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Background: Network models are useful tools for researchers to simplify and understand investigated systems. Yet, the assessment of methods for network construction is often uncertain. Random resampling simulations can aid to assess methods, provided synthetic data exists for reliable network construction.
Objectives: We implemented a new Monte Carlo algorithm to create simulated data for network reconstruction, tested the influence of adjusted parameters and used simulations to select a method for network model estimation based on real-world data. We hypothesized, that reconstructs based on Monte Carlo data are scored at least as good compared to a benchmark.
Methods: Simulated data was generated in R using the Monte Carlo algorithm of the mcgraph package. Benchmark data was created by the huge package. Networks were reconstructed using six estimator functions and scored by four classification metrics. For compatibility tests of mean score differences, Welch’s t-test was used. Network model estimation based on real-world data was done by stepwise selection.
Samples: Simulated data was generated based on 640 input graphs of various types and sizes. The real-world dataset consisted of 67 medieval skeletons of females and males from the region of Refshale (Lolland) and Nordby (Jutland) in Denmark.
Results: Results after t-tests and determining confidence intervals (CI95%) show, that evaluation scores for network reconstructs based on the mcgraph package were at least as good compared to the benchmark huge. The results even indicate slightly better scores on average for the mcgraph package.
Conclusion: The results confirmed our objective and suggested that Monte Carlo data can keep up with the benchmark in the applied test framework. The algorithm offers the feature to use (weighted) un- and directed graphs and might be useful for assessing methods for network construction.
No evidence of growth impairment after forced migration in Polish school children after World War II
(2023)
Background: Migration is omnipresent. It can come hand in hand with emotional stress which is known to influence the growth of children.
Objective: The aim of this study was to analyse whether type of migration (forced or voluntary) and the geographic direction had influenced the growth of Polish children after World War II.
Sample and Methods: A sub dataset of 2,208 individuals between the ages of 2-20, created from data of the 2nd Polish Anthropological Survey carried out in 1966–1969, including anthropometrical data and social and demographic information based on questionnaire, was used to analyse migration effects.
Results: No association could be found between the direction of migration and the height of the children. The confidence intervals of the means of all classified migration categories overlap significantly and the effect size of the influence of migration category on height is ds=.140, which is too low to see any effects, even if there were one.
Conclusion: Neither forced nor voluntary migration in Poland after World War II led to a change in height in children of migrating families.
The discovery that certain diseases have specific miRNA signatures which correspond to disease progression opens a new biomarker category. The detection of these small non-coding RNAs is performed routinely using body fluids or tissues with real-time PCR, next-generation sequencing, or amplification-based miRNA assays. Antibody-based detection systems allow an easy onset handling compared to PCR or sequencing and can be considered as alternative methods to support miRNA diagnostic in the future. In this study, we describe the generation of a camelid heavy-chain-only antibody specifically recognizing miRNAs to establish an antibody-based detection method. The generation of nucleic acid-specific binders is a challenge. We selected camelid binders via phage display, expressed them as VHH as well as full-length antibodies, and characterized the binding to several miRNAs from a signature specific for dilated cardiomyopathy. The described workflow can be used to create miRNA-specific binders and establish antibody-based detection methods to provide an additional way to analyze disease-specific miRNA signatures.
Nutrition, size, and tempo
(2023)
Nutrition is a prerequisite, but not a regulator of growth. Growth is defined as increase in size over time. The understanding of growth includes an understanding of the binary concept of physical time and individual tempo. Excess food causes tempo acceleration. Food restriction delays tempo. Tempo reflects the pace of life. It is a dynamic physical response to a broad spectrum of social, economic, political, and emotional (SEPE) factors and can affect life expectancy. Variations in tempo create distortions of the z-score patterns of height and weight. Illness or intermediate food shortage lead to intermediate halts in development and create short dips in the z-score patterns. Children who develop throughout life at delayed pace usually run at lower z-scores for height and weight, and show a characteristic adolescent trough; children who develop throughout life at faster than average pace usually run at higher z-scores and show a characteristic adolescent peak in their z-score patterns. During adolescence, almost half of the height variance is due to tempo variation. There is not one tempo for the whole body. Different organ systems grow and mature at different pace.
The intake of high-fat diets (HFDs) containing large amounts of saturated long-chain fatty acids leads to obesity, oxidative stress, inflammation, and insulin resistance. The trace element selenium, as a crucial part of antioxidative selenoproteins, can protect against the development of diet-induced insulin resistance in white adipose tissue (WAT) by increasing glutathione peroxidase 3 (GPx3) and insulin receptor (IR) expression. Whether selenite (Se) can attenuate insulin resistance in established lipotoxic and obese conditions is unclear. We confirm that GPX3 mRNA expression in adipose tissue correlates with BMI in humans. Cultivating 3T3-L1 pre-adipocytes in palmitate-containing medium followed by Se treatment attenuates insulin resistance with enhanced GPx3 and IR expression and adipocyte differentiation. However, feeding obese mice a selenium-enriched high-fat diet (SRHFD) only resulted in a modest increase in overall selenoprotein gene expression in WAT in mice with unaltered body weight development, glucose tolerance, and insulin resistance. While Se supplementation improved adipocyte morphology, it did not alter WAT insulin sensitivity. However, mice fed a SRHFD exhibited increased insulin content in the pancreas. Overall, while selenite protects against palmitate-induced insulin resistance in vitro, obesity impedes the effect of selenite on insulin action and adipose tissue metabolism in vivo.
Collagen is the most abundant protein in mammals. In many tissues, collagen molecules assemble to form a hierarchical structure. In the smallest supramolecular unit, named fibril, each molecule is displaced in the axial direction with respect to its neighbors. This staggering creates a periodic gap and overlap regions, where the gap regions exhibit 20% less density. These fibril-forming collagens play an essential role in the strength of connective tissues. Despite much effort, directed at understanding collagen function and regulation, the influence of the chemical environment on the local structural and mechanical properties remains poorly understood. Recent studies, aimed at elucidating the effect of osmotic pressure, showed that collagen contracts upon water removal. This observation highlights the importance of water for the stabilization and mechanics of the collagen molecule.
Using collagen mimetic peptides (CMPs), which fold into triple helical structures reminiscent of natural collagen, the primary goal of this work was to investigate the effect of the osmotic pressure on specific collagen-mimetic sequences. CMPs were used as the model system as they provide sequence control, which is essential for discriminating local from global structural changes and for relating the observed effects to existing knowledge about the full-length collagen molecule. Of specific interest was the structure of individual collagen triple helices as well as their organization into self-assembled higher order structures. These key structural features were monitored with infrared spectroscopy (IR) and synchrotron X-ray scattering, while varying the osmotic pressure. For controlling the osmotic pressure, CMP powder samples were incubated in air of defined relative humidity, ranging from dry conditions to highly “humid”. In addition, to obtain more biologically relevant conditions, the CMPs were measured in ultrapure water and in solutions containing small molecule osmolytes.
Using the sequences (Pro-Pro-Gly)10, (Pro-Hyp-Gly)10 and (Hyp-Hyp-Gly)10, it was shown that CMPs with different degrees of proline hydroxylation (Hyp = hydroxyproline) exhibit a sequence-specific response to osmotic pressure. IR spectroscopy revealed that osmotic pressure changes affect the strength of the triple helix stabilizing, interchain hydrogen bond and that the extent of this change depends on the degree of hydroxylation. X-ray scattering experiments further showed that changes in osmotic pressure affect both the molecular length as well as the higher order organization of CMPs. Starting from a pseudo-hexagonal packing in the dry state, all three CMPs showed isotropic swelling when increasing the water content to approximately 1.2 water molecules per amino acid, again to different extents depending on the degree of hydroxylation. When increasing the water content further, this pseudo-hexagonal arrangement breaks down. In the fully hydrated state, each CMP is characterized by its own specific and more complex packing geometry.
While these changes in the lateral packing arrangement suggest swelling upon hydration, an overall decrease of the molecular length (i.e. contraction) was observed in the axial direction. Also for this structural feature, a strong dependency on the specific amino acid sequence was found. Interestingly, the observed contraction is the opposite of what has been reported for natural collagen. As (Pro-Pro-Gly)n, (Pro-Hyp-Gly)n and (Hyp-Hyp-Gly)n repeat units are found in collagen with a relatively high abundance, this suggests that other collagen sequence fragments need to respond to hydration in the opposite way to obtain a net elongation of the full-length collagen molecule.
To test this hypothesis, sequences predicted to be sensitive to osmotic pressure were considered. One such sequence, consisting of two repeat units (Ala-Arg-Gly-Ser-Asp-Gly), was inserted as a guest into a (Pro-Pro-Gly) host. When compared to the canonical CMP sequences investigated earlier, the lateral helix packing follows a similar trend with increasing hydration; however, the host-guest CMP axially elongates with increasing water content. This behavior is more similar to what has been found for natural collagen and suggests that different sequences do determine the molecular length of collagen sequences differently. Interestingly, the canonical sequences are more abundant in the overlap region while the guest sequence is found in the gap region. This allows to speculate that sequences in the gap and overlap regions possess a specifically fine-tuned local response to osmotic pressure changes. Clearly, more experiments with additional sequences are needed to confirm this.
