bluuebunny/crossref_metadata_2025_split huggingface dataset:
Competing adaptations maintain non-adaptive variation in a wild cricket population
Authors: Rayner Jack G. , Eichenberger Franca , Bainbridge Jessica V. A. , Zhang Shangzhe , Zhang Xiao , Yusuf Leeban H. , Balenger Susan , Gaggiotti Oscar E. , Bailey Nathan W. 
Published: October 2023

AbstractHow emerging adaptive variants interact is an important factor in the evolution of wild populations. However, the opportunity to empirically study this interaction is rare. We recently documented the emergence of an adaptive phenotype ‘curly-wing’ in Hawaiian populations of field crickets (Teleogryllus oceanicus). Curly-wing inhibits males’ ability to sing, protecting them from eavesdropping parasitoid flies (Ormia ochracea). Surprisingly, curly-wing co-occurs with similarly protective silent ‘flatwing’ phenotypes in multiple populations, in which neither phenotype has spread to fixation. These two phenotypes are frequently co-expressed, but since either phenotype sufficiently reduces song amplitude to evade the fly, co-expression confers no additional fitness benefit. Numerous negative fitness consequences are known to accompany flatwing, and we find that curly-wing, too, incurs fitness costs via reduced male courtship success and reduced female longevity. We show through crosses, genomic and mRNA sequencing that curly-wing expression is associated with variation on a single autosome. In parallel analyses of flatwing, our results reinforce previous findings of X-linked single-locus inheritance, with the phenotype likely arising through down-regulation ofdoublesex. By combining insights about the genetic architecture of these alternative phenotypes with simulations and field observations, we show that the co-occurrence of these two adaptations impedes either from fixing, despite extreme fitness benefits. Interestingly, both flatwing and curly-wing are statistically associated with nearby inversions, which are also retained as polymorphisms. This co-occurrence of similar adaptive forms in the same populations might be more common than generally considered, and could be an important force inhibiting adaptive evolution in wild populations.
Information gathering explains decision dynamics during human and monkey reward foraging
Authors: Barack David L , Parodi Felipe , Ludwig Vera , Platt Michael L 
Published: October 2023

AbstractForaging in humans and other animals requires a delicate balance between exploitation of current resources and exploration for new ones. The tendency to overharvest—lingering too long in depleting patches—is a routine behavioral deviation from predictions of optimal foraging theories. To characterize the computational mechanisms driving these deviations, we modeled foraging behavior using a virtual patch-leaving task with human participants and validated our findings in an analogous foraging task in two monkeys. Both humans and monkeys overharvested and stayed longer in patches with longer travel times compared to shorter ones. Critically, patch residence times in both species declined over the course of sessions, enhancing reward rates in humans. These decisions were best explained by a logistic transformation that integrated both current rewards and information about declining rewards. This parsimonious model demystifies both the occurrence and dynamics of overharvesting, highlighting the role of information gathering in foraging. Our findings provide insight into computational mechanisms shaped by ubiquitous foraging dilemmas, underscoring how behavioral modeling can reveal underlying motivations of seemingly irrational decisions.
Design of universal Ebola virus vaccine candidatesviaimmunofocusing
Authors: Xu Duo , Powell Abigail E. , Utz Ashley , Sanyal Mrinmoy , Do Jonathan , Patten J.J. , Moliva Juan I. , Sullivan Nancy J. , Davey Robert A. , Kim Peter S. 
Published: October 2023

ABSTRACTEbola virus causes hemorrhagic fever in humans and poses a significant threat to global public health. Although two viral vector vaccines have been approved to prevent Ebola virus disease, they are distributed in the limited ring vaccination setting and only indicated for prevention of infection fromorthoebolavirus zairense(EBOV) – one of threeorthoebolavirusspecies that have caused previous outbreaks. Ebola virus glycoprotein GP mediates viral infection and serves as the primary target of neutralizing antibodies. Here we describe a universal Ebola virus vaccine approach using structure-guided design of candidates with hyperglycosylation that aims to direct antibody responses away from variable regions and toward conserved epitopes of GP. We first determined the hyperglycosylation landscape on Ebola virus GP and used that to generate hyperglycosylated GP variants with two to four additional glycosylation sites to mask the highly variable glycan cap region. We then created vaccine candidates by displaying wild-type or hyperglycosylated GP variants on ferritin nanoparticles (Fer). Immunization with these antigens elicited potent neutralizing antisera against EBOV in mice. Importantly, we observed consistent cross-neutralizing activity against Bundibugyo virus and Sudan virus from hyperglycosylated GP-Fer with two or three additional glycans. In comparison, elicitation of cross-neutralizing antisera was rare in mice immunized with wild-type GP-Fer. These results demonstrate a potential strategy to develop universal Ebola virus vaccines that confer cross-protective immunity against existing and emerging filovirus species.SIGNIFICANCE STATEMENTEbola virus outbreaks cause hemorrhagic fever with high mortality rates. Current viral vaccines require cold-chain storage and are distributed in limited ring vaccination settings. They are only indicated for protection againstorthoebolavirus zairense(EBOV), one of three human-pathogenic Ebola virus species. Here we harness hyperglycosylation as an immunofocusing approach to design universal Ebola virus vaccine candidates based on Ebola virus glycoprotein (GP) displayed on ferritin nanoparticles (Fer). Compared with wild-type GP-Fer, immunization with hyperglycosylated GP-Fer elicited potently neutralizing antisera against EBOV, and more importantly, consistent cross-neutralizing activity against the other two orthoebolavirus species. Our work shows that immunofocusing antibody responses toward conserved and neutralizing epitopes of GP represents a promising strategy for vaccine design against antigenically diverse Ebola virus species.
Spatial processing of limbs reveals the center-periphery bias in high level visual cortex follows a nonlinear topography
Authors: Daniel Hertz Edan , Yao Jewelia K. , Gregorek Sidney , Hoyos Patricia M. , Gomez Jesse 
Published: October 2023

AbstractHuman visual cortex contains regions selectively involved in perceiving and recognizing ecologically important visual stimuli such as people and places. Located in the ventral temporal lobe, these regions are organized consistently relative to cortical folding, a phenomenon thought to be inherited from how centrally or peripherally these stimuli are viewed with the retina. While this eccentricity theory of visual cortex has been one of the best descriptions of its functional organization, whether or not it accurately describes visual processing in all category-selective regions is not yet clear. Through a combination of behavioral and functional MRI measurements, we demonstrate that a limb-selective region neighboring well-studied face-selective regions defies predictions from the eccentricity theory of cortical organization. We demonstrate that the spatial computations performed by the limb-selective region are consistent with visual experience, and in doing so, make the novel observation that there may in fact be two eccentricity gradients, forming a parabolic topography across visual cortex. These data expand the current theory of cortical organization to provide a unifying principle that explains the broad functional features of many visual regions, showing that viewing experience interacts with innate wiring principles to drive the location of cortical specialization.
Viromes vs. mixed community metagenomes: choice of method dictates interpretation of viral community ecology
Authors: Kosmopoulos James C. , Klier Katherine M. , Langwig Marguerite V. , Tran Patricia Q. , Anantharaman Karthik 
Published: October 2023

