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Exendin-4 is a pharmaceutical peptide used in the control of insulin secretion. Structural information on exendin-4 and related peptides especially on the level of quaternary structure is scarce. We present the first published association equilibria of exendin-4 directly measured by static and dynamic light scattering. We show that exendin-4 oligomerization is pH dependent and that these oligomers are of low compactness. We relate our experimental results to a structural hypothesis to describe molecular details of exendin-4 oligomers. Discussion of the validity of this hypothesis is based on NMR, circular dichroism and fluorescence spectroscopy, and light scattering data on exendin-4 and a set of exendin-4 derived peptides. The essential forces driving oligomerization of exendin-4 are helix–helix interactions and interactions of a conserved hydrophobic moiety. Our structural hypothesis suggests that key interactions of exendin-4 monomers in the experimentally supported trimer take place between a defined helical segment and a hydrophobic triangle constituted by the Phe22 residues of the three monomeric subunits. Our data rationalize that Val19 might function as an anchor in the N-terminus of the interacting helix-region and that Trp25 is partially shielded in the oligomer by C-terminal amino acids of the same monomer. Our structural hypothesis suggests that the Trp25 residues do not interact with each other, but with C-terminal Pro residues of their own monomers.
Atmospheric water vapour content is a key variable that controls the development of deep convective storms and rainfall extremes over the central Andes. Direct measurements of water vapour are challenging; however, recent developments in microwave processing allow the use of phase delays from L-band radar to measure the water vapour content throughout the atmosphere: Global Navigation Satellite System (GNSS)-based integrated water vapour (IWV) monitoring shows promising results to measure vertically integrated water vapour at high temporal resolutions. Previous works also identified convective available potential energy (CAPE) as a key climatic variable for the formation of deep convective storms and rainfall in the central Andes. Our analysis relies on GNSS data from the Argentine Continuous Satellite Monitoring Network, Red Argentina de Monitoreo Satelital Continuo (RAMSAC) network from 1999 to 2013. CAPE is derived from version 2.0 of the ECMWF’s (European Centre for Medium-Range Weather Forecasts) Re-Analysis (ERA-interim) and rainfall from the TRMM (Tropical Rainfall Measuring Mission) product. In this study, we first analyse the rainfall characteristics of two GNSS-IWV stations by comparing their complementary cumulative distribution function (CCDF). Second, we separately derive the relation between rainfall vs. CAPE and GNSS-IWV. Based on our distribution fitting analysis, we observe an exponential relation of rainfall to GNSS-IWV. In contrast, we report a power-law relationship between the daily mean value of rainfall and CAPE at the GNSS-IWV station locations in the eastern central Andes that is close to the theoretical relationship based on parcel theory. Third, we generate a joint regression model through a multivariable regression analysis using CAPE and GNSS-IWV to explain the contribution of both variables in the presence of each other to extreme rainfall during the austral summer season. We found that rainfall can be characterised with a higher statistical significance for higher rainfall quantiles, e.g., the 0.9 quantile based on goodness-of-fit criterion for quantile regression. We observed different contributions of CAPE and GNSS-IWV to rainfall for each station for the 0.9 quantile. Fourth, we identify the temporal relation between extreme rainfall (the 90th, 95th, and 99th percentiles) and both GNSS-IWV and CAPE at 6 h time steps. We observed an increase before the rainfall event and at the time of peak rainfall—both for GNSS-integrated water vapour and CAPE. We show higher values of CAPE and GNSS-IWV for higher rainfall percentiles (99th and 95th percentiles) compared to the 90th percentile at a 6-h temporal scale. Based on our correlation analyses and the dynamics of the time series, we show that both GNSS-IWV and CAPE had comparable magnitudes, and we argue to consider both climatic variables when investigating their effect on rainfall extremes.
We consider a sequential cascade of molecular first-reaction events towards a terminal reaction centre in which each reaction step is controlled by diffusive motion of the particles. The model studied here represents a typical reaction setting encountered in diverse molecular biology systems, in which, e.g. a signal transduction proceeds via a series of consecutive 'messengers': the first messenger has to find its respective immobile target site triggering a launch of the second messenger, the second messenger seeks its own target site and provokes a launch of the third messenger and so on, resembling a relay race in human competitions. For such a molecular relay race taking place in infinite one-, two- and three-dimensional systems, we find exact expressions for the probability density function of the time instant of the terminal reaction event, conditioned on preceding successful reaction events on an ordered array of target sites. The obtained expressions pertain to the most general conditions: number of intermediate stages and the corresponding diffusion coefficients, the sizes of the target sites, the distances between them, as well as their reactivities are arbitrary.
