bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chronic social defeat stress induces a depression-relevant outcome in male prairie voles
Authors: Rodriguez Minerva , Themann Anapaula , Garcia-Carachure Israel , Lira Omar , Robison Alfred J. , Cushing Bruce S. , Iñiguez Sergio D. 
Published: October 2023

AbstractBackgroundStress-induced illnesses, like major depression, are among the leading causes of disability across the world. Consequently, there is a dire need for the validation of translationally-suited animal models incorporating social stress to uncover the etiology of depression. Prairie voles (Microtus ochrogaster) are more translationally relevant than many other rodent models as they display monogamous social and parental behaviors and more primate-like neuroanatomy. Therefore, we evaluated whether a novel social defeat stress (SDS) model in male prairie voles induces depression-relevant behavioral outcomes.MethodsAdult sexually-naïve male prairie voles experienced SDS bouts from a conspecific pair-bonded male aggressor, 10 min per day for 10 consecutive days. Non-stressed controls (same-sex siblings) were housed in similar conditions but never experienced physical stress. Twenty-four hr later, voles were evaluated in social interaction, sucrose preference, and Morris water maze tests – behavioral endpoints validated to assess social withdrawal, anhedonia-related behavior, and spatial memory performance, respectively.ResultsSDS-exposed voles displayed lower sociability and body weight, decreased preference for a sucrose solution, and impairment of spatial memory retrieval. Importantly, no differences in general locomotor activity were observed as a function of SDS exposure.LimitationsThis study does not include female voles in the experimental design.ConclusionsWe found that repeated SDS exposure, in male prairie voles, results in a depression-relevant phenotype resembling an anhedonia-like outcome (per reductions in sucrose preference) along with social withdrawal and spatial memory impairment – highlighting that the prairie vole is a valuable model with potential to study the neurobiology of social stress-induced depression-related outcomes.
MACROPHAGES COORDINATE IMMUNE RESPONSE TO LASER-INDUCED INJURY VIA EXTRACELLULAR TRAPS
Authors: Conedera Federica M. , Kokona Despina , Zinkernagel Martin S. , Stein Jens V. , Alt Clemens , Enzmann Volker , Lin Charles P. 
Published: October 2023

ABSTRACTMacrophages/monocytes, the primary contributors to chronic inflammation in degenerated retinas, orchestrate intricate immune responses. They remain enigmatic in their local coordination and activation mechanisms. Innovations in experimental systems enable real-time exploration of immune cell interactions and temporal dimensions in response. In preclinical mouse models, we usein vivomicroscopy to unravel how macrophages/monocytes govern microglia and PL responses spatio-temporally.Our findings underscore the pivotal role of innate immune cells, especially macrophages/monocytes, in regulating retinal repair. The absence of neutrophil and macrophage infiltration aids parenchymal integrity restoration, while their depletion, particularly macrophages/monocytes, impedes vascular recovery. Innate immune cells, when activated, release chromatin and granular proteins, forming extracellular traps (ETs), critical for tissue repair by modulating neutrophil and T-cell responses.Our investigations demonstrate that pharmacological inhibition of ETosis with Cl-amidine enhances retinal and vascular repair, surpassing the effects of blocking innate immune cell recruitment. Simultaneously, Cl-amidine treatment reshapes the inflammatory response, causing neutrophils, helper, and cytotoxic T-cells to cluster primarily in the superficial capillary plexus, affecting retinal microvasculature perfusion. Our data offer novel insights into innate immunity’s role in responding to retinal damage, potentially informing more effective immunotherapeutic strategies for neurodegenerative diseases.
The breath shape controls intonation of mouse vocalizations
Authors: MacDonald Alastair , Hebling Alina , Wei Xin Paul , Yackle Kevin 
Published: October 2023

AbstractIntonation in speech is the control of vocal pitch to layer expressive meaning to communication, like increasing pitch to indicate a question. Also, stereotyped patterns of pitch are used to create distinct sounds with different denotations, like in tonal languages and, perhaps, the ten sounds in the murine lexicon. A basic tone is created by exhalation through a constricted laryngeal voice box, and it is thought that more complex utterances are produced solely by dynamic changes in laryngeal tension. But perhaps, the shifting pitch also results from altering the swiftness of exhalation. Consistent with the latter model, we describe that intonation in most vocalization types follows deviations in exhalation that appear to be generated by the re-activation of the cardinal breathing muscle for inspiration. We also show that the brainstem vocalization central pattern generator, the iRO, can create this breath pattern. Consequently, ectopic activation of the iRO not only induces phonation, but also the pitch patterns that compose most of the vocalizations in the murine lexicon. These results reveal a novel brainstem mechanism for intonation.
Surface Generative Modelling of Neurodevelopmental Trajectories
Authors: Fawaz Abdulah , Masui Saga N. B. , Williams Logan Z. J. , Dahan Simon , Edwards A. David , Robinson Emma C. 
Published: October 2023

AbstractCortical neurodevelopment is sensitive to disruption following preterm birth, with lasting impact on cognitive outcomes. The creation of generative models of neurodevelopment could aid clinicians in identifying atrisk subjects but is complicated by the degree of subject variability in cortical folding, and significant heterogeneity in the effect of preterm birth. In this work, we propose a graph convolutional generative adversarial network (GAN) and a training scheme to simulate neonatal cortical surface developmental trajectories. The proposed model is used to smoothly modify two cortical phenotypes: post-menstrual age at scan (PMA) and gestational age at birth (GA) on data from the developing Human Connectome Project (dHCP) [1]. The synthetic images were validated with an independently trained regression network, and compared against follow up scans, indicating that the model can realistically age individuals whilst preserving subject-specific cortical morphology. Deviation between simulated ‘healthy’ scans, and preterm follow up scans generated a metric of individual atypicality, which improved prediction of 18-month cognitive outcome over GA alone.
Learning enhances representations of taste-guided decisions in the mouse gustatory insular cortex
Authors: Kogan Joshua F. , Fontanini Alfredo 
Published: October 2023

SUMMARYLearning to discriminate overlapping gustatory stimuli that predict distinct outcomes – a feat known as discrimination learning – can mean the difference between ingesting a poison or a nutritive meal. Despite the obvious importance of this process, very little is known on the neural basis of taste discrimination learning. In other sensory modalities, this form of learning can be mediated by either sharpening of sensory representations, or enhanced ability of “decision-making” circuits to interpret sensory information. Given the dual role of the gustatory insular cortex (GC) in encoding both sensory and decision-related variables, this region represents an ideal site for investigating how neural activity changes as animals learn a novel taste discrimination.Here we present results from experiments relying on two photon calcium imaging of GC neural activity in mice performing a taste-guided mixture discrimination task. The task allows for recording of neural activity before and after learning induced by training mice to discriminate increasingly similar pairs of taste mixtures. Single neuron and population analyses show a time-varying pattern of activity, with early sensory responses emerging after taste delivery and binary, choice encoding responses emerging later in the delay before a decision is made. Our results demonstrate that while both sensory and decision-related information is encoded by GC in the context of a taste mixture discrimination task, learning and improved performance are associated with a specific enhancement of decision-related responses.
Revisiting Hox gene evolution and Hox cluster linkage across Nematoda
Authors: Kirangwa Joseph , Laetsch Dominik R , King Erna , Stevens Lewis , Blaxter Mark , Holovachov Oleksandr , Schiffer Philipp 
Published: October 2023

ABSTRACTHox genes are central to metazoan body plan formation, patterning and evolution, playing a critical role in cell fate decisions early in embryonic development in invertebrates and vertebrates. While the archetypical Hox gene cluster consists of members of nine ortholog groups (HOX1-HOX9), arrayed in close linkage in the order in which they have their anterior-posterior patterning effects, nematode Hox gene sets do not fit this model. TheCaenorhabditis elegansHox gene set is not clustered and contains only six Hox genes from four of the ancestral groups. The pattern observed inC. elegansis not typical of the phylum, and variation in orthologue set presence and absence and in genomic organisation has been reported. Recent advances in genome sequencing have resulted in the availability of many novel genome assemblies in Nematoda, especially from taxonomic groups that had not been analysed previously. Here, we explored Hox gene complements in high-quality genomes of 80 species from all major clades of Nematoda to understand the evolution of this key set of body pattern genes and especially to probe the origins of the “dispersed” cluster observed inC. elegans. We also included the recently available high-quality genomes of some Nematomorpha as an outgroup. We find that nematodes can have Hox genes from up to six orthology groups. While nematode Hox “clusters” are often interrupted by unrelated genes we identify species in which the cluster is intact and not dispersed.
Chst9Marks a Spatially and Transcriptionally Unique Population ofOprm1-Expressing Neurons in the Nucleus Accumbens
Authors: Andraka Emma , Phillips Robert A. , Brida Kasey L. , Day Jeremy J. 
Published: October 2023

SummaryOpioids produce addictive, analgesic, and euphoric effects via actions at mu opioid receptors (μORs). The μOR is encoded by theOprm1gene and is expressed in multiple brain regions that regulate reward and motivation, such as the nucleus accumbens (NAc).Oprm1expression in NAc medium spiny neurons (MSNs) mediates opioid place preference, seeking, and consumption. However, recent single nucleus RNA sequencing (snRNA-seq) studies in rodent, primate, and human NAc have revealed that multiple subpopulations of NAc neurons expressOprm1mRNA, making it unclear which populations mediate diverse behaviors resulting from μOR activation. Using published snRNA-seq datasets from the rat NAc, we identified a novel population of MSNs that express the highest levels ofOprm1of any NAc cell type. Here, we show that this population is selectively marked by expression ofChst9, a gene encoding a carbohydrate sulfotransferase. To validate this observation and characterize spatial localization of this population in the rat NAc, we performed multiplexed RNAscope fluorescencein situhybridization studies to detect expression ofOprm1andChst9mRNA along with well-validated markers of MSNs. Notably,Chst9+ neurons exhibited more abundant expression ofOprm1as compared to other cell types, and formed discrete cellular clusters along the medial and ventral borders of the NAc shell subregion. Moreover,CHST9mRNA was also found to mark specific MSN populations in published human and primate snRNA-seq studies, indicating that this unique population may be conserved across species. Together, these results identify a spatially and transcriptionally distinct NAc neuron population characterized by the expression ofChst9. The abundant expression ofOprm1in this population and the conservation of these cells across species suggests that they may play a key functional role in opioid response and identify this subpopulation as a target for further investigation.
A tale of two phage tails: Engineering the host range of bacteriophages infectingClostridioides difficile
Authors: Steczynska Joanna P. , Kerr Sarah J. , Kelly Michelle L. , Whittle Michaella J. , Bilverstone Terry W. , Minton Nigel P. 
Published: October 2023

AbstractClostridioides difficileinfection (CDI) is a leading cause of antibiotic-associated diarrhoea across the globe. Although treatable with a restricted number of antibiotics, the emergence of resistant variants and high relapse rates necessitate alternative countermeasures. Phage therapy represents an attractive option. However, its implementation is handicapped by the narrow host specificity of theC. difficilebacteriophages isolated to date. One strategy to rationally expand phage host range would be to make appropriate modifications to the phage receptor binding protein (RBP). Here, we identify the tail fibre as the RBP of twoMyoviridaephages, ΦCD1801 and ΦCD2301, which were previously isolated and propagated using theC. difficilestrains CD1801 (RT078) and CD2301 (RT014), respectively. Contrary to studies into reprogramming the host ranges of phage of other bacterial other species, exchanging the tail fibre genes (tcf/tfp) alone between the two phage was insufficient to change host specificity. Rather, alterations to host range were dependent their exchange together with a putative chaperone encoded byhyp, localised adjacent to the tail fibre gene. Capitalising on this discovery, CRISPR/Cas9 was used to change the host range of one phage to that of the other by swapping the respectivetcf/tfpandhypgenes. Significantly, one of the resulting mutants, surpassed both parental phages in terms of host range and efficiency of infection. This is the first time that genome engineering has successfully expanded the host range of aC. difficilephage, a prerequisite for implementing phage for the treatment of CDI.ImportanceAlternatives to antibiotics for treatingClostridioides difficileinfection (CDI) are urgently required. Phage therapy presents an attractive option as it has the potential to clear the infection with minimal microbiome disruption and eliminate the possibility of recurrence. However, theC. difficilebacteriophages isolated to date have highly restricted host ranges. Moreover, rational strategies to alter specificity have till now been precluded as the identity of the phage receptor binding proteins involved was largely unknown. Here, we demonstrated that tail fibre proteins and an associated putative chaperone determine the host range of twoMyoviridaephage. This enabled the alteration of specificity through CRISPR-mediated genome editing and the creation of a phage derivative with a host range and infection efficiency exceeding that of the parental phages. This is the first time that the host range of aC. difficilephage has been successfully expanded through rational genome engineering.
Exhaustive search for DNA binding sites ofBasillus subtilistranscription factor YsiA by KaScape method
Authors: Huang Bing-yao , Huang Mia , Chen Hong , Su Xiao-dong 
Published: October 2023

AbstractBasillus subtilis(B. subtilis) YsiA is also known as FadR is a pre-formed dimeric repressor to regulate fatty acid degradation. However, the knowledge about double-stranded DNA(dsDNA) binding sites of YsiA in the whole genome level is limited so far. In this report, we have applied a newly established high-throughput method, KaScape, to exhaustively study the relative binding sites and energy landscape of YsiA and confirmed the resuls with gel-shift experiments. We’ve found that half-binding site is enough for YsiA to bind with dsDNA. Besides detecting the known consensus sequence which is bound by YsiA, we have also detected other minor binding site sequences through the KaScape method. It thus demonstrates that KaScape can be used to study dimeric transcription factors (TFs) in general.
Adaptive modeling and inference of higher-order coordination in neuronal assemblies: a dynamic greedy estimation approach
Authors: Mukherjee Shoutik , Babadi Behtash 
Published: October 2023

AbstractCentral in the study of population codes, coordinated ensemble spiking activity is widely observable in neural recordings with hypothesized roles in robust stimulus representation, interareal communication, and learning and memory formation. Model-free measures of synchrony characterize coherent pairwise activity but not higher-order interactions, a limitation transcended by statistical models of ensemble spiking activity. However, existing model-based analyses often impose assumptions about the relevance of higher-order interactions and require repeated trials to characterize dynamics in the correlational structure of ensemble activity. To address these shortcomings, we propose an adaptive greedy filtering algorithm based on a discretized mark point-process model of ensemble spiking and a corresponding statistical inference framework to identify significant higher-order coordination. In the course of developing a precise statistical test, we show that confidence intervals can be constructed for greedily estimated parameters. We demonstrate the utility of our proposed methods on simulated neuronal assemblies. Applied to multi-electrode recordings from human and rat cortical assemblies, our proposed methods provide new insights into the dynamics underlying localized population activity during transitions between brain states.Author summarySimultaneous ensemble spiking is hypothesized to have important roles in neural encoding; however, neurons can also spike simultaneously by chance. In order to characterize the potentially time-varying higher-order correlational structure of ensemble spiking, we propose an adaptive greedy filtering algorithm that estimates the rate of all reliably-occurring simultaneous ensemble spiking events. Moreover, we propose an accompanying statistical inference framework to distinguish the chance occurrence of simultaneous spiking events from coordinated higher-order spiking. We demonstrate the proposed methods accurately differentiate coordinated simultaneous spiking from chance occurrences in simulated data. In application to human and rat cortical data, the proposed methods reveal time-varying dynamics in higher-order coordination that coincide with changing brain states.
HIV incidence among women engaging in sex work in sub-Saharan Africa: a systematic review and meta-analysis
Authors: Jones Harriet S , Anderson Rebecca L , Cust Henry , McClelland R. Scott , Richardson Barbra A. , Thirumurthy Harsha , Malama Kalonde , Hensen Bernadette , Platt Lucy , Rice Brian , Cowan Frances M , Imai-Eaton Jeffrey W. , Hargreaves James R , Stevens Oliver 
Published: October 2023

AbstractIntroductionHIV incidence among women in sub-Saharan Africa (SSA) has declined steadily, but it is unknown whether new infections among women who engage in sex work (WESW) have declined at a similar rate. We synthesised estimates of HIV incidence among WESW in SSA and compared these to the wider female population to understand levels and trends in incidence over time.MethodsWe searched Medline, Embase, Global Health, Popline, Web of Science, and Google Scholar from January 1990 to October 2022, and grey literature for estimates of HIV incidence among WESW in SSA. We included studies reporting empirical estimates in any SSA country. We calculated incidence rate ratios (IRR) compared to age-district-year matched total female population incidence estimates. We conducted a meta-analysis of IRRs and used a continuous mixed-effects model to estimate changes in IRR over time.ResultsFrom 32 studies between 1985 and 2020, 2,194 new HIV infections were observed in WESW over 51,000 person-years (py). Median HIV incidence was 4.3/100py (IQR 2.8-7.0/100py), declining from a median of 5.96/100py between 1985 and 1995 to a median of 3.2/100py between 2010 and 2020. Incidence among WESW was nine times higher than in matched total population women (RR 8.6, 95%CI: 5.7-12.9), and greater in Western and Central Africa (RR 22.4, 95%CI: 11.3-44.3) than in Eastern and Southern Africa (RR 5.3, 95%CI: 3.7–7.6). Annual changes in log IRRs were minimal (–0.1% 95%CI: −6.9 to +6.8%).ConclusionsAcross SSA, HIV incidence among WESW remains disproportionately high compared to the total female population but showed similar rates of decline between 1990 and 2020. Improved surveillance and standardisation of approaches to obtain empirical estimates of sex worker incidence would enable a clearer understanding of whether we are on track to meet global targets for this population and better support data-driven HIV prevention programming.
Understanding and Predicting Polycystic Ovary Syndrome through Shared Genetics with Testosterone, SHBG, and Chronic Inflammation
Authors: Petersen Lillian Kay , Brixi Garyk , Li Jun , Hu Jie , Wang Zicheng , Han Xikun , Meir Anat Yaskolka , Tyrmi Jaakko , Mahalingaiah Shruthi , Piltonen Terhi , Liang Liming 
Published: October 2023

AbstractPolycystic ovary syndrome (PCOS) is a common hormonal disorder that affects one out of eight women and has high metabolic and psychological comorbidities. PCOS is thought to be associated with increased systemic low-grade inflammation, but the underlying mechanisms remain unclear. Here we study the genetic relationship between PCOS and obesity, testosterone, sex hormone binding globulin (SHBG), and chronic inflammation. First we create a large meta-analysis of PCOS (7,747 PCOS cases and 498,227 controls) and identify four novel genetic loci associated with PCOS. These novel loci have been previously associated with changes in gene expression in multiple tissues including the thyroid and ovary. We then analyze the PCOS meta analysis alongside GWASs for obesity (n=681,275), SHBG (n=190,366), testosterone (n=176,687), and meta-analyses of 130 inflammatory biomarkers (average n=30,000). We replicate potential causal relationships (via Mendelian randomization) from obesity and SHBG to PCOS and find extensive genetic correlations and causality between these traits and inflammatory biomarkers. We identify significant genetic correlations between PCOS and eight inflammatory biomarkers, including new relationships such as a strong correlation to death receptor 5 (LDSC rg = 0.54, FDR = 0.043). Although these results point to a shared genetic architecture between PCOS and inflammation, we did not find statistically significant causality between them; however, we did find 27 inflammatory biomarkers with significant causal effects on SHBG and four biomarkers with significant causal effects on testosterone. These results support the hypothesis that chronic inflammation can influence androgen and SHBG levels, though more research is needed to verify these results. Finally, we show that combining the polygenic risk scores of PCOS-related traits improves genetic prediction of PCOS cases in the UK Biobank and MGB Biobank compared to using only PCOS risk scores (0.72 AUC from 0.59 AUC and 0.61 AUC from 0.59 AUC in each biobank respectively).