ABSTRACTBackgroundViruses, the majority of which are uncultivated, are among the most abundant biological entities on Earth. From altering microbial physiology to driving community dynamics, viruses are fundamental members of microbiomes. While the number of studies leveraging viral metagenomics (viromics) for studying uncultivated viruses is growing, standards for viromics research are lacking. Viromics can utilize computational discovery of viruses from total metagenomes of all community members (hereafter metagenomes) or use physical separation of virus-specific fractions (hereafter viromes). However, differences in the recovery and interpretation of viruses from metagenomes and viromes obtained from the same samples remain understudied.ResultsHere, we compare viral communities from paired viromes and metagenomes obtained from 60 diverse samples across human gut, soil, freshwater, and marine ecosystems. Overall, viral communities obtained from viromes were more abundant and species rich than those obtained from metagenomes, although there were some exceptions. Despite this, metagenomes still contained many viral genomes not detected in viromes. We also found notable differences in the predicted lytic state of viruses detected in viromes vs metagenomes at the time of sequencing. Other forms of variation observed include genome presence/absence, genome quality, and encoded protein content between viromes and metagenomes, but the magnitude of these differences varied by environment.ConclusionsOverall, our results show that the choice of method can lead to differing interpretations of viral community ecology. We suggest that the choice of whether to target a metagenome or virome to study viral communities should be dependent on the environmental context and ecological questions being asked. However, our overall recommendation to researchers investigating viral ecology and evolution is to pair both approaches to maximize their respective benefits.
Bioinformatics Illustrations Decoded by ChatGPT: The Good, The Bad, and The Ugly
Authors: Wang Jinge , Ye Qing , Liu Li , Guo Nancy Lan , Hu Gangqing 
Published: October 2023

AbstractEmerging studies underscore the promising capabilities of large language model-based chatbots in conducting fundamental bioinformatics data analyses. The recent feature of accepting image-inputs by ChatGPT motivated us to explore its efficacy in deciphering bioinformatics illustrations. Our evaluation with examples in cancer research, including sequencing data analysis, multimodal network-based drug repositioning, and tumor clonal evolution, revealed that ChatGPT can proficiently explain different plot types and apply biological knowledge to enrich interpretations. However, it struggled to provide accurate interpretations when quantitative analysis of visual elements was involved. Furthermore, while the chatbot can draft figure legends and summarize findings from the figures, stringent proofreading is imperative to ensure the accuracy and reliability of the content.
Proteome-wide Mendelian randomization identifies candidate causal proteins for cardiovascular diseases
Authors: Li Chen , Jay Nicolas De , Sharma Supriya , Catalano Katrina A. , Holzinger Emily R. , Sridharan Venkatesh , Wang Zhaoqing , Zhao Lei , Szustakowski Joseph D. , Chang Ching-Pin , Maranville Joseph C. , Kvikstad Erika M. 
Published: October 2023

AbstractBackgroundCardiovascular diseases (CVD) remain the leading cause of death worldwide, while a lack of clarity on underlying mechanisms has hindered development of novel therapies. Integration of human genetics and proteomics across different ancestries can provide novel, affordable, and systematic approach for target identification and prioritization.MethodsMendelian randomization approach was applied to unravel causal associations between 2,940 circulating proteins and 21 CVD. Genome-wide summary statistics from the largest genetic mapping of human plasma proteome and meta-analyses on CVD across FinnGen, UK Biobank and Biobank Japan were used. Forward and reverse causation were studied to distinguish respective targets and biomarkers. Genetic instruments for Europeans and East Asians were derived separately and applied to the cardiovascular outcomes in cohorts from corresponding ancestries. We further prioritized drug targets by integrating biological, clinical and population study evidence from cross-database annotations and literature review. Single-cell enrichment analysis and phenome-wide causality scan were performed to further understand target mechanism of action.ResultsWe found 221 novel candidate causal proteins that impacted risk of one or more CVD through forward MR, and 16 biomarkers whose expression levels were affected by CVD through reverse MR (Bonferroni-adjustedP-value <= 0.05). Forward and reverse MR found largely non-overlapping proteins among CVD (only 2 overlapped: LGALS4 and MMP12), suggesting distinct proteomic causes and consequences of CVD. Many of the candidate causal proteins (73.4%) identified are supported by strong literature evidence for a role in immune response and atherosclerotic lesion formation, angiogenesis and vascular remodeling, myogenesis and cardiac progenitor cell differentiation, and energy metabolism. Single cell integration further prioritized ADAM23 for cardiomegaly, PAM for stable angina pectoris and ventricular arrythmia and LPL for peripheral artery disease, whose transcript expression were enriched in cardiomyocytes. Three protein functional groups were highlighted in the phenome-wide scan for their specific enrichment for CVD, including blood coagulation and fibrinolysis, angiogenesis and vascular remodeling, and cell proliferation and myogenesis.ConclusionsOur study identified potential therapeutic targets for CVD and distinguished them from biomarkers due to reverse causation. This study provides human genetics-based evidence of novel candidate genes, a foundational step towards full-scale causal human biology-based drug discovery for CVD.
Evolutionary transitions from female to hermaphrodite reproduction remodel olfactory and mating-receptive behaviors
Authors: Ebert Margaret S. , Bargmann Cornelia I. 
Published: October 2023

