bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biotic interactions are more important at species’ warm vs. cool range-edges: a synthesis
Authors: Paquette Alexandra , Hargreaves Anna L. 
Published: April 2021

ABSTRACTPredicting which ecological factors constrain species distributions is a fundamental question in ecology and critical to forecasting geographic responses to global change. Darwin hypothesized that abiotic factors generally impose species’ high-latitude and high-elevation (typically cool) range limits, whereas biotic interactions more often impose species’ low-latitude/low-elevation (typically warm) limits, but empirical support has been mixed. Here, we clarify three predictions arising from Darwin’s hypothesis, and show that previously mixed support is partially due to researchers testing different predictions. Using a comprehensive literature review (886 range limits), we find that biotic interactions, including competition, predation, and parasitism, influenced species’ warm limits more often than species’ cool limits. At cool limits, abiotic factors were consistently more important than biotic interactions, but temperature contributed strongly to cool and warm limits. Our results suggest that most range limits will be sensitive to climate warming, but warm limit responses will depend strongly on biotic interactions.“When we travel southward and see a species decreasing in numbers, we may feel sure that the cause lies quite as much in other species being favored, as in this one being hurt. (Whereas)… the number of species, and therefore of competitors, deceases northwards; hence in going northward or in ascending a mountain, we far oftener meet with stunted forms, due to the directly injurious action of climate”–Darwin 1859
Unbalanced dietary patterns contribute to the pathogenesis of precocious puberty by affecting gut microbiota and host metabolites
Authors: Wang Ying , Wu Dingfeng , Li Hongying , Liang Xiangrong , Jiao Na , Gao Wenxing , Zhao Lu , Yu Han , Wang Qian , Ge Yongsheng , Zhao Changying , Huo Meiling , Cao Ruifang , Gao Sheng , Tao Liwen , Ling Yunchao , Zhao Lingna , Lv Xin , Liu Yi , Zhang Lehai , Zhou Haokui , Zhang Guoqing , Zhao Guoping , Zhang Lei , Zhu Ruixin , Gai Zhongtao 
Published: April 2021

ABSTRACTPrecocious puberty (PP) mostly stems from endocrine disorders. However, its triggering factors, especially for the early onset of partial PP, and the associated pathogenic mechanisms remain ambiguous. In this study, a systematic analysis in the form of a questionnaire of lifestyles, gut microbiome, and serum metabolome data was carried out to examine the pathogenesis of PP in a cohort comprised of 200 girls, with or without PP. The analysis revealed substantial alterations in gut microbiota, serum metabolites, as well as lifestyle patterns in the PP group, which were characterized by an elevated abundance of β-glucuronidase-producing and butyrate-producing bacteria, and excessive lipid concentration with decreased levels of organic nitrogen compounds in the serum of the participants. These differential microbes and metabolites tend to be reliable non-invasive diagnostic biomarkers aiding the early diagnosis of PP and exhibit a strong discriminative power (AUC = 0.93 and AUC = 0.97, respectively). Furthermore, the microbial biomarkers were confirmed in an independent validation cohort (n = 83, AUC = 0.85). Moreover, structural equation modeling revealed that unhealthy dietary habits were the primary contributors for the alteration of gut microbiota and serum metabolites, triggering the imbalance in the host hormones that leads to premature physical development. Our study determines a causal relationship among the gut microbiota, host metabolites, diet, and clinical characteristics of preadolescent girls who experienced early onset of PP, and formulates non-invasive diagnostic tools demonstrating excellent performance for the early detection of PP.
Combinatorial interactions between viral proteins expand the functional landscape of the viral proteome
Authors: Wang Liping , Tan Huang , Medina-Puche Laura , Wu Mengshi , Gómez Borja Garnelo , Gao Man , Shi Chaonan , Jimenez-Góngora Tamara , Fan Pengfei , Ding Xue , Zhang Dan , Yi Ding , Rosas-Diaz Tábata , Liu Yujing , Aguilar Emmanuel , Fu Xing , Lozano-Durán Rosa 
Published: April 2021

ABSTRACTAs intracellular parasites, viruses need to manipulate the molecular machinery of their host cells in order to enable their own replication and spread. This manipulation is based on the activity of virus-encoded proteins. The reduced size of viral genomes imposes restrictions in coding capacity; how the action of the limited number of viral proteins results in the massive cell reprogramming observed during the viral infection is a long-standing conundrum in virology. In this work, we explore the hypothesis that combinatorial interactions expand the multifunctionality of viral proteins, which may exert different activities individually and when in combination, physical or functional. We show that the proteins encoded by a plant-infecting DNA virus physically associate with one another in an intricate network. Our results further demonstrate that these interactions can modify the subcellular localization of the viral proteins involved, and that co-expressed interacting viral proteins can exert novel biological functionsin plantathat go beyond the sum of their individual functions. Based on this, we propose a model in which combinatorial physical and functional interactions between viral proteins enlarge the functional landscape of the viral proteome, which underscores the importance of studying the role of viral proteins in the context of the infection.
Immunoprofiling of HTLV-1-infected individuals shows altered innate cell responsiveness in HAM/TSP patients
Authors: Rocamonde Brenda , Futsch Nicolas , Orii Noemia , Allatif Omran , Penalva de Oliveira Augusto Cesar , Mahieux Renaud , Caseb Jorge , Dutartre Hélène 
Published: April 2021

AbstractThe Human T-cell Leukemia Virus-1 (HTLV-1)-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is a devastating neurodegenerative disease with no effective treatment, which affects an increasing number of people in Brazil. A biological blood factor allowing the prediction of the disease occurrence is so far not available. In this study, we analyzed innate immunity responses at steady state and after blood cell stimulation using an agonist of the toll-like receptor (TLR)7/8-signaling pathway in blood samples from HTLV-1-infected volunteers, including asymptomatic carriers and HAM/TSP patients. We observed a lower responsiveness in dendritic cells to produce IFNα. Moreover, we found higher production of IL-12 and Mip-1α by monocytes together with higher levels of IFNγ produced by Natural Killer cells. These deregulations could represent a signature for progression towards HAM/TSP.
Fast and adaptive protein structure representations for machine learning
Authors: Durairaj Janani , Akdel Mehmet , Ridder Dick de , Dijk Aalt DJ van 
Published: April 2021

AbstractThe growing prevalence and popularity of protein structure data, both experimental and computationally modelled, necessitates fast tools and algorithms to enable exploratory and interpretable structure-based machine learning. Alignment-free approaches have been developed for divergent proteins, but proteins sharing func-tional and structural similarity are often better understood via structural alignment, which has typically been too computationally expensive for larger datasets. Here, we introduce the concept of rotation-invariant shape-mers to multiple structure alignment, creating a structure aligner that scales well with the number of proteins and allows for aligning over a thousand structures in 20 minutes. We demonstrate how alignment-free shape-mer counts and aligned structural features, when used in machine learning tasks, can adapt to different levels of functional hierarchy in protein kinases, pinpointing residues and structural fragments that play a role in catalytic activity.
bayesynergy: flexible Bayesian modelling of synergistic interaction effects in in-vitro drug combination experiments
Authors: Rønneberg Leiv , Cremaschi Andrea , Hanes Robert , Enserink Jorrit M. , Zucknick Manuela 
Published: April 2021

AbstractThe effect of cancer therapies is often tested pre-clinically viain-vitroexperiments, where the post-treatment viability of the cancer cell population is measured through assays estimating the number of viable cells. In this way, large libraries of compounds can be tested, comparing the efficacy of each treatment. Drug interaction studies focus on the quantification of the additional effect encountered when two drugs are combined, as opposed to using the treatments separately. In thebayesynergyR package, we implement a probabilistic approach for the description of the drug combination experiment, where the observed dose response curve is modelled as a sum of the expected response under a zero-interaction model and an additional interaction effect (synergistic or antagonistic). The interaction is modelled in a flexible manner, using a Gaussian process formulation. Since the proposed approach is based on a statistical model, it allows the natural inclusion of replicates, handles missing data and uneven concentration grids, and provides uncertainty quantification around the results. The model is implemented in the Stan programming language providing a computationally efficient sampler, a fast approximation of the posterior through variational inference, and features parallel processing for working with large drug combination screens.
Suppression of aminoglycoside-induced premature termination codon readthrough by the TRP channel inhibitor AC1903
Authors: Baradaran-Heravi Alireza , Bauer Claudia C. , Pickles Isabelle B. , Hosseini-Farahabadi Sara , Balgi Aruna D. , Choi Kunho , Linley Deborah M. , Beech David J. , Roberge Michel , Bon Robin S. 
Published: April 2021

AbstractNonsense mutations, which occur in ~11% of patients with genetic disorders, introduce premature termination codons (PTCs) that lead to truncated proteins and promote nonsense-mediated mRNA decay. Aminoglycosides such as gentamicin and G418 permit PTC readthrough and so may address this problem. However, their effects are variable between patients, making clinical use of aminoglycosides challenging. In this study, we addressed the hypothesis that TRP non-selective cation channels contribute to the variable effect of aminoglycosides by controlling their cellular uptake. To attempt to identify the channel type involved, we tested AC1903, a 2-aminobenzimidazole derivative recently reported to selectively inhibit TRPC5 cation channels. AC1903 consistently suppressed G418 uptake and G418-induced PTC readthrough in the DMS-114 cell line and patient-derived JEB01 keratinocytes. In an effort to validate the suggested role of TRPC5, we tested an independent and more potent inhibitor called Pico145, which affects channels containing TRPC1, TRPC4 and TRPC5 but not other TRPCs or other channels. Unexpectedly, Pico145 was completely without effect, suggesting that AC1903 may work through other or additional targets. Consistent with this suggestion, AC1903 inhibited multiple TRPC channels including homomeric TRPC3, TRPC4, TRPC5, TRPC6 as well as concatemeric TRPC4–C1 and TRPC5–C1 channels, all with low micromolar IC50values. It also inhibited TRPV4 channels but had weak or no effects on TRPV1 and no effect on another non-selective cation channel, PIEZO1. Overall, our study reveals a suppressor of aminoglycoside-mediated PTC readthrough (i.e., AC1903) but suggests that this compound has previously unrecognised effects. These effects require further investigation to determine the molecular mechanism by which AC1903 suppresses aminoglycoside uptake and PTC readthrough.
Land-use history impacts spatial patterns and composition of woody plant species across a 35-hectare temperate forest plot
Authors: Orwig D.A. , Aylward J.A. , Buckley H.L. , Case B.S. , Ellison A.M. 
Published: April 2021

AbstractLand-use history is the template upon which contemporary plant and tree populations establish and interact with one another and exerts a legacy on the structure and dynamics of species assemblages and ecosystems. We use the first census (2010–2014) of a 35-ha forest-dynamics plot at the Harvard Forest in central Massachusetts to explore such legacies. The plot includes 108,632 live stems ≥ 1 cm in diameter (2215 individuals/ha) and 7,595 dead stems ≥ 5 cm in diameter. Fifty-one woody plant species were recorded in the plot, but two tree species—Tsuga canadensis(eastern hemlock) andAcer rubrum(red maple)—and one shrub—Ilex verticillata(winterberry)—comprised 56% of all stems. Live tree basal area averaged 42.25 m2/ha, of which 84% was represented byT. canadensis(14.0 m2/ ha),Quercus rubra(northern red oak; 9.6 m2/ ha),A. rubrum(7.2 m2/ ha) andPinus strobus(eastern white pine; 4.4 m2/ ha). These same four species also comprised 78% of the live aboveground biomass, which averaged 245.2 Mg/ ha, and were significantly clumped at distances up to 50 m within the plot. Spatial distributions ofA. rubrumandQ. rubrashowed negative intraspecific correlations in diameters up to at least a 150-m spatial lag, likely indicative of competition for light in dense forest patches. Bivariate marked point-pattern analysis showed thatT. canadensisandQ. rubradiameters were negatively associated with one another, indicating resource competition for light. Distribution and abundance of the common overstory species are predicted best by soil type, tree neighborhood effects, and two aspects of land-use history: when fields were abandoned in the late 19thcentury and the succeeding forest types recorded in 1908. In contrast, a history of intensive logging prior to 1950 and a damaging hurricane in 1938 appear to have had little effect on the distribution and abundance of present-day tree species.
Flight-induced compass representation in the monarch butterfly heading network
Authors: Beetz M. Jerome , Kraus Christian , Franzke Myriam , Dreyer David , Strube-Bloss Martin F. , Rössler Wolfgang , Warrant Eric J. , Merlin Christine , el Jundi Basil 
Published: April 2021

AbstractFor navigation, animals use a robust internal compass. Compass navigation is especially crucial for long-distance migrating animals like monarch butterflies, which use a sun compass to navigate every fall over 4,000 km to their overwintering sites. The central complex, a brain region equipped with sun-compass neurons, is proposed to control the butterfly’s heading. Although the activity of central-complex neurons exhibits a locomotor-dependent modulation in many insects, the consequences of such modulations for the coding of heading remain unexplored. Here, we developed tetrode recordings from tethered flying monarch butterflies to reveal how flight modulates heading representation. We found that during flight, heading-direction neurons change their tuning, transforming the central-complex network to function as a global compass. This compass coding is characterized by the dominance of steering feedback and allows for robust heading representation even under unreliable visual scenarios, an ideal strategy for maintaining a migratory heading over enormous distances.
morse: an R-package in support of Environmental Risk Assessment
Authors: Baudrot Virgile , Charles Sandrine 
Published: April 2021

SummaryPackagemorseis devoted to the analysis of experimental data collected from standard toxicity tests. It provides ready-to-use functions to visualize a data set and to estimate several toxicity indices to be further used in support of environmental risk assessment in full compliance with regulatory requirements. Such toxicity indices are indeed classical requested by standardized regulatory guidelines on which national agencies base their evaluation of applications for marketing authorisation of chemical active substances.Packagemorsecan be used to get estimates ofLCx(x% Lethal Concentration) orECx(x% Effective Concentration) by fitting standard exposure-response models on toxicity test data. Risk indicator estimates as well as model parameters are provided along with the quantification of their uncertainty. Packagemorsecan also be used to get estimates of theNEC(No Effect Concentration) by fitting a Toxicokinetic-Toxicodynamic (TKTD) model (namelyGUTSmodels, that isGeneral Unified Threshold models of Survival). UsingGUTSmodels also allow to get estimates ofLC(x,t)(whateverxandt) andLP(x,t), this later being defined by EFSA as the x% multiplication factor leading to an additional reduction of x% in survival at the end of the exposure profile. Above all,GUTSmodels can be used on data collected under time-variable exposure profiles.This paper illustrates a typical use ofmorsewith survival data collected over time and at different increasing exposure concentrations, analysed with the reduced version of GUTS models based on the stochastic death hypothesis (namely, theGUTS-RED-SDmodel). This example can be followed step-by-step to analyse any new data set, as long as the data set format is respected.
Investigating a trade-off between the quality of nest grown feathers and pace of development in an altricial bird
Authors: Taff Conor C. , Johnson Brianna A. , Anker Allison T. , Rodriguez Alyssa M. , Houtz Jennifer L. , Uehling Jennifer J. , Vitousek Maren N. 
Published: April 2021

ABSTRACTLife history theory provides a framework for understanding how trade-offs generate negative trait associations. Among nestling birds, developmental rate, risk of predation, and lifespan covary, but some associations are only found within species while others are only observed between species. A recent comparative study suggests that allocation trade-offs may be alleviated by disinvestment in ephemeral traits, such as nest-grown feathers, that are quickly replaced. However, direct resource allocation trade-offs cannot be inferred from inter-specific trait-associations without complementary intra-specific studies. Here, we asked whether there is evidence for a within-species allocation trade-off between feather quality and developmental speed in tree swallows (Tachycineta bicolor). Consistent with the idea that ephemeral traits are deprioritized, nest-grown feathers had lower barb density than adult feathers. However, despite substantial variation in fledging age among nestlings, there was no evidence for a negative association between developmental pace and feather quality. Furthermore, accounting for differences in resource availability by considering provisioning rate and a nest predation treatment did not reveal a trade-off that was masked by variation in resources. Our results are most consistent with the idea that the inter-specific association between development and feather quality arises from adaptive specialization, rather than from a direct allocation trade-off.
Sex dependent glial-specific changes in the chromatin accessibility landscape in late-onset Alzheimer’s disease brains
Authors: Barrera Julio , Song Lingyun , Safi Alexias , Yun Young , Garrett Melanie E. , Gamache Julia , Premasinghe Ivana , Sprague Daniel , Chipman Danielle , Li Jeffrey , Fradin Hélène , Soldano Karen , Gordân Raluca , Ashley-Koch Allison E. , Crawford Gregory E. , Chiba-Falek Ornit 
Published: April 2021

