bluuebunny/crossref_metadata_2025_split huggingface dataset:
Salmonella enterica serovar Typhimurium from Wild Birds in the United States Represent Distinct Lineages Defined by Bird Type
Authors: Fu Yezhi , M’ikanatha Nkuchia M. , Whitehouse Chris A. , Li Shaoting , Deng Xiangyu , Smith Jared C. , Shariat Nikki W. , Nawrocki Erin M. , Dudley Edward G. 
Published: November 2021

ABSTRACTSalmonella enterica serovar Typhimurium is typically considered a host generalist, however certain strains are associated with specific hosts and show genetic features of host adaptation. Here, we sequenced 131 S. Typhimurium strains from wild birds collected in 30 U.S. states during 1978-2019. We found that isolates from broad taxonomic host groups including passerine birds, water birds (Aequornithes), and larids (gulls and terns) represented three distinct lineages and certain S. Typhimurium CRISPR types presented in individual lineages. We also showed that lineages formed by wild bird isolates differed from most strains originating from domestic animal sources, and genomes from these lineages substantially improved source attribution of Typhimurium genomes to wild birds by a machine learning classifier. Furthermore, virulence gene signatures that differentiated S. Typhimurium from passerines, water birds, and larids were detected. Passerine isolates tended to lack S. Typhimurium-specific virulence plasmids. Isolates from the passerine, water bird, and larid lineages had close genetic relatedness with human clinical isolates, including those from a 2021 U.S. outbreak linked to passerine birds. These observations indicate that S. Typhimurium from wild birds in the U.S. are likely host-adapted, and the representative genomic dataset examined in this study can improve source prediction and facilitate outbreak investigation.IMPORTANCEWithin-host evolution of S. Typhimurium may lead to pathovars adapted to specific hosts. Here, we report the emergence of disparate avian S. Typhimurium lineages with distinct virulence gene signatures. The findings highlight the importance of wild birds as a reservoir for S. Typhimurium and contribute to our understanding of the genetic diversity of S. Typhimurium from wild birds. Our study indicates that S. Typhimurium may have undergone adaptive evolution within wild birds in the U.S. The representative S. Typhimurium genomes from wild birds, together with the virulence gene signatures identified in these bird isolates, are valuable for S. Typhimurium source attribution and epidemiological surveillance.
The base-editing enzyme APOBEC3A catalyzes cytosine deamination in RNA with low proficiency and high selectivity
Authors: Barka Aleksia , Berríos Kiara N. , Bailer Peter , Schutsky Emily K. , Wang Tong , Kohli Rahul M. 
Published: November 2021

ABSTRACTHuman APOBEC3A (A3A) is a nucleic acid-modifying enzyme that belongs to the cytidine deaminase family. Canonically, A3A catalyzes the deamination of cytosine into uracil in single-stranded DNA, an activity that makes A3A both a critical antiviral defense factor and a useful tool for targeted genome editing. However, off-target mutagenesis by A3A has been readily detected in both cellular DNA and RNA, which has been shown to promote oncogenesis. Given the importance of substrate discrimination for the physiological, pathological, and biotechnological activities of A3A, here we explore the mechanistic basis for its preferential targeting of DNA over RNA. Using a chimeric substrate containing a target ribocytidine within an otherwise DNA backbone, we demonstrate that a single hydroxyl at the sugar of the target base acts as a major selectivity determinant for deamination. To assess the contribution of bases neighboring the target cytosine, we show that overall RNA deamination is greatly reduced relative to that of DNA, but can be observed when ideal features are present, such as preferred sequence context and secondary structure. A strong dependence on idealized substrate features can also be observed with a mutant of A3A (eA3A, N57G) which has been employed for genome editing due to altered selectivity for DNA over RNA. Altogether, our work reveals a relationship between the overall decreased reactivity of A3A and increased substrate selectivity, and our results hold implications both for characterizing off-target mutagenesis and for engineering optimized DNA deaminases for base-editing technologies.
Remote Deep Brain Stimulation by Transgene-free Magnetomechanical Approach
Authors: Su Chih-Lun , Yen Ping-Hsiang , Cheng Chao-Chun , Chiang Po-Han 
Published: November 2021

