bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors influencing modern contraceptive use in Kinshasa, Democratic Republic of Congo
Authors: Mokeke Reagan Ingoma , Han Whiejong M. , Kang Hee Cheol , Kim Han Nah 
Published: February 2023

ABSTRACTFamily planning allows individuals and couples to schedule and regulate births at the appropriate time and number. Women who carry unplanned pregnancies are susceptible to postnatal complications, which directly impact their well-being, making them a burden to society. There are 27600 adolescent abortions in the Democratic Republic of the Congo (DRC), accounting for about 19 percent of abortion cases in Kinshasa in 2021 while the reproduction rate remains one of the highest in the world at 5.7 and a low contraceptive prevalence across all methods (28%) in 2022. This study aims to determine the factors that influence modern contraceptive use among women in Kinshasa city in the Democratic Republic of Congo by using data from the PMA 2020 cross-sectional survey to assess the association between predictors and modern contraceptive use through logistic regression analysis (OR and 95% CI).Findings show that older women are more likely to use modern contraceptive than younger (15-22) and their sensitivity diminishes as they age. This likelihood is also high when women do not discuss this topic with their partner. As household size increases, women’s use of modern contraceptives is positively affected (OR: 4.993). The same is true for women who have given birth at least compared to those who have never given birth (OR: 2.313). Wanting fewer children makes her more likely to use these contraceptives than when she wants more (OR: 1.244). Male condoms, emergency contraceptives and pills were used more by women aged 15-31 while the most common contraceptive method used only by older women is female sterilization.In a country with rapid population growth such as the DRC, the strategy should focus on raising awareness among young women through school programs, health facilities, community outreach, and other means to achieve optimal use of modern contraceptives based on commonly used methods and involving adult men and women.
The fading of the mpox outbreak among men who have sex with men: a mathematical modelling study
Authors: Xiridou Maria , Miura Fuminari , Adam Philippe , Op de Coul Eline , de Wit John , Wallinga Jacco 
Published: February 2023

ABSTRACTBackgroundIn the Netherlands, the number of mpox cases started declining before mpox vaccination was initiated. Most cases were men who have sex with men (MSM). We investigated whether the decline in mpox could be attributed to infection-induced immunity or behavioural adaptations.MethodsWe developed a transmission model and accounted for possible behavioural adaptations: less casual partners and shorter time until MSM with mpox refrain from sexual contacts.ResultsWithout behavioural adaptations, the peak in modelled cases matched observations, but the decline was less steep than observed. With behavioural adaptations in the model, we found a decline of 16-18% in numbers of casual partners in June and 13-22% in July 2022. Model results showed a halving of the time before refraining from sex. When mpox vaccination started, 57% of MSM with very high sexual activity in the model had been infected. Model scenarios revealed that the outbreak could have waned by November 2022 even without vaccination.ConclusionsThe limited duration of the mpox outbreak in the Netherlands can be ascribed primarily to infection-induced immunity among MSM with high sexual activity levels. The decline was accelerated by behavioural adaptations. Immunity among those most sexually active is essential to impede mpox resurgence.Short summaryModelling study shows that the decline in mpox cases among MSM in the Netherlands was primarily due to infection-induced immunity among those with high sexual activity levels and accelerated by behavioural adaptions. The outbreak could have faded even without vaccination.
Influence of root cortical aerenchyma on the rhizosphere microbiome of field-grown maize
Authors: Galindo-Castañeda Tania , Rojas Claudia , Karaöz Ulas , Brodie Eoin L. , Brown Kathleen M. , Lynch Jonathan P. 
Published: February 2023

