bluuebunny/crossref_metadata_2025_split huggingface dataset:
Involvement of a serotonin/GLP-1 circuit in adolescent isolation-induced diabetes
Authors: Kolling Louis J. , Khan Kanza , Balasubramanian Nagalakshmi , Guo Deng-Fu , Rahmouni Kamal , Marcinkiewcz Catherine A. 
Published: June 2023

AbstractIn 2020, stay-at-home orders were implemented to stem the spread of SARS-CoV-2 worldwide. Social isolation can be particularly harmful to children and adolescents—during the pandemic, the prevalence of obesity increased by ∼37% in persons aged 2-19. Obesity is often comorbid with type 2 diabetes, which was not assessed in this human pandemic cohort. Here, we investigated whether male mice isolated throughout adolescence develop type 2 diabetes in a manner consistent with human obesity-induced diabetes, and explored neural changes that may underlie such an interaction. We find that isolating C57BL/6J mice throughout adolescence is sufficient to induce type 2 diabetes. We observed fasted hyperglycemia, diminished glucose clearance in response to an insulin tolerance test, decreased insulin signaling in skeletal muscle, decreased insulin staining of pancreatic islets, increased nociception, and diminished plasma cortisol levels compared to group-housed control mice. Using Promethion metabolic phenotyping chambers, we observed dysregulation of sleep and eating behaviors, as well as a time-dependent shift in respiratory exchange ratio of the adolescent-isolation mice. We profiled changes in neural gene transcription from several brain areas and found that a neural circuit between serotonin-producing and GLP-1-producing neurons is affected by this isolation paradigm. Overall, spatial transcription data suggest decreased serotonin neuron activity (via decreased GLP-1-mediated excitation) and increased GLP-1 neuron activity (via decreased serotonin-mediated inhibition). This circuit may represent an intersectional target to further investigate the relationship between social isolation and type 2 diabetes, as well as a pharmacologically-relevant circuit to explore the effects of serotonin and GLP-1 receptor agonists.Article HighlightsIsolating C57BL/6J mice throughout adolescence is sufficient to induce type 2 diabetes, presenting with fasted hyperglycemia.Adolescent-isolation mice have deficits in insulin responsiveness, impaired peripheral insulin signaling, and decreased pancreatic insulin production.Transcriptional changes across the brain include the endocannabinoid, serotonin, and GLP-1 neurotransmitters and associated receptors.The neural serotonin/GLP-1 circuit may represent an intersectional target to further investigate the relationship between social isolation and type 2 diabetes. Serotonin-producing neurons of adolescent-isolation mice produce fewer transcripts for the GLP-1 receptor, and GLP-1 neurons produce fewer transcripts for the 5-HT1Aserotonin receptor.
Sustained growth and rapid dispersal of chitin-associated marine bacteria
Authors: Guessous Ghita , Patsalo Vadim , Balakrishnan Rohan , Çağlar Tolga , Williamson James R. , Hwa Terence 
Published: June 2023

ABSTRACTMany biogeochemical functions involve bacteria utilizing solid substrates. However, little is known about the coordination of bacterial growth with the kinetics of attachment to and detachment from such substrates. In this quantitative study ofVibrio sp. 1A01growing on chitin particles, we reveal the heterogeneous nature of the exponentially growing culture, comprised of two co-existing subpopulations: a minority replicating on chitin particles and a non-replicating majority which was planktonic. This partition resulted from a high rate of cell detachment from particles. Despite high detachment, sustained exponential growth of cells on particles was enabled by the enrichment of extra-cellular chitinases excreted and left behind by detached cells. The “inheritance” of these chitinases sustains the colonizing subpopulation despite its reduced density. This simple mechanism helps to circumvent a tradeoff between growth and dispersal, allowing particle-associated marine heterotrophs to explore new habitats without compromising their fitness on the habitat they have already colonized.
Construction of a multi-tissue cell atlas reveals cell-type-specific regulation of molecular and complex phenotypes in pigs
Authors: Chen Lijuan , Li Houcheng , Teng Jinyan , Wang Zhen , Qu Xiaolu , Chen Zhe , Cai Xiaodian , Zeng Haonan , Bai Zhonghao , Li Jinghui , Pan Xiangchun , Yan Leyan , Wang Fei , Lin Lin , Luo Yonglun , Sahana Goutam , Lund Mogens Sandø , Ballester Maria , Crespo-Piazuelo Daniel , Karlskov-Mortensen Peter , Fredholm Merete , Clop Alex , Amills Marcel , Loving Crystal , Tuggle Christopher K. , Madsen Ole , Li Jiaqi , Zhang Zhe , Liu George E. , Jiang Jicai , Fang Lingzhao , Yi Guoqiang 
Published: June 2023

