bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiple vaccine comparison in the same adults from the VITAL study reveals vaccine-specific and age-related humoral response patterns
Authors: van der Heiden Marieke , Shetty Sudarshan , Bijvank Elske , Beckers Lisa , Cevirgel Alper , van Sleen Yannick , Tcherniaeva Irina , Ollinger Thierry , Burny Wivine , van Binnendijk Rob S , van Houten Marianne A , Buisman Anne-Marie , Rots Nynke Y. , van Beek Josine , van Baarle Debbie 
Published: January 2024

AbstractVaccine responsiveness is often reduced in older adults. Yet, our lack of understanding of low vaccine responsiveness hampers the development of effective vaccination strategies to reduce the impact of infectious diseases in the ageing population.Young-adult, middle-aged and older-adult participants of the VITAL clinical trials (n=315, age range: 28-98y), were consecutively vaccinated with a booster quadrivalent influenza (QIV) vaccine, a primary 13-valent pneumococcal-conjugate (PCV13) vaccine, and a primary series of SARS-CoV2 mRNA-1273 vaccines within the timeframe of 2 years. This unique setup allowed investigation of humoral responsiveness towards multiple vaccines within the same individuals over the entire adult age-range.Booster QIV vaccination induced comparable H3N2 hemagglutination inhibition (HI) titers in all age groups, whereas primary PCV13 and mRNA-1273 vaccination induced lower antibody concentrations in older as compared to younger adults. The persistence of humoral responses towards the 6 months timepoint was shorter in older adults for all vaccines. Interestingly, the quantity of vaccine-induced humoral immunity within one individual differed between vaccines. Yet, a small group of mostly older male adults responded low to multiple vaccines.This study aids the identification of risk groups for low vaccine responsiveness and guides the design of more targeted vaccination strategies for the ageing population.
Application of polygenic scores to a deeply phenotyped sample enriched for substance use disorders reveals extensive pleiotropy with psychiatric and medical traits
Authors: Hartwell Emily E. , Jinwala Zeal , Milone Jackson , Ramirez Sarah , Gelernter Joel , Kranzler Henry R. , Kember Rachel L. 
Published: January 2024

AbstractCo-occurring psychiatric, medical, and substance use disorders (SUDs) are common, but the complex pathways leading to such comorbidities are poorly understood. A greater understanding of genetic influences on this phenomenon could inform precision medicine efforts. We used the Yale-Penn dataset, a cross-sectional sample enriched for individuals with SUDs, to examine pleiotropic effects of genetic liability for psychiatric and medical traits. Participants completed an in-depth interview that provides information on demographics, environment, medical illnesses, and psychiatric and SUDs. Polygenic scores (PGS) for psychiatric disorders and medical traits were calculated in European-ancestry (EUR; n=5,691) participants and, when discovery datasets were available, for African-ancestry (AFR; n=4,918) participants. Phenome-wide association studies (PheWAS) were then conducted. In AFR participants, the only PGS with significant associations was bipolar disorder (BD), all of which were with substance use phenotypes. In EUR participants, PGS for major depressive disorder (MDD), generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), schizophrenia (SCZ), body mass index (BMI), coronary artery disease (CAD), and type 2 diabetes (T2D) all showed significant associations, the majority of which were with phenotypes in the substance use categories. For instance, PGSMDDwas associated with over 200 phenotypes, 15 of which were depression-related (e.g., depression criterion count), 55 of which were other psychiatric phenotypes, and 126 of which were substance use phenotypes; and PGSBMIwas associated with 138 phenotypes, 105 of which were substance related. Genetic liability for psychiatric and medical traits is associated with numerous phenotypes across multiple categories, indicative of the broad genetic liability of these traits.
Constipation is associated with an increased risk of major adverse cardiac events in a UK population
Authors: Zheng Tenghao , Camargo Tavares Leticia , D’Amato Mauro , Marques Francine Z. 
Published: January 2024

