bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of a novel papillomavirus from a New Zealand fur seal (Arctocephalus forsteri) with oral papilloma-like lesions
Authors: Mifsud Jonathon C.O. , Hall Jane , Van Brussel Kate , Rose Karrie , Parry Rhys H. , Holmes Edward C. , Harvey Erin 
Published: November 2023

AbstractDespite being the predominant seal species in the Australian-New Zealand region and serving as a key indicator of marine environmental health, little is known about infectious diseases in New Zealand fur seals (Long-nosed fur seal;Arctocephalus forsteri). Several papillomaviruses have been identified in earless seals and sea lions, with the latter linked to cutaneous plaques and invasive squamous cell carcinoma. To date, no papillomaviruses have been reported in fur seals. We used traditional veterinary diagnostic techniques and metatranscriptomic sequencing of tissue samples to investigate the virome of New Zealand fur seals. We identified a novel papillomavirus, provisionally termed Arctocephalus forsteri papillomavirus 1 (AfPV1) in an animal with clinically and histologically identified oral papilloma-like lesions. RT-PCR confirmed the presence of AfPV1 only in oral papilloma samples from the affected individual. Phylogenetic analysis of the complete 7,926 bp genome of AfPV1 revealed that it clustered with taupapillomaviruses found in related Carnivora species. In addition, we identified the partial genome of a novel Gammaherpesvirus, Arctocephalus forsteri gammaherpesvirus 1 (AfGHV1), in a different individual without pathological evidence of viral infection. These findings highlight the need for further research into the disease associations and impact of undiagnosed and novel viruses on New Zealand fur seals.
“Comparative Analysis of Ovarian Transcriptome Changes Across Gestational Stages in Kari Sheep”
Authors: Ali Haidar , Ahmad Sohail 
Published: November 2023

ABSTRACTThis study aimed to investigate the genetic determinants of gestation length in Kari sheep, employing RNA-Seq technology. Employing a comprehensive whole transcriptome analysis, we sought to pinpoint differentially expressed genes (DEGs) while also delving into gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway assessments. The analysis revealed the identification of a total of 19,546 genes expressed in ovary. While comparing the transcriptomes of Kari sheep with Balkhi, yielding 976 DEGs (p < 0.05, Log2fc>1, <-1). Notably, among these DEGs, an upregulation of genes was observed associated with Ubiquitin-protein transferase activity, such asCNOT4, RC3H1, andXIAP. Concurrently, DEGs likeNFAT5, EPAS1, ZNF644, RBPJ, andFOXP2exhibited associations with RNA polymerase II core promoter proximal region sequence-specific DNA binding. Conversely, downregulated genes, includingEEA1, CNOT4, FGD4, MBNL1, ZRANB2, REV3L, XIAP, ATP13A3, RPAP2, FOXP2, and ADAMTS6, were implicated in the mRNA surveillance pathway. In addition, several Gene Ontology terms, such as GO:0001228 (transcriptional activator activity) and GO:0004842, along with GO:0000978 (transcriptional activator activity), were linked to the DEGs. KEGG pathways, including “Glycosaminoglycan biosynthesis - chondroitin sulfate/dermatan sulfate” (KEGG:532) and “basal cell carcinoma” (KEGG:5217), were associated with our findings. Our principal component analysis (PCA) demonstrated a cohesive clustering of gene expression profiles among the four samples, with subtle distinctions. Protein-protein interaction (PPI) analysis indicated the functional relationships among the DEGs. Notably, genes such asABHD16BandNPBWR2exhibited strong co-expression among the down-regulated DEGs, whileDNAH7/TBC1D31andMBNL1/NOVA1displayed prominent co-expression among the up-regulated DEGs. Consequently, our study offers a comprehensive understanding of Kari sheep genetics and the pivotal genes involved in gestation length determinants. These findings carry significant genetic implications, enhancing genetic resources, furthering reproductive biology comprehension, and contributing to the advancement of sustainable sheep farming practices.
A DNA condensation code for linker histones
Authors: Watson Matthew , Sabirova Dilyara , Hardy Megan C. , Pan Yuming , Yates Henry , Wright Charlotte J. , Chan W. H. , Destan Ebru , Stott Katherine 
Published: November 2023

