bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Multivalent Polyomavirus Vaccine Elicits Durable Neutralizing Antibody Responses in Macaques
Authors: Peretti Alberto , Scorpio Diana G. , Kong Wing-Pui , Pang Yuk-Ying S. , McCarthy Michael , Ren Kuishu , Jackson Moriah , Graham Barney S. , Buck Christopher B. , McTamney Patrick M. , Pastrana Diana V. 
Published: September 2022

ABSTRACTIn 2019, there were about 100,000 kidney transplants globally, with more than a quarter of them performed in the United States. Unfortunately, some engrafted organs are lost to polyomavirus-associated nephropathy (PyVAN) caused by BK and JC viruses (BKPyV and JCPyV). Transplant patients are routinely monitored for BKPyV viremia, which is an accepted hallmark of nascent nephropathy. If viremia is detected, a reduction in immunosuppressive therapy is standard care, but the intervention comes with increased risk of immune rejection of the engrafted organ. Recent reports have suggested that transplant recipients with high levels of polyomavirus-neutralizing antibodies are protected against PyVAN. Virus-like particle (VLP) vaccines, similar to approved human papillomaviruses vaccines, have an excellent safety record and are known to induce high levels of neutralizing antibodies associated and long-lasting protection from infection. In this study, we demonstrate that VLPs representing BKPyV genotypes I, II, and IV, as well as JCPyV genotype 2 produced in insect cells elicit robust antibody titers. In rhesus macaques, all monkeys developed neutralizing antibody titers above a previously proposed protective threshold of 10,000. A second inoculation, administered 19 weeks after priming, boosted titers to a plateau of ≥25,000 that was maintained for almost two years. No vaccine-related adverse events were observed in any macaques. A multivalent BK/JC VLP immunogen did not show inferiority compared to the single-genotype VLP immunogens. Considering these encouraging results, we believe a clinical trial administering the multivalent VLP vaccine in patients waiting to receive a kidney transplant is warranted to evaluate its ability to reduce or eliminate PyVAN.HIGHLIGHTSRecombinant virus-like particle vaccine was safely administered to rhesus macaquesVaccination generated high-titer neutralizing antibody responsesMultivalent BK/JC polyomavirus vaccine was as effective as monovalent vaccinesHigh neutralizing titers were sustained for 92 weeks without appreciable decline
Drug interaction mapping with proximity dependent enzyme recruiting chimeras
Authors: Venable John D , Vashisht Ajay A , Rayatpisheh Shima , Lajiness James P , Phillips Dean P , Brock Ansgar 
Published: September 2022

AbstractProximity dependent labeling using engineered enzymes has been used extensively to identify protein-protein interactions, and map protein complexesin-vitroandin-vivo. Here, we extend the use of engineered promiscuous biotin ligases to the identification of small molecule protein targets. Chimeric bi-functional chemical probes (“recruiters”) are used to effectively recruit tagged biotin ligases for proximity dependent labeling of target and target interactors. The broad applicability of this approach is demonstrated with probes developed from a multi-kinase inhibitor, a bromodomain targeting moiety, and an FKBP targeting molecule. While complementary to traditional chemo-proteomic strategies such as photo-affinity labeling (PAL), and activity-based protein profiling (ABPP), this approach is a useful addition to the target ID toolbox with opportunities for tunability based on the inherent labeling efficiencies of different engineered enzymes and control over the enzyme cellular localization.
HB-EGF Promotes Horizontal Basal Cell Proliferation and Olfactory Sensory Neuron Regeneration in the Zebrafish Olfactory Epithelium
Authors: Sireci Siran , Kocagöz Yigit , Alkiraz Aysu Sevval , Güler Kardelen , Dokuzluoglu Zeynep , Balcioglu Ecem , Demirler Mehmet Can , Fuss Stefan Herbert 
Published: September 2022

