bluuebunny/crossref_metadata_2025_split huggingface dataset:
WITHDRAWN: Genomic characterization of Crimean-Congo Hemorrhagic Fever Virus detected during nosocomial outbreak (2023) in Balochistan province of Pakistan
Authors: Umair Massab , Haider Syed Adnan , Ali Qasim , Hakim Rabia , Raisani Maqbool Ahmed , Ayub Adnan , Salman Muhammad 
Published: November 2023

Withdrawal StatementThe authors have withdrawn their manuscript owing to lack of approval by provincial health authorities to publish this work. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.
Examining the association of live virus neutralisation activity of capillary microsamples and risk of SARS-CoV-2 infections: a nested case control study within the Virus Watch community cohort
Authors: Yavlinsky Alexei , Nguyen Vincent G. , Beale Sarah , Wall Emma , Wu Mary Y , Braithwaite Isobel , Kovar Jana , Shrotri Madhumita , Navaratnam Annalan M D , Fong Wing Lam Erica , Byrne Thomas E. , Balloux François , Abubakar Ibrahim , Cowling Benjamin J. , Hayward Andrew C. , Aldridge Robert W. 
Published: November 2023

AbstractDue to the proliferation of new SARS-CoV-2 variants, most COVID-19 cases are now caused by post-vaccine infections and a substantial proportion are reinfections. While prior research on correlates of protection has focused on the role of anti-spike antibodies, the results of the corresponding antibody assays may not accurately predict the risk of infection with new SARS-CoV-2 variants. In this study, we investigated the association between live virus neutralising antibody activity and SARS-CoV-2 infection risk using self-administered capillary microsample blood tests from VirusWatch participants. The study was conducted during the transition between the dominance of the B.1.617.2 (Delta) and B.1.1.529 (Omicron BA.1) SARS-CoV-2 variants, enabling us to investigate the association between variant-specific virus inhibition and subsequent infections within each dominance period. Greater inhibition of Omicron BA.1 live virus was associated with a reduction in infection risk during both the Delta and Omicron BA.1 dominance periods. Delta virus inhibition was associated with infection risk reduction during the Delta dominance period, but we found no association between Delta inhibition and protection against infection during the Omicron BA.1 dominance period. Our results are consistent with earlier findings and suggest that variant-specific serosurveillance of immunity and protection against SARS-CoV-2 infection at the population level could inform public health policy in near-real time using inexpensive and accessible home-based testing.
Pathogenic IgE-fated B cell memory retains functional plasticity
Authors: Bruton Kelly , Phelps Allyssa , Ariaz Atai , Walker Tina D. , Wen Jianping , Khavkine-Binstock Sharon S. , Fang Allison , Mann-Delany Olivia , Knudsen Niels Peter H. , Gadkar Siyon , Grydziuszko Emily , Koenig Joshua F. E. , Gagnon Aidan , Waserman Susan , Andersen Peter S. , Jordana Manel 
Published: November 2023

AbstractLong-lived immunoglobulin (Ig) E responses against innocuous environmental and dietary antigens (Ags) are maintained by an IgG1-dominant memory B cell (MBC) compartment primed for IL-4 responsiveness. In this work, we investigated the plasticity of the MBC compartment fated for IgE class switch recombination upon Ag re-exposure. Antibody-mediated IL-4R( blockade augmented the germinal center response and uncovered an IL-4/IL-13 dependency within the type 2 memory B cell (MBC2) skewed phenotype. In the absence of IL-4/IL-13 signaling during the recall response, a long-lived Ag-specific IgG2c MBC population emerged, shifting the MBC response away from a type 2 phenotype and towards type 1. The emergence of this IgG2c response was dependent on IFN-( signaling and arose from both unswitched and class-switched Ag-specific B cells in vivo. We further demonstrated that a type 1-polarizing adjuvant can augment the redirection of type 2-polarized class-switched MBCs, suggesting with the correct cues pathogenic MBCs can be functionally reprogrammed.One Sentence SummaryB cell responses to allergens can be reprogrammed away from a pathogenic fate through IL-4/IL-13 signaling blockade.
Hydrothermal vent fauna of the Galápagos Rift: Updated species list with new records
Authors: Chen Chong , Jamieson John W. , Tunnicliffe Verena 
Published: November 2023