AbstractLinker histones play an essential role in chromatin packaging by facilitating compaction of the 11-nm fibre of nucleosomal “beads on a string”. The result is a heterogeneous condensed state with local properties that range from dynamic, irregular and liquid-like, to stable and regular structures (the 30-nm fibre), which in turn impact chromatin-dependent activities at a fundamental level. The properties of the condensed state depend on the type of linker histone, particularly on the highly disordered C-terminal tail, which is the most variable region of the protein, both between species, and within the various subtypes and cell-type specific variants of a given organism. We have developed anin-vitromodel system comprising linker histone tail and linker DNA, which although very minimal, displays surprisingly complex behaviour, and is sufficient to model the known states of linker-histone-condensed chromatin: disordered “fuzzy” complexes (“open” chromatin), dense liquid-like assemblies (dynamic condensates) and higher-order structures (organised 30-nm fibres). A crucial advantage of such a simple model is that it allows the study of the various condensed states by NMR, CD and scattering methods. Moreover, it allows capture of the thermodynamics underpinning the transitions between states through calorimetry. We have leveraged this to rationalise the distinct condensing properties of linker histone subtypes and variants across species that are encoded by the amino acid content of their C-terminal tails. Three properties emerge as key to defining the condensed state: charge density, lysine/arginine ratio, and proline-free regions, and we evaluate each separately using a strategic mutagenesis approach.
Modelling low-dimensional interacting brain networks reveals organising principle in human cognition
Authors: Sanz Perl Yonatan , Geli Sebastian , Pérez-Ordoyo Eider , Zonca Lou , Idesis Sebastian , Vohryzek Jakub , Jirsa Viktor K. , Kringelbach Morten L. , Tagliazucchi Enzo , Deco Gustavo 
Published: November 2023

SummaryThe discovery of resting state networks shifted the focus from the role of local regions in cognitive tasks to the ongoing spontaneous dynamics in global networks. Recently, efforts have been invested to reduce the complexity of brain activity recordings through the application of nonlinear dimensionality reduction algorithms. Here, we investigate how the interaction between these networks emerges as an organising principle in human cognition. We combine deep variational auto-encoders with computational modelling to construct a dynamical model of brain networks fitted to the whole-brain dynamics measured with functional magnetic resonance imaging (fMRI). Crucially, this allows us to infer the interaction between these networks in resting state and 7 different cognitive tasks by determining the effective functional connectivity between networks. We found a high flexible reconfiguration of task-driven network interaction patterns and we demonstrate that can be used to classify different cognitive tasks. Importantly, compared to using all the nodes in a parcellation, we obtain better results by modelling the dynamics of interacting networks in both model and classification performance. These findings show the key causal role of manifolds as a fundamental organising principle of brain function, providing evidence that interacting networks are the computational engines brain during cognitive tasks.
Excitatory neurons in stratum radiatum provide an alternative pathway for excitation flow that escapes perisomatic inhibition
Authors: Lebedeva Julia , Jappy David , Nasretdinov Azat , Vazetdinova Alina , Krut’ Viktoria , Sokolov Rostislav , Dobryakova Yulia , Eliava Marina , Grinevich Valery , Rozov Andrei 
Published: November 2023

AbstractFor over half a century, it has been postulated that the internal excitatory circuit in the hippocampus consists of three relay stations. Excitation arrives from the entorhinal cortex to the DG granule cells, is transmitted through the mossy fibers to CA3 pyramidal cells, and is then transmitted through Schaffer collaterals to CA1 pyramidal neurons. In all three structures (DG, CA3 and CA1), the activity of the excitatory neurons involved in the synaptic transmission of excitation are under the control of inhibitory basket neurons that are recruited into network activity via feed-forward and feed-back excitation. However, in the late 90s “stratum radiatum giant cells” were described as a novel type of neuron with the anatomical features of excitatory cells. Since then, the role of these cells in the hippocampal circuitry has not been well understood. Here, using optogenetic and electrophysiological techniques we characterized the functional location of these neurons within the hippocampal network. We show that: (i) the main excitatory drive to giant excitatory neurons in stratum radiatum (ExNR) comes via Schaffer collaterals; (ii) within the CA1 field, ExNRare not directly connected with local pyramidal cells, but provide massive and efficient excitatory input to parvalbumin positive (PV+) interneurons; (iii) ExNRare reciprocally innervated by bistratified cells, but not inhibited by backet interneurons; (iv) the efficiency of ExNRexcitation to PV+ interneurons is sufficient for a single ExNRaction potential to trigger massive inhibition of downstream CA1 pyramidal cells. Taken together, our data shows that ExNRconstitute an alternative pathway of excitation for CA1 interneurons that avoids the burden of perisomatic inhibition.
Roles for CEP170 in cilia function and dynein-2 assembly
Authors: Weijman Johannes F , Vuolo Laura , Shak Caroline , Pugnetti Anna , Mukhopadhyay Aakash G , Hodgson Lorna R , Heesom Kate J , Roberts Anthony J , Stephens David J 
Published: November 2023

AbstractPrimary cilia are essential eukaryotic organelles required for signalling and secretion. Dynein-2 is a microtubule-motor protein complex and is required for ciliogenesis via its role in facilitating retrograde intraflagellar transport from the cilia tip to the cell body. Dynein-2 must be assembled and loaded onto IFT-trains for entry into cilia for this process to occur but how dynein-2 is assembled at the base and how it is recycled back into a cilium remain poorly understood. Here, we identify Centrosomal Protein of 170 kDa (CEP170) as a dynein-2 interacting protein. We show that loss of CEP170 perturbs intraflagellar transport, Hedgehog signalling, and alters the stability of dynein-2 holoenzyme complex. Together, our data indicate a role for CEP170 in supporting cilia function and dynein-2 assembly.SummaryIntraflagellar transport is required for the function of primary cilia. In this work, we show that Centrosomal Protein 170 (CEP170) interacts with the IFT motor dynein-2 and loss of CEP170 causes defects in dynein-2 assembly and cilia function.
Fish Playpens – Method for raising individual juvenile zebrafish on a recirculating system for studies requiring repeated measures
Authors: Moll Tabea O.C. , Farber Steven A. 
Published: November 2023

AbstractEven though many experimental approaches benefit from tracking individual larval animals, there is yet to be a commercial zebrafish rack system designed to accomplish this task. Thus, we invented playpens, an acrylic and screen container, to raise 12 individual zebrafish juveniles per standard 10 L tank on an existing recirculating fish system. During a week-long experiment, fish raised in playpens grow to the same size as conventionally raised juveniles.
Peripheral gating of pain by glial endozepine
Authors: Li Xinmeng , Prudente Arthur Silveira , Prato Vincenzo , Guo Xianchuan , Hao Han , Jones Frederick , Figoli Sofia , Mullen Pierce , Wang Yujin , Tonnello Raquel , Lee Sang Hoon , Shah Shihab , Maffei Benito , Berta Temugin , Du Xiaona , Gamper Nikita 
Published: November 2023

AbstractWe report that diazepam binding inhibitor (DBI) is a glial messenger mediating satellite glia-sensory neuron crosstalk in the dorsal root ganglion (DRG). DBI is highly and specifically expressed in satellite glia cells (SGCs) of mice, rat and human, but not in sensory neurons or other DRG-resident cells. Knockdown of DBI results in a robust mechanical hypersensitivity without significant effects on other sensory modalities.In vivooverexpression of DBI in SGCs reduces sensitivity to mechanical stimulation and alleviates mechanical allodynia in neuropathic and inflammatory pain models. We further show that DBI acts as a partial agonist and positive allosteric modulator at the neuronal GABAAreceptors, particularly strongly effecting those with a high-affinity benzodiazepine binding site. Such receptors are selectively expressed by a subpopulation of mechanosensitive DRG neurons and these are also more enwrapped with DBI-expressing glia, as compared to other DRG neurons, suggesting a mechanism for specific effect of DBI on mechanosensation. These findings identified a new, peripheral neuron-glia communication mechanism modulating pain signalling, which can be targeted therapeutically.
Structural and mechanistic insights into disease-associated endolysosomal exonucleases PLD3 and PLD4
Authors: Yuan Meng , Peng Linghang , Huang Deli , Gavin Amanda , Luan Fangkun , Tran Jenny , Feng Ziqi , Zhu Xueyong , Matteson Jeanne , Wilson Ian A. , Nemazee David 
Published: November 2023

ABSTRACTEndolysosomal exonucleases PLD3 and PLD4 (phospholipases D3 and D4) are associated with autoinflammatory and autoimmune diseases. We report structures of these enzymes, and the molecular basis of their catalysis. The structures reveal an intra-chain dimer topology forming a basic active site at the interface. Like other PLD superfamily members, PLD3 and PLD4 carry HxKxxxxD/E motifs and participate in phosphodiester-bond cleavage. The enzymes digest ssDNA and ssRNA in a 5′-to-3′ manner and are blocked by 5′-phosphorylation. We captured structures in apo, intermediate, and product states and revealed a ‘link-and-release’ two-step catalysis. We also unexpectedly demonstrated phosphatase activity via a covalent 3’- phosphistidine intermediate. PLD4 contains an extra hydrophobic clamp that stabilizes substrate and could affect oligonucleotide substrate preference and product release. Biochemical and structural analysis of disease-associated mutants of PLD3/4 demonstrated reduced enzyme activity or thermostability and the possible basis for disease association. Furthermore, these findings provide insight into therapeutic design.
Combining behavior and mechanics approaches reveals the dynamics of animal impacts in mantis shrimp (Stomatopoda)
Authors: Green P.A. 
Published: November 2023

AbstractAnimals deliver and withstand physical impacts in diverse behavioral contexts, from competing rams clashing their antlers together to archerfish impacting prey with jets of water. Though the ability of animals to withstand impact has generally been studied by focusing on morphology, behaviors may also influence impact resistance. Mantis shrimp exchange high-force strikes on each other’s coiled, armored telsons (tailplates) during contests over territory. Prior work has shown that telson morphology has high impact resistance. I hypothesized that the behavior of coiling the telson also contributes to impact energy dissipation. By measuring impact dynamics from high-speed videos of strikes exchanged during contests between freely-moving animals, I found that over 20% more impact energy was dissipated as compared to a prior study that focused solely on morphology. This increase is likely due to behavior: because the telson is lifted off the substrate, the entire body flexes after contact, dissipating more energy than exoskeletal morphology does on its own. While variation in the degree of telson coil did not affect energy dissipation, higher velocity strikes resulted in greater energy dissipation, suggesting striking individuals may vary their behavior to affect impacts. Overall, these findings show that analysis of both behavior and morphology is crucial to understanding impact resistance, and suggest future research on the evolution of structure and function under the selective pressure of biological impacts.Summary statementFreely competing mantis shrimp dissipated over 90% of the energy of high-force strikes by raising their impact-resistant tailplates off the substrate; faster strikes led to greater energy dissipation.
Vaccination of cattle with a virus-vectored vaccine against a major membrane protein ofMycobacterium a. subsp.paratuberculosiselicits CD8 cytotoxic T cells that kill intracellular bacteria
Authors: Mahmoud Asmaa H. , Abdellrazeq Gaber S. , Franceschi Valentina , Schneider David A. , Bannantine John P. , Fry Lindsay M. , Hulubei Victoria , De Matteis Giovanna , Park Kun Taek , Davis William C. , Donofrio Gaetano 
Published: November 2023

AbstractInfection of cattle withMycobacterium a. subsp.Paratuberculosis (Map), the causative agent of paratuberculosis, induces an immune response directed toward a 35 kD major membrane protein (MMP) ofMap. CD8 cytotoxic T cells (CTL) are elicited when peripheral blood mononuclear cells from healthy cattle are incubated ex vivo with antigen-presenting cells (APC) primed with bacterial recombinant MMP. Ex vivo development of CTL was MHC-restricted and required the presence of both CD4 and CD8 T cells. The geneMAP2121c,encoding MMP, was modified to express a modified form of MMP (p35NN) in a mammalian cell line, also capable of eliciting an ex vivo CTL response. In the present study, the modified gene for p35NN was placed into a BoHV4 vector to determine the potential use of BoHV-4AΔTK-p35NN as a peptide-based vaccine. Subcutaneous vaccination of healthy cattle with BoHV-4AΔTK-p35NN elicited a CTL recall response, as detected ex vivo. Further studies are warranted to conduct a challenge study to determine if CD8 CTL elicited by vaccination with BoHV-4AΔTK-p35NN prevents the establishment of a persistent infection byMap.
The effect of ciprofloxacin and gentamicin on wound healing inex vivosheep cornea model
Authors: Okurowska K. , Suarez D. R. Manrique , Karunakaran E. 
Published: November 2023