ABSTRACTThe root anatomical phenotype root cortical aerenchyma (RCA) decreases the metabolic cost of soil exploration and improves plant growth under drought and low soil fertility. RCA may also change the microenvironment of rhizosphere microorganisms by increasing oxygen availability or by reducing carbon rhizodeposition. We tested the hypothesis that plants with contrasting expression of RCA have different rhizosphere prokaryotic communities. Maize inbreds were grown in two field sites, Limpopo Province, South Africa and Pennsylvania, USA, and their rhizosphere soil sampled at flowering. High- and low-nitrogen fertilization was imposed as separate treatments in the experiment in South Africa. The rhizosphere microbial composition of plants with contrasting RCA was characterized by metabarcoding of the 16S rRNA genes. Geographic location was the most important factor related to the composition of rhizosphere microbial communities. In the site in South Africa, RCA explained greater percent of variance (9%) in the composition of microbial communities than genotype (7%). Although other root anatomical and architectural phenotypes were studied as possible cofactors affecting the microbial composition, RCA was among the best significant explanatory variables for the South African site although it was neutral in the Pennsylvania site. High-RCA rhizospheres significantly enriched OTUs of the familiesBurkholderiaceae(in South Africa) andBacillaceae(in USA), compared to low-RCA plants, and OTUs of the familiesBeijerinckiaceaeandSphingomonadaceaewere enriched at the two nitrogen levels in high RCA plants in South Africa. Our results are consistent with the hypothesis that RCA is an important factor for rhizosphere microbial communities, especially under suboptimal nitrogen conditions.
Perturb-tracing enables high-content screening of multiscale 3D genome regulators
Authors: Cheng Yubao , Hu Mengwei , Yang Bing , Jensen Tyler B , Yang Tianqi , Yu Ruihuan , Ma Zhaoxia , Radda Jonathan S D , Jin Shengyan , Zang Chongzhi , Wang Siyuan 
Published: February 2023

AbstractThree-dimensional (3D) genome organization becomes altered during development, aging, and disease1–23, but the factors regulating chromatin topology are incompletely understood and currently no technology can efficiently screen for new regulators of multiscale chromatin organization. Here, we developed an image-based high-content screening platform (Perturb-tracing) that combines pooled CRISPR screen, a new cellular barcode readout method (BARC-FISH), and chromatin tracing. We performed a loss-of-function screen in human cells, and visualized alterations to their genome organization from 13,000 imaging target-perturbation combinations, alongside perturbation-paired barcode readout in the same single cells. Using 1.4 million 3D positions along chromosome traces, we discovered tens of new regulators of chromatin folding at different length scales, ranging from chromatin domains and compartments to chromosome territory. A subset of the regulators exhibited 3D genome effects associated with loop-extrusion and A-B compartmentalization mechanisms, while others were largely unrelated to these known 3D genome mechanisms. We found that the ATP-dependent helicase CHD7, the loss of which causes the congenital neural crest syndrome CHARGE24and a chromatin remodeler previously shown to promote local chromatin openness25–27, counter-intuitively compacts chromatin over long range in different genomic contexts and cell backgrounds including neural crest cells, and globally represses gene expression. The DNA compaction effect of CHD7 is independent of its chromatin remodeling activity and does not require other protein partners. Finally, we identified new regulators of nuclear architectures and found a functional link between chromatin compaction and nuclear shape. Altogether, our method enables scalable, high-content identification of chromatin and nuclear topology regulators that will stimulate new insights into the 3D genome functions, such as global gene and nuclear regulation, in health and disease.
AGAP1-associated endolysosomal trafficking abnormalities link gene-environment interactions in a neurodevelopmental disorder
Authors: Lewis Sara A. , Bakhtiari Somayeh , Forstrom Jacob , Bayat Allan , Bilan Frédéric , Le Guyader Gwenaël , Alkhunaizi Ebba , Vernon Hilary , Padilla-Lopez Sergio R. , Kruer Michael C. 
Published: February 2023