In conclusion, the results obtained in this work indicate a highly sequence specific interaction between collagen and water. Osmotic pressure-induced conformational changes mostly originate from local geometries and bonding patterns and affect both the structure of individual triple helices as well as higher order assemblies. One key remaining question is how these conformational changes affect the local mechanical properties of the collagen molecule. As a first step, the stiffness (persistence length) of full-length collagen was determined using atomic force microscopy. In the future, experimental strategies need to be developed that allow for investigating the mechanical properties of specific collagen sequences, e.g. performing single-molecule force spectroscopy of CMPs.
Inverted perovskite solar cells still suffer from significant non-radiative recombination losses at the perovskite surface and across the perovskite/C₆₀ interface, limiting the future development of perovskite-based single- and multi-junction photovoltaics. Therefore, more effective inter- or transport layers are urgently required. To tackle these recombination losses, we introduce ortho-carborane as an interlayer material that has a spherical molecular structure and a three-dimensional aromaticity. Based on a variety of experimental techniques, we show that ortho-carborane decorated with phenylamino groups effectively passivates the perovskite surface and essentially eliminates the non-radiative recombination loss across the perovskite/C₆₀ interface with high thermal stability. We further demonstrate the potential of carborane as an electron transport material, facilitating electron extraction while blocking holes from the interface. The resulting inverted perovskite solar cells deliver a power conversion efficiency of over 23% with a low non-radiative voltage loss of 110 mV, and retain >97% of the initial efficiency after 400 h of maximum power point tracking. Overall, the designed carborane based interlayer simultaneously enables passivation, electron-transport and hole-blocking and paves the way toward more efficient and stable perovskite solar cells.
Cellulose and chitin are the most abundant polymeric, organic carbon source globally. Thus, microbes degrading these polymers significantly influence global carbon cycling and greenhouse gas production. Fungi are recognized as important for cellulose decomposition in terrestrial environments, but are far less studied in marine environments, where bacterial organic matter degradation pathways tend to receive more attention. In this study, we investigated the potential of fungi to degrade kelp detritus, which is a major source of cellulose in marine systems. Given that kelp detritus can be transported considerable distances in the marine environment, we were specifically interested in the capability of endophytic fungi, which are transported with detritus, to ultimately contribute to kelp detritus degradation. We isolated 10 species and two strains of endophytic fungi from the kelp Ecklonia radiata. We then used a dye decolorization assay to assess their ability to degrade organic polymers (lignin, cellulose, and hemicellulose) under both oxic and anoxic conditions and compared their degradation ability with common terrestrial fungi. Under oxic conditions, there was evidence that Ascomycota isolates produced cellulose-degrading extracellular enzymes (associated with manganese peroxidase and sulfur-containing lignin peroxidase), while Mucoromycota isolates appeared to produce both lignin and cellulose-degrading extracellular enzymes, and all Basidiomycota isolates produced lignin-degrading enzymes (associated with laccase and lignin peroxidase). Under anoxic conditions, only three kelp endophytes degraded cellulose. We concluded that kelp fungal endophytes can contribute to cellulose degradation in both oxic and anoxic environments. Thus, endophytic kelp fungi may play a significant role in marine carbon cycling via polymeric organic matter degradation.
Importance Alcohol consumption (AC) leads to death and disability worldwide. Ongoing discussions on potential negative effects of the COVID-19 pandemic on AC need to be informed by real-world evidence.
Objective To examine whether lockdown measures are associated with AC and consumption-related temporal and psychological within-person mechanisms.
Design, Setting, and Participants This quantitative, intensive, longitudinal cohort study recruited 1743 participants from 3 sites from February 20, 2020, to February 28, 2021. Data were provided before and within the second lockdown of the COVID-19 pandemic in Germany: before lockdown (October 2 to November 1, 2020); light lockdown (November 2 to December 15, 2020); and hard lockdown (December 16, 2020, to February 28, 2021).
Main Outcomes and Measures Daily ratings of AC (main outcome) captured during 3 lockdown phases (main variable) and temporal (weekends and holidays) and psychological (social isolation and drinking intention) correlates.
Results Of the 1743 screened participants, 189 (119 [63.0%] male; median [IQR] age, 37 [27.5-52.0] years) with at least 2 alcohol use disorder (AUD) criteria according to the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) yet without the need for medically supervised alcohol withdrawal were included. These individuals provided 14 694 smartphone ratings from October 2020 through February 2021. Multilevel modeling revealed significantly higher AC (grams of alcohol per day) on weekend days vs weekdays (β = 11.39; 95% CI, 10.00-12.77; P < .001). Alcohol consumption was above the overall average on Christmas (β = 26.82; 95% CI, 21.87-31.77; P < .001) and New Year’s Eve (β = 66.88; 95% CI, 59.22-74.54; P < .001). During the hard lockdown, perceived social isolation was significantly higher (β = 0.12; 95% CI, 0.06-0.15; P < .001), but AC was significantly lower (β = −5.45; 95% CI, −8.00 to −2.90; P = .001). Independent of lockdown, intention to drink less alcohol was associated with lower AC (β = −11.10; 95% CI, −13.63 to −8.58; P < .001). Notably, differences in AC between weekend and weekdays decreased both during the hard lockdown (β = −6.14; 95% CI, −9.96 to −2.31; P = .002) and in participants with severe AUD (β = −6.26; 95% CI, −10.18 to −2.34; P = .002).
Conclusions and Relevance This 5-month cohort study found no immediate negative associations of lockdown measures with overall AC. Rather, weekend-weekday and holiday AC patterns exceeded lockdown effects. Differences in AC between weekend days and weekdays evinced that weekend drinking cycles decreased as a function of AUD severity and lockdown measures, indicating a potential mechanism of losing and regaining control. This finding suggests that temporal patterns and drinking intention constitute promising targets for prevention and intervention, even in high-risk individuals.
Background
Animal personality has emerged as a key concept in behavioral ecology. While many studies have demonstrated the influence of personality traits on behavioral patterns, its quantification, especially in wild animal populations, remains a challenge. Only a few studies have established a link between personality and recurring movements within home ranges, although these small-scale movements are of key importance for identifying ecological interactions and forming individual niches. In this regard, differences in space use among individuals might reflect different exploration styles between behavioral types along the shy-bold continuum.
Methods
We assessed among-individual differences in behavior in the European hare (Lepus europaeus), a characteristic mammalian herbivore in agricultural landscapes using a standardized box emergence test for captive and wild hares. We determined an individuals’ degree of boldness by measuring the latencies of behavioral responses in repeated emergence tests in captivity. During capture events of wild hares, we conducted a single emergence test and recorded behavioral responses proven to be stable over time in captive hares. Applying repeated novel environment tests in a near-natural enclosure, we further quantified aspects of exploration and activity in captive hares. Finally, we investigated whether and how this among-individual behavioral variation is related to general activity and space use in a wild hare population. Wild and captive hares were treated similarly and GPS-collared with internal accelerometers prior to release to the wild or the outdoor enclosure, respectively. General activity was quantified as overall dynamic body acceleration (ODBA) obtained from accelerometers. Finally, we tested whether boldness explained variation in (i) ODBA in both settings and (ii) variation in home ranges and core areas across different time scales of GPS-collared hares in a wild population.
Results
We found three behavioral responses to be consistent over time in captive hares. ODBA was positively related to boldness (i.e., short latencies to make first contact with the new environment) in both captive and wild hares. Space use in wild hares also varied with boldness, with shy individuals having smaller core areas and larger home ranges than bold conspecifics (yet in some of the parameter space, this association was just marginally significant).
Conclusions
Against our prediction, shy individuals occupied relatively large home ranges but with small core areas. We suggest that this space use pattern is due to them avoiding risky, and energy-demanding competition for valuable resources. Carefully validated, activity measurements (ODBA) from accelerometers provide a valuable tool to quantify aspects of animal personality along the shy-bold continuum remotely. Without directly observing—and possibly disturbing—focal individuals, this approach allows measuring variability in animal personality, especially in species that are difficult to assess with experiments. Considering that accelerometers are often already built into GPS units, we recommend activating them at least during the initial days of tracking to estimate individual variation in general activity and, if possible, match them with a simple novelty experiment. Furthermore, information on individual behavioral types will help to facilitate mechanistic understanding of processes that drive spatial and ecological dynamics in heterogeneous landscapes.
