bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global conservation prioritization approach provides credible results at a regional scale
Authors: Roswell Michael , Espíndola Anahí 
Published: September 2023

AbstractAimConservationists and managers must direct resources and enact measures to protect species, despite uncertainty about their present status. One approach to covering the data gap is borrowing information from data-rich species or populations to guide decisions about data-poor ones, via machine learning. Recent efforts demonstrated proof-of-concept at the global scale, leaving unclear whether similar approaches are feasible at the local and regional scales at which conservation actions most typically occur. To address this gap, we tested a global-scale predictive approach at a regional scale, using two groups of taxa.LocationState of Maryland, USA.TaxaVascular land plants and lepidopterans.MethodsUsing publicly available occurrence and biogeographic data, we trained random forest classifiers to predict the State-level conservation status of species in each of the two focal taxa. We assessed model performance with cross-validation, and explored trends in the predictions.ResultsOur models had strong discriminatory ability, accurately predicting status for species with existing status assessments. They predict that the northwestern part of Maryland, USA, which overlaps the Appalachian Mountains, harbors a higher concentration of unassessed, but likely threatened plants and lepidopterans. Our predictions track known biogeographic patterns, and unassessed species predicted as most likely threatened in Maryland were often recognized as also needing conservation in nearby jurisdictions, providing external validation to our results.Main ConclusionsWe demonstrate that a modelling approach developed for global analysis can be downscaled and credible when applied at a regional scale that is smaller than typical species ranges. We identified select unassessed plant and lepidopteran species, and the western, montane region of Maryland as priority targets for additional monitoring, assessment, and conservation. By rapidly aggregating disparate data and integrating information across taxa, models like those we used can complement traditional assessment tools and assist in prioritization for formal assessments, as well as protection.
Consideration of a Liquid mutation-accumulation Experiment to Measure Mutation Rates by Successive Serial Dilution
Authors: Baehr Stephan , Ho Wei-Chin , Perez Sam , Cenzano Alyssa , Hancock Katelyn , Patrick Lea , Brown Adalyn , Miller Sam , Lynch Michael 
Published: September 2023

AbstractThe mutation-accumulation (MA) experiment is a fixture of evolutionary biology, though it is laborious to perform. MA experiments typically take between months and years to acquire sufficient mutations to measure DNA mutation rates and mutation spectra. MA experiments for many organisms rely on colony formation on agar plates and repetitive streaking, an environment which at first glance appears somewhat contrived, a poor imitation of real environmental living conditions. We propose that a fully liquid-phase mutation-accumulation experiment may at times more accurately reflect the environment of an organism. We note also that whereas automation of streaking plates is a daunting prospect, automation of liquid handling and serial dilution is already commonplace. In principle, this type of MA experiment can be automated so as to reduce the human capital requirements of measuring mutation rates. We demonstrate that a liquid MA recapitulates the mutation rate estimated for MMR-E. coliin liquid LB culture vs. plate LB culture. We detect a modified mutation spectrum with a transition skew of 4:1 of A:T→G:C vs G:C→A:T mutations, highlighting the potential role of tautomerization as a DNA mutation mechanism. We also find that using a plate reader to measure OD600 as a proxy for cell growth to be incapable of measuring carrying capacity for MA lines burdened with many mutations.
Time-lapse mesoscopy ofCandida albicansandStaphylococcus aureusdual-species biofilms reveals a structural role for the hyphae ofC. albicansin biofilm formation
Authors: Baxter Katherine J. , Sargison Fiona A. , Fitzgerald J. Ross , McConnell Gail , Hoskisson Paul A. 
Published: September 2023

AbstractPolymicrobial infection withCandida albicansandStaphylococcus aureusmay result in a concomitant increase in virulence and resistance to antimicrobial drugs. This enhanced pathogenicity phenotype is mediated by numerous factors including metabolic processes and direct interaction ofS. aureuswithC. albicanshyphae. The overall structure of biofilms is known to contribute to their recalcitrance to treatment, however the dynamics of direct interaction between species and how it contributes to pathogenicity is poorly understood. To address this, a novel time-lapse mesoscopic optical imaging method was developed to enable the formation ofC. albicans/S. aureuswhole dual-species biofilms to be followed. It was found that yeast-form or hyphal-formC. albicansin the biofilm founder-population profoundly affects the structure of the biofilm as it matures. Different sub-populations ofC. albicansandS. aureusarise within each biofilm as a result of the differentC. albicansmorphotypes, resulting in distinct sub-regions. These data reveal thatC. albicanscell morphology is pivotal in the development of global biofilm architecture and the emergence of colony macrostructures and may temporally influence synergy in infection.
Space wandering in the rodent default mode network
Authors: Nghiem Trang-Anh Estelle , Lee Byeongwook , Chao Tzu-Hao Harry , Branigan Nicholas K. , Mistry Percy K. , Shih Yen-Yu Ian , Menon Vinod 
Published: September 2023

AbstractThe default mode network (DMN) is a large-scale brain network known to be suppressed during a wide range of cognitive tasks. However, our comprehension of its role in naturalistic and unconstrained behaviors has remained elusive because most research on the DMN has been conducted within the restrictive confines of MRI scanners. Here we use multisite GCaMP fiber photometry with simultaneous videography to probe DMN function in awake, freely exploring rats. We examined neural dynamics in three core DMN nodes— the retrosplenial cortex, cingulate cortex, and prelimbic cortex— as well as the anterior insula node of the salience network, and their association with the rats’ spatial exploration behaviors. We found that DMN nodes displayed a hierarchical functional organization during spatial exploration, characterized by stronger coupling with each other than with the anterior insula. Crucially, these DMN nodes encoded the kinematics of spatial exploration, including linear and angular velocity. Additionally, we identified latent brain states that encoded distinct patterns of time-varying exploration behaviors and discovered that higher linear velocity was associated with enhanced DMN activity, heightened synchronization among DMN nodes, and increased anticorrelation between the DMN and anterior insula. Our findings highlight the involvement of the DMN in collectively and dynamically encoding spatial exploration in a real-world setting. Our findings challenge the notion that the DMN is primarily a “ task-negative” network disengaged from the external world. By illuminating the DMN’s role in naturalistic behaviors, our study underscores the importance of investigating brain network function in ecologically valid contexts.Significance statementOur research advances understanding of the default mode network (DMN), a brain network implicated in numerous neuropsychiatric and neurological disorders. In contrast to previous research examining immobilized subjects, we took the novel approach of investigating DMN function during naturalistic behaviors in freely moving rodents. Using a combination of multisite fiber photometry, video tracking, and computational modeling, we discovered a prominent role for the DMN in naturalistic real-world spatial exploration. Our findings challenge conventional views that the DMN is disengaged from interactions with the external world and underscore the importance of probing brain function in ecologically relevant settings. This work enriches our understanding of brain function and has important implications for pre-clinical investigations of disorders involving DMN dysfunction.
Characterization of low copy number human angiotensin-converting enzyme 2 (hACE2)-transgenic mice as an improved model of SARS-CoV-2 infection
Authors: Bradshaw Christine M. , Georgieva Teodora , Tankersley Trevor N. , Taylor-Doyle Tama , Johnson Larry , Uhrlaub Jennifer L. , Besselsen David , Nikolich Janko Ž. 
Published: September 2023

ABSTRACTCoronaviridae are significant human pathogens, as evidenced by several outbreaks of severe respiratory infections in the past 20 years and culminating with the COVID-19 pandemic. Mouse models of COVID-19 have included transgenic expression of the main SARS coronavirus entry receptor on human cells, human angiotensin-converting enzyme 2 (hACE2). However, the original hACE2-Tg mouse strain overexpresses many copies of the transgene, leading to neuropathology not representative of human infection. Aiming to improve physiological relevance, we generated two new lines of hACE2-Tg mice using the original transgene construct expressing hACE2 under the control of the keratin 18 promoter (K18-hACE2).We show that relative to the original strain, which expressed 8 copies of the transgene (8-hACE2-Tg), lines 1 and 2 expressed 1 and 2 copies of the transgene (1-hACE-2-Tg and 2-hACE-2-Tg, respectively). Upon intranasal (i.n.) infection with 103plaque-forming units (pfu) SARS-CoV-2 WA-1/US, 8-hACE2-Tg mice succumbed to infection by d. 7. 2-hACE2-Tg mice exhibited 31% survival, with less viral replication in the lung and brain when compared to 8-hACE2-Tg mice. Furthermore, SARS-CoV-2 infection in 1-hACE2-Tg mice exhibited no mortality and had no detectable virus in the brain, although they did show clear virus replication in the lung. All three mouse strains analyzed showed SARS-CoV-2-related weight loss that tracked with the mortality rates. 1-hACE2-Tg mice mounted detectable primary and memory T effector cell and antibody responses. We conclude that these strains, particularly 1-hACE2-Tg mice, provide improved models to study hACE2-mediated viral infections.
Alternating Magnetic Fields Drive Stimulation of Gene Expression via Generation of Reactive Oxygen Species
Authors: Mundell Jordan W. , Brier Matthew I. , Orloff Everest , Stanley Sarah A. , Dordick Jonathan S. 
Published: September 2023

SummaryMagnetogenetics represents a method for remote control of cellular function. Despite successful use of magnetic fields to control gene expressionin vitroandin vivo, the mechanism underlying magnetogenetics is largely unknown, thereby hindering further development and applications. Previous work suggests a chemical-based mechanism involving the generation of reactive oxygen species (ROS) as a platform initiator and downstream signaling molecule. Herein, a chemical biology approach was used to elucidate further the mechanism of radio frequency-alternating magnetic field (RF-AMF) stimulation of a TRPV1-ferritin magnetogenetics platform that leads to Ca2+gating. RF-AMF stimulation of HEK 293T cells expressing TRPV1-Ferritin resulted in a ∼30% and ∼140% increase in intra- and extracellular ROS levels, respectively. Mutations to specific cysteine residues in TRPV1 responsible for ROS sensitivity eliminated RF-AMF driven Ca2+-dependent transcription of secreted embryonic alkaline phosphatase (SEAP). Using a non-tethered (to TRPV1) ferritin also eliminated RF-AMF driven SEAP production. These results suggest ferritin-dependent ROS activation of TRPV1 plays a key role in the initiation of magnetogenetics. Furthermore, inhibition of IP3R-based endoplasmic reticulum (ER) Ca2+release with Xestospongin C, inhibition of protein kinase C (PKC) activity with Gö 6983, or inhibition of NADPH oxidase (NOX) isoforms 1/2 gp91phoxcytochrome with GSK 2795039 eliminated short-term RF-AMF potentiation of SEAP production with capsaicin. Similarly, Gö 6983 significantly reduced long-term RF-AMF capsaicin potentiation of SEAP production. These results suggest that ROS-activated TRPV1 signaling to increase intracellular Ca2+includes pathways involving PKC, NOX, and the ER. Together, these findings fill in current knowledge gaps in the mechanism of magnetogenetics, which may lead to translational applications in medicine and biotechnology.
Immunogenicity and efficacy of a subcutaneously administered, adjuvanted vaccine containing modified S1 spike protein of SARS-CoV-2 variant C.1.2
Authors: Bowe Michael , Wright Emily , Pushko Peter , Backstedt Brian , Gardner Casey , Short-Freeman Micah , Kar Swagata , Wright David Craig 
Published: September 2023

AbstractDuring the COVID-19 pandemic, vaccines have produced protective immunity sufficient enough to cause a decrease in hospitalizations and deaths; however, the pandemic continues due to mutational events, predominantly occurring in the S1 sequence of the spike protein of SARS-CoV-2. We have developed a baculovirus-expressed, modified S1 SARS-CoV-2 protein based on the C.1.2 variant, which was first identified in South Africa.1This was encapsulated in a vitamin E containing, nonphospholipid liposome, which was then used to subcutaneously immunize Syrian hamsters. This vaccine, when administered at day 1 generates IgG responses that react to the modified C.1.2 S1 protein; full-length spike proteins from Wuhan-Hu-1, Delta, Omicron BA.1; and the Omicron recombinant variant XBB.1.5 in 100% of the animals. The second dose administered subcutaneously on day 28 demonstrated anamnestic response in the quantitative IgG assay to the Wuhan-Hu-1 spike Receptor Binding Domain (RBD). In addition, antibody IgA and IgM responses in sera were demonstrated. Serum IgG antibody responses to the spike proteins of the modified C.1.2 S1 and full-length spike proteins Wuhan-Hu-1, Delta, Omicron BA.1, and Omicron recombinant XBB.1.5 variants are elevated for over 120 days. Challenge of vaccinated and unvaccinated hamsters at day 126 of the study with an Omicron BA.1 resulted in a difference in weight change and viral load based on the qRT-PCR assay seven days after challenge.
Soil Prokaryotic and Fungal Biome Structures Associated with Crop Disease Status across the Japan Archipelago
Authors: Fujita Hiroaki , Yoshida Shigenobu , Suzuki Kenta , Toju Hirokazu 
Published: September 2023