AbstractAGAP1is an Arf1 GAP that regulates endolysosomal trafficking. Damaging variants have been linked to cerebral palsy and autism. We report 3 new individuals with microdeletion variants inAGAP1. Affected individuals have intellectual disability (3/3), autism (3/3), dystonia with axial hypotonia (1/3), abnormalities of brain maturation (1/3), growth impairment (2/3) and facial dysmorphism (2/3). We investigated mechanisms potentially underlyingAGAP1neurodevelopmental impairments using theDrosophilaortholog,CenG1a. We discovered reduced axon terminal size, increased neuronal endosome abundance, and elevated autophagy at baseline. Given potential incomplete penetrance, we assessed gene-environment interactions. We found basal elevation in phosphorylation of the integrated stress-response protein eIF2α and inability to further increase eIF2α-P with subsequent cytotoxic stressors.CenG1a-mutant flies have increased lethality from exposure to environmental insults. We propose a model wherein disruption ofAGAP1function impairs endolysosomal trafficking, chronically activating the integrated stress response, and leaving AGAP1-deficient cells susceptible to a variety of second hit cytotoxic stressors. This model may have broader applicability beyondAGAP1in instances where both genetic and environmental insults co-occur in individuals with neurodevelopmental disorders.Summary statementWe describe 3 additional patients with heterozygous AGAP1 deletion variants and use a loss of functionDrosophilamodel to identify defects in synaptic morphology with increased endosomal sequestration, chronic autophagy induction, basal activation of eIF2α-P, and sensitivity to environmental stressors.
Integrase-associated niche differentiation of endogenous large DNA viruses in crustaceans
Authors: Kawato Satoshi , Nozaki Reiko , Kondo Hidehiro , Hirono Ikuo 
Published: February 2023

AbstractCrustacean genomes harbor sequences originating from nimaviruses, a family of large double-stranded DNA viruses infecting crustaceans. In this study, we recovered metagenome-assembled genomes of 25 endogenous nimaviruses from crustacean genome data. Phylogenetic analysis revealed four major lineages withinNimaviridae, and for three of these lineages, we propose novel genera of endogenous nimaviruses: “Majanivirus” and “Pemonivirus” identified from penaeid shrimp genomes, and “Clopovirus” identified from terrestrial isopods. Majanivirus genomes contain multiple eukaryotic-like genes such as baculoviral inhibitor of apoptosis repeat-containing genes, innexins, and heat shock protein 70-like genes, some of which contain introns. An alignment of long reads revealed that that each endogenous nimavirus species specifically inserts into host microsatellites or within 28S rDNA. This insertion preference was associated with the type of virus-encoded DNA recombination enzymes, the integrases. Majaniviruses, pemoniviruses, some whispoviruses, and possibly clopoviruses specifically insert into the arthropod telomere repeat motif (TAACC/GGTTA)n and all possessed a specific tyrosine recombinase family. Pasiphaea japonica whipovirus and Portunus trituberculatus whispovirus, the closest relatives of white spot syndrome virus, integrate into the host 28S rDNA and are equipped with members of another family of tyrosine recombinases that are distantly related to telomere-specific tyrosine recombinases. Endogenous nimavirus genomes identified from sesarmid crabs, which lack tyrosine recombinases and are flanked by a 46-bp inverted terminal repeat, integrate into (AT/TA)n microsatellites through the acquisition of a Ginger2-like cut- and-paste DDE transposase. These results suggest that endogenous nimaviruses are giant transposable elements that occupy different sequence niches through the acquisition of different integrase families.ImportanceCrustacean genomes harbor sequences originating from a family of large DNA viruses called nimaviruses, but it is unclear why they are present. We show that endogenous nimaviruses selectively insert into repetitive sequences within the host genome, and this insertion specificity was correlated with different types of integrases, which are DNA recombination enzymes encoded by the nimaviruses themselves. This suggests that endogenous nimaviruses have colonized various genomic niches through the acquisition of integrases with different insertion specificities. Our results point to a novel survival strategy of endogenous large DNA viruses colonizing the host genomes. These findings may clarify the evolution and spread of nimaviruses in crustaceans and lead to measures to control and prevent the spread of pathogenic nimaviruses in aquaculture settings.
Dopamine increases accuracy and lengthens deliberation time in explicit motor skill learning
Authors: Leow Li-Ann , Bernheine Lena , Carroll Timothy J , Dux Paul E , Filmer Hannah L 
Published: February 2023