AbstractThe sighting of giant bivalves and tubeworms at the Rose Garden vent field on the Galápagos Rift in 1977 marked the discovery of hydrothermal vents, a turning point for modern biology. The following decade saw a flurry of taxonomic descriptions of vent endemic species from the first vents. With the finding of high-temperature ‘black smokers’ on the East Pacific Rise, exploration shifted away from Galápagos. A faunal list of Galápagos vents with 65 species was published in 1991, then updated to 74 species in 2006. Since then, few expeditions returned to the Galápagos Rift. Here, we revisited several Galápagos vents including recently confirmed high-temperature sites and inactive sulfide mounds. From our collecting efforts and observations, as well as revisions from the literature, we update the faunal list to 92 species including 15 new records, restricted to obvious vent associates. Accurate regional faunal lists are important for understanding the biogeography of vent fauna, and our list will also be valuable for setting management strategies.
Inference of the core gene regulatory network underlying seam cell development inCaenorhabditis elegans
Authors: Brożek Alicja , Ceccarelli Arianna , Jørgensen Andreas Christ Sølvsten , Hintze Mark , Barkoulas Michalis , Shahrezaei Vahid 
Published: November 2023

AbstractGene regulatory networks are fundamental in cellular decision-making, yet even in well-studied systems, their topologies are often poorly characterised. The nematodeCaenorhabditis eleganscontains a population of stem-like cells, known as seam cells. While seam cells are essential to generate the majority of the animal epidermis as well as specific neurons, the architecture of the underlying gene network has not been elucidated. Here, we combine experiments, mathematical modelling and statistical inference to uncover the architecture of the seam cell gene network focusing on three core transcription factors (TFs), the GATA factors ELT-1, EGL-18 and the Engrailed homolog CEH-16. We use single-molecule FISH (smFISH) to quantify TF mRNA abundance in single seam cells in both wild type and mutant backgrounds. We then predict potential TF interactions and their quantitative strengths using a combination of Modular Response Analysis, ordinary differential equations and a Bayesian model discovery approach. Taken together, our findings suggest new relationships between core TFs in seam cells and highlight an approach that can be used to infer quantitative networks from smFISH data.
(R,S)-ketamine’s rapid-acting antidepressant effects are modulated by NR2B-containing NMDA receptors on adult-born hippocampal neurons
Authors: Bulthuis Nicholas E. , McGowan Josephine C. , Ladner Liliana R. , LaGamma Christina T. , Lim Sean C. , Shubeck Claire X. , Brachman Rebecca A. , Sydnor Ezra , Pavlova Ina P. , Seo Dong-oh , Drew Michael R. , Denny Christine A. 
Published: November 2023

ABSTRACTStandard antidepressant treatments often take weeks to reach efficacy and are ineffective for many patients. (R,S)-ketamine, anN-methyl-D-aspartate (NMDA) antagonist, has been shown to be a rapid-acting antidepressant and to decrease depressive symptoms within hours of administration. While previous studies have shown the importance of the NR2B subunit of the NMDA receptor (NMDAR) on interneurons in the medial prefrontal cortex (mPFC), no study has investigated the influence of NR2B-expressing adult-born granule cells (abGCs). In this study, we examined whether (R,S)-ketamine’s efficacy depends upon these adult-born hippocampal neurons using a genetic strategy to selectively ablate the NR2B subunit of the NMDAR from Nestin+cells. To validate our findings, we also used several other transgenic lines including one in which NR2B was deleted from an interneuron (Parvalbumin (PV)+) population. We report that in male mice, NR2B expression on 6-week-old adult-born neurons is necessary for (R,S)-ketamine’s effects on behavioral despair in the forced swim test (FST) and on hyponeophagia in the novelty suppressed feeding (NSF) paradigm, as well on fear behavior following contextual fear conditioning (CFC). In female mice, NR2B expression is necessary for effects on hyponeophagia in the NSF. We also find that ablating neurogenesis increases fear expression in CFC, which is buffered by (R,S)-ketamine administration. In line with previous studies, these results suggest that 6-week-old adult-born hippocampal neurons expressing NR2B partially modulate (R,S)-ketamine’s rapid-acting effects. Future work targeting these 6-week-old adult-born neurons may prove beneficial for increasing the efficacy of (R,S)-ketamine’s antidepressant actions.
Effects of transient, persistent, and resurgent sodium currents on excitability and spike regularity in vestibular ganglion neurons
Authors: Baeza-Loya Selina , Eatock Ruth Anne 
Published: November 2023

