bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptomic Signatures of WNT-Driven Pathways and Granulosa Cell-Oocyte Interactions during Primordial Follicle Activation
Authors: Takase Hinako M. , Mishina Tappei , Hayashi Tetsutaro , Yoshimura Mika , Kuse Mariko , Nikaido Itoshi , Kitajima Tomoya S. 
Published: February 2024

AbstractPrimordial follicle activation (PFA) is a pivotal event in female reproductive biology, coordinating the transition from quiescent to growing follicles. This study employed comprehensive single-cell RNA sequencing to gain insights into the detailed regulatory mechanisms governing the synchronized dormancy and activation between granulosa cells (GCs) and oocytes with the progression of the PFA process.Wntless(Wls) conditional knockout (cKO) mice served as a unique model, suppressing the transition from pre-GCs to GCs, and disrupting somatic cell-derived WNT signaling in the ovary. Our data revealed immediate transcriptomic changes in GCs post-PFA inWlscKO mice, leading to a divergent trajectory, while oocytes exhibited modest transcriptomic alterations. Subpopulation analysis identified the molecular pathways affected by WNT signaling on GC maturation, along with specific gene signatures linked to dormant and activated oocytes. Despite minimal evidence of continuous up-regulation of dormancy-related genes in oocytes, the loss of WNT signaling in (pre-)GCs impacted gene expression in oocytes even before PFA, subsequently influencing them globally. The infertility observed inWlscKO mice was attributed to compromised GC-oocyte molecular crosstalk and the microenvironment for oocytes. Our study highlights the pivotal role of the WNT-signaling pathway and its molecular signature, emphasizing the importance of intercellular crosstalk between (pre-)GCs and oocytes in orchestrating folliculogenesis.Author summaryIn mammalian ovaries, primordial follicles protect dormant oocytes from wasteful consumption. We explored the complex molecular dynamics of the critical process of primordial follicle activation (PFA) that underlies female reproductive health, with a focus on the role of WNT signaling. By utilizing a unique mouse model with disrupted WNT signaling, our study reveals novel insights into the regulatory dynamics of granulosa cells (GCs) and oocytes during PFA. Single-cell transcriptome profiling uncovered distinct cell populations and highlighted the impact of WNT signaling on ovarian cell types. This study reveals distinct transcriptomic changes in GCs post-PFA, which affects their differentiation trajectories and highlights the critical role of WNT signaling in establishing GC function. We further examined the consequences of disrupted microenvironments on oocytes and GC-oocyte interactions, which elucidated altered oocyte subclusters and potential links to infertility. These findings provide a foundation for understanding the connections between WNT signaling and ovarian function. Our comprehensive analysis contributes valuable knowledge to reproductive biology, emphasizing the clinical relevance of WNT signaling in female fertility.
Exploring the impact of interthalamic adhesion on human cognition: insights from healthy subjects and thalamic stroke patients
Authors: Vidal Julie P. , Rachita Kévin , Servais Anaïs , Péran Patrice , Pariente Jérémie , Bonneville Fabrice , Albucher Jean-François , Danet Lola , Barbeau Emmanuel J. 
Published: February 2024

AbstractBackground and ObjectivesInterthalamic adhesion (IA), also known as the massa intermedia, is a structure that connects the median borders of both thalami across the third ventricle. Given it is difficult to identify on routine neuroimaging, its anatomical variants and function remain poorly studied. The main objective of this study was to clarify the role of IA on cognition. Our main hypothesis was that thalamus stroke patientswithan IA would show better performance on neuropsychological tests than individualswithoutan IA through possible compensatory mechanisms.MethodsThe study comprised a group of healthy subjects and a cohort of patients with isolated thalamic strokes at the chronic stage. All participants underwent 3T research T1w and FLAIR MRI as well as a neuropsychological assessment. The presence or absence of an IA and type of IA anatomical variant were evaluated by two independent reviewers.Results42 healthy subjects (mean age= 49) and 40 patients (mean age= 51) were finally included. 76% of participants had an IA, with a higher prevalence among women (92%) than men (61%). The presence or absence of an IA did not effect the neuropsychological performance of healthy subjects nor did the type of IA variant. Across all the tests, patientswithan IA (n = 18) showed the lowest BF10(157) while thosewithoutan IA (n = 10) exhibited the highest BF10(10648) when compared to healthy subjects using a Bayesian rmANOVA. More specifically, patientswithoutan IA performed more poorly in the verbal memory or Stroop task versus healthy subjects than patientswithan IA. This effect was not explained by age, laterality of the infarct, volume or, localization of the lesion. Patients with an IA and lesions extending into the IA presented a similar trend to non-IA subjects which could however be explained by a greater volume of lesions.DiscussionIA does not appear to have a major role in cognition for healthy subjects but could play a compensatory part in patients with thalamic lesions.
Community density patterns estimated by species distribution modeling: the case study of an insect virus interaction
Authors: Dupas Stéphane , Zeddam Jean-Louis , Orbe Katherine , Gloria Patricia Barrera Cubillos , Villamizar Laura Fernanda , Mora Patricia , Suquillo Jovanni , Dangles Olivier , Lopez-Avilla Aristóbulo , Cotes-Prado Alba-Marina , Silvain Jean-Francois 
Published: February 2024