AbstractBackgroundTraditional cardiovascular risk factors, including hypertension, only explain part of major adverse cardiac events (MACE). Understanding what other risk factors contribute to MACE is essential for prevention. Constipation shares common risk factors with hypertension and is associated with an increased risk of several cardiovascular diseases. We hypothesised that constipation is an under-appreciated risk factor for MACE.MethodsWe used the population healthcare and genomic data in the UK Biobank (UKBB) (n=408,354) to study the contribution of constipation (ICD-10 K59.0) to the risk of MACE, defined by any episode of acute coronary syndrome (ACS), ischemic stroke and heart failure (HF). Analyses were controlled for traditional cardiovascular risk factors. We also assessed genetic correlations (rg) between constipation and MACE.ResultsConstipation cases (N=23,814) exhibited significantly higher risk of MACE compared to those with normal bowel habits (OR=2.15, P<1.00×10-300). Constipation was also significantly associated with individual MACE subgroups, in order: HF (OR=2.72, P<1.00×10-300), ischemic stroke (OR=2.36, P=2.02×10-230), and ACS (OR=1.62, P=5.82×10-113). In comparison with constipation-free hypertensive patients, hypertensive patients with constipation showed significantly higher odds of MACE (OR=1.68, P=1.05×10-136) and a 34% increased risk of death (P=2.3×10-50) after adjustment for medications that affect gut motility and other traditional cardiovascular risk factors. Finally, we detected positive genetic correlations between constipation and MACE subgroups ACS (rg=0.27, P=2.12×10-6), ischemic stroke (rg=0.23, P=0.011), and HF (rg=0.21, P=0.0062).ConclusionWe identified constipation as a potential risk factor independently associated with higher MACE prevalence. These findings warrant further studies on their causal relationship and identification of pathophysiological mechanisms.
PRIMARY CENTRAL NERVOUS SYSTEM VASCULITIS WITH INTRACRANIAL ANEURYSM
Authors: Salvarani Carlo , Brown Robert D. , Christianson Teresa J. H. , Huston John , Giannini Caterina , Hunder Gene G. 
Published: January 2024

AbstractBackgroundUnruptured intracranial aneurysms (UIAs) are rarely reported in primary central nervous system vasculitis (PCNSV). In this study we described the clinical findings, response to therapy, and outcomes of UIA in a large cohort of PCNSV patients.MethodsWe retrospectively studied 216 consecutive patients with PCNSV, selected by predetermined diagnostic criteria, who were seen during a 40-year period. UIAs were identified on cerebral angiography. The clinical, laboratory, radiologic and pathologic findings, management, and outcomes of patients with UIA were described and compared with those without UIA.Results12/216 (5.5%) PCNSV patients had at least one UIA. In the only positive patient biopsy showed necrotizing vasculitis. Eleven patients had evidence of UIA on angiogram at diagnosis. One patient developed an aneurysm during the follow-up associated with a worsening of vasculitic radiological findings. The most common presenting symptom for PCNSV in the setting of UIA was headache (67%), followed by persistent neurologic deficit or stroke (50%). Most patients with UIA presented with multiple cerebral infarcts on MRI (67%), one patient had subarachnoid hemorrhage, and one left parieto-occipital intracerebral hematoma, both unrelated to the aneurysm. Black blood imaging was performed in 4 patients and 2 showed segmental circumferential mural enhancement involving multiple vessels. Two patients had 2 UIAs, while the other 10 had 1. The most frequent UIA location was internal carotid artery (50%), followed by anterior cerebral artery (21%). Ten of the UIAs were < 5 mm in diameter, and 3 were 5-7 mm in diameter; the size was not available for one. All UIAs were unchanged in size and configuration during follow-up and no new aneurysms were detected. Compared to the 204 patients with PCNSV without a UIA, no significant clinical differences were observed, except for a reduced disability at last follow-up (p = 0.038).ConclusionsUIAs uncommonly occur in PCNSV.
TDP-43 nuclear loss in FTD/ALS causes widespread alternative polyadenylation changes
Authors: Zeng Yi , Lovchykova Anastasiia , Akiyama Tetsuya , Liu Chang , Guo Caiwei , Jawahar Vidhya Maheswari , Sianto Odilia , Calliari Anna , Prudencio Mercedes , Dickson Dennis W. , Petrucelli Leonard , Gitler Aaron D. 
Published: January 2024