AbstractVestibular afferent neurons occur as two populations with differences in spike timing regularity that are independent of rate. The more excitable regular afferents have lower current thresholds and sustained spiking responses to injected currents, while irregular afferent neurons have higher thresholds and transient responses. Differences in expression of low-voltage-activated potassium (KLV) channels are emphasized in models of spiking regularity and excitability in these neurons, leaving open the potential contributions of the voltage-gated sodium (NaV) channels responsible for the spike upstroke. We investigated the impact of different NaVcurrent modes (transient, persistent, and resurgent) with whole-cell patch clamp experiments in mouse vestibular ganglion neurons (VGNs), the cultured and dissociated cell bodies of afferents. All VGNs had transient NaVcurrent, many had a small persistent (non-inactivating) NaVcurrent, and a few had resurgent current, which flows after the spike peak when NaVchannels that were blocked are unblocked. NaV1.6 channels conducted most or all of each NaVcurrent mode, and a NaV1.6-selective blocker decreased spike rate and altered spike waveforms in both sustained and transient VGNs. A NaVchannel agonist enhanced persistent current and increased spike rate and regularity. We hypothesized that persistent and resurgent currents have different effects on sustained (regular) VGNs vs. transient (irregular) VGNs. Lacking blockers specific for the different current modes, we used modeling to isolate their effects on spiking of simulated transient and sustained VGNs, driven by simulated current steps and noisy trains of simulated EPSCs. In all simulated neurons, increasing transient NaVcurrent increased spike rate and rate-independent regularity. In simulated sustained VGNs, adding persistent current increased both rate and rate-independent regularity, while adding resurgent current had limited impact. In transient VGNs, adding persistent current had little impact, while adding resurgent current increased both rate and rate-independent irregularity by enhancing sensitivity to synaptic noise. These experiments show that the small NaVcurrent modes may enhance the differentiation of afferent populations, with persistent currents selectively making regular afferents more regular and resurgent currents selectively making irregular afferents less regular.
Length control emerges from cytoskeletal network geometry
Authors: McInally Shane G. , Reading Alexander J.B. , Rosario Aldric , Jelenkovic Predrag R. , Goode Bruce L. , Kondev Jane 
Published: November 2023

AbstractMany cytoskeletal networks consist of individual filaments that are organized into elaborate higher order structures. While it is appreciated that the size and architecture of these networks are critical for their biological functions, much of the work investigating control over their assembly has focused on mechanisms that regulate the turnover of individual filaments through size-dependent feedback. Here, we propose a very different, feedback-independent mechanism to explain how yeast cells control the length of their actin cables. Our findings, supported by quantitative cell imaging and mathematical modeling, indicate that actin cable length control is an emergent property that arises from the cross-linked and bundled organization of the filaments within the cable. Using this model, we further dissect the mechanisms that allow cables to grow longer in larger cells, and propose that cell length-dependent tuning of formin activity allows cells to scale cable length with cell length. This mechanism is a significant departure from prior models of cytoskeletal filament length control and presents a new paradigm to consider how cells control the size, shape, and dynamics of higher order cytoskeletal structures.Significance StatementCells control the sizes of their cytoskeletal networks to ensure that these structures can efficiently perform their cellular functions. Until now, this ability has been attributed to molecular feedback mechanisms that control the rates at which individual filaments are assembled and disassembled. We find that size control of cytoskeletal networks does not require this type of feedback and can instead be encoded through the physical arrangement of the filaments within that network. These findings have important implications for understanding how the underlying geometry of higher order cytoskeletal networks contributes to cellular control over these structures.
Single nucleus transcriptome of a “Super RV” shows increased insulin and angiogenesis signaling
Authors: Turaga Diwakar , Li Xiao , Zhao Yi , Tsai Chang-Ru , Moreira Axel , Hickey Edward , Adachi Iki , Martin James 
Published: November 2023