AbstractThe systematic characterization of cellular heterogeneity among tissues and cell-type-specific regulation underlying complex phenotypes remains elusive in pigs. Within the Pig Genotype-Tissue Expression (PigGTEx) project, we present a single-cell transcriptome atlas of adult pigs encompassing 229,268 high-quality nuclei from 19 tissues, annotated to 67 major cell types. Besides cellular heterogeneity within and across tissues, we further characterize prominent tissue-specific features and functions of muscle, epithelial, and immune cells. Through deconvoluting 3,921 bulk RNA-seq samples from 17 matching tissues, we dissect thousands of genetic variants with cell-type interaction effects on gene expression (ieQTL). By colocalizing these ieQTL with variants associated with 268 complex traits, we provide new insights into the cellular mechanisms behind these traits. Moreover, we highlight that orthologous genes with cell-type-specific regulation in pigs exhibit significant heritability enrichment for some human complex phenotypes. Altogether, our work provides a valuable resource and highlights novel insights in cellular regulation of complex traits for accelerating pig precision breeding and human biomedical research.
The SOCE system is critical for membrane bleb formation to drive avian primordial germ cell migration
Authors: Morita Mizuki , Morimoto Manami , Teramoto Takayuki , Ikenouchi Junichi , Atsuta Yuji , Saito Daisuke 
Published: June 2023

SUMMARYAmoeboid cell migration is driven by the specialized cell protrusion, membrane bleb. A recentin vitroanalysis of bleb formation using a cancer cell line showed that store-operated calcium entry (SOCE)-mediated local elevation of Ca2+concentration triggers bleb formation, but it remains unknown how commonly this system is utilized in the bleb formation and bleb-driven cell migrationin vivo. We demonstrate with avian primordial germ cell (PGC) model that that chick PGCs use SOCE, triggered by stem cell factor (SCF), to induce bleb formation and that it is essential forin vivomigration including trans-endothelial and mesenchymal cell migration. Our discovery also provides insight into the correlation between cancer metastasis/invasion and SOCE-mediated bleb formation.
Saccharomyces cerevisiaeDmo2p is involved in the mitochondrial copper metabolism and is required for the stability of newly translated Cox2p
Authors: Soares Maria Antônia Kfouri Martins , Franco Letícia Veloso Ribeiro , Chagas Jhulia Almeida Clarck , Gomes Fernando , Barros Mário H. 
Published: June 2023

AbstractBased on available platforms ofSaccharomyces cerevisiaemitochondrial proteome and other high throughput studies, we identified the yeast geneDMO2with a profile of genetic and physical interactions that indicate a putative role in mitochondrial respiration. Dmo2p is a homolog to human DMAC1 with two conserved cysteines in a Cx2C motif. Here, we localized Dmo2p in the mitochondrial inner membrane with the conserved cysteines facing the intermembrane space. The observed phenotypes of thedmo2null mutant indicate a general function in cellular stress response; the mutant displayed poor growth on non-fermentative media at 37°C, and in oleate, it is more sensitive to heat and oxidative stress while its overexpression confers resistance to some of the tested stressors. Dmo2p topology and modeled structure suggested a functional redox role for the Cx2C motif sustained by site-directed mutagenesis of both cysteine residues. The respiratory deficiency ofdmo2mutants at 37°C led to a reduction in cytochromecoxidase activity (COX) and the formation ofbc1-COX supercomplexes; we also observed a rapid turnover of Cox2p, the subunit two of the cytochromecoxidase complex that harbors the binuclear CuAcenter. Moreover, Dmo2p co-immunoprecipitated with Cox2p and components of CuAcenter maturation such as Sco1p and Sco2p; and finally,DMO2overexpression can suppresscox23respiratory deficiency, a mutant that has the mitochondrial copper homeostasis impaired. Overall, our data suggest that Dmo2p is required for Cox2p maturation, potentially by aiding proteins involved in copper transport and incorporation into Cox2p.
Performance analysis of conventional and AI-based variant callers using short and long reads
Authors: Abdelwahab Omar , Belzile François , Torkamaneh Davoud 
Published: June 2023