AbstractPurposeOur objective was to assess the efficacy of anex vivosheep corneal model as an alternative for live animal testing in screening drug cytotoxicity. In pursuit of this goal, we investigated the impact of two commonly used topical antibiotics, ciprofloxacin and gentamicin, on wound healing. Furthermore, we examined different antibiotic dosages and dosing regimens to understand their effects comprehensively.MethodsThe epithelium onex vivo sheep corneas was removed with a scalpel, and the area was treated with ciprofloxacin (0.1, 0.3, and 1 mg mL-1), gentamicin (0.25, 1, and 3 mg mL-1), or phosphate-buffered saline (control). The corneas were exposed to treatments continuously or twice daily for ten minutes. Wound closure was observed by fluorescein retention and histological staining.ResultsUntreated corneas healed within 41 hours. Continuous exposure to both ciprofloxacin and gentamicin significantly reduced the corneal healing ability in a time- and concentration-dependent manner. Overall, ciprofloxacin was found to be more toxic than gentamycin. However, this model showed that the corneal epithelium could heal effectively when both antibiotics were administered intermittently.ConclusionCiprofloxacin demonstrated greater inhibition of wound healing compared to gentamicin, aligning within vivostudies. The administration of drops several times daily mitigated the toxic effects of antibiotics. Theex vivosheep wound healing model holds promise as an alternative approach toin vivotoxicity testing, enabling the swift evaluation of novel antimicrobial treatments and eye drop additives.
Phenotype projections accelerate biobank-scale GWAS
Authors: Zietz Michael , Gisladottir Undina , Brown Kathleen LaRow , Tatonetti Nicholas P. 
Published: November 2023

ABSTRACTUnderstanding the genetic basis of complex disease is a critical research goal due to the immense, worldwide burden of these diseases. Pan-biobank genome-wide association studies (GWAS) provide a powerful resource in complex disease genetics, generating shareable summary statistics on thousands of phenotypes. Biobank-scale GWAS have two notable limitations: they are resource-intensive to compute and do not inform about hand-crafted phenotype definitions, which are often more relevant to study. Here we present Indirect GWAS, a summary-statistic-based method that addresses these limitations. Indirect GWAS computes GWAS statistics for any phenotype defined as a linear combination of other phenotypes. Our method can reduce runtime by an order of magnitude for large pan-biobank GWAS, and it enables ultra-rapid (roughly one minute) GWAS on hand-crafted phenotype definitions using only summary statistics. Overall, this method advances complex disease research by facilitating more accessible and cost-effective genetic studies using large observational data.
MaUGT79confers drought tolerance by regulating scopolin biosynthesis in plants
Authors: Duan Zhen , Wu Fan , Yan Qi , Wang Shengsheng , Wang Yimeng , Jones Chris Stephen , Zhou Pei , Zhang Caibin , Zhang Jiyu 
Published: November 2023

AbstractThe coumarin scopoletin and its glycosylated form scopolin constitute a vast class of natural products that are considered to be high-value compounds, distributed widely in the plant kingdom, they help plants adapt to environmental stresses. However, the underlying molecular mechanism of how scopolin is involved in the regulation of plant drought tolerance remains largely unexplored. Here, UDP-glycosyltransferase 79 (MaUGT79) was genetically mapped as the target gene by bulk segregant analysis sequencing (BSA-seq) from twoMelilotus albusnear-isogenic lines (NILs). MaUGT79 exhibits glucosyltransferase activity toward scopoletin. The expression ofMaUGT79is induced by drought stress and it was found to mediate scopolin accumulation and reactive oxygen species (ROS) scavenging under drought stress. Moreover, the transcription ofMaUGT79was demonstrated to be directly and positively regulated by MaMYB4, which is a key integrator of both scopolin biosynthesis and drought tolerance. Collectively, this study reveals that MaMYB4 is a positive regulator in drought stress by targeting theMaUGT79promoter and activating its expression to coordinately mediate scopolin biosynthesis and drought tolerance, providing insights into the regulatory mechanism for plant growth adaption to environmental changes through accumulation of scopolin.
Acidic media promotes quiescence entry inSaccharomyces cerevisiae
Authors: Greenlaw Alison C. , Tsukiyama Toshio 
Published: November 2023

AbstractQuiescence is a conserved cellular state wherein cells cease proliferation and remain poised to re-enter the cell cycle when conditions are appropriate. Budding yeast is a powerful model for studying cellular quiescence. In this work, we demonstrate that the pH of the YPD media strongly affects quiescence entry efficiency inSaccharomyces cerevisiae. Adjusting media pH to 5.5 significantly improves quiescence entry efficiency compared to unadjusted YPD media. Thermotolerance of the produced quiescence yeast are similar, suggesting the media pH influences the quantity of quiescent cells more than quality of quiescence reached.