidative properties and can trigger redox-related signalling pathways in cells and tissue, leading to various impacts of therapeutic relevance. Dependent on the intensity of plasma exposure, redox balance in cells can be influenced in a way that oxidative eustress leads to stimulation of cellular processes or oxidative distress leads to cell death. Currently, clinical CAP application is realized mainly in wound healing. The use of plasma in cancer treatment (i.e. plasma oncology) is a currently emerging field of research. Future perspectives and challenges in plasma medicine are mainly directed towards the control and optimization of CAP devices, to broaden and establish its medical applications, and to open up new plasma-based therapies in medicine.
AbstractGas puff modulation experiments are performed at ASDEX Upgrade in L-mode plasmas. We model the discharge with the ASTRA transport code in order to determine transport coefficients outside of a normalized radius of ρ
pol = 0.95. The experimental data is consistent with a range of particle diffusivities and pinch velocities of the order of D = (0.20 ± 0.13) m2 s−1 and v = (−1 ± 2) m s−1, respectively. The electron temperature response caused by the gas modulation permits to estimate also that heat diffusivity χ
e increases almost linearly when collisionality rises due to fuelling. The fuelling particle flux is amplified by recycling, overcompensating losses.
AbstractArchetype analysis is a promising approach in sustainability science to identify patterns and explain mechanisms shaping the sustainability of social-ecological systems. Although considerable efforts have been devoted to developing quality standards and methodological advances for archetype analysis, archetype validation remains a major challenge. Drawing on the insights from two international workshops on archetype analysis and on broader literature on validity, we propose a framework that identifies and describes six dimensions of validity: conceptual; construct; internal; external; empirical; and application validity. We first discuss the six dimensions in relation to different methodological approaches and purposes of archetype analysis. We then present an operational use of the framework for researchers to assess the validity of archetype analysis and to support sound archetype identification and policy-relevant applications. Finally, we apply our assessment to 18 published archetype analyses, which we use to describe the challenges and insights in validating the different dimensions and suggest ways to holistically improve the validity of identified archetypes. With this, we contribute to more rigorous archetype analyses, helping to develop the potential of the approach for guiding sustainability solutions.
Synopsis
By interaction with electrons in ion storage devices (ion-cyclotron-resonance and radio-frequency traps) negatively charged clusters of gold and aluminum have been produced up to the 6th and 10th charge state, respectively. The production of these poly-anions opens exciting new possibilities to measure their lifetimes, to monitor their relaxation schemes after laser radiation, as well as to probe their Coulomb barriers.
Synopsis
C+60 has been proposed to be responsible for two of the diffuse interstellar bands (DIBs), the absorption features observed in the visible-to-near-infrared spectra of the interstellar medium. However, a confirmation requires laboratory gas-phase spectra, which are so far not available. We plan to develop a novel spectroscopy technique that will allow us to obtain the first gas-phase spectra of C+60, and that will be applicable to other complex organic molecules such as polycyclic aromatic hydrocarbons. The current status of the experimental setup, the ideas behind the measurement scheme and the preparatory work toward its implementation will be presented.
AbstractThe 2022 Roadmap is the next update in the series of Plasma Roadmaps published by Journal of Physics D with the intent to identify important outstanding challenges in the field of low-temperature plasma (LTP) physics and technology. The format of the Roadmap is the same as the previous Roadmaps representing the visions of 41 leading experts representing 21 countries and five continents in the various sub-fields of LTP science and technology. In recognition of the evolution in the field, several new topics have been introduced or given more prominence. These new topics and emphasis highlight increased interests in plasma-enabled additive manufacturing, soft materials, electrification of chemical conversions, plasma propulsion, extreme plasma regimes, plasmas in hypersonics, data-driven plasma science and technology and the contribution of LTP to combat COVID-19. In the last few decades, LTP science and technology has made a tremendously positive impact on our society. It is our hope that this roadmap will help continue this excellent track record over the next 5–10 years.
Detecting changes in plasmas is compulsory for control and the detection of novelties.
Moreover, automated novelty detection allows one to investigate large data sets to substantially
enhance the efficiency of data mining approaches. To this end we introduce permutation entropy
(PE) for the detection of changes in plasmas. PE is an information-theoretic complexity measure
based in fluctuation analysis that quantifies the degree of randomness (resp. disorder,
unpredictability) of the ordering of time series data. This method is computationally fast and
robust against noise, which allows the evaluation of large data sets in an automated procedure.
PE is applied on electron cyclotron emission and soft x-ray measurements in different
Wendelstein 7-X low-iota configuration plasmas. A spontaneous transition to high core-electron
temperature (Te) was detected, as well as a localized low-coherent intermittent oscillation which
ceased when Te increased in the transition. The results are validated with spectrogram analysis
and provide evidence that a complexity measure such as PE is a method to support in-situ
monitoring of plasma parameters and for novelty detection in plasma data. Moreover, the
acceleration in processing time offers implementations of plasma-state-detection that provides
results fast enough to induce control actions even during the experiment.
Abstract
We present experiments on the luminescence of excitons confined in a potential trap at milli-Kelvin bath temperatures under continuous-wave (cw) excitation. They reveal several distinct features like a kink in the dependence of the total integrated luminescence intensity on excitation laser power and a bimodal distribution of the spatially resolved luminescence. Furthermore, we discuss the present state of the theoretical description of Bose–Einstein condensation of excitons with respect to signatures of a condensate in the luminescence. The comparison of the experimental data with theoretical results with respect to the spatially resolved as well as the integrated luminescence intensity shows the necessity of taking into account a Bose–Einstein condensed excitonic phase in order to understand the behaviour of the trapped excitons.
Abstract
Nanoscale multilayer thin films of W and PC (Polycarbonate) show, due to the great difference of the components’ characteristics, fascinating properties for a variety of possible applications and provide an interesting research field, but are hard to fabricate with low layer thicknesses. Because of the great acoustic mismatch between the two materials, such nanoscale structures are promising candidates for new phononic materials, where phonon propagation is strongly reduced. In this article we show for the first time that W/PC-multilayers can indeed be grown with high quality by pulsed laser deposition. We analyzed the polymer properties depending on the laser fluence used for deposition, which enabled us to find best experimental conditions for the fabrication of high-acoustic-mismatch W/PC multilayers. The multilayers were analyzed by fs pump-probe spectroscopy showing that phonon dynamics on the ps time-scale can strongly be tailored by structural design. While already periodic multilayers exhibit strong phonon localization, especially aperiodic structures present outstandingly low phonon propagation properties making such 1D-layered W/PC nano-structures interesting for new phononic applications.
Abstract
We have demonstrated efficient injection and trapping of a cold positron beam in a dipole magnetic field configuration. The intense 5 eV positron beam was provided by the NEutron induced POsitron source MUniCh facility at the Heinz Maier-Leibnitz Zentrum, and transported into the confinement region of the dipole field trap generated by a supported, permanent magnet with 0.6 T strength at the pole faces. We achieved transport into the region of field lines that do not intersect the outer wall using the
drift of the positron beam between a pair of tailored plates that created the electric field. We present evidence that up to 38% of the beam particles are able to reach the intended confinement region and make at least a 180° rotation around the magnet where they annihilate on an insertable target. When the target is removed and the
plate voltages are switched off, confinement of a small population persists for on the order of 1 ms. These results lend optimism to our larger aims to apply a magnetic dipole field configuration for trapping of both positrons and electrons in order to test predictions of the unique properties of a pair plasma.
Abstract
Experimental studies on dusty plasmas containing systems of (super-)paramagnetic dust particles are presented. In our experiments, external (homogeneous as well as inhomogeneous) magnetic fields in the mT range are applied to study the effect on single particles or few-particle systems that are trapped inside the sheath region. The behavior of the paramagnetic dust particles is considerably different than that of dielectric plastic particles, which are widely used in dusty plasmas. It is revealed that especially non-magnetic contributions play an important role in the interaction between superparamagnetic particles.
Abstract
Many processes in nature are governed by the interaction of electro-magnetic radiation with matter. New tools such as femtosecond and free-electron lasers allow one to study the interaction in unprecedented detail with high temporal and spatial resolution. In addition, much work is devoted to the exploration of novel target systems that couple to radiation in an effective and controllable way or that could serve as efficient sources of energetic particles when being subjected to intense laser fields. The interaction between matter and radiation fields as well as their mutual modification via correlations constitutes a rich field of research that is impossible to cover exhaustively. The papers in this focus issue represent a selection that largely reflects the program of the international conference on ‘Correlation Effects in Radiation Fields’ held in 2011 in Rostock, Germany.