AbstractMaintenance and regeneration of the zebrafish olfactory epithelium (OE) are supported by distinct progenitor cell populations that occupy discrete stem cell niches and respond to different tissue conditions. Globose basal cells (GBCs) reside at the inner and peripheral margins of the sensory OE and are constitutively active to replace sporadically dying olfactory sensory neurons (OSNs). In contrast, horizontal basal cells (HBCs) are more uniformly distributed across the tissue, including basal layers of the sensory region, and are selectively activated by acute injury conditions that affect the morphological integrity of the OE. Here we show that expression of the heparin-binding epidermal growth factor-like growth factor (HB-EGF) is strongly and transiently upregulated in response to OE injury and signals through the EGF receptor (EGFR), which is expressed by HBCs. Exogenous stimulation of the OE with recombinant HB-EGF promotes HBC expansion and OSN neurogenesis within the sensory OE, resembling the tissue response to injury. In contrast, pharmacological inhibition of HB-EGF shedding, HB-EGF availability, and EGFR signaling strongly attenuate or delay injury-induced HBC activity and OSN restoration without affecting maintenance neurogenesis by GBCs. Thus, HB-EGF/EGFR signaling appears to be a critical component of a complex signaling network that controls HBC activity and, consequently, repair neurogenesis in the zebrafish OE.
Influenza A virus reassortment is strain dependent
Authors: Taylor Kishana Y. , Agu Ilechukwu , José Ivy , Mäntynen Sari , Campbell A.J. , Mattson Courtney , Chou Tsui-wen , Zhou Bin , Gresham David , Ghedin Elodie , Díaz Muñoz Samuel L. 
Published: September 2022

AbstractRNA viruses can exchange genetic material during coinfection, an interaction that creates novel strains with implications for viral evolution and public health. Influenza A viral genetic exchange occurs when genome segments from distinct strains reassort in coinfection. Predicting potential reassortment between influenza strains is a longstanding goal. Experimental coinfection studies have shed light on factors that limit or promote reassortment. However, determining the reassortment potential between diverse Influenza A strains has remained an elusive goal. To fill this gap, we developed a high throughput genotyping approach to quantify reassortment among a diverse panel of human influenza virus strains, encompassing 41 years of epidemics, multiple geographic locations, and both circulating human subtypes A/H1N1 and A/H3N2. We found that the reassortment rate (proportion of reassortants) is an emergent property of a pair of strains where strain identity is a predictor of the reassortment rate. We show little evidence that antigenic subtype drives reassortment as intersubtype (H1N1xH3N2) and intrasubtype reassortment rates were, on average, similar. Instead, our data suggest that certain strains bias the reassortment rate up or down, independently of the coinfecting partner. We also observe that viral productivity is an emergent property of coinfections and that it is not correlated to reassortment rate, thus affecting the total number of reassortant progeny produced. Assortment of individual segments among progeny, and pairwise segment combinations within progeny, were not random and generally favored homologous combinations. This outcome was not related to strain similarity or shared subtype. Reassortment rate was closely correlated to both the proportion of unique genotypes and the proportion of progeny with heterologous pairwise segment combinations. We provide experimental evidence that viral genetic exchange is potentially an individual social trait subject to natural selection, which implies the propensity for reassortment is not evenly shared among strains. This study highlights the need for research incorporating diverse strains to discover the traits that shift the reassortment potential as we work towards the goal of predicting influenza virus evolution resulting from segment exchange.
The assembly of wild natural isolates define neuronal integrity and life history traits of co-inhabiting C. elegans
Authors: Urquiza-Zurich Sebastian , Garcia-Angulo Victor Antonio , Burdisso Paula , Palominos M. Fernanda , Fernandez-Hubeid Lucia , Castillo Juan Pablo , Calixto Andrea 
Published: September 2022

