bluuebunny/crossref_metadata_2025_split huggingface dataset:
The chromatin remodeler CHD3 is highly expressed in mature neurons and regulates genes involved in synaptic development and function
Authors: den Hoed Joery , Wong Maggie M. K. , Claassen Willemijn J. J. , de Hoyos Lucía , Lütje Lukas , Heide Michael , Huttner Wieland B. , Fisher Simon E. 
Published: May 2024

AbstractChanges in the dynamics of chromatin state that control spatiotemporal gene expression patterns are crucial during brain development. CHD3 is a chromatin remodeler that is highly expressed during neurogenesis and that functions as a core member of the NuRD complex, a large multiprotein complex mediating chromatin state. Genetic disruptions inCHD3have been implicated in a neurodevelopmental disorder characterized by intellectual disability, macrocephaly and severe speech deficits. To study the roles of CHD3 during early human brain development, we generated induced pluripotent stem cells with heterozygous and homozygous loss-of-function mutations, differentiated them into unguided neural organoids and cortical neurons, and analyzed these by immunohistochemistry, bulk RNA-, single-cell RNA-, and ChIP-sequencing. Loss ofCHD3expression had no detectable effects on early neuroepithelium formation and organoid growth, nor did it significantly affect cell type composition or neuronal differentiation speed. Instead, upon loss ofCHD3, we observed dysregulation of genes related to axon guidance and synapse development across all datasets, identifying a novel role for the protein as a regulator that facilitates neurogenesis, in particular neuronal maturation. Our results based on genetically engineered knockout organoids pave the way for future studies modeling the neurobiological pathways affected in CHD3-related disorder.
Atomic resolution map of the solvent interactions driving SOD1 unfolding in CAPRIN1 condensates
Authors: Ahmed Rashik , Liang Mingyang , Hudson Rhea P. , Rangadurai Atul K. , Huang Shuya Kate , Forman-Kay Julie D. , Kay Lewis E. 
Published: May 2024

AbstractBiomolecules can be sequestered into membrane-less compartments, referred to as biomolecular condensates. Experimental and computational methods have helped define the physical-chemical properties of condensates. Less is known about how the high macromolecule concentrations in condensed phases contribute “solvent” interactions that can remodel the free-energy landscape of other condensate-resident proteins, altering thermally accessible conformations and, in turn, modulating function. Here, we use solution Nuclear Magnetic Resonance (NMR) spectroscopy to obtain atomic resolution insights into the interactions between the immature form of superoxide dismutase 1 (SOD1), which can mislocalize and aggregate in stress granules, and the RNA-binding protein CAPRIN1, a component of stress granules. NMR studies of CAPRIN1:SOD1, focused on both unfolded and folded SOD1 states in mixed phase and de-mixed CAPRIN1-based condensates, establish that CAPRIN1 shifts the folding equilibrium of SOD1 towards the unfolded state through preferential interactions with the unfolded ensemble, with little change to the structure of the folded conformation. Key contacts between CAPRIN1 and the H80-H120 region of unfolded SOD1 are identified, as well as SOD1 interaction sites near both the arginine-rich and aromatic-rich regions of CAPRIN1. Unfolding of immature SOD1 in the CAPRIN1 condensed phase is shown to be coupled to aggregation, while a more stable zinc-bound, dimeric form of SOD1 is less susceptible to unfolding when solvated by CAPRIN1. Our work underscores the impact of the condensate solvent environment on the conformational states of resident proteins and supports the hypothesis that ALS mutations that decrease metal binding or dimerization function as drivers of aggregation in condensates.Significance StatementBiomolecular condensates concentrate proteins and nucleic acids to regulate and perform key biological functions. Although the material properties of these condensates are well-studied, much less is understood about how the structure and dynamics of proteins within them are affected by the high concentration of biomolecules. In this study we have used NMR spectroscopy to study how the folding equilibrium and structural dynamics of the ALS protein SOD1 are modulated inside a condensate formed by CAPRIN1. Our study reveals that the CAPRIN1 condensed phase biases an immature form of SOD1 towards unfolded states that are susceptible to aggregation and provides insights into why this is the case, while a more mature form of the protein is much less affected.
A central role for Numb/Nbl in multiple Shh-mediated axon repulsion processes
Authors: Dolique Tiphaine , Baudet Sarah , Charron Frederic , Ferent Julien 
Published: May 2024