Abstract
Emperor penguins breed during the Antarctic winter and have to endure temperatures as low as −50 °C and wind speeds of up to 200 km h−1. To conserve energy, they form densely packed huddles with a triangular lattice structure. Video recordings from previous studies revealed coordinated movements in regular wave-like patterns within these huddles. It is thought that these waves are triggered by individual penguins that locally disturb the huddle structure, and that the traveling wave serves to remove the lattice defects and restore order. The mechanisms that govern wave propagation are currently unknown, however. Moreover, it is unknown if the waves are always triggered by the same penguin in a huddle. Here, we present a model in which the observed wave patterns emerge from simple rules involving only the interactions between directly neighboring individuals, similar to the interaction rules found in other jammed systems, e.g. between cars in a traffic jam. Our model predicts that a traveling wave can be triggered by a forward step of any individual penguin located within a densely packed huddle. This prediction is confirmed by optical flow velocimetry of the video recordings of emperor penguins in their natural habitat.
Abstract
The spectral properties of three-dimensional dust clusters confined in gaseous discharges are investigated using both a fluid mode description and the normal mode analysis (NMA). The modes are analysed for crystalline clusters as well as for laser-heated fluid-like clusters. It is shown that even for clusters with low particle numbers and under presence of damping fluid modes can be identified. Laser-heating leads to the excitation of several, mainly transverse, modes. The mode frequencies are found to be nearly independent of the coupling parameter and support the predictions of the underlying theory. The NMA and the fluid mode spectra demonstrate that the wakefield attraction is present for the experimentally observed Yukawa balls at low pressure. Both methods complement each other, since NMA is more suitable for crystalline clusters, whereas the fluid modes allow to explore even fluid-like dust clouds.
on-healing wounds continue to be a clinical challenge for patients and medical staff.
These wounds have a heterogeneous etiology, including diabetes and surgical trauma wounds. It is
therefore important to decipher molecular signatures that reflect the macroscopic process of wound
healing. To this end, we collected wound sponge dressings routinely used in vacuum assisted therapy
after surgical trauma to generate wound-derived protein profiles via global mass spectrometry.
We confidently identified 311 proteins in exudates. Among them were expected targets belonging to
the immunoglobulin superfamily, complement, and skin-derived proteins, such as keratins. Next to
several S100 proteins, chaperones, heat shock proteins, and immune modulators, the exudates
presented a number of redox proteins as well as a discrete neutrophil proteomic signature, including
for example cathepsin G, elastase, myeloperoxidase, CD66c, and lipocalin 2. We mapped over 200
post-translational modifications (PTMs; cysteine/methionine oxidation, tyrosine nitration, cysteine
trioxidation) to the proteomic profile, for example, in peroxiredoxin 1. Investigating manually
collected exudates, we confirmed presence of neutrophils and their products, such as microparticles
and fragments containing myeloperoxidase and DNA. These data confirmed known and identified
less known wound proteins and their PTMs, which may serve as resource for future studies on
human wound healing
For the last two decades, heparins have been widely used as anticoagulants. Besides
numerous advantages, up to 5% patients with heparin administration suffer from a major adverse
drug effect known as heparin-induced thrombocytopenia (HIT). This typical HIT can result in deep
vein thrombosis, pulmonary embolism, occlusion of a limb artery, acute myocardial infarct, stroke, and
a systemic reaction or skin necrosis. The basis of HIT may lead to clinical insights. Recent studies using
single-molecule force spectroscopy (SMFS)-based atomic force microscopy revealed detailed binding
mechanisms of the interactions between platelet factor 4 (PF4) and heparins of different lengths in
typical HIT. Especially, SMFS results allowed identifying a new mechanism of the autoimmune HIT
caused by a subset of human-derived antibodies in patients without heparin exposure. The findings
proved that not only heparin but also a subset of antibodies induce thrombocytopenia. In this review,
the role of SMFS in unraveling a major adverse drug effect and insights into molecular mechanisms
inducing thrombocytopenia by both heparins and antibodies will be discussed.
The G protein-coupled receptor proteinase-activated receptor 2 (PAR2) has been implicated
in various aspects of cellular physiology including inflammation, obesity and cancer. In cancer,
it usually acts as a driver of cancer progression in various tumor types by promoting invasion and
metastasis in response to activation by serine proteinases. Recently, we discovered another mode
through which PAR2 may enhance tumorigenesis: crosstalk with transforming growth factor-β
(TGF-β) signaling to promote TGF-β1-induced cell migration/invasion and invasion-associated gene
expression in ductal pancreatic adenocarcinoma (PDAC) cells. In this chapter, we review what is
known about the cellular TGF-β responses and signaling pathways affected by PAR2 expression,
the signaling activities of PAR2 required for promoting TGF-β signaling, and the potential molecular
mechanism(s) that underlie(s) the TGF-β signaling–promoting effect. Since PAR2 is activated through
various serine proteinases and biased agonists, it may couple TGF-β signaling to a diverse range of
other physiological processes that may or may not predispose cells to cancer development such as
local inflammation, systemic coagulation and pathogen infection.
: An enhanced indoleamine 2,3-dioxygenase 1 (IDO1) activity is associated with an increased
mortality risk in sepsis patients. Thus, the preventive inhibition of IDO1 activity may be
a promising strategy to attenuate the severity of septic shock. 1-methyltryptophan (1-MT)
is currently in the interest of research due to its potential inhibitory effects on IDO1 and
immunomodulatory properties. The present study aims to investigate the protective and
immunomodulatory effects of 1-methyltryptophan against endotoxin-induced shock in a porcine
in vivo model. Effects of 1-MT were determined on lipopolysaccharide (LPS)-induced tryptophan
(TRP) degradation, immune response and sickness behaviour. 1-MT increased TRP and its metabolite
kynurenic acid (KYNA) in plasma and tissues, suppressed the LPS-induced maturation of neutrophils
and increased inactivity of the animals. 1-MT did not inhibit the LPS-induced degradation of TRP
to kynurenine (KYN)—a marker for IDO1 activity—although the increase in KYNA indicates that
degradation to one branch of the KYN pathway is facilitated. In conclusion, our findings provide
no evidence for IDO1 inhibition but reveal the side effects of 1-MT that may result from the proven
interference of KYNA and 1-MT with aryl hydrocarbon receptor signalling. These effects should be
considered for therapeutic applications of 1-MT.
Leukocyte telomere length (TL) has been suggested as a marker of biological age in healthy
individuals, but can also reflect inherited and acquired hematopoietic dysfunctions or indicate an
increased turnover of the hematopoietic stem and progenitor cell compartment. In addition, TL is able
to predict the response rate of tyrosine kinase inhibitor therapy in chronic myeloid leukemia (CML),
indicates clinical outcomes in chronic lymphocytic leukemia (CLL), and can be used as screening tool
for genetic sequencing of selected genes in patients with inherited bone marrow failure syndromes
(BMFS). In tumor cells and clonal hematopoietic disorders, telomeres are continuously stabilized by
reactivation of telomerase, which can selectively be targeted by telomerase-specific therapy. The use of
the telomerase inhibitor Imetelstat in patients with essential thrombocythmia or myelofibrosis as well
as the use of dendritic cell-based telomerase vaccination in AML patients with complete remissions are
promising examples for anti-telomerase targeted strategies in hematologic malignancies. In contrast,
the elevation in telomerase levels through treatment with androgens has become an exciting clinical
intervention for patients with BMFS. Here, we review recent developments, which highlight the
impact of telomeres and telomerase targeted therapies in hematologic dysfunctions.
: Human osteosarcoma (OS) is the most common primary malignant bone tumor occurring
most commonly in adolescents and young adults. Major improvements in disease-free survival have
been achieved by implementing a combination therapy consisting of radical surgical resection of the
tumor and systemic multi-agent chemotherapy. However, long-term survival remains poor, so novel
targeted therapies to improve outcomes for patients with osteosarcoma remains an area of active
research. This includes immunotherapy, photodynamic therapy, or treatment with nanoparticles.
Cold atmospheric plasma (CAP), a highly reactive (partially) ionized physical state, has been shown
to inherit a significant anticancer capacity, leading to a new field in medicine called “plasma oncology.”
The current article summarizes the potential of CAP in the treatment of human OS and reviews the
underlying molecular mode of action.
Multiple evidence in animal models and in humans suggest a beneficial role of cold physical
plasma in wound treatment. Yet, risk assessment studies are important to further foster therapeutic
advancement and acceptance of cold plasma in clinics. Accordingly, we investigated the long-term
side effects of repetitive plasma treatment over 14 consecutive days in a rodent full-thickness ear
wound model. Subsequently, animals were housed for 350 days and sacrificed thereafter. In blood,
systemic changes of the pro-inflammatory cytokines interleukin 1β and tumor necrosis factor α
were absent. Similarly, tumor marker levels of α-fetoprotein and calcitonin remained unchanged.
