bluuebunny/crossref_metadata_2025_split huggingface dataset:
A 3D approach to understanding heterogeneity in early developing autisms
Authors: Mandelli Veronica , Severino Ines , Eyler Lisa , Pierce Karen , Courchesne Eric , Lombardo Michael V. 
Published: May 2024

AbstractPhenotypic heterogeneity in early language, intellectual, motor, and adaptive functioning (LIMA) features are amongst the most striking features that distinguish different types of autistic individuals. Yet the current diagnostic criteria uses a single label of autism and implicitly emphasizes what individuals have in common as core social-communicative and restricted repetitive behavior difficulties. Subtype labels based on the non-core LIMA features may help to more meaningfully distinguish types of autisms with differing developmental paths and differential underlying biology. Using relatively large (n=615) publicly available data from early developing (24-68 months) standardized clinical tests tapping LIMA features, we show that stability-based relative cluster validation analysis can identify two robust and replicable clusters in the autism population with high levels of generalization accuracy (98%). These clusters can be described as Type I versus Type II autisms differentiated by relatively high versus low scores on LIMA features. These two types of autisms are also distinguished by different developmental trajectories over the first decade of life. Finally, these two types of autisms reveal striking differences in functional and structural neuroimaging phenotypes and their relationships with gene expression. This work emphasizes the potential importance of stratifying autism by a Type I versus Type II distinction focused on LIMA features and which may be of high prognostic and biological significance.
The association betweenToxoplasma gondiiinfection and asthma in the United States: A cross-sectional survey analysis
Authors: Anholt Heather 
Published: May 2024

ABSTRACTThe hygiene hypothesis proposes that declining exposure to microbial influences early in life is implicated in the rising trend of allergy and asthma in high-income societies. Approximately 8% of Americans have been diagnosed with asthma, representing 25 million people, and understanding how the human microbiome affects asthma could help guide exposure recommendations or microbe-based therapeutics.Toxoplasma gondiiis a common gastro-intestinal microorganism that may modulate immune function. We used a cross-sectional study design to examine a public database of U.S. residents aged 6 to 80 years or older from the 2012-2014 survey cycles of the American National Health and Nutrition Examination Survey (NHANES) to construct an ordinal logistic regression model of the relationship betweenT. gondiiinfection and asthma. There was no significant relationship detected betweenT. gondiiinfection and asthma when the model was adjusted for key demographic factors.
Oncogenic human papillomavirus and anal microbiota in men who have sex with men and are living with HIV in Northern Taiwan
Authors: Cheng Shu-Hsing , Yang Yu-Chen , Chen Cheng-Pin , Hsieh Hui-Ting , Lin Yi-Chun , Cheng Chien-Yu , Liao Kuo-Sheng , Chu Fang-Yeh , Liu Yun-Ru 
Published: May 2024

AbstractFew studies have demonstrated the interplay between human immunodeficiency virus (HIV), anal human papillomavirus (HPV), and anal microbiota, especially in persons living with HIV who are men who have sex with men. We therefore explored these interrelationships in a cohort of persons living with HIV, mainly comprising men who have sex with men. HPV genotyping using a commercial genotyping kit and ThinPrep cytology interpreted by Bethesda systems were performed on samples from 291 patients. Samples were characterized by high-throughput sequencing of dual-index barcoded 16s rRNA (V3–4). Bacterial diversity was diminished in individuals living with HIV with CD4+ T cells <500 cells/µL and anal cytology yielding atypical squamous cells of undetermined significance or higher grades (ASCUS+) with detectable HPV 16/18 compared with those with CD4+ T cells ≥500 cells/µL with ASCUS+ and HPV 16/18 and those with normal anal cytology or inflammation without HPV 16/18. Enterobacteriaceae, Ruminococcus, and Bacilli were significantly abundant in persons living with HIV with CD4+ T cells <500 cells/µL with ASCUS+ and HPV 16/18. Bacterial diversity, composition, and homogeneity of dispersion were different in individuals living with HIV with low CD4+ T cells with ASCUS+ and HPV 16/18. These patients should be followed up for the development of anal precancerous lesions.
Assessing the impact of Covid-19 on Nurturing Care in Nairobi Slums: Findings from 5 rounds of cross-sectional telephone surveys
Authors: Hughes Robert C , Onyango Silas , Langat Nelson , Muendo Ruth , Juel Rachel , Kimani-Murage Elizabeth , Hill Zelee , Kirkwood Betty , Bhopal Sunil S , Kitsao-Wekulo Patricia 
Published: May 2024

AbstractIntroductionThis study investigates the multifaceted impacts of the Covid-19 pandemic on early childhood in three of Nairobi’s informal settlements or slums. Focusing on the first five years of life, a critical period for human capital development, we analyse how Nurturing Care across five domains (Health, Nutrition, Responsive Caring, Early Learning, Security and Safety) was influenced by the pandemic and the mitigation measures that were implemented.MethodsUsing a longitudinal design, we conducted five rounds of cross-sectional surveys (with between 578 and 774 respondents in each) over 13 months, correlating with different phases of the pandemic and varying levels of Covid-19 restrictions.ResultsOur findings reveal significant disruptions in healthcare services, particularly pronounced in early rounds with missed vaccinations (reported by 1 in 5 parents of infants) and therapeutic healthcare seeking (missed by up to 21% of families). The study also highlights persistent food and nutrition insecurity, with a large majority of families struggling to feed their children (up to 72% in Round 1) due to financial constraints. Economic shocks were near-universal, with widespread losses in income and employment reported; 99.7% of respondents reporting earning less since the start of the pandemic. The use of paid childcare initially plummeted but showed a resurgence over time (up to 21% usage by Round 5) as the pandemic and control measures evolved. Young children were commonly left alone in all rounds, but especially earlier in the pandemic; 24% in Round 1, and at least 13% in all rounds, underscoring the enduring challenges in providing consistent nurturing care in these settings. Very few (less than 2%) of study participants reported direct experience of Covid-19 in their family in any round.ConclusionDespite adaptations over time and the decrease in reported disruptions, the prolonged economic shock was associated with multiple adverse effects Nurturing Care. The study’s longitudinal scope provides insights into the dynamic nature of ensuring young children in slums thrive during crises, highlighting the need for tailored interventions and policies that address the compounded vulnerabilities of young children in these communities.
Depletion of m6A-RNA inEscherichia colireduces the infectious potential of T5 bacteriophage
Authors: Saikia Bibakhya , Riquelme-Barrios Sebastian , Carell Thomas , Brameyer Sophie , Jung Kirsten 
Published: May 2024

AbstractN6-methyladenosine (m6A) is the most abundant internal modification of mRNA in eukaryotes that plays, among other mechanisms, an essential role in virus replication. However, the understanding of m6A RNA modification in prokaryotes, especially in relation to phage replication, is limited. To address this knowledge gap, we investigated the effects of m6A RNA modification on phage replication in two model organisms:Vibrio campbelliiBAA-1116 (previouslyV. harveyiBB120) andEscherichia coliMG1655. An m6A-RNA depletedV. campbelliimutant (ΔrlmFΔrlmJ) did not differ from the wild type in the induction of lysogenic phages or in susceptibility to the lytic Virtus phage. In contrast, the infection potential of the T5 phage, but not that of other T phages or the lambda phage, was reduced in an m6A-RNA depletedE. colimutant (ΔrlmFΔrlmJ) compared to the wild type. This was shown by a lower efficiency of plaquing and a higher percentage of surviving cells. There were no differences in T5 phage adsorption rate, but the mutant exhibited a 5 min delay in the rise period during the one-step growth curve. This is the first report demonstrating thatE. colicells with lower m6A RNA levels have a higher chance of surviving T5 phage infection.ImportanceThe importance of RNA modifications has been thoroughly studied in the context of eukaryotic viral infections. However, their role in bacterial hosts during phage infections is largely unexplored. Our research delves into this gap by investigating the effect of host m6A-RNA modifications during phage infection. We found that anE. colimutant depleted of m6A-RNA is more resistant to T5 infection than the wild type. This finding emphasizes the need to further investigate how RNA modifications affect the fine-tuned regulation of individual bacterial survival in the presence of phages to ensure population survival.
Patterning effects of FGF17 and cAMP on generation of dopaminergic progenitors for cell replacement therapy in Parkinson’s disease
Authors: Nygaard Amalie Holm , Schörling Alrik L. , Abay-Nørgaard Zehra , Hänninen Erno , Li Yuan , Santoja Adrian , Rathore Gaurav Singh , Salvador Alison , Rusimbi Charlotte , Zhang Yu , Kirkeby Agnete 
Published: May 2024

Cell replacement therapies using human pluripotent stem cell-derived ventral midbrain (VM) dopaminergic (DA) progenitors are currently in clinical trials for treatment of Parkinson’s disease (PD). Recapitulating developmental patterning cues, such as fibroblast growth factor 8 (FGF8), secreted at the midbrain-hindbrain boundary (MHB), is critical for thein vitroproduction of authentic VM DA progenitors. Here, we explore the application of alternative MHB-secreted FGF-family members, FGF17 and FGF18, for VM DA pro-genitor patterning. We show that while FGF17 and FGF18 both recapitulate VM DA progenitor patterning events, FGF17 induced expression of key VM DA progenitor markers at higher levels than FGF8 and transplanted FGF17-patterned progenitors fully reversed motor deficits in a rat PD model. Early activation of the cAMP pathway mimicked FGF17-induced patterning, although strong cAMP activation came at the expense of EN1 expression. In summary, we identified FGF17 as a promising candidate for more robust VM DA progenitor patterning, with the potential to improve cell products for treatment of PD.Summary statementIn this article we find that FGF17 induces high expression of key dopamine progenitor markers and that these cells can provide functional rescue in a rat model of Parkinson’s disease.
Mapping the spatial proteomic signature of dorsal and ventral hippocampus in a mouse model of early Alzheimer’s disease: changes in synaptic plasticity-related proteins associated with sexual dimorphism
Authors: Contreras Ana , Jiménez-Herrera Raquel , Djebari Souhail , Navarro-López Juan D. , Jiménez-Díaz Lydia 
Published: May 2024

AbstractBackgroundAn initial neuropathological hallmark of Alzheimer’s disease (AD) is the hippocampal dysfunction caused by amyloid-β(Aβ) peptides accumulation. Soluble oligomeric forms of Aβshift synaptic plasticity induction threshold leading to memory deficits in male and female mice in early amyloidosis models. Some protein changes underlying those deficits have been previously studied, but the spatial distribution within the hippocampus, as well as the potential sex differences, remain unknown. Since each hippocampal region (dorsalvs. ventral) has clearly distinct functionality and connectivity, we postulated that some protein changes may be unique to each and might also be sex-dependent.MethodsAn innovative spatial proteomics study was performed to map whole hippocampal proteome distribution using matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry, which allows protein detection with spatial resolution directly on tissue sections. Brains from sixteen adult male and female mice intracerebroventricularly injected with Aβ1-42oligomers or vehicle were sectioned. MALDI imaging was performed using a RapifleXTM MALDI TissuetyperTM TOF/TOF mass spectrometer followed by protein identification by traditional tandem mass spectrometry (MS/MS) directly on the tissue. To precisely delineate both dorsal and ventral hippocampus, a Nissl staining was performed on succeeding tissue sections.ResultsOf the 234 detected peptides, significant differences in expression levels were found in 34 proteins, due to treatment, sex, or hippocampal location. Moreover, a significant protein-protein interaction (PPI) was observed, showing a relationship to long-term potentiation (LTP), the functional basis of memory. Accordingly, 14 proteins related to synaptic plasticity and/or AD were selected to further study. Results showed many of the altered protein to modulate glycogen synthase kinase-3β(GSK-3β), a protein widely involved in the regulation of synaptic plasticity induction threshold. In fact, hippocampal GSK-3βwas found overactivated suggesting a facilitated long-term depression (LTD) instead of LTP in AD models.ConclusionsThis study offers for the first time the specific protein changes in dorsal/ventral hippocampus in both male and female mice, that modulate GSK-3βactivity, providing new insight in the pathogenesis of early AD and valuable potential biomarkers for early diagnosis and therapeutic targets.
Primary role of the Tol-Pal complex in bacterial outer membrane lipid homeostasis
Authors: Tan Wee Boon , Chng Shu-Sin 
Published: May 2024