AbstractIn frontotemporal dementia and amyotrophic lateral sclerosis, the RNA-binding protein TDP-43 is depleted from the nucleus. TDP-43 loss leads to cryptic exon inclusion but a role in other RNA processing events remains unresolved. Here, we show that loss of TDP-43 causes widespread changes in alternative polyadenylation, impacting expression of disease-relevant genes (e.g.,ELP1, NEFL,andTMEM106B) and providing evidence that alternative polyadenylation is a new facet of TDP-43 pathology.
An evolutionary-conserved VPS34-PIKfyve-TRPML1-Myosin II axis regulates the speed of amoeboid cell migration
Authors: Dehio Philippe , Michard Céline , Yam-Puc Juan Carlos , Martí i Líndez Adrià-Arnau , Fabre Lucien , Schaefer Thorsten , Wymann Matthias P. , Okkenhaug Klaus , Soldati Thierry , Mehling Matthias , Hess Christoph 
Published: January 2024

AbstractAmoeboid cell migration is key to efficient T cell immunity. Spatial polarization of organelles within cells, including endo-lysosomes, is a prerequisite of migration. However, how ultrastructural polarization is linked to the signaling requirements governing T cell migration, remains unknown. Here we show that signaling molecules generated by endo-lysosome-localized kinases regulate velocity of amoeboid migration. Specifically, imaging of T cells identified accumulation of endo-lysosomes decorated with the lipid kinases VPS34–PIKfyve at the uropod of polarized cells. Activity of VPS34 and PIKfyve regulated speed, but not directedness, of migrating T cells. Mechanistically, PI(3,5)P2generated by the sequential action of VPS34 and PIKfyve mediated Ca2+efflux from lysosomes via the mucolipin TRP cation channel 1 (TRPML1), thus controlling activity of myosin IIA and hence the generation of propulsive force through retrograde actin flow. The VPS34–PIKfyve kinases also regulated velocity of myeloid cells, as well as of the amoebaDictyostelium discoideum– establishing the axis as an evolutionary conservedspeed control systemof amoeboid cell migration.Graphical AbstractThe VPS34–PIKfyve axis is active on endo-lysosomes at the uropod of migrating T cells.VPS34 and PIKfyve promote myosin IIA activation and retrograde action flow.Amoeboid cell migration speed is controlled by VPS34 and PIKfyve via TRPML1.Regulation of amoeboid migration speed is a conserved function of the VPS34–PIKfyve axis.
Conditional knockout ofShank3in the ventral CA1 by quantitativein vivogenome-editing impairs social memory
Authors: Chung Myung , Imanaka Katsutoshi , Huang Ziyan , Watarai Akiyuki , Wang Mu-Yun , Tao Kentaro , Ejima Hirotaka , Aida Tomomi , Feng Guoping , Okuyama Teruhiro 
Published: January 2024

AbstractIndividuals with autism spectrum disorder (ASD) have a higher prevalence of social memory impairment. A series of our previous studies revealed that hippocampal ventral CA1 (vCA1) neurons possess social memory engram and that the neurophysiological representation of social memory in the vCA1 neurons is disrupted in ASD-associatedShank3knockout mice. However, whether the dysfunction of Shank3 in vCA1 causes the social memory impairment observed in ASD remains unclear. In this study, we found that vCA1-specificShank3conditional knockout (cKO) by the adeno-associated virus (AAV)- or specialized extracellular vesicle (EV)-mediatedin vivogene editing was sufficient to recapitulate the social memory impairment in male mice. Furthermore, the utilization of EV-mediatedShank3-cKO allowed us to quantitatively examine the role of Shank3 in social memory. Our results suggested that there is a certain threshold for the proportion ofShank3-cKO neurons required for social memory disruption. Thus, our study provides insight into the population coding of social memory in vCA1, as well as the pathological mechanisms underlying social memory impairment in ASD.
Glycolysis–Wnt signaling axis tunes developmental timing of embryo segmentation
Authors: Miyazawa Hidenobu , Rada Jona , Sanchez Paul Gerald Layague , Esposito Emilia , Bunina Daria , Girardot Charles , Zaugg Judith , Aulehla Alexander 
Published: January 2024