Using quantitative PCR, the expression levels of several cytokines and tumor markers in liver,
lung, and skin were found to be similar in the control and treatment group as well. Likewise,
histological and immunohistochemical analysis failed to detect abnormal morphological changes
and the presence of tumor markers such as carcinoembryonic antigen, α-fetoprotein, or the neighbor
of Punc 11. Absence of neoplastic lesions was confirmed by non-invasive imaging methods such as
anatomical magnetic resonance imaging and positron emission tomography-computed tomography.
Our results suggest that the beneficial effects of cold plasma in wound healing come without apparent
side effects including tumor formation or chronic inflammation.
Determination of the Pathological Features of NPC1 Variants in a Cellular Complementation Test
(2019)
Niemann-Pick Type C (NP-C) is a rare disorder of lipid metabolism caused by mutations
within the NPC1 and NPC2 genes. NP-C is a neurovisceral disease leading to a heterogeneous,
multisystemic spectrum of symptoms in those affected. Until now, there is no investigative tool to
demonstrate the significance of single variants within the NPC genes. Hence, the aim of the study
was to establish a test that allows for an objective assessment of the pathological potential of NPC1
gene variants. Chinese hamster ovary cells defective in the NPC1 gene accumulate cholesterol in
lysosomal storage organelles. The cells were transfected with NPC1-GFP plasmid vectors carrying
distinct sequence variants. Filipin staining was used to test for complementation of the phenotype.
The known variant p.Ile1061Thr showed a significantly impaired cholesterol clearance after 12 and
24 h compared to the wild type. Among the investigated variants, p.Ser954Leu and p.Glu1273Lys
showed decelerated cholesterol clearance as well. The remaining variants p.Gln60His, p.Val494Met,
and p.Ile787Val showed a cholesterol clearance indistinguishable from wild type. Further, p.Ile1061Thr
acquired an enhanced clearance ability upon 25-hydroxycholesterol treatment. We conclude that the
variants that caused an abnormal clearance phenotype are highly likely to be of clinical relevance.
Moreover, we present a system that can be utilized to screen for new drugs.
GPR68 (OGR1) belongs to the proton-sensing G protein-coupled receptors that are involved
in cellular adaptations to pH changes during tumour development. Although expression of GPR68
has been described in many tumour cell lines, little is known about its presence in human tumour
entities. We characterised the novel rabbit monoclonal anti-human GPR68 antibody 16H23L16
using various cell lines and tissue specimens. The antibody was then applied to a large series of
formalin-fixed, paraffin-embedded normal and neoplastic human tissue samples. Antibody specificity
was demonstrated in a Western blot analysis of GPR68-expressing cells using specific siRNAs.
Immunocytochemical experiments revealed pH-dependent changes in subcellular localisation of the
receptor and internalisation after stimulation with lorazepam. In normal tissue, GPR68 was present in
glucagon-producing islet cells, neuroendocrine cells of the intestinal tract, gastric glands, granulocytes,
macrophages, muscle layers of arteries and arterioles, and capillaries. GPR68 was also expressed
in neuroendocrine tumours, where it may be a positive prognostic factor, in pheochromocytomas,
cervical adenocarcinomas, and endometrial cancer, as well as in paragangliomas, medullary thyroid
carcinomas, gastrointestinal stromal tumours, and pancreatic adenocarcinomas. Often, tumour
capillaries were also strongly GPR68-positive. The novel antibody 16H23L16 will be a valuable tool for
basic research and for identifying GPR68-expressing tumours during histopathological examinations.
Renal drug transporters such as the organic cation transporters (OCTs), organic anion
transporters (OATs) and multidrug resistance proteins (MRPs) play an important role in the tubular
secretion of many drugs influencing their efficacy and safety. However, only little is known about
the distinct protein abundance of these transporters in human kidneys, and about the impact of
age and gender as potential factors of inter-subject variability in their expression and function.
The aim of this study was to determine the protein abundance of MDR1, MRP1-4, BCRP, OAT1-3,
OCT2-3, MATE1, PEPT1/2, and ORCTL2 by liquid chromatography-tandem mass spectrometry-based
targeted proteomics in a set of 36 human cortex kidney samples (20 males, 16 females; median age
53 and 55 years, respectively). OAT1 and 3, OCT2 and ORCTL2 were found to be most abundant
renal SLC transporters while MDR1, MRP1 and MRP4 were the dominating ABC transporters.
Only the expression levels of MDR1 and ORCTL2 were significantly higher abundant in older donors.
Moreover, we found several significant correlations between different transporters, which may
indicate their functional interplay in renal vectorial transport processes. Our data may contribute to
a better understanding of the molecular processes determining renal excretion of drugs.
Background: Recently, the expression of proteinase-activated receptor 2 (PAR2) has been
shown to be essential for activin receptor-like kinase 5 (ALK5)/SMAD-mediated signaling and cell
migration by transforming growth factor (TGF)-β1. However, it is not known whether activation
of non-SMAD TGF-β signaling (e.g., RAS–RAF–MEK–extracellular signal-regulated kinase (ERK)
signaling) is required for cell migration and whether it is also dependent on PAR2. Methods: RNA
interference was used to deplete cells of PAR2, followed by xCELLigence technology to measure
cell migration, phospho-immunoblotting to assess ERK1/2 activation, and co-immunoprecipitation
to detect a PAR2–ALK5 physical interaction. Results: Inhibition of ERK signaling with the MEK
inhibitor U0126 blunted the ability of TGF-β1 to induce migration in pancreatic cancer Panc1 cells.
ERK activation in response to PAR2 agonistic peptide (PAR2–AP) was strong and rapid, while it was
moderate and delayed in response to TGF-β1. Basal and TGF-β1-dependent ERK, but not SMAD
activation, was blocked by U0126 in Panc1 and other cell types indicating that ERK activation is
downstream or independent of SMAD signaling. Moreover, cellular depletion of PAR2 in HaCaT
cells strongly inhibited TGF-β1-induced ERK activation, while the biased PAR2 agonist GB88 at 10
and 100 µM potentiated TGF-β1-dependent ERK activation and cell migration. Finally, we provide
evidence for a physical interaction between PAR2 and ALK5. Our data show that both PAR2–APand TGF-β1-induced cell migration depend on ERK activation, that PAR2 expression is crucial for
TGF-β1-induced ERK activation, and that the functional cooperation of PAR2 and TGF-β1 involves a
physical interaction between PAR2 and ALK5
The platinum(II) complexes carboplatin (CBDCA), cisplatin (CDDP) and oxaliplatin
(1-OHP) are used as anticancer drugs in a large number of tumour chemotherapy regimens.
Many attempts have been made to combine Pt(II)-based chemotherapy with alternative treatment
strategies. One such alternative anticancer approach is known as photodynamic therapy (PDT),
where a non-toxic photosensitizer (PS) produces oxidative stress via the formation of reactive
oxygen species (ROS) after local illumination of the affected tissue. A very promising PS is
5,10,15,20-tetra(m-hydroxyphenyl)chlorin (mTHPC, Temoporfin), which is approved for the treatment
of head and neck cancer in Europe. In the present study, a combination of mTHPC-mediated PDT
and either CBDCA, CDDP, or 1-OHP was applied to five human cancer cell lines from different
tumour origins. Cytotoxicity was determined by the MTT assay and synergistic effects on cytotoxicity
were evaluated by calculation of Combination Indices (CI). Synergy was identified in some of the
combinations, for example, with 1-OHP in three of the tested cell lines but antagonism was also
observed for a number of combinations in certain cell lines. In cases of synergy, elevated ROS levels
were observed after combination but apoptosis induction was not necessarily increased compared
to a treatment with a single compound. Cell cycle analysis revealed a formation of apoptotic
subG1 populations and S phase as well as G2/M phase arrests after combination. In conclusion,
pre-treatment with mTHPC-PDT has the potential to sensitize some types of tumour cells towards
Pt(II) complexes, in particular 1-OHP but synergy is highly dependent on the type of cancer.