AbstractGram-negative bacteria are defined by an outer membrane (OM) that contributes to envelope integrity and barrier function. Building this bilayer require proper assembly of lipopolysaccharides, proteins, and phospholipids, yet how the balance of these components is achieved is unclear. One system long known for ensuring OM stability is the Tol-Pal complex, which has been implicated in maintaining OM lipid homeostasis. However, assignment of Tol-Pal function has been challenging, owing to its septal localization and associated role(s) during division. Here, we uncouple the function of Tol-Pal in OM lipid homeostasis from its impact on cell division inEscherichia coli, by engineering a chimeric complex that loses septal enrichment. We demonstrate that this peripherally-localized Tol-Pal complex is fully capable of maintaining lipid balance in the OM, thus restoring OM integrity and barrier. Our work establishes the primary function of the Tol-Pal complex in OM lipid homeostasis, independent of its role during division.
Fine-scale movement data reveal surface foraging and nocturnal flight activity in the endangered Bermuda petrel
Authors: Becciu Paolo , Patterson Allison , Gjerdrum Carina , Madeiros Jeremy , Campioni Letizia 
Published: May 2024

AbstractForaging behavior plays a fundamental role in animal fitness and population dynamics, particularly in marine ecosystems where seabirds like petrels (small Procellariiformes) showcase a diverse array of foraging strategies finely adapted to the pelagic environment. The extent and remote nature of their foraging grounds makes direct observation of foraging behaviour impractical, thereby requiring the use of remote tracking technologies. We deployed miniaturized multi-sensor biologgers and collected fine scale movement data to investigate the at-sea behaviours of the Bermuda petrelPterodroma cahow, a poorly studied and highly threatened gadfly petrel, specialised on mesopelagic prey. GPS-tracking data revealed extensive foraging trips, in consistent directions, over remote oceanic regions. Time-depth-recorders provided new insights into petrel feeding techniques suggesting that the meso-bathypelagic prey targeted by petrels must be available in the very upper layer of the water surface, given their very limited diving activity (99.99% of dives had 0.1 m of depth). Accelerometer data revealed 3 flying- and 3 water-related behaviours. Flying behaviours reflected the expected dynamic soaring flight strategy of procellariforms; individuals spent more than three-quarters of their time in flight with flying-non-flapping being the most common behaviour under all conditions. The behaviour classified as “flying-intensive” was infrequently observed but could indicate aerial dipping, a characteristic foraging technique ofPterodromaspecies. The remaining time was spent in three water behaviours: active, inactive and intensive, with the latter being less common but thought to reflect scavenging and prey seizing. Flying-related behaviours increased with negative sun elevation values, highlighting greater flight activity during night compared to the day, while water behaviours were more common during the day. While some of our findings may require further validation to confirm their relevance to foraging behaviour, our work offers new and valuable insights to consider when assessing the extent and nature of offshore anthropogenic-related risks faced by petrels.
Reinforcement learning when your life depends on it: a neuro-economic theory of learning
Authors: Jiang Jiamu , Foyard Emilie , van Rossum Mark C.W. 
Published: May 2024

AbstractSynaptic plasticity enables animals to adapt to their environment, but memory formation can consume a substantial amount of metabolic energy, potentially impairing survival. Hence, a neuro-economic dilemma arises whether learning is a profitable investment or not, and the brain must therefore judiciously regulate learning. Indeed, in experiments it was observed that during starvation, Drosophila suppress formation of energy-intensive aversive memories. Here we include energy considerations in a reinforcement learning framework. Simulated flies learned to avoid noxious stimuli through synaptic plasticity in either the energy expensive long-term memory (LTM) pathway, or the decaying anesthesia-resistant memory (ARM) pathway. The objective of the flies is to maximize their lifespan, which is calculated with a hazard function. We find that strategies that switch between the LTM and ARM pathways based on energy reserve and reward prediction error, prolong lifespan. Our study highlights the significance of energy-regulation of memory pathways and dopaminergic control for adaptive learning and survival. It might also benefit engineering applications of reinforcement learning under resources constraints.
Experience-dependent, sexually dimorphic synaptic connectivity defined by sex-specific cadherin expression
Authors: Liao Chien-Po , Majeed Maryam , Hobert Oliver 
Published: May 2024

