bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diverging maternal and infant cord antibody functions from SARS-CoV-2 infection and vaccination in pregnancy
Authors: Adhikari Emily H. , Lu Pei , Kang Ye jin , McDonald Ann R. , Pruszynski Jessica E. , Bates Timothy A. , McBride Savannah K. , Trank-Greene Mila , Tafesse Fikadu G. , Lu Lenette L. 
Published: May 2023

AbstractImmunization in pregnancy is a critical tool that can be leveraged to protect the infant with an immature immune system but how vaccine-induced antibodies transfer to the placenta and protect the maternal-fetal dyad remains unclear. Here, we compare matched maternal-infant cord blood from individuals who in pregnancy received mRNA COVID-19 vaccine, were infected by SARS-CoV-2, or had the combination of these two immune exposures. We find that some but not all antibody neutralizing activities and Fc effector functions are enriched with vaccination compared to infection. Preferential transport to the fetus of Fc functions and not neutralization is observed. Immunization compared to infection enriches IgG1-mediated antibody functions with changes in antibody post-translational sialylation and fucosylation that impact fetal more than maternal antibody functional potency. Thus, vaccine enhanced antibody functional magnitude, potency and breadth in the fetus are driven more by antibody glycosylation and Fc effector functions compared to maternal responses, highlighting prenatal opportunities to safeguard newborns as SARS-CoV-2 becomes endemic.One Sentence SummarySARS-CoV-2 vaccination in pregnancy induces diverging maternal and infant cord antibody functions
Repetition-dependent adaptation and Prediction error signalling in Schizophrenia patients with auditory hallucinations: A Roving Mismatch Negativity Study
Authors: Bose Anushree , Nayok Swarna Buddha , Pathak Harsh , Bagali Kiran Basawaraj , Chhabra Harleen , Suhas Satish , Shivakumar Venkataram , Sreeraj Vanteemar S. , Narayanaswamy Janardhanan C. , Venkatasubramanian Ganesan 
Published: May 2023

ABSTRACTBackgroundPrediction error is the surprise that is elicited when the sensory expectations are first established and then violated. Positive symptoms of schizophrenia, like auditory hallucinations (AH), are thought to arise from dysregulated prediction error-signalling. Roving mismatch negativity (rMMN) is a unique event-related potential (ERP) based assessment that allows examination of repetition-dependent adaptation and deviance detection—complimentary processes that are integral to prediction-error signalling. In the rMMN paradigm, the deviant tone becomes the new standard with several repetitions. Also, the number of repetitions of the standard stimuli keeps changing throughout the experiment; longer repetitions yield a more positive ERP response; this phenomenon is Repetition Positivity (RP). Longer repetitions of standard stimuli elicit stronger deviance detection when interrupted, and this is called deviant negativity (DN). A difference waveform between RP and DN reflects the strength of prediction error signalling, the mismatch negativity (MMN).MethodsTwenty-three schizophrenia patients with auditory hallucinations (SZ-AH) and twenty-three healthy controls (HC) underwent rMMN assessment. Standard stimuli were repeated in sets of 3, 8 and 33. The first tone of the succeeding set became the deviant for the preceding set, yielding three components for RP (RP3, RP8, RP33), DN (DN3, DN8, DN33), and MMN (MMN3, MMN8, MMN33). Amplitudes and latencies of these components were compared between SZ-AH and HC. We also looked for potential associations between rMMN indices (amplitudes and latencies) and clinical scores in SZ-AVH. We examined the correlation between the RP-DN pair for all three repetition sets (3, 8, 33).ResultsSZ-AH had suppressed DN (DN3, DN8, DN33) and MMN33 amplitudes in comparison to HC. However, none of the RP amplitudes were diminished. Only MMN33 latency was significantly longer in SZ-AH than in HC. Amplitudes and latencies associated with repetition set of 8 showed a significant correlation with the frequency and loudness of AH. HC showed a strong positive correlation between RP-DN pairs; SZ-AH did not, except for the RP33-DN33 pair.DiscussionThe link between repetition-dependent sensory adaptation and deviance detection is compromised in SZ-AH patients. Though RP profile (RP3, RP8, RP33) is unimpaired in SZ-AVH, it is potentially due to AH interfering with auditory information processing and not because of intact short-term plasticity of the echoic memory trace.
Molecular Spectrum and Chromatographic- Haematological Characterisation of Alpha Thalassemia Minor (-α/-α), and Alpha Silent Carriers (-α/-αα)
Authors: Uçucu Süheyl 
Published: May 2023