Monoclonal antibodies are used worldwide as highly potent and efficient detection reagents for research and diagnostic applications. Nevertheless, the specific targeting of complex antigens such as whole microorganisms remains a challenge. To provide a comprehensive workflow, we combined bioinformatic analyses with novel immunization and selection tools to design monoclonal antibodies for the detection of whole microorganisms. In our initial study, we used the human pathogenic strain E. coli O157:H7 as a model target and identified 53 potential protein candidates by using reverse vaccinology methodology. Five different peptide epitopes were selected for immunization using epitope-engineered viral proteins. The identification of antibody-producing hybridomas was performed by using a novel screening technology based on transgenic fusion cell lines. Using an artificial cell surface receptor expressed by all hybridomas, the desired antigen-specific cells can be sorted fast and efficiently out of the fusion cell pool. Selected antibody candidates were characterized and showed strong binding to the target strain E. coli O157:H7 with minor or no cross-reactivity to other relevant microorganisms such as Legionella pneumophila and Bacillus ssp. This approach could be useful as a highly efficient workflow for the generation of antibodies against microorganisms.
Objective
The Caribbean is an important global biodiversity hotspot. Adaptive radiations there lead to many speciation events within a limited period and hence are particularly prominent biodiversity generators. A prime example are freshwater fish of the genus Limia, endemic to the Greater Antilles. Within Hispaniola, nine species have been described from a single isolated site, Lake Miragoâne, pointing towards extraordinary sympatric speciation. This study examines the evolutionary history of the Limia species in Lake Miragoâne, relative to their congeners throughout the Caribbean.
Results
For 12 Limia species, we obtained almost complete sequences of the mitochondrial cytochrome b gene, a well-established marker for lower-level taxonomic relationships. We included sequences of six further Limia species from GenBank (total N = 18 species). Our phylogenies are in concordance with other published phylogenies of Limia. There is strong support that the species found in Lake Miragoâne in Haiti are monophyletic, confirming a recent local radiation. Within Lake Miragoâne, speciation is likely extremely recent, leading to incomplete lineage sorting in the mtDNA. Future studies using multiple unlinked genetic markers are needed to disentangle the relationships within the Lake Miragoâne clade.
Background
Relatively little is known about protective factors and the emergence and maintenance of positive outcomes in the field of adolescents with chronic conditions. Therefore, the primary aim of the study is to acquire a deeper understanding of the dynamic process of resilience factors, coping strategies and psychosocial adjustment of adolescents living with chronic conditions.
Methods/design
We plan to consecutively recruit N = 450 adolescents (12–21 years) from three German patient registries for chronic conditions (type 1 diabetes, cystic fibrosis, or juvenile idiopathic arthritis). Based on screening for anxiety and depression, adolescents are assigned to two parallel groups – “inconspicuous” (PHQ-9 and GAD-7 < 7) vs. “conspicuous” (PHQ-9 or GAD-7 ≥ 7) – participating in a prospective online survey at baseline and 12-month follow-up. At two time points (T1, T2), we assess (1) intra- and interpersonal resiliency factors, (2) coping strategies, and (3) health-related quality of life, well-being, satisfaction with life, anxiety and depression. Using a cross-lagged panel design, we will examine the bidirectional longitudinal relations between resiliency factors and coping strategies, psychological adaptation, and psychosocial adjustment. To monitor Covid-19 pandemic effects, participants are also invited to take part in an intermediate online survey.
Discussion
The study will provide a deeper understanding of adaptive, potentially modifiable processes and will therefore help to develop novel, tailored interventions supporting a positive adaptation in youths with a chronic condition. These strategies should not only support those at risk but also promote the maintenance of a successful adaptation.
Trial registration
German Clinical Trials Register (DRKS), no. DRKS00025125. Registered on May 17, 2021.
