bluuebunny/crossref_metadata_2025_split huggingface dataset:
Experiences of children’s self-wetting (including incontinence) in Cox’s Bazar’s Rohingya refugee camps, Bangladesh
Authors: Alam Mahbub-Ul , Gupta Sudipta Das , Rosato-Scott Claire , Shoaib Dewan Muhammad , Ritu Asmaul Husna , Nowshin Rifat , Rahat Md Assaduzzaman , Akram Nowshad , Rose Joanne , Evans Barbara E. , Barrington Dani J. 
Published: August 2023

AbstractSelf-wetting, including incontinence, affects people of all ages, ethnicities, and cultural backgrounds, and can have a significant negative impact on quality of life. We thus explored the attitudes towards self-wetting and experiences of children (ages five to 11), their caregivers, and humanitarian experts in the Rohingya refugee camps in Cox’s Bazar, Bangladesh.We purposively selected participants from two camps where our partner organisation, World Vision Bangladesh - Cox’s Bazar, works. We conducted Key Informant Interviews (KIIs) with community members and camp officials, Story Book (SB) sessions with Rohingya children and in-depth Interviews (IDIs) with caregivers of children who participated in the SB sessions, as well as surveying the communal toilets used by children of the caregivers.Self-wetting was commonly seen among the children. Due to self-wetting, children were likely to feel embarrassed, upset and uncomfortable, and frightened to use the toilet at night; many also indicated that they would be punished by their caregivers for self-wetting. Key informants indicated that caregivers have difficulty handling children’s self-wetting because they have a limited amount of clothing, pillows, and blankets, and difficulty cleaning these items. In the sanitation survey it was evident that the toilets are not appropriate and/or accessible for children.Children in the Rohingya camps studied self-wet due to both urinary incontinence (when unable to reach a toilet in time) and because the sanitation facilities offered are inappropriate. They are teased by their peers and punished by their caregivers. The lives of children who self-wet in these camps could be improved by increasing awareness on self-wetting to decrease stigma and ease the concerns of caregivers, as well as increasing the number of toilets, ensuring they are well-lit, providing child-friendly toilets and cubicles, fixing the roads/paths that lead to sanitation to facilities and increasing the provision of relevant continence management materials.
Variant-to-function analysis of the childhood obesity chr12q13 locus implicates rs7132908 as a causal variant within the 3’ UTR ofFAIM2
Authors: Littleton Sheridan H. , Trang Khanh B. , Volpe Christina M. , Cook Kieona , DeBruyne Nicole , Maguire Jean Ann , Weidekamp Mary Ann , Boehm Keith , Chesi Alessandra , Pippin James A. , Anderson Stewart A. , Wells Andrew D. , Pahl Matthew C. , Grant Struan F.A. 
Published: August 2023

SUMMARYThe ch12q13 obesity locus is among the most significant childhood obesity loci identified in genome-wide association studies. This locus resides in a non-coding region withinFAIM2; thus, the underlying causal variant(s) presumably influence disease susceptibility via an influence oncis-regulation within the genomic region. We implicated rs7132908 as a putative causal variant at this locus leveraging a combination of our inhouse 3D genomic data, public domain datasets, and several computational approaches. Using a luciferase reporter assay in human primary astrocytes, we observed allele-specificcis-regulatory activity of the immediate region harboring rs7132908. Motivated by this finding, we went on to generate isogenic human embryonic stem cell lines homozygous for either rs7132908 allele with CRISPR-Cas9 homology-directed repair to assess changes in gene expression due to genotype and chromatin accessibility throughout a differentiation to hypothalamic neurons, a key cell type known to regulate feeding behavior. We observed that the rs7132908 obesity risk allele influenced the expression ofFAIM2along with other genes, decreased the proportion of neurons produced during differentiation, up-regulated cell death gene sets, and conversely down-regulated neuron differentiation gene sets. We have therefore functionally validated rs7132908 as a causal obesity variant which temporally regulates nearby effector genes at the ch12q13 locus and influences neurodevelopment and survival.
One Method to Sequence Them All? Comparison between Whole-Genome Sequencing (WGS) and Target Enrichment (TE) of museum specimens from the moth families Epicopeiidae and Sematuridae (Lepidoptera)
Authors: Call Elsa , Twort Victoria , Espeland Marianne , Wahlberg Niklas 
Published: August 2023

ABSTRACTThere are various possibilities for sequencing highly degraded DNA, such as target enrichment (TE), or whole-genome sequencing (WGS). Here we compare TE and WGS methods using old museum specimens of two families of moths in the superfamily Geometroidea: Epicopeiidae and Sematuridae. Until recently, the relationships of these two families were unclear, as few studies had been done. Recently two studies used the TE approach, either on relatively fresh specimens, or on old museum specimens. Here, we aim to increase the sampling of the families Epicopeiidae and Sematuridae from museum specimens using the WGS method. We show that both sequencing methods give comparable results, but, unsurprisingly, WGS recovers more data. By combining TE and WGS data, we confirm that Sematuridae are sister to Pseudobistonidae+Epicopeiidae. Relationships of genera within the families are well supported. With the costs of WGS decreasing, we suggest that using low-coverage whole genome sequencing is becoming an increasingly viable option in the phylogenomics of insects.
How a reaction-diffusion signal can control spinal cord regeneration in axolotls: A modelling study
Authors: Caliaro Valeria , Peurichard Diane , Chara Osvaldo 
Published: August 2023