AbstractIn the post-GWAS era, there is an unmet need to decode the underpinning genetic etiologies of late-onset Alzheimer’s disease (LOAD) and translate the associations to causation. Toward that goal, we conducted ATAC-seq profiling using neuronal nuclear protein (NeuN) sorted-nuclei from 40 frozen brain tissues to determine LOAD-specific changes in chromatin accessibility landscape in a cell-type specific manner. We identified 211 LOAD-specific differential chromatin accessibility sites in neuronal-nuclei, four of which overlapped with LOAD-GWAS regions (±100kb of SNP). While the non-neuronal nuclei did not show LOAD-specific differences, stratification by sex identified 842 LOAD-specific chromatin accessibility sites in females. Seven of these sex-dependent sites in the non-neuronal samples overlapped LOAD-GWAS regions including APOE. LOAD loci were functionally validated using single-nuclei RNA-seq datasets. In conclusion, using brain sorted-nuclei enabled the identification of sex-dependent cell type-specific LOAD alterations in chromatin structure. These findings enhance the interpretation of LOAD-GWAS discoveries, provide potential pathomechanisms, and suggest novel LOAD-loci. Furthermore, our results convey mechanistic insights into sex differences in LOAD risk and clinicopathology.GRAPHICAL ABSTRACT
IL-22BP production is heterogeneously distributed in Crohn’s disease
Authors: Fantou Aurélie , Lagrue Eric , Laurent Thomas , Delbos Laurence , Blandin Stéphanie , Jarry Anne , Beriou Gaëlle , Braudeau Cécile , Salabert Nina , Marin Eros , Moreau Aurélie , Podevin Juliette , Bourreille Arnaud , Josien Régis , Martin Jérôme C 
Published: April 2021

AbstractCrohn’s disease (CD), a form of inflammatory bowel disease (IBD), is characterized by impaired epithelial barrier functions and dysregulated mucosal immune responses. IL-22 binding protein (IL-22BP) is a soluble inhibitor regulating IL-22 bioactivity, a cytokine proposed to play protective roles during CD. We and others have shown that IL-22BP is produced in IBD inflamed tissues, hence suggesting a role in CD. In this work, we extended the characterization of IL-22BP production and distribution in CD tissues by applying enzyme-linked immunosorbent assays to supernatants obtained from the culture of endoscopic biopsies of patients, and reverse transcription-quantitative polymerase chain reaction on sorted immune cell subsets. We reveal that IL-22BP levels are higher in inflamed ileums than colons. We observe that in a cell-intrinsic fashion, populations of mononuclear phagocytes and eosinophils express IL-22BP at the highest levels in comparison to other sources of T cells. We suggest the enrichment of intestinal eosinophils could explain higher IL-22BP levels in the ileum. In inflamed colon, we reveal the presence of increased IL-22/IL22BP ratios compared to controls, and a strong correlation between IL-22BP and CCL24. We identify monocyte-derived dendritic cells (moDC) as a cellular subtype co-expressing both cytokines and validate our finding usingin vitroculture systems. We also show that retinoic acid induces the secretion of both IL-22BP and CCL24 by moDC. Finally, we report on higher IL-22BP levels in active smokers. In conclusion, our work provides new information relevant to therapeutic strategies modulating IL-22 bioactivity in CD, especially in the context of disease location.
The hexose transporter SWEET5 confers galactose sensitivity to Arabidopsis pollen germination via the galactokinase GALK
Authors: Wang Jiang , Yu Ya-Chi , Li Ye , Chen Li-Qing 
Published: April 2021

AbstractGalactose is an abundant and essential sugar used for the biosynthesis of many macromolecules in different organisms, including plants. Galactose metabolism is tightly and finely controlled since excess galactose and derivatives are inhibitory. In Arabidopsis, root growth and pollen germination were strongly inhibited by excess galactose. However, the mechanism of galactose induced inhibition during pollen germination remains obscure. In this study, we characterized a plasma-membrane localized transporter, AtSWEET5, that transports glucose and galactose. SWEET5 protein level started to accumulate at the tricellular stage of pollen development and peaked in mature pollen before rapidly declining after pollen was germinated. SWEET5 levels are responsible for the dosage-dependent sensitivity of galactose and galactokinase (GALK) is essential for the inhibitory effects of galactose during pollen germination. Overall, SWEET5 and GALK contribute to the maintenance of galactose metabolic homeostasis during pollen germination. SWEET5 serves as a major low-affinity hexose transporter at the early stage of pollen germination.One-sentence summarySWEET5 mediates pollen galactose sensitivity via GALK that is required for efficient galactose uptake in pollen during pollen germination.