AbstractBackground and aimsAlpha-thalassaemia is a group of disorders characterised by wide phenotypic variation caused by mutations in the α-globin genes (α1 and α2) of chromosome 16.The aim of this study was to investigate the molecular profile of α-thalassemia variants and to compare and characterise the chromatographic behaviour and haematological properties of α-thalassemia minor (-α/-α, --/ααα) and α-silent carriers (-α/ααα) on HPLC.Materials & MethodsA dataset of 200 individuals consisting of 42 alpha thalassemia minor (-α/-α, -- /ααα), 103 alpha silent carriers (-α/αα) and 55 normal participants from the Human Genetics Unit (HGU) of the Faculty of Medicine, Colombo, Srilanka was included. Blood samples from each patient were analysed by PCR for genotyping, haemogram and high performance liquid chromatography (HPLC) for characterisation. These data were then comparatively analysed using standard descriptive statistics.ResultsIt was analysed in three sections as haematological, biochemical and molecular. Haematologically, alpha thalassaemia silent carrier was completely normal; alpha thalassaemia minor: decreased haemoglobin level; decreased MCV and MCH, normal RBC count. Alpha Thalassaemia Minor patients show a statistically significant difference from alpha silent carriers and normal population in terms of MCV, MCH, HGB, PCV, RDW.Biochemically, alpha thalassaemia silent carriers were found to have normal alpha-globin chain production, alpha thalassaemia minor: low HBA2 as determined by HPLC. In terms of HPLC tests, similar results were observed between alpha thalassaemia minor patients and alpha silent carriers and between alpha thalassaemia minor patients and the normal group, with no statistical significance for all parameters except HBA2. Molecularly, the most common mutations in both variants are _α3.7 and _α4.2 mutations.ConclusionIn summary, despite the haematological and biochemical differences between α-thalassaemia minor and normal individuals, both variants of alpha thalassaemia present a diagnostic conundrum, as CBC and HPLC results for individuals are comparable to normal humans. Although MCV, MCH, HGB, PCV and HBA2 levels differ between alpha thalassaemia minor carriers, alpha silent carriers and the normal group, conventional haemoglobin electrophoresis and haemogram alone have been found insufficient for the diagnosis of alpha thalassaemia. Therefore, although HPLC does not seem to be sufficient to distinguish between normal individuals and the two variants, the decrease in HBA2 levels is an important finding. Identifying a mutated alpha globin gene requires newer molecular diagnostic tests such as next generation sequencing (NGS) and quantitative PCR (qPCR). It should be noted that a given genotype can greatly alter the clinical manifestation by the presence of additional mutations, making the relationship between genotype and phenotype highly variable.
Reduced Spinal Cord Gray Matter in Patients with Fibromyalgia Using Opioids Long-term
Authors: Baker Anne K. , Park Su Hyoun , Weber Kenneth A. , Martucci Katherine T. 
Published: May 2023

AbstractObjectiveChronic pain involves alterations in brain gray matter volume (GMV). Moreover, opioid medications are known to reduce GMV in numerous brain regions involved in pain processing. However, no research has evaluated (1) chronic pain-related GMV alterations in the spinal cord or (2) the effect of opioids on spinal cord GMV. Accordingly, this study evaluated spinal cord GMV in health controls and patients with fibromyalgia who were using and not using opioids long-term.MethodsWe analyzed average C5 - C7 GMV of the spinal cord dorsal and ventral horns in separate female cohorts of healthy controls (HC, n = 30), fibromyalgia patients not using opioids (FMN, n = 31), and fibromyalgia patients using opioids long-term (FMO, n = 27). To assess the effect of group on average dorsal and ventral horn GMV, we conducted a one-way multivariate analysis of covariance.ResultsAfter controlling for age, we observed a significant effect of group on ventral horn GMV (p= 0.03, η2= 0.09), and on dorsal horn GMV (p= 0.05, η2= 0.08). Tukey’s posthoc comparisons showed that, compared to HC participants, FMOs had significantly lower ventral (p= 0.01) and dorsal (p= 0.02) GMVs. Among FMOs only, ventral horn GMV was significantly positively associated with pain severity and interference, and both dorsal and ventral GMVs were significantly positively associated with cold pain tolerance.ConclusionLong-term opioid use may impact sensory processing in fibromyalgia via gray matter changes within the cervical spinal cord.
Pushed to extremes: distinct effects of high temperature vs. pressure on the structure of an atypical phosphatase
Authors: Guerrero Liliana , Ebrahim Ali , Riley Blake T. , Kim Minyoung , Huang Qingqiu , Finke Aaron D. , Keedy Daniel A. 
Published: May 2023