ABSTRACTArchaea, bacteria, and fungi in the soil are increasingly recognized as determinants of agricultural productivity and sustainability. A crucial step for exploring soil microbiomes with high ecosystem functions is to perform statistical analyses on potential relationship between microbiome structure and functions based on comparisons of hundreds or thousands of environmental samples collected across broad geographic ranges. In this study, we integrated agricultural field metadata with microbial community analyses by targeting > 2,000 soil samples collected along a latitudinal gradient from cool-temperate to subtropical regions in Japan (26.1– 42.8 °N). The data involving 632 archaeal, 26,868 bacterial, and 4,889 fungal operational taxonomic units detected across the fields of 19 crop plant species allowed us to conduct statistical analyses (permutational analyses of variance, generalized linear mixed models, and randomization analyses) on relationship among edaphic factors, microbiome compositions, and crop disease prevalence. We then examined whether the diverse microbes form species sets varying in potential ecological impacts on crop plants. A network analysis suggested that the observed prokaryotes and fungi were actually classified into several species sets (network modules), which differed substantially in associations with crop disease prevalence. Within the network of microbe-to-microbe coexistence, ecologically diverse microbes, such as an ammonium-oxidizing archaeum, an antibiotics-producing bacterium, and a potentially mycoparasitic fungus, were inferred to play key roles in shifts between crop-disease-promotive and crop-disease-suppressive states of soil microbiomes. The bird’s-eye view of soil microbiome structure will provide a basis for designing and managing agroecosystems with high disease-suppressive functions.IMPORTANCEUnderstanding how microbiome structure and functions are organized in soil ecosystems is one of the major challenges in both basic ecology and applied microbiology. Given the ongoing worldwide degradation of agroecosystems, building frameworks for exploring structural diversity and functional profiles of soil microbiomes is an essential task. Our study provides an overview of cropland microbiome states in light of potential crop-disease-suppressive functions. The large dataset allowed us to explore highly functional species sets that may be stably managed in agroecosystems. Furthermore, an analysis of network architecture highlighted species that are potentially used to cause shifts from disease-prevalent states of agroecosystems to disease-suppressive states. By extending the approach of comparative analyses towards broader geographic ranges and diverse agricultural practices, agroecosystem with maximized biological functions will be further explored.
Protein Kinase Structure and Dynamics: Role of the αC-β4 Loop
Authors: Wu Jian , Jonniya Nisha A. , Hirakis Sophia P. , Olivieri Cristina , Veglia Gianluigi , Kornev Alexandr P. , Taylor Susan S. 
Published: September 2023

AbstractAlthough the αC-β4 loop is a stable feature of all protein kinases, the importance of this motif as a conserved element of secondary structure, as well as its links to the hydrophobic architecture of the kinase core, has been underappreciated. We first review the motif and then describe how it is linked to the hydrophobic spine architecture of the kinase core, which we first discovered using a computational tool, Local Spatial Pattern (LSP) alignment. Based on NMR predictions that a mutation in this motif abolishes the synergistic high-affinity binding of ATP and a pseudo substrate inhibitor, we used LSP to interrogate the F100A mutant. This comparison highlights the importance of the αC-β4 loop and key residues at the interface between the N- and C-lobes. In addition, we delved more deeply into the structure of the apo C-subunit, which lacks ATP. While apo C-subunit showed no significant changes in backbone dynamics of the αC-β4 loop, we found significant differences in the side chain dynamics of K105. The LSP analysis suggests disruption of communication between the N- and C-lobes in the F100A mutant, which would be consistent with the structural changes predicted by the NMR spectroscopy.
Expression of mRNAs Encoding Hypothalamic Small Proteins, Neurosecretory Protein GL and Neurosecretory Protein GM, in the Japanese Quail,Coturnix japonica
Authors: Kato Masaki , Iwakoshi-Ukena Eiko , Narimatsu Yuki , Furumitsu Megumi , Ukena Kazuyoshi 
Published: September 2023

