bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cerebro-spinal somatotopic organization uncovered through functional connectivity mapping
Authors: Landelle Caroline , Kinany Nawal , De Leener Benjamin , Murphy Nicholas D. , Lungu Ovidiu , Marchand-Pauvert Véronique , Van De Ville Dimitri , Doyon Julien 
Published: April 2024

AbstractSomatotopy, the topographical arrangement of sensorimotor pathways corresponding to distinct body parts, is a fundamental feature of the human central nervous system (CNS). Traditionally, investigations into brain and spinal cord somatotopy have been conducted independently, primarily utilizing body stimulations or movements. To date, however, no study has probed the somatotopic arrangement of cerebro-spinal functional connectionsin vivoin humans. In this study, we used simultaneous brain and cervical spinal cord functional magnetic resonance imaging (fMRI) to demonstrate how the coordinated activities of these two CNS levels at rest can reveal their shared somatotopy. Using functional connectivity analyses, we mapped preferential correlation patterns between each spinal cord segment and distinct brain regions, revealing a somatotopic gradient within the cortical sensorimotor network. We then validated this large-scale somatotopic organization through a complementary data-driven analysis, where we effectively identified spinal cord segments through the connectivity profiles of their voxels with the sensorimotor cortex. These findings underscore the potential of resting-state cerebro-spinal cord fMRI to probe the large-scale organization of the human sensorimotor system with minimal experimental burden, holding promise for gaining a more comprehensive understanding of normal and impaired somatosensory-motor functions.
Top-down modulation of visual cortical stimulus encoding and gamma independent of firing rates
Authors: Lewis Christopher M. , Wunderle Thomas , Fries Pascal 
Published: April 2024

SummaryNeurons in primary visual cortex integrate sensory input with signals reflecting the animal’s internal state to support flexible behavior. Internal variables, such as expectation, attention, or current goals, are imposed in a top-down manner via extensive feedback projections from higher-order areas. We optogenetically activated a high-order visual area, area 21a, in the lightly anesthetized cat (OptoTD), while recording from neuronal populations in V1. OptoTD induced strong, up to several fold, changes in gamma-band synchronization together with much smaller changes in firing rate, and the two effects showed no correlation. OptoTD effects showed specificity for the features of the simultaneously presented visual stimuli. OptoTD-induced changes in gamma synchronization, but not firing rates, were predictive of simultaneous changes in the amount of encoded stimulus information. Our findings suggest that one important role of top-down signals is to modulate synchronization and the information encoded by populations of sensory neurons.
Cortexa – a comprehensive resource for studying gene expression and alternative splicing in the murine brain
Authors: Weißbach Stephan , Milkovits Jonas , Pastore Stefan , Heine Martin , Gerber Susanne , Todorov Hristo 
Published: April 2024

AbstractMotivationGene expression and alternative splicing are strictly regulated processes that shape brain development and determine the cellular identity of differentiated neural cell populations. Despite the availability of multiple valuable datasets, many functional implications, especially those related to alternative splicing, remain poorly understood. Moreover, neuroscientists working primarily experimentally often lack the bioinformatics expertise required to process alternative splicing data and produce meaningful and interpretable results. Notably, re-analyzing publicly available datasets and integrating them with in-house data can provide substantial novel insights. However, such analyses necessitate devel-oping harmonized data handling and processing pipelines which in turn requires considerable computational resources and in-depth bioinformatics expertise.ResultsHere, we present Cortexa – a comprehensive web-portal that incorporates RNA-sequencing datasets from the mouse cerebral cortex (longitudinal or cell-specific) and the hippocampus. Cortexa facilitates understandable visualization of the expression and alternative splicing patterns of individual genes. Our platform also provides SplicePCA – a tool that allows users to integrate their alternative splicing dataset and compare it to cell-specific or developmental neocortical splicing patterns. All gene expression and alternative splicing data have been processed in a standardized manner and they can also be downloaded for further in-depth down-stream analysis.AvailabilityThe data portal is available athttps://cortexa-rna.com/Contacthristo.todorov@uni-mainz.de.
Comparative analysis based on shared amplicon sequence variants reveals that cohabitation influences gut microbiota sharing between humans and dogs
Authors: Ito Yutaro , Nagasawa Miho , Koyama Kahori , Ito Kohei , Kikusui Takefumi 
Published: April 2024

AbstractIntroductionThe One Health concept is a comprehensive understanding of the interaction between humans, animals, and the environment. The cohabitation of humans and dogs positively affects their physical, mental, and social well-being. It is recognized as an essential factor from the One Health perspective. Furthermore, a healthy balance in the gut microbiome is essential for good health, and the sharing of gut microbes between humans and dogs may positively impact the health of both hosts. Therefore, elucidating the sharing of gut bacteria between humans and dogs is important for understanding One Health. However, most studies have examined sharing at the taxonomic level, and it remains unclear whether the same bacteria are transferred between humans and dogs, and whether they mutually influence each other.MethodsHere, microbiome analysis and 16S rRNA gene amplicon sequence variant (ASV) analysis was performed to address this question.Results16S rRNA gene ASVs analysis indicated that gut microbes have been transferred between humans and dogs. The overall structure of the gut microbiota within human-dog pairs remained unchanged after three months of adaptation. However, some ASVs were shared within human-dog pairs. Many shared ASVs were highly abundant within each host, and this high abundance may be considered a factor that influences bacterial transfer between hosts.DiscussionOur results demonstrate the possibility of the direct transfer of gut bacteria between humans and dogs, providing an important insight for achieving good health through human-dog cohabitation.
Triglyceride metabolism controls inflammation andAPOE4-associated disease states in microglia
Authors: Stephenson Roxan A. , Johnson Kory R. , Cheng Linling , Yang Linda G. , Root Jessica T. , Gopalakrishnan Jaanam , Shih Han-Yu , Narayan Priyanka S. 
Published: April 2024

AbstractMicroglia modulate their cell state in response to various stimuli. Changes to cellular lipids often accompany shifts in microglial cell state, but the functional significance of these metabolic changes remains poorly understood. In human induced pluripotent stem cell-derived microglia, we observed that both extrinsic activation (by lipopolysaccharide treatment) and intrinsic triggers (the Alzheimer’s disease-associatedAPOE4genotype) result in accumulation of triglyceride-rich lipid droplets. We demonstrate that lipid droplet accumulation is not simply concomitant with changes in cell state but rather necessary for microglial activation. We discovered that both triglyceride biosynthesis and catabolism are needed for the transcription and secretion of proinflammatory cytokines and chemokines in response to extrinsic stimuli. Additionally, we reveal that triglyceride biosynthesis and catabolism are necessary for the activation-associated phagocytosis of multiple substrates including the disease-associated amyloid-beta peptide. In microglia harboring the Alzheimer’s disease riskAPOE4genotype, triglyceride-rich lipid droplets accumulate even in the absence of any external stimuli. Inhibiting triglyceride biosynthesis inAPOE4microglia not only modifies the transcription of immune response genes but also attenuates disease-associated transcriptional states. This work establishes that triglyceride metabolism is necessary for microglia to respond to extrinsic activation. InAPOE4microglia, this metabolic process modulates both immune signaling and a disease-associated transcriptional state. Importantly, our work identifies metabolic pathways that can be used to tune microglial immunometabolism inAPOE4-associated disease.
Safety, effectiveness, and skin immune response in a controlled human infection model of sand fly transmitted cutaneous leishmaniasis
Authors: Parkash Vivak , Ashwin Helen , Dey Shoumit , Sadlova Jovana , Vojtkova Barbora , Bocxlaer Katrien Van , Wiggins Rebecca , Thompson David , Dey Nidhi Sharma , Jaffe Charles L. , Schwartz Eli , Volf Petr , Lacey Charles J. N. , Layton Alison M. , Kaye Paul M. 
Published: April 2024