AbstractVarious physical stimulation methods are developed to minimize the invasiveness of deep brain stimulation (DBS)1–3. Among them, only magnetic field can penetrate into the biological tissues without scattering or absorption4, which makes it ideal for untethered DBS. Recently developed magnetogenetics have shown the potential of developing treatments for neurological disorders5. However, magnetogenetic approaches have potential side effects from overexpression of exogenous ion channels and gene delivery with viral vectors6,7. Here, we demonstrated that the iron oxide magnetic nanodiscs (~270 nm) can be used as transducers to trigger calcium responses in the wild-type cultured neurons during the application of slow varying weak magnetic fields (50 mT at 10 Hz). Moreover, we identified that the intrinsic mechanosensitive ion channel transient receptor potential canonical (TRPC), which were widely expressed in the brain8, plays the main roles in this magnetomechanical stimulation. Finally, when we applied magnetic fields to the awake mice with magnetic nanodiscs injecting into subthalamic nucleus, the magnetomechanical stimulation triggered neuronal activities in the targeted region and the downstream region. Overall, this research demonstrated a magnetomechanical approach that can be used for wireless neuronal stimulation in vitro and untethered DBS in awake mice in vivo without implants or genetic manipulation.
Therapeutic downregulation of neuronal PAS domain 2 (Npas2) promotes surgical skin wound healing
Authors: Shibuya Yoichiro , Hokugo Akishige , Okawa Hiroko , Kondo Takeru , Khalil Daniel , Wang Lixin , Roca Yvonne , Clements Adam , Sasaki Hodaka , Berry Ella , Nishimura Ichiro , Jarrahy Reza 
Published: December 2021

AbstractAttempts to minimize scarring remain among the most difficult challenges facing surgeons, despite the use of optimal wound closure techniques. Previously, we reported improved healing of dermal excisional wounds in circadian clock neuronal PAS domain 2 (Npas2)-null mice. In this study, we performed high-throughput drug screening to identify a compound that downregulates Npas2 activity. The hit compound (Dwn1) suppressed circadian Npas2 expression, increased murine dermal fibroblast cell migration, and decreased collagen synthesis in vitro. Based on the in vitro results, Dwn1 was topically applied to iatrogenic full-thickness dorsal cutaneous wounds in a murine model. The Dwn1-treated dermal wounds healed faster with favorable mechanical strength and developed less granulation tissue than the controls. The expression of type I collagen, Tgfβ1, and α-smooth muscle actin was significantly decreased in Dwn1-treated wounds, suggesting that hypertrophic scarring and myofibroblast differentiation are attenuated by Dwn1 treatment. NPAS2 may represent an important target for therapeutic approaches to optimal surgical wound management.
Using a Champion-Oriented Mindset to Overcome the Challenges of Graduate School
Authors: Marshall Andrea G. , Palavicino-Maggio Caroline B. , Neikirk Kit , Vue Zer , Beasley Heather , Garza-Lopez Edgar , Murray Sandra , Martinez Denise , Davis Jamaine , Shuler Haysetta , Spencer Elsie C. , Morton Derrick , Hinton Antentor 
Published: December 2021

AbstractDespite efforts to increase diversity, a glaring underrepresentation of minorities (URM) persists in the fields of science, technology, engineering, and mathematics (STEM). Graduate school can be a stressful step in the STEM pipeline, especially for students previously unaware of the structure and challenges of post-graduate education. To promote successful minority participation in STEM and prepare prospective students for the impending challenges of graduate school, we developed a workshop based on the mentoring and fostering of a champion-oriented mindset entitled, “The Trials and Tribulations of Graduate School: How Do You Make an Impact?”. We administered the workshop to a cohort of university undergraduates and conducted pre- and post-workshop surveys to measure students’ perceived need for instruction on specific workshop topics. The results suggest that the workshop was well received by the students and provided information that they considered helpful to help navigate the graduate school process.
Mapping nationally and globally at-risk species to identify hotspots for (and gaps in) conservation
Authors: Hardouin Marie E , Hargreaves Anna L 
Published: December 2021

