bluuebunny/crossref_metadata_2025_split huggingface dataset:
Robust Determination of Protein Allosteric Signaling Pathways
Authors: Botello-Smith Wesley M. , Luo Yun 
Published: March 2019

AbstractTo understand how protein function changes upon an allosteric perturbation, such as ligand binding and mutation, significant progress in characterizing allosteric network from molecular dynamics (MD) simulations has been made. However, determining which amino acid(s) play an essential role in the propagation of signals may prove challenging, even when the location of the source and sink is known for a protein or protein complex. This challenge is mainly due to the large fluctuations in protein dynamics that cause instability of the network topology within a single trajectory or between multiple replicas. To solve this problem, we introduce the current-flow betweenness scheme, originated from electrical network theory, to protein dynamical network analysis. To demonstrate the benefit of this new method, we chose a prototypic allosteric enzyme (IGPS or HisH-HisF dimer) as our benchmark system. Using multiple replicas of simulations and multiple network topology comparison metrics (edge ranking, path length, and node frequency), we show that the current-flow betweenness provides a significant improvement in the convergence of the allosteric networks. The improved stability of the network topology allows us to generate a delta-network between the apo and holo forms of the protein. We illustrated that the delta-network is a more rigorous way to capture the subtle changes in the networks that would otherwise be neglected by comparing node usage frequencies alone. We have also investigated the use of a linear smoothing function to improve the stability of the contact map. The methodology presented here is general and may be applied to other topology and weighting schemes. We thus conclude that, for determining protein signaling pathways between the pair(s) of source and sink, multiple MD simulation replicas are necessary and the current-flow betweenness scheme introduced here provides a more robust approach than the geodesic scheme based on correlation edge weighting.For Table of Contents Only
Advancing Computational Biology and Bioinformatics Research Through Open Innovation Competitions
Authors: Blasco Andrea , Endres Michael G. , Sergeev Rinat A. , Jonchhe Anup , Macaluso Max , Narayan Rajiv , Natoli Ted , Paik Jin H. , Briney Bryan , Wu Chunlei , Su Andrew I. , Subramanian Aravind , Lakhani Karim R. 
Published: March 2019

SummaryOpen data science and algorithm development competitions offer a unique avenue for rapid discovery of better computational strategies. We highlight three examples in computational biology and bioinformatics research where the use of competitions has yielded significant performance gains over established algorithms. These include algorithms for antibody clustering, imputing gene expression data, and querying the Connectivity Map (CMap). Performance gains are evaluated quantitatively using realistic, albeit sanitized, data sets. The solutions produced through these competitions are then examined with respect to their utility and the prospects for implementation in the field. We present the decision process and competition design considerations that lead to these successful outcomes as a model for researchers who want to use competitions and non-domain crowds as collaborators to further their research.
A Mathematical Model for the Immune-Mediated Theory of Metastasis
Authors: Rhodes Adam , Hillen Thomas 
Published: March 2019

AbstractAccumulating experimental and clinical evidence suggest that the immune response to cancer is not exclusively anti-tumor. Indeed, the pro-tumor roles of the immune system — as suppliers of growth and pro-angiogenic factors or defenses against cytotoxic immune attacks, for example — have been long appreciated, but relatively few theoretical works have considered their effects. Inspired by the recently proposed “immune-mediated” theory of metastasis, we develop a mathematical model for tumor-immune interactions at two anatomically distant sites, which includes both anti-and pro-tumor immune effects, and the experimentally observed tumor-induced phenotypic plasticity of immune cells (tumor “education” of the immune cells). Upon confrontation of our model to experimental data, we use it to evaluate the implications of the immune-mediated theory of metastasis. We find that tumor education of immune cells may explain the relatively poor performance of immunotherapies, and that many metastatic phenomena, including metastatic blow-up, dormancy, and metastasis to sites of injury, can be explained by the immune-mediated theory of metastasis. Our results suggest that further work is warranted to fully elucidate the protumor effects of the immune system in metastatic cancer.
Low-dose antibiotics can collapse gut bacterial populations via a gelation transition
Authors: Schlomann Brandon H. , Wiles Travis J. , Wall Elena S. , Guillemin Karen , Parthasarathy Raghuveer 
Published: March 2019

AbstractAntibiotics can profoundly alter the intestinal microbiome even at the sublethal concentrations often encountered through environmental contamination. The mechanisms by which low-dose antibiotics induce large yet highly variable changes in gut communities have remained elusive. We therefore investigated the impact of antibiotics on intestinal bacteria using larval zebrafish, whose experimental tractability enables high-resolution in vivo examination of response dynamics. Live imaging revealed that sublethal doses of the common antibiotic ciprofloxacin lead to severe drops in bacterial abundance, coincident with changes in spatial organization that increase susceptibility to intestinal expulsion. Strikingly, our data can be mapped onto a physical model of living gels that links bacterial aggregation and expulsion to nonequilibrium abundance dynamics, providing a framework for predicting the impact of antibiotics on the intestinal microbiome.
Trophy hunting mediates sex‐specific associations between early‐life environmental conditions and adult mortality in bighorn sheep
Authors: Douhard Mathieu , Festa‐Bianchet Marco , Landes Julie , Pelletier Fanie 
Published: March 2019

Abstract

Environmental conditions during early development, from conception to sexual maturity, can have lasting consequences on fitness components. Although adult life span often accounts for much of the variation in fitness in long‐lived animals, we know little about how early environment affects adult life span in the wild, and even less about whether these effects differ between the sexes.

Using data collected over 45 years from wild bighorn sheep (Ovis canadensis), we investigated the effects of early environment on adult mortality in both sexes, distinguishing between natural and anthropogenic sources of mortality.

We used the average body mass of yearlings (at about 15 months of age) as a yearly index of environmental quality. We first examined sex differences in natural mortality responses to early environment by censoring harvested males in the year they were shot. We then investigated sex differences in the effects of early environment on overall mortality (natural and hunting mortality combined). Finally, we used path analysis to separate the direct influence of early environment from indirect influences, mediated by age at first reproduction, adult mass and horn length.

As early environmental conditions improved, natural adult mortality decreased in both sexes, although for males the effect was not statistically supported. Sex differences in the effects of early environment on adult mortality were detected only when natural and hunting mortality were pooled. Males that experienced favourable early environment had longer horns as adults and died earlier because of trophy hunting, which does not mimic natural mortality. Females that experienced favourable early environment started to reproduce earlier and early primiparity was associated with reduced mortality, suggesting a silver‐spoon effect.

Our results show that early conditions affect males and females differently because of trophy hunting. These findings highlight the importance of considering natural and anthropogenic environmental factors across different life stages to understand sex differences in mortality.
Determinants of elephant foraging behaviour in a coupled human‐natural system: Is brown the new green?
Authors: Branco Paola S. , Merkle Jerod A. , Pringle Robert M. , Pansu Johan , Potter Arjun B. , Reynolds Alana , Stalmans Marc , Long Ryan A. 
Published: March 2019

AbstractCrop raiding by wildlife poses major threats to both wildlife conservation and human well‐being in agroecosystems worldwide. These threats are particularly acute in many parts of Africa, where crop raiders include globally threatened megafauna such as elephants, and where smallholder agriculture is a primary source of human livelihood. One framework for understanding herbivore feeding behaviour, the forage‐maturation hypothesis, predicts that herbivores should align their movements with intermediate forage biomass (i.e., peak green‐up); this phenomenon is known as “surfing the green wave.” Crop‐raiding elephants, however, often consume not just foliage, but also fruits and tubers (e.g., maize and potatoes), which generally mature after seasonal peaks in photosynthetic activity. Thus, although elephants have been reported to surf the green wave in natural habitats, they may utilize a different strategy in cultivated landscapes by selecting crops that are “browning down.”We sought to understand the factors that underpin movement of elephants into agricultural landscapes.In Mozambique's Gorongosa National Park, we used movement data from GPS‐collared elephants, together with precipitation records, remotely sensed estimates of landscape greenness (NDVI), DNA‐based diet analysis, measurements of plant nutritional quality and survey‐based metrics of crop availability to understand spatiotemporal variation in elephant crop‐raiding behaviour.Elephants tracked peak NDVI while foraging inside the Park. During the dry season, however, when NDVI within the Park declined and availability of mature crops was high, crop raiding increased dramatically, and elephants consistently selected crop plants that were browning down while foraging in cultivated landscapes. Crops contained significantly higher digestible energy than wild food plants, but comparable (and sometimes lower) levels of digestible protein, suggesting that this foraging strategy maximized energy rather than protein intake.Our study is the first to combine GPS tracking data with high‐resolution diet analysis and community‐based reporting of crop availability to reveal fine‐scale plasticity in foraging behaviour of elephants at the human–wildlife interface. Our results extend the forage‐maturation hypothesis by showing that elephants surf waves of plant brown‐down in cultivated landscapes. These findings can aid efforts to reduce human–elephant conflict by enabling wildlife managers to prioritize mitigation actions in time and space with limited resources.
Modelling multi‐species and multi‐mode contact networks: Implications for persistence of bovine tuberculosis at the wildlife–livestock interface
Authors: Wilber Mark Q. , Pepin Kim M. , Campa Henry , Hygnstrom Scott E. , Lavelle Michael J. , Xifara Tatiana , VerCauteren Kurt C. , Webb Colleen T. 
Published: March 2019

Abstract

Individual‐ and species‐level heterogeneity in contact rates can alter the ability of a pathogen to invade a host community. Many pathogens have multiple modes of transmission—by direct or indirect contact. It is important to identify the role of heterogeneity in different types of transmission when managing the risk of disease spillover at the interface among different host species.

We developed a network‐based analysis to explore how individual‐ and species‐level heterogeneity shape multi‐mode contact networks. We applied this network‐based approach to contact data from proximity loggers collected in a multi‐species host community that contributes to the spillover of the disease bovine tuberculosis (bTB) to cattle populations in Michigan, USA. We used this approach to (a) quantify how individual‐ and species‐level heterogeneity influence direct and indirect contacts in this system, (b) explore how management interventions to control spillovers, such as the installation of deer fences, can alter observed contact networks and c) predict the role that wildlife species have in maintaining bTB in the community.

We found that individual‐ and species‐level heterogeneity disproportionately influenced indirect and direct contact networks, with individual‐level heterogeneity having a greater effect on indirect contact networks and species‐level heterogeneity having a greater effect on direct contact networks. We also found that the installation of deer fences significantly reduced deer‐specific indirect contacts. We used the results from our network analysis to show that white‐tailed deer (Odocoileus virginianus) could act as the sole reservoir host for bTB in this community with important implications for understanding past bTB dynamics and managing the persistence of bTB in the future.

Synthesis and applications. Analyses of epidemiological networks rarely account for multiple modes of contact, which can lead to an incomplete understanding of how individual‐ and species‐level heterogeneity affect disease transmission. The multi‐mode, multi‐species network analysis we develop in this study illustrates that individual‐ and species‐level heterogeneity can play significantly different roles depending on the type of contact network considered. This has important implications when managing disease at the wildlife–livestock interface, where strategies may need to be multi‐pronged to account for the variable role of heterogeneity on different modes of contact.
Relationships between plant traits, soil properties and carbon fluxes differ between monocultures and mixed communities in temperate grassland
Authors: De Long Jonathan R. , Jackson Benjamin G. , Wilkinson Anna , Pritchard William J. , Oakley Simon , Mason Kelly E. , Stephan Jörg G. , Ostle Nicholas J. , Johnson David , Baggs Elizabeth M. , Bardgett Richard D. 
Published: March 2019

Abstract

The use of plant traits to predict ecosystem functions has been gaining growing attention. Above‐ground plant traits, such as leaf nitrogen (N) content and specific leaf area (SLA), have been shown to strongly relate to ecosystem productivity, respiration and nutrient cycling. Furthermore, increasing plant functional trait diversity has been suggested as a possible mechanism to increase ecosystem carbon (C) storage. However, it is uncertain whether below‐ground plant traits can be predicted by above‐ground traits, and if both above‐ and below‐ground traits can be used to predict soil properties and ecosystem‐level functions.

Here, we used two adjacent field experiments in temperate grassland to investigate if above‐ and below‐ground plant traits are related, and whether relationships between plant traits, soil properties and ecosystem C fluxes (i.e. ecosystem respiration and net ecosystem exchange) measured in potted monocultures could be detected in mixed field communities.

We found that certain shoot traits (e.g. shoot N and C, and leaf dry matter content) were related to root traits (e.g. root N, root C:N and root dry matter content) in monocultures, but such relationships were either weak or not detected in mixed communities. Some relationships between plant traits (i.e. shoot N, root N and/or shoot C:N) and soil properties (i.e. inorganic N availability and microbial community structure) were similar in monocultures and mixed communities, but they were more strongly linked to shoot traits in monocultures and root traits in mixed communities. Structural equation modelling showed that above‐ and below‐ground traits and soil properties improved predictions of ecosystem C fluxes in monocultures, but not in mixed communities on the basis of community‐weighted mean traits.

Synthesis. Our results from a single grassland habitat detected relationships in monocultures between above‐ and below‐ground plant traits, and between plant traits, soil properties and ecosystem C fluxes. However, these relationships were generally weaker or different in mixed communities. Our results demonstrate that while plant traits can be used to predict certain soil properties and ecosystem functions in monocultures, they are less effective for predicting how changes in plant species composition influence ecosystem functions in mixed communities.
The relationship of woody plant size and leaf nutrient content to large‐scale productivity for forests across the Americas
Authors: Šímová Irena , Sandel Brody , Enquist Brian J. , Michaletz Sean T. , Kattge Jens , Violle Cyrille , McGill Brian J. , Blonder Benjamin , Engemann Kristine , Peet Robert K. , Wiser Susan K. , Morueta‐Holme Naia , Boyle Brad , Kraft Nathan J. B. , Svenning Jens‐Christian 
Published: March 2019

Abstract

Ecosystem processes are driven by both environmental variables and the attributes of component species. The extent to which these effects are independent and/or dependent upon each other has remained unclear. We assess the extent to which climate affects net primary productivity (NPP) both directly and indirectly via its effect on plant size and leaf functional traits.

Using species occurrences and functional trait databases for North and South America, we describe the upper limit of woody plant height within 200 × 200 km grid‐cells. In addition to maximum tree height, we quantify grid‐cell means of three leaf traits (specific leaf area, and leaf nitrogen and phosphorus concentration) also hypothesized to influence productivity. Using structural equation modelling, we test the direct and indirect effects of environment and plant traits on remotely sensed MODIS‐derived estimates of NPP, using plant size (satellite‐measured canopy height and potential maximum tree height), leaf traits, growing season length, soil nutrients, climate and disturbances as explanatory variables.

Our results show that climate affects NPP directly as well as indirectly via plant size in both tropical and temperate forests. In tropical forests NPP further increases with leaf phosphorus concentration, whereas in temperate forests it increases with leaf nitrogen concentration. In boreal forests, NPP most strongly increases with increasing temperature and neither plant size nor leaf traits have a significant influence.

Synthesis. Our results suggest that at large spatial scales plant size and leaf nutrient traits can improve predictions of forest productivity over those based on climate alone. However, at higher latitudes their role is overridden by stressful climate. Our results provide independent empirical evidence for where and how global vegetation models predicting carbon fluxes could benefit from including effects of plant size and leaf stoichiometry.
Making the subjects of mental health care: a cross‐cultural comparison of mental health policy in Hong Kong, China and New South Wales, Australia
Authors: Cui Jialiang , Lancaster Kari , Newman Christy E. 
Published: March 2019

AbstractConstituting ‘social problems’ in particular ways has a range of effects, including for how subjects are positioned within policy and discourse. Employing an approach grounded in poststructuralist and social constructionist thinking, this analysis interrogates how the subjects of mental health care were constituted and problematised in mental health policies in two distinctive contexts, unsettling the taken‐for granted assumptions which underpin these problematisations. Two policies were selected for analysis as exemplar pieces of mental health policy reform in Hong Kong and New South Wales (NSW). Subjects were constituted as ‘patientised’ individuals (in Hong Kong) encouraged to depend on professionals who help them reintegrate into the ‘normal’ community, and as ‘traumatised’ individuals (in NSW) expected to take responsibility to guide the delivery of mental health care and respected as a part of diversity in community settings. While both policies constituted subjects as ‘unwell individuals’ and enacted ‘dividing practices’, subjectivities were shaped by distinctive cultural and socio‐political contexts. This analysis shifts our attention away from a focus on the effectiveness of policy solutions to the heterogeneity and contingency of policy ‘problems’ and ‘subjects’, opening up new possibilities for ‘out‐of‐the‐box’ policy responses to mental health.
Population augmentation had no effect on the abundance or body condition of conspecifics and co‐occurring lizard species in a native grassland community
Authors: Clive Lucy F. R. , Gardner Michael G. , Clayton Jessica , Baring Ryan , Hutchinson Mark N. , Fenner Aaron , Bull C. Michael 
Published: March 2019

AbstractWildlife translocations have been historically plagued by failure. As more species gain endangered status, we must increase the success rate through use of pre‐emptive empirical, evidence‐based research. The main ecological risk is the potential for the relocated individuals to have competitive advantage at the recipient site, acting invasively and, potentially, outcompeting the native fauna for food, shelter or other resources. Here we investigated the ecological risk of increased population density, following a population augmentation of the pygmy bluetongue lizard (Tiliqua adelaidensis) an endangered lizard, endemic to South Australia. We experimentally increased T. adelaidensis density to ascertain if a sudden increase in T. adelaidensis density would negatively affect the abundance or body condition of the resident conspecifics and co‐existing lizard species found at the recipient site. Twenty‐four individuals, from two populations, were relocated into previously built enclosures at a recipient site in grassland habitat, north of Adelaide, South Australia. For one activity‐season pre and post the augmentation, co‐existing lizard species were sampled in an effort to detect any changes inabundance or body condition. Comparisons were also made between experimental enclosures, containing residents and translocated individuals and control enclosures, containing only residents. Using Menetia greyii as a proxy for all of the competing species, our results show there was no reduction in abundance or body condition post augmentation. Our lack of evidence indicating a negative impact of the T. adelaidensis translocation on the body condition and abundance of the resident lizard species is a positive outcome for future conservation of this species. This study provides a new way of approaching wildlife movements, through identification of potential risks using small‐scale translocations in an enclosed area before conducting large‐scale releases into unfenced areas; the results are intended to facilitate higher translocation success rates and limit the negative effects upon the wider ecological community at recipient sites.