AbstractProtein function hinges on small shifts of three-dimensional structure. Elevating temperature or pressure may provide experimentally accessible insights into such shifts, but the effects of these distinct perturbations on protein structures have not been compared in atomic detail. To quantitatively explore these two axes, we report the first pair of structures at physiological temperature vs. high pressure for the same protein, STEP (PTPN5). We show that these perturbations have distinct and surprising effects on protein volume, patterns of ordered solvent, and local backbone and side-chain conformations. This includes novel interactions between key catalytic loops only at physiological temperature, and a distinct conformational ensemble for another active-site loop only at high pressure. Strikingly, in torsional space, physiological temperature shifts STEP toward previously reported active-like states, while high pressure shifts it toward a previously uncharted region. Together, our work argues that temperature and pressure are complementary, powerful, fundamental macromolecular perturbations.
Enhanced Feature Selection for Microbiome Data using FLORAL: Scalable Log-ratio Lasso Regression
Authors: Fei Teng , Funnell Tyler , Waters Nicholas R. , Raj Sandeep S. , Sadeghi Keimya , Dai Anqi , Miltiadous Oriana , Shouval Roni , Lv Meng , Peled Jonathan U. , Ponce Doris M. , Perales Miguel-Angel , Gönen Mithat , van den Brink Marcel R. M. 
Published: May 2023

AbstractIdentifying predictive biomarkers of patient outcomes from high-throughput microbiome data is of high interest, while existing computational methods do not satisfactorily account for complex survival endpoints, longitudinal samples, and taxa-specific sequencing biases. We presentFLORAL(https://vdblab.github.io/FLORAL/), an open-source computational tool to perform scalable log-ratio lasso regression and microbial feature selection for continuous, binary, time-to-event, and competing risk outcomes, with compatibility of longitudinal microbiome data as time-dependent covariates. The proposed method adapts the augmented Lagrangian algorithm for a zero-sum constraint optimization problem while enabling a two-stage screening process for extended false-positive control. In extensive simulation and real-data analyses,FLORALachieved consistently better false-positive control compared to other lasso-based approaches, and better sensitivity over popular differential abundance testing methods for datasets with smaller sample size. In a survival analysis in allogeneic hematopoietic-cell transplant, we further demonstrated considerable improvement byFLORALin microbial feature selection by utilizing longitudinal microbiome data over only using baseline microbiome data.
SAP: Synteny-aware gene function prediction for bacteria using protein embeddings
Authors: Urhan Aysun , Cosma Bianca-Maria , Earl Ashlee M. , Manson Abigail L. , Abeel Thomas 
Published: May 2023

AbstractMotivationToday, we know the function of only a small fraction of the protein sequences predicted from genomic data. This problem is even more salient for bacteria, which represent some of the most phylogenetically and metabolically diverse taxa on Earth. This low rate of bacterial gene annotation is compounded by the fact that most function prediction algorithms have focused on eukaryotes, and conventional annotation approaches rely on the presence of similar sequences in existing databases. However, often there are no such sequences for novel bacterial proteins. Thus, we need improved gene function prediction methods tailored for prokaryotes. Recently, transformer-based language models - adopted from the natural language processing field - have been used to obtain new representations of proteins, to replace amino acid sequences. These representations, referred to as protein embeddings, have shown promise for improving annotation of eukaryotes, but there have been only limited applications on bacterial genomes.ResultsTo predict gene functions in bacteria, we developed SAP, a novel synteny-aware gene function prediction tool based on protein embeddings from state-of-the-art protein language models. SAP also leverages the unique operon structure of bacteria through conserved synteny. SAP outperformed both conventional sequence-based annotation methods and state-of-the-art methods on multiple bacterial species, including for distant homolog detection, where the sequence similarity to the proteins in the training set was as low as 40%. Using SAP to identify gene functions across diverse enterococci, of which some species are major clinical threats, we identified 11 previously unrecognized putative novel toxins, with potential significance to human and animal health.Availabilityhttps://github.com/AbeelLab/sapContactt.abeel@tudelft.nlSupplementary informationSupplementary data are available atBioinformaticsonline.
A stable microtubule bundle formed through an orchestrated multistep process controls quiescence exit
Authors: Laporte Damien , Massoni-Laporte Aurélie , Lefranc Charles , Dompierre Jim , Mauboules David , Nsamba Emmanuel. T. , Royou Anne , Gal Lihi , Schuldiner Maya , Gupta Mohan L. , Sagot Isabelle 
Published: May 2023