ABSTRACTProtecting habitat of species-at-risk is critical to their recovery, but can be contentious. For example, protecting species that are locally imperilled but globally common (e.g. species that only occur in a jurisdiction at the edge of their geographic range) is often thought to distract from protecting globally-imperilled species. However, such perceived trade-offs are based on the assumption that threatened groups have little spatial overlap, which is rarely quantified. Here, we compile range maps of terrestrial species-at-risk in Canada to assess the geographic overlap of nationally and globally at-risk species with each other, among taxonomic groups, and with protected areas. While many nationally-at-risk taxa only occurred in Canada at their northern range edge (median=4% of range in Canada), nationally-at-risk species were not significantly more peripheral in Canada than globally-at-risk species. Further, 56% of hotspots of nationally-at-risk taxa were also hotspots of globally-at-risk taxa in Canada, undercutting the perceived trade-off in their protection. Hotspots of nationally-at-risk taxa also strongly overlapped with hotspots of individual taxonomic groups, though less so for mammals. While strong spatial overlap across threat levels and taxa should facilitate efficient habitat protection, <7% of the area in Canada’s at-risk hotspots is protected, and more than 70% of nationally and globally-at-risk species in Canada have <10% of their Canadian range protected. Our results counter the perception that protecting nationally vs. globally at-risk species are at odds, and identify critical areas to target as Canada strives to increase its protected areas and promote species-at-risk recovery.
Oxytocin signaling in the posterior hypothalamus prevents hyperphagic obesity in mice
Authors: Inada Kengo , Tsujimoto Kazuko , Yoshida Masahide , Nishimori Katsuhiko , Miyamichi Kazunari 
Published: December 2021

SummaryDecades of studies have revealed molecular and neural circuit bases for body weight homeostasis. Neural hormone oxytocin (OT) has received attention in this context because it is produced by neurons in the paraventricular hypothalamic nucleus (PVH), a known output center of hypothalamic regulation of appetite. OT has an anorexigenic effect, as shown in human studies, and can mediate satiety signals in rodents. However, the function of OT signaling in the physiological regulation of appetite has remained in question, because whole-body knockout (KO) ofOTorOT receptor (OTR)has little effect on food intake. We herein show that acute conditional KO (cKO) of OT selectively in the adult PVH, but not in the supraoptic nucleus, markedly increases body weight and food intake, with an elevated level of plasma triglyceride and leptin. Intraperitoneal administration of OT rescues the hyperphagic phenotype of the PVH OT cKO model. Furthermore, we show that cKO of OTR selectively in the posterior hypothalamic regions, especially the arcuate hypothalamic nucleus, a primary center for appetite regulations, phenocopies hyperphagic obesity. Collectively, these data reveal that OT signaling in the arcuate nucleus suppresses excessive food intake.
Micronized curcumin causes hyperlocomotion in zebrafish larvae
Authors: Sachett Adrieli , Benvenutti Radharani , Reis Carlos G. , Gallas-Lopes Matheus , Bastos Leonardo M. , Aguiar Gean Pablo S. , Herrmann Ana P. , Oliveira J. Vladimir , Siebel Anna M. , Piato Angelo 
Published: December 2021