AbstractBacterivore nematodes are the most abundant animals in the biosphere, largely contributing to global biogeochemistry. The effect of environmental microbes as source of associated microbiota and natural diet on their life history traits of nematodes is likely to impact the general health of the biosphere. Caenorhabditis elegans is a unique model to study the behavioral and physiological outputs of different available microbial diets. Nonetheless, most studies are on monoaxenic cultures of laboratory bacteria while the effect of natural microbiota isolates has only recently started to be reported. Here, we quantified physiological, phenotypical and behavioral traits of worms feeding on two bacteria that co-isolated with wild nematodes and tested how combinations of these isolates with other bacteria affected the traits measured. These bacteria were identified as a putative novel species of Stenotrophomonas denominated Stenotrophomonas sp. Iso1 and a strain of Bacillus pumilus designated Iso2. The isolates induced distinctive behaviors and development patterns that changed in mixes of the two bacteria and/or the pathogen Salmonella enterica. Focusing on the degeneration rate of the touch circuit of C. elegans we show that B. pumilus alone is protective while the mix with Stenotrophomonas sp. is degenerative. The analysis of the metabolite content of each isolate and their combination identified NAD+ as potentially neuroprotective. In vivo supplementation shows that NAD+ restores neuroprotection to the mixes and also to individual non-protective bacteria. The results highlight the need to study the physiological effects of bacteria resembling native diets in a multicomponent scenario rather than using single isolates.ImportanceThe behavioral decisions of animals depend on their microbiota. In nature it is unknown how this interaction affects the health of the biosphere. To study how the nematode-bacteria relationship impacts the life history traits of these animals, we isolated bacteria found in association with wild nematodes and tested their influence as single species and consortia, in the life history traits of the model C. elegans. We identify metabolites from wild bacteria that change these traits. The bacteria isolated were identified a Stenotrophomonas sp and a B. pumilus. We find that all traits depend on the biota composition. For example, B. pumilus is neuroprotective to degenerating neurons of the touch circuit of C. elegans needed to sense and escape from predators in the wild. The co-culture with Stenotrophomonas sp. eliminates the protection. We identified NAD+ as the metabolite lost in the mix, and show that NAD+ by itself is neuroprotective.
Label-based meta-analysis of functional brain dysconnectivity across mood and psychotic disorders
Authors: Grot Stéphanie , Smine Salima , Potvin Stéphane , Darcey Maëliss , Pavlov Vilena , Genon Sarah , Nguyen Hien , Orban Pierre 
Published: September 2022

ABSTRACTBACKGROUNDPsychiatric diseases are increasingly conceptualized as brain network disorders. Hundreds of resting-state functional magnetic resonance imaging (rsfMRI) studies have revealed patterns of functional brain dysconnectivity in disorders such as major depression disorder (MDD), bipolar disorder (BD) and schizophrenia (SZ). Although these disorders have been mostly studied in isolation, there is mounting evidence of shared neurobiological alterations across disorders.METHODSTo uncover the nature of the relatedness between these psychiatric disorders, we conducted an innovative meta-analysis of past functional brain dysconnectivity findings obtained separately in MDD, BD and SZ. Rather than relying on a classical coordinate-based approach at the voxel level, our procedure extracted relevant neuroanatomical labels from text data and reported findings at the whole brain network level. Data were drawn from 428 rsfMRI studies investigating MDD (158 studies, 7429 patients / 7414 controls), BD (81 studies, 3330 patients / 4096 patients) and/or SZ (223 studies, 11168 patients / 11754 controls). Permutation testing revealed commonalities and specificities in hypoconnectivity and hyperconnectivity patterns across disorders.RESULTSAmong 78 connections within or between 12 cortico-subcortical networks, hypoconnectivity and hyperconnectivity patterns of higher-order cognitive (default-mode, fronto-parietal, cingulo-opercular) networks were similarly observed across the 3 disorders. By contrast, dysconnectivity of lower-order (somatomotor, visual, auditory) networks in some cases differed between disorders, notably dissociating SZ from BD and MDD.CONCLUSIONSOur label-based meta-analytic approach allowed a comprehensive inclusion of prior studies. Findings suggest that functional brain dysconnectivity of higher-order cognitive networks is largely transdiagnostic in nature while that of lower-order networks may best discriminate mood and psychotic disorders, thus emphasizing the relevance of motor and sensory networks to psychiatric neuroscience.
Regulating the timing of enhancer transitions is key to defining sharp boundaries of Fushi tarazu expression in the Drosophila embryo
Authors: Birnie Anthony , Plat Audrey , Bothma Jacques P. 
Published: September 2022