AbstractTime delays complicates the analysis of trophic dependence, which requires large time series data to study local associations.Here we propose using species distribution modeling. This approach removes confounding time lag effects and allows using data obtained separately in the different species.Since the approach is correlative, it cannot be interpreted in terms of causality.We apply the method to the interaction between the invasive potato moth Tecia solanivora and its granulovirus PhoGV in the Northern Andes. Host density was analyzed based on 1206 pheromone trap data from 106 sampled sites in Ecuador, Colombia and Venezuela. Virus prevalence was evaluated in 15 localities from 3 regions in Ecuador and Colombia. glm models were optimized for both variables on bioclimatic variables. Predicted virus prevalence was not significantly correlated to host density in the sampled virus sites. Across the climatic range covered by the study, correlation was R=−0.053. Of the total population of insect in this range, 26% were expected to be infected.Infection status was also analyzed for spatial structure at different scales: storage bag, storage room, field, locality, country. Locality and storage bag explained respectively 8% and 26% of the total deviance in infection status in glm analysis. Field and storage structure differed within locality but not always in the same direction.This basic method may help studying statistical relationships between species density across a number of trophic models making use of existing non sympatric data, with none or limited additional sampling effort.
PLA-complexity ofk-mer multisets
Authors: Abrar Md. Hasin , Medvedev Paul 
Published: February 2024

AbstractMotivationUnderstanding structural properties ofk-mer multisets is crucial to designing space-efficient indices to query them. A potentially novel source of structure can be found in the rank function of ak-mer multiset. In particular, the rank function of ak-mer multiset can be approximated by a piece-wise linear function with very few segments. Such an approximation was shown to speed up suffix array queries and sequence alignment. However, a more comprehensive study of the structure of rank functions ofk-mer multisets and their potential applications is lacking.ResultsWe study a measure of ak-mer multiset complexity, which we call the PLA-complexity. The PLA-complexity is the number of segments necessary to approximate the rank function of ak-mer multiset with a piece-wise linear function so that the maximum error is bounded by a predefined threshold. We describe, implement, and evaluate the PLA-index, which is able to construct, compact, and query a piece-wise linear approximation of thek-mer rank function. We examine the PLA-complexity of more than 500 genome spectra and several other genomic multisets. Finally, we show how the PLA-index can be applied to several downstream applications to improve on existing methods: speeding up suffix array queries, decreasing the index memory of a short-read aligner, and decreasing the space of a direct access table ofk-mer ranks.AvailabilityThe software and reproducibility information is freely available athttps://github.com/medvedevgroup/pla-index
Related PP2C phosphatases Pic3 and Pic12 negatively regulate immunity in tomato toPseudomonas syringae
Authors: Xia Fan , Zhang Ning , Smith Renee E. , Chakraborty Joydeep , Sobol Guy , Tang Xuemei , Fei Zhangjun , Sessa Guido , Martin Gregory B. 
Published: February 2024

AbstractType 2C protein phosphatases (PP2Cs) constitute a large family in most plant species but relatively few of them have been implicated in immunity. To identify and characterize PP2C phosphatases that affect tomato immunity, we used CRISPR/Cas9 to generate loss-of-function mutations in 11 PP2C-encoding genes whose expression is altered in response to immune elicitors or pathogens. We report that two closely related PP2C phosphatases, Pic3 and Pic12, are involved in regulating resistance to the bacterial pathogenPseudomonas syringaepv.tomato(Pst). Loss-of-function mutations inPic3lead to enhanced resistance toPstin older but not younger leaves, whereas such mutations inPic12resulted in enhanced resistance in both older and younger leaves. Overexpression of Pic3 and Pic12 proteins in leaves ofNicotiana benthamianainhibited resistance toPstand this effect was dependent on Pic3/12 phosphatase activity and an N-terminal palmitoylation motif associated with localization to the cell periphery. Pic3 but not Pic12 had a slight negative effect on flagellin-associated reactive oxygen species generation, although their involvement in the response toPstappeared independent of flagellin. RNA-sequencing analysis of Rio Grande (RG)-PtoR wild-type plants and two independent RG-pic3 mutants revealed that the enhanced disease resistance in RG-pic3 older leaves is associated with increased transcript abundance of multiple defense related genes. RG-pic3/RG-pic12 double mutant plants exhibited stronger disease resistance than RG-pic3 or RG-pic12 single mutants. Together, our results reveal that Pic3 and Pic12 negatively regulate tomato immunity in an additive manner through flagellin-independent pathways.
Microsporidian coinfection reduces fitness of a fungal pathogen due to rapid host mortality
Authors: Dziuba Marcin K. , McIntire Kristina M. , Davenport Elizabeth S. , Baird Emma , Huerta Cristian , Jaye Riley , Corcoran Fiona , McCreadie Paige , Nelson Taleah , Duffy Meghan A. 
Published: February 2024

AbstractInfection outcomes can be strongly context-dependent, shifting a host-symbiont relationship along a parasitism-mutualism continuum. Numerous studies show that under stressful conditions, symbionts that are typically mutualistic can become parasitic. The reverse possibility – a parasite becoming mutualistic – has received much less study. We investigated whether the parasitic microsporidiumOrdospora pajuniican become beneficial for its hostDaphnia dentiferain the presence of the more virulent fungal pathogenMetschnikowia bicuspidata. We found that, even though infection withO. pajuniireduces the frequency of penetration ofM. bicuspidataspores into the host body cavity, it does not improve the survival or reproduction of the host; conversely, coinfection increased the mortality ofDaphnia. However, the shorter lifespan of coinfected hosts disrupted the life cycle ofM. bicuspidata, greatly reducing its fitness. Thus, coinfection with both pathogens was detrimental to the host at the individual level, but might be beneficial for the host population as a result of greatly reduced production ofM. bicuspidataspores. If so, this would mean thatO. pajuniioutbreaks should delay or preventM. bicuspidataoutbreaks. In support of this, in an analysis of dynamics of naturally occurring outbreaks in two lakes where these pathogens co-occur, we found a time lag in occurrence betweenO. pajuniiandM. bicuspidata, withM. bicuspidataepidemics only occurring after the collapse ofO. pajuniiepidemics. Thus, these results suggest that the interaction between co-occurring symbionts – and the net impact of a symbiont on a host – might be qualitatively different at different scales.ImportanceUnderstanding the factors that modify infection probability and virulence is crucial for identifying the drivers of infection outbreaks and modeling disease epidemic progression, and increases our ability to control diseases and reduce the harm they cause. One factor that can strongly influence infection probability and virulence is the presence of other pathogens. However, while coexposures and coinfections are incredibly common, we still have only a limited understanding of how pathogen interactions alter infection outcomes, or whether their impacts are scale-dependent. We used a system of one host and two pathogens to show that sequential coinfection can have a tremendous impact on the host and on the infecting pathogens, and that the outcome of (co-)infection can be negative or positive depending on the focal organization level.
Spatial Multi-Omics Connect SHROOM3 and COL18A1 in Chronic Kidney Disease
Authors: Gaheer Pukhraj S. , Uppal Nikhil , Paul Amy , Mohammadi-Shemirani Pedrum , Perrot Nicolas , Paré Guillaume , Bridgewater Darren , Lanktree Matthew B. 
Published: February 2024

AbstractShroom Family Member 3 (SHROOM3)encodes an actin-binding protein that impacts kidney development. Genome-wide association studies (GWAS) identified CKD-associated common variants aroundSHROOM3andShroom3knock-out mice develop glomerular abnormalities. We sought to evaluate the impact of genetically predictedSHROOM3expression on kidney traits and the circulating proteome, and validate findings in a mouse model. Genetic instruments forSHROOM3expression in distinct kidney compartments (glomerular n=240, tubulointerstitial n=311) were constructed using single cell sequencing data from NephQTL2. Using two-sample Mendelian randomization, we evaluated the effects of glomerular and tubulointerstitialSHROOM3expression on kidney traits and the concentration of 1,463 plasma proteins in the UK Biobank and CKDGen Consortium. Genetically predicted tubulointerstitialSHROOM3expression colocalized with the genetic signals for eGFR and albuminuria. A 34% reduction in genetically predicted tubulointerstitialSHROOM3expression was associated with a 0.3% increase in cross-sectional eGFR (P= 6.8×10-4), a 1.5% increase in albuminuria (P= 0.01), and a 2.2% reduction in plasma COL18A1 concentration (P= 1.2×10-5). In contrast, genetically predicted glomerularSHROOM3expression showed neither colocalization nor significant Mendelian randomization results. Using immunofluorescence, heterozygousShroom3knockout mice had a concordant reduction of Col18a1 in their kidneys, primarily around the tubules. Thus, reduced tubulointerstitialSHROOM3expression, but not glomerular, is associated with increased cross-sectional eGFR, increased uACR, and reduced plasma COL18A1 andShroom3knockout leads to reduced kidney Col18a1, agnostically linkingSHROOM3andCOL18A1in CKD pathogenesis.Lay SummaryTheSHROOM3gene is consistently linked to kidney disease, but we have yet to fully understand why. We looked at how genetic changes affectingSHROOM3impact different regions of the kidney. We found that lessSHROOM3in kidney tubules led to increased kidney filtration, but also increased leakage of protein into the urine. After looking at over 1000 proteins, we identified a new link betweenSHROOM3and a collagen protein called COL18A1. We then confirmed the link between SHROOM3 and COL18A1 by imaging the kidneys of mice designed to have less SHROOM3. Our results suggest an interaction of SHROOM3 and COL18A1 leads to increased pressure on the kidney filtration system.
A platform for brain network sensing and stimulation with quantitative behavioral tracking: Application to limbic circuit epilepsy
Authors: Kremen Vaclav , Sladky Vladimir , Mivalt Filip , Gregg Nicholas M. , Balzekas Irena , Marks Victoria , Brinkmann Benjamin H. , Lundstrom Brian Nils , Cui Jie , St Louis Erik K. , Croarkin Paul , Alden Eva C , Fields Julie , Crockett Karla , Adolf Jindrich , Bilderbeek Jordan , Hermes Dora , Messina Steven , Miller Kai J. , Van Gompel Jamie , Denison Timothy , Worrell Gregory A. 
Published: February 2024

AbstractTemporal lobe epilepsy is a common neurological disease characterized by recurrent seizures. These seizures often originate from limbic networks and people also experience chronic comorbidities related to memory, mood, and sleep (MMS). Deep brain stimulation targeting the anterior nucleus of the thalamus (ANT-DBS) is a proven therapy, but the optimal stimulation parameters remain unclear. We developed a neurotechnology platform for tracking seizures and MMS to enable data streaming between an investigational brain sensing-stimulation implant, mobile devices, and a cloud environment. Artificial Intelligence algorithms provided accurate catalogs of seizures, interictal epileptiform spikes, and wake-sleep brain states. Remotely administered memory and mood assessments were used to densely sample cognitive and behavioral response during ANT-DBS. We evaluated the efficacy of low-frequency versus high-frequency ANT-DBS. They both reduced seizures, but low-frequency ANT-DBS showed greater reductions and better sleep and memory. These results highlight the potential of synchronized brain sensing and behavioral tracking for optimizing neuromodulation therapy.
Selective enrichment of high-affinity clade II N2O-reducers in a mixed culture
Authors: Laureni Michele , Rubio Francesc Corbera , Kim DaeHyun Daniel , Browne Savanna , Roothans Nina , Weissbrodt David G. , Olavaria Karel , de Jonge Nadieh , Yoon Sukhwan , Pabst Martin , van Loosdrecht Mark C.M. 
Published: February 2024

AbstractMicroorganisms encoding for the N2O reductase (NosZ) are the only known biological sink of the potent greenhouse gas N2O, and are central to global N2O mitigation efforts. Yet, the ecological constraints selecting for different N2O-reducers strains and controlling the assembly of N2O-respiring communities remain largely unknown. Of particular biotechnological interest are clade II NosZ populations, which usually feature high N2O affinities and often lack other denitrification genes. Two planktonic N2O-respiring mixed cultures were enriched under limiting and excess dissolved N2O availability to assess the impact of substrate affinity and N2O cytotoxicity, respectively. Genome-resolved metaproteomics was used to infer the metabolism of the enriched populations. We show that clade II N2O-reducers outcompete clade I affiliates for N2O at sufficiently low sludge dilution rates (0.006 h-1), a scenario previously only theorized based on pure-cultures. Under N2O limitation, all enriched N2O-reducers encoded and expressed only clade II NosZ, while also possessing other denitrification genes. TwoAzonexusandThaueragenera affiliates dominated the culture. We explain their coexistence with the genome-inferred metabolic exchange of cobalamin intermediates. Conversely, under excess N2O, clade I and II populations coexisted. Notably, the single dominant N2O-reducer (genusAzonexus) expressed most cobalamin biosynthesis marker genes, likely to contrast the continuous cobalamin inactivation by dissolved cytotoxic N2O concentrations (400 µM). Ultimately, we demonstrate that the solids dilution rate controls the selection among NosZ clades, albeit the conditions selecting for genomes possessing the solenosZremain elusive. Additionally, we suggest the significance of N2O-cobalamin interactions in shaping the composition of N2O-respiring microbiomes.
Trehalose mediates salinity-stress tolerance in a crustacean
Authors: Santos Joana L. , Nick Fabienne , Adhitama Nikko , Fields Peter D. , Stillman Jonathon H. , Kato Yasuhiko , Watanabe Hajime , Ebert Dieter 
Published: February 2024

AbstractSalinization poses an increasing problem worldwide, threatening freshwater organisms and raising questions about ability to adapt. We explore the mechanisms enabling a planktonic crustacean to tolerate elevated salinity. By gradually raising water salinity in clonal cultures from 185Daphnia magnapopulations, we showed that salt tolerance strongly correlates with native habitat salinity, indicating local adaptation. A GWAS revealed a major effect of theAlpha,alpha-trehalose-phosphate synthase(TPS) gene, suggesting that trehalose production facilitates salinity tolerance. We found a positive correlation between water salinity and trehalose concentrations in tolerant animals, while intolerant animals failed to produce trehalose. Using CRISPR/Cas9, a silencedTPSgene supported the role of trehalose under salt stress. Our study highlights how a keystone freshwater animal adapts to salinity stress using an evolutionarily conserved mechanism known in plants and bacteria, but not in metabolic-active animals.HighlightsSalinity tolerance is a locally adapted trait inDaphnia magnaThe trehaloseTPSgene shows a strong association with salinity toleranceTrehalose content increases with water salinity allowing survival of tolerant genotypesNon-functionalTPSgenes reduce salinity tolerance by preventing trehalose production
Liquid footprinting: A novel approach for DNA footprinting using short double-stranded cell-free DNA from plasma
Authors: Müller Jan , Hartwig Christina , Sonntag Mirko , Bitzer Lisa , Adelmann Christopher , Vainshtein Yevhen , Glanz Karolina , Decker Sebastian O. , Brenner Thorsten , Weber Georg F. , Haeseler Arndt von , Sohn Kai 
Published: February 2024

AbstractThe diagnostic potential of short double-stranded cell-free DNA (cfDNA) in blood plasma has not been recognized, yet. Here, we present a method for enrichment of double-stranded cfDNA with an average length of about 40 base pairs from cfDNA for high-throughput DNA sequencing. This class of cfDNA is enriched at gene promoters and binding sites of transcription factors or structural DNA-binding proteins, so that a genome-wide DNA footprint is directly captured from liquid biopsies. In short double-stranded cfDNA from healthy individuals, we found significant enrichment of 203 transcription factor motifs. Additionally, short double-stranded cfDNA signals at specific genomic regions correlate negatively with DNA-methylation, positively with H3K4me3 histone modifications and gene transcription. When comparing short double-stranded cfDNA from patient samples of pancreatic ductal adenocarcinoma with colorectal carcinoma or septic with post-operative controls, we identified 731 and 1,107 differentially enriched loci, respectively. Using these differentially enriched loci, the disease types can be clearly distinguished by principal component analysis demonstrating the diagnostic potential of short double-stranded cfDNA signals as a new class of biomarkers for liquid biopsies.