bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemo-architecture of area prostriata in adult and developing mice: comparison with presubiculum and parasubiculum
Authors: Chen Sheng-Qiang , Chen Chang-Hui , Xiang Xiao-Jun , Zhang Shun-Yu , Ding Song-Lin 
Published: March 2022

AbstractRetrosplenial area 29e, which was a cortical region described mostly in earlier rodent literature, is often included in the dorsal presubiculum (PrSd) or postsubiculum (PoS) in modern literature and commonly used brain atlases. Recent anatomical and molecular studies have revealed that retrosplenial area 29e belongs to the superficial layers of area prostriata, which in primates is found to be important in fast analysis of quickly moving objects in far peripheral visual field. As in primates, the prostriata in rodents adjoins area 29 (granular retrosplenial area), area 30 (agranular retrosplenial area), medial visual cortex, PrSd-PoS, parasubiculum (PaS) and postrhinal cortex (PoR). The present study aims to reveal the chemo-architecture of the prostriata versus PrSd-PoS or PaS by means of a systematic survey of gene expression patterns in adult and developing mouse brains. First, we find many genes that display differential expression across the prostriata, PrSd-PoS and PaS and that show obvious laminar expression patterns. Second, we reveal subsets of genes that selectively express in the dorsal or ventral parts of the prostriata, suggesting the existence of at least two subdivisions. Third, we detect some genes that shows differential expression in the prostriata of postnatal mouse brains from adjoining regions, thus enabling identification of the developing area prostriata. Fourth, gene expression difference of the prostriata from the medial visual cortex and PoR is also observed. Finally, molecular and connectional features of the prostriata in rodents and non-human primates are discussed and compared.
Determining the optimal SARS-CoV-2 mRNA vaccine dosing interval for maximum immunogenicity
Authors: Asamoah-Boaheng Michael , Goldfarb David M. , Prusinkiewicz Martin A. , Golding Liam , Karim Mohammad Ehsanul , Barakauskas Vilte , Wall Nechelle , Jassem Agatha N. , Marquez Ana Citlali , MacDonald Chris , O’Brien Sheila F. , Lavoie Pascal , Grunau Brian 
Published: March 2022

ABSTRACTObjectiveEmerging evidence indicates that longer SARS-CoV-2 vaccine dosing intervals results in an enhanced immune response. However, the optimal vaccine dosing interval for achieving maximum immunogenicity is unclear.MethodsThis study included samples from adult paramedics in Canada who received two doses of either BNT162b2 or mRNA-1273 vaccines and provided blood samples 6 months (170 to 190 days) after the first vaccine dose. The main exposure variable was vaccine dosing interval (days), categorized as “short” (first quartile), “moderate” (second quartile), “long” (third quartile), and “longest” interval (fourth quartile). The primary outcome was total spike antibody concentrations, measured using the Elecsys SARS-CoV-2 total antibody assay. Secondary outcomes included: spike and RBD IgG antibody concentrations, and inhibition of angiotensin-converting enzyme 2 (ACE-2) binding to wild-type spike protein and several different Delta variant spike proteins. We fit a multiple log-linear regression model to investigate the association between vaccine dosing intervals and the antibody concentrations.ResultsA total of 564 adult paramedics (mean age 40 years, SD=10) were included. Compared to “short interval” (≤30 days), higher dosing interval quartiles (moderate: 31-38 days; long: 39-73 days and longest: ≥74 days) were all associated with increased Elescys spike total antibody concentration. Compared to the short interval, “long” and “longest” interval quartiles were associated with higher spike and RBD IgG antibody concentrations. Similarly, increasing dosing intervals increased inhibition of ACE-2 binding to viral spike protein, regardless of the vaccine type.ConclusionIncreased mRNA vaccine dosing intervals longer than 30 days result in higher levels of circulating antibodies and viral neutralization when assessed at 6 months.
Mathematical Analysis of a Zika Model with reservoirs and Human Movement
Authors: Al-Maqrashi Kifah , Al-Musalhi Fatma , Elmojtaba Ibrahim M. , Al-Salti Nasser 
Published: March 2022