SummaryCoordinating the action of different enhancers is crucial to correctly specify cell fate decisions during development. Yet it remains poorly understood how the activity of multiple enhancers is choregraphed in time. To shed light on this question we used new live imaging approaches to quantify transcription and protein expression in single cells of Drosophila melanogaster embryos. We employed these tools to dissect the regulation of Fushi tarazu (Ftz), a transcription factor expressed in a series of stripes by two distinct enhancers: autoregulatory and zebra. The anterior edges of the Ftz stripes are sharply defined and specify essential signaling centers. Here, we determined the time at which each boundary cell commits to either a high-Ftz or low-Ftz fate using dynamic features of time-resolved Ftz protein traces. By following the activity of each enhancer individually, we showed that the autoregulatory enhancer does not establish this fate choice. Instead, it perpetuates the decision defined by zebra. This is contrary to the prevailing view that autoregulation drives the fate decision by causing bi-stable Ftz expression. Furthermore, we showed that the autoregulatory enhancer is not activated based on a Ftz concentration threshold, but through a timing-based mechanism. We hypothesize that this is regulated by a set of pioneer-like transcription factors, which have recently been shown to act as timers in the embryo. Our work provides new insight into the genetic mechanisms that directly regulate the dynamics of gene regulatory networks, and supports the emerging view that this regulation is vital for reliable cell fate specification.
Real-Time Spatial Registration for 3D Human Atlas
Authors: Chen Lu , Teng Dejun , Zhu Tian , Kong Jun , Herr Bruce W. , Bueckle Andreas , Borner Katy , Wang Fusheng 
Published: September 2022

AbstractThe human body is made up of about 37 trillion cells (adults). Each cell has its own unique role and is affected by its neighboring cells and environment. The NIH Human BioMolecular Atlas Program (HuBMAP) aims at developing a 3D atlas of human body consisting of organs, vessels, tissues to singe cells with all 3D spatially registered in a single 3D human atlas using tissues obtained from normal individuals across a wide range of ages. A critical step of building the atlas is to register 3D tissue blocks in real-time to the right location of a human organ, which itself consists of complex 3D substructures. The complexity of the 3D organ model, e.g., 35 meshes for a typical kidney, poses a significant computational challenge for the registration. In this paper, we propose a comprehensive framework TICKET (TIssue bloCK rEgisTration) for tissue block registration for 3D human atlas, including (1) 3D mesh pre-processing, (2) spatial queries on intersection relationship and (3) intersection volume computation between organs and tissue blocks. To minimize search space and computation cost, we develop multi-level indexing on both the anatomical structure level and mesh level, and utilize OpenMP for parallel computing. Considering cuboid based shape of the tissue block, we propose an efficient voxelization-based method to estimate the intersection volume. Our experiments demonstrate that the proposed framework is practical and efficient. TICKET is now integrated into the HuBMAP CCF registration portal [1].
Characterization of membrane vesicles inAlteromonas macleodiiindicates potential roles in their copiotrophic lifestyle
Authors: Fadeev Eduard , Bastos Cécile Carpaneto , Hennenfeind Jennifer , Biller Steven J , Sher Daniel , Wietz Matthias , Herndl Gerhard J 
Published: September 2022

AbstractBacterial membrane vesicles (MVs) are likely abundant in the oceans. Based on observations from non-marine bacteria, MVs are involved in a range of physiological processes and play important roles in interactions between microbial cells. In this study we characterized MV production of six different strains ofAlteromonas macleodii, a cosmopolitan marine bacterium.A. macleodiistrains produced MVs at rates of up to 30 MVs cell-1generation-1. The produced MVs had high morphological diversity that could potentially define their functional roles. Proteomic characterization revealed that MVs are rich in membrane proteins related to iron and phosphate uptake, as well as proteins with potential functions in biofilm formation. Furthermore, MVs were harboring hydrolytic enzymes. Taken together, our results suggest that in the largely oligotrophic oceans,A. macleodiiMVs may support its growth through generation of extracellular “hotspots” that facilitate access to essential substrates. This study provides an important basis for further investigation of the ecological relevance of MVs in heterotrophic marine bacteria.
Sharing GWAS summary statistics results in more citations: evidence from the GWAS catalog
Authors: Reales Guillermo , Wallace Chris 
Published: September 2022

