bluuebunny/crossref_metadata_2025_split huggingface dataset:
Axiomatic-deductive theory of competition of complete competitors: coexistence, exclusion and neutrality in one model
Authors: Kalmykov Lev V. , Kalmykov Vyacheslav L. 
Published: July 2020

AbstractBackgroundThe long-standing contradiction between formulations of the competitive exclusion principle and natural diversity of trophically similar species is known as the biodiversity paradox. Earlier we found that coexistence of complete competitors is possible despite 100% difference in competitiveness, but only under certain conditions – at their moderate propagation and at the particular initial location of individuals. Here we verify a hypothesis that completely competing species with aggressive propagation may coexist with less than 100% difference in competitiveness regardless of random initial location of competing individuals in ecosystem.MethodsWe investigate a role of competitiveness differences in coexistence of two completely competing species by individual-based modeling based on a transparent artificial intelligence. We propose and investigate an individual-based model of ecosystem dynamics supplemented by a probabilistic determination of the competitiveness of competing individuals without cooperative effects and with cooperative effects based on the numerical superiority of individuals of the species.ResultsWe have found that two aggressively propagating complete competitors can stably coexist, despite one species has some advantage in competitiveness over the other and all other characteristics of the species are equal. The found competitive coexistence occurred regardless of the initial random location of individuals in the ecosystem. When colonization of a free habitat started from a single individual of each species, then the complete competitors coexisted up to 31% of their difference in competitiveness. And when on initial stage half of the territory was probabilistically occupied, the complete competitors coexisted up to 22% of their difference in competitiveness. In the experiments with cooperative dependence on the numerical superiority of individuals of the species complete competitors stably co-existed despite 10% difference in basic competitiveness.DiscussionThe results additionally support our earlier reformulation of the competitive exclusion principle. Besides that, we revealed classical cases of competitive exclusion and “neutrality”. Our approach unifies models of competitive exclusion (“niche”), neutrality and coexistence of complete competitors in one theory. Our individual-based modeling of a complex system based on a transparent artificial intelligence opens up great prospects for a variety of theoretical and applied fields.
A meta-analysis of clinical cases of reversion mutations inBRCAgenes identifies signatures of DNA end-joining repair mechanisms driving therapy resistance
Authors: Tobalina Luis , Armenia Joshua , Irving Elsa , O’Connor Mark J. , Forment Josep V. 
Published: July 2020

AbstractGermline mutations in theBRCA1orBRCA2genes predispose to hereditary breast and ovarian cancer and, mostly in the case ofBRCA2, are also prevalent in cases of pancreatic and prostate malignancies. Tumours from these patients tend to lose both copies of the wild typeBRCAgene, which makes them exquisitely sensitive to platinum drugs and PARP inhibitors (PARPi), treatments of choice in these disease settings. Reversion secondary mutations with the capacity of restoring BRCA protein expression have been documented in the literature asbona fidemechanisms of resistance to these treatments. Here, we perform a detailed analysis of clinical cases of reversion mutations described inBRCA1andBRCA2, which underlines the different importance of BRCA protein domains in contributing to resistance and the potential key role of mutagenic end-joining DNA repair pathways in generating reversions. Our analyses suggest that pharmacological inhibition of these repair pathways could improve durability of drug treatments and highlights potential interventions to both prevent the appearance of reversions and provide new therapeutic opportunities after their acquisition.HighlightsComprehensive analysis of reversion mutations inBRCAgenes identified in clinical cases of resistance to platinum or PARPiRevertant proteins devoid of parts of the original sequence, identifying key protein functions involved in resistanceHypomorph revertant BRCA proteins suggest potential new therapeutic opportunities to overcome resistancePrevalence of mutational end-joining DNA repair mechanisms leading to reversions, especially in those affectingBRCA2Pharmacological inhibition of mutational end-joining DNA repair could improve durability of drug treatments
Wing musculature reconstruction in extinct flightless auks (PinguinusandMancalla) reveals incomplete convergence with penguins (Spheniscidae) due to differing ancestral states
Authors: Watanabe Junya , Field Daniel J. , Matsuoka Hiroshige 
Published: July 2020