AbstractA mathematical model for Zika virus is proposed describing the spread of the disease in three interacting populations, namely, human, vector (mosquitoes) and non-human primate (monkeys) inhabiting forests area. Human movement between rural and forest areas has been also considered. It is assumed that Zika virus spreads within non-human primate population, which in turn acts as a reservoir of infection, and then transmitted to the human population through infected mosquitoes. The proposed model incorporates vertical transmission and direct transmission in all populations. The proposed model has been first normalized. The normalized model has been then fully analyzed both qualitatively and quantitatively to investigate the role of the interaction between forest mosquitoes and primates on the ZIKV transmission dynamics. The mathematical analysis includes positivity and boundedness of solutions, derivation of the basic reproduction numberR0using the next generation matrix method, sensitivity analysis, existence and stability analysis of all equilibria and bifurcation analysis. Finally, numerical simulations have been carried out to illustrate the obtained theoretical results and to demonstrate the effect of some model parameters in the disease transmission dynamics. The results show that the interaction between forest mosquitoes and primates has a significant impact on the ZIKV transmission dynamics among human population through the fraction of susceptible moving to forest areas. Furthermore, the results highlight that the transmission probabilities are as important as the ratios of population size between vector population and human or primate populations in the disease transmission dynamics.
A structural atlas of the developing zebrafish telencephalon based on spatially-restricted transgene expression
Authors: Turner Katherine J. , Hawkins Thomas A. , Henriques Pedro M. , Valdivia Leonardo E. , Bianco Isaac H. , Wilson Stephen W. , Folgueira Mónica 
Published: March 2022

1.AbstractZebrafish telencephalon acquires an everted morphology by a two-step process that occurs from 1 to 5 days post-fertilization (dpf). Little is known about how this process affects the positioning of discrete telencephalic cell populations, hindering our understanding of how eversion impacts telencephalic structural organisation. In this study, we characterise the neurochemistry, cycle state and morphology of an EGFP positive (+) cell population in the telencephalon of Et(gata2:EGFP)bi105 transgenic fish during eversion and up to 20dpf. We map the transgene insertion to the early-growth-response-gene-3 (egr3) locus and show that EGFP expression recapitulates endogenous egr3 expression throughout much of the pallial telencephalon. Using the gata2:EGFPbi105 transgene, in combination with other well-characterised transgenes and structural markers, we track the development of various cell populations in the zebrafish telencephalon as it undergoes the morphological changes underlying eversion. These datasets were registered to reference brains to form an atlas of telencephalic development at key stages of the eversion process (1dpf, 2dpf and 5dpf) and compared to expression in adulthood. Finally, we registered gata2:EGFPbi105 expression to the Zebrafish Brain Browser 6dpf reference brain (ZBB, see Marquart et al., 2015, 2017; Tabor et al. 2019), to allow comparison of this expression pattern with anatomical data already in ZBB.
Defining cellular population dynamics at single cell resolution during prostate cancer progression
Authors: Germanos Alexandre A. , Arora Sonali , Zheng Ye , Goddard Erica T. , Coleman Ilsa M. , Ku Anson T. , Wilkinson Scott , Amezquita Robert A. , Zager Michael , Long Annalysa , Yang Yu Chi , Bielas Jason H. , Gottardo Raphael , Ghajar Cyrus M. , Nelson Peter S. , Sowalsky Adam G. , Setty Manu , Hsieh Andrew C. 
Published: March 2022

SummaryAdvanced prostate malignancies are a leading cause of cancer-related deaths in men, in large part due to our incomplete understanding of cellular drivers of disease progression. We investigated prostate cancer cell dynamics at single-cell resolution from disease onset to the development of androgen independence in vivo. We observe a dramatic expansion of a castration-resistant intermediate luminal cell type that correlates with treatment resistance and poor prognosis in human patients. Moreover, transformed epithelial cells and associated fibroblasts create a microenvironment conducive to pro-tumorigenic immune infiltration, which is in part androgen responsive. Androgen independent prostate cancer leads to significant diversification of intermediate luminal cell populations characterized by a range of androgen signaling activity inversely correlated with proliferation and mRNA translation. Accordingly, distinct epithelial populations are exquisitely sensitive to translation inhibition which leads to epithelial cell death, loss of pro-tumorigenic signaling, and decreased tumor heterogeneity. Our findings reveal a complex tumor environment largely dominated by castration-resistant luminal cells and immunosuppressive infiltrates.
Parametric effects of light acting via multiple photoreceptors contribute to circadian entrainment inDrosophila melanogaster
Authors: Abhilash Lakshman , Shafer Orie Thomas 
Published: March 2022

