bluuebunny/crossref_metadata_2025_split huggingface dataset:
The differential role of practical and emotional support in infant feeding experience in the UK
Authors: Myers S. , Page A. E. , Emmott E. H. 
Published: May 2021

Social support is a known determinant of breastfeeding behaviour and is generally considered beneficial. However, social support encompasses a myriad of different supportive acts, providing scope for diverse infant feeding outcomes. Given the vulnerability of postpartum mental health, this paper aims to explore both how support prolongs breastfeeding and which forms of support promote the positive experience of all infant feeding. Using survey data collected online from 515 UK mothers with infants aged 0–108 weeks, Cox regression models assessed the relationship between receiving different types of support, support need and breastfeeding duration. Quasi-binomial logistic regression models assessed the relationship between receiving support, infant feeding mode and maternal experience of infant feeding. Rates of negative infant feeding experience indicate the widespread need for support: e.g. 38% of currently, 47% of no longer and 31% of never breastfeeding women found infant feeding stressful. Overall, practical support via infant feeding broadly predicted shorter breastfeeding durations and poorer feeding experience; results in relation to other forms of support were more complex. Our findings indicate different forms of support have different associations with infant feeding experience. They also highlight the wide range of individuals beyond the nuclear family on which postpartum mothers in the UK rely.
This article is part of the theme issue ‘Multidisciplinary perspectives on social support and maternal–child health’.
Does maternal grandmother's support improve maternal and child nutritional health outcomes? Evidence from Merida, Yucatan, Mexico
Authors: Vázquez-Vázquez Adriana , Fewtrell Mary S. , Chan-García Hidekel , Batún-Marrufo Carolina , Dickinson Federico , Wells Jonathan C. 
Published: May 2021

In humans, high levels of investment are required to raise offspring, because of the prolonged developmental period and short interbirth intervals. The costs borne by individual mothers may be mitigated by obtaining social support from others. This strategy could be particularly valuable for first-time mothers, who lack first-hand experience and whose offspring have higher mortality risk than later-born siblings. As raising children is potentially stressful, mothers may gain from others sharing their experience, providing knowledge/information and emotional support. Being genetically related to both mother and grandchild, maternal grandmothers may be especially well placed to provide such support, while also gaining fitness benefits. We tested the over-arching hypothesis that first-time mothers and their young children supported by the maternal grandmother would have lower levels of stress and better health outcomes, compared to mother–infant dyads lacking such grandmaternal support. A cohort of 90 mother–infant dyads (52 with grandmaternal support, 38 without) was recruited in Merida, Mexico. We assessed anthropometry and body composition in both mother and child, along with maternally perceived stress and child temperament, and documented maternal social relationships. No differences were found in perceived stress/temperament or anthropometry of either mothers or children, according to the presence/absence of grandmaternal support. However, a composite score of whether grandmothers provided advice on infant feeding was positively associated with child nutritional status. Mothers without grandmaternal support reported seeking more informational and emotional support from other female relatives for childcare, potentially compensating for limited/absent grandmaternal support. Our findings may help develop interventions to improve maternal and child health by targeting the dynamics of maternal social networks.
This article is part of the theme issue ‘Multidisciplinary perspectives on social support and maternal–child health’.
Modulated TRPC1 expression predicts sensitivity of breast cancer to doxorubicin and magnetic field therapy: segue towards a precision medicine approach
Authors: Tai Yee Kit , Wing Chan Karen Ka , Hua Fong Charlene Hui , Ramanan Sharanya , Yee Yap Jasmine Lye , Yin Jocelyn Naixin , Yip Yun Sheng , Tan Wei Ren , Fern Koh Angele Pei , Tan Nguan Soon , Chan Ching Wan , Ju Huang Ruby Yun , Franco-Obregón Alfredo 
Published: May 2021