AbstractCells fine-tune microtubule assembly in both space and time, to give rise to distinct edifices with specific cellular functions. In proliferating cells, microtubules are highly dynamics, and proliferation cessation often leads to their stabilization. One of the most stable microtubule structures identified to date is the nuclear bundle assembled in quiescent yeast. In this report, we characterize the original multistep process driving the assembly of this structure. This Aurora B-dependent mechanism follows a precise temporality that relies on the sequential actions of kinesin-14, kinesins-5 and involves both microtubule-kinetochore and kinetochore-kinetochore interactions. Upon quiescence exit, the microtubule bundle is disassembled via a cooperative process involving kinesin-8 and its full disassembly is required prior to cells re-entry into proliferation. Overall, our study provides the first description, at the molecular scale, of the entire life cycle of a stable microtubule structurein vivo, and sheds light on its physiological function.
LEADER (Leaf Element Accumulation from Deep Roots): a nondestructive phenotyping platform to estimate rooting depth in the field
Authors: Hanlon Meredith T. , Brown Kathleen M. , Lynch Jonathan P. 
Published: May 2023

AbstractDeeper rooted crops are an avenue to increase plant water and nitrogen uptake under limiting conditions and increase long-term soil carbon storage. Measuring rooting depth, however, is challenging due to the destructive, laborious, or imprecise methods that are currently available. Here, we present LEADER (Leaf Element Accumulation from DEep Roots) as a method to estimate in-field root depth of maize plants. We use both X-Ray fluorescence spectroscopy (XRF) and ICP-OES (Inductively Coupled Plasma Optical Emission spectroscopy) to measure leaf elemental content and relate this to metrics of root depth. Principal components of leaf elemental content correlate with measures of root length in four genotypes (R2= 0.8 for total root length), and we use linear discriminant analysis to classify plants as having different metrics related to root depth across four field sites in the United States. We can correctly classify the plots with the longest root length at depth with high accuracy (accuracy greater than 0.6) at two of our field sites (Hancock, WI and Rock Spring, PA). We also use strontium (Sr) as a tracer element in both greenhouse and field studies, showing that elemental accumulation of Sr in leaf tissue can be measured with XRF and can estimate root depth. We propose the adoption of LEADER as a tool for measuring root depth in different plant species and soils. LEADER is faster and easier than any other methods that currently exist and could allow for extensive study and understanding of deep rooting.
Cognitive outcome and its neural correlates after cardiorespiratory arrest in childhood
Authors: Geva Sharon , Hoskote Aparna , Saini Maneet , Clark Christopher A. , Banks Tina , Chong Kling W. K. , Baldeweg Torsten , de Haan Michelle , Vargha-Khadem Faraneh 
Published: May 2023

AbstractHypoxia-ischaemia (HI) can result in structural brain abnormalities, which in turn can lead to behavioural deficits in various cognitive and motor domains, in both adult and paediatric populations. Cardiorespiratory arrest (CA) is a major cause of hypoxia-ischaemia in adults, but it is relatively rare in infants and children. While the effects of adult CA on brain and cognition have been widely studied, to date, there are no studies examining the neurodevelopmental outcome of children who suffered CA early in life.Here, we studied the long-term outcome of 28 children who suffered CA during infancy or childhood (i.e., before age 16). They were compared to a group of control participants (n = 28) matched for age, gender and socio-economic status. The patient group had impairments in the domains of memory, language and academic attainment (measured using standardised tests; impairment defined as a score > 1.5 standard deviations below the control group mean). Individual scores within the impaired range were most commonly found within the memory domain (79%), followed by attainment (50%), and language (36%). The patient group also had reduced whole brain grey matter volume, and reduced volume and fractional anisotropy of the white matter.In addition, lower performance on memory tests was correlated with bilaterally reduced volume of the hippocampi, thalami, and striatum, while lower attainment scores were correlated with bilateral reduction of fractional anisotropy in the superior cerebellar peduncle, the main output tract of the cerebellum.We conclude that patients who suffered early CA are at risk of developing specific cognitive deficits associated with structural brain abnormalities.
Impaired microglia-mediated synaptic pruning in the nucleus accumbens during adolescence results in persistent dysregulation of familiar, but not novel social interactions in sex-specific ways
Authors: Kirkland Julia M. , Edgar Erin L. , Patel Ishan , Kopec Ashley M. 
Published: May 2023

ABSTRACTEvolutionarily conserved, peer-directed social behaviors are essential to participate in many aspects of human society. These behaviors directly impact psychological, physiological, and behavioral maturation. Adolescence is an evolutionarily conserved period during which reward-related behaviors, including social behaviors, develop via developmental plasticity in the mesolimbic dopaminergic ‘reward’ circuitry of the brain. The nucleus accumbens (NAc) is an intermediate reward relay center that develops during adolescence and mediates both social behaviors and dopaminergic signaling. In several developing brain regions, synaptic pruning mediated by microglia, the resident immune cells of the brain, is important for normal behavioral development. In rats, we previously demonstrated that microglial synaptic pruning also mediates NAc and social development during sex-specific adolescent periods and via sex-specific synaptic pruning targets. In this report, we demonstrate that interrupting microglial pruning in NAc during adolescence persistently dysregulates social behavior towards a familiar, but not novel social partner in both sexes, via sex-specific behavioral expression. This leads us to infer thatnaturally occurringNAc pruning serves to reduce social behaviors primarily directed toward a familiar conspecific in both sexes, but in sex-specific ways.
A short isoform of the UNC-6/Netrin receptor UNC-5 is required for growth cone polarity and robust growth cone protrusion inCaenorhabditis elegans
Authors: Mahadik Snehal S. , Lundquist Erik A. 
Published: May 2023

AbstractUNC-6/Netrin is a conserved bi-functional guidance cue which regulates dorsal-ventral axon guidance inC. elegans. In the Polarity/Protrusion model of UNC-6/Netrin mediated dorsal growth away from UNC-6/Netrin, The UNC-5 receptor first polarizes the VD growth cone such that filopodial protrusions are biased dorsally. Based on this polarity, the UNC-40/DCC receptor stimulates growth cone lamellipodial and filopodial protrusion dorsally. The UNC-5 receptor maintains dorsal polarity of protrusion, and inhibits growth cone protrusion ventrally, resulting in net dorsal growth cone advance. Work presented here demonstrates a novel role of a previously undescribed, conserved short isoform of UNC-5 (UNC-5B). UNC-5B lacks the cytoplasmic domains of UNC-5 long, including the DEATH domain, the UPA/DB domain, and most of the ZU5 domain. Mutations that specifically affect only theunc-5long isoforms were hypomorphic, suggesting a role ofunc-5Bshort. A mutation specifically affectingunc-5Bcause loss of dorsal polarity of protrusion and reduced growth cone filopodial protrusion, the opposite ofunc-5long mutations. Transgenic expression ofunc-5Bpartially rescuedunc-5axon guidance defects, and resulted in large growth cones. Tyrosine 482 (Y482) in the cytoplasmic juxtamembrane region has been shown to be important for UNC-5 function, and is present in both UNC-5 long and UNC-5B short. Results reported here show that Y482 is required for the function of UNC-5 long and for some functions of UNC-5B short. Finally, genetic interactions withunc-40andunc-6suggest that UNC-5B short acts in parallel to UNC-6/Netrin to ensure robust growth cone lamellipodial protrusion. In sum, these results demonstrate a previously-undescribed role for the UNC-5B short isoform, which is required for dorsal polarity of growth cone filopodial protrusion and to stimulate growth cone protrusion, in contrast to the previously-described role of UNC-5 long in inhibiting growth cone protrusion.
descSPIM: Affordable and Easy-to-Build Light-Sheet Microscopy for Tissue Clearing Technique Users
Authors: Otomo Kohei , Omura Takaki , Nozawa Yuki , Saito Yuri , Susaki Etsuo A. 
Published: May 2023

SummaryDespite the easier use of multiple tissue clearing techniques in recent years, poor access to adequate light-sheet fluorescence microscopy remains a major obstacle for biomedical end users. Here, we propose a solution by developing descSPIM (desktop-equipped SPIM forcleared specimens) as a low-cost ($20,000–50,000), low-expertise (one-day installation by a non-expert), yet practically substantial do-it-yourself light-sheet microscopy. Academically open-sourced (https://github.com/dbsb-juntendo/descSPIM), descSPIM allows routine three-dimensional imaging of cleared samples in minutes.