bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reward processing in young people with self-harm behaviour
Authors: Yavuz Emre , Rodrigues Rachel , Sanchez Ana Pascual , Lingford-Hughes Anne , Simplicio Martina Di 
Published: December 2023

AbstractTwenty percent of young people report a lifetime presence of self-harm (SH) behaviour, associated with negative health and functional outcomes. Understanding the underlying cognitive mechanisms is needed to develop targeted early interventions. Reward processing biases may underlie SH, aligning with accounts of the behaviour acquiring “addictive” characteristics. However, the specific nature of such biases remains unclear, particularly its relationship with negative affect (NA) that frequently triggers SH. In Study 1, we compared young people (aged 16-25) with SH to a group with NA but no SH history and a healthy control group on performance of a novel Incentive Delay Task (IDT), with SH-related (SH trials), positive social (social trials) or monetary images (money trials) as stimuli. In Study 2, a different sample of SH and HC participants completed the same IDT following NA induction via an online Trier Social Stress Test. For both studies, we hypothesised faster and more correct responses in the SH group than control groups on SH trials. Contradicting our hypothesis, there were no significant between-group differences in IDT performance on SH, social and money trials in either study. Certain SH characteristics (positive reinforcement, SH mental imagery, urge) were significantly correlated with better performance on SH trials in SH participants. Thus, broadly SH behaviour may not be underpinned by motivational biases towards SH-related cues or naturalistic rewards. Future studies should clarify whether incentivisation of SH-related cues instead explains individual differences in SH behaviour and its relation with treatment and prognosis.
Neuropathology-based GWAS for Alzheimer’s disease reveals novel susceptibility loci and highlights sex-specific pathways
Authors: Jin Yin , Topaloudi Apostolia , Shekhar Sudhanshu , Scott Alicia Nicole , Colon Bryce David , Drineas Petros , Rochet Chris , Paschou Peristera 
Published: December 2023

AbstractDementia refers to an umbrella phenotype of many different underlying pathologies with Alzheimer’s disease (AD) being the most common type. While Genome-wide Association Studies (GWAS) of clinically defined AD have identified multiple AD susceptibility variants, a significant portion of the heritability remains unexplained highlighting the phenotypic and genetic heterogeneity of the clinically defined entity. Furthermore, despite women’s increased susceptibility to dementia there is a lack of sex-specific genetic studies and understanding of sex-specific background for the disorder. Here, we aim to tackle the heterogeneity of AD by specifically concentrating on neuropathological features which are the gold standard for diagnosis and pursuing sex-specific analysis. We bring together 13 different genomic and neuropathology datasets (6,960 individuals) and we integrate our GWAS findings with transcriptomic and proteomic data (ROSMAP and Mayo studies) aiming to also identify in vivo biomarkers for AD progression. We uncover novel genetic associations to AD neuropathology, including BIN1, OPCML, and CDH4. Our sex-specific analysis points to a role for BIN1 specifically in women as well as novel AD loci including QRFPR and SGCZ. Tissue-specific associations in females, particularly in the ovary issue, suggest a connection between sex hormones and AD. Finally, we pursue the identification of in-vivo biomarkers associated with AD neuropathology, with a goal to offer insights into disease progression and potential therapeutic targets. Our findings contribute to unraveling the molecular basis of AD, emphasizing the importance of sex-specific analyses and multi-omics approaches. Further research is needed to validate and explore the clinical utility of these findings.
Global associations of macronutrient supply and asthma disease burden
Authors: Ni Duan , Senior Alistair M. , Raubenheimer David , Simpson Stephen J. , Macia Laurence , Nanan Ralph 
Published: December 2023