AbstractBackgroundChemotherapy is the mainstream treatment modality for invasive breast cancer. Nonetheless, chemotherapy-associated adverse events can result in a patient terminating treatment. We show that transient receptor potential channel 1 (TRPC1) expression level predicts breast cancer sensitivity to doxorubicin (DOX) and pulsed electromagnetic field (PEMF) therapies.MethodsThe effects of PEMFs were examined with respect to:1) the growth of MCF-7 cellsin vitro;2) MCF-7 tumors implanted into a chicken chorioallantoic membrane (CAM) model and;3) patient-derived and MCF-7 breast cancer xenografts in mice.Potential synergisms between DOX and PEMF therapies were examined in these model systems and under conditions of TRPC1 overexpression or silencingin vitro.ResultsPEMF exposure impaired the survival of MCF-7 cells, but not that of nonmalignant MCF10A breast cells. The effects of PEMF- and DOX-therapies synergizedin vitroat compromising MCF-7 cell growth. Synergism could be corroboratedin vivowith patient-derived xenograft mouse models, wherein PEMF exposure alone or in combination with DOX reduced tumor size. Stable overexpression of TRPC1 enhanced the vulnerability of MCF-7 cells to both DOX and PEMF exposure and promoted proliferation, whereas chronic DOX exposure reduced TRPC1 expression, induced chemoresistance, precluded response to PEMF exposure and mitigated proliferation. Markers of metastasis includingSLUG, SNAIL, VIMENTIN, andE-CADHERINas well as invasiveness were also positively correlated with TRPC1 channel expression.ConclusionThe presented data supports a potential role of PEMF-therapy as an effective companion therapy to DOX-based chemotherapy for the treatment of breast cancers characterized by elevated TRPC1 expression levels.
Coordinated changes in glycosylation regulate the germinal centre through CD22
Authors: Enterina Jhon R. , Sarkar Susmita , Streith Laura , Jung Jaesoo , Arlian Britni M. , Meyer Sarah J. , Takematsu Hiromu , Xiao Changchun , Baldwin Troy A. , Nitschke Lars , Shlomchick Mark J. , Paulson James C. , Macauley Matthew S. 
Published: May 2021

AbstractGerminal centres (GC) are sites of B-cell expansion and selection, which are essential for antibody affinity maturation. Compared to naive follicular B-cells, GC B-cells have several notable changes in their cell surface glycans. While these changes are routinely used to identify the GC, functional roles for these changes have yet to be ascribed. Detection of GCs by the antibody GL7 reflects a reduction in the glycan ligands for CD22, which is an inhibitory co-receptor of the B-cell receptor (BCR). To test a functional role for downregulated CD22 ligands in the GC, we generated a mouse model that maintains CD22 ligands on GC B-cells. With this model, we demonstrate that glycan remodeling is crucial for proper GC B-cell response, including plasma cell output and affinity maturation of antibodies. The defect we observe in this model is dependent on CD22, highlighting that coordinated downregulation of CD22 ligands on B cells plays a critical function in the GC. Collectively, our study uncovers a crucial role for glycan remodeling and CD22 in B-cell fitness in the GC.
Mitotic checkpoint gene expression is tuned by coding sequences
Authors: Esposito Eric , Weidemann Douglas E. , Rogers Jessie M. , Morton Claire M. , Baybay Erod Keaton , Chen Jing , Hauf Silke 
Published: May 2021

AbstractThe mitotic checkpoint (also called spindle assembly checkpoint, SAC) is a signaling pathway that safeguards proper chromosome segregation. Proper functioning of the SAC depends on adequate protein concentrations and appropriate stoichiometries between SAC proteins. Yet very little is known about SAC gene expression. Here, we show in fission yeast (S. pombe) that a combination of short mRNA half-lives and long protein half-lives supports stable SAC protein levels. For the SAC genesmad2+andmad3+, their short mRNA half-lives are supported by a high frequency of non-optimal codons. In contrast,mad1+mRNA has a short half-life despite a low frequency of non-optimal codons and despite the lack of known destabilizing motifs. Hence, different SAC genes employ different strategies of expression. We further show that Mad1 homodimers form co-translationally, which may necessitate a certain codon usage pattern. Taken together, we propose that the codon usage of SAC genes is fine-tuned for proper SAC function. Our work shines light on gene expression features that promote spindle assembly checkpoint function and suggests that synonymous mutations may weaken the checkpoint.
Passive and active immunity in infants born to mothers with SARS-CoV-2 infection during pregnancy: Prospective cohort study
Authors: Song Dongli , Prahl Mary , Gaw Stephanie L. , Narasimhan SudhaRani , Rai Daljeet , Huang Angela , Flores Claudia , Lin Christine Y. , Jigmeddagva Unurzul , Wu Alan H.B. , Warrier Lakshmi , Levan Justine , Nguyen Catherine B.T. , Callaway Perri , Farrington Lila , Acevedo Gonzalo R. , Gonzalez Veronica J. , Vaaben Anna , Nguyen Phuong , Atmosfera Elda , Marleau Constance , Anderson Christina , Misra Sonya , Stemmle Monica , Cortes Maria , McAuley Jennifer , Metz Nicole , Patel Rupalee , Nudelman Matthew , Abraham Susan , Byrne James , Jegatheesan Priya 
Published: May 2021