AbstractThe accurate detection of variants is essential for genomics-based studies. Currently, there are various tools designed to detect genomic variants, however, it has always been a challenge to decide which tool to use, especially when various major genome projects have chosen to use different tools. Thus far, most of the existing tools were mainly developed to work on short-read data (i.e., Illumina); however, other sequencing technologies (e.g. PacBio, and Oxford Nanopore) have recently shown that they can also be used for variant calling. In addition, with the emergence of artificial intelligence (AI)-based variant calling tools, there is a pressing need to compare these tools in terms of efficiency, accuracy, computational power, and ease of use. In this study, we evaluated the most widely used conventional and AI-based variant calling tools (BCFTools, GATK4, Platypus, DNAscope, and DeepVariant) in terms of accuracy and computational cost using both short-read and long-read data derived from three different sequencing technologies for the same set of samples from the Genome In A Bottle (GIAB) project. The analysis showed that AI-based variant calling tools supersede conventional ones for calling SNVs and INDELs using both long and short reads. In addition, we demonstrate the advantages and drawbacks of each tool while ranking them in each aspect of these comparisons. This study provides best practices for variant calling using AI-based and conventional variant callers with different types of sequencing data.
How formate dehydrogenase-lacking acetogenClostridium bovifaecisutilize formate as the sole carbon source for its acetogenic growth?
Authors: Guan Ziwei , Fu Bo , Conrad Ralf , Qian Qingqing , Han Dongfei , Liu Hongbo , Liu He 
Published: June 2023

ABSTRACTLittle is known about the growth of formate dehydrogenase-lacking acetogen on formate as sole carbon source. Here, we analyzed formate metabolism inClostridium bovifaecisstrain BXX using different concentrations of formate. The results show thatC. bovifaecisconverted formate (11.5-96 mM) into acetate with molar ratio of 2.0:1∼2.6:1 by using L-cysteine in the anaerobic medium as electron source according to the stoichiometry of acetogenesis. Genome analysis ofC. bovifaecisrevealed genes encoding anaerobic ribonucleoside triphosphate reductase (nrdDandnrdG) catalyzing the oxidation of formate to CO2while ATP is being reduced to the desoxy form. The existence ofnrdDwas verified by PCR, reverse transcription-PCR analysis and acetogenesis from formate. The process mode of acetogenesis from formate inC. bovifaecisprovides insight into the unique metabolic feature of an FDH-lacking acetogen.IMPORTANCEWood-Ljungdahl pathway (WLP) lacking formate dehydrogenase (FDH) which catalyzes CO2reduction to formate has been reported to occur acetogenesis only in the presence of formate and exogenous CO2, which seems to result from the formate-rich habitats adaptation of gastrointestinal acetogens. Here, we found FDH-lackingClostridium bovifaecisstrain BXX converted formate (11.5-96 mM) into acetate with molar ratio of 2.0:1∼2.6:1 fitting the stoichiometry of acetogenesis when using formate as the sole carbon source. CO2needed in the carbonyl branch of WLP was from the oxidation of formate to CO2catalyzed by anaerobic ribonucleoside triphosphate reductase while ATP is being reduced to the desoxy form. L-cysteine in the anaerobic medium was the electron source of WLP. The process mode of acetogenesis from formate inC. bovifaecisprovides insight into how an FDH-lacking acetogen can make a living from the simplest resources as carbon source, which has both ecological and biotechnological significance.
Identification of signalling pathways involved in gill regeneration in zebrafish
Authors: Cadiz Laura , Reed Maddison , Monis Simon , Akimenko Marie-Andrée , Jonz Michael G. 
Published: June 2023