AbstractDespite longstanding interest in convergent evolution, factors that result in deviations from fully convergent phenotypes remain poorly understood. In birds, the evolution of flightless wing-propelled diving has emerged as a classic example of convergence, having arisen in disparate lineages including penguins (Sphenisciformes) and auks (Pan-Alcidae, Charadriiformes). Nevertheless, little is known about the functional anatomy of the wings of flightless auks because all such taxa are extinct, and their morphology is almost exclusively represented by skeletal remains. Here, in order to re-evaluate the extent of evolutionary convergence among flightless wing-propelled divers, wing muscles and ligaments were reconstructed in two extinct flightless auks, representing independent transitions to flightlessness:Pinguinus impennis(a crown-group alcid), andMancalla(a stem-group alcid). Extensive anatomical data were gathered from dissections of 12 species of extant charadriiforms and 4 aequornithine waterbirds including a penguin. It was found that the wings of both flightless auk taxa were characterized by an increased mechanical advantage of wing elevator/retractor muscles, and decreased mobility of distal wing joints, both of which are likely advantageous for wing-propelled diving and parallel similar functional specializations in penguins. However, the conformations of individual muscles and ligaments underlying these specializations differ markedly between penguins and flightless auks, instead resembling those in each respective group’s close relatives. Thus, the wings of these flightless wing-propelled divers can be described as convergent as overall functional units, but are incompletely convergent at lower levels of anatomical organization—a result of retaining differing conditions from each group’s respective volant ancestors. Detailed investigations such as this one may indicate that, even in the face of similar functional demands, courses of phenotypic evolution are dictated to an important degree by ancestral starting points.
Identification of a new regulation pathway of EGFR and E-cadherin dynamics
Authors: Proux-Gillardeaux Veronique , Advedissian Tamara , Perin Charlotte , Gelly Jean-Christophe , Viguier Mireille , Deshayes Fredérique 
Published: July 2020

ABSTRACTEGFR plays key roles in multiple cellular processes such as cell differentiation, cell proliferation, migration and epithelia homeostasis. Phosphorylation of the receptor, intracellular signaling and trafficking are major events regulating EGFR functions. Galectin-7, a soluble lectin expressed in epithelia such as the skin, has been shown to be involved in cell differentiation. Through this study we demonstrate that galectin-7 regulates EGFR function by a direct interaction with its extracellular domain hence modifying its downstream signaling and endocytic pathway. From observations in mice we focused on the molecular mechanisms deciphering the glycosylation dependent interaction between EGFR and galectin-7. Interestingly, we also revealed that galectin-7 is a direct binder of both EGFR and E-cadherin bridging them together. Strikingly this study not only deciphers a new molecular mechanism of EGFR regulation but also points out a novel molecular interaction between EGFR and E-cadherin, two major regulators of the balance between proliferation and differentiation.SUMMARYEGFR and E-cadherin are known to interact and to regulate epithelial homeostasis. In this study we unravel in the epidermis a new partner and regulator of EGFR which also binds E-cadherin reciprocally bridging their dynamics and functions.
Selective targeting of non-centrosomal AURKA functions through use of a targeted protein degradation tool
Authors: Wang Richard , Ascanelli Camilla , Abdelbaki Ahmed , Fung Alex , Rasmusson Tim , Michaelides Iacovos , Roberts Karen , Lindon Catherine 
Published: July 2020

AbstractTargeted protein degradation tools are becoming a new therapeutic modality, allowing small molecule ligands to be reformulated as heterobifunctional molecules (PROteolysis Targeting Chimeras, PROTACs) that recruit ubiquitin ligases to targets of interest, leading to ubiquitination and destruction of the targets. Several PROTACs against targets of clinical interest have been described, but detailed descriptions of the cell biology modulated by PROTACs are missing from the literature. Here we describe the functional characterization of a PROTAC derived from AURKA inhibitor MLN8237 (alisertib). We demonstrate efficient and specific destruction of both endogenous and overexpressed AURKA by Cereblon-directed PROTACs. At the subcellular level, we find differential targeting of AURKA on the mitotic spindle compared to centrosomes. The phenotypic consequences of PROTAC treatment are therefore distinct from those mediated by alisertib, and in mitotic cells differentially regulate centrosome- and chromatin-based microtubule spindle assembly pathways. In interphase cells PROTAC-mediated clearance of non-centrosomal AURKA modulates the cytoplasmic role played by AURKA in mitochondrial dynamics, whilst the centrosomal pool is refractory to PROTAC-mediated clearance. Our results point to differential sensitivity of subcellular pools of substrate, governed by substrate conformation or localization-dependent accessibility to PROTAC action, a phenomenon not previously described for this new class of degrader compounds.
Single-cell Long Non-coding RNA Landscape of T Cells in Human Cancer Immunity
Authors: Luo Haitao , Bu Dechao , Shao Lijuan , Li Yang , Sun Liang , Wang Ce , Wang Jing , Yang Wei , Yang Xiaofei , Dong Jun , Zhao Yi , Li Furong 
Published: July 2020

AbstractThe development of new therapeutic targets for cancer immunotherapies and the development of new biomarkers require deep understanding of T cells. To date, the complete landscape and systematic characterization of long noncoding RNAs (lncRNAs) in T cells in cancer immunity are lacking. Here, by systematically analyzing full-length single-cell RNA sequencing (scRNA-seq) data of more than 20,000 T cell libraries across three cancer types, we provide the first comprehensive catalog and the functional repertoires of lncRNAs in human T cells. Specifically, we developed a custom pipeline forde novotranscriptome assembly obtaining 9,433 novel lncRNA genes that increased the number of current human lncRNA catalog by 16% and nearly doubled the number of lncRNAs expressed in T cells. We found that a portion of expressed genes in single T cells were lncRNAs which have been overlooked by the majority of previous studies. Based on metacell maps constructed by MetaCell algorithm that partition scRNA-seq datasets into disjointed and homogenous groups of cells (metacells), 154 signature lncRNAs associated with effector, exhausted, and regulatory T cell states are identified, 84 of which are functionally annotated based on co-expression network, indicating that lncRNAs might broadly participate in regulation of T cell functions. Our findings provide a new point of view and resource for investigating the mechanisms of T cell regulation in cancer immunity as well as for novel cancer-immune biomarker development and cancer immunotherapies.
Different computations underlie overt and covert spatial attention
Authors: Li Hsin-Hung , Pan Jasmine , Carrasco Marisa 
Published: July 2020

AbstractPerception and action are tightly coupled: visual responses at the saccade target are enhanced right before saccade onset. This phenomenon, presaccadic attention, is a form of overt attention—deployment of visual attention with concurrent eye movements. Presaccadic attention is well-documented, but its underlying computational process remains unknown. This is in stark contrast with covert attention—deployment of visual attention without concurrent eye movements—for which the computational process is well characterized. Here, a series of psychophysical experiments reveal that presaccadic attention modulates visual performance only via response gain changes even when attention field size increases, violating the predictions of a normalization model of attention, which has been widely used to explain the computations underlying covert attention. Our empirical results and model comparisons reveal that the perceptual modulations by overt and covert spatial attention are mediated through different computations.
Coupling between lipid miscibility and phosphotyrosine driven protein condensation at the membrane
Authors: Chung J. K. , Huang W. Y. C. , Carbone C. B. , Nocka L. M. , Parikh A. N. , Vale R. D. , Groves J. T. 
Published: July 2020