ABSTRACTNeurosecretory protein GL (NPGL) and neurosecretory protein GM (NPGM) are novel neuropeptides that have been discovered in the hypothalamic infundibulum of chickens. NPGL and NPGM play important roles in lipid metabolism in juvenile chickens. The physiological functions of NPGL and NPGM in sexually mature birds remain unknown. The Japanese quail (Coturnix japonica) seems to be an appropriate model for analyzing NPGL and NPGM during sexual maturity. However, studies on NPGL or NPGM have yet to be reported in the Japanese quail. In the present study, we identified cDNAs encoding precursor proteins of NPGL and NPGM in the quail hypothalamus. In situ hybridization revealed thatNPGLmRNA-expressing cells in the hypothalamus were localized in the infundibular nucleus and median eminence, andNPGMmRNA-expressing cells were only found in the mammillary nucleus. Immunohistochemistry revealed that NPGM-like immunoreactive cells were distributed in the mammillary nucleus, whereas NPGL-like immunoreactive cells were not detected in the hypothalamus. Real-time PCR analysis indicated that the expression ofNPGLmRNA was higher in the hypothalamus of females than in males, andNPGMmRNA expression showed no sex differences.NPGLandNPGMmRNA expression in males was upregulated after 24 h of food deprivation. In females, onlyNPGMmRNA expression was increased by fasting. These results suggest that the physiological functions of NPGL and NPGM are different in quail, and these factors are involved in sex differences in energy metabolism.
Community ecology of phages on a clonal bacterial host
Authors: Pyenson Nora C. , Leeks Asher , Nweke Odera , Goldford Joshua E. , Turner Paul E. , Foster Kevin R. , Sanchez Alvaro 
Published: September 2023

AbstractBacteriophages are the most abundant and diverse biological entities on Earth, yet the ecological mechanisms that sustain this extraordinary diversity remain unclear. Here, we have discovered a general mechanism that allows phage diversity to outstrip the diversity of their bacterial hosts. We assembled and passaged dozens of diverse phage communities on a single, non-coevolving strain ofEscherichia coliuntil the phage communities reached equilibrium. In all cases, we found multiple phage species coexisted stably, despite competition for a single, clonal host population. Coexistence within these communities was supported through host phenotypic heterogeneity, whereby phages specialized on cells adopting different growth phenotypes. Our experiments reveal a rich community ecology of bacteriophages where multiple phage species coexist and interact at the scale of a single bacterial host.One-Sentence SummaryDiverse communities of phages emerge stably and consistently on a clonal bacterial host, enabled by phenotypic heterogeneity.
AIRR-C Human IG Reference Sets: curated sets of immunoglobulin heavy and light chain germline genes
Authors: Collins Andrew M. , Ohlin Mats , Corcoran Martin , Heather James M. , Ralph Duncan , Law Mansun , Martínez-Barnetche Jesus , Ye Jian , Richardson Eve , Gibson William S. , Rodriguez Oscar L. , Peres Ayelet , Yaari Gur , Watson Corey T. , Lees William D. 
Published: September 2023

AbstractAnalysis of an individual’s immunoglobulin (IG) gene repertoire requires the use of high-quality germline gene Reference Sets. The Adaptive Immune Receptor Repertoire-Community (AIRR-C) Reference Sets have been developed to include only human IG heavy and light chain alleles that have been confirmed by evidence from multiple high-quality sources. By including only those alleles with a high level of support, including some new sequences that currently lack official names, AIRR-seq analysis will have greater accuracy and studies of the evolution of immunoglobulin genes, their allelic variants and the expressed immune repertoire will be facilitated. Although containing less than half the previously recognised IG alleles (e.g. just 198 IGHV sequences), the Reference Sets eliminated erroneous calls and provided excellent coverage when tested on a set of repertoires from 99 individuals comprising over 4 million V(D)J rearrangements. To improve AIRR-seq analysis, some alleles have been extended to deal with short 3’ or 5’ truncations that can lead them to be overlooked by alignment utilities. To avoid other challenges for analysis programs, exact paralogs (e.g. IGHV1-69*01 and IGHV1-69D*01) are only represented once in each set, though alternative sequence names are noted in accompanying metadata. The Reference Sets also include novel alleles: 8 IGHV alleles, 2 IGKV alleles and 5 IGLV alleles. The version-tracked AIRR-C Reference Sets are freely available at the OGRDB website (https://ogrdb.airr-community.org/germline_sets/Human) and will be regularly updated to include newly-observed and previously-reported sequences that can be confirmed by new high-quality data.