ABSTRACTThe occurrence of regeneration of the organs involved in respiratory gas exchange amongst vertebrates is heterogeneous. In aquatic animals, such as amphibians and fishes, the gills regenerate completely following resection or amputation; whereas in mammals, only partial, facultative regeneration of lung tissue occurs following injury. Given the homology between gills and lungs, the capacity of gill regeneration in aquatic species is of major interest in determining the underlying molecular or signalling pathways involved in respiratory organ regeneration. In the present study, we used adult zebrafish (Danio rerio) to characterize signalling pathways involved in the early stages of gill regeneration. Regeneration of the gills, including the gas exchange surfaces, was induced by resection of the gill filaments and observed over a period of up to 10 days. We screened for the effects of the drugs, SU5402, dorsomorphin, and LY411575, which inhibit FGF, BMP or Notch signalling, respectively, on development of the blastema. Exposure to each drug for 5 days significantly reduced blastema formation in regenerates, compared to unresected controls. In separate experiments, and under normal conditions of regeneration, we used quantitative real-time PCR and observed an increased expression of genes encoding for the bone morphogenetic factor, Bmp2b, fibroblast growth factor, Fgf8a, a transcriptional regulator (Her6) involved in Notch signalling, and Sonic Hedgehog (Shha), in regenerating gills at 10 day post-resection, compared to unresected controls.In situhybridization confirmed that all four genes were expressed in regenerating gill tissue. This study implicates BMP, FGF, Notch and Shh signalling in gill regeneration in zebrafish.SUMMARY STATEMENTGill regeneration in zebrafish is mediated by multiple signalling pathways, including BMP, FGF, Notch and Sonic Hedgehog.
Spatio-temporal mechanisms of consolidation, recall and reconsolidation in reward-related memory trace
Authors: Hamed Adam , Kursa Miron Bartosz , Karwicka Wiktoria , Piwoński Krzysztof Piotr , Falińska Monika , Danielewski Konrad , Rejmak-Kozicka Emilia , Włodkowska Urszula , Kubik Stepan , Czajkowski Rafał 
Published: June 2023

AbstractThe formation of memories is a complex, multi-scale phenomenon, especially when it involves integration of information from various brain systems. We have investigated the differences between a novel and consolidated association of spatial cues and amphetamine administration, using an in-situ hybridisation method to track the short-term dynamics during the recall testing. We have found that remote recall group involves smaller, but more consolidated groups of neurons, which is consistent with their specialisation. By employing machine learning analysis, we have shown this pattern is especially pronounced in the VTA; furthermore, we also uncovered significant activity patterns in retrosplenial and prefrontal cortices, as well as in the DG and CA3 subfields of the hippocampus. The behavioural propensity towards the associated localisation appears to be driven by the nucleus accumbens, however, further modulated by a trio of the amygdala, VTA and hippocampus, as the trained association is confronted with test experience. These results show that memory mechanisms must be modelled considering individual differences in motivation, as well as covering dynamics of the process.
Phosphatases modified by LH signaling in ovarian follicles: testing their role in regulating the NPR2 guanylyl cyclase
Authors: Egbert Jeremy R. , Silbern Ivan , Uliasz Tracy F. , Lowther Katie M. , Yee Siu-Pok , Urlaub Henning , Jaffe Laurinda A. 
Published: June 2023

AbstractIn response to luteinizing hormone, multiple proteins in rat and mouse granulosa cells are rapidly dephosphorylated, but the responsible phosphatases remain to be identified. Because the phosphorylation state of phosphatases can regulate their interaction with substrates, we searched for phosphatases that might function in LH signaling by using quantitative mass spectrometry. We identified all proteins in rat ovarian follicles whose phosphorylation state changed detectably in response to a 30-minute exposure to LH, and within this list, identified protein phosphatases or phosphatase regulatory subunits that showed changes in phosphorylation. Phosphatases in the PPP family were of particular interest because of their requirement for dephosphorylating the natriuretic peptide receptor 2 (NPR2) guanylyl cyclase in the granulosa cells, which triggers oocyte meiotic resumption. Among the PPP family regulatory subunits, PPP1R12A and PPP2R5D showed the largest increases in phosphorylation, with 4-10 fold increases in signal intensity on several sites. Although follicles from mice in which these phosphorylations were prevented by serine-to-alanine mutations in eitherPpp1r12aorPpp2r5dshowed normal LH-induced NPR2 dephosphorylation, these regulatory subunits and others could act redundantly to dephosphorylate NPR2. Our identification of phosphatases and other proteins whose phosphorylation state is rapidly modified by LH provides clues about multiple signaling pathways in ovarian follicles.Graphical AbstractSummary sentenceQuantitative mass spectrometric analysis of phosphatases whose phosphorylation state is rapidly modified by luteinizing hormone provides clues about how LH signaling dephosphorylates NPR2 as well as a resource for future studies.
Unsupervised Machine Learning for Species Delimitation, Integrative Taxonomy, and Biodiversity Conservation
Authors: Pyron R. Alexander 
Published: June 2023