Organisms often employ ecophysiological strategies to exploit environmental conditions and ensure bio-energetic success. However, the many complexities involved in the differential expression and flexibility of these strategies are rarely fully understood. Therefore, for the first time, using a three-part cross-disciplinary laboratory experimental analysis, we investigated the diversity and plasticity of photoresponsive traits employed by one family of environmentally contrasting, ecologically important phytoflagellates. The results demonstrated an extensive inter-species phenotypic diversity of behavioural, physiological, and compositional photoresponse across the Chlamydomonadaceae, and a multifaceted intra-species phenotypic plasticity, involving a broad range of beneficial photoacclimation strategies, often attributable to environmental predisposition and phylogenetic differentiation. Deceptively diverse and sophisticated strong (population and individual cell) behavioural photoresponses were observed, with divergence from a general preference for low light (and flexibility) dictated by intra-familial differences in typical habitat (salinity and trophy) and phylogeny. Notably, contrasting lower, narrow, and flexible compared with higher, broad, and stable preferences were observed in freshwater vs. brackish and marine species. Complex diversity and plasticity in physiological and compositional photoresponses were also discovered. Metabolic characteristics (such as growth rates, respiratory costs and photosynthetic capacity, efficiency, compensation and saturation points) varied elaborately with species, typical habitat (often varying more in eutrophic species, such as Chlamydomonas reinhardtii), and culture irradiance (adjusting to optimise energy acquisition and suggesting some propensity for low light). Considerable variations in intracellular pigment and biochemical composition were also recorded. Photosynthetic and accessory pigments (such as chlorophyll a, xanthophyll-cycle components, chlorophyll a:b and chlorophyll a:carotenoid ratios, fatty acid content and saturation ratios) varied with phylogeny and typical habitat (to attune photosystem ratios in different trophic conditions and to optimise shade adaptation, photoprotection, and thylakoid architecture, particularly in freshwater environments), and changed with irradiance (as reaction and harvesting centres adjusted to modulate absorption and quantum yield). The complex, concomitant nature of the results also advocated an integrative approach in future investigations. Overall, these nuanced, diverse, and flexible photoresponsive traits will greatly contribute to the functional ecology of these organisms, addressing environmental heterogeneity and potentially shaping individual fitness, spatial and temporal distribution, prevalence, and ecosystem dynamics.
The increasing development of antibiotic resistance in bacteria has been a major problem for years, both in human and veterinary medicine. Prophylactic measures, such as the use of vaccines, are of great importance in reducing the use of antibiotics in livestock. These vaccines are mainly produced based on formaldehyde inactivation. However, the latter damages the recognition elements of the bacterial proteins and thus could reduce the immune response in the animal. An alternative inactivation method developed in this work is based on gentle photodynamic inactivation using carbon nanodots (CNDs) at excitation wavelengths λex > 290 nm. The photodynamic inactivation was characterized on the nonvirulent laboratory strain Escherichia coli K12 using synthesized CNDs. For a gentle inactivation, the CNDs must be absorbed into the cytoplasm of the E. coli cell. Thus, the inactivation through photoinduced formation of reactive oxygen species only takes place inside the bacterium, which means that the outer membrane is neither damaged nor altered. The loading of the CNDs into E. coli was examined using fluorescence microscopy. Complete loading of the bacterial cells could be achieved in less than 10 min. These studies revealed a reversible uptake process allowing the recovery and reuse of the CNDs after irradiation and before the administration of the vaccine. The success of photodynamic inactivation was verified by viability assays on agar. In a homemade flow photoreactor, the fastest successful irradiation of the bacteria could be carried out in 34 s. Therefore, the photodynamic inactivation based on CNDs is very effective. The membrane integrity of the bacteria after irradiation was verified by slide agglutination and atomic force microscopy. The method developed for the laboratory strain E. coli K12 could then be successfully applied to the important avian pathogens Bordetella avium and Ornithobacterium rhinotracheale to aid the development of novel vaccines.
Background
The aim of this study was to analyze the shoulder functional profile (rotation range of motion [ROM] and strength), upper and lower body performance, and throwing speed of U13 versus U15 male handball players, and to establish the relationship between these measures of physical fitness and throwing speed.
Methods
One-hundred and nineteen young male handball players (under (U)-13 (U13) [n = 85]) and U15 [n = 34]) volunteered to participate in this study. The participating athletes had a mean background of sytematic handball training of 5.5 ± 2.8 years and they exercised on average 540 ± 10.1 min per week including sport-specific team handball training and strength and conditioning programs. Players were tested for passive shoulder range-of-motion (ROM) for both internal (IR) and external rotation (ER) and isometric strength (i.e., IR and ER) of the dominant/non-dominant shoulders, overhead medicine ball throw (OMB), hip isometric abductor (ABD) and adductor (ADD) strength, hip ROM, jumps (countermovement jump [CMJ] and triple leg-hop [3H] for distance), linear sprint test, modified 505 change-of-direction (COD) test and handball throwing speed (7 m [HT7] and 9 m [HT9]).
Results
U15 players outperformed U13 in upper (i.e., HT7 and HT9 speed, OMB, absolute IR and ER strength of the dominant and non-dominant sides; Cohen’s d: 0.76–2.13) and lower body (i.e., CMJ, 3H, 20-m sprint and COD, hip ABD and ADD; d: 0.70–2.33) performance measures. Regarding shoulder ROM outcomes, a lower IR ROM was found of the dominant side in the U15 group compared to the U13 and a higher ER ROM on both sides in U15 (d: 0.76–1.04). It seems that primarily anthropometric characteristics (i.e., body height, body mass) and upper body strength/power (OMB distance) are the most important factors that explain the throw speed variance in male handball players, particularly in U13.
Conclusions
Findings from this study imply that regular performance monitoring is important for performance development and for minimizing injury risk of the shoulder in both age categories of young male handball players. Besides measures of physical fitness, anthropometric data should be recorded because handball throwing performance is related to these measures.
Background: Child growth is a dynamic process. When measured at short intervals, children’s growth shows characteristic patterns that can be of great importance for clinical purposes.
Objective: To study whether measuring height on a daily basis using an APP is practicable and user-friendly.
Methods: Recruitment took place via Snowball Sampling. Thirteen out of 14 contacted families signed up for a study period of 12 weeks with altogether 22 healthy children aged 3 to 13 years (response rate 93%). The study started with a visit to the family home for the setup of the measurement site, conventional height measuring and initial training of the new measurement process. Follow-up appointments were made at four, eight and 12 weeks. The children’s height was measured at daily intervals at their family homes over a period of three months.
Results: The parents altogether recorded 1704 height measurements and meticulously documented practicability and problems when using the device.
A 93% response rate in recruitment was achieved by maintaining a high motivation within the families. Contact with the principal investigator was permanently available, including open communication, personal training and attendance during the appointments at the family homes.
Conclusion: Measuring height by photographic display is interesting for children and parents and can be used for height measurements at home. A positive response rate of 13 out of 14 families with altogether 22 children highlights feasible recruitment and the high convenience and user-friendliness of daily APP-supported height measurements. Daily APP measurements appear to be a promising new tool for longitudinal growth studies.
Large-scale databases that report the inhibitory capacities of many combinations of candidate drug compounds and cultivated cancer cell lines have driven the development of preclinical drug-sensitivity models based on machine learning. However, cultivated cell lines have devolved from human cancer cells over years or even decades under selective pressure in culture conditions. Moreover, models that have been trained on in vitro data cannot account for interactions with other types of cells. Drug-response data that are based on patient-derived cell cultures, xenografts, and organoids, on the other hand, are not available in the quantities that are needed to train high-capacity machine-learning models. We found that pre-training deep neural network models of drug sensitivity on in vitro drug-sensitivity databases before fine-tuning the model parameters on patient-derived data improves the models’ accuracy and improves the biological plausibility of the features, compared to training only on patient-derived data. From our experiments, we can conclude that pre-trained models outperform models that have been trained on the target domains in the vast majority of cases.
Prediction of hybrid biomass in Arabidopsis thaliana by selected parental SNP and metabolic markers
(2009)
A recombinant inbred line (RIL) population, derived from two Arabidopsis thaliana accessions, and the corresponding testcrosses with these two original accessions were used for the development and validation of machine learning models to predict the biomass of hybrids. Genetic and metabolic information of the RILs served as predictors. Feature selection reduced the number of variables (genetic and metabolic markers) in the models by more than 80% without impairing the predictive power. Thus, potential biomarkers have been revealed. Metabolites were shown to bear information on inherited macroscopic phenotypes. This proof of concept could be interesting for breeders. The example population exhibits substantial mid-parent biomass heterosis. The results of feature selection could therefore be used to shed light on the origin of heterosis. In this respect, mainly dominance effects were detected.
The knowledge of transformation pathways and identification of transformation products (TPs) of veterinary drugs is important for animal health, food, and environmental matters. The active agent Monensin (MON) belongs to the ionophore antibiotics and is widely used as a veterinary drug against coccidiosis in broiler farming. However, no electrochemically (EC) generated TPs of MON have been described so far. In this study, the online coupling of EC and mass spectrometry (MS) was used for the generation of oxidative TPs. EC-conditions were optimized with respect to working electrode material, solvent, modifier, and potential polarity. Subsequent LC/HRMS (liquid chromatography/high resolution mass spectrometry) and MS/MS experiments were performed to identify the structures of derived TPs by a suspected target analysis. The obtained EC-results were compared to TPs observed in metabolism tests with microsomes and hydrolysis experiments of MON. Five previously undescribed TPs of MON were identified in our EC/MS based study and one TP, which was already known from literature and found by a microsomal assay, could be confirmed. Two and three further TPs were found as products in microsomal tests and following hydrolysis, respectively. We found decarboxylation, O-demethylation and acid-catalyzed ring-opening reactions to be the major mechanisms of MON transformation.
Creative thinking is an indispensable cognitive skill that is becoming increasingly important. In the present research, we tested the impact of games on creativity and emotions in a between-subject online experiment with four conditions (N = 658). (1) participants played a simple puzzle game that allowed many solutions (priming divergent thinking); (2) participants played a short game that required one fitting solution (priming convergent thinking); (3) participants performed mental arithmetic; (4) passive control condition. Results show that divergent and convergent creativity were higher after playing games and lower after mental arithmetic. Positive emotions did not function as a mediator, even though they were also heightened after playing the games and lower after mental arithmetic. However, contrary to previous research, we found no direct effect of emotions, creative self-efficacy, and growth- vs. fixed on creative performance. We discuss practical implications for digital learning and application settings.