AbstractGenome-wide association studies (GWAS) have been a crucial tool in genomics and an example of applied reproducible science principles for almost two decades.1 Their output, summary statistics, are especially suited for sharing, which in turn enables new hypothesis testing and scientific discovery. However, GWAS summary statistics sharing rates have been historically low due to a lack of incentives and strong data sharing mandates, privacy concerns and standard guidelines.2 Albeit imperfect, citations are a key metric to evaluate the research impact. We hypothesised that data sharing might benefit authors through increased citation rates and investigated this using GWAS catalog3 data. We found that sharers get on average ~75% more citations, independently of journal of publication and impact factor, and that this effect is sustained over time. This work provides further incentivises authors to share their GWAS summary statistics in standard repositories, such as the GWAS catalog.
High-resolution analysis of individualDrosophila melanogasterlarvae within groups uncovers inter- and intra-individual variability in locomotion and its neurogenetic modulation
Authors: Thane Michael , Paisios Emmanouil , Stöter Torsten , Krüger Anna-Rosa , Gläß Sebastian , Dahse Anne-Kristin , Scholz Nicole , Gerber Bertram , Lehmann Dirk J. , Schleyer Michael 
Published: September 2022

AbstractNeuronally orchestrated muscular movement and locomotion are defining faculties of multicellular animals. Due to its numerically simple brain and neuromuscular system and its genetic accessibility, the larva of the fruit flyDrosophila melanogasteris an established model to study these processes at tractable levels of complexity. However, although the faculty of locomotion clearly pertains to the individual animal, present studies of locomotion in larvalDrosophilamostly use group assays and measurements aggregated across individual animals. The alternative is to measure animals one at a time, an extravagance for larger-scale analyses. In principle or in practice, this in particular rules out grasping the inter- and intra-individual variability in locomotion and its genetic and neuronal determinants. Here we present the IMBA (Individual Maggot Behaviour Analyser) for tracking and analysing the behaviour of individual larvae within groups. Using a combination of computational modelling and statistical approaches, the IMBA reliably resolves individual identity across collisions. It does not require specific hardware and can therefore be used in non-expert labs. We take advantage of the IMBA first to systematically describe the inter- and intra-individual variability in free, unconstrained locomotion in wild-type animals. We then report the discovery of a novel, complex locomotion phenotype of a mutant lacking an adhesion-type GPCR. The IMBA further allows us to determine, at the level of individual animals, the modulation of locomotion across repeated activations of dopamine neurons. Strikingly, IMBA can also be used to analyse ‘silly walks’, that is patterns of locomotion it was not originally designed to investigate. This is shown for the transient backward locomotion induced by brief optogenetic activation of the brain-descending ‘mooncrawler’ neurons, and the variability in this behaviour. Thus, the IMBA is an easy-to-use toolbox allowing an unprecedentedly rich view of the behaviour and behavioural variability of individualDrosophilalarvae, with utility in multiple biomedical research contexts.
The structure of monkeypox virus 2’-O-ribose methyltransferase VP39 in complex with sinefungin provides the foundation for inhibitor design
Authors: Silhan Jan , Klima Martin , Chalupska Dominika , Kozic Jan , Boura Evzen 
Published: September 2022

AbstractMonkeypox is an emerging, rapidly spreading disease with pandemic potential. It is caused by the monkeypox virus (MPXV), a dsDNA virus from the Poxviridae family, that replicates in the cytoplasm and must encode for its own RNA processing machinery including the capping machinery. Here, we present the crystal structure of its 2’-O-RNA methyltransferase (MTase) VP39 in complex with the pan-MTase inhibitor sinefungin. A comparison of this 2’-O RNA MTase with enzymes from unrelated ssRNA viruses (SARS-CoV-2 and Zika) reveals a surprisingly conserved sinefungin binding mode implicating that a single inhibitor could be used against unrelated viral families.
MHC class I and MHC class II reporter mice enable analysis of immune oligodendroglia in mouse models of multiple sclerosis
Authors: Harrington Em P , Catenacci Riley B , Smith Matthew D , Heo Dongeun , Miller Cecilia E , Meyers Keya R , Glatzer Jenna , Bergles Dwight E , Calabresi Peter A 
Published: September 2022

AbstractOligodendrocytes and their progenitors upregulate MHC pathways in response to inflammation, but the frequency of this phenotypic change is unknown and the features of these immune oligodendroglia are poorly defined. We generated MHC class I and II transgenic reporter mice to define their dynamics in response to inflammatory demyelination, providing a means to monitor MHC activation in diverse cell types in living mice and define their roles in aging, injury and disease.