A tale of shifting relations
(2021)
Understanding the dynamics between the East Asian summer (EASM) and winter monsoon (EAWM) is needed to predict their variability under future global warming scenarios. Here, we investigate the relationship between EASM and EAWM as well as the mechanisms driving their variability during the last 10,000 years by stacking marine and terrestrial (non-speleothem) proxy records from the East Asian realm. This provides a regional and proxy independent signal for both monsoonal systems. The respective signal was subsequently analysed using a linear regression model. We find that the phase relationship between EASM and EAWM is not time-constant and significantly depends on orbital configuration changes. In addition, changes in the Atlantic Meridional Overturning circulation, Arctic sea-ice coverage, El Niño-Southern Oscillation and Sun Spot numbers contributed to millennial scale changes in the EASM and EAWM during the Holocene. We also argue that the bulk signal of monsoonal activity captured by the stacked non-speleothem proxy records supports the previously argued bias of speleothem climatic archives to moisture source changes and/or seasonality.
Background: High-intensity muscle actions have the potential to temporarily improve the performance which has been denoted as postactivation performance enhancement.
Objectives: This study determined the acute effects of different stretch-shortening (fast vs. low) and strength (dynamic vs. isometric) exercises executed during one training session on subsequent balance performance in youth weightlifters.
Materials and Methods: Sixteen male and female young weightlifters, aged 11.3±0.6years, performed four strength exercise conditions in randomized order, including dynamic strength (DYN; 3 sets of 3 repetitions of 10 RM) and isometric strength exercises (ISOM; 3 sets of maintaining 3s of 10 RM of back-squat), as well as fast (FSSC; 3 sets of 3 repetitions of 20-cm drop-jumps) and slow (SSSC; 3 sets of 3 hurdle jumps over a 20-cm obstacle) stretch-shortening cycle protocols. Balance performance was tested before and after each of the four exercise conditions in bipedal stance on an unstable surface (i.e., BOSU ball with flat side facing up) using two dependent variables, i.e., center of pressure surface area (CoP SA) and velocity (CoP V).
Results: There was a significant effect of time on CoP SA and CoP V [F(1,60)=54.37, d=1.88, p<0.0001; F(1,60)=9.07, d=0.77, p=0.003]. In addition, a statistically significant effect of condition on CoP SA and CoP V [F(3,60)=11.81, d=1.53, p<0.0001; F(3,60)=7.36, d=1.21, p=0.0003] was observed. Statistically significant condition-by-time interactions were found for the balance parameters CoP SA (p<0.003, d=0.54) and CoP V (p<0.002, d=0.70). Specific to contrast analysis, all specified hypotheses were tested and demonstrated that FSSC yielded significantly greater improvements than all other conditions in CoP SA and CoP V [p<0.0001 (d=1.55); p=0.0004 (d=1.19), respectively]. In addition, FSSC yielded significantly greater improvements compared with the two conditions for both balance parameters [p<0.0001 (d=2.03); p<0.0001 (d=1.45)].
Conclusion: Fast stretch-shortening cycle exercises appear to be more effective to improve short-term balance performance in young weightlifters. Due to the importance of balance for overall competitive achievement in weightlifting, it is recommended that young weightlifters implement dynamic plyometric exercises in the fast stretch-shortening cycle during the warm-up to improve their balance performance.
Populations adapt to novel environmental conditions by genetic changes or phenotypic plasticity. Plastic responses are generally faster and can buffer fitness losses under variable conditions. Plasticity is typically modeled as random noise and linear reaction norms that assume simple one-to- one genotype–phenotype maps and no limits to the phenotypic response. Most studies on plasticity have focused on its effect on population viability. However, it is not clear, whether the advantage of plasticity depends solely on environmental fluctuations or also on the genetic and demographic properties (life histories) of populations. Here we present an individual-based model and study the relative importance of adaptive and nonadaptive plasticity for populations of sexual species with different life histories experiencing directional stochastic climate change. Environmental fluctuations were simulated using differentially autocorrelated climatic stochasticity or noise color, and scenarios of directiona
climate change. Nonadaptive plasticity was simulated as a random environmental effect on trait development, while adaptive plasticity as a linear, saturating, or sinusoidal reaction norm. The last two imposed limits to the plastic response and emphasized flexible interactions of the genotype with the environment. Interestingly, this assumption led to (a) smaller phenotypic than genotypic variance in the population (many-to- one genotype–phenotype map) and the coexistence of polymorphisms, and (b) the maintenance of higher genetic variation—compared to linear reaction norms and genetic determinism—even when the population was exposed to a constant environment for several generations. Limits to plasticity led to genetic accommodation, when costs were negligible, and to the appearance of cryptic variation when limits were exceeded. We found that adaptive plasticity promoted population persistence under red environmental noise and was particularly important for life histories with low fecundity. Populations produing more offspring could cope with environmental fluctuations solely by genetic changes or random plasticity, unless environmental change was too fast.