AbstractCircadian rhythms in physiology and behavior have near 24-hour periodicities that must adjust to the exact 24-hour geophysical cycles on earth to ensure adaptive daily timing. Such adjustment is called entrainment. One major mode of entrainment is via the continuous modulation of circadian period by the prolonged presence of light. AlthoughDrosophila melanogasteris a prominent insect model of chronobiology, there is little evidence for such continuous effects of light in the species. In this study, we demonstrate that prolonged light exposure at specific times of the day shapes the daily timing of activity in flies. We also establish that continuous blue- and UV-blocked light lengthens the circadian period ofDrosophilaand provide evidence that this is produced by the combined action of multiple photoreceptors which, includes the cell autonomous photoreceptorcryptochrome. Finally, we introduce ramped light cycles as an entrainment paradigm that produces light entrainment that lacks the large light-driven startle responses typically displayed by flies and requires multiple days for entrainment to shifted cycles. These features are reminiscent of entrainment in mammalian models systems and make possible new experimental approaches to understanding the mechanisms underlying entrainment in the fly.
The Coronavirus Calendar (CoronaCal): a Simplified SARS-CoV-2 Test System for Sampling and Retrospective Analysis
Authors: Thaler David S. , Kazmi Manija A. , Åberg Karina C. , Mattheisen Jordan M. , Huber Thomas , Sakmar Thomas P. 
Published: March 2022

ABSTRACTBackgroundThe testing of saliva samples for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA has become a useful and common method to diagnose coronavirus disease 2019 (Covid-19). However, there are limited examples of serial testing with correlated clinical metadata, especially in the outpatient setting.MethodWe developed a method to collect serial saliva samples on ordinary white printer paper, which can be subsequently analyzed for the presence of SARS-CoV-2 RNA using established polymerase chain reaction (PCR) procedures. The collection systems consisted of a biological diary (CoronaCal) where subjects dab their saliva onto ovals printed onto paper. The dried samples are covered with a sticker that includes a symptom checklist to create a biological diary. Each sheet of letter paper can accommodate up to 14 serial samples.ResultsIn a pilot study, ten subjects used CoronaCals for durations of nine to 44 days. SARS-CoV-2 RNA was extracted and detected in CoronaCals from nine of nine people with either Covid-19 symptoms or exposure to someone with Covid-19, and in zero of one asymptomatic person. The CoronaCals were stored for up to 70 days at room temperature during collection and then frozen for up to four months before analysis, suggesting that SARS-CoV-2 RNA is stable once dried onto paper. Interestingly, the temporal pattern of symptoms was not well correlated with SARS-CoV-2 RNA in serial daily collections for up to 44 days. In addition, SARS-CoV-2 positivity was discontinuous over time in most cases but persisted for up to 24 days.ConclusionsWe conclude that sampling of saliva on simple paper CoronaCals may provide a useful method to study the natural history and epidemiology of Covid-19. The CoronaCal collection and testing method we developed is also easy to implement, inexpensive, non-invasive, and scalable. More broadly, the approach can be used to archive biological samples for retrospective analysis to deepen epidemiological understanding during viral disease outbreaks and to provide information about the natural history of emerging infections.
Endothelial FOXC1 and FOXC2 promote intestinal regeneration after ischemia-reperfusion injury
Authors: Tan Can , Norden Pieter R. , Liu Ting , Ujiie Naoto , Yan Xiaocai , Aoto Kazushi , Ortega Sagrario , De Plaen Isabelle G. , Kume Tsutomu 
Published: March 2022

AbstractIntestinal ischemia induces mucosal damage while simultaneously activating intestinal stem cells (ISCs), which subsequently regenerate the damaged intestinal epithelium. However, whether paracrine factors secreted from vascular endothelial cells (ECs) - blood and lymphatic ECs (BECs and LECs, respectively) – regulate ISC-mediated regeneration have yet to be elucidated. Here, we identify FOXC1 and FOXC2 as essential regulators of paracrine signaling in regeneration of the small intestine after ischemia-reperfusion (I/R) injury. EC- and LEC-specific deletions of Foxc1, Foxc2, or both in mice augment I/R-induced intestinal damage by causing defects in vascular regrowth, expression of the chemokine CXCL12 and the Wnt activator R- spondin 3 in BECs and LECs, respectively, and activation of Wnt signaling in ISCs. Treatment with CXCL12 and R-spondin 3 rescues the I/R-induced intestinal damage in EC- and LEC-Foxc mutant mice, respectively. This study provides evidence that FOXC1 and FOXC2 are required for intestinal regeneration by stimulating paracrine CXCL12 and Wnt signaling.
Subgroups of Eating Behavior Traits Independent of Obesity Defined Using Functional Connectivity and Feature Representation Learning
Authors: Choi Hyoungshin , Byeon Kyoungseob , Lee Jong-eun , Hong Seok-Jun , Park Bo-yong , Park Hyunjin 
Published: March 2022

