bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ecological and life history traits are associated with Ross River virus infection among sylvatic mammals in Australia
Authors: Walsh Michael G. 
Published: November 2018

AbstractBackgroundRoss River virus (RRV) is Australia’s most important arbovirus given its annual burden of disease and the relatively large number of Australians at risk for infection. This mosquito-borne arbovirus is also a zoonosis, making its epidemiology and infection ecology complex and cryptic. Our grasp of enzootic, epizootic, and zoonotic RRV transmission dynamics is imprecise largely due to a poor understanding of the role of wild mammalian hosts in the RRV system.MethodsThe current study applied a piecewise structural equation model (PSEM) toward an interspecific comparison of sylvatic Australian mammals to characterize the ecological and life history profile of species with a history of RRV infection relative to those species with no such history among all wild mammalian species surveyed for RRV infection. The effects of species traits were assessed through multiple causal pathways within the PSEM framework.ResultsSylvatic mammalian species with a history of RRV infection tended to express dietary specialization and smaller population density. These species were also characterized by a longer gestation length.ConclusionsThis study provides the first interspecific comparison of wild mammals for RRV infection and identifies some potential targets for future wildlife surveys into the infection ecology of this important arbovirus. An applied RRV macroecology may prove invaluable to the epidemiological modeling of RRV epidemics across diverse sylvatic landscapes, as well as to the development of human and animal health surveillance systems.
TCR and inflammatory signals tune human MAIT cells to exert specific tissue repair and effector functions
Authors: Leng Tianqi , Akther Hossain Delowar , Hackstein Carl-Philipp , King Thomas , Friedrich Matthias , Christoforidou Zoe , McCuaig Sarah , Neyazi Mastura , Arancibia-Cárcamo Carolina V. , Powrie Fiona ,   Oxford IBD Investigators, Marchi Emanuele , Peres Raphael Sanches , Millar Val , Ebner Danie , Willberg Chris , Klenerman Paul 
Published: November 2018

SUMMARYMAIT cells are an abundant T-cell population enriched in peripheral tissues such as the liver. They are activated both through TCR-dependent and - independent mechanisms. However, the different specific functional responses of MAIT cells to these distinct signals remain elusive. We examined the impact of combinations of TCR-dependent and -independent signals in blood and tissue-derived human MAIT cells. TCR-independent activation of MAIT cells from blood and gut was maximised by extending the panel of cytokines to including TNF-superfamily member TL1A. RNAseq experiments revealed that TCR-dependent and -independent signals drive MAIT cells to exert overlapping and unique effector functions, impacting both host defence and tissue homeostasis. While TCR-triggering alone is insufficient to drive sustained activation, TCR-triggered MAIT cells did show specific enrichment of tissue-repair functions at the level of gene expression, protein production and in in vitro assays and these functions were amplified by cytokine costimulation. Taken together, these data indicate the blend of TCR-dependent and -independent signalling to MAIT cells may play a role in controlling the balance between healthy and pathological processes of tissue inflammation and repair.
The Flowering Hormone Florigen Accelerates Secondary Cell Wall Biogenesis to Harmonize Vascular Maturation with Reproductive Development
Authors: Shalit-Kaneh Akiva , Eviatar–Ribak Tamar , Horev Guy , Suss Naomi , Aloni Roni , Eshed Yuval , Lifschitz Eliezer 
Published: November 2018

AbstractThe protein hormone florigen is a universal systemic inducer of flowering and a generic growth terminator across meristems. To understand the developmental rational for its pleiotropic functions and to uncover the deep cellular systems mobilized by florigen beyond flowering we explored termination of radial expansion of stems. Employing the power of tomato genetics along with RNAseq and histological validations we show that endogenous, mobile, or induced florigen accelerates secondary cell wall biogenesis (SCWB), and hence vascular maturation, independently of flowering. This finding is supported by a systemic florigen antagonist from the non-floweringGinkgo biloba, which arrests SCWB and byMADSandMIFgenes downstream of florigen that similarly suppress or enhance, respectively, vascular maturation independent of flowering. We also show that florigen is remarkably stable and distributed to all organs regardless of existing endogenous levels. By accelerating SCWB, florigen reprograms the distribution of resources, signals and mechanical loads required for the ensuing reproductive phase it had originally set into motion.Developmental HighlightsFlorigen accelerates SCWB: A prime case for a long-range regulation of a complete metabolic network by a plant hormone.The dual acceleration of flowering and vascular maturation by Florigen provides a paradigm for a dynamic regulation of global, independent, developmental programs.The growth termination functions of florigen and the auto-regulatory mechanism for its production and distribution provide a communication network enveloping the shoot system.A stable florigen provides a possible mechanism for the quantitative regulation of floweringLateral stimulation of xylem differentiation links the phloem-travelling florigen with the annual rings in trunks.MADS genes are common relay partners in Florigen circuits; vascular maturation in stems and reproductive transition in apical meristems.
Multi-stage models for the failure of complex systems, cascading disasters, and the onset of disease
Authors: Webster Anthony J. 
Published: November 2018

AbstractComplex systems can fail through different routes, often progressing through a series of (rate-limiting) steps and modified by environmental exposures. The onset of disease, cancer in particular, is no different. Multi-stage models provide a simple but very general mathematical framework for studying the failure of complex systems, or equivalently, the onset of disease. They include the Armitage-Doll multi-stage cancer model as a particular case, and have potential to provide new insights into how failures and disease, arise and progress. A method described by E.T. Jaynes is developed to provide an analytical solution for a large class of these models, and highlights connections between the convolution of Laplace transforms, sums of random variables, and Schwinger/Feynman parameterisations. Examples include: exact solutions to the Armitage-Doll model, the sum of Gamma-distributed variables with integer-valued shape parameters, a clonal-growth cancer model, and a model for cascading disasters. Applications and limitations of the approach are discussed in the context of recent cancer research. The model is sufficiently general to be used in many contexts, such as engineering, project management, disease progression, and disaster risk for example, allowing the estimation of failure rates in complex systems and projects. The intended result is a mathematical toolkit for applying multi-stage models to the study of failure rates in complex systems and to the onset of disease, cancer in particular.
Realtime 2-5A kinetics suggests interferons β and λ evade global arrest of translation by RNase L
Authors: Chitrakar Alisha , Rath Sneha , Donovan Jesse , Demarest Kaitlin , Li Yize , Sridhar Raghavendra Rao , Weiss Susan R. , Kotenko Sergei V. , Wingreen Ned S. , Korennykh Alexei 
Published: November 2018

AbstractCells of all mammals recognize double-stranded RNA (dsRNA) as a foreign material. In response, they release interferons (IFNs) and activate a ubiquitously expressed pseudokinase/endoribonuclease RNase L. RNase L executes regulated RNA decay and halts global translation. Here we developed a biosensor for 2’,5’-oligoadenylate (2-5A), the natural activator of RNase L. We found that 2-5A was acutely synthesized by cells in response to dsRNA sensing, which immediately triggered cellular RNA cleavage by RNase L and arrested host protein synthesis. However, translation-arrested cells still transcribed IFN-stimulated genes (ISGs) and secreted IFNs of types I and III (IFN-β and IFN-λ). Our data suggests that IFNs escape from the action of RNase L on translation. We propose that 2-5A/RNase L pathway serves to rapidly and accurately suppress basal protein synthesis, preserving privileged production of defense proteins of the innate immune system.SignificanceRNase L is a mammalian enzyme that can stop global protein synthesis during interferon response. Cells must balance the need to make interferons (which are proteins) with the risk to lose cell-wide translation due to RNase L. This balance can most simply be achieved if RNase L was activated late in the interferon response. However, we show by engineering a biosensor for the RNase L pathway, that on the contrary, RNase L activation precedes interferon synthesis. Further, translation of interferons evades the action of RNase L. Our data suggest that RNase L facilitates a switch of protein synthesis from homeostasis to specific needs of innate immune signaling.
Temporal shifts in intraspecific and interspecific diet variation: effects of predator body size and identity across seasons in a stream community
Authors: Falke Landon P. , Henderson Jeremy S. , Novak Mark , Preston Daniel L. 
Published: November 2018

AbstractIntraspecific variation is increasingly recognized as an important factor in ecological interactions, sometimes exceeding the role of interspecific variation. Few studies, however, have examined how intra-versus interspecific variation affect trophic interactions over time within a seasonally dynamic food web. We collected stomach contents from 2028 reticulate sculpin (Cottus perplexus), 479 cutthroat trout (Oncorhynchus clarkii clarkii), and 107 Pacific giant salamanders (Dicamptodon tenebrosus) in western Oregon streams and compared diets among predator species and size classes over three seasons. Predator body size and species identity both showed strong effects on dietary niche breadth, proportional prey composition, and prey size, with seasonal variation in the relative magnitudes of intraspecific and interspecific diet variation. Size-associated diet variation was high in summer and fall but was heavily outweighed by species-associated diet variation in spring. This pattern was driven primarily by a 50-fold increase in the consumption of terrestrial thrips (Order: Thysanoptera) by cutthroat trout in spring compared to summer and fall. Mean dietary niche breadth generally increased with body size and was roughly half as wide in sculpin as in trout and was intermediate in salamanders. Predator-specific responses to the seasonality of terrestrial prey availability were associated with interspecific differences in foraging mode (e.g., benthic vs drift-feeding) and contributed to temporal variation in the roles of predator size and identity in trophic niche differentiation. Our results thereby demonstrate that intraspecific and interspecific diet variation can exhibit strong seasonality in stream predators, emphasizing the dynamic nature of food webs and the need to incorporate sampling over relevant temporal scales in efforts to understand species interactions.
Human IL-2 receptor β mutations associated with defects in immunity and peripheral tolerance
Authors: Zhang Zinan , Gothe Florian , Pennamen Perrine , James John , MacDonald David , Mata Carlos P. , Modis Yorgo , Acres Meghan , Haller Wolfram , Bowen Claire , Doffinger Rainer , Sinclair Jan , Brothers Shannon , Alazami Anas , Zhang Yu , Matthews Helen , Naudion Sophie , Pelluard Fanny , Yamazaki Yasuhiro , Notarangelo Luigi , Almousa Hamoud , Thaventhiran James , Engelhardt Karin R. , Hambleton Sophie , Rooryck Caroline , Smith Ken , Lenardo Michael J. 
Published: November 2018

AbstractInterleukin-2, which conveys essential signals for effective immunity and immunological tolerance, operates through a heterotrimeric receptor comprised of α, β and γ chains. Genetic deficiency of the α or γ chain causes debilitating disease. Here we identify human interleukin-2 receptor (IL-2R) β chain (CD122) gene defects as a cause of life-threatening dysregulation of immunity and peripheral tolerance. We report homozygous mutations in the human IL-2Rβ gene from four consanguineous families, comprising either recessive missense mutations in five children or an early stop-gain mutation in two deceased fetuses and a premature neonate. All patients surviving to childhood presented with autoantibodies, hypergammaglobulinemia, bowel inflammation, and dermatological abnormalities, as well as cytomegalovirus disease in most cases. Patient T lymphocytes lacked surface expression of IL-2Rβ and were unable to normally respond to high-dose IL-2 stimulation. By contrast, patient natural killer (NK) cells retained partial IL-2Rβ expression and cytotoxic function. IL-2Rβ loss of function was recapitulated in a recombinant system, in which endoplasmic reticulum sequestration was revealed as the mechanism by which certain missense mutations cause disease. Hematopoietic stem cell transplant resulted in resolution of clinical symptoms in one patient. The hypomorphic nature of this disease highlights the significance of variable IL-2Rβ expression in different lymphocyte subsets as a means of modulating immune function. Insights from these patients can inform the development of IL-2-based therapeutics for immunological diseases and cancer.
Two distributed semi-supervised algorithms for mining of complex networks using Giraph
Authors: Maleki Erfan Farhangi , Ghadiri Nasser , Shahreza Maryam Lotfi , Maleki Zeinab 
Published: November 2018

AbstractBackground and ObjectiveHeterogeneous complex networks are large graphs consisting of different types of nodes and edges. The process of mining and knowledge extraction from these networks is so complicated. Moreover, the scale of these networks is steadily increasing. Thus, scalable methods are required.MethodsIn this paper, two distributed label propagation algorithms for heterogeneous networks, namely DHLP-1 and DHLP-2 have been introduced. Biological networks are one type of the heterogeneous complex networks. As a case study, we have measured the efficiency of our proposed DHLP-1 and DHLP-2 algorithms on a biological network consisting of drugs, diseases, and targets. The subject we have studied in this network is drug repositioning but our algorithms can be used as general methods for heterogeneous networks other than the biological network.ResultsWe compared the proposed algorithms with similar non-distributed versions of them namely MINProp and Heter-LP. The experiments revealed the good performance of the algorithms in terms of running time and accuracy.
Molecular complexity of the major urinary protein system of the Norway rat,Rattus norvegicus
Authors: Gómez-Baena Guadalupe , Armstrong Stuart D. , Halstead Josiah O. , Prescott Mark , Roberts Sarah A. , McLean Lynn , Mudge Jonathan M. , Hurst Jane L. , Beynon Robert J. 
Published: November 2018

ABSTRACTMajor urinary proteins (MUP) are the major component of the urinary protein fraction in house mice (Musspp.) and rats (Rattusspp.). The structure, polymorphism and functions of these lipocalins have been well described in the western European house mouse (Mus musculus domesticus), clarifying their role in semiochemical communication. The complexity of these roles in the mouse raises the question of similar functions in other rodents, including the Norway rat,Rattus norvegicus. Norway rats express MUPs in urine but information about specific MUP isoform sequences and functions is limited. In this study, we present a detailed molecular characterization of the MUP proteoforms expressed in the urine of two laboratory strains, Wistar Han and Brown Norway, and wild caught animals, using a combination of manual gene annotation, intact protein mass spectrometry and bottom-up mass spectrometry-based proteomic approaches. Detailed sequencing of the proteins reveals a less complex pattern of primary sequence polymorphism than the mouse. However, unlike the mouse, rat MUPs exhibit added complexity in the form of post-translational modifications including phosphorylation and exoproteolytic trimming of specific isoforms. The possibility that urinary MUPs may have different roles in rat chemical communication than those they play in the house mouse is also discussed.
Reverse vaccinology approach to design a novel multi-epitope subunit vaccine against avian influenza A (H7N9) virus
Authors: Hasan Mahmudul , Ghosh ProggaParomita , Azim KaziFaizul , Mukta Shamsunnahar , Abir Ruhshan Ahmed , Nahar Jannatun , Hasan Khan Mohammad Mehedi 
Published: November 2018

AbstractH7N9, a novel strain of avian origin influenza was the first recorded incidence where a human was transited by a N9 type influenza virus. Effective vaccination against influenza A (H7N9) is a major concern, since it has emerged as a life threatening viral pathogen. Here, an in silico reverse vaccinology strategy was adopted to design a unique chimeric subunit vaccine against avian influenza A (H7N9). Induction of humoral and cell-mediated immunity is the prime concerned characteristics for a peptide vaccine candidate, hence both T cell and B cell immunity of viral proteins were screened. Antigenicity testing, transmembrane topology screening, allergenicity and toxicity assessment, population coverage analysis and molecular docking approach were adopted to generate the most antigenic epitopes of avian influenza A (H7N9) proteome. Further, a novel subunit vaccine was designed by the combination of highly immunogenic epitopes along with suitable adjuvant and linkers. Physicochemical properties and secondary structure of the designed vaccine were assessed to ensure its thermostability, hydrophilicity, theoretical PI and structural behavior. Homology modeling, refinement and validation of the designed vaccine allowed to construct a three dimensional structure of the predicted vaccine, further employed to molecular docking analysis with different MHC molecules and human immune TLR8 receptor present on lymphocyte cells. Moreover, disulfide engineering was employed to lessen the high mobility region of the designed vaccine in order to extend its stability. Furthermore, we investigated the molecular dynamic simulation of the modeled subunit vaccine and TLR8 complexed molecule to strengthen our prediction. Finally, the suggested vaccine was reverse transcribed and adapted forE. colistrain K12 prior to insertion within pET28a(+) vector for checking translational potency and microbial expression.
Quantitative Estimation of Long-Range Interactions at the Nanoscale
Authors: Sood Vishesh , Dhar Sunandan , Katti Dhirendra S. 
Published: November 2018

AbstractNano-bio interfaces attune nanoparticle-mediated biological responses. The nano-bio interface, like all interfacial interactions, is governed by non-covalent long-range interactions (LRIs). These LRIs include electrostatic, electrodynamic and acid-base interactions. There is a lack of understanding about the contribution of LRIs at the nano-bio interface for want of suitable methods for the estimation of dispersive, acidic, and basic components of the surface tension of nanoparticles. To address this, we developed an experimental and theoretical framework for the estimation of surface tension components of nanoparticles and biomacromolecules by partitioning them in a biphasic system. The work presented here is the first instance in the literature for estimating the surface tension components of nanoparticles and biomacromolecules suspended in aqueous suspensions. We also observed that LRIs have a deterministic role in biologically relevant phenomena such as salt-induced nanoparticle agglomeration and protein-nanoparticle interaction. Collectively, the results presented in this work provide a rapid and inexpensive framework for predicting the energetics of nanoparticle-nanoparticle and nanoparticle-protein interactions by estimating average ensemble surface characteristics like surface tension and surface charge density.
Historical contingency shapes adaptive radiation in Antarctic fishes
Authors: Daane Jacob M. , Dornburg Alex , Smits Patrick , MacGuigan Daniel J. , Hawkins M. Brent , Near Thomas J. , Detrich H. William , Harris Matthew P. 
Published: November 2018

AbstractAdaptive radiation illustrates the links between ecological opportunity, natural selection, and the generation of biodiversity (1). Central to adaptive radiation is the association between a diversifying lineage and the evolution of key traits that facilitate the utilization of novel environments or resources (2, 3). However, is not clear whether adaptive evolution or historical contingency is more important for the origin of key phenotypic traits in adaptive radiation (4, 5). Here we use targeted sequencing of >250,000 loci across 46 species to examine hypotheses concerning the origin and diversification of key traits in the adaptive radiation of Antarctic notothenioid fishes. Contrary to expectations of adaptive evolution, we show that notothenioids experienced a punctuated burst of genomic diversification and evolved key skeletal modifications before the onset of polar conditions in the Southern Ocean. We show that diversifying selection in pathways associated with human skeletal dysplasias facilitates ecologically important variation in buoyancy among Antarctic notothenioid species, and demonstrate the sufficiency of alteredtrip11, col1a2andcol1a1function in zebrafish (Danio rerio) to phenocopy skeletal reduction in Antarctic notothenioids. Rather than adaptation being driven by the cooling of the Antarctic (6), our results highlight the role of exaptation and historical contingency in shaping the adaptive radiation of notothenioids. Understanding the historical and environmental context for the origin of key traits in adaptive radiations provides context in forecasting the effects of climate change on the stability and evolvability of natural populations.
Lipid Droplet metabolism dependent microbial defense in pre-immune zebrafish embryos
Authors: Dutta Asmita , Banerjee Sampali , Sinha Deepak Kumar 
Published: November 2018

AbstractMicrobes present survival challenge to pre-immune embryos. Our study provides evidence for antimicrobial-secretion-based strategy of zebrafish embryos against microbes during pre-immune stages. Chorion prevents physical contact between embryos and microbes, yet microbes compromise embryonic survival through their secretions. Development of embryos in microbe-free medium involves secretion of pro-microbial compounds that bacteria utilize to accelarete growth. Embryo senses presence of microbes through microbial secretions. They respond by altering their secretions to include antimicrobial compounds along with regular pro-microbial ones. Upon sensing embryonic anti-microbial secretions, microbes too alter their secretions to include more potent toxins for embryos. In response to this embryos alter their secretions to include more potent antimicrobial compounds. Ability of embryos to secrete antimicrobial compounds is positively correlated with amount of lipid droplets (LDs) in them. Inhibition of LD metabolism prevents antimicrobial secretions by embryos. Thus, LDs protect zebrafish embryos from microbes. This manuscript establishes that pre-immune embryos employ dynamically evolving biochemical warfare to protect themselves from harmful microbes.