ABSTRACTZebrafish larvae have been widely used in neuroscience and drug research and development. In the larval stage, zebrafish present a broad behavioral repertoire and physiological responses similar to adults. Curcumin (CUR), a major component of Curcuma longa L. (Zingiberaceae), has demonstrated the ability to modulate several neurobiological processes relevant to mental disorders in animal models. However, the low bioavailability of this compound can compromise its in vivo biological potential. Interestingly, it has been shown that micronization can increase the biological effects of several compounds. Thus, in this study, we compared the effects of acute exposure for 30 minutes to the following solutions: water (control), 0.1% DMSO (vehicle), 1 μM CUR, or 1 μM micronized curcumin (MC) in zebrafish larvae 7 days post-fertilization (dpf). We analyzed locomotor activity (open tank test), anxiety (light/dark test), and avoidance behavior (aversive stimulus test). Moreover, we evaluated parameters of oxidative status (thiobarbituric acid reactive substances and non-protein thiols levels). MC increased the total distance traveled and absolute turn angle in the open tank test. There were no significant differences in the other behavioral or neurochemical outcomes. The increase in locomotion induced by MC may be associated with a stimulant effect on the central nervous system, which was evidenced by the micronization process.
Neuropeptide signalling shapes feeding and reproductive behaviours in male C. elegans
Authors: Gadenne Matthew J. , Hardege Iris , Suleski Djordji , Jaggers Paris , Beets Isabel , Schafer William R , Chew Yee Lian 
Published: December 2021

AbstractSexual dimorphism occurs where different sexes of the same species display differences in characteristics not limited to reproduction. For the nematode Caenorhabditis elegans, in which the complete neuroanatomy has been solved for both hermaphrodites and males, sexually dimorphic features have been observed both in terms of the number of neurons and in synaptic connectivity. In addition, male behaviours, such as food-leaving to prioritise searching for mates, have been attributed to neuropeptides released from sex-shared or sex-specific neurons.In this study, we show that the lury-1 neuropeptide gene shows a sexually dimorphic expression pattern; being expressed in pharyngeal neurons in both sexes but displaying additional expression in tail neurons only in the male. We also show that lury-1 mutant animals show sex differences in feeding behaviours, with pharyngeal pumping elevated in hermaphrodites but reduced in males. LURY-1 also modulates male mating efficiency, influencing motor events during contact with a hermaphrodite. Our findings indicate sex-specific roles of this peptide in feeding and reproduction in C. elegans, providing further insight into neuromodulatory control of sexually dimorphic behaviours.
TOPOVIBL-REC114 interaction regulates meiotic DNA double-strand breaks
Authors: Nore Alexandre , Juarez-Martinez Ariadna B , Clément Julie , Brun Christine , Diagouraga Boubou , Grey Corinne , Bourbon Henri Marc , Kadlec Jan , Robert Thomas , de Massy Bernard 
Published: December 2021

AbstractMeiosis requires the formation of programmed DNA double strand breaks (DSBs), essential for fertility and for generating genetic diversity. DSBs are induced by the catalytic activity of the TOPOVIL complex formed by SPO11 and TOPOVIBL. To ensure genomic integrity, DNA cleavage activity is tightly regulated, and several accessory factors (REC114, MEI4, IHO1, and MEI1) are needed for DSB formation in mice. How and when these proteins act is not understood. Here, we show that REC114 is a direct partner of TOPOVIBL, and identified their conserved interacting domains by structural analysis. We then analysed the role of this interaction by monitoring meiotic DSBs in female and male mice carrying point mutations in TOPOVIBL that decrease or disrupt its binding to REC114. In these mutants, DSB activity was strongly reduced genome-wide in oocytes, and only in sub-telomeric regions in spermatocytes. In addition, in mutant spermatocytes, DSB activity was delayed in autosomes. These results provide evidence that REC114 is a key member of the TOPOVIL catalytic complex, and that the REC114/TOPOVIBL interaction ensures the efficiency and timing of DSB activity.
Modelling the effect of ephaptic coupling on spike propagation in peripheral nerve fibres
Authors: Schmidt Helmut , Knösche Thomas R. 
Published: December 2021