AbstractThe question of how metabolism impacts development is seeing a renaissance [1, 2]. How metabolism exerts instructive signaling functions is one of the central issues that need to be resolved. We tackled this question in the context of mouse embryonic axis segmentation. Previous studies have shown that changes in central carbon metabolism impact Wnt signaling [3–6] and the period of the segmentation clock [7], which controls the timing of axis segmentation. Here, we reveal that glycolysis tunes the segmentation clock period in an anti-correlated manner: higher glycolytic flux slows down the clock, and vice versa. Transcriptome and gene regulatory network analyses identified Wnt signaling and specifically the transcription factor Tcf7l2, previously associated with increased risk for diabetes [8, 9], as potential mechanisms underlying flux-dependent control of the clock period. Critically, we show that deletion of the Wnt antagonist Dkk1 rescued the slow segmentation clock phenotype caused by increased glycolysis, demonstrating that glycolysis instructs Wnt signaling to control the clock period. In addition, we demonstrate metabolic entrainment of the segmentation clock: periodic changes in the levels of glucose or glycolytic sentinel metabolite fructose 1,6-bisphosphate (FBP) synchronize signaling oscillations. Notably, periodic FBP pulses first entrained Wnt signaling oscillations and subsequently Notch signaling oscillations. We hence conclude that metabolic entrainment has an immediate, specific effect on Wnt signaling. Combined, our work identifies a glycolysis-FBP-Wnt signaling axis that tunes developmental timing, highlighting the instructive signaling role of metabolism in embryonic development.
Concurrent processing of the prosodic hierarchy is supported by cortical entrainment and phase-amplitude coupling
Authors: Oderbolz Chantal , Sauppe Sebastian , Meyer Martin 
Published: January 2024

AbstractModels of phonology posit a hierarchy of prosodic units that are relatively independent from syntactic structure, requiring its own parsing. Surprisingly, it remains unexplored how this prosodic hierarchy is represented in the brain. We investigated this foundational question by means of an EEG study. Thirty young adults listened to German sentences containing manipulations at different levels of the prosodic hierarchy. Evaluating speech-to-brain cortical entrainment and phase-amplitude coupling revealed that prosody’s hierarchical structure is maintained at the neural level. The faithfulness of this tracking varied as a function of the hierarchy’s degree of intactness as well as systematic inter-individual differences in audio-motor synchronization. The results underscore the role of complex oscillatory mechanisms in configuring the continuous and hierarchical nature of the speech signal and firmly situate prosody as a structure indispensable from theoretical perspectives on spoken language comprehension in the brain.
Exploring functional connectivity in clinical and data-driven groups of preterm and term adults
Authors: Hadaya Laila , Váša František , Dimitrakopoulou Konstantina , Saqi Mansoor , Shergill Sukhwinder S , Edwards David A , Batalle Dafnis , Leech Robert , Nosarti Chiara 
Published: January 2024

AbstractBackgroundAdults born very preterm (i.e., at <33 weeks’ gestation) are more susceptible to long-lasting structural and functional brain alterations and cognitive and socio-emotional difficulties, compared to full-term controls. However, behavioural heterogeneity within very preterm and full-term individuals makes it challenging to find biomarkers of specific outcomes. To address these questions, we parsed brain-behaviour heterogeneity in participants subdivided according to their clinical birth status (very preterm vs full-term) and/or data-driven behavioural phenotype (regardless of birth status).MethodsThe Network Based Statistic approach was used to identify topological components of resting state functional connectivity differentiating between i) 116 very preterm and 83 full-term adults (43% and 57% female, respectively), and ii) data-driven behavioural subgroups identified using consensus clustering (n= 156, 46% female). Age, sex, socio-economic status, and in-scanner head motion were used as confounders in all analyses. Post-hoc two-way group interactions between clinical birth status and behavioural data-driven subgrouping classification labels explored whether functional connectivity differences between very preterm and full-term adults varied according to distinct behavioural outcomes.ResultsVery preterm compared to full-term adults had poorer scores in selective measures of cognitive and socio-emotional processing and displayed complex patterns of hyper- and hypo-connectivity in subsections of the default mode, visual, and ventral attention networks. Stratifying the study participants in terms of their behavioural profiles (irrespective of birth status), identified two data-driven subgroups: An “At-risk”subgroup, characterised by increased cognitive, mental health, and socio-emotional difficulties, displaying hypo-connectivity anchored in frontal opercular and insular regions, relative to a“Resilient”subgroup with more favourable outcomes. No significant interaction was noted between clinical birth status and behavioural data-driven subgrouping classification labels in terms of functional connectivity.ConclusionsFunctional connectivity differentiating between very preterm and full-term adults was dissimilar to functional connectivity differentiating between the data-driven behavioural subgroups. We speculate that functional connectivity alterations observed in very preterm relative to full-term adults may confer both risk and resilience to developing behavioural sequelae associated with very preterm birth, while the localised functional connectivity alterations seen in the “At-risk”subgroup relative to the “Resilient” subgroup may underlie less favourable behavioural outcomes in adulthood, irrespective of birth status.
Condensin-mediated restriction of retrotransposable elements facilitates brain development inDrosophila melanogaster
Authors: Crawford Bert I. , Talley Mary Jo , Russman Joshua , Riddle James , Torres Sabrina , Williams Troy , Longworth Michelle S. 
Published: January 2024