For life-long learning, an effective learning strategy repertoire is particularly important during acquisition of knowledge in lower secondary school—an educational level characterized with transition into more autonomous learning environments with increased complex academic demands. Using latent profile analysis, we explored the occurrence of different secondary school learner profiles depending on their various combinations of cognitive and metacognitive learning strategy use, as well as their differences in perceived autonomy support, intrinsic motivation, and gender. Data were collected from 576 ninth grade students in Uganda using self-report questionnaires. Four learner profiles were identified: competent strategy user, struggling user, surface-level learner, and deep-level learner profiles. Gender differences were noted in students’ use of elaboration and organization strategies to learn Physics, in favor of girls. In terms of profile memberships, significant differences in gender, intrinsic motivation and perceived autonomy support were also noted. Girls were 2.4–2.7 times more likely than boys to be members of the competent strategy user and surface-level learner profiles. Additionally, higher levels of intrinsic motivation predicted an increased likelihood membership into the deep-level learner profile, while higher levels of perceived teacher autonomy predicted an increased likelihood membership into the competent strategy user profile as compared to other profiles. Further, implications of the findings were discussed.
The aim of this review was to describe and summarize the scientific literature on programming parameters related to jump or plyometric training in male and female soccer players of different ages and fitness levels. A literature search was conducted in the electronic databases PubMed, Web of Science and Scopus using keywords related to the main topic of this study (e.g., “ballistic” and “plyometric”). According to the PICOS framework, the population for the review was restricted to soccer players, involved in jump or plyometric training. Among 7556 identified studies, 90 were eligible for inclusion. Only 12 studies were found for females. Most studies (n = 52) were conducted with youth male players. Moreover, only 35 studies determined the effectiveness of a given jump training programming factor. Based on the limited available research, it seems that a dose of 7 weeks (1–2 sessions per week), with ~80 jumps (specific of combined types) per session, using near-maximal or maximal intensity, with adequate recovery between repetitions (<15 s), sets (≥30 s) and sessions (≥24–48 h), using progressive overload and taper strategies, using appropriate surfaces (e.g., grass), and applied in a well-rested state, when combined with other training methods, would increase the outcome of effective and safe plyometric-jump training interventions aimed at improving soccer players physical fitness. In conclusion, jump training is an effective and easy-to-administer training approach for youth, adult, male and female soccer players. However, optimal programming for plyometric-jump training in soccer is yet to be determined in future research.
The effects of exercise interventions on unspecific chronic low back pain (CLBP) have been investigated in many studies, but the results are inconclusive regarding exercise types, efficiency, and sustainability. This may be because the influence of psychosocial factors on exercise induced adaptation regarding CLBP is neglected. Therefore, this study assessed psychosocial characteristics, which moderate and mediate the effects of sensorimotor exercise on LBP. A single-blind 3-arm multicenter randomized controlled trial was conducted for 12-weeks. Three exercise groups, sensorimotor exercise (SMT), sensorimotor and behavioral training (SMT-BT), and regular routines (CG) were randomly assigned to 662 volunteers. Primary outcomes (pain intensity and disability) and psychosocial characteristics were assessed at baseline (M1) and follow-up (3/6/12/24 weeks, M2-M5). Multiple regression models were used to analyze whether psychosocial characteristics are moderators of the relationship between exercise and pain, meaning that psychosocial factors and exercise interact. Causal mediation analysis were conducted to analyze, whether psychosocial characteristics mediate the exercise effect on pain. A total of 453 participants with intermittent pain (mean age = 39.5 ± 12.2 years, f = 62%) completed the training. It was shown, that depressive symptomatology (at M4, M5), vital exhaustion (at M4), and perceived social support (at M5) are significant moderators of the relationship between exercise and the reduction of pain intensity. Further depressive mood (at M4), social-satisfaction (at M4), and anxiety (at M5 SMT) significantly moderate the exercise effect on pain disability. The amount of moderation was of clinical relevance. In contrast, there were no psychosocial variables which mediated exercise effects on pain. In conclusion it was shown, that psychosocial variables can be moderators in the relationship between sensorimotor exercise induced adaptation on CLBP which may explain conflicting results in the past regarding the merit of exercise interventions in CLBP. Results suggest further an early identification of psychosocial risk factors by diagnostic tools, which may essential support the planning of personalized exercise therapy.
Level of Evidence: Level I.
Clinical Trial Registration: DRKS00004977, LOE: I, MiSpEx: grant-number: 080102A/11-14. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00004977.
Pokhara (ca. 850 m a.s.l.), Nepal's second-largest city, lies at the foot of the Higher Himalayas and has more than tripled its population in the past 3 decades. Construction materials are in high demand in rapidly expanding built-up areas, and several informal settlements cater to unregulated sand and gravel mining in the Pokhara Valley's main river, the Seti Khola. This river is fed by the Sabche glacier below Annapurna III (7555 m a.s.l.), some 35 km upstream of the city, and traverses one of the steepest topographic gradients in the Himalayas. In May 2012 a sudden flood caused >70 fatalities and intense damage along this river and rekindled concerns about flood risk management. We estimate the flow dynamics and inundation depths of flood scenarios using the hydrodynamic model HEC-RAS (Hydrologic Engineering Center’s River Analysis System). We simulate the potential impacts of peak discharges from 1000 to 10 000 m3 s−1 on land cover based on high-resolution Maxar satellite imagery and OpenStreetMap data (buildings and road network). We also trace the dynamics of two informal settlements near Kaseri and Yamdi with high potential flood impact from RapidEye, PlanetScope, and Google Earth imagery of the past 2 decades. Our hydrodynamic simulations highlight several sites of potential hydraulic ponding that would largely affect these informal settlements and sites of sand and gravel mining. These built-up areas grew between 3- and 20-fold, thus likely raising local flood exposure well beyond changes in flood hazard. Besides these drastic local changes, about 1 % of Pokhara's built-up urban area and essential rural road network is in the highest-hazard zones highlighted by our flood simulations. Our results stress the need to adapt early-warning strategies for locally differing hydrological and geomorphic conditions in this rapidly growing urban watershed.
Computation of the instantaneous phase and amplitude via the Hilbert Transform is a powerful tool of data analysis. This approach finds many applications in various science and engineering branches but is not proper for causal estimation because it requires knowledge of the signal’s past and future. However, several problems require real-time estimation of phase and amplitude; an illustrative example is phase-locked or amplitude-dependent stimulation in neuroscience. In this paper, we discuss and compare three causal algorithms that do not rely on the Hilbert Transform but exploit well-known physical phenomena, the synchronization and the resonance. After testing the algorithms on a synthetic data set, we illustrate their performance computing phase and amplitude for the accelerometer tremor measurements and a Parkinsonian patient’s beta-band brain activity.
Recreational exercising and self-reported cardiometabolic diseases in German people living with HIV
(2021)
Exercise is known for its beneficial effects on preventing cardiometabolic diseases (CMDs) in the general population. People living with the human immunodeficiency virus (PLWH) are prone to sedentarism, thus raising their already elevated risk of developing CMDs in comparison to individuals without HIV. The aim of this cross-sectional study was to determine if exercise is associated with reduced risk of self-reported CMDs in a German HIV-positive sample (n = 446). Participants completed a self-report survey to assess exercise levels, date of HIV diagnosis, CD4 cell count, antiretroviral therapy, and CMDs. Participants were classified into exercising or sedentary conditions. Generalized linear models with Poisson regression were conducted to assess the prevalence ratio (PR) of PLWH reporting a CMD. Exercising PLWH were less likely to report a heart arrhythmia for every increase in exercise duration (PR: 0.20: 95% CI: 0.10–0.62, p < 0.01) and diabetes mellitus for every increase in exercise session per week (PR: 0.40: 95% CI: 0.10–1, p < 0.01). Exercise frequency and duration are associated with a decreased risk of reporting arrhythmia and diabetes mellitus in PLWH. Further studies are needed to elucidate the mechanisms underlying exercise as a protective factor for CMDs in PLWH.
The highly conserved protein complex containing the Target of Rapamycin (TOR) kinase is known to integrate intra- and extra-cellular stimuli controlling nutrient allocation and cellular growth. This thesis describes three studies aimed to understand how TOR signaling pathway influences carbon and nitrogen metabolism in Chlamydomonas reinhardtii. The first study presents a time-resolved analysis of the molecular and physiological features across the diurnal cycle. The inhibition of TOR leads to 50% reduction in growth followed by nonlinear delays in the cell cycle progression. The metabolomics analysis showed that the growth repression is mainly driven by differential carbon partitioning between anabolic and catabolic processes. Furthermore, the high accumulation of nitrogen-containing compounds indicated that TOR kinase controls the carbon to nitrogen balance of the cell, which is responsible for biomass accumulation, growth and cell cycle progression. In the second study the cause of the high accumulation of amino acids is explained. For this purpose, the effect of TOR inhibition on Chlamydomonas was examined under different growth regimes using stable 13C- and 15N-isotope labeling. The data clearly showed that an increased nitrogen uptake is induced within minutes after the inhibition of TOR. Interestingly, this increased N-influx is accompanied by increased activities of nitrogen assimilating enzymes. Accordingly, it was concluded that TOR inhibition induces de-novo amino acid synthesis in Chlamydomonas. The recognition of this novel process opened an array of questions regarding potential links between central metabolism and TOR signaling. Therefore a detailed phosphoproteomics study was conducted to identify the potential substrates of TOR pathway regulating central metabolism. Interestingly, some of the key enzymes involved in carbon metabolism as well as amino acid synthesis exhibited significant changes in the phosphosite intensities immediately after TOR inhibition. Altogether, these studies provide a) detailed insights to metabolic response of Chlamydomonas to TOR inhibition, b) identification of a novel process causing rapid upshifts in amino acid levels upon TOR inhibition and c) finally highlight potential targets of TOR signaling regulating changes in central metabolism. Further biochemical and molecular investigations could confirm these observations and advance the understanding of growth signaling in microalgae.