AbstractAlthough animal research implicates a central role for dopamine in motor skill learning, a direct causal link has yet to be established in neurotypical humans. Here, we tested if a pharmacological manipulation of dopamine alters motor learning, using a paradigm which engaged explicit, goal-directed strategies. Participants (27 females, 11 males, aged 18-29 years) first consumed either 100mg of Levodopa (n=19), a dopamine precursor that increases dopamine availability, or placebo (n=19). Then, during training, participants learnt the explicit strategy of aiming away from presented targets by instructed angles of varying sizes. Targets shifted mid-movement by the instructed aiming angle. Task success was thus contingent upon aiming accuracy. The effect of the dopamine manipulations on skill learning was assessed during training, and at an overnight follow-up. Increasing dopamine availability improved aiming accuracy and lengthened reaction times, particularly for larger, more difficult aiming angles, both at training, and at follow-up. Results support the proposal that dopamine is important in decisions to engage instrumental motivation to optimise performance, particularly when learning to execute goal-directed strategies in motor skill learning.
Evaluation of Fecal Occult Blood Testing Kits for Rapid Point-of-Care Diagnosis of Invasive Diarrhea in Young Children
Authors: Kwasi David A. , Adewole Pelumi D. , Akinlabi Olabisi C. , Ekpo Stella E. , Okeke Iruka N. 
Published: February 2023

AbstractBackgroundAntimicrobials are only indicated in acute childhood diarrhea when the infection is invasive (and therefore often bloody), or persistent. Rapid and cost-effective screening for invasive diarrhea at the point of care can therefore inform treatment decisions. Multiple rapid fecal occult blood testing (FOBT) kit brands are widely available in Nigeria. This study aimed to compare the diagnostic utility of locally procurable FOBT kits in invasive infantile diarrhea to the innovators product, using fecal microscopy as the gold standard.Materials and MethodsFecal specimens from 46 children under 5 years old with diarrhea, being collected as part of ongoing case-control studies, were tested according to manufacturers’ instructions for each of five FOBT kits. Fecal microscopy for occult blood, and culture for bacterial pathogens were also performed concomitantly using standard procedures.ResultsStool microscopy confirmed almost ubiquitous presence of white blood cells in stool from children with diarrhea, whereas red blood cells were less commonly detected. A positive FOBT reaction was only seen when red blood cells were present at more than trace levels and was partially correlated with the presence of a potentially invasive pathogen. Each of the five FOBT kits tested showed 54-61% sensitivity, 87-90% specificity, and acceptable positive- and negative-predictive values for invasive diarrhea.ConclusionsFour inexpensive, locally available kits identified invasive pediatric diarrheas showed reasonable performance for detecting likely invasive diarrhea and performed similarly to the more difficult-to-procure innovator’s product. FOBT kits are a rapid option for presumptive diagnosis of invasive diarrhea, are a viable alternative to stool microscopy for paediatric specimens at the point-of-care, and could serve as early warning indicators for dysentery outbreaks.
Deciphering transcriptomic signatures explaining the phenotypic plasticity of non-heading lettuce genotypes under artificial light conditions
Authors: Yamashita Hiroto , Wada Kaede C. , Inagaki Noritoshi , Fujimoto Zui , Yonemaru Jun-ichi , Itoh Hironori 
Published: February 2023

AbstractElucidating the mechanisms and pathways involved in genotype–environment (G×E) interactions and phenotypic plasticity is critical for improving plant growth. Controlled environment agricultural systems allow growers to modulate the environment for particular genotypes. In this study, we evaluated the effects of interactions among 14 genotypes and four artificial light environments on leaf lettuce phenotypes and dissected the underlying molecular mechanism via transcriptome-based modeling. Variations in morphological traits and phytochemical contents in response to artificial light treatments revealed significant G×E interactions. The appropriate genotype and artificial light combinations for maximizing phenotypic expression were determined on the basis of a joint regression analysis and the additive main effect and multiplicative interaction model for these G×E interactions. Transcriptome-based regression modeling explained approximately 50%–90% of the G×E variations. Further analyzes indicatedRed Lettuce Leaves 4 (RLL4) regulates UV-B and blue light signaling through the effects of the HY5–MBW pathway on flavonoid biosynthesis and contributes to natural variations in the light-responsive plasticity of lettuce traits. Our study represents an important step toward elucidating the phenotypic variations due to G×E interactions in non-heading lettuce under artificial light conditions.HighlightsSeveral morphological characteristics of lettuce genotypes were altered by different light wavelengths.A defectiveRLL4allele (rll4) induces the expression of downstream genes related to UV-B and blue light signaling through activation of the HY5–MBW pathway, which enhances phytochemical accumulation in lettuce.G×E analyzes identified the ideal genotype and artificial light combinations for individual phenotypes.Transcriptome-based modeling explained approximately 50%–90% of the G×E variations.
Imaging interorganelle phospholipid transport by extended synaptotagmins using bioorthogonally tagged lipids
Authors: Liang Dongjun , Luan Lin , Baskin Jeremy M. 
Published: February 2023