AbstractLipid miscibility phase separation has long been considered to be a central element of cell membrane organization. More recently, protein condensation phase transitions, into three-dimensional droplets or in two-dimensional lattices on membrane surfaces, have emerged as another important organizational principle within cells. Here, we reconstitute the LAT:Grb2:SOS protein condensation on the surface of giant unilamellar vesicles capable of undergoing lipid phase separations. Our results indicate that assembly of the protein condensate on the membrane surface can drive lipid phase separation. This phase transition occurs isothermally and is governed by tyrosine phosphorylation on LAT. Furthermore, we observe that the induced lipid phase separation drives localization of the SOS substrate, K-Ras, into the LAT:Grb2:SOS protein condensate.Statement of SignificanceProtein condensation phase transitions are emerging as an important organizing principles in cells. One such condensate plays a key role in T cell receptor signaling. Immediately after receptor activation, multivalent phosphorylation of the adaptor protein LAT at the plasma membrane leads to networked assembly of a number of signaling proteins into a two-dimensional condensate on the membrane surface. In this study, we demonstrate that LAT condensates in reconstituted vesicles are sufficient to drive lipid phase separation. This lipid reorganization drives another key downstream signaling molecule, Ras, into the LAT condensates. These results show that the LAT condensation phase transition, which is actively controlled by phosphorylation reactions, extends its influence to control lipid phase separation in the underlying membrane.
Plasticity in astrocyte subpopulations regulates heroin relapse
Authors: Kruyer Anna , Angelis Ariana , Garcia-Keller Constanza , Li Hong , Kalivas Peter W. 
Published: July 2020

ABSTRACTOpioid use disorder (OUD) produces detrimental personal and societal consequences. Astrocytes are a major cell group in the brain that receives little attention in mediating OUD. We determined how astrocytes and the astroglial glutamate transporter, GLT-1, in the nucleus accumbens core adapt and contribute to heroin seeking in rats. Seeking heroin, but not sucrose, produced two transient forms of plasticity in different astroglial subpopulations. Increased morphological proximity to synapses occurred in one subpopulation and increased extrasynaptic GLT-1 expression in another. Augmented synapse proximity by astroglia occurred selectively at D2-dopamine receptor expressing dendrites, while changes in GLT-1 were not neuron-subtype specific. Importantly, mRNA-antisense inhibition of either morphological or GLT-1 plasticity promoted cue-induced heroin seeking. We show that heroin cues induce two distinct forms of transient plasticity in separate astroglial subpopulations that dampen heroin relapse.TEASERDifferent subpopulations of astrocytes engage with accumbens synapses to dampen heroin relapse.
ERRα coordinates actin and focal adhesion dynamics
Authors: Tribollet Violaine , Cerutti Catherine , Géloën Alain , Danty-Berger Emmanuelle , De Mets Richard , Balland Martial , Courchet Julien , Vanacker Jean-Marc , Forcet Christelle 
Published: July 2020

AbstractCell migration depends on the dynamic organization of the actin cytoskeleton and assembly and disassembly of focal adhesions (FA). However the precise mechanisms coordinating these processes remain poorly understood. We previously identified the estrogen-related receptor α (ERRα) as a major regulator of cell migration. Here, we show that loss of ERRα leads to abnormal accumulation of actin filaments that is associated with an increase in the level of inactive form of the actin-depolymerizing factor cofilin. We further show that ERRα depletion decreases cell adhesion and promotes defective FA formation and turnover. Interestingly, specific inhibition of the RhoA-ROCK-LIMK-cofilin pathway rescues the actin polymerization defects resulting from ERRα silencing, but not cell adhesion. Instead we found that MAP4K4 is a direct target of ERRα and down-regulation of its activity rescues cell adhesion and FA formation in the ERRα-depleted cells. Altogether, our results highlight a crucial role of ERRα in coordinating the dynamic of actin network and focal adhesion through the independent regulation of the RhoA and MAP4K4 pathways.
Spatial phylogenetics of butterflies in relation to environmental drivers and angiosperm diversity across North America
Authors: Earl Chandra , Belitz Michael W. , Laffan Shawn W. , Barve Vijay , Barve Narayani , Soltis Douglas E. , Allen Julie M. , Soltis Pamela S. , Mishler Brent D. , Kawahara Akito Y. , Guralnick Robert 
Published: July 2020