The purpose of this study was to examine the test-retest reliability, and convergent and discriminative validity of a new taekwondo-specific change-of-direction (COD) speed test with striking techniques (TST) in elite taekwondo athletes. Twenty (10 males and 10 females) elite (athletes who compete at national level) and top-elite (athletes who compete at national and international level) taekwondo athletes with an average training background of 8.9 ± 1.3 years of systematic taekwondo training participated in this study. During the two-week test-retest period, various generic performance tests measuring COD speed, balance, speed, and jump performance were carried out during the first week and as a retest during the second week. Three TST trials were conducted with each athlete and the best trial was used for further analyses. The relevant performance measure derived from the TST was the time with striking penalty (TST-TSP). TST-TSP performances amounted to 10.57 ± 1.08 s for males and 11.74 ± 1.34 s for females. The reliability analysis of the TST performance was conducted after logarithmic transformation, in order to address the problem of heteroscedasticity. In both groups, the TST demonstrated a high relative test-retest reliability (intraclass correlation coefficients and 90% compatibility limits were 0.80 and 0.47 to 0.93, respectively). For absolute reliability, the TST’s typical error of measurement (TEM), 90% compatibility limits, and magnitudes were 4.6%, 3.4 to 7.7, for males, and 5.4%, 3.9 to 9.0, for females. The homogeneous sample of taekwondo athletes meant that the TST’s TEM exceeded the usual smallest important change (SIC) with 0.2 effect size in the two groups. The new test showed mostly very large correlations with linear sprint speed (r = 0.71 to 0.85) and dynamic balance (r = −0.71 and −0.74), large correlations with COD speed (r = 0.57 to 0.60) and vertical jump performance (r = −0.50 to −0.65), and moderate correlations with horizontal jump performance (r = −0.34 to −0.45) and static balance (r = −0.39 to −0.44). Top-elite athletes showed better TST performances than elite counterparts. Receiver operating characteristic analysis indicated that the TST effectively discriminated between top-elite and elite taekwondo athletes. In conclusion, the TST is a valid, and sensitive test to evaluate the COD speed with taekwondo specific skills, and reliable when considering ICC and TEM. Although the usefulness of the TST is questioned to detect small performance changes in the present population, the TST can detect moderate changes in taekwondo-specific COD speed.
Many widely used observational data sets are comprised of several overlapping instrument records. While data inter-calibration techniques often yield continuous and reliable data for trend analysis, less attention is generally paid to maintaining higher-order statistics such as variance and autocorrelation. A growing body of work uses these metrics to quantify the stability or resilience of a system under study and potentially to anticipate an approaching critical transition in the system. Exploring the degree to which changes in resilience indicators such as the variance or autocorrelation can be attributed to non-stationary characteristics of the measurement process – rather than actual changes in the dynamical properties of the system – is important in this context. In this work we use both synthetic and empirical data to explore how changes in the noise structure of a data set are propagated into the commonly used resilience metrics lag-one autocorrelation and variance. We focus on examples from remotely sensed vegetation indicators such as vegetation optical depth and the normalized difference vegetation index from different satellite sources. We find that time series resulting from mixing signals from sensors with varied uncertainties and covering overlapping time spans can lead to biases in inferred resilience changes. These biases are typically more pronounced when resilience metrics are aggregated (for example, by land-cover type or region), whereas estimates for individual time series remain reliable at reasonable sensor signal-to-noise ratios. Our work provides guidelines for the treatment and aggregation of multi-instrument data in studies of critical transitions and resilience.
Background
Millions of people in Germany suffer from chronic pain, in which course and intensity are multifactorial. Besides physical injuries, certain psychosocial risk factors are involved in the disease process. The national health care guidelines for the diagnosis and treatment of non-specific low back pain recommend the screening of psychosocial risk factors as early as possible, to be able to adapt the therapy to patient needs (e.g., unimodal or multimodal). However, such a procedure has been difficult to implement in practice and has not yet been integrated into the rehabilitation care structures across the country.
Methods
The aim of this study is to implement an individualized therapy and aftercare program within the rehabilitation offer of the German Pension Insurance in the area of orthopedics and to examine its success and sustainability in comparison to the previous standard aftercare program.
The study is a multicenter randomized controlled trial including 1204 patients from six orthopedic rehabilitation clinics. A 2:1 allocation ratio to intervention (individualized and home-based rehabilitation aftercare) versus the control group (regular outpatient rehabilitation aftercare) is set. Upon admission to the rehabilitation clinic, participants in the intervention group will be screened according to their psychosocial risk profile. They could then receive either unimodal or multimodal, together with an individualized training program. The program is instructed in the clinic (approximately 3 weeks) and will continue independently at home afterwards for 3 months. The success of the program is examined by means of a total of four surveys. The co-primary outcomes are the Characteristic Pain Intensity and Disability Score assessed by the German version of the Chronic Pain Grade questionnaire (CPG).
Discussion
An improvement in terms of pain, work ability, patient compliance, and acceptance in our intervention program compared to the standard aftercare is expected. The study contributes to provide individualized care also to patients living far away from clinical centers.
Trial registration
DRKS, DRKS00020373. Registered on 15 April 2020
How do different reset protocols affect ergodicity of a diffusion process in single-particle-tracking experiments? We here address the problem of resetting of an arbitrary stochastic anomalous-diffusion process (ADP) from the general mathematical points of view and assess ergodicity of such reset ADPs for an arbitrary resetting protocol. The process of stochastic resetting describes the events of the instantaneous restart of a particle’s motion via randomly distributed returns to a preset initial position (or a set of those). The waiting times of such resetting events obey the Poissonian, Gamma, or more generic distributions with specified conditions regarding the existence of moments. Within these general approaches, we derive general analytical results and support them by computer simulations for the behavior of the reset mean-squared displacement (MSD), the new reset increment-MSD (iMSD), and the mean reset time-averaged MSD (TAMSD). For parental nonreset ADPs with the MSD(t)∝ tμ we find a generic behavior and a switch of the short-time growth of the reset iMSD and mean reset TAMSDs from ∝ _μ for subdiffusive to ∝ _1 for superdiffusive reset ADPs. The critical condition for a reset ADP that recovers its ergodicity is found to be more general than that for the nonequilibrium stationary state, where obviously the iMSD and the mean TAMSD are equal. The consideration of the new statistical quantifier, the iMSD—as compared to the standard MSD—restores the ergodicity of an arbitrary reset ADP in all situations when the μth moment of the waiting-time distribution of resetting events is finite. Potential applications of these new resetting results are, inter alia, in the area of biophysical and soft-matter systems.
Introduction: The ongoing COVID-19 pandemic situation caused by SARS-CoV-2 and variants of concern such as B.1.617.2 (Delta) and recently, B.1.1.529 (Omicron) is posing multiple challenges to humanity. The rapid evolution of the virus requires adaptation of diagnostic and therapeutic applications.
Objectives: In this study, we describe camelid heavy-chain-only antibodies (hcAb) as useful tools for novel in vitro diagnostic assays and for therapeutic applications due to their neutralizing capacity.
Methods: Five antibody candidates were selected out of a naïve camelid library by phage display and expressed as full length IgG2 antibodies. The antibodies were characterized by Western blot, enzyme-linked immunosorbent assays, surface plasmon resonance with regard to their specificity to the recombinant SARS-CoV-2 Spike protein and to SARS-CoV-2 virus-like particles. Neutralization assays were performed with authentic SARS-CoV-2 and pseudotyped viruses (wildtype and Omicron).
Results: All antibodies efficiently detect recombinant SARS-CoV-2 Spike protein and SARS-CoV-2 virus-like particles in different ELISA setups. The best combination was shown with hcAb B10 as catcher antibody and HRP-conjugated hcAb A7.2 as the detection antibody. Further, four out of five antibodies potently neutralized authentic wildtype SARS-CoV-2 and particles pseudotyped with the SARS-CoV-2 Spike proteins of the wildtype and Omicron variant, sublineage BA.1 at concentrations between 0.1 and 0.35 ng/mL (ND50).
Conclusion: Collectively, we report novel camelid hcAbs suitable for diagnostics and potential therapy.
Mediterranean ecosystems are particularly vulnerable to climate change and the associated increase in climate anomalies. This study investigates extreme ecosystem responses evoked by climatic drivers in the Mediterranean Basin for the time span 1999–2019 with a specific focus on seasonal variations as the seasonal timing of climatic anomalies is considered essential for impact and vulnerability assessment. A bivariate vulnerability analysis is performed for each month of the year to quantify which combinations of the drivers temperature (obtained from ERA5-Land) and soil moisture (obtained from ESA CCI and ERA5-Land) lead to extreme reductions in ecosystem productivity using the fraction of absorbed photosynthetically active radiation (FAPAR; obtained from the Copernicus Global Land Service) as a proxy.
