bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating abundance of a recovering transboundary brown bear population with capture-recapture models
Authors: Vanpé Cécile , Piédallu Blaise , Quenette Pierre-Yves , Sentilles Jérôme , Queney Guillaume , Palazón Santiago , Jordana Ivan Afonso , Jato Ramón , Irurtia Miguel Mari Elósegui , de la Torre Jordi Solà , Gimenez Olivier 
Published: December 2021

AbstractEstimating the size of small populations of large mammals can be achieved via censuses, or complete counts, of recognizable individuals detected over a time period: minimum detected (population) size (MDS). However, as a population grows larger and its spatial distribution expands, the risk of under-estimating population size using MDS rapidly increases because the assumption of perfect detection of all individuals in the population is violated. The need to report uncertainty around population size estimates consequently becomes crucial. We explored these biases using the monitoring framework of the critically endangered Pyrenean brown bear that was close to extinction in the mid-1990s, with only five individuals remaining, but was subsequently bolstered by the introduction of 11 bears from Slovenia. Each year since 1996, the abundance of the population has been assessed using MDS and minimum retained (population) size (MRS), which corresponded to a reassessment of the MDS in the light of the new information collected in subsequent years (e.g., adding bears which were not detected the previous years but detected the current year). We used Pollock’s closed robust design (PCRD) capture-recapture models applied to the cross-border non-invasive sampling data from France, Spain and Andorra to provide the first published annual abundance and temporal trend estimates of the Pyrenean brown bear population since 2008. Annual population size increased fivefold between 2008 and 2020, going from 13 to 66 individuals. PCRD estimates were globally close to MRS counts and had reasonably narrow associated 95% Credibility Intervals. Even in cases where sampling effort is large compared to population size, the PCRD estimates of population size can diverge from the MDS counts. We report individual heterogeneity in detection that might stem from intraspecific home range size variation that result in individuals that move the most being most likely to be detected. We also found that cubs had a higher mortality rate than adults and subadults, because of infanticide by males, predation, maternal death, or abandonment. Overall, the PCRD capture-recapture modelling approach provides estimates of abundance and demographic rates of the Pyrenean brown bear population, together with associated uncertainty, while minimizing bias due to inter-individual heterogeneity in detection probabilities. We strongly encourage wildlife ecologists and managers to use robust approaches when researching large mammal populations. Such information is vital for informing management decision-making and assessing population conservation status.
Can pyrethroid-piperonyl butoxide (PBO) nets reduce the efficacy of indoor residual spraying with pirimiphos-methyl against pyrethroid-resistant malaria vectors?
Authors: Syme Thomas , Gbegbo Martial , Obuobi Dorothy , Fongnikin Augustin , Agbevo Abel , Todjinou Damien , Ngufor Corine 
Published: December 2021

AbstractAs the uptake of pyrethroid-PBO ITNs increases, their combination with IRS insecticides could become an operational reality in many malaria-endemic communities. Pirimiphos-methyl is a pro-insecticide requiring activation by mosquito cytochrome P450 enzymes to induce toxicity while PBO blocks activation of these enzymes in pyrethroid-resistant vector mosquitoes. PBO may thus antagonise the toxicity of pirimiphos-methyl IRS when combined with pyrethroid-PBO ITNs. The impact of combining two major brands of pyrethroid-PBO ITNs (Olyset® Plus, PermaNet® 3.0) with pirimiphos-methyl IRS (Actellic® 300CS) was evaluated against pyrethroid-resistant Anopheles gambiae sl in two parallel experimental hut trials in southern Benin in comparison to bendiocarb IRS and each intervention alone. The wild vector population was resistant to pyrethroids but susceptible to pirimiphos-methyl and bendiocarb. PBO pre-exposure partially restored deltamethrin toxicity but not permethrin. Mosquito mortality in experimental huts was significantly improved in the combinations of bendiocarb IRS with Olyset® Plus (33%) and PermaNet® 3.0 (38%) compared to bendiocarb IRS alone (14–16%, p<0.001), demonstrating an additive effect. Conversely, mortality was significantly reduced in the combinations of pirimiphos-methyl IRS with Olyset® Plus (59%) and PermaNet® 3.0 (55%) compared to pirimiphos-methyl IRS alone (77–78%, p<0.001), demonstrating an antagonistic effect. Combining pirimiphos-methyl IRS with the pyrethroid-PBO ITNs provided significantly improved mosquito mortality (55-59%) compared to the pyrethroid-PBO ITNs alone (22-26%) and improved blood-feeding inhibition relative to the IRS alone. This study provided evidence of an antagonistic effect when pyrethroid-PBO ITNs were combined with pirimiphos-methyl IRS in the same household resulting in lower levels of vector mosquito mortality compared to the IRS alone. Pirimiphos-methyl IRS also showed potential to significantly enhance malaria control when deployed to complement pyrethroid-PBO ITNs in an area where PBO fails to fully restore susceptibility to pyrethroids.
Ca2+ oscillations, waves, and networks in islets from human donors with and without type 2 diabetes
Authors: Gosak Marko , Yan-Do Richard , Lin Haopeng , MacDonald Patrick E. , Stožer Andraž 
Published: December 2021

AbstractPancreatic islets are highly interconnected structures that produce pulses of insulin and other hormones, maintaining normal homeostasis of glucose and other nutrients. Normal stimulus-secretion and intercellular coupling are essential to regulated secretory responses and these hallmarks are known to be altered in diabetes. In the present study, we used calcium imaging of isolated human islets to assess their collective cell behavior. The activity occurred in the form of calcium oscillations, was synchronized across different regions of islets through calcium waves, and was glucose-dependent: higher glucose enhanced the activity, elicited a greater proportion of global calcium waves, and led to denser and less fragmented functional networks. Hub regions were identified in stimulatory conditions, and they represented the most active islet regions. Moreover, calcium waves were found to be initiated in different subregions and the roles of initiators and hubs did not overlap. In type 2 diabetes, glucose-dependence was retained, but a reduced activity, locally restricted waves, and more segregated networks were detected compared with control islets. Interestingly, hub regions seemed to suffer the most by losing a disproportionately large fraction of connections. These changes affected islets from donors with diabetes in a heterogeneous manner.
The channel capacity of multilevel linguistic features constrains speech comprehension
Authors: Giroud Jérémy , Lerousseau Jacques Pesnot , Pellegrino François , Morillon Benjamin 
Published: December 2021

AbstractHumans are expert at processing speech but how this feat is accomplished remains a major question in cognitive neuroscience. Capitalizing on the concept of channel capacity, we developed a unified measurement framework to investigate the respective influence of seven acoustic and linguistic features on speech comprehension, encompassing acoustic, sub-lexical, lexical and supra-lexical levels of description. We show that comprehension is independently impacted by all these features, but at varying degrees and with a clear dominance of the syllabic rate. Comparing comprehension of French words and sentences further reveals that when supra-lexical contextual information is present, the impact of all other features is dramatically reduced. Finally, we estimated the channel capacity associated with each linguistic feature and compared them with their generic distribution in natural speech. Our data point towards supra-lexical contextual information as the feature limiting the flow of natural speech. Overall, this study reveals how multilevel linguistic features constrain speech comprehension.
Differential Compositional Variation Feature Selection: A Machine Learning Framework with Log Ratios for Compositional Metagenomic Data
Authors: Hinton Andrew L. , Mucha Peter J. 
Published: December 2021