AbstractThe leishmaniases are globally important parasitic diseases for which no human vaccines are currently available. To facilitate vaccine development, we conducted an open label observational study to establish a controlled human infection model of sand fly-transmitted cutaneous leishmaniasis caused byL. major. Between 24thJanuary and 12thAugust 2022, we exposed 14 (8F, 6M) participants to infectedPhlebotomus duboscqi. The primary objective was to demonstrate effectiveness (take rate) and safety (absence of CL lesion at 12 months), whereas secondary and exploratory objectives included rate of lesion development, parasite load and analysis of local immune responses by immunohistology and spatial transcriptomics. We estimated an overall take rate for CL development of 64% (9/14), or 82% (9/11) if calculated using only participants having confirmed bites following exposure. Lesion development was terminated by therapeutic biopsy in 10 participants with confirmed bites. 2/10 had one and 1/10 had two lesion recurrences 4-8 months after biopsy that were treated successfully with cryotherapy. No severe or serious adverse events were recorded, but scarring was evident as expected. All participants were lesion-free at >12 month follow up. We provide the first comprehensive map of immune cell distribution and cytokine/chemokine expression in human CL lesions, revealing discrete immune niches. This controlled human infection model offers opportunities for rapid vaccine candidate selection and a greater understanding of immune-mediated protection and pathology.
COVID19 vaccines as boosters or first doses: Simulating scenarios to minimize infections and deaths
Authors: El Deeb Omar , El Khoury Edde Joseph 
Published: April 2024

AbstractPublic health authorities face the issue of optimal vaccine distribution during spread of pandemics. In this paper, we study the optimal way to distribute a finite stock of COVID-19 doses between first or second doses for unvaccinated individuals and third doses (booster shots) for fully vaccinated individuals. We introduce a novel compartmental model that accommodates for vaccinated populations. This Booster model is implemented to simulate two prototypes of populations: one with a highly infected and highly vaccinated proportion, and another with a low infected and vaccinated percentage. We namely use sample data from Russia and Djibouti respectively.Our findings show that, to minimize the deaths for the first type of populations, around one quarter of the vaccines should be employed as booster shots and the rest as first and second doses. On the other hand, the second type of populations can minimize their number of deaths by mainly focusing on administering the initial two doses, rather than giving any booster shots. The novel Booster model allows us to study the effect of the third dose on a community and provides a useful tool to draw public policies on the distribution of vaccines during pandemics.
Applying the Nova food classification to food product databases using discriminative ingredients: a methodological proposal
Authors: Fagundes Grilo Mariana , Silva Nunes Beatriz , Duran Ana Clara , Zancheta Ricardo Camila , Galastri Baraldi Larissa , Martinez Steele Euridice , Borges Camila Aparecida 
Published: April 2024

AbstractBackgroundGrowing interest in the Nova food classification system surged among various stakeholders, driven primarily by compelling evidence linking the consumption of ultra-processed foods (UPF) to negative health outcomes. However, a more standardized approach could incentivize the identification of UPF in regulatory processes.ObjectiveTo propose replicable methods to identify UPF that, by testing the sensitivity and specificity of these methods using a large sample of packaged foods from the 2017 Brazilian Food Labels Database.MethodsWe created five scenarios to identify UPF using food substances and food additives typically found in UPF and compared them with the most frequently employed Nova food classification process based on the product name and food categories, considered the ‘classic method’ to identify UPF. We estimated the proportion of foods and beverages identified as UPF using different scenarios based on the presence of discriminative ingredients. We used a diagnostic test and a receiver operating characteristic (ROC) to understand which of the five scenarios performed better compared to the ‘classic method’ to identify UPF. Finally, we conducted a sensitivity analysis to test the role of vitamins and minerals in identifying UPF.ResultsWe found variations in UPF prevalence from 47% to 72% across scenarios, compared to 70% using the ‘classic method’ to identify UPF in Brazilian packaged foods. Despite its cautious approach, the scenario using additives of a sole cosmetic function and food byproducts (scenario 3) identified a 65% UPF, while maintaining reasonable sensitivity and specificity, and the best-performing ROC curve. There was no significant difference in identifying UPF when comparing the addition of vitamins and minerals to the food additives with sole cosmetic function.ConclusionOur study sheds light on the importance of detailed criteria to identify UPF and offers the research community a standardized method to identify UPF.
Linking Altered Neuronal and Synaptic Properties to Nicotinic Receptor Alpha5 Subunit Gene Dysfunction: A Translational Investigation in Rat mPFC and Human Cortical Layer 6
Authors: Yang Danqing , Qi Guanxiao , Delev Daniel , Maskos Uwe , Feldmeyer Dirk 
Published: April 2024