AbstractSonic hedgehog (Shh) is an axon guidance molecule that can act as either a chemorepellent or a chemoattractant, depending on the neuron type and their developmental stage. In the developing spinal cord, Shh initially attracts commissural axons to the floor plate and later induces their repulsion after they cross the midline. In the developing visual system, Shh repels ipsilateral retinal ganglion cell (iRGC) axons at the optic chiasm. Although Shh requires the endocytic adaptor Numb for attraction of commissural neurons, the molecular mechanisms underlying Shh dual function in attraction and repulsion are still unclear. In this study, we investigate whether Numb also regulates repulsive axon guidance. We show that Numb is essential for two Shh-mediated repulsion processes: iRGC axon repulsion at the optic chiasm and antero-posterior commissural axon repulsion in the spinal cord. Therefore, Numb is required for Shh-mediated attraction and repulsion. These results position Numb as a central player in the non-canonical Shh signalling pathway mediating axon repulsion.Summary statementHere, we show that Numb is required for Shh-mediated midline repulsion of ipsilateral retinal ganglion cell axons and post-crossing commissural axons of the spinal cord.
Divergent short-term plasticity creates parallel pathways for computation and behavior in an olfactory circuit
Authors: Kim Hyong S. , Jeanne James M. 
Published: May 2024

SUMMARYTo enable diverse sensory processing and behavior, central circuits use divergent connectivity to create parallel pathways. However, linking subcellular mechanisms to the circuit-level segregation of computation has been challenging. Here, we investigate the generation of parallel processing within a divergent network in theDrosophilaolfactory system, where single projection neurons target multiple types of lateral horn neuron (LHN). One LHN type generates sustained responses and adapts divisively to encode temporal odor contrast. The other generates transient responses and adapts subtractively to encode a form of positive temporal prediction error. These coding differences originate from subcellular differences in short-term plasticity in projection neuron axons. Prediction error arises from strongly facilitating synapses, which depend on the presynaptic priming factor Unc13B. The temporal contrast code arises from mildly depressing synapses that engage additional gain control implemented by the Na+/K+ATPase in the postsynaptic neuron. Each LHN type makes corresponding dynamic contributions to behavioral odor attraction. Subcellular synaptic specialization is a compact and efficient way to generate diverse parallel information streams.
Adolescent and adult mice use both incremental reinforcement learning and short term memory when learning concurrent stimulus-action associations
Authors: Chase Juliana B. , Xia Liyu , Tai Lung-Hao , Lin Wan Chen , Collins Anne G.E. , Wilbrecht Linda 
Published: May 2024

AbstractComputational modeling has revealed that human research participants use both rapid working memory (WM) and incremental reinforcement learning (RL) (RL+WM) to solve a simple instrumental learning task, relying on WM when the number of stimuli is small and supplementing with RL when the number of stimuli exceeds WM capacity. Inspired by this work, we examined which learning systems and strategies are used by adolescent and adult mice when they first acquire a conditional associative learning task. In a version of the human RL+WM task translated for rodents, mice were required to associate odor stimuli (from a set of 2 or 4 odors) with a left or right port to receive reward. Using logistic regression and computational models to analyze the first 200 trials per odor, we determined that mice used both incremental RL and stimulus-insensitive, one-back strategies to solve the task. While these one-back strategies may be a simple form of short-term or working memory, they did not approximate the boost to learning performance that has been observed in human participants using WM in a comparable task. Adolescent and adult mice also showed comparable performance, with no change in learning rate or softmax beta parameters with adolescent development and task experience. However, reliance on a one-back perseverative, win-stay strategy increased with development in males in both odor set sizes. Our findings advance a simple conditional associative learning task and new models to enable the isolation and quantification of reinforcement learning alongside other strategies mice use while learning to associate stimuli with rewards within a single behavioral session. These data and methods can inform and aid comparative study of reinforcement learning across species.Author summaryHere we studied the strategies and mechanisms mice use to learn a simple two choice odor based task in a single session. Using a set size manipulation and computational models we find evidence that mice use incremental reinforcement learning as well as several short-term (one-back) strategies to earn water reward. Our data and models clarify how mice learn a simple task and establish methods by which mouse and human reinforcement learning may be isolated for cross-species comparison of learning.
Clinical epidemiology of the endoscopic, laparoscopic, and surgical resection of malignant gastric tumors in Japan, 2014-2021: a retrospective study using open data from a national claims database
Authors: Sako Akahito , Yada Tomoyuki , Fujiya Keiichi , Nakashima Ryo , Yoshimura Kensuke , Yanai Hidekatsu , Uemura Naomi 
Published: May 2024