ABSTRACTThe demand for tight integration of compositional data analysis and machine learning methodologies for predictive modeling in high-dimensional settings has increased dramatically with the increasing availability of metagenomics data. We develop the differential compositional variation machine learning framework (DiCoVarML) with robust multi-level log ratio bio-marker discovery for metagenomic datasets. Our framework makes use of the full set of pairwise log ratios, scoring ratios according to their variation between classes and then selecting out a small subset of log ratios to accurately predict classes. Importantly, DiCoVarML supports a targeted feature selection mode enabling researchers to define the number of predictors used to develop models. We demonstrate the performance of our framework for binary classification tasks using both synthetic and real datasets. Selecting from all pairwise log ratios within the DiCoVarML framework provides greater flexibility that can in demonstrated cases lead to higher accuracy and enhanced biological insight.
Induced fit with replica exchange improves protein complex structure prediction
Authors: Harmalkar Ameya , Mahajan Sai Pooja , Gray Jeffrey J. 
Published: December 2021

Despite the progress in prediction of protein complexes over the last decade, recent blind protein complex structure prediction challenges revealed limited success rates (less than 20% models with DockQ score > 0.4) on targets that exhibit significant conformational change upon binding. To overcome limitations in capturing backbone motions, we developed a new, aggressive sampling method that incorporates temperature replica exchange Monte Carlo (T-REMC) and conformational sampling techniques within docking protocols in Rosetta. Our method, ReplicaDock 2.0, mimics induced-fit mechanism of protein binding to sample backbone motions across putative interface residues on-the-fly, thereby recapitulating binding-partner induced conformational changes. Furthermore, ReplicaDock 2.0 clocks in at 150-500 CPU hours per target (protein-size dependent); a runtime that is significantly faster than Molecular Dynamics based approaches. For a benchmark set of 88 proteins with moderate to high flexibility (unbound-to-bound iRMSD over 1.2 Å), ReplicaDock 2.0 successfully docks 61% of moderately flexible complexes and 35% of highly flexible complexes. Additionally, we demonstrate that by biasing backbone sampling particularly towards residues comprising flexible loops or hinge domains, highly flexible targets can be predicted to under 2 Å accuracy. This indicates that additional gains are possible when mobile protein segments are known.Significance StatementProteins bind each other in a highly specific and regulated manner, and these associated dynamics of binding are intimately linked to their function. Conventional techniques of structure determination such as cryo-EM, X-ray crystallography and NMR are time-consuming and arduous. Using a temperature-replica exchange Monte Carlo approach that mimics the kinetic mechanism of “induced fit” binding, we improved prediction of protein complex structures, particularly for targets that exhibit considerable conformational changes upon binding (Interface root mean square deviation (unbound-bound) > 1.2 Å. Capturing these binding-induced conformational changes in proteins can aid us in better understanding biological mechanisms and suggest intervention strategies for disease mechanisms.
A Graph Convolutional Network-based screening strategy for rapid identification of SARS-CoV-2 cell-entry inhibitors
Authors: Gao Peng , Xu Miao , Zhang Qi , Chen Catherine Z , Guo Hui , Ye Yihong , Zheng Wei , Shen Min 
Published: December 2021

AbstractThe cell entry of SARS-CoV-2 has emerged as an attractive drug development target. We previously reported that the entry of SARS-CoV-2 depends on the cell surface heparan sulfate proteoglycan (HSPG) and the cortex actin, which can be targeted by therapeutic agents identified by conventional drug repurposing screens. However, this drug identification strategy requires laborious library screening, which is time-consuming and often limited number of compounds can be screened. As an alternative approach, we developed and trained a graph convolutional network (GCN)-based classification model using information extracted from experimentally identified HSPG and actin inhibitors. This method allowed us to virtually screen 170,000 compounds, resulting in ∼2000 potential hits. A hit confirmation assay with the uptake of a fluorescently labeled HSPG cargo further shortlisted 256 active compounds. Among them, 16 compounds had modest to strong inhibitory activities against the entry of SARS-CoV-2 pseudotyped particles into Vero E6 cells. These results establish a GCN-based virtual screen workflow for rapid identification of new small molecule inhibitors against validated drug targets.Graphical TOC Entry
Functional modulation of PTH1R activation and signalling by RAMP2
Authors: Nemec Katarina , Schihada Hannes , Kleinau Gunnar , Zabel Ulrike , Grushevskyi Eugene O. , Scheerer Patrick , Lohse Martin J. , Maiellaro Isabella 
Published: December 2021

AbstractReceptor-activity-modifying proteins (RAMPs) are ubiquitously expressed membrane proteins that associate with different G protein-coupled receptors (GPCRs) including the parathyroid hormone 1 receptor (PTH1R), a class B GPCR and an important modulator of mineral ion homeostasis and bone metabolism. However, it is unknown whether and how RAMP proteins may affect PTH1R function.Using different optical biosensors to measure the activation of PTH1R and its downstream signalling, we describe here that RAMP2 acts as a specific allosteric modulator of PTH1R, shifting PTH1R to a unique pre-activated state that permits faster activation in a ligand-specific manner. Moreover, RAMP2 modulates PTH1R downstream signalling in an agonist-dependent manner, most notably increasing the PTH-mediated Gi3 signalling sensitivity. Additionally, RAMP2 increases both PTH- and PTHrP-triggered β-arrestin2 recruitment to PTH1R. Employing homology modelling we describe the putative structural molecular basis underlying our functional findings.These data uncover a critical role of RAMPs in the activation and signalling of a GPCR that may provide a new venue for highly specific modulation of GPCR function and advanced drug design.
Simultaneous quantification of ankle, muscle, and tendon impedance in humans
Authors: Jakubowski Kristen L. , Ludvig Daniel , Bujnowski Daniel , Lee Sabrina S.M. , Perreault Eric J. 
Published: December 2021

AbstractObjectiveRegulating the impedance of our joints is essential for the effective control of posture and movement. The impedance of a joint is governed mainly by the mechanical properties of the muscle-tendon units spanning it. Many studies have quantified the net impedance of joints but not the specific contributions from the muscles and tendons. The inability to quantify both muscle and tendon impedance limits the ability to determine the causes underlying altered movement control associated with aging, neuromuscular injury, and other conditions that have different effects on muscle and tendon properties. Therefore, we developed a technique to quantify joint, muscle, and tendon impedance simultaneously and evaluated this technique at the human ankle.MethodsWe used a single degree of freedom actuator to deliver pseudorandom rotations to the ankle while measuring the corresponding torques. We simultaneously measured the displacement of the medial gastrocnemius muscle-tendon junction with B-mode ultrasound. From these experimental measurements, we were able to estimate ankle, muscle, and tendon impedance using non-parametric system identification.ResultsWe validated our estimates by comparing them to previously reported muscle and tendon stiffness, the position-dependent component of impedance, to demonstrate that our technique generates reliable estimates of these properties.ConclusionOur approach can be used to clarify the respective contributions from the muscle and tendon to the net mechanics of a joint.SignificanceThis is a critical step forward in the ultimate goal of understanding how muscles and tendons govern ankle impedance during posture and movement.
Damaraland mole-rats are not obligate cooperative breeders
Authors: Thorley Jack , Bensch Hanna M. , Finn Kyle , Clutton-Brock Tim , Zöttl Markus 
Published: December 2021

ABSTRACTDamaraland mole-rats (Fukomys damarensis) are usually viewed as a eusocial or obligate cooperative breeder in which successful reproduction is dependent on help from closely related group members. However, because longitudinal studies of mole-rats in their natural environment are uncommon, the extent to which successful reproduction by breeders relies on assistance from other group members is unclear, and for non-breeders, the immediate and delayed fitness consequences of staying and helping are poorly understood. Using data from a 7-year field study of marked individuals, we investigate whether increasing group size confers reproductive and survival benefits to breeders and non-breeders, and explore the different routes through which individuals acquire breeding positions. We show that solitary natal dispersal was the most common route to breeding for both sexes and that the inheritance of dominant breeding positions was uncommon in both sexes. After dispersing, females typically settled alone in new burrow systems where they enjoyed high survival rates and remained in good body condition - often for several years - before being joined by males. In contrast to most obligately cooperative species, pairs of potential breeders reproduced successfully without helpers and experimentally formed pairs had the same reproductive success as larger established groups. Though larger breeding groups recruited slightly more pups on average, our data suggest that neither survival nor reproduction depend on the presence of non-breeding helpers, indicating that Damaraland mole-rats are not obligate cooperative breeders. We suggest that extended philopatry and group living in Damaraland mole-rats have evolved because of the high costs and constraints of dispersal rather than because of strong indirect benefits accrued through cooperative behaviour and that similarities between their breeding systems and those of obligatorily eusocial insects have been over-emphasized.Significance StatementThe social mole-rats are often considered eusocial mammals in which successful reproduction depends on assistance from non-breeding helpers. In this study we show that in wild Damaraland mole-rats, the presence of non-breeders is associated with both costs and benefits and that nascent breeding pairs show high reproductive success despite the lack of non-breeding helpers. These findings indicate that Damaraland mole-rats are not obligate cooperative breeders and suggest that similarities between their breeding systems and those of obligatorily eusocial insects have been over-emphasized.
Mapping of the autophagosomal degradome identifies IL-7Rα as key cargo in proliferating CD4+ T-cells
Authors: Zhou Dingxi , Borsa Mariana , Puleston Daniel J. , Zellner Susanne , Capera Jesusa , Sanderson Sharon , Jostins Luke , Behrends Christian , Alsaleh Ghada , Simon Anna Katharina 
Published: December 2021

AbstractCD4+ T cells orchestrate both humoral and cytotoxic immune responses. While it is known that CD4+ T cell proliferation relies on autophagy, direct identification of the autophagosomal cargo involved is still missing. Here, we created a transgenic mouse model, which, for the first time, enables us to directly map the proteinaceous content of autophagosomes in any primary cell by LC3 proximity labelling. IL-7Rα, a cytokine receptor mostly found in naïve and memory T cells, was reproducibly detected in autophagosomes of activated CD4+ T cells. Consistently, CD4+ T cells lacking autophagy showed increased IL-7Rα surface expression, while no defect in internalisation was observed. Mechanistically, excessive surface IL-7Rα sequestrates the common gamma chain, impairing the IL-2R assembly and downstream signalling crucial for T cell proliferation. This study provides proof-of-principle that key autophagy substrates can be reliably identified with this model to help mechanistically unravel autophagy’s contribution to healthy physiology and disease.
Microbiome Analysis of Gut Bacterial Communities of Healthy and Diseased Malaysian Mahseer (Tor tambroides)
Authors: Lau Melinda Mei Lin , Kho Cindy Jia Yung , Lim Leonard Whye Kit , Sia Siew Chuiang , Chung Hung Hui , Lihan Samuel , Apun Kasing 
Published: December 2021

ABSTRACTAimsThe gut microbiota is referred to an ‘extra organ’ and is ciritical in assisting the host in terms of nutrition and immunity. Environmental stressors could alter gut microbial community and cause gut inflammation. This study aimed to investigate and compare the gut microbiota community between healthy and diseasedTor tambroides.Methodology and resultsIn this study, such gut microbial alterations were explored using NGS-based 16S rDNA sequencing on the Malaysian mahseer (T. tambroides). Three adult healthy and three diseased adult Malaysian mahseers (showing signs of exophthalmia, coelomic distension and petechial haemorrhage) were obtained from LTT Aquaculture Sdn Bhd. Our results revealed significant differences in microbial diversity, composition and function between both populations ofT. tambroides.Alpha diversity analysis depicts lower diversity of gut microbiota composition in diseasedT. tambroidesas compared to the healthy group. In particular,Enterobacteriaceae,Aeromonas, Bacteroides, VibrioandPseudomonaswere found within gut microbiota of the diseased fishes. In addition, cellulose-degrading bacteria and protease-producing bacteria were identified from the gut ofT. tambroides.Conclusion significance and impact of studyThus, our findings emphasised on the association between the alteration in gut microbiota composition and infectious abdominal dropsy (IAD) inT. tambroides.This finding is important to provide basic information for further diagnosis, prevention and treatment of intestinal diseases in fish.