AbstractOBJECTIVETo investigate maternal immunoglobulins’ (IgM, IgG) response to SARS-CoV-2 infection during pregnancy and IgG transplacental transfer, to characterize neonatal antibody response to SARS-CoV-2 infection, and to longitudinally follow actively- and passively-acquired SARS-CoV-2 antibodies in infants.DESIGNA prospective observational study.SETTINGA public healthcare system in Santa Clara County (CA, USA).PARTICIPANTSWomen with SARS-CoV-2 infection during pregnancy and their infants were enrolled between April 15, 2020 and March 31, 2021.OUTCOMESSARS-CoV-2 serology analyses in the cord and maternal blood at delivery and longitudinally in infant blood between birth and 28 weeks of life.RESULTSOf 145 mothers who tested positive for SARS-CoV-2 during pregnancy, 86 had symptomatic infections: 78 with mild-moderate symptoms, and eight with severe-critical symptoms. Of the 147 newborns, two infants showed seroconversion at two weeks of age with high levels of IgM and IgG, including one premature infant with confirmed intrapartum infection. The seropositivity rates of the mothers at delivery was 65% (95% CI 0.56-0.73) and the cord blood was 58% (95% CI 0.49-0.66). IgG levels significantly correlated between the maternal and cord blood (Rs= 0.93, p< 0.0001). IgG transplacental transfer ratio was significantly higher when the first maternal positive PCR was 60-180 days before delivery compared to <60 days (1.2 vs. 0.6, p=<0.0001). Infant IgG negative conversion rate over follow-up periods of 1-4, 5-12, and 13-28 weeks were 8% (4/48), 12% (3/25), and 38% (5/13), respectively. The IgG seropositivity in the infants was positively related to IgG levels in the cord blood and persisted up to six months of age.CONCLUSIONSMaternal SARS-CoV-2 IgG is efficiently transferred across the placenta when infections occur more than two months before delivery. Maternally-derived passive immunity may protect infants up to six months of life. Neonates mount a strong antibody response to perinatal SARS-CoV-2 infection.
Arrestin-mediated Desensitization Enables Olfactory Discrimination inC. elegans
Authors: Merritt Daniel M. , MacKay-Clackett Isabel , Almeida Sylvia M. T. , Tran Celina , Ansar Safa , van der Kooy Derek 
Published: May 2021

AbstractIn the mammalian olfactory system, crosstalk among diverse olfactory signals is minimized through labelled line coding: individual neurons express one or few olfactory receptors among those encoded in the genome. Labelled line coding allows for separation of stimuli during mammalian olfactory signal transduction, however, in the nematode wormCaenorhabditis elegans, 1,300 olfactory receptors are primarily expressed in only 32 neurons, precluding this strategy. Here we report genetic, pharmacological and behavioural evidence that β-arrestin-mediated desensitization of olfactory receptors, working downstream of the kinase GRK-1, enables discrimination between intra-neuronal olfactory stimuli, but that this discrimination relies on quantitative, rather than qualitative differences in signalling. Our findings suggest thatC. elegansexploits β-arrestin desensitization to maximize responsiveness to novel odors, allowing for behaviourally appropriate responses to olfactory stimuli despite the large number of olfactory receptors signalling in single cells. This represents a fundamentally different solution to the problem of olfactory discrimination than that which evolved in mammals, allowing for economical use of an extremely limited number of sensory neurons.
Quantifying the Tissue-Specific Regulatory Information within Enhancer DNA Sequences
Authors: Benner Philipp , Vingron Martin 
Published: May 2021