AbstractObjectivesGlobal age-standardized prevalence of asthma has decreased over time, in parallel with which, the gross domestic product (GDP) per capita and nutritional landscapes also changed at a global level. Both socioeconomic status and nutritional factors are critical confounder for asthma, but most studies so far neglected to interrogate their correlations and interactions comprehensively. Hence, we aim to systematically investigate the relationship between nutrient supply, a good proxy of food environment, socioeconomic status and asthma disease burden at a global level over time.MethodsAsthma disease burden, macronutrient (protein, carbohydrate and fat) supply and GDP data covering more than 150 countries around the globe from 1990 to 2018 was collated. Various multi-response generalized additive mixed models (GAMMs) were used to analyze the effects of macronutrient supplies and GDP over time on asthma disease burden.ResultsA model considering the interactions between macronutrient supplies and GDP, with an additive effect of time was favoured. Modelling results showed that carbohydrate supply was most strongly associated with increase of asthma disease burden, while fat supply had an opposite effect, and protein supply conferred less influences.ConclusionsGlobally, carbohydrate supply seems to play a driving role for asthma disease burden while fat supply might be the opposite. This is supported by previous studies about the amelioration of established asthma by ketogenic diet and might be linked to the diet quality. Further in-depth studies are warranted, which will be critical for future clinical research and practice and public health intervention.
Long-Term Outcomes of SARS-CoV-2 Variants and Other Respiratory Infections: Evidence from the Virus Watch Prospective Cohort in England
Authors: Beale Sarah , Yavlinsky Alexei , Fong Wing Lam Erica , Nguyen Vincent G , Kovar Jana , Vos Theo , Hansen Sarah Wulf , Hayward Andrew C , Abubakar Ibrahim , Aldridge Robert W 
Published: December 2023

AbstractBackgroundGiven the considerable prevalence of long-term sequelae following SARS-CoV-2 infection, understanding pathogen-related factors that influence long-term outcomes is warranted. We aimed to compare the likelihood of long-term symptoms for SARS-CoV-2 variants, other acute respiratory infections (ARIs) and non-infected individuals.MethodData were from 5,630 individuals participating in Virus Watch, a prospective community cohort study of SARS-CoV-2 epidemiology in England. We used logistic regression to compare the predicted probability of developing long-term symptoms (>2 months duration) during different variant dominance periods according to infection status (SARS-CoV-2, other ARI, or no infection), adjusting for confounding by demographic and clinical factors and vaccination status.ResultsPredicted probability of long-term sequelae was greater following SARS-CoV-2 infection during the Wild Type (adjusted predicted probability (PP) 0.28, 95% confidence interval (CI) =0.14-0.43), Alpha (PP= 0.28, 95% CI =0.14-0.42), Delta (PP= 0.34, 95% CI=0.25-0.43) and Omicron BA.1 periods (PP= 0.27, 95% CI =0.22-0.33) compared to later Omicron sub-variants (PP range from 0.11, 95% CI 0.08-0.15 to 0.14, 95% CI 0.10-0.18). While differences between SARS-CoV-2 and other ARIs (PP range 0.08, 95% CI 0.04-0.11 to 0.23, 95% CI 0.18-0.28) varied by period, estimates for long-term symptoms following both infection types substantially exceeded those for non-infected participants (PP range 0.01, 95% CI 0.00,0.02 to 0.03, 95% CI 0.01-0.06) across all variant periods.ConclusionsBetween-variant differences influenced the likelihood of post-infection sequelae for SARS-CoV-2, with lower predicted probabilities for recent Omicron sub-variants similar to those for other contemporaneous ARIs. Both SARS-CoV-2 and other ARIs were associated with long-term symptom development, and further aetiological investigation including between-pathogen comparison is recommended.
Investigation of choroid plexus variability in schizophrenia-spectrum disorders – insights from a multimodal study
Authors: Yakimov Vladislav , Moussiopoulou Joanna , Roell Lukas , Kallweit Marcel S. , Boudriot Emanuel , Mortazavi Matin , Papiol Sergi , Krčmář Lenka , Campana Mattia , Schulte Eva C. , Glaichenhaus Nicolas , Martinuzzi Emanuela , Halstead Sean , Warren Nicola , Siskind Dan , Maurus Isabel , Hasan Alkomiet , Falkai Peter , Schmitt Andrea , Raabe Florian ,   CDP Working Group, Keeser Daniel , Wagner Elias 
Published: December 2023