The multifunctional sphingosine-1-phosphate (S1P) is a lipid signaling molecule and central
regulator in the development of several cancer types. In recent years, intriguing information has
become available regarding the role of S1P in the progression of Glioblastoma multiforme (GBM),
the most aggressive and common brain tumor in adults. S1P modulates numerous cellular processes
in GBM, such as oncogenesis, proliferation and survival, invasion, migration, metastasis and stem cell
behavior. These processes are regulated via a family of five G-protein-coupled S1P receptors (S1PR1-5)
and may involve mainly unknown intracellular targets. Distinct expression patterns and multiple
intracellular signaling pathways of each S1PR subtype enable S1P to exert its pleiotropic cellular
actions. Several studies have demonstrated alterations in S1P levels, the involvement of S1PRs
and S1P metabolizing enzymes in GBM pathophysiology. While the tumorigenic actions of S1P
involve the activation of several kinases and transcription factors, the specific G-protein (Gi, Gq,
and G12/13)-coupled signaling pathways and downstream mediated effects in GBM remain to be
elucidated in detail. This review summarizes the recent findings concerning the role of S1P and its
receptors in GBM. We further highlight the current insights into the signaling pathways considered
fundamental for regulating the cellular processes in GMB and ultimately patient prognosis.
Sphingosine-1-phosphate (S1P) regulates the migration of follicular B cells
(B2 cells) and directs the positioning of Marginal zone B cells (MZ B cells) within the spleen. The
function of S1P signalling in the third B cell lineage, B1 B cells, mainly present in the pleural and
peritoneal cavity, has not yet been determined. Methods: S1P receptor expression was analysed
in peritoneal B cells by real-time polymerase chain reaction (qPCR). The chemotactic response to
S1P was studied in vitro. The role of S1P signalling was further explored in a s1p4
−/− mouse
strain. Results: Peritoneal B cells expressed considerable amounts of the S1P receptors 1 and 4
(S1P1 and S1P4, respectively). S1P1 showed differential expression between the distinct peritoneal B
cell lineages. While B2 cells showed no chemotactic response to S1P, B1 B cells showed a migration
response to S1P. s1p4
−/− mice displayed significant alterations in the composition of peritoneal
B cell populations, as well as a significant reduction of mucosal immunoglobulin A (IgA) in the
gut. Discussion: S1P signalling influences peritoneal B1 B cell migration. S1P4 deficiency alters the
composition of peritoneal B cell populations and reduces secretory IgA levels. These findings suggest
that S1P signalling may be a target to modulate B cell function in inflammatory intestinal pathologies.
Salivary glands provide secretory functions, including secretion of xenobiotics and among
them drugs. However, there is no published information about protein abundance of drug transporters
measured using reliable protein quantification methods. Therefore, mRNA expression and absolute
protein content of clinically relevant ABC (n = 6) and SLC (n = 15) family member transporters in the
human parotid gland, using the qRT-PCR and liquid chromatography-tandem mass spectrometry
(LC−MS/MS) method, were studied. The abundance of nearly all measured proteins ranged between
0.04 and 0.45 pmol/mg (OCT3 > MRP1 > PEPT2 > MRP4 > MATE1 > BCRP). mRNAs of ABCB1,
ABCC2, ABCC3, SLC10A1, SLC10A2, SLC22A1, SLC22A5, SLC22A6, SLC22A7, SLC22A8, SLCO1A2,
SLCO1B1, SLCO1B3 and SLCO2B1 were not detected. The present study provides, for the first time,
information about the protein abundance of membrane transporters in the human parotid gland,
which could further be used to define salivary bidirectional transport (absorption and secretion)
mechanisms of endogenous compounds and xenobiotics.
Bioinformatics Algorithms and Predictive Models: The Grand Challenge in Computational Virology
(2021)
Never in the past has the relevance of bioinformatic and predictive tools been more central
in the field of virology as today. SARS-CoV-2 has brought along a huge health burden, but also
a deeper awareness that scientific progress can no longer be effective without extensive systems
for data storage, sharing and analysis, as well as computational tools dedicated to molecular
epidemiology, NGS data analysis, prediction of drug targets, multi-OMIC data integration, and
many other applications.
Objectives: An inverse relationship between education and cardiovascular risk has been described, however, the combined association of education, income, and neighborhood socioeconomic status with macrovascular disease is less clear. The aim of this study was to evaluate the association of educational level, equivalent household income and area deprivation with macrovascular disease in Germany.
Methods: Cross-sectional data from two representative German population-based studies, SHIP-TREND (n = 3,731) and KORA-F4 (n = 2,870), were analyzed. Multivariable logistic regression models were applied to estimate odds ratios and 95% confidence intervals for the association between socioeconomic determinants and macrovascular disease (defined as self-reported myocardial infarction or stroke).
Results: The study showed a higher odds of prevalent macrovascular disease in men with low and middle educational level compared to men with high education. Area deprivation and equivalent income were not related to myocardial infarction or stroke in any of the models.
Conclusion: Educational level, but not income or area deprivation, is significantly related to the macrovascular disease in men. Effective prevention of macrovascular disease should therefore start with investing in individual education.
Although the nose, as a gateway for organism–environment interactions, may have a key role in asthmatic exacerbation, the rhinobiome of exacerbated children with asthma was widely neglected to date. The aim of this study is to understand the microbiome, the microbial immunology, and the proteome of exacerbated children and adolescents with wheeze and asthma. Considering that a certain proportion of wheezers may show a progression to asthma, the comparison of both groups provides important information regarding clinical and phenotype stratification. Thus, deep nasopharyngeal swab specimens, nasal epithelial spheroid (NAEsp) cultures, and blood samples of acute exacerbated wheezers (WH), asthmatics (AB), and healthy controls (HC) were used for culture (n = 146), 16 S-rRNA gene amplicon sequencing (n = 64), and proteomic and cytokine analyses. Interestingly, Proteobacteria were over-represented in WH, whereas Firmicutes and Bacteroidetes were associated with AB. In contrast, Actinobacteria commonly colonized HCs. Moreover, Staphylococcaceae, Enterobacteriaceae, Burkholderiaceae, Xanthobacteraceae, and Sphingomonadaceae were significantly more abundant in AB compared to WH and HC. The α-diversity analyses demonstrated an increase of bacterial abundance levels in atopic AB and a decrease in WH samples. Microbiome profiles of atopic WH differed significantly from atopic AB, whereby atopic samples of WH were more homogeneous than those of non-atopic subjects. The NAEsp bacterial exposure experiments provided a disrupted epithelial cell integrity, a cytokine release, and cohort-specific proteomic differences especially for Moraxella catarrhalis cultures. This comprehensive dataset contributes to a deeper insight into the poorly understood plasticity of the nasal microbiota, and, in particular, may enforce our understanding in the pathogenesis of asthma exacerbation in childhood.
Coastal sand dunes near the Baltic Sea are a dynamic environment marking the boundary between land and sea and oftentimes covered by Scots pine (Pinus sylvestris L.) forests. Complex climate-environmental interactions characterize these ecosystems and largely determine the productivity and state of these coastal forests. In the face of future climate change, understanding interactions between coastal tree growth and climate variability is important to promote sustainable coastal forests. In this study, we assessed the effect of microsite conditions on tree growth and the temporal and spatial variability of the relationship between climate and Scots pine growth at nine coastal sand dune sites located around the south Baltic Sea. At each site, we studied the growth of Scots pine growing at microsites located at the ridge and bottom of a dune and built a network of 18 ring-width and 18 latewood blue intensity chronologies. Across this network, we found that microsite has a minor influence on ring-width variability, basal area increment, latewood blue intensity, and climate sensitivity. However, at the local scale, microsite effects turned out to be important for growth and climate sensitivity at some sites. Correlation analysis indicated that the strength and direction of climate-growth responses for the ring-width and blue intensity chronologies were similar for climate variables over the 1903–2016 period. A strong and positive relationship between ring-width and latewood blue intensity chronologies with winter-spring temperature was detected at local and regional scales. We identified a relatively strong, positive influence of winter-spring/summer moisture availability on both tree-ring proxies. When climate-growth responses between two intervals (1903–1959, 1960–2016) were compared, the strength of growth responses to temperature and moisture availability for both proxies varied. More specifically, for the ring-width network, we identified decreasing temperature-growth responses, which is in contrast to the latewood blue intensity network, where we documented decreasing and increasing temperature-growth relationships in the north and south respectively. We conclude that coastal Scots pine forests are primarily limited by winter-spring temperature and winter-spring/summer drought despite differing microsite conditions. We detected some spatial and temporal variability in climate-growth relationships that warrant further investigation.