The bivariate analysis clearly showed that, in many cases, it is not just one but a combination of both drivers that causes ecosystem vulnerability. The overall pattern shows that Mediterranean ecosystems are prone to three soil moisture regimes during the yearly cycle: they are vulnerable to hot and dry conditions from May to July, to cold and dry conditions from August to October, and to cold conditions from November to April, illustrating the shift from a soil-moisture-limited regime in summer to an energy-limited regime in winter. In late spring, a month with significant vulnerability to hot conditions only often precedes the next stage of vulnerability to both hot and dry conditions, suggesting that high temperatures lead to critically low soil moisture levels with a certain time lag. In the eastern Mediterranean, the period of vulnerability to hot and dry conditions within the year is much longer than in the western Mediterranean. Our results show that it is crucial to account for both spatial and temporal variability to adequately assess ecosystem vulnerability. The seasonal vulnerability approach presented in this study helps to provide detailed insights regarding the specific phenological stage of the year in which ecosystem vulnerability to a certain climatic condition occurs.
How to cite.
Vogel, J., Paton, E., and Aich, V.: Seasonal ecosystem vulnerability to climatic anomalies in the Mediterranean, Biogeosciences, 18, 5903–5927, https://doi.org/10.5194/bg-18-5903-2021, 2021.
Simultaneous Barcode Sequencing of Diverse Museum Collection Specimens Using a Mixed RNA Bait Set
(2022)
A growing number of publications presenting results from sequencing natural history collection specimens reflect the importance of DNA sequence information from such samples. Ancient DNA extraction and library preparation methods in combination with target gene capture are a way of unlocking archival DNA, including from formalin-fixed wet-collection material. Here we report on an experiment, in which we used an RNA bait set containing baits from a wide taxonomic range of species for DNA hybridisation capture of nuclear and mitochondrial targets for analysing natural history collection specimens. The bait set used consists of 2,492 mitochondrial and 530 nuclear RNA baits and comprises specific barcode loci of diverse animal groups including both invertebrates and vertebrates. The baits allowed to capture DNA sequence information of target barcode loci from 84% of the 37 samples tested, with nuclear markers being captured more frequently and consensus sequences of these being more complete compared to mitochondrial markers. Samples from dry material had a higher rate of success than wet-collection specimens, although target sequence information could be captured from 50% of formalin-fixed samples. Our study illustrates how efforts to obtain barcode sequence information from natural history collection specimens may be combined and are a way of implementing barcoding inventories of scientific collection material.
In numerical processing, the functional role of Spatial-Numerical Associations (SNAs, such as the association of smaller numbers with left space and larger numbers with right space, the Mental Number Line hypothesis) is debated. Most studies demonstrate SNAs with lateralized responses, and there is little evidence that SNAs appear when no response is required. We recorded passive holding grip forces in no-go trials during number processing. In Experiment 1, participants performed a surface numerical decision task (“Is it a number or a letter?”). In Experiment 2, we used a deeper semantic task (“Is this number larger or smaller than five?”). Despite instruction to keep their grip force constant, participants' spontaneous grip force changed in both experiments: Smaller numbers led to larger force increase in the left than in the right hand in the numerical decision task (500–700 ms after stimulus onset). In the semantic task, smaller numbers again led to larger force increase in the left hand, and larger numbers increased the right-hand holding force. This effect appeared earlier (180 ms) and lasted longer (until 580 ms after stimulus onset). This is the first demonstration of SNAs with passive holding force. Our result suggests that (1) explicit motor response is not a prerequisite for SNAs to appear, and (2) the timing and strength of SNAs are task-dependent. (216 words).
Models are useful tools for understanding and predicting ecological patterns and processes. Under ongoing climate and biodiversity change, they can greatly facilitate decision-making in conservation and restoration and help designing adequate management strategies for an uncertain future. Here, we review the use of spatially explicit models for decision support and to identify key gaps in current modelling in conservation and restoration. Of 650 reviewed publications, 217 publications had a clear management application and were included in our quantitative analyses. Overall, modelling studies were biased towards static models (79%), towards the species and population level (80%) and towards conservation (rather than restoration) applications (71%). Correlative niche models were the most widely used model type. Dynamic models as well as the gene-to-individual level and the community-to-ecosystem level were underrepresented, and explicit cost optimisation approaches were only used in 10% of the studies. We present a new model typology for selecting models for animal conservation and restoration, characterising model types according to organisational levels, biological processes of interest and desired management applications. This typology will help to more closely link models to management goals. Additionally, future efforts need to overcome important challenges related to data integration, model integration and decision-making. We conclude with five key recommendations, suggesting that wider usage of spatially explicit models for decision support can be achieved by 1) developing a toolbox with multiple, easier-to-use methods, 2) improving calibration and validation of dynamic modelling approaches and 3) developing best-practise guidelines for applying these models. Further, more robust decision-making can be achieved by 4) combining multiple modelling approaches to assess uncertainty, and 5) placing models at the core of adaptive management. These efforts must be accompanied by long-term funding for modelling and monitoring, and improved communication between research and practise to ensure optimal conservation and restoration outcomes.
Transitory starch plays a central role in the life cycle of plants. Many aspects of this important metabolism remain unknown; however, starch granules provide insight into this persistent metabolic process. Therefore, monitoring alterations in starch granules with high temporal resolution provides one significant avenue to improve understanding. Here, a previously established method that combines LCSM and safranin-O staining for in vivo imaging of transitory starch granules in leaves of Arabidopsis thaliana was employed to demonstrate, for the first time, the alterations in starch granule size and morphology that occur both throughout the day and during leaf aging. Several starch-related mutants were included, which revealed differences among the generated granules. In ptst2 and sex1-8, the starch granules in old leaves were much larger than those in young leaves; however, the typical flattened discoid morphology was maintained. In ss4 and dpe2/phs1/ss4, the morphology of starch granules in young leaves was altered, with a more rounded shape observed. With leaf development, the starch granules became spherical exclusively in dpe2/phs1/ss4. Thus, the presented data provide new insights to contribute to the understanding of starch granule morphogenesis.
In intervention research, single-case experimental designs are an important way to gain insights into the causes of individual changes that yield high internal validity. They are commonly applied to examine the effectiveness of classroom-based interventions to reduce problem behavior in schools. At the same time, there is no consensus on good design characteristics of single-case experimental designs when dealing with behavioral problems in schools. Moreover, specific challenges arise concerning appropriate approaches to analyzing behavioral data. Our study addresses the interplay between the test power of piecewise regression analysis and important design specifications of single-case research designs. Here, we focus on the influence of the following specifications of single-case research designs: number of measurement times, the initial frequency of the behavior, intervention effect, and data trend. We conducted a Monte-Carlo study. First, simulated datasets were created with specific design conditions based on reviews of published single-case intervention studies. Following, data were analyzed using piecewise Poisson-regression models, and the influence of specific design specifications on the test power was investigated. Our results indicate that piecewise regressions have a high potential of adequately identifying the effects of interventions for single-case studies. At the same time, test power is strongly related to the specific design specifications of the single-case study: Few measurement times, especially in phase A, and low initial frequencies of the behavior make it impossible to detect even large intervention effects. Research designs with a high number of measurement times show robust power. The insights gained are highly relevant for researchers in the field, as decisions during the early stage of conceptualizing and planning single-case experimental design studies may impact the chance to identify an existing intervention effect during the research process correctly.
We introduce and study a Lévy walk (LW) model of particle spreading with a finite propagation speed combined with soft resets, stochastically occurring periods in which an harmonic external potential is switched on and forces the particle towards a specific position. Soft resets avoid instantaneous relocation of particles that in certain physical settings may be considered unphysical. Moreover, soft resets do not have a specific resetting point but lead the particle towards a resetting point by a restoring Hookean force. Depending on the exact choice for the LW waiting time density and the probability density of the periods when the harmonic potential is switched on, we demonstrate a rich emerging response behaviour including ballistic motion and superdiffusion. When the confinement periods of the soft-reset events are dominant, we observe a particle localisation with an associated non-equilibrium steady state. In this case the stationary particle probability density function turns out to acquire multimodal states. Our derivations are based on Markov chain ideas and LWs with multiple internal states, an approach that may be useful and flexible for the investigation of other generalised random walks with soft and hard resets. The spreading efficiency of soft-rest LWs is characterised by the first-passage time statistic.
Purpose: The aim of this study was to compare the effects of moderate intensity, low volume (MILV) vs. low intensity, high volume (LIHV) strength training on sport-specific performance, measures of muscular fitness, and skeletal muscle mass in young kayakers and canoeists.
Methods: Semi-elite young kayakers and canoeists (N = 40, 13 ± 0.8 years, 11 girls) performed either MILV (70–80% 1-RM, 6–12 repetitions per set) or LIHV (30–40% 1-RM, 60–120 repetitions per set) strength training for one season. Linear mixed-effects models were used to compare effects of training condition on changes over time in 250 and 2,000 m time trials, handgrip strength, underhand shot throw, average bench pull power over 2 min, and skeletal muscle mass. Both between- and within-subject designs were used for analysis. An alpha of 0.05 was used to determine statistical significance.