AbstractNeural stem and progenitor cell (NSPC) maintenance are essential for ensuring that organisms are born with proper brain volumes and head sizes. Microcephaly is a disorder in which babies are born with significantly smaller head sizes and cortical volumes. Mutations in subunits of the DNA organizing complexes, condensins have been identified in microcephaly patients. However the molecular mechanisms by which condensin insufficiency causes microcephaly remain elusive. We previously identified conserved roles for condensins in repression of retrotransposable elements (RTEs). Here, we show that condensin subunit knockdown in NSPCs of theDrosophilalarval central brain increases RTE expression and mobility which causes cell death, and significantly decreases adult head sizes and brain volumes. These findings suggest that unrestricted RTE expression and activity may lead to improper brain development in condensin insufficient organisms, and lay the foundation for future exploration of causative roles for RTEs in other microcephaly models.
Contrasting contribution of embryo- and postnatally-derived brain-resident macrophages in sustaining sleep-wake circuitry
Authors: Seifinejad Ali , Bandarabadi Mojtaba , Haddar Meriem , Wundt Saskia , Tafti Mehdi , Vassalli Anne , Khani Abbas , Monaco Gianni 
Published: January 2024

SummarySleep is a complex behavior regulated by various brain cell types. However, the roles of brain-resident macrophages, including microglia and CNS-associated macrophages (CAMs), particularly those derived postnatally, in sleep regulation remain poorly understood. Here, we investigated the effects of natural (embryo-derived) and repopulated (postnatally derived) brain-resident macrophages on the regulation of vigilance states. We found that depletion in embryonically-derived brain macrophages caused increased sleep in the active period, but reduced its quality, reflected in reduced power of brain sleep oscillations. This was observed both for the Non-REM and REM sleep stages. Subsequent repopulation by postnatal brain macrophages unexpectedly failed to reestablish normal sleep-wake patterns and additionally induced sleep fragmentation. Furthermore, brain macrophage depletion caused excitatory-inhibitory synaptic imbalance, which was resistant to repopulation, and led to increased inhibitory synapses. At the metabolite level, the distinct metabolite profile induced by brain macrophage depletion largely returned to normal after repopulation. Our findings suggest a so far largely unknown interaction between brain-resident macrophages and sleep and emphasizes striking functional differences between embryonic and postnatally-derived brain macrophages, paving the way to future exploration of the role of brain macrophages of different origin in sleep disorders and synaptic connectivity.
When the tap runs dry: The multi-tissue gene expression and physiological responses of water deprivedPeromyscus eremicus
Authors: Blumstein Danielle M. , MacManes Matthew D. 
Published: January 2024

AbstractThe harsh and dry conditions of desert environments have resulted in genomic adaptations, allowing for desert organisms to withstand prolonged drought, extreme temperatures, and limited food resources. Here, we present a comprehensive exploration of gene expression across five tissues (kidney, liver, lung, gastrointestinal tract, and hypothalamus) and 19 phenotypic measurements to explore the whole-organism physiological and genomic response to water deprivation in the desert-adapted cactus mouse (Peromyscus eremicus). The findings encompass the identification of differentially expressed genes and correlative analysis between phenotypes and gene expression patterns across multiple tissues. Specifically, we found robust activation of the vasopressin renin-angiotensin-aldosterone system (RAAS) pathways, whose primary function is to manage water and solute balance. Animals reduce food intake during water deprivation, and upregulation ofPCK1highlights the adaptive response to reduced oral intake via its actions aimed at maintained serum glucose levels. Even with such responses to maintain water balance, hemoconcentration still occurred, prompting a protective downregulation of genes responsible for the production of clotting factors while simultaneously enhancing angiogenesis which is thought to maintains tissue perfusion. In this study, we elucidate the complex mechanisms involved in water balance in the desert-adapted cactus mouse,P. eremicus. By prioritizing a comprehensive analysis of whole-organism physiology and multi-tissue gene expression in a simulated desert environment, we describe the complex and successful response of regulatory processes.