ABSTRACTWe describe here the molecular mechanisms by which juvenile experience defines patterns of sexually dimorphic synaptic connectivity in the adult nervous system of the nematodeC. elegans. We show that starvation of juvenile males disrupts serotonin- dependent activation of the CREB transcription factor in a nociceptive sensory neuron, PHB. CREB acts through a cascade of transcription factors to control expression of an atypical cadherin protein, FMI-1/Flamingo. During postembryonic development, FMI-1/Flamingo has the capacity to promote and maintain synaptic connectivity of the PHB nociceptive sensory to a command interneuron, AVA, in both sexes, but the serotonin transcriptional regulatory cassette antagonizes FMI-1/Flamingo expression in males, thereby establishing sexually dimorphic connectivity between PHB and AVA. A critical regulatory node in this process is the CREB-target LIN-29, a Zn finger transcription factor which integrates four different layers of information – sexual specificity, past feeding status, time and cell-type specificity. Our findings provide the mechanistic details of how an early juvenile experience defines sexually dimorphic synaptic connectivity.
Cadherin 4 assembles a family of color-selective retinal circuits that respond to light offset
Authors: Olguin Aline Giselle Rangel , Rochon Pierre-Luc , Theriault Catherine , Brown Thomas , Cayouette Michel , Cook Erik P. , Krishnaswamy Arjun 
Published: May 2024

AbstractRetinal interneurons and projection neurons (retinal ganglion cells, RGCs) connect in specific combinations in a specialized neuropil called the inner plexiform layer (IPL). The IPL is divided into multiple sublaminae, with neurites of each neuronal type confined to one or a few layers. This laminar specificity is a major determinant of circuit specificity and circuit function. Using a combination of approaches we show that RGCs targeting IPL sublamina 1 and 3a express the adhesion molecule cadherin 4 (Cdh4). Using calcium imaging and iterative immunostaining, we classified Cdh4-RGCs into 9 types that each encode unique aspects of dark visual stimuli. Cdh4 loss selectively disrupted the layer- targeting of these RGCs, reduced their synaptic inputs from interneurons, and severely altered their visual responses. Overexpression of Cdh4 in other retinal neurons directed their neurites to s1-3a through homophilic interactions. Taken together, these results demonstrate that Cdh4 is a novel layer targeting system for nearly a third of all RGC.
Domain consolidation in Bacterial 50S assembly revealed by Anti-Sense Oligonucleotide Probing
Authors: Sheng Kai , Dong Xiyu , Aiyer Sriram , Lee Joan , Marquardt Selena Djordjevic , Lyumkis Dmitry , Williamson James R. 
Published: May 2024

AbstractInvestigating the intricate and rapid folding kinetics of large RNA-protein complexes (RNPs), like the bacterial ribosome, remains a formidable challenge in structural biology. Previous genetic approaches to probe assembly have focused on modulating the expression of either r-proteins or assembly factors. Here, anti-sense oligonucleotides (ASOs) were used to disrupt native RNA/RNA and RNA/protein interactions, in order to generate novel folding intermediates. In anin vitroco-transcriptional assembly assay, 8 assembly inhibitor ASOs were identified. Using cryo-electron microscopy, 38 new intermediate structures were determined resulting from the specific inhibitions. In particular a novel intermediate class provided compelling evidence of independent rRNA domain folding before proper interdomain docking. Three PNAs targeting domain-I of 23S- rRNA further subdivided the previously identified assembly core into smaller blocks representing the earliest steps in assembly. The resulting assembly graph reveals template-directed RNA foldon docking and domain consolidation, which provides a hierarchical view of the RNP assembly process.
A common computational and neural anomaly across mouse models of autism
Authors: Noel Jean-Paul , Balzani Edoardo , Acerbi Luigi , Benson Julius ,   The International Brain Laboratory, Savin Cristina , Angelaki Dora E. 
Published: May 2024

AbstractComputational psychiatry has suggested that humans within the autism spectrum disorder (ASD) inflexibly update their expectations (i.e., Bayesian priors). Here, we leveraged high-yield rodent psychophysics (n = 75 mice), extensive behavioral modeling (including principled and heuristics), and (near) brain-wide single cell extracellular recordings (over 53k units in 150 brain areas) to ask (1) whether mice with different genetic perturbations associated with ASD show this same computational anomaly, and if so, (2) what neurophysiological features are shared across genotypes in subserving this deficit. We demonstrate that mice harboring mutations inFmr1,Cntnap2, andShank3Bshow a blunted update of priors during decision-making. Neurally, the differentiating factor between animals flexibly and inflexibly updating their priors was a shift in the weighting of prior encoding from sensory to frontal cortices. Further, in mouse models of ASD frontal areas showed a preponderance of units coding for deviations from the animals’ long-run prior, and sensory responses did not differentiate between expected and unexpected observations. These findings demonstrate that distinct genetic instantiations of ASD may yield common neurophysiological and behavioral phenotypes.