ABSTRACTBackgroundGastric cancer is one of the most common malignancies and its incidence is high in East Asia. Several options are available for resection of malignant gastric tumors, ranging from endoscopic resection of early-stage cancer to open total gastrectomy. However, there has been a lack of nationwide data on gastric resection in Japan.MethodsThis observational study analyzed data from the publicly accessible National Database of Health Insurance Claims and Specific Health Checkups, which includes most national health insurance claims data in Japan. Trends in the various types of resection performed for malignant gastric tumors between 2014 and 2021, the age and sex distributions of patients undergoing these procedures, and regional disparities were investigated.ResultsThe annual number of resections was highest in 2015 (109,000) and lowest in 2020 (90,000) after the COVID-19 pandemic. The proportion of endoscopic resections increased from 47% in 2014 to 57% in 2021 while the proportion of total gastrectomies performed during this period decreased from 17% to 10%. In 2021, 70% of patients who underwent resection were men. That year, 83.8% of all patients who underwent any type of gastric resection and 87.1% of those who underwent endoscopic submucosal dissection (ESD) were aged ≥65 years. The annual incidence of gastric resection per million general population was highest in Tottori (n=1,236) and lowest in Okinawa (n=251). The proportion of endoscopic resections was highest in Miyagi (66%) and lowest in Aichi (45%) and that of open surgery was highest in Aomori (36%) and lowest in Wakayama (5%).ConclusionsGastric malignancy is increasingly treated by endoscopic submucosal dissection rather than by open total gastrectomy. However, there are regional disparities in the resection methods used. Standardization of screening and treatment and a more even distribution of specialists are needed.
Long-COVID improves in 50% of patients after a year in a Midwestern cohort
Authors: Stalker Grant , Tudas Rosarie , Garg Alpana , Graham Lauren , Thurman Andrew L. , Wiblin R. Todd , Hamzeh Nabeel , Blount Robert J. , Villacreses Raul , Zabner Joseph , Comellas Alejandro , Cho Josalyn L. , Pezzulo Alejandro 
Published: May 2024

AbstractBackgroundMany of those infected with COVID-19 experience long-term disability due to persistent symptoms known as Long-COVID, which include ongoing respiratory issues, loss of taste and smell, and impaired daily functioning.Research QuestionThis study aims to better understand the chronology of long-COVID symptoms.Study Design and MethodsWe prospectively enrolled 403 adults from the University of Iowa long-COVID clinic (June 2020 to February 2022). Participants provided symptom data during acute illness, symptom progression, and other clinical characteristics. Patients in this registry received a survey containing questions including current symptoms and status since long-COVID diagnosis (sliding status scale, PHQ2, GAD2, MMRC). Those >12 months since acute-COVID diagnosis had chart review done to track their symptomology.ResultsOf 403 participants contacted, 129 (32%) responded. The mean age (in years) was 50.17 +/−14.28, with 31.8% male and 68.2% female. Severity of acute covid treatment was stratified by treatment in the outpatient (70.5%), inpatient (16.3%), or ICU (13.2%) settings. 51.2% reported subjective improvement (sliding scale scores of 67-100) since long-COVID onset. Ages 18-29 reported significantly higher subjective status scores. Subjective status scores were unaffected by severity. 102 respondents were >12 months from their initial COVID-19 diagnosis and were tracked for longitudinal symptom persistence. All symptoms tracked had variance (mean fraction 0.58, range 0.34-0.75) in the reported symptoms at the time of long-COVID presentation when compared with patient survey report. 48 reported persistent dyspnea, 23 (48%) had resolved it at time of survey. For fatigue, 44 had persistence, 12 (27%) resolved.InterpretationOverall, 51.2% respondents improved since their long-COVID began. Pulmonary symptoms were more persistent than neuromuscular symptoms (anosmia, dysgeusia, myalgias). Gender, time since acute COVID infection, and its severity didn’t affect subjective status or symptoms. This study highlights recall bias that may be prevalent in other long-COVID research reliant on participant memory.
Altered Brain Glucose Metabolism in COVID-19 disease: An activation likelihood estimation Meta-analysis
Authors: Kang Dongju , Jung Hyunji , Pak Kyoungjune 
Published: May 2024

ABSTRACTPurposeCOVID-19, caused by the SARS-CoV-2 virus, has significantly altered modern society and lifestyles. We investigated its impact on brain glucose metabolism by meta-analyzing existing studies that utilized 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) scans of the brain.MethodsWe conducted a systematic search of MEDLINE and EMBASE databases from inception to August 2023 for English-language publications using the keywords “positron emission tomography,” “single-photon emission computed tomography,” and “COVID-19.” We included original research articles that reported changes in brain glucose metabolism following COVID-19 infection. ALE values from these studies were aggregated and tested against a null hypothesis that anticipated a random distribution of ALE values, which proved to be significantly higher than chance.ResultsWe identified eight papers that met our inclusion criteria. Significant increases in brain glucose metabolism were noted in the left anterior cingulate gyrus, right thalamus, and brainstem. In children with COVID-19, decreased glucose metabolism was observed in the right and left cerebellum, left amygdala/hippocampus, left anterior cingulate gyrus, and right amygdala. In adults with COVID-19, decreased metabolism was seen in the right temporal lobe, brainstem (acute phase), left posterior cingulate gyrus, left precuneus, right cerebellum, right insula, right anterior cingulate gyrus, left occipital lobe, and left globus pallidus (chronic phase).ConclusionCOVID-19 impacts brain glucose metabolism, typically manifesting as areas of decreased metabolism in18F-FDG PET scans, though increases are also observed. These changes in metabolism vary with the patient’s age and the time elapsed between the diagnosis of COVID-19 and the PET scan.
Envelope-dimer epitope-like broadly protective antibodies against dengue in children following natural infection and vaccination
Authors: Mpingabo Patrick I. , Ylade Michelle , Aogo Rosemary A. , Crisostomo Maria Vinna , Thiono Devina J. , Daag Jedas Veronica , Agrupis Kristal-An , Escoto Ana Coello , Raimundi-Rodriguez Guillermo L. , Odio Camila D. , Fernandez Maria Abad , White Laura , de Silva Aravinda M. , Deen Jacqueline , Katzelnick Leah C. 
Published: May 2024

AbstractCross-reactive antibodies (Abs) to epitopes that span envelope proteins on the virion surface are hypothesized to protect against dengue. Here, we measured Abs targeting the quaternary envelope dimer epitope (EDE) as well as neutralizing and binding Abs and evaluate their association with dengue virus (DENV) infection, vaccine response, and disease outcome in dengue vaccinated and unvaccinated children (n=252) within a longitudinal cohort in Cebu, Philippines (n=2,996). Abs targeting EDE were prevalent and strongly associated with broad neutralization of DENV1-4 in those with baseline multitypic immunity. Subsequent natural infection and vaccination boosted EDE-like, neutralizing, and binding Abs. EDE-like Abs were associated with reduced dengue risk and mediated the protective effect of binding and neutralizing Abs on symptomatic and severe dengue. Thus, Abs targeting quaternary epitopes help explain broad cross protection in those with multiple prior DENV exposures, making them useful for evaluation and development of future vaccines and therapeutics.
Moving out and moving on: the impact of mobility in a context of union dissolution on antidepressants intake in Belgium
Authors: Damiens Joan , Schnor Christine , Willaert Didier 
Published: May 2024