AbstractRecent efforts to measure epigenetic marks across a wide variety of different cell types and tissues provide insights into the cell type-specific regulatory landscape. We use this data to study if there exists a correlate of epigenetic signals in the DNA sequence of enhancers and explore with computational methods to what degree such sequence patterns can be used to predict cell type-specific regulatory activity. By constructing classifiers that predict in which tissues enhancers are active, we are able to identify sequence features that might be recognized by the cell in order to regulate gene expression. While classification performances vary greatly between tissues, we show examples where our classifiers correctly predict tissue specific regulation from sequence alone. We also show that many of the informative patterns indeed harbor transcription factor footprints.
Genomic sequences and RNA binding proteins predict RNA splicing kinetics in various single-cell contexts
Authors: Hou Ruiyan , Huang Yuanhua 
Published: May 2021

AbstractRNA splicing is a key step of gene expression in higher organisms. Accurate quantification of the two-step splicing kinetics is of high interests not only for understanding the regulatory machinery, but also for estimating the RNA velocity in single cells. However, the kinetic rates remain poorly understood due to the intrinsic low content of unspliced RNAs and its stochasticity across contexts. Here, we estimated the relative splicing efficiency across a variety of single-cell RNA-Seq data with scVelo. We further extracted three large feature sets including 92 basic genomic sequence features, 65,536 octamers and 120 RNA binding proteins features and found they are highly predictive to RNA splicing efficiency across multiple tissues on human and mouse. A set of important features have been identified with strong regulatory potentials on splicing efficiency. This predictive power brings promise to reveal the complexity of RNA processing and to enhance the estimation of single-cell RNA velocity.
Inferring species compositions of complex fungal communities from long- and short-read sequence data
Authors: Hu Yiheng , Irinyi Laszlo , Vi Hoang Minh Thuy , Eenjes Tavish , Graetz Abigail , Stone Eric , Meyer Wieland , Schwessinger Benjamin , Rathjen John P. 
Published: May 2021

AbstractBackgroundThe kingdom fungi is crucial for life on earth and is highly diverse. Yet fungi are challenging to characterize. They can be difficult to culture and may be morphologically indistinct in culture. They can have complex genomes of over 1 Gb in size and are still underrepresented in whole genome sequence databases. Overall their description and analysis lags far behind other microbes such as bacteria. At the same time, classification of species via high throughput sequencing without prior purification is increasingly becoming the norm for pathogen detection, microbiome studies, and environmental monitoring. However, standardized procedures for characterizing unknown fungi from complex sequencing data have not yet been established.ResultsWe compared different metagenomics sequencing and analysis strategies for the identification of fungal species. Using two fungal mock communities of 44 phylogenetically diverse species, we compared species classification and community composition analysis pipelines using shotgun metagenomics and amplicon sequencing data generated from both short and long read sequencing technologies. We show that regardless of the sequencing methodology used, the highest accuracy of species identification was achieved by sequence alignment against a fungi-specific database. During the assessment of classification algorithms, we found that applying cut-offs to the query coverage of each read or contig significantly improved the classification accuracy and community composition analysis without significant data loss.ConclusionOverall, our study expands the toolkit for identifying fungi by improving sequence-based fungal classification, and provides a practical guide for the design of metagenomics analyses.
Fine-tuning of β-catenin in thymic epithelial cells is required for postnatal T cell development
Authors: Fujimori Sayumi , Ohigashi Izumi , Abe Hayato , Taketo Makoto M. , Takahama Yousuke , Takada Shinji 
Published: May 2021

AbstractIn the thymus, the thymic epithelium provides a microenvironment essential for the development of functionally competent and self-tolerant T cells. Previous findings showed that modulation of Wnt/β-catenin signaling in thymic epithelial cells (TECs) disrupts embryonic thymus organogenesis. However, the role of β-catenin in TECs for postnatal T cell development remains to be elucidated. Here, we analyzed gain-of-function (GOF) and loss-of-function (LOF) of β-catenin highly specific in TECs. We found that GOF of β-catenin in TECs results in severe thymic dysplasia and T cell deficiency beginning from the embryonic period. By contrast, LOF of β-catenin in TECs reduces the number of cortical TECs and thymocytes modestly and only postnatally. These results indicate that fine-tuning of β-catenin expression within a permissive range is required for TECs to generate an optimal microenvironment to support postnatal T cell development.
Frizzled3 inhibits Vangl2-Prickle3 association to establish planar cell polarity in the vertebrate neural plate
Authors: Chuykin Ilya , Itoh Keiji , Kim Kyeongmi , Sokol Sergei Y. 
Published: May 2021

SUMMARYThe orientation of epithelial cells in the plane of the tissue, known as planar cell polarity (PCP), is regulated by interactions of asymmetrically localized PCP protein complexes. In theXenopusneural plate, Van Gogh-like2 (Vangl2) and Prickle3 (Pk3) proteins form a complex at the anterior cell boundaries, but how this complex is regulatedin vivoremains largely unknown. Here we show that Vangl2-Pk3 association is inhibited by Frizzled3 (Fz3), a core PCP protein that is specifically expressed in the neuroectoderm and is essential for the establishment of PCP in this tissue. Proximity biotinylation and crosslinking studies revealed that the Vangl2-Pk3 interaction is suppressed by overexpressed Fz3, but enhanced in Fz3 morphants. In addition, Fz3 induced Vangl2 phosphorylation on T76 and T78, and this phosphorylation was required for Fz3-mediated inhibition of Vangl2-Pk3 complex formation. Consistent with this observation, the complex of Pk3 with nonphosphorylatable Vangl2 was not polarized in the neural plate. These findings provide evidence forin vivoregulation of the Vangl2-Pk3 complex formation and localization by a Frizzled receptor.
Density-dependent effects are the main determinants of variation in growth dynamics between closely related bacterial strains
Authors: Hilau Sabrin , Katz Sophia , Wasserman Tanya , Hershberg Ruth , Savir Yonatan 
Published: May 2021

AbstractAlthough closely related genetically, bacterial strains belonging to the same species show significant variability in their growth and death dynamics. However, our understanding of the underlying processes that lead to this variability is still lacking. Here, we measured the growth and death dynamics of 11 strains ofE. colioriginating from different hosts and developed a mathematical model that captures their growth and death dynamics. Our model considers two environmental factors that determine growth dynamics: resource utilization efficiency and density-dependent growth inhibition. Here we show that both factors are required to capture the measured dynamics. Interestingly, our model results indicate that the main process that determines the major differences between the strains is the critical density at which they slow down their growth, rather than maximal growth rate or death rate. Finally, we found that bacterial growth and death dynamics can be reduced to only two dimensions and described by death rates and density-dependent growth inhibition alone.ImportanceUnderstanding the dynamics of bacterial growth has been an area of intense study. However, these dynamics have often been characterized through the narrow prism of describing growth rates, without considering parameters that may modulate these rates. Here, we generate a model that describes bacterial growth and death dynamics, incorporating two essential, growth-modulating factors: density-dependent reductions in growth rates and resource utilization efficiency. This model allows us to demonstrate that variation in the growth curves of closely related bacterial strains can be reduced to two dimensions and explained almost entirely by variation in the cellular density at which bacteria slow down their growth, combined with their death rates.
Neuronal genetic rescue normalizes brain network dynamics in a lysosomal storage disorder despite persistent storage accumulation
Authors: Ahrens-Nicklas Rebecca C. , Tecedor Luis , Hall Arron F. , Kane Owen , Chung Richard J. , Lysenko Elena , Marsh Eric D. , Stein Colleen S. , Davidson Beverly L. 
Published: May 2021

AbstractAlthough neurologic symptoms occur in two-thirds of lysosomal storage disorders (LSDs), for most we do not understand the mechanisms underlying brain dysfunction. A major unanswered question is if the pathogenic hallmark of LSDs, storage accumulation, induces functional defects directly or is a disease bystander. Also, for most LSDs we do not know the impact of loss-of-function in individual cell types. Understanding these critical questions are essential to therapy development. Here, we determined the impact of genetic rescue in distinct cell types on neural circuit dysfunction in CLN3 disease, the most common pediatric dementia and a representative LSD. We restoredCln3expression via AAV-mediated gene delivery and conditional genetic rescue in a CLN3 mouse model. Surprisingly, we found that low-level rescue ofCln3expression in neurons alone normalized clinically-relevant electrophysiologic markers of network dysfunction, despite the presence of substantial residual histopathology, in contrast to restoring expression in astrocytes. Thus, loss of Cln3 function in neurons, not storage accumulation, underlies neurologic dysfunction in CLN3 disease, implying that storage clearance may be an inappropriate target for therapy development and an ineffectual biomarker.