AbstractBroad-scale quantitative assessments of biodiversity and the factors shaping it remain particularly poorly explored in insects. Here, we undertook a spatial phylogenetic analysis of North American butterflies via assembly of a time-calibrated phylogeny of the region coupled with a unique, complete range assessment for ~75% of the known species. We utilized a suite of phylodiversity metrics and associated environmental data to test whether climate stability and temperature gradients have shaped North American butterfly phylogenetic diversity and endemism. We also undertook the first direct, quantitative comparisons of spatial phylogenetic patterns between butterflies and flowering plants in North America. We expected concordance between butterflies and angiosperms based on both shared historical environmental drivers and presumed strong butterfly-host plant specializations. We instead found that biodiversity patterns in butterflies are strikingly different from flowering plants in some regions of the continent. In particular, the warm desert regions of the southwestern United States and Mexico showed surprisingly high butterfly phylogenetic diversity and endemism, in contrast to much lower values for angiosperms. Butterflies did not show patterns of phylogenetic clustering as found in flowering plants, suggesting differences in habitat conservation between the two groups. Finally, we found weak relationships and spatially structured biases in relative branching timing between angiosperms and butterflies. These results suggest that shared biogeographic histories and trophic associations do not necessarily assure similar diversity outcomes. The work has applied value in conservation planning, documenting warm deserts as an important North American butterfly biodiversity hotspot.
Sister chromatid repair maintains genomic integrity during meiosis inCaenorhabditis elegans
Authors: Toraason Erik , Clark Cordell , Horacek Anna , Glover Marissa L. , Salagean Alina , Libuda Diana E. 
Published: July 2020

SummaryDuring meiosis, the maintenance of genome integrity is critical for generating viable haploid gametes [1]. In meiotic prophase I, double-strand DNA breaks (DSBs) are induced and a subset of these DSBs are repaired as interhomolog crossovers to ensure proper chromosome segregation. DSBs in excess of the permitted number of crossovers must be repaired by other pathways to ensure genome integrity [2]. To determine if the sister chromatid is engaged for meiotic DSB repair during oogenesis, we developed an assay to detect sister chromatid repair events at a defined DSB site duringCaenorhabditis elegansmeiosis. Using this assay, we directly demonstrate that the sister chromatid is available as a meiotic repair template for both crossover and noncrossover recombination, with noncrossovers being the predominant recombination outcome. We additionally find that the sister chromatid is the exclusive recombination partner for DSBs during late meiotic prophase I. Analysis of noncrossover conversion tract sequences reveals that DSBs are processed similarly throughout prophase I and recombination intermediates remain central around the DSB site. Further, we demonstrate that the SMC-5/6 complex is required for long conversion tracts in early prophase I and intersister crossovers during late meiotic prophase I; whereas, the XPF-1 nuclease is required only in late prophase to promote sister chromatid repair. In response to exogenous DNA damage at different stages of meiosis, we find that mutants for SMC-5/6 and XPF-1 have differential effects on progeny viability. Overall, we propose that SMC-5/6 both processes recombination intermediates and promotes sister chromatid repair within meiotic prophase I, while XPF-1 is required as an intersister resolvase only in late prophase I.
MicrobeTrace: Retooling Molecular Epidemiology for Rapid Public Health Response
Authors: Campbell Ellsworth M. , Boyles Anthony , Shankar Anupama , Kim Jay , Knyazev Sergey , Switzer William M. 
Published: July 2020

AbstractMotivationOutbreak investigations use data from interviews, healthcare providers, laboratories and surveillance systems. However, integrated use of data from multiple sources requires a patchwork of software that present challenges in usability, interoperability, confidentiality, and cost. Rapid integration, visualization and analysis of data from multiple sources can guide effective public health interventions.ResultsWe developed MicrobeTrace to facilitate rapid public health responses by overcoming barriers to data integration and exploration in molecular epidemiology. Using publicly available HIV sequences and other data, we demonstrate the analysis of viral genetic distance networks and introduce a novel approach to minimum spanning trees that simplifies results. We also illustrate the potential utility of MicrobeTrace in support of contact tracing by analyzing and displaying data from an outbreak of SARS-CoV-2 in South Korea in early 2020.Availability and ImplementationMicrobeTrace is a web-based, client-side, JavaScript application (https://microbetrace.cdc.gov) that runs in Chromium-based browsers and remains fully-operational without an internet connection. MicrobeTrace is developed and actively maintained by the Centers for Disease Control and Prevention. The source code is available athttps://github.com/cdcgov/microbetrace.Contactells@cdc.gov