ABSTRACTThis research investigates the role of residential mobility in the relation between union dissolution and antidepressants intake. The dataset gathers information on 20 to 64-year-old individuals affiliated with the Belgian socialist health insurance fund – the largest public health insurance fund in French-speaking Belgium – and who lived in marital or non-marital opposite-sex partnerships in 2008 and separated between 2009 to 2018 (N=68,048). We used antidepressant consumption (>= 90 defined daily doses per year) as a dependent variable and conducted random-effect logistic regression models. Controlling for observed and unobserved individuals’ characteristics, we found that, mobility – defined by a change of municipality – during the year and/or the year following the separation is not associated with higher or lower antidepressants intake than staying on the previously shared place after the separation. However, we observe anticipatory effects for women: women who moved during their separation year had a higher medication use than women who stayed in the previously shared municipality. Repartnership is associated with lower antidepressants consumption for women, especially if they leave the shared place.
An ultrasound-guided biopsy technique for obtaining supraclavicular brown fat biopsies and preadipocytes
Authors: Andersen Eline S. , Jespersen Naja Zenius , Henriksen Tora Ida , Pedersen Bente Klarlund , Scheele Camilla , Nielsen Michael Bachmann , Nielsen Søren 
Published: May 2024

AbstractStudying activated human brown adipose tissue (BAT) in vivo poses challenges due to its intricate anatomical positioning. Through the implementation of an ultrasound-guided biopsy technique, we successfully collected BAT samples from the supraclavicular region of 27 healthy individuals. As a comparative control, subcutaneous white adipose tissue (WAT) was similarly extracted from the same participants. Furthermore, we isolated progenitor cells from four tissue biopsies in both regions, subsequently subjecting them to a 12-day in vitro differentiation protocol following stimulation with 10 µM norepinephrine. To assess the mRNA expression of thermogenic genes within these small tissue samples, we employed a targeted cDNA amplification procedure, followed by conventional quantitative PCR (qPCR). Our study demonstrated that, with further refinement, this biopsy methodology can be used to obtain thermogenic adipose tissue. However, the expression data exhibited considerable diversity, and no statistically significant overall trends emerged for any of the five BAT marker genes (UCP1, PPARGC1A, PRDM16, CIDEA, CITED1), nor for the WAT marker HOXC8. The differentiation capacity of the progenitor cells revealed irregularities, with only three adipocyte cultures (two WAT and one BAT) displaying satisfactory differentiation potential. Remarkably, the differentiated BAT culture displayed a significantly elevated basal UCP mRNA expression level, further induced by 1.7-fold upon stimulation with norepinephrine. In summary, based on the in vitro data, brown adipose samples can be obtained using our ultrasound-guided biopsy technique approach. However, significant refinements are necessary before robust in vivo data can be generated in future intervention studies.
Arachidonic acid incorporation into phosphatidylinositol by LPLAT11/MBOAT7 ensures radial glial cell integrity in developing neocortex
Authors: Ishino Yuki , Kishi Yusuke , Iwama Taiga , Kuwayama Naohiro , Arai Hiroyuki , Gotoh Yukiko , Aoki Junken , Kono Nozomu 
Published: May 2024

AbstractArachidonic acid, a vital polyunsaturated fatty acid in brain development, is enriched in phosphatidylinositol (PI). The arachidonic acyl chain in PI is introduced by lysophospholipid acyltransferase 11 (LPLAT11)/membrane-bound O-acyltransferase 7 (MBOAT7), the loss of which causes cortical atrophy in humans and mice. Here, we show that LPLAT11 deficiency impaired indirect neurogenesis in the developing neocortex, resulting in fewer layer II-V neurons. LPLAT11-deficient radial glial cells had defects in differentiation into intermediate progenitor cells and increased apoptosis. Prior to these anomalies, LPLAT11 deficiency caused a fragmentation of the Golgi apparatus, accompanied by impaired apical trafficking of E-cadherin, and deregulated apical detachment. Moreover, impaired PI acyl chain remodeling led to a decreased amount of PI(4,5)P2, leading to Golgi apparatus fragmentation. Thus, these results clarify the underlying mechanism of cortical atrophy by LPLAT11 deficiency and highlight the critical role of arachidonic acid in PI in the integrity of radial glial cells.