SummaryMale/hermaphrodite species have arisen multiple times from a male/female ancestral state in nematodes, providing a model to study behavioral adaptations to different reproductive strategies. Here we examined the mating behaviors of male/female (gonochoristic)Caenorhabditisspecies in comparison to male/hermaphrodite (androdiecious) close relatives. We find that females from two species in theElegansgroup chemotax to volatile odor from males, a behavior described in only a few animal species. The females also display known mating-receptive behaviors such as sedation when male reproductive structures contact the vulva. Focusing on the male/female speciesC. nigoni,we show that female chemotaxis to males is limited to adult females approaching adult or near-adult males, and relies upon the AWA neuron-specific transcription factor ODR-7, as does male chemotaxis to female odor as previously shown inC. elegans. However, female receptivity during mating contact isodr-7-independent. All female behaviors are suppressed by mating, and all are absent in young hermaphrodites from the sister speciesC. briggsae. However, latent receptivity during mating contact can be uncovered in mutant or agedC. briggsaehermaphrodites that lack self-sperm. Young hermaphrodites from a second androdioecious species,C. tropicalis, are similarly unreceptive to males, but recover all female behaviors upon aging. These results reveal two mechanistically distinct components of the shift from female to hermaphrodite behavior: the loss of female-specificodr-7-dependent chemotaxis, and a sperm-dependent state of reduced receptivity to mating contact. The recovery of receptivity after sperm depletion has the potential to maximize hermaphrodite fitness across the lifespan.HighlightsFemale and hermaphrodite mating behaviors differ in closely related nematode speciesFemales are attracted to volatile male odors, but hermaphrodites are notThe same olfactory neuron pair drives female attraction to males and vice versaLatent female mating behaviors are revealed in hermaphrodites that lack self-sperm
Macrophage differentiation requires DNA damage caused by Caspase-Activated DNase
Authors: Maurya Deepak , Rai Gayatri , Mandal Debleena , Mondal Bama Charan 
Published: October 2023

SummaryPhagocytic macrophages are crucial for innate immunity and tissue homeostasis. Most macrophages develop from embryonic precursors that populate every organ before birth to self-renew lifelong. However, the mechanisms for macrophage differentiation remain unknown. Using in vivo genetic analysis of theDrosophilalarval hematopoietic organ, the lymph gland, we show that the developmentally regulated transient activation of Caspase-Activated DNase (CAD)-mediated DNA breaks in intermediate progenitors is essential for macrophage differentiation. Insulin receptor-mediated PI3K/Akt signaling triggers apoptotic signaling and causes DNA breaks during macrophage development. However, the same Akt signaling attenuates Apoptosis signal-regulating kinase 1 (Ask1) to control apoptotic and JNK activity in differentiating macrophages. DNA-damaged differentiating cells display autophagy activity as a survival strategy. Furthermore, caspase activity is required for embryonic-origin macrophage development and efficient phagocytosis. This study reveals a previously unknown relationship between developmental signals and caspase-activated DNA breaks necessary for multifunctional macrophage differentiation.
Neutrophilia with damage to the blood-brain barrier and neurovascular unit following acute lung injury
Authors: Li Herman , Le Linh , Marrero Mariah , David-Bercholz Jennifer , Caceres Ana I , Lim Claire , Chiang Wesley , Majewska Ania K , Terrando Niccolò , Gelbard Harris A 
Published: October 2023