Results: Between- and within-subject analyses showed that monthly changes were greater in LIHV vs. MILV for the 2,000 m time trial (between: 9.16 s, SE = 2.70, p < 0.01; within: 2,000 m: 13.90 s, SE = 5.02, p = 0.01) and bench pull average power (between: 0.021 W⋅kg–1, SE = 0.008, p = 0.02; within: 0.010 W⋅kg–1, SE = 0.009, p > 0.05). Training conditions did not affect other outcomes.
Conclusion: Young sprint kayakers and canoeists benefit from LIHV more than MILV strength training in terms of 2,000 m performance and muscular endurance (i.e., 2 min bench pull power).
Background: As the number of cardiac diseases continuously increases within the last years in modern society, so does cardiac treatment, especially cardiac catheterization. The procedure of a cardiac catheterization is challenging for both patients and practitioners. Several potential stressors of psychological or physical nature can occur during the procedure. The objective of the study is to develop and implement a stress management intervention for both practitioners and patients that aims to reduce the psychological and physical strain of a cardiac catheterization.
Methods: The clinical study (DRKS00026624) includes two randomized controlled intervention trials with parallel groups, for patients with elective cardiac catheterization and practitioners at the catheterization lab, in two clinic sites of the Ernst-von-Bergmann clinic network in Brandenburg, Germany. Both groups received different interventions for stress management. The intervention for patients comprises a psychoeducational video with different stress management technics and additional a standardized medical information about the cardiac catheterization examination. The control condition includes the in hospitals practiced medical patient education before the examination (usual care). Primary and secondary outcomes are measured by physiological parameters and validated questionnaires, the day before (M1) and after (M2) the cardiac catheterization and at a postal follow-up 6 months later (M3). It is expected that people with standardized information and psychoeducation show reduced complications during cardiac catheterization procedures, better pre- and post-operative wellbeing, regeneration, mood and lower stress levels over time. The intervention for practitioners includes a Mindfulness-based stress reduction program (MBSR) over 8 weeks supervised by an experienced MBSR practitioner directly at the clinic site and an operative guideline. It is expected that practitioners with intervention show improved perceived and chronic stress, occupational health, physical and mental function, higher effort-reward balance, regeneration and quality of life. Primary and secondary outcomes are measured by physiological parameters (heart rate variability, saliva cortisol) and validated questionnaires and will be assessed before (M1) and after (M2) the MBSR intervention and at a postal follow-up 6 months later (M3). Physiological biomarkers in practitioners will be assessed before (M1) and after intervention (M2) on two work days and a two days off. Intervention effects in both groups (practitioners and patients) will be evaluated separately using multivariate variance analysis.
Discussion: This study evaluates the effectiveness of two stress management intervention programs for patients and practitioners within cardiac catheter laboratory. Study will disclose strains during a cardiac catheterization affecting both patients and practitioners. For practitioners it may contribute to improved working conditions and occupational safety, preservation of earning capacity, avoidance of participation restrictions and loss of performance. In both groups less anxiety, stress and complications before and during the procedures can be expected. The study may add knowledge how to eliminate stressful exposures and to contribute to more (psychological) security, less output losses and exhaustion during work. The evolved stress management guidelines, training manuals and the standardized patient education should be transferred into clinical routines
Strong as a Hippo’s Heart: Biomechanical Hippo Signaling During Zebrafish Cardiac Development
(2021)
The heart is comprised of multiple tissues that contribute to its physiological functions. During development, the growth of myocardium and endocardium is coupled and morphogenetic processes within these separate tissue layers are integrated. Here, we discuss the roles of mechanosensitive Hippo signaling in growth and morphogenesis of the zebrafish heart. Hippo signaling is involved in defining numbers of cardiac progenitor cells derived from the secondary heart field, in restricting the growth of the epicardium, and in guiding trabeculation and outflow tract formation. Recent work also shows that myocardial chamber dimensions serve as a blueprint for Hippo signaling-dependent growth of the endocardium. Evidently, Hippo pathway components act at the crossroads of various signaling pathways involved in embryonic zebrafish heart development. Elucidating how biomechanical Hippo signaling guides heart morphogenesis has direct implications for our understanding of cardiac physiology and pathophysiology.
Background: Physical fitness is decreased in malnourished children and adults. Poor appearance and muscular flaccidity are among the first signs of malnutrition. Malnutrition is often associated with stunting.
Objectives: We test the hypotheses that stunted children of low social strata are physically less fit than children of high social strata.
Sample: We investigated 354 school girls and 369 school boys aged 5.83 to 13.83 (mean 9.54) years from three different social strata in Kupang (West-Timor, Indonesia) in 2020.
Methods: We measured height, weight, and elbow breadth, calculated standard deviation (SDS) of height and weight according to CDC references, and the Frame index as an indicator of long-term physical fitness, and we tested physical fitness in standing long jump and hand grip strength.
Results: Children of low social strata are physically fittest. They jump longer distances, and they have higher values in the Frame index. No association exists between height SDS and physical fitness, neither in respect to standing long jump, nor to hand grip strength.
Conclusion: Stunting does not impair physical fitness in Indonesian school children. Our results support the concept that SEPE (social-economic-political-emotional) factors are involved in the regulation of human growth.
Glaciated high-alpine areas are fundamentally altered by climate change, with well-known implications for hydrology, e.g., due to glacier retreat, longer snow-free periods, and more frequent and intense summer rainstorms. While knowledge on how these hydrological changes will propagate to suspended sediment dynamics is still scarce, it is needed to inform mitigation and adaptation strategies. To understand the processes and source areas most relevant to sediment dynamics, we analyzed discharge and sediment dynamics in high temporal resolution as well as their patterns on several spatial scales, which to date few studies have done.
We used a nested catchment setup in the Upper Ötztal in Tyrol, Austria, where high-resolution (15 min) time series of discharge and suspended sediment concentrations are available for up to 15 years (2006–2020). The catchments of the gauges in Vent, Sölden and Tumpen range from 100 to almost 800 km2 with 10 % to 30 % glacier cover and span an elevation range of 930 to 3772 m a.s.l. We analyzed discharge and suspended sediment yields (SSY), their distribution in space, their seasonality and spatial differences therein, and the relative importance of short-term events. We complemented our analysis by linking the observations to satellite-based snow cover maps, glacier inventories, mass balances and precipitation data.
Our results indicate that the areas above 2500 m a.s.l., characterized by glacier tongues and the most recently deglaciated areas, are crucial for sediment generation in all sub-catchments. This notion is supported by the synchronous spring onset of sediment export at the three gauges, which coincides with snowmelt above 2500 m but lags behind spring discharge onsets. This points at a limitation of suspended sediment supply as long as the areas above 2500 m are snow-covered. The positive correlation of annual SSY with glacier cover (among catchments) and glacier mass balances (within a catchment) further supports the importance of the glacier-dominated areas. The analysis of short-term events showed that summer precipitation events were associated with peak sediment concentrations and yields but on average accounted for only 21 % of the annual SSY in the headwaters. These results indicate that under current conditions, thermally induced sediment export (through snow and glacier melt) is dominant in the study area.
Our results extend the scientific knowledge on current hydro-sedimentological conditions in glaciated high-alpine areas and provide a baseline for studies on projected future changes in hydro-sedimentological system dynamics.
Development of chronic pain after a low back pain episode is associated with increased pain sensitivity, altered pain processing mechanisms and the influence of psychosocial factors. Although there is some evidence that multimodal therapy (such as behavioral or motor control therapy) may be an important therapeutic strategy, its long-term effect on pain reduction and psychosocial load is still unclear. Prospective longitudinal designs providing information about the extent of such possible long-term effects are missing. This study aims to investigate the long-term effects of a homebased uni- and multidisciplinary motor control exercise program on low back pain intensity, disability and psychosocial variables. 14 months after completion of a multicenter study comparing uni- and multidisciplinary exercise interventions, a sample of one study center (n = 154) was assessed once more. Participants filled in questionnaires regarding their low back pain symptoms (characteristic pain intensity and related disability), stress and vital exhaustion (short version of the Maastricht Vital Exhaustion Questionnaire), anxiety and depression experiences (the Hospital and Anxiety Depression Scale), and pain-related cognitions (the Fear Avoidance Beliefs Questionnaire). Repeated measures mixed ANCOVAs were calculated to determine the long-term effects of the interventions on characteristic pain intensity and disability as well as on the psychosocial variables. Fifty four percent of the sub-sample responded to the questionnaires (n = 84). Longitudinal analyses revealed a significant long-term effect of the exercise intervention on pain disability. The multidisciplinary group missed statistical significance yet showed a medium sized long-term effect. The groups did not differ in their changes of the psychosocial variables of interest. There was evidence of long-term effects of the interventions on pain-related disability, but there was no effect on the other variables of interest. This may be partially explained by participant's low comorbidities at baseline. Results are important regarding costless homebased alternatives for back pain patients and prevention tasks. Furthermore, this study closes the gap of missing long-term effect analysis in this field.
