Multiscale Simulations Suggest a Mechanism for the Association of the Dok7 PH Domain with PIP-Containing Membranes

Dok7 is a peripheral membrane protein that is associated with the MuSK receptor tyrosine kinase. Formation of the Dok7/MuSK/membrane complex is required for the activation of MuSK. This is a key step in the complex exchange of signals between neuron and muscle, which lead to neuromuscular junction formation, dysfunction of which is associated with congenital myasthenic syndromes. The Dok7 structure consists of a Pleckstrin Homology (PH) domain and a Phosphotyrosine Binding (PTB) domain. The mechanism of the Dok7 association with the membrane remains largely unknown. Using multi-scale molecular dynamics simulations we have explored the formation of the Dok7 PH/membrane complex. Our simulations indicate that the PH domain of Dok7 associates with membranes containing phosphatidylinositol phosphates (PIPs) via interactions of the β1/β2, β3/β4, and β5/β6 loops, which together form a positively charged surface on the PH domain and interact with the negatively charged headgroups of PIP molecules. The initial encounter of the Dok7 PH domain is followed by formation of additional interactions with the lipid bilayer, and especially with PIP molecules, which stabilizes the Dok7 PH/membrane complex. We have quantified the binding of the PH domain to the model bilayers by calculating a density landscape for protein/membrane interactions. Detailed analysis of the PH/PIP interactions reveal both a canonical and an atypical site to be occupied by the anionic lipid. PH domain binding leads to local clustering of PIP molecules in the bilayer. Association of the Dok7 PH domain with PIP lipids is therefore seen as a key step in localization of Dok7 to the membrane and formation of a complex with MuSK

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

TRY plant trait database - enhanced coverage and open access

Plant traits—the morphological, anatomical, physiological, biochemical and phenological characteristics of plants—determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits—almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Search for gravitational waves associated with gamma-ray bursts detected by Fermi and Swift during the LIGO–Virgo run O3b

We search for gravitational-wave signals associated with gamma-ray bursts (GRBs) detected by the Fermi and Swift satellites during the second half of the third observing run of Advanced LIGO and Advanced Virgo (2019 November 1 15:00 UTC–2020 March 27 17:00 UTC). We conduct two independent searches: a generic gravitational-wave transients search to analyze 86 GRBs and an analysis to target binary mergers with at least one neutron star as short GRB progenitors for 17 events. We find no significant evidence for gravitational-wave signals associated with any of these GRBs. A weighted binomial test of the combined results finds no evidence for subthreshold gravitational-wave signals associated with this GRB ensemble either. We use several source types and signal morphologies during the searches, resulting in lower bounds on the estimated distance to each GRB. Finally, we constrain the population of low-luminosity short GRBs using results from the first to the third observing runs of Advanced LIGO and Advanced Virgo. The resulting population is in accordance with the local binary neutron star merger rate

Cardiopulmonary response and body composition changes after prolonged high altitude exposure in women.

Weight loss in men is commonly observed during prolonged high altitude exposure as a result of a daily negative energy balance. Its amount depends mainly on duration of exposure, altitude reached, and level of physical activity. This reduction in body weight often comes with a loss of muscular mass, likely contributing to the decreased physical performance generally reported. Limited data is, however, available on body composition, functional capacity, and cardiopulmonary response to exercise after high altitude exposure in women. The aim of this study was to evaluate the effects of prolonged high altitude exposure on body composition and on cardiopulmonary response to maximal exercise in a group of young, moderately active women. Twelve female subjects, aged 21.5 \u2013 3.1 (mean \u2013 SD), BMI 22.1 \u2013 1.9kg$m- 2 and Vo2max 33.8 \u2013 3.5mL$kg- 1$min- 1, participated in this study, by residing for 21 days at high altitude (5050 m, Pyramid, EV-K2-CNR laboratory). Before and after high altitude exposure, all subjects underwent both a body composition evaluation using two methods (bioimpedance analysis and DEXA) and a functional evaluation based on a maximal exercise test on a cycle ergometer with breath-by-breath gas analysis. After high altitude exposure, data showed a slight, nonsignificant reduction in body weight, with an average 3:2 reduction ratio between fat and fat-free mass evaluated by DEXA, in addition to a significant decrease in Vo2max on the cycle ergometer test ( p < 0.01). Changes in Vo2max correlated to changes of leg muscle mass variations, evaluated by DEXA (r2 = 0.72; p < 0.0001). No changes were observed in the maximal heart rate, work capacity, and ventilatory thresholds, while the Vo2/W slope was significantly reduced ( p < 0.05). Finally, Ve/Vo2 and VE/Vco2max slopes were increased ( p < 0.01), suggesting a possible long-term modulation of the exercise ventilatory response after prolonged high altitude exposure

Cardiopulmonary response and body composition changes after prolonged high altitude exposure in women.

Weight loss in men is commonly observed during prolonged high altitude exposure as a result of a daily negative energy balance. Its amount depends mainly on duration of exposure, altitude reached, and level of physical activity. This reduction in body weight often comes with a loss of muscular mass, likely contributing to the decreased physical performance generally reported. Limited data is, however, available on body composition, functional capacity, and cardiopulmonary response to exercise after high altitude exposure in women. The aim of this study was to evaluate the effects of prolonged high altitude exposure on body composition and on cardiopulmonary response to maximal exercise in a group of young, moderately active women. Twelve female subjects, aged 21.5 \ub1 3.1 (mean \ub1 SD), BMI 22.1 \ub1 1.9 kg \ub7 m(-2) and Vo(2max) 33.8 \ub1 3.5 mL \ub7 kg(-1) \ub7 min(-1), participated in this study, by residing for 21 days at high altitude (5050 m, Pyramid, EV-K(2)-CNR laboratory). Before and after high altitude exposure, all subjects underwent both a body composition evaluation using two methods (bioimpedance analysis and DEXA) and a functional evaluation based on a maximal exercise test on a cycle ergometer with breath-by-breath gas analysis. After high altitude exposure, data showed a slight, nonsignificant reduction in body weight, with an average 3:2 reduction ratio between fat and fat-free mass evaluated by DEXA, in addition to a significant decrease in Vo(2max) on the cycle ergometer test (p<0.01). Changes in Vo(2max) correlated to changes of leg muscle mass, evaluated by DEXA (r(2) = 0.72; p<0.0001). No changes were observed in the maximal heart rate, work capacity, and ventilatory thresholds, while the Vo(2)/W slope was significantly reduced (p<0.05). Finally, Ve/Vo(2) and VE/Vco(2max) slopes were increased (p<0.01), suggesting a possible long-term modulation of the exercise ventilatory response after prolonged high altitude exposure