AbstractEating behavior is highly heterogeneous across individuals, and thus, it cannot be fully explained using only the degree of obesity. We utilized unsupervised machine learning and functional connectivity measures to explore the heterogeneity of eating behaviors. This study was conducted on 424 healthy adults. We generated low-dimensional representations of functional connectivity defined using the resting-state functional magnetic resonance imaging, and calculated latent features using the feature representation capabilities of an autoencoder by nonlinearly compressing the functional connectivity information. The clustering approaches applied to latent features identified three distinct subgroups. The subgroups exhibited different disinhibition and hunger traits; however, their body mass indices were comparable. The model interpretation technique of integrated gradients revealed that these distinctions were associated with the functional reorganization in higher-order associations and limbic networks and reward-related subcortical structures. The cognitive decoding analysis revealed that these systems are associated with reward- and emotion-related systems. We replicated our findings using an independent dataset, thereby suggesting generalizability. Our findings provide insights into the macroscopic brain organization of eating behavior-related subgroups independent of obesity.
A selective bottleneck during host entry drives the evolution of new legume symbionts
Authors: Doin de Moura Ginaini Grazielli , Mouffok Saida , Gaudu Nil , Cazalé Anne-Claire , Milhes Marine , Bulach Tabatha , Valière Sophie , Roche David , Ferdy Jean-Baptiste , Masson-Boivin Catherine , Capela Delphine , Remigi Philippe 
Published: March 2022

AbstractDuring the emergence of new host-microbe symbioses, multiple selective pressures-acting at the different steps of the microbial life cycle–shape the phenotypic traits that jointly determine microbial fitness. However, the relative contribution of these different selective pressures to the adaptive trajectories of microbial symbionts are still poorly known. Here we characterized the dynamics of phenotypic adaptation and its underlying genetic bases during the experimental evolution of a plant pathogenic bacterium into a legume symbiont. We observed that fast adaptation was predominantly driven by selection acting on competitiveness for host entry, which outweighed selection acting on within-host proliferation. Whole-population sequencing of evolved bacteria revealed that phenotypic adaptation was supported by the continuous accumulation of new mutations and the sequential sweeps of cohorts of mutations with similar temporal trajectories. The identification of adaptive mutations within the fixed mutational cohorts showed that all of them improved competitiveness for host entry, while only a subset of those also improved within host proliferation. Computer simulations predict that this effect emerges from the presence of a strong selective bottleneck at host entry. Together, these results show how selective bottlenecks can alter the relative influence of selective pressures acting during bacterial adaptation to multistep infection processes.
Concurrent mapping of brain ontogeny and phylogeny within a common connectivity space
Authors: Warrington S. , Thompson E. , Bastiani M. , Dubois J. , Baxter L. , Slater R. , Jbabdi S. , Mars R. B. , Sotiropoulos S. N. 
Published: March 2022

AbstractDevelopmental and evolutionary effects on brain organisation are complex, yet linked, as evidenced by the striking correspondence in cortical expansion changes. However, it is still not possible to study concurrently the ontogeny and phylogeny of cortical areal connections, which is arguably more relevant to brain function than allometric changes. Here, we propose a novel framework that allows the integration of connectivity maps from humans (adults and neonates) and non-human primates (macaques) onto a common space. We use white matter bundles to anchor the definition of the common space and employ the uniqueness of the areal connection patterns to these bundles to probe areal specialisation. This enables us to quantitatively study divergences and similarities in cortical connectivity over both evolutionary and developmental scales. It further allows us to map brain maturation trajectories, including the effect of premature birth, and to translate cortical atlases between diverse brains.
MiR-182-5p regulates Nogo-A expression and promotes neurite outgrowth of hippocampal neurons in vitro
Authors: Soto Altea , Nieto-Díaz Manuel , Reigada David , Muñoz-Galdeano Teresa , Barreda-Manso M. Asunción , Maza Rodrigo M. 
Published: March 2022