AbstractBackground and HypothesisPrevious studies have suggested that choroid plexus (ChP) enlargement occurs in individuals with schizophrenia-spectrum disorders (SSD) and is associated with peripheral inflammation. However, it is unclear whether such an enlargement delineates a biologically defined subgroup of SSD. Moreover, it remains elusive how ChP is linked to brain regions, associated with peripheral inflammation in SSD.Study DesignA cross-sectional cohort of 132 individuals with SSD and 107 age-matched healthy controls (HC) underwent magnetic resonance imaging (MRI) of the brain and clinical phenotyping to investigate the ChP and associated regions. Case-control comparison of ChP volumes was conducted and structural variance was analysed by employing the variability ratio (VR). K-means clustering analysis was used to identify subgroups with distinct patterns of the ventricular system and the clusters were compared in terms of demographic, clinical and immunological measures. The relationship between ChP volumes and brain regions, previously associated with peripheral inflammation, was investigated.Study ResultsWe could not find a significant enlargement of the ChP in SSD compared to HC but detected an increased VR of ChP and lateral ventricle volumes. Based on these regions we identified 3 clusters with differences in age, symbol coding test scores and possibly inflammatory markers. Larger ChP volume was associated with higher volumes of hippocampus, putamen, and thalamus in SSD, but not in HC.ConclusionsThis study suggests that ChP variability, but not mean volume, is increased in individuals with SSD, compared to HC. Larger ChP volumes in SSD were associated with higher volumes of regions, previously associated with peripheral inflammation.
Ghrelin is associated with an elevated mood after an overnight fast in depression
Authors: Fahed Rauda , Schulz Corinna , Klaus Johannes , Ellinger Sabine , Walter Martin , Kroemer Nils B. 
Published: December 2023

AbstractBackgroundMajor depressive disorder (MDD) comprises subtypes with distinct symptom profiles. For example, patients with melancholic and atypical MDD differ in the direction of appetite and body weight changes as well as mood reactivity. Despite reported links to altered energy metabolism, the role of circulating neuropeptides from the gut in modulating such symptoms remains largely elusive.MethodsWe collected data from 103 participants, including 51 patients with MDD and 52 healthy control participants (HCP). After an overnight fast, we measured blood levels of (acyl and des-acyl) ghrelin and participants reported their current metabolic and mood states using visual analog scales (VAS). Furthermore, they completed symptom-related questionnaires (i.e., STAI-T).ResultsPatients with atypical versus melancholic MDD reported less negative affect (p= .025). Higher levels of acyl ghrelin (corrected for BMI) were associated with improved mood (p= .012), specifically in patients with MDD. These associations of ghrelin were not mood-item specific and exceeded correlations with trait markers of negative affectivity. In contrast to associations with mood state, higher levels of ghrelin were not associated with increased hunger per se or changes in appetite in patients with MDD.LimitationsThe study is limited by the cross-sectional design without an intervention.ConclusionsOur results reveal potentially mood-enhancing effects of ghrelin in fasting individuals that exceed associations with metabolic state ratings. These associations with circulating neuropeptides might help explain anti-depressive effects of fasting interventions and could complement conventional treatments in patients with melancholic MDD.Graphical abstract
Regulatory networks of KRAB zinc finger genes and transposable elements changed during human brain evolution and disease
Authors: Chen Yao-Chung , Maupas Arnaud , Nowick Katja 
Published: December 2023

AbstractEvidence indicates that transposable elements (TEs) can contribute to the evolution of new traits, despite often being considered deleterious. In vertebrates, some KRAB-ZNF proteins repress TEs, offering genomic protection. Notably, KRAB-ZNF genes evolve rapidly and exhibit diverse expression patterns in primate brains, where TEs remain active. This prompts questions about their interactions in primate brains and potential roles in human brain evolution and disease. For a systematic comparative analysis of TE interactions with other genes, we developed the tool TEKRABber, and focused on strong and experimentally validated cases. Our bipartite network analysis revealed significantly more interactions between KRAB-ZNF genes and TEs in humans than in other primates, especially with recently evolved, i.e. Simiiformes specific, TEs. Notably, ZNF528, under positive selection in humans, shows numerous human-specific TE interactions. Most negative interactions in our network, indicative of repression by KRAB-ZNF proteins, entail Alu TEs, while links to other TEs are generally positive. In Alzheimer’s patients, a subnetwork involving 21 interactions with an Alu module appears diminished or lost. Our findings suggest that KRAB-ZNF and TE interactions vary across TE families, have increased throughout human evolution, and may influence susceptibility to Alzheimer’s disease.Graphical AbstractFigure 1.
A Functional Schizophrenia-associated genetic variant near theTSNARE1andADGRB1genes
Authors: Wahbeh Marah H. , Boyd Rachel J. , Yovo Christian , Rike Bailey , McCallion Andrew S. , Avramopoulos Dimitrios 
Published: December 2023