ABSTRACTThe right ventricle (RV) is one of the four pumping chambers of the heart, pumping blood to the lungs. In severe forms of congenital heart disease and pulmonary hypertension, the RV is made to pump into the systemic circulation. Such systemic RVs typically display early failure due to pressure overload. In rare cases a systemic RV persists into later decades of life – colloquially called a ‘Super RV’. Here we present the single-nucleus transcriptome of a systemic RV from a 60-year-old with congenitally corrected transposition of great arteries (ccTGA). Our data shows two specific signaling pathways enriched in the ccTGA RV myocardium. First, we show increased insulin like growth factor (IGF1) signaling within the systemic RV myocardium: there is increased expression of the main receptor IGFR1 within the cardiomyocytes, and IGF1 ligands within the cardiofibroblasts and macrophages. Second, we find increased VEGF and Wnt9 ligand expression in cardiomyocytes and increased VEGF1R and Wnt9 receptors in endothelial cells, which are implicated in angiogenesis. We show that increased insulin and angiogenesis signaling are potentially beneficial RV adaptations to increased pressure overload. This study of an adult systemic RV provides an important framework for understanding RV remodeling to systemic pressures in congenital heart disease and pulmonary hypertension.
Fluctuating temperatures exacerbate the effects of nutritional stress during development inDrosophila melanogaster
Authors: Zanco Brooke , Morimoto Juliano , Cockerell Fiona , Mirth Christen , Sgrò Carla M. 
Published: November 2023

AbstractRecent studies suggest that elevated temperatures interact with nutrition to exacerbate the negative effects of poor nutrition. Furthermore, populations adapted to distinct environments differ in their sensitivity to combined thermal and nutritional stress. However, most studies have tested these effects using constant temperatures, even though animals in the wild experience daily and seasonal thermal fluctuations. Here, we used two locally-adapted populations ofD. melanogasterfrom the east coast of Australia (a tropical and a temperate population) to ask whether temperature fluctuations interact with nutrition in the same manner as constant temperature conditions to shape life history traits, and how this differs across populations. We found that fluctuating temperatures exacerbate the negative effects of a poor diet when compared to constant temperatures. Moreover, the negative effects of nutritional stress were significantly greater in the tropical population. In contrast, we found that the temperate population was able to utilize nutrition in unique ways to maintain optimal viability under warmer temperatures. Our findings reveal the ways in which temperature and nutrition interact to impact key life history traits in geographically distinct populations, while also highlighting the importance of using temperature assays representative of natural diel cycles when examining insect responses to climate change.
Altered Metabolism and DAM-signatures in Female Brains and Microglia with Aging
Authors: Cleland Nicholas R W , Potter Garrett J , Buck Courtney , Quang Daphne , Oldham Dean , Neal Mikaela , Saviola Anthony , Niemeyer Christy S. , Dobrinskikh Evgenia , Bruce Kimberley D. 
Published: November 2023