AbstractNogo-A protein is a key myelin-associated inhibitor for axonal growth, regeneration, and plasticity in the central nervous system (CNS). Regulation of the Nogo-A/NgR1 pathway facilitates functional recovery and neural repair after spinal cord trauma and ischemic stroke. MicroRNAs are described as effective tools for the regulation of important processes in CNS such as neuronal differentiation, neuritogenesis, and plasticity. Our results showed that miR-182-5p mimic specifically downregulates the expression of the luciferase reporter gene fused to the mouse Nogo-A 3’UTR, and Nogo-A protein expression in Neuro-2a and C6 cells. Finally, we observed that when rat primary hippocampal neurons are co-cultured with C6 cells transfected with miR-182-5p mimic, there is a promotion of the outgrowth of neuronal neurites in length. From all these data we suggest that miR-182-5p may be a potential therapeutic tool for the promotion of axonal regeneration in different diseases of the CNS.Graphical abstractHighlightsBioinformatics analyses show that miR-182-5p targets Nogo-A 3’UTR.MiR-182-5p downregulates Nogo-A protein expression in murine cell lines.MiR-182-5p promotes neurite outgrowth of rat primary hippocampal neurons in vitro.MiR-182-5p is suggested as a potential therapeutic tool for the promotion of axonal regeneration in different pathologies/diseases of the central nervous system.
Z-RNA and the flipside of the SARS Nsp13 helicase
Authors: Herbert Alan , Poptsova Maria 
Published: March 2022

AbstractWe present evidence that the severe acute respiratory syndrome coronavirus (SARS) non-structural protein 13 (Nsp13) modulates the Z-RNA dependent regulated cell death pathways [1]. We show that Z-prone sequences (called flipons [2]) exist in coronavirus and provide a signature (Z-sig) that enables identification of the animal viruses from which the human pathogens arose. We also identify a potential RIP Homology Interaction Motif (RHIM) in the helicase Nsp13 that resembles those present in proteins that initiate Z-RNA-dependent cell death through interactions with the Z-RNA sensor protein ZBP1. These two observations allow us to suggest a model in which Nsp13 down regulates Z-RNA activated innate immunity by two distinct mechanisms. The first involves a novel ATP-independent Z-flipon helicase (flipase) activity in Nsp13 that differs from that of canonical A-RNA helicases. This flipase prevents formation of Z-RNAs that would otherwise activate cell death pathways. The second mechanism likely inhibits the interactions between ZBP1 and the Receptor Interacting Proteins Kinases RIPK1 and RIPK3 by targeting their RHIM domains. Together the described Nsp13 RHIM and flipase activities have the potential to alter the host response to coronaviruses and impact the design of drugs targeting the Nsp13 protein. The Z-sig and RHIM domains may provide a way of identifying previously uncharacterized viruses that are potentially pathogenic for humans.
Stress promotes RNA G-quadruplex folding in human cells
Authors: Kharel Prakash , Fay Marta , Manasova Ekaterina V. , Anderson Paul J. , Kurkin Aleksander V. , Guo Junjie U. , Ivanov Pavel 
Published: March 2022

AbstractGuanine-rich nucleic acids can fold into G-quadruplex (G4) structures. Although endogenous RNAs contain sequences that can fold into RNA G4s (rG4s) in vitro, their folding and functions in vivo are not well understood. We show that the folding of putative rG4s in human cells into bona fide rG4 structures is dynamically regulated by stress. By using a high-throughput approach based on differential reactivity of dimethyl sulfate (DMS) towards Gs within folded vs unfolded rG4s, we identified hundreds of endogenous rG4s whose folding is promoted by cellular stress and validated them using a newly developed rG4-specific ligand. Stress-dependent rG4s are enriched in mRNA 3′-untranslated regions, suggesting their role in regulating mRNA stability under stress. Lastly, rG4 folding is reversible upon stress removal or adaptation. Our study show that rG4s function as regulatory elements in regulating mRNA stability and cellular stress response.One-Sentence SummaryRNA G-quadruplexes assemble under stress in human cells