Symmetric, elegantly entangled structures are a curious mathematical construction that has found their way into the heart of the chemistry lab and the toolbox of constructive geometry. Of particular interest are those structures—knots, links and weavings—which are composed locally of simple twisted strands and are globally symmetric. This paper considers the symmetric tangling of multiple 2-periodic honeycomb networks. We do this using a constructive methodology borrowing elements of graph theory, low-dimensional topology and geometry. The result is a wide-ranging enumeration of symmetric tangled honeycomb networks, providing a foundation for their exploration in both the chemistry lab and the geometers toolbox.
This thesis covers the synthesis of conjugates of 2-Deoxy-D-ribose-5-phosphate aldolase (DERA) with suitable polymers and the subsequent immobilization of these conjugates in thin films via two different approaches.
2-Deoxy-D-ribose-5-phosphate aldolase (DERA) is a biocatalyst that is capable of converting acetaldehyde and a second aldehyde as acceptor into enantiomerically pure mono- and diyhydroxyaldehydes, which are important structural motifs in a number of pharmaceutically active compounds. Conjugation and immobilization renders the enzyme applicable for utilization in a continuously run biocatalytic process which avoids the common problem of product inhibition. Within this thesis, conjugates of DERA and poly(N-isopropylacrylamide) (PNIPAm) for immobilization via a self-assembly approach were synthesized and isolated, as well as conjugates with poly(N,N-dimethylacrylamide) (PDMAA) for a simplified and scalable spray-coating approach. For the DERA/PNIPAm-conjugates different synthesis routes were tested, including grafting-from and grafting-to, both being common methods for the conjugation. Furthermore, both lysines and cysteines were addressed for the conjugation in order to find optimum conjugation conditions. It turned out that conjugation via lysine causes severe activity loss as one lysine plays a key role in the catalyzing mechanism. The conjugation via the cysteines by a grafting-to approach using pyridyl disulfide (PDS) end-group functionalized polymers led to high conjugation efficiencies in the presence of polymer solubilizing NaSCN. The resulting conjugates maintained enzymatic activity and also gained high acetaldehyde tolerance which is necessary for their use later on in an industrial relevant process after their immobilization.
The resulting DERA/PNIPAm conjugates exhibited enhanced interfacial activity at the air/water interface compared to the single components, which is an important pre-requisite for the immobilization via the self-assembly approach. Conjugates with longer polymer chains formed homogeneous films on silicon wafers and glass slides while the ones with short chains could only form isolated aggregates. On top of that, long chain conjugates showed better activity maintenance upon the immobilization.
The crosslinking of conjugates, as well as their fixation on the support materials, are important for the mechanical stability of the films obtained from the self-assembly process. Therefore, in a second step, we introduced the UV-crosslinkable monomer DMMIBA to the PNIPAm polymers to be used for conjugation. The introduction of DMMIBA reduced the lower critical solution temperature (LCST) of the polymer and thus the water solubility at ambient conditions, resulting in lower conjugation efficiencies and in turn slightly poorer acetaldehyde tolerance of the resulting conjugates. Unlike the DERA/PNIPAm, the conjugates from the copolymer P(NIPAM-co-DMMIBA) formed continuous, homogenous films only after the crosslinking step via UV-treatment. For a firm binding of the crosslinked films, a functionalization protocol for the model support material cyclic olefin copolymer (COC) and the final target support, PAN based membranes, was developed that introduces analogue UV-reactive groups to the support surface. The conjugates immobilized on the modified COC films maintained enzymatic activity and showed good mechanical stability after several cycles of activity assessment. Conjugates with longer polymer chains, however, showed a higher degree of crosslinking after the UV-treatment leading to a pronounced loss of activity. A porous PAN membrane onto which the conjugates were immobilized as well, was finally transferred to a dead end filtration membrane module to catalyze the aldol reaction of the industrially relevant mixture of acetaldehyde and hexanal in a continuous mode. Mono aldol product was detectable, but yields were comparably low and the operational stability needs to be further improved
Another approach towards immobilization of DERA conjugates that was followed, was to generate the conjugates in situ by simply mixing enzyme and polymer and spray coat the mixture onto the membrane support. Compared to the previous approach, the focus was more put on simplicity and a possible scalability of the immobilization. Conjugates were thus only generated in-situ and not further isolated and characterized. For the conjugation, PDMAA equipped with N-2-thiolactone acrylamide (TlaAm) side chains was used, an amine-reactive comonomer that can react with the lysine residues of DERA, as well as with amino groups introduced to a desired support surface. Furthermore disulfide formation after hydrolysis of the Tla groups causes a crosslinking effect. The synthesized copolymer poly(N,N-Dimethylacrylamide-co-N-2-thiolactone acrylamide) (P(DMAA-co-TlaAm)) thus serves a multiple purpose including protein binding, crosslinking and binding to support materials. The mixture of DERA and polymer could be immobilized on the PAN support by spray-coating under partial maintenance of enzymatic activity. To improve the acetaldehyde tolerance, the polymer in used was further equipped with cysteine reactive PDS end-groups that had been used for the conjugation as described in the first part of the thesis. The generated conjugates indeed showed good acetaldehyde tolerance and were thus used to be coated onto PAN membrane supports. Post treatment with a basic aqueous solution of H2O2 was supposed to further crosslink the spray-coated film hydrolysis and oxidation of the thiolactone groups. However, a washing off of the material was observed. Optimization is thus still necessary.
Intelligence, as well as working memory and attention, affect the acquisition of mathematical competencies. This paper aimed to examine the influence of working memory and attention when taking different mathematical skills into account as a function of children’s intellectual ability. Overall, intelligence, working memory, attention and numerical skills were assessed twice in 1868 German pre-school children (t1, t2) and again at 2nd grade (t3). We defined three intellectual ability groups based on the results of intellectual assessment at t1 and t2. Group comparisons revealed significant differences between the three intellectual ability groups. Over time, children with low intellectual ability showed the lowest achievement in domain-general and numerical and mathematical skills compared to children of average intellectual ability. The highest achievement on the aforementioned variables was found for children of high intellectual ability. Additionally, path modelling revealed that, depending on the intellectual ability, different models of varying complexity could be generated. These models differed with regard to the relevance of the predictors (t2) and the future mathematical skills (t3). Causes and conclusions of these findings are discussed.
The study examined the potential future changes of drought characteristics in the Greater Lake Malawi Basin in Southeast Africa. This region strongly depends on water resources to generate electricity and food. Future projections (considering both moderate and high emission scenarios) of temperature and precipitation from an ensemble of 16 bias-corrected climate model combinations were blended with a scenario-neutral response surface approach to analyses changes in: (i) the meteorological conditions, (ii) the meteorological water balance, and (iii) selected drought characteristics such as drought intensity, drought months, and drought events, which were derived from the Standardized Precipitation and Evapotranspiration Index. Changes were analyzed for a near-term (2021–2050) and far-term period (2071–2100) with reference to 1976–2005. The effect of bias-correction (i.e., empirical quantile mapping) on the ability of the climate model ensemble to reproduce observed drought characteristics as compared to raw climate projections was also investigated. Results suggest that the bias-correction improves the climate models in terms of reproducing temperature and precipitation statistics but not drought characteristics. Still, despite the differences in the internal structures and uncertainties that exist among the climate models, they all agree on an increase of meteorological droughts in the future in terms of higher drought intensity and longer events. Drought intensity is projected to increase between +25 and +50% during 2021–2050 and between +131 and +388% during 2071–2100. This translates into +3 to +5, and +7 to +8 more drought months per year during both periods, respectively. With longer lasting drought events, the number of drought events decreases. Projected droughts based on the high emission scenario are 1.7 times more severe than droughts based on the moderate scenario. That means that droughts in this region will likely become more severe in the coming decades. Despite the inherent high uncertainties of climate projections, the results provide a basis in planning and (water-)managing activities for climate change adaptation measures in Malawi. This is of particular relevance for water management issues referring hydro power generation and food production, both for rain-fed and irrigated agriculture.
In this study, we analyze interactions in lake and lake catchment systems of a continuous permafrost area. We assessed colored dissolved organic matter (CDOM) absorption at 440 nm (a(440)(CDOM)) and absorption slope (S300-500) in lakes using field sampling and optical remote sensing data for an area of 350 km(2) in Central Yamal, Siberia. Applying a CDOM algorithm (ratio of green and red band reflectance) for two high spatial resolution multispectral GeoEye-1 and Worldview-2 satellite images, we were able to extrapolate the a()(CDOM) data from 18 lakes sampled in the field to 356 lakes in the study area (model R-2 = 0.79). Values of a(440)(CDOM) in 356 lakes varied from 0.48 to 8.35 m(-1) with a median of 1.43 m(-1). This a()(CDOM) dataset was used to relate lake CDOM to 17 lake and lake catchment parameters derived from optical and radar remote sensing data and from digital elevation model analysis in order to establish the parameters controlling CDOM in lakes on the Yamal Peninsula. Regression tree model and boosted regression tree analysis showed that the activity of cryogenic processes (thermocirques) in the lake shores and lake water level were the two most important controls, explaining 48.4% and 28.4% of lake CDOM, respectively (R-2 = 0.61). Activation of thermocirques led to a large input of terrestrial organic matter and sediments from catchments and thawed permafrost to lakes (n = 15, mean a(440)(CDOM) = 5.3 m(-1)). Large lakes on the floodplain with a connection to Mordy-Yakha River received more CDOM (n = 7, mean a(440)(CDOM) = 3.8 m(-1)) compared to lakes located on higher terraces.