Determining the effect of a changing climate on tree growth will ultimately depend on our understanding of wood formation processes and how they can be affected by environmental conditions. In this context, monitoring intra-annual radial growth with high temporal resolution through point dendrometers has often been used. Another widespread approach is the microcoring method to follow xylem and phloem formation at the cellular level. Although both register the same biological process (secondary growth), given the limitations of each method, each delivers specific insights that can be combined to obtain a better picture of the process as a whole. To explore the potential of visualizing combined dendrometer and histological monitoring data and scrutinize intra-annual growth data on both dimensions (dendrometer → continuous; microcoring → discrete), we developed DevX (Dendrometer vs. Xylogenesis), a visualization application using the “Shiny” package in the R programming language. The interactive visualization allows the display of dendrometer curves and the overlay of commonly used growth model fits (Gompertz and Weibull) as well as the calculation of wood phenology estimates based on these fits (growth onset, growth cessation, and duration). Furthermore, the growth curves have interactive points to show the corresponding histological section, where the amount and development stage of the tissues at that particular time point can be observed. This allows to see the agreement of dendrometer derived phenology and the development status at the cellular level, and by this help disentangle shrinkage and swelling due to water uptake from actual radial growth. We present a case study with monitoring data for Acer pseudoplatanus L., Fagus sylvatica L., and Quercus robur L. trees growing in a mixed stand in northeastern Germany. The presented application is an example of the innovative and easy to access use of programming languages as basis for data visualization, and can be further used as a learning tool in the topic of wood formation and its ecology. Combining continuous dendrometer data with the discrete information from histological-sections provides a tool to identify active periods of wood formation from dendrometer series (calibrate) and explore monitoring datasets.
Food craving (FC) peaks are highly context-dependent and variable. Accurate prediction of FC might help preventing disadvantageous eating behavior. Here, we examine whether data from 2 weeks of ecological momentary assessment (EMA) questionnaires on stress and emotions (active EMA, aEMA) alongside temporal features and smartphone sensor data (passive EMA, pEMA) are able to predict FCs ~2.5 h into the future in N = 46 individuals. A logistic prediction approach with feature dimension reduction via Best Item Scale that is Cross-Validated, Weighted, Informative and Transparent (BISCWIT) was performed. While overall prediction accuracy was acceptable, passive sensing data alone was equally predictive to psychometric data. The frequency of which single predictors were considered for a model was rather balanced, indicating that aEMA and pEMA models were fully idiosyncratic.
Reduction and oxidation reactions are essential for biochemical processes. They are part of metabolic pathways and signal transduction. Reactive oxygen species (ROS) as second messengers and oxidative modifications of cysteinyl (Cys) residues are key to transduce and translate intracellular and intercellular signals. Dysregulation of cellular redox signaling is known as oxidative distress, which has been linked to various pathologies, including neurodegeneration. Alzheimer's disease (AD) is a neurodegenerative pathology linked to both, abnormal amyloid precursor protein (APP) processing, generating Aβ peptide, and Tau hyperphosphorylation and aggregation. Signs of oxidative distress in AD include: increase of ROS (H2O2, O2•−), decrease of the levels or activities of antioxidant enzymes, abnormal oxidation of macromolecules related to elevated Aβ production, and changes in mitochondrial homeostasis linked to Tau phosphorylation. Interestingly, Cys residues present in APP form disulfide bonds that are important for intermolecular interactions and might be involved in the aggregation of Aβ. Moreover, two Cys residues in some Tau isoforms have been shown to be essential for Tau stabilization and its interaction with microtubules. Future research will show the complexities of Tau, its interactome, and the role that Cys residues play in the progression of AD. The specific modification of cysteinyl residues in redox signaling is also tightly connected to the regulation of various metabolic pathways. Many of these pathways have been found to be altered in AD, even at very early stages. In order to analyze the complex changes and underlying mechanisms, several AD models have been developed, including animal models, 2D and 3D cell culture, and ex-vivo studies of patient samples. The use of these models along with innovative, new redox analysis techniques are key to further understand the importance of the redox component in Alzheimer's disease and the identification of new therapeutic targets in the future.
Background
The Symbol Digit Modalities Test (SDMT) is most frequently used to test processing speed in patients with multiple sclerosis (MS). Functional imaging studies emphasize the importance of frontal and parietal areas for task performance, but the influence of frontoparietal tracts has not been thoroughly studied. We were interested in tract-specific characteristics and their association with processing speed in MS patients.
Methods
Diffusion tensor imaging was obtained in 100 MS patients and 24 healthy matched controls to compare seed-based tract characteristics descending from the superior parietal lobule [Brodman area 7A (BA7A)], atlas-based tract characteristics from the superior longitudinal fasciculus (SLF), and control tract characteristics from the corticospinal tract (CST) and their respective association with ability on the SDMT.
Results
Patients had decreased performance on the SDMT and decreased white matter volume (each p < 0.05). The mean fractional anisotropy (FA) for the BA7A tract and CST (p < 0.05), but not the SLF, differed between MS patients and controls. Furthermore, only the FA of the SLF was positively associated with SDMT performance even after exclusion of the lesions within the tract (r = 0.25, p < 0.05). However, only disease disability and total white matter volume were associated with information processing speed in a linear regression model.
Conclusions
Processing speed in MS is associated with the structural integrity of frontoparietal white matter tracts.
Upon antigen recognition by the T cell receptor (TCR), a complex signaling network orchestrated by protein-tyrosine kinases (PTKs) and protein-tyrosine phosphatases (PTPs) regulates the transmission of the extracellular signal to the nucleus. The role of the PTPs Src-homology 2 (SH2) domain-containing phosphatase 1 (SHP1, Ptpn6) and Src-homology 2 (SH2) domain-containing phosphatase 2 (SHP2, Ptpn11) have been studied in various cell types including T cells. Whereas SHP1 acts as an essential negative regulator of the proximal steps in T cell signalling, the role of SHP2 in T cell activation is still a matter of debate. Here, we analyzed the role of the constitutively active SHP2-D61Y-mutant in T cell activation using knock-in mice expressing the mutant form Ptpn11D61Y
in T cells. We observed reduced numbers of CD8+ and increased numbers of CD4+ T cells in the bone marrow and spleen of young and aged SHP2-D61Y-mutant mice as well as in Influenza A Virus (IAV)-infected mice compared to controls. In addition, we found elevated frequencies of effector memory CD8+ T cells and an upregulation of the programmed cell death protein 1 (PD-1)-receptor on both CD4+ and CD8+ T cells. Functional analysis of SHP2-D61Y-mutated T cells revealed an induction of late apoptosis/necrosis, a reduced proliferation and altered signaling upon TCR stimulation. However, the ability of D61Y-mutant mice to clear viral infection was not affected. In conclusion, our data indicate an important regulatory role of SHP2 in T cell function, where the effect is determined by the kinetics of SHP2 phosphatase activity and differs in the presence of the permanently active and the temporally regulated phosphatase. Due to interaction of SHP2 with the PD-1-receptor targeting the protein-tyrosine phosphatase might be a valuable tool to enhance T cell activities in immunotherapy.
Many of the world’s most biodiverse regions are found in the poorest and second most populous continent of Africa; a continent facing exceptional challenges. Africa is projected to quadruple its population by 2100 and experience increasingly severe climate change and environmental conflict—all of which will ravage biodiversity. Here we assess conservation threats facing Africa and consider how these threats will be affected by human population growth, economic expansion, and climate change. We then evaluate the current capacity and infrastructure available to conserve the continent’s biodiversity. We consider four key questions essential for the future of African conservation: (1) how to build societal support for conservation efforts within Africa; (2) how to build Africa’s education, research, and management capacity; (3) how to finance conservation efforts; and (4) is conservation through development the appropriate approach for Africa? While the challenges are great, ways forward are clear, and we present ideas on how progress can be made. Given Africa’s current modest capacity to address its biodiversity crisis, additional international funding is required, but estimates of the cost of conserving Africa’s biodiversity are within reach. The will to act must build on the sympathy for conservation that is evident in Africa, but this will require building the education capacity within the continent. Considering Africa’s rapidly growing population and the associated huge economic needs, options other than conservation through development need to be more effectively explored. Despite the gravity of the situation, we believe that concerted effort in the coming decades can successfully curb the loss of biodiversity in Africa.
Feasible Cluster Model Method for Simulating the Redox Potentials of Laccase CueO and Its Variant
(2022)
Laccases are regarded as versatile green biocatalysts, and recent scientific research has focused on improving their redox potential for broader industrial and environmental applications. The density functional theory (DFT) quantum mechanics approach, sufficiently rigorous and efficient for the calculation of electronic structures, is conducted to better comprehend the connection between the redox potential and the atomic structural feature of laccases. According to the crystal structure of wild type laccase CueO and its variant, a truncated miniature cluster model method was established in this research. On the basic of thermodynamic cycle, the overall Gibbs free energy variations before and after the one-electron reduction were calculated. It turned out that the trends of redox potentials to increase after variant predicted by the theoretical calculations correlated well with those obtained by experiments, thereby validating the feasibility of this cluster model method for simulating the redox potentials of laccases.