AbstractIntegrative taxonomy combining data from multiple axes of biologically relevant variation is a major recent goal of systematics. Ideally, such taxonomies would be backed by similarly integrative species-delimitation analyses. Yet, most current methods rely solely or primarily on molecular data, with other layers often incorporated only in apost hocqualitative or comparative manner. A major limitation is the difficulty of deriving and implementing quantitative parametric models linking different datasets in a unified ecological and evolutionary framework. Machine Learning methods offer flexibility in this arena by learning high-dimensional associations between observations (e.g., individual specimens) across a wide array of input features (e.g., genetics, geography, environment, and phenotype) to delineate statistical clusters. Here, I implement an unsupervised method using Self-Organizing (or “Kohonen”) Maps (SOMs). Recent extensions called SuperSOMs can integrate an arbitrary number of layers, each of which exerts independent influence on the two-dimensional output clustering via empirically estimated weights. These output clusters can then be delimited intoKsignificant units that are interpreted as species or other entities. I show an empirical example inDesmognathussalamanders with layers representing alleles, space, climate, and traits. Simulations reveal that the SOM/SuperSOM approach can detectK=1, does not over-split, reflects contributions from all layers with signal, and does not allow layer size (e.g., large genetic matrices) to overwhelm other datasets, desirable properties addressing major concerns from previous methods. Finally, I suggest that these and similar methods could integrate conservation-relevant layers such as population trends and human encroachment to delimit management units from an explicitly quantitative framework grounded in the ecology and evolution of species limits and boundaries.
Competition for iron shapes metabolic antagonism betweenBacillus subtilisandPseudomonas
Authors: Lyng Mark , Jørgensen Johan P. B. , Schostag Morten D. , Jarmusch Scott A. , Aguilar Diana K. C. , Lozano-Andrade Carlos N. , Kovács Ákos T. 
Published: June 2023

AbstractSiderophores have long been implicated in sociomicrobiology as determinants of bacterial interrelations. For plant-associated genera likeBacillusandPseudomonas, siderophores are well known for their biocontrol functions. Here, we explored the functional role of theBacillus subtilissiderophore bacillibactin in an antagonistic interaction withPseudomonas marginalis. The presence of bacillibactin strongly influenced the outcome of the interaction in an iron-dependent manner. The bacillibactin producerB. subtilisrestricts colony spreading ofP. marginalisby repressing the transcription of histidine kinase-encoding genegacS, thereby abolishing production of secondary metabolites such as pyoverdine and viscosin. By contrast, lack of bacillibactin restrictedB. subtiliscolony growth in a mechanism reminiscent of a siderophore tug-of-war for iron. Our analysis revealed that theBacillus-Pseudomonasinteraction is conserved across fluorescentPseudomonasspp., expanding our understanding of the interplay between two genera of the most well-studied soil microbes.
Dissociating the Contributions of Frontal Eye Field Activity to Spatial Working Memory and Motor Preparation
Authors: Jonikaitis Donatas , Noudoost Behrad , Moore Tirin 
Published: June 2023

AbstractNeurons within dorsolateral prefrontal cortex of primates are characterized by robust persistent spiking activity exhibited during the delay period of working memory tasks. This includes the frontal eye field (FEF) where nearly half of the neurons are active when spatial locations are held in working memory. Past evidence has established the FEF’s contribution to the planning and triggering of saccadic eye movements as well as to the control of visual spatial attention. However, it remains unclear if persistent delay activity reflects a similar dual role in movement planning and visuospatial working memory. We trained monkeys to alternate between different forms of a spatial working memory task which could dissociate remembered stimulus locations from planned eye movements. We tested the effects of inactivation of FEF sites on behavioral performance in the different tasks. Consistent with previous studies, FEF inactivation impaired the execution of memory-guided saccades, and impaired performance when remembered locations matched the planned eye movement. In contrast, memory performance was largely unaffected when the remembered location was dissociated from the correct eye movement response. Overall, the inactivation effects demonstrated clear deficits on eye movements, regardless of task type, but little or no evidence of a deficit in spatial working memory. Thus, our results indicate that persistent delay activity in the FEF contributes primarily to the preparation of eye movements and not to spatial working memory.