AbstractBackgroundGenetic variation in the α5 nicotinic acetylcholine receptor (nAChR) subunit of mice results in behavioral deficits linked to the prefrontal cortex (PFC). A Single Nucleotide Polymorphisms (SNP) in CHRNA5 imparts a partial loss of function to the α5 subunit-containing (α5*) nAChRs and have been demonstrated to be associated with psychiatric disorders in humans, including schizophrenia, nicotine dependence, cocaine and alcohol addiction.MethodsWe performed single cell-electrophysiology combined with morphological reconstructions on layer 6 (L6) excitatory neurons in the medial PFC (mPFC) of wild type (WT) rats (n = 25), rats carrying the human coding polymorphism rs16969968 inChrna5(n = 11) and α5 knockout (KO) rats (n = 28). Neuronal and synaptic properties were compared among three rat genotypes. Galantamine was applied to identified L6 neuron populations to specifically boost the nicotinic responses mediated by α5*nAChRs in the rat mPFC and human neocortex (n = 6 patients).ResultsCompared with neurons in WT rats, L6 regular spiking (RS) neurons in the α5KO group exhibited altered electrophysiological properties, while those in α5SNP rats remained unchanged. L6 RS neurons in mPFC of α5SNP and α5KO rats differed from WT rats in dendritic morphology, spine density and spontaneous synaptic activity. Galantamine acted as a positive allosteric modulator of α5*nAChRs in RS but not burst spiking (BS) neurons in both rat and human cortical L6.ConclusionOur findings suggest that dysfunction in the α5 subunit gene leads to aberrant neuronal and synaptic properties, shedding light on the underlying mechanisms of cognitive deficits observed in human populations carrying α5SNPs. They highlight a potential pharmacological target for restoring the relevant behavioral output.
Complex bacterial diversity of Guaymas Basin hydrothermal sediments revealed by synthetic long-read sequencing (LoopSeq)
Authors: Hinkle John E. , Chanton Jeffrey P. , Moynihan Molly A. , Ruff S. Emil , Teske Andreas 
Published: April 2024

AbstractHydrothermal sediments host phylogenetically diverse and physiologically complex microbial communities. Previous studies of microbial community structure in hydrothermal sediments have typically used short-read sequencing approaches. To improve on these approaches, we use LoopSeq, a high-throughput synthetic long-read sequencing method that has yielded promising results in analyses of microbial ecosystems, such as the human gut microbiome. In this study, LoopSeq is used to obtain near-full length (approximately 1400 - 1500 nucleotides) bacterial 16S rRNA gene sequences from hydrothermal sediments in Guaymas Basin. Based on these sequences, high-quality alignments and phylogenetic analyses provided new insights into previously unrecognized taxonomic diversity of sulfur-cycling microorganisms and their distribution along a lateral hydrothermal gradient. Detailed phylogenies for free-living and syntrophic sulfur-cycling bacterial lineages identified well-supported monophyletic clusters that have implications for the taxonomic classification of these groups. Particularly, we identify clusters withinCandidatusDesulfofervidus that represent unexplored physiological and genomic diversity. In general, LoopSeq-derived 16S rRNA gene sequences aligned consistently with reference sequences in GenBank; however, chimeras were prevalent in sequences as affiliated with the thermophilicCandidatusDesulfofervidus andThermodesulfobacterium, and in smaller numbers within the sulfur-oxidizing familyBeggiatoaceae. Our analysis of sediments along a well-documented thermal and geochemical gradient show how sulfur-cycling bacteria of different taxonomic groups persist as active catalysts of the sulfur cycle throughout surficial hydrothermal sediments in the Guaymas Basin.
Fetal programming by the parental microbiome of offspring behavior, and DNA methylation and gene expression within the hippocampus
Authors: Gustafson Kevin L. , Busi Susheel Bhanu , McAdams Zachary L. , McCorkle Rachael E. , Khodakivskyi Pavlo , Bivens Nathan J. , Davis Daniel J. , Raju Murugesan , Coghill Lyndon M. , Goun Elena A. , Amos-Landgraf James , Franklin Craig L. , Wilmes Paul , Cortese Rene , Ericsson Aaron C. 
Published: April 2024

AbstractBackgroundThe microorganisms colonizing the gastrointestinal tract of animals, collectively referred to as the gut microbiome, affect numerous host behaviors dependent on the central nervous system (CNS). Studies comparing germ-free mice to normally colonized mice have demonstrated influences of the microbiome on anxiety-related behaviors, voluntary activity, and gene expression in the CNS. Additionally, there is epidemiologic evidence supporting an intergenerational influence of the maternal microbiome on neurodevelopment of offspring and behavior later in life. There is limited experimental evidence however directly linking the maternal microbiome to long-term neurodevelopmental outcomes, or knowledge regarding mechanisms responsible for such effects.ResultsHere we show that that the maternal microbiome has a dominant influence on several offspring phenotypes including anxiety-related behavior, voluntary activity, and body weight. Adverse outcomes in offspring were associated with features of the maternal microbiome including bile salt hydrolase activity gene expression (bsh), abundance of certain bile acids, and hepatic expression ofSlc10a1. In cross-foster experiments, offspring resembled their birth dam phenotypically, despite faithful colonization in the postnatal period with the surrogate dam microbiome. Genome-wide methylation analysis of hippocampal DNA identified microbiome- associated differences in methylation of 196 loci in total, 176 of which show conserved profiles between mother and offspring. Further, single-cell transcriptional analysis revealed accompanying differences in expression of several differentially methylated genes within certain hippocampal cell clusters, and vascular expression of genes associated with bile acid transport.Inferred cell-to-cell communication in the hippocampus based on coordinated ligand-receptor expression revealed differences in expression of neuropeptides associated with satiety.ConclusionsCollectively, these data provide proof-of-principle that the maternal gut microbiome has a dominant influence on the neurodevelopment underlying certain offspring behaviors and activities, and selectively affects genome methylation and gene expression in the offspring CNS in conjunction with that neurodevelopment.
High-throughput Tn-seq screens identify both known and novelPseudomonas putidaKT2440 genes involved in metal resistance
Authors: Royet Kevin , Kergoat Laura , Lutz Stefanie , Oriol Charlotte , Parisot Nicolas , Schori Christian , Ahrens Christian H. , Rodrigue Agnes , Gueguen Erwan 
Published: April 2024

AbstractChemical waste with toxic effects is released into the environment by industrial and urban activities.Pseudomonas putida, a rhizosphere bacterium, harbors a wide variety of genes capable of degrading hydrocarbons and xenobiotic compounds in its natural environment. This bacterium harbors also a large set of metal resistance genes. Most studies that identify genes involved in metal resistance inP. putidafocus on over/underexpressed genes and may miss other genes important for metal resistance whose expression does not change. In this study, we used a Tn-seq approach to determine the essential genome ofP. putidarequired for growth in the presence of an excess of metals in a culture medium. Tn-seq enables the detection of mutants with reduced or increased fitness in the presence of metal excess. We validated our screen by identifying known metal resistance gene such asczcA-1(PP_0043),cadA-3(PP_5139),cadR(PP_5140) andpcoA2(PP_5380). Their mutants were underrepresented in the presence of zinc, cadmium (forcadA-3andcadR) or copper respectively. In this study, we demonstrate by targeted mutagenesis and complementation assay thatPP_5337andPP_0887are putative transcriptional regulators involved in copper and cadmium resistance, respectively, inP. putida. The study revealed the role of two genes,PP_1663andPP_5002, in cadmium and cobalt resistance respectively. This is the first evidence linking these genes to metal resistance and highlights the incomplete understanding of metal resistance mechanisms inP. putida.