Photosynthetic activity in both algae and cyanobacteria changes in response to cues of predation
(2022)
A plethora of adaptive responses to predation has been described in microscopic aquatic producers. Although the energetic costs of these responses are expected, with their consequences going far beyond an individual, their underlying molecular and metabolic mechanisms are not fully known. One, so far hardly considered, is if and how the photosynthetic efficiency of phytoplankton might change in response to the predation cues. Our main aim was to identify such responses in phytoplankton and to detect if they are taxon-specific. We exposed seven algae and seven cyanobacteria species to the chemical cues of an efficient consumer, Daphnia magna, which was fed either a green alga, Acutodesmus obliquus, or a cyanobacterium, Synechococcus elongatus (kairomone and alarm cues), or was not fed (kairomone alone). In most algal and cyanobacterial species studied, the quantum yield of photosystem II increased in response to predator fed cyanobacterium, whereas in most of these species the yield did not change in response to predator fed alga. Also, cyanobacteria tended not to respond to a non-feeding predator. The modal qualitative responses of the electron transport rate were similar to those of the quantum yield. To our best knowledge, the results presented here are the broadest scan of photosystem II responses in the predation context so far.
Introduction
Privacy concerns are an important barrier to adoption and continued use of digital technologies, particularly in the health sector. With the introduction of mobile health applications (mHealth apps), the construct of app information privacy concerns has received increased attention. However, few validated measures exist to capture said concerns in population samples, although they can help to improve public health efforts.
Methods
Using a cross-sectional survey of German adults (mean age = 35.62; 63.5% female), this study examined psychometric properties of the app information privacy concerns scale (AIPC). Analyses comprised confirmatory factor analysis, factorial validity (exploratory factor analysis), internal consistency, convergent validity (i.e., correlations with privacy victimhood, and app privacy concerns), and discriminant validity (i.e., daily app use, adoption intentions, and attitudes toward COVID-19 contact tracing app use).
Results
The analysis did not support the proposed three-factor structure of the AIPC (i.e., anxiety, personal attitude, and requirements). Instead, a four-factor model was preferable that differentiated requirements regarding disclosure policies, and personal control. In addition, factors mirroring anxiety and personal attitude were extracted, but shared a significant overlap. However, these factors showed good reliability, convergent and discriminant validity.
Discussion
The findings underline the role of app information privacy concerns as a significant barrier to mHealth app use. In this context, anxiety and personal attitudes seemed particularly relevant, which has implications for health communication. Moreover, the observed differentiation of external (disclosure) and internal (control) requirements aligns with health behavior change models and thus is a promising area for future research.
Background
Observational and in-vivo research suggested a bidirectional relationship between depression and periodontitis. We estimated the genetic correlation and examined directionality of causation.
Methods
The study used summary statistics from published genome wide association studies, with sample sizes ranging from 45,563 to 797,563 individuals of European ancestry. We performed linkage disequilibrium score regression (LDSC) to estimate global correlation and used Heritability Estimation from Summary Statistics (ρ-HESS) to further examine local genetic correlation. Latent Heritable Confounder Mendelian randomization (LHC-MR), Causal Analysis using Summary Effect estimates (CAUSE), and conventional MR approaches assessed bidirectional causation.
Results
LDSC observed only weak genetic correlation (rg = 0.06, P-Value = 0.619) between depression and periodontitis. Analysis of local genetic correlation using ρ-HESS did not reveal loci of significant local genetic covariance. LHC-MR, CAUSE and conventional MR models provided no support for bidirectional causation between depression and periodontitis, with odds ratios ranging from 1.00 to 1.06 in either direction.
Conclusions
Results do not support shared heritability or a causal connection between depression and periodontitis.
Polybutylene adipate terephthalate (PBAT) is a biodegradable alternative to polyethylene and can be broadly used in various applications. These polymers can be degraded by hydrolases of terrestrial and aquatic origin. In a previous study, we identified tandem PETase-like hydrolases (Ples) from the marine microbial consortium I1 that were highly expressed when a PBAT blend was supplied as the only carbon source. In this study, the tandem Ples, Ple628 and Ple629, were recombinantly expressed and characterized. Both enzymes are mesophilic and active on a wide range of oligomers. The activities of the Ples differed greatly when model substrates, PBAT-modified polymers or PET nanoparticles were supplied. Ple629 was always more active than Ple628. Crystal structures of Ple628 and Ple629 revealed a structural similarity to other PETases and can be classified as member of the PETases IIa subclass, α/β hydrolase superfamily. Our results show that the predicted functions of Ple628 and Ple629 agree with the bioinformatic predictions, and these enzymes play a significant role in the plastic degradation by the consortium.
Melioidosis is a seasonal infectious disease in tropical and subtropical areas caused by the soil bacterium Burkholderia pseudomallei. In many parts of the world, including South West India, most cases of human infections are reported during times of heavy rainfall, but the underlying causes of this phenomenon are not fully understood. India is among the countries with the highest predicted melioidosis burden globally, but there is very little information on the environmental distribution of B. pseudomallei and its determining factors. The present study aimed (i) to investigate the prevalence of B. pseudomallei in soil in South West India, (ii) determine geochemical factors associated with B. pseudomallei presence and (iii) look for potential seasonal patterns of B. pseudomallei soil abundance. Environmental samplings were performed in two regions during the monsoon and post-monsoon season and summer from July 2016 to November 2018. We applied direct quantitative real time PCR (qPCR) together with culture protocols to overcome the insufficient sensitivity of solely culture-based B. pseudomallei detection from soil. A total of 1,704 soil samples from 20 different agricultural sites were screened for the presence of B. pseudomallei. Direct qPCR detected B. pseudomallei in all 20 sites and in 30.2% (517/1,704) of all soil samples, whereas only two samples from two sites were culture-positive. B. pseudomallei DNA-positive samples were negatively associated with the concentration of iron, manganese and nitrogen in a binomial logistic regression model. The highest number of B. pseudomallei-positive samples (42.6%, p < 0.0001) and the highest B. pseudomallei loads in positive samples [median 4.45 × 103 genome equivalents (GE)/g, p < 0.0001] were observed during the monsoon season and eventually declined to 18.9% and a median of 1.47 × 103 GE/g in summer. In conclusion, our study from South West India shows a wide environmental distribution of B. pseudomallei, but also considerable differences in the abundance between sites and within single sites. Our results support the hypothesis that nutrient-depleted habitats promote the presence of B. pseudomallei. Most importantly, the highest B. pseudomallei abundance in soil is seen during the rainy season, when melioidosis cases occur.
Editorial: Streptococci in infectious diseases – pathogenic mechanisms and host immune responses
(2022)
Complex problem solving (CPS) can be interpreted as the number of psychological mechanisms that allow us to reach our targets in difficult situations, that can be classified as complex, dynamic, non-transparent, interconnected, and multilayered, and also polytelic. The previous results demonstrated associations between the personality dimensions neuroticism, conscientiousness, and extraversion and problem-solving performance. However, there are no studies dealing with personality disorders in connection with CPS skills. Therefore, the current study examines a clinical sample consisting of people with personality and/or depressive disorders. As we have data for all the potential personality disorders and also data from each patient regarding to potential depression, we meet the whole range from healthy to impaired for each personality disorder and for depression. We make use of a unique operationalization: CPS was surveyed in a simulation game, making use of the microworld approach. This study was designed to investigate the hypothesis that personality traits are related to CPS performance. Results show that schizotypal, histrionic, dependent, and depressive persons are less likely to successfully solve problems, while persons having the additional behavioral characteristics of resilience, action orientation, and motivation for creation are more likely to successfully solve complex problems.
Objective
Obesity, often associated with non-alcoholic fatty liver disease (NAFLD), is characterized by an imbalance between energy expenditure and food intake, which is also reflected by desensitization of fibroblast growth factor 21 (FGF21). FGF21 is strongly influenced, among others, by TNFα, which is known to be upregulated in obesity-induced inflammation. Successful long-term treatments of NAFLD might be dietary modification, exercise, or fasting.
Materials and methods
Whether succeeded NAFLD recovery is linked with improved FGF21 sensitivity and finally reverted FGF21 resistance was the focus of the present study. For this purpose, mice received a high-fat diet (HFD) for 6 months to establish obesity. Afterward, the mice were subjected to three different weight loss interventions, namely, dietary change to low-fat diet (LFD), treadmill training, and/or time-restricted feeding for additional 6 months, whereas one group remained on HFD.