AbstractDespite Alzheimer’s disease (AD) disproportionately affecting women, the mechanisms remain elusive. In AD, microglia undergo ‘metabolic reprogramming’, which contributes to microglial dysfunction and AD pathology. However, how sex and age contribute to metabolic reprogramming in microglia is understudied. Here, we use metabolic imaging, transcriptomics, and metabolic assays to probe age-and sex-associated changes in brain and microglial metabolism. Glycolytic and oxidative metabolism in the whole brain was determined using Fluorescence Lifetime Imaging Microscopy (FLIM). Young female brains appeared less glycolytic than male brains, but with aging, the female brain became ‘male-like.’ Transcriptomic analysis revealed increased expression of disease-associated microglia (DAM) genes (e.g.,ApoE,Trem2,LPL), and genes involved in glycolysis and oxidative metabolism in microglia from aged females compared to males. To determine whether estrogen can alter the expression of these genes, BV-2 microglia-like cell lines, which abundantly express DAM genes, were supplemented with 17β-estradiol (E2). E2 supplementation resulted in reduced expression of DAM genes, reduced lipid and cholesterol transport, and substrate-dependent changes in glycolysis and oxidative metabolism. Consistent with the notion that E2 may suppress DAM-associated factors, LPL activity was elevated in the brains of aged female mice. Similarly, DAM gene and protein expression was higher in monocyte-derived microglia-like (MDMi) cells derived from middle-aged females compared to age-matched males and was responsive to E2 supplementation. FLIM analysis of MDMi from young and middle-aged females revealed reduced oxidative metabolism and FAD+ with age. Overall, our findings show that altered metabolism defines age-associated changes in female microglia and suggest that estrogen may inhibit the expression and activity of DAM-associated factors, which may contribute to increased AD risk, especially in post-menopausal women.
Context versus aiming in motor learning when both feedforward and feedback control processes are engaged
Authors: Crossley Matthew J. , Hewitson Christopher L. , Kaplan David M. 
Published: November 2023

AbstractTheories of human motor learning commonly assume that movement plans are adjusted in response to the precision of sensory feedback received regarding their success. However, support for this assumption has mainly come from experiments that limit feedback correction during an ongoing movement. In contrast, we have recently shown that when this restriction is relaxed, and both within-movement and between-movement corrections can occur, movement plans undergo large and abrupt changes that are strongly correlated with the degree of sensory uncertainty present on the previous trial and are insensitive to the magnitude and direction of recently experienced movement errors. A class of models in which sensory uncertainty influences an aiming process with no retention from one trial to the next best accounted for these data. Here, we examine an alternative possibility that sensory uncertainty acts as a contextual cue to shunt motor learning and control to one of many context-specific internal models. Although both aiming and context models provide good fits for our data, the aiming model performed best.Author summaryA large body of literature shows that sensory uncertainty inversely scales the degree of error-driven corrections made to motor plans from one trial to the next. However, by limiting sensory feedback to the endpoint of movements, these studies prevent corrections from taking place during the movement. We have recently shown that when such corrections are permitted, sensory uncertainty punctuates between-trial movement corrections with abrupt changes that closely track the degree of sensory uncertainty but are insensitive to the magnitude and direction of recently experienced movement error. Here, we ask whether this pattern of behaviour is more consistent with sensory uncertainty driving changes in an aiming process or context-specific motor learning.
Novel Missing Data Imputation Approaches Enhance Quantitative Trait Loci Discovery in Multi-Omics Analysis
Authors: Qi Zining , Pelletier Alexandre , Willwerscheid Jason , Cao Xuewei , Wen Xiao , Cruchaga Carlos , De Jager Philip , Julia TCW , Wang Gao 
Published: November 2023

AbstractHandling missing values in multi-omics datasets is essential for a broad range of analyses. While several benchmarks for multi-omics data imputation methods have recommended certain approaches for practical applications, these recommendations are not widely adopted in real-world data analyses. Consequently, the practical reliability of these methods remains unclear. Furthermore, no existing benchmark has assessed the impact of missing data and imputation on molecular quantitative trait loci (xQTL) discoveries. To establish the best practice for xQTL analysis amidst missing values in multi-omics data, we have thoroughly benchmarked 16 imputation methods. This includes methods previously recommended and in use in the field, as well as two new approaches we developed by extending existing methods. Our analysis indicates that no established method consistently excels across all benchmarks; some can even result in significant false positives in xQTL analysis. However, our extension to a recent Bayesian matrix factorization method,FLASH, exhibits superior performance in multi-omics data imputation across various scenarios. Notably, it is both powerful and well-calibrated for xQTL discovery compared to all the other methods. To support researchers in practically implementing our approach, we have integrated our extension toFLASHinto the R package flashier, accessible athttps://github.com/willwerscheid/flashier. Additionally, we provide a bioinformatics pipeline that implementsFLASHand other methods compatible with xQTL discovery workflows based on tensorQTL, available athttps://cumc.github.io/xqtl-pipeline/code/data_preprocessing/phenotype/phenotype_imputation.html.