AbstractBackgroundLinks between acute lung injury (ALI), infectious disease, and neurological outcomes have been frequently discussed over the past few years, especially due to the COVID-19 pandemic. Yet, much of the cross-communication between organs, particularly the lung and the brain, has been understudied. Here, we have focused on the role of neutrophils in driving changes to the brain endothelium with ensuing microglial activation and neuronal loss in a model of ALI.MethodsWe have applied a three-dose paradigm of 10µg/40µl intranasal lipopolysaccharide (LPS) to induce neutrophilia accompanied by proteinaceous exudate in bronchoalveolar lavage fluid (BALF) in adult C57BL/6 mice. Brain endothelial markers, microglial activation, and neuronal cytoarchitecture were evaluated 24hr after the last intranasal dose of LPS or saline. C57BL/6-Ly6g(tm2621(Cre-tdTomato)Arte (Catchup mice) were used to measure neutrophil and blood-brain barrier permeability following LPS exposure with intravital 2-photon imaging.ResultsThree doses of intranasal LPS induced robust neutrophilia accompanied by proteinaceous exudate in BALF. ALI triggered central nervous system pathology as highlighted by robust activation of the cerebrovascular endothelium (VCAM1, CD31), accumulation of plasma protein (fibrinogen), microglial activation (IBA1, CD68), and decreased expression of proteins associated with postsynaptic terminals (PSD-95) in the hippocampal stratum lacunosum moleculare, a relay station between the entorhinal cortex and CA1 of the hippocampus. 2-photon imaging of Catchup mice revealed neutrophil homing to the cerebral endothelium in the blood-brain barrier and neutrophil extravasation from cerebral vasculature 24hr after the last intranasal treatment.ConclusionsOverall, these data demonstrate ensuing brain pathology resulting from ALI, highlighting a key role for neutrophils in driving brain endothelial changes and subsequent neuroinflammation. This paradigm may have a considerable translational impact on understanding how infectious disease with ALI can lead to neurodegeneration, particularly in the elderly.
Exploring the bounded rationality in human decision anomalies through an assemblable computational framework
Authors: Lu Yi-Long , Lu Yang-Fan , Ren Xiangjuan , Zhang Hang 
Published: October 2023

AbstractSome seemingly irrational decision behaviors (anomalies), once seen as flaws in human cognition, have recently received explanations from a rational perspective. The basic idea is that the brain has limited cognitive resources to process the quantities (e.g., value, probability, time, etc.) required for decision making, with specific biases arising as byproducts of the resource allocation that is optimized for the environment. While appealing for providing normative accounts, the existing resource-rational models have limitations such as inconsistent assumptions across models, a focus on single environmental factors, and limited coverage of decision anomalies. One challenging anomaly is the peanuts effect, a pervasive phenomenon in decision-making under risk that implies an interdependence between the processing of value and probability. To extend the resource rationality approach to explain the peanuts effect, here we develop a computational framework—the Assemblable Resource-Rational Modules (ARRM)—that integrates ideas from different lines of boundedly-rational decision models as freely assembled modules. The framework can accommodate the joint functioning of multiple environmental factors, and allow new models to be built and tested along with the existing ones, potentially opening a wider range of decision phenomena to bounded rationality modeling. For one new and three published datasets that cover two different task paradigms and both the gain and loss domains, our boundedly-rational models reproduce two characteristic features of the peanuts effect and outperform previous models in fitting human decision behaviors.