AbstractExperimental and theoretical studies have shown that ephaptic coupling leads to the synchronisation and slowing down of spikes propagating along the axons within peripheral nerve bundles. However, the main focus thus far has been on a small number of identical axons, whereas realistic peripheral nerve bundles contain numerous axons with different diameters. Here, we present a computationally efficient spike propagation model, which captures the essential features of propagating spikes and their ephaptic interaction, and facilitates the theoretical investigation of spike volleys in large, heterogeneous fibre bundles. The spike propagation model describes an action potential, or spike, by its position on the axon, and its velocity. The velocity is primarily defined by intrinsic features of the axons, such as diameter and myelination status, but it is also modulated by changes in the extracellular potential. These changes are due to transmembrane currents that occur during the generation of action potentials. The resulting change in the velocity is appropriately described by a linearised coupling function, which is calibrated with a biophysical model. We first lay out the theoretical basis to describe how the spike in an active axon changes the membrane potential of a passive axon. These insights are then incorporated into the spike propagation model, which is calibrated with a biophysically realistic model based on Hodgkin-Huxley dynamics. The fully calibrated model is then applied to fibre bundles with a large number of axons and different types of axon diameter distributions. One key insight of this study is that the heterogeneity of the axonal diameters has a dispersive effect, and that with increasing level of heterogeneity the ephaptic coupling strength has to increase to achieve full synchronisation between spikes. Another result of this study is that in the absence of full synchronisation, a subset of spikes on axons with similar diameter can form synchronised clusters. These findings may help interpret the results of noninvasive experiments on the electrophysiology of peripheral nerves.
An atlas of the developing Tribolium castaneum brain reveals conserved anatomy and divergent timing to Drosophila melanogaster
Authors: Farnworth Max S. , Bucher Gregor , Hartenstein Volker 
Published: December 2021

AbstractInsect brains are formed by conserved sets of neural lineages whose fibres form cohesive bundles with characteristic projection patterns. Within the brain neuropil these bundles establish a system of fascicles constituting the macrocircuitry of the brain. The overall architecture of the neuropils and the macrocircuitry appear to be conserved. However, variation is observed e.g., in size and shape and timing of development. Unfortunately, the developmental and genetic basis of this variation is poorly understood although the rise of new genetically tractable model organisms such as the red flour beetle Tribolium castaneum allows the possibility to gain mechanistic insights. To facilitate such work, we present an atlas of the developing brain of T. castaneum, covering the first larval instar, the prepupal stage and the adult, by combining wholemount immunohistochemical labelling of fibre bundles (acetylated tubulin) and neuropils (synapsin) with digital 3D reconstruction using the TrakEM2 software package. Upon comparing this anatomical dataset with the published work in D. melanogaster, we confirm an overall high degree of conservation. Fibre tracts and neuropil fascicles, which can be visualized by global neuronal antibodies like anti-acetylated tubulin in all invertebrate brains, create a rich anatomical framework to which individual neurons or other regions of interest can be referred to. The framework of a largely conserved pattern allowed us to describe differences between the two species with respect to parameters such as timing of neuron proliferation and maturation. These features likely reflect adaptive changes in developmental timing that govern the change from larval to adult brain.
Strategic behavior of nontraditional lenders in agricultural credit markets
Authors: Tetteh Iuliia , Boehlje Michael , Giri Anil K. , Sharma Sankalp 
Published: December 2021

PurposeThis paper examines credit products, operational performance and business models employed by nontraditional lenders (NTLs) in agricultural credit markets.Design/methodology/approachTwo research methods were employed in this study: (1) an executive interview to collect primary data and (2) a case study approach to analyze the findings and develop insights.FindingsThe findings indicate the presence of significant differences among lenders across and within three categories of NTLs (large volume, vendor financing and collateral-based NTLs). For example, collateral-based NTLs employ different strategies focusing on types of loans, funding sources, commodities they support and geographic coverage to further segment the market. NTLs in this study were able to capture market by successfully identifying gaps in the supply side of agricultural credit and developing products that meet the needs of that niche (e.g. heavy renters, large operations, producers seeking fixed interest rates for term loans, financially fragile producers). Most of the interviewed NTLs had credit standards comparable to those of traditional lenders and consider them both competitors and partners since many NTLs partner with traditional lenders on participation loans, loan servicing and/or sourcing funds.Originality/valueThe supply side of a nontraditional lending has not been studied extensively due to the proprietary nature of data. The executive interviews conducted in this study allowed for accumulation of industry data, which is not available otherwise.