ABSTRACTThe proper distribution of lipids within organelle membranes requires rapid, interorganelle lipid transport, much of which occurs at membrane contact sites and is mediated by lipid transfer proteins (LTPs). Our current understanding of LTP mechanism and function is based largely on structural studies and in vitro reconstitution. Existing cellular assays for LTP function use indirect readouts, and it remains an open question as to whether substrate specificity and transport kinetics established in vitro are similar in cellular settings. Here, we harness bioorthogonal chemistry to develop tools for direct visualization of interorganelle transport of phospholipids between the plasma membrane (PM) and the endoplasmic reticulum (ER). Unnatural fluorescent phospholipid analogs generated by the transphosphatidylation activity of phospholipase D (PLD) at the PM are rapidly transported to the ER dependent in large part upon extended synaptotagmins (E-Syts), a family of LTPs at ER-PM contact sites. Ectopic expression of an artificial E-Syt-based tether at ER-mitochondria contact sites results in fluorescent phospholipid accumulation in mitochondria. Finally, in vitro reconstitution assays demonstrate that the fluorescent lipids are bona fide E-Syt substrates. Thus, fluorescent lipids generated in situ via PLD activity and bioorthogonal chemical tagging can enable direct visualization of the activity of LTPs that mediate bulk phospholipid transport at ER-PM contact sites.
Single-Nucleus RNA Sequencing of Developing and Mature Superior Colliculus Identifies Neuronal Diversity and Candidate Mediators of Circuit Assembly
Authors: Ayupe Ana C. , Choi James S. , Beckedorff Felipe , Catanuto Paola , Mccartan Robyn , Levay Konstantin , Park Kevin K. 
Published: February 2023

SummaryThe superior colliculus (SC) is a sensorimotor structure in the midbrain that integrates input from multiple sensory modalities to initiate motor commands. It undergoes well-characterized steps of circuit assembly during development, rendering the mouse SC a popular model to study establishment and refinement of neural connectivity. Here we performed single nucleus RNA-sequencing analysis of the mouse SC isolated at various developmental time points. Our study provides a transcriptomic landscape of the cell types that comprise the SC across murine development with particular emphasis on neuronal heterogeneity. We used these data to identify Pax7 as a marker for an anatomically homogeneous population of GABAergic neurons. Lastly, we report a repertoire of genes differentially expressed across the different postnatal ages, many of which are known to regulate axon guidance and synapse formation. Our data provide a valuable resource for interrogating the mechanisms of circuit development, and identifying markers for manipulating specific SC neuronal populations and circuits.
Ets-1 transcription factor regulates glial cell regeneration and function in planarians
Authors: Chandra Bidushi , Voas Matthew G. , Davies Erin L. , Roberts-Galbraith Rachel H. 
Published: February 2023

AbstractGlia play multifaceted roles in nervous systems in response to injury. Depending on the species, extent of injury, and glial cell type in question, glia can help or hinder the regeneration of neurons. Studying glia in the context of successful regeneration could reveal key features of pro-regenerative glia that could be exploited for improvement of human therapies. Planarian flatworms completely regenerate their nervous systems after injury—including glia—and thus provide a strong model system with which to explore glia in the context of regeneration. Here, we report that planarian glia regenerate after neurons and that glia require neural structures to regenerate near the eyespot. We find that the planarian transcription factor-encoding geneets-1promotes glial cell maintenance and regeneration. We also find thatets-1(RNAi) impairs nervous system architecture, neuronal gene expression, and animal behavior. Taken together, the discovery ofets-1as a regulator of glial persistence presents a critical first step in understanding glial regulation and potential roles of glia in planarian neurobiology. More importantly, we elucidate interrelationships between glia and neurons in the context of robust neural regeneration.