ABSTRACTRecent collaborative genome wide association studies (GWAS) have identified >200 independent loci contributing to risk for schizophrenia (SCZ). The genes closest to these loci have diverse functions, supporting the potential involvement of multiple relevant biological processes; yet there is no direct evidence that individual variants are functional or directly linked to specific genes. Nevertheless, overlap with certain epigenetic marks suggest that most GWAS-implicated variants are regulatory. Based on the strength of association with SCZ and the presence of regulatory epigenetic marks, we chose one such variant nearTSNARE1andADGRB1, rs4129585, to test for functional potential and assay differences that may drive the pathogenicity of the risk allele. We observed that the variant-containing sequence drives reporter expression in relevant neuronal populations in zebrafish. Next, we introduced each allele into human induced pluripotent cells and differentiated 4 isogenic clones homozygous for the risk allele and 5 clones homozygous for the non-risk allele into neural precursor cells. Employing RNA-seq, we found that the two alleles yield significant transcriptional differences in the expression of 109 genes at FDR <0.05 and 259 genes at FDR <0.1. We demonstrate that these genes are highly interconnected in pathways enriched for synaptic proteins, axon guidance, and regulation of synapse assembly. Exploration of genes near rs4129585 suggests that this variant does not regulateTSNARE1transcripts, as previously thought, but may regulate the neighboringADGRB1, a regulator of synaptogenesis. Our results suggest that rs4129585 is a functional common variant that functions in specific pathways likely involved in SCZ risk.
Amyloid precursor protein induces reactive astrogliosis
Authors: Jauregui Gretsen Velezmoro , Vukić Dragana , Onyango Isaac G. , Arias Carlos , Novotný Jan S. , Texlová Kateřina , Wang Shanshan , Kovačovicova Kristina Locker , Polakova Natalie , Zelinkova Jana , Čarna Maria , Strašil Valentina Lacovich , Head Brian P. , Havas Daniel , Mistrik Martin , Zorec Robert , Verkhratsky Alexei , Keegan Liam , O’Connel Mary , Rissman Robert , Stokin Gorazd B. 
Published: December 2023

ABSTRACTWe presentin vitroandin vivoevidence demonstrating that Amyloid Precursor Protein (APP) acts as an essential instigator of reactive astrogliosis. Cell-specific overexpression of APP in cultured astrocytes led to remodelling of the intermediate filament network, enhancement of cytokine production and activation of cellular programs centred around the interferon (IFN) pathway, all signs of reactive astrogliosis. Conversely, APP deletion in cultured astrocytes abrogated remodelling of the intermediate filament network and blunted expression of IFN stimulated gene (ISG) products in response to lipopolysaccharide (LPS). Following traumatic brain injury (TBI), mouse reactive astrocytes also exhibited an association between APP and IFN, while APP deletion curbed the increase in glial fibrillary acidic protein (GFAP) observed canonically in astrocytes in response to TBI. Thus, APP represents a molecular inducer and regulator of reactive astrogliosis.
HURP facilitates spindle assembly by stabilizing microtubules and working synergistically with TPX2
Authors: Valdez Venecia , Ma Meisheng , Gouveia Bernardo , Zhang Rui , Petry Sabine 
Published: December 2023

AbstractIn large vertebrate spindles, the majority of microtubules are formed via branching microtubule nucleation, whereby microtubules nucleate along the side of pre-existing microtubules. Hepatoma up-regulated protein (HURP) is a microtubule-associated protein that has been implicated in spindle assembly, but its mode of action is yet to be defined. In this study, we show that HURP is necessary for RanGTP-induced branching microtubule nucleation inXenopusegg extract. Specifically, HURP stabilizes the microtubule lattice to promote microtubule formation from γ- TuRC. This function is shifted to promote branching microtubule nucleation in the presence of TPX2, another branching-promoting factor, as HURP’s localization to microtubules is enhanced by TPX2 condensation. Lastly, we provide a structure of HURP on the microtubule lattice, revealing how HURP binding stabilizes the microtubule lattice. We propose a model in which HURP stabilizes microtubules during their formation, and TPX2 preferentially enriches HURP to microtubules to promote branching microtubule nucleation and thus spindle assembly.
The diallelic self-incompatibility system in Oleaceae is controlled by a hemizygous genomic region expressing a gibberellin pathway gene
Authors: Castric Vincent , Batista Rita A. , Carré Amélie , Mousavi Soraya , Mazoyer Clément , Godé Cécile , Gallina Sophie , Ponitzki Chloé , Theron Anthony , Bellec Arnaud , Marande William , Santoni Sylvain , Mariotti Roberto , Rubini Andrea , Legrand Sylvain , Billiard Sylvain , Vekemans Xavier , Vernet Philippe , Saumitou-Laprade Pierre 
Published: December 2023

SUMMARYSexual reproduction in flowering plants is commonly controlled by self-incompatibility (SI) systems that are either homomorphic (and typically governed by large numbers of distinct allelic specificities), or heteromorphic (and then typically governed by only two allelic specificities). The SI system of the Oleaceae family is a striking exception to this rule and represents an evolutionary conundrum, with the long-term maintenance of only two allelic specificities, but often in the complete absence of morphological differentiation between them. To elucidate the genomic architecture and molecular bases of this highly unusual SI system, we obtained chromosome-scale genome assemblies ofPhillyrea angustifoliaindividuals belonging to the two SI specificities and connected them to a genetic map. Comparison of the S-locus region revealed a segregating 543-kb indel specific to one of the two specificities, suggesting a hemizygous genetic architecture. Only one of the predicted genes in this indel is conserved with the olive treeOlea europaea,where we also confirmed the existence of a segregating hemizygous indel. We demonstrated full association between presence/absence of this gene and the SI groups phenotypically assessed across six distantly related Oleaceae species. This gene is predicted to be involved in catabolism of the Gibberellic Acid (GA) hormone, and experimental manipulation of GA levels in developing buds modified the male and female SI responses in an S-allele-specific manner. Thus, our results provide a unique example of a reproductive system where a single conserved gibberellin-related gene in a 500-700kb hemizygous indel underlies the long-term maintenance of two groups of reproductive compatibility.
VPS13B is localized at the cis-trans Golgi complex interface and is a functional partner of FAM177A1
Authors: Ugur Berrak , Schueder Florian , Shin Jimann , Hanna Michael G. , Wu Yumei , Leonzino Marianna , Su Maohan , McAdow Anthony R. , Wilson Catherine , Postlethwait John , Solnica-Krezel Lilianna , Bewersdorf Joerg , Camilli Pietro De 
Published: December 2023

ABSTRACTMutations in VPS13B, a member of a protein family implicated in bulk lipid transport between adjacent membranes, cause Cohen syndrome. VPS13B is known to be concentrated in the Golgi complex, but its precise location within this organelle and thus the site(s) where it achieves lipid transport remains unclear. Here we show that VPS13B is localized at the interface between cis and trans Golgi sub-compartments and that Golgi complex re-formation after Brefeldin A (BFA) induced disruption is delayed inVPS13BKO cells. This delay is phenocopied by loss of FAM177A1, a Golgi complex protein of unknown function reported to be a VPS13B interactor and whose mutations also result in a developmental disorder. In zebrafish, thevps13borthologue, not previously annotated in this organism, genetically interacts withfam177a1. Collectively, these findings raise the possibility that bulk lipid transport by VPS13B may play a role in expanding Golgi membranes and that VPS13B may be assisted in this function by FAM177A1.
How to predict binding specificity and ligands for new MHC-II alleles with MixMHC2pred
Authors: Racle Julien , Gfeller David 
Published: December 2023

AbstractMHC-II molecules are key mediators of antigen presentation in vertebrate species and bind to their ligands with high specificity. The very high polymorphism of MHC-II genes within species and the fast-evolving nature of these genes across species has resulted in tens of thousands of different alleles, with hundreds of new alleles being discovered yearly through large sequencing projects in different species. Here we describe how to use MixMHC2pred to predict the binding specificity of any MHC-II allele directly from its amino acid sequence. We then show how both MHC-II ligands and CD4+T-cell epitopes can be predicted in different species with our approach. MixMHC2pred is available athttp://mixmhc2pred.gfellerlab.org/.