Results
In addition to the expected decrease in NAFLD activity with dietary change, this was also observed in the HFD group with additional time-restricted feeding. There was also an associated decrease in hepatic TNFα and FGF21 expression and an increase in ß-klotho expression, demonstrated mainly by using principal component analysis. Pearson correlation analysis shows that independent of any intervention, TNFα expression decreased with improved NAFLD recovery. This was accompanied with higher FGF21 sensitivity, as expressed by an increase in β-klotho and FGFR1c expression and concomitantly decreased FGF21 levels.
Conclusion
In summary, we conclude that successful NAFLD therapy is associated with a reversion of the TNFα-triggered FGF21-resistant state or desensitization.
Introduction
Neurofilament light (NfL) can be detected in blood of healthy individuals and at elevated levels in those with different neurological diseases. We investigated if the choice of biological matrix can affect results when using NfL as biomarker in epidemiological studies.
Method
We obtained paired serum and EDTA-plasma samples of 299 individuals aged 37–67 years (BiDirect study) and serum samples of 373 individuals aged 65–83 years (MEMO study). In BiDirect, Passing–Bablok analyses were performed to assess proportional and systematic differences between biological matrices. Associations between serum or EDTA-plasma NfL and renal function (serum creatinine, serum cystatin C, glomerular filtration rate, and kidney disease) were investigated using linear or logistic regression, respectively. All regression coefficients were estimated (1) per one ng/L increase and (2) per one standard deviation increase (standardization using z-scores). In MEMO, regression coefficients were estimated (1) per one ng/L increase of serum or calculated EDTA-plasma NfL and (2) per one standard deviation increase providing a comparison to the results from BiDirect.
Results
We found proportional and systematic differences between paired NfL measurements in BiDirect, i.e., serum NfL [ng/L] = −0.33 [ng/L] + 1.11 × EDTA-plasma NfL [ng/L]. Linear regression coefficients for the associations between NfL and renal function did not vary between the different NfL measurements. In MEMO, one standard deviation increase in serum NfL was associated with greater changes in the outcomes than in BiDirect.
Conclusion
Although there are differences between serum and EDTA-plasma NfL, results can be used interchangeably if standardized values are used.
Background
Fatigue is a common symptom in patients with multiple sclerosis. Several studies suggest that outdoor temperature can impact fatigue severity, but a systematic study of seasonal variations is lacking.
Methods
Fatigue was assessed with the Fatigue Scale for Motor and Cognitive Functions (FSMC) in a temperate climatic zone with an average outdoor temperature of 8.8°C. This study included 258 patients with multiple sclerosis from 572 visits temporally distributed over the year. The data were adjusted for age, sex, cognition, depression, disease severity, and follow-up time. Linear regression models were performed to determine whether the temporal course of fatigue was time-independent, linearly time dependent, or non-linearly time dependent.
Results
Fatigue was lowest during January (mean FSMC: 49.84) and highest during August (mean FSMC: 53.88). The regression analysis showed the best fit with a model that included months + months2, which was a non-linear time dependency. Mean FSMC per month correlated significantly with the average monthly temperature (ρ = 0.972; p < 0.001).
Conclusion
In multiple sclerosis, fatigue showed a natural temporal fluctuation. Fatigue was higher during summer compared to winter, with a significant relationship of fatigue with outdoor temperature. This finding should be carefully taken into account when clinically monitoring patients over time to not interpret higher or lower scores independent of seasonal aspects.
Self-regulated learning (SRL) is critical for learning across tasks, domains, and contexts. Despite its importance, research shows that not all learners are equally skilled at accurately and dynamically monitoring and regulating their self-regulatory processes. Therefore, learning technologies, such as intelligent tutoring systems (ITSs), have been designed to measure and foster SRL. This paper presents an overview of over 10 years of research on SRL with MetaTutor, a hypermedia-based ITS designed to scaffold college students’ SRL while they learn about the human circulatory system. MetaTutor’s architecture and instructional features are designed based on models of SRL, empirical evidence on human and computerized tutoring principles of multimedia learning, Artificial Intelligence (AI) in educational systems for metacognition and SRL, and research on SRL from our team and that of other researchers. We present MetaTutor followed by a synthesis of key research findings on the effectiveness of various versions of the system (e.g., adaptive scaffolding vs. no scaffolding of self-regulatory behavior) on learning outcomes. First, we focus on findings from self-reports, learning outcomes, and multimodal data (e.g., log files, eye tracking, facial expressions of emotion, screen recordings) and their contributions to our understanding of SRL with an ITS. Second, we elaborate on the role of embedded pedagogical agents (PAs) as external regulators designed to scaffold learners’ cognitive and metacognitive SRL strategy use. Third, we highlight and elaborate on the contributions of multimodal data in measuring and understanding the role of cognitive, affective, metacognitive, and motivational (CAMM) processes. Additionally, we unpack some of the challenges these data pose for designing real-time instructional interventions that scaffold SRL. Fourth, we present existing theoretical, methodological, and analytical challenges and briefly discuss lessons learned and open challenges.
Essential Oils as Multicomponent Mixtures and Their Potential for Human Health and Well-Being
(2022)
Essential oils (EOs) and their individual volatile organic constituents have been an inherent part of our civilization for thousands of years. They are widely used as fragrances in perfumes and cosmetics and contribute to a healthy diet, but also act as active ingredients of pharmaceutical products. Their antibacterial, antiviral, and anti-inflammatory properties have qualified EOs early on for both, the causal and symptomatic therapy of a number of diseases, but also for prevention. Obtained from natural, mostly plant materials, EOs constitute a typical example of a multicomponent mixture (more than one constituent substances, MOCS) with up to several hundreds of individual compounds, which in a sophisticated composition make up the property of a particular complete EO. The integrative use of EOs as MOCS will play a major role in human and veterinary medicine now and in the future and is already widely used in some cases, e.g., in aromatherapy for the treatment of psychosomatic complaints, for inhalation in the treatment of respiratory diseases, or topically administered to manage adverse skin diseases. The diversity of molecules with different functionalities exhibits a broad range of multiple physical and chemical properties, which are the base of their multi-target activity as opposed to single isolated compounds. Whether and how such a broad-spectrum effect is reflected in natural mixtures and which kind of pharmacological potential they provide will be considered in the context of ONE Health in more detail in this review.
Exogenous glucocorticoids increase the risk for osteoporosis, but the role of endogenous glucocorticoids remains elusive. Here, we describe the generation and validation of a loss- and a gain-of-function model of the cortisol producing enzyme 11β-HSD1 (HSD11B1) to modulate the endogenous glucocorticoid conversion in SCP-1 cells — a model for human mesenchymal stem cells capable of adipogenic and osteogenic differentiation. CRISPR-Cas9 was successfully used to generate a cell line carrying a single base duplication and a 5 bp deletion in exon 5, leading to missense amino acid sequences after codon 146. These inactivating genomic alterations were validated by deep sequencing and by cloning with subsequent capillary sequencing. 11β-HSD1 protein levels were reduced by 70% in the knockout cells and cortisol production was not detectable. Targeted chromosomal integration was used to stably overexpress HSD11B1. Compared to wildtype cells, HSD11B1 overexpression resulted in a 7.9-fold increase in HSD11B1 mRNA expression, a 5-fold increase in 11β-HSD1 protein expression and 3.3-fold increase in extracellular cortisol levels under adipogenic differentiation. The generated cells were used to address the effects of 11β-HSD1 expression on adipogenic and osteogenic differentiation. Compared to the wildtype, HSD11B1 overexpression led to a 3.7-fold increase in mRNA expression of lipoprotein lipase (LPL) and 2.5-fold increase in lipid production under adipogenic differentiation. Under osteogenic differentiation, HSD11B1 knockout led to enhanced alkaline phosphatase (ALP) activity and mRNA expression, and HSD11B1 overexpression resulted in a 4.6-fold and 11.7-fold increase in mRNA expression of Dickkopf-related protein 1 (DKK1) and LPL, respectively. Here we describe a HSD11B1 loss- and gain-of-function model in SCP-1 cells at genetic, molecular and functional levels. We used these models to study the effects of endogenous cortisol production on mesenchymal stem cell differentiation and demonstrate an 11β-HSD1 dependent switch from osteogenic to adipogenic differentiation. These results might help to better understand the role of endogenous cortisol production in osteoporosis on a molecular and cellular level.
Tafazzin—an acyltransferase—is involved in cardiolipin (CL) remodeling. CL is associated with mitochondrial function, structure and more recently with cell proliferation. Various tafazzin isoforms exist in humans. The role of these isoforms in cardiolipin remodeling is unknown. Aim of this study was to investigate if specific isoforms like Δ5 can restore the wild type phenotype with respect to CL composition, cellular proliferation and gene expression profile. In addition, we aimed to determine the molecular mechanism by which tafazzin can modulate gene expression by applying promoter analysis and (Ingenuity Pathway Analyis) IPA to genes regulated by TAZ-deficiency. Expression of Δ5 and rat full length TAZ in C6-TAZ- cells could fully restore CL composition and—as proven for Δ5—this is naturally associated with restoration of mitochondrial respiration. A similar restoration of CL-composition could not be observed after re-expression of an enzymatically dead full-length rat TAZ (H69L; TAZMut). Re-expression of only rat full length TAZ could restore proliferation rate. Surprisingly, the Δ5 variant failed to restore wild-type proliferation. Further, as expected, re-expression of the TAZMut variant completely failed to reverse the gene expression changes, whereas re-expression of the TAZ-FL variant largely did so and the Δ5 variant to somewhat less extent. Very likely TAZ-deficiency provokes substantial long-lasting changes in cellular lipid metabolism which contribute to changes in proliferation and gene expression, and are not or only very slowly reversible.
We present the first systematic literature review on stress and burnout in K−12 teachers during the COVID-19 pandemic. Based on a systematic literature search, we identified 17 studies that included 9,874 K−12 teachers from around the world. These studies showed some indication that burnout did increase during the COVID-19 pandemic. There were, however, almost no differences in the levels of stress and burnout experienced by K−12 teachers compared to individuals employed in other occupational fields. School principals' leadership styles emerged as an organizational characteristic that is highly relevant for K−12 teachers' levels of stress and burnout. Individual teacher characteristics associated with burnout were K−12 teachers' personality, self-efficacy in online teaching, and perceived vulnerability to COVID-19. In order to reduce stress, there was an indication that stress-management training in combination with training in technology use for teaching may be superior to stress-management training alone. Future research needs to adopt more longitudinal designs and examine the interplay between individual and organizational characteristics in the development of teacher stress and burnout during the COVID-19 pandemic and beyond.
To reduce global greenhouse gas emissions in order to limit global warming to 1.5°C, individuals and households play a key role. Behavior change interventions to promote pro-environmental behavior in individuals are needed to reduce emissions globally. This systematic literature review aims to assess the a) evidence-based effectiveness of such interventions and b) the content of very successful interventions without limiting the results to specific emitting sectors or countries. Based on the “PICOS” mnemonic and PRISMA statement, a search strategy was developed, and eligibility criteria were defined. Three databases (Embase, PsycInfo, and Web of Science) were searched to retrieve and review potential literature. As a result, 54 publications from 2010 to 2021 were included in the analysis. The results show that most interventions only have small positive effects or none at all. A total of 15 very successful interventions focused on the sectors of mobility, energy, and waste and incorporated improved (infra-) structures, education, feedback, enablement or made the sustainable option the default. Six evidence-based recommendations for content, timing, and setting are deducted and given for interventions on enhancing pro-environmental behavior (PEB). In summary, although the various interventions and intervention types to promote PEB differ in their effectiveness, very successful interventions have common elements. Future research should focus on high-/low-impact and high-/low-cost behavior to develop interventions that aim at high-impact but low-cost behavior changes, or avoid low-impact but high-cost behavior.
The effects of climate change lead to increasing social injustice and hence justice is intrinsically linked to a socio-ecological transformation. In this study, we investigate whether justice sensitivity motivates pro-environmental intention (PEI) and behavior (PEB) and, if so, to what extent emotions and moral disengagement determine this process. For this purpose, we conducted two quota-sampling surveys (Study 1: N = 174, Study 2: N = 880). Multiple regression analyses in both studies suggest that a higher perception of injustice from a perpetrator’s, beneficiary’s, and observer’s perspective is associated with an increased PEI. However, moral disengagement best predicted PEB and PEI. Guilt and authentic pride were found to be emotional predictors of PEI. Additionally, mediation analyses demonstrated that guilt mediates the connection between both perpetrator and beneficiary sensitivity and PEI. These results suggest that when the predominant originators of climate change (i.e., individuals from industrialized countries) perceive global climate injustice from the perspective of a beneficiary or a perpetrator, they experience guilt and have a higher PEI. Based on this mechanism, it seems promising to render global injustice more salient to those responsible for activities that lead to climate change to motivate them to adapt their behavior. The role of moral disengagement and victim sensitivity as barriers to pro-environmental behavior is discussed in this context.
Alternative splicing (AS) is a major mechanism for gene expression in eukaryotes, increasing proteome diversity but also regulating transcriptome abundance. High temperatures have a strong impact on the splicing profile of many genes and therefore AS is considered as an integral part of heat stress response. While many studies have established a detailed description of the diversity of the RNAome under heat stress in different plant species and stress regimes, little is known on the underlying mechanisms that control this temperature-sensitive process. AS is mainly regulated by the activity of splicing regulators. Changes in the abundance of these proteins through transcription and AS, post-translational modifications and interactions with exonic and intronic cis-elements and core elements of the spliceosomes modulate the outcome of pre-mRNA splicing. As a major part of pre-mRNAs are spliced co-transcriptionally, the chromatin environment along with the RNA polymerase II elongation play a major role in the regulation of pre-mRNA splicing under heat stress conditions. Despite its importance, our understanding on the regulation of heat stress sensitive AS in plants is scarce. In this review, we summarize the current status of knowledge on the regulation of AS in plants under heat stress conditions. We discuss possible implications of different pathways based on results from non-plant systems to provide a perspective for researchers who aim to elucidate the molecular basis of AS under high temperatures.
Cryptochromes are evolutionary ancient blue-light photoreceptors that are part of the circadian clock in the nervous system of many organisms. Cryptochromes transfer information of the predominant light regime to the clock which results in the fast adjustment to photoperiod. Therefore, the clock is sensitive to light changes and can be affected by anthropogenic Artificial Light At Night (ALAN). This in turn has consequences for clock associated behavioral processes, e.g., diel vertical migration (DVM) of zooplankton. In freshwater ecosystems, the zooplankton genus Daphnia performs DVM in order to escape optically hunting predators and to avoid UV light. Concomitantly, Daphnia experience circadian changes in food-supply during DVM. Daphnia play the keystone role in the carbon-transfer to the next trophic level. Therefore, the whole ecosystem is affected during the occurrence of cyanobacteria blooms as cyanobacteria reduce food quality due to their production of digestive inhibitors (e.g., protease inhibitors). In other organisms, digestion is linked to the circadian clock. If this is also the case for Daphnia, the expression of protease genes should show a rhythmic expression following circadian expression of clock genes (e.g., cryptochrome 2). We tested this hypothesis and demonstrated that gene expression of the clock and of proteases was affected by ALAN. Contrary to our expectations, the activity of one type of proteases (chymotrypsins) was increased by ALAN. This indicates that higher protease activity might improve the diet utilization. Therefore, we treated D. magna with a chymotrypsin-inhibitor producing cyanobacterium and found that ALAN actually led to an increase in Daphnia’s growth rate in comparison to growth on the same cyanobacterium in control light conditions. We conclude that this increased tolerance to protease inhibitors putatively enables Daphnia populations to better control cyanobacterial blooms that produce chymotrypsin inhibitors in the Anthropocene, which is defined by light pollution and by an increase of cyanobacterial blooms due to eutrophication.
N6-methyladenosine (m6A) RNA methylation is an emerging epigenetic modification in recent years and epigenetic regulation of the immune response has been demonstrated, but the potential role of m6A modification in GBM tumor microenvironment (TME) cell infiltration and stemness remain unknown. The m6A modification patterns of 310 GBM samples were comprehensively evaluated based on 21 m6A regulators, and we systematically correlated these modification patterns with TME cell infiltration characteristics and stemness characteristics. Construction of m6Ascore to quantify the m6A modification patterns of individual GBM samples using a principal component analysis algorithm. We identified two distinct patterns of m6A modification. The infiltration characteristics of TME cells in these two patterns were highly consistent with the immunophenotype of the GBM, including the immune activation differentiation pattern and the immune desert dedifferentiation pattern. We also identified two modes of regulation of immunity and stemness by m6A methylation. Stromal activation and lack of effective immune infiltration were observed in the high m6Ascore subtype. Pan-cancer analysis results illustrate a significant correlation between m6AScore and tumor clinical outcome, immune infiltration, and stemness. Our work reveals that m6A modifications play an important role in the development of TME and stemness diversity and complexity. Patients with a low m6AScore showed significant therapeutic advantages and clinical benefits. Assessing the m6A modification pattern of individual tumors will help enhance our knowledge of TME infiltration and stemness characteristics, contribute to the development of immunotherapeutic strategies.