AbstractAxolotls are uniquely able to completely regenerate the spinal cord after amputation. The underlying governing mechanisms of this regenerative response have not yet been fully elucidated. We previously found that spinal cord regeneration is mainly driven by cell cycle acceleration of ependymal cells, recruited by a hypothetical signal propagating from the injury. However, the nature of the signal and its propagation remain unknown. In this theoretical study, we investigated whether the regeneration-inducing signal can follow a reaction-diffusion process. We developed a computational model, validated it with experimental data and showed that the signal dynamics can be understood in terms of reaction-diffusion mechanism. By developing a theory of the regenerating outgrowth in the limit of fast reaction-diffusion, we demonstrate that control of regenerative response solely relies on cell-to-signal sensitivity and the signal reaction-diffusion characteristic length. This study lays foundations for further identification of the signal controlling regeneration of the spinal cord.
Starvation resistance in the nematodePristionchus pacificusrequires a conserved supplementary nuclear receptor
Authors: Theska Tobias , Renahan Tess , Sommer Ralf J. 
Published: August 2023

AbstractNuclear hormone receptors (NHRs) are a deeply-conserved superfamily of metazoan transcription factors, which fine-tune the expression of their regulatory target genes in response to a plethora of sensory inputs. In nematodes, NHRs underwent an explosive expansion and many species have hundreds ofnhrgenes, most of which remain functionally uncharacterized. However, recent studies elucidated that two sister receptors,Ppa-NHR-1 andPpa-NHR-40, are crucial regulators of feeding-structure morphogenesis in the diplogastrid model nematodePristionchus pacificus. In this study, we functionally characterizePpa-NHR-10, the sister paralog ofPpa-NHR-1 andPpa-NHR-40, aiming to reveal whether it too regulates aspects of feeding-structure development. We used CRISPR/CAS9-mediated mutagenesis to create knock-out mutations of this receptor and applied a combination of geometric morphometrics and unsupervised clustering to characterize potential mutant phenotypes. However, we found thatPpa-NHR-10 does not affect feeding-structures morphogenesis. Instead, multiple RNA-seq experiments revealed that many of the target genes of this receptor are involved in lipid catabolic processes. We hypothesized that their mis-regulation could affect the survival of mutant worms during starvation, where lipid catabolism is often essential. Indeed, using novel survival assays, we found that mutant worms show drastically decreased starvation resistance, both as young adults and as dauer larvae. We also characterized genome-wide changes to the transcriptional landscape inP. pacificuswhen exposed to 24hrs of acute starvation, and found thatPpa-NHR-10 partially regulates some of these responses. Taken together, we were able to demonstrate thatPpa-NHR-10 is broadly required for starvation resistance and regulates different biological processes than its closest paralogsPpa-NHR-1 andPpa-NHR-40.
Reconstructing the genetic relationship between ancient and present-day Siberian populations
Authors: Gill Haechan , Lee Juhyeon , Jeong Choongwon 
Published: August 2023

AbstractHuman populations across a vast area in northern Eurasia, from Fennoscandia to Chukotka, share a distinct genetic component often referred to as the Siberian ancestry. Most enriched in present-day Samoyedic-speaking populations such as Nganasans, its origins and history still remain elusive despite the growing list of ancient and present-day genomes from Siberia. Here we reanalyze published ancient and present-day Siberian genomes focusing on the Baikal and Yakutia, resolving key questions regarding their genetic history. First, we show a long-term presence of a unique genetic profile in southern Siberia, up to 6,000 years ago, which distinctly shares a deep ancestral connection with Native Americans. Second, in the Baikal we find no direct contribution of the Early Neolithic Kitoi people to Late Neolithic and Early Bronze Age Serovo-Glazkovo ones. Third, the Middle Neolithic individual from Yakutia, belonging to the Belkachi culture, serves as the best source so far available for the spread of the Siberian ancestry into Fennoscandia and Greenland. These findings shed light on the genetic legacy of the Siberian ancestry and provide insights into the complex interplay between different populations in northern Eurasia throughout history.
Comparison of the cattle rumen bacterial community and drinker water in different livestock farm buildings using NGS sequencing
Authors: Yildirim E.A. , Ilina L.A. , Filippova V.A. 
Published: August 2023

AbstractThe aim of the study was to analyze samples of ruminal fluid from highly productive lactating cows of black-motley Holsteinized breed and water from drinkers from three livestock farm buildings using the molecular genetic method NGS -sequencing. The experiment was carried out in a commercial farm of the Tula region of Russia. The composition of microorganisms in samples of rumen fluid and water from drinking bowls was studied using the molecular genetic method of NGS-sequencing. In all samples, including water samples from drinking bowls, a variety of pathogenic microorganisms were found, including campylobacter, mycoplasma, pathogenic Clotridia, leptotrichia, Salmonella and others. Interestingly, a number of these microorganisms were also found in the rumen of cows. Thus, the proportion of pathogenic Campylobacter in samples of cicatricial contents ranged from 0.01±0.0006% to 0.03±0.0009%. Also, these bacteria were found in water samples from the drinking bowls of two buildings: in the amount of 0.02±0.0015% and 0.002±0.0001%.Improper sanitary condition of water in cowsheds creates the risk of various diseases.
Switching Gō-Martinifor Investigating Protein Conformational Transitions and Associated Protein-Lipid Interactions
Authors: Yang Song , Song Chen 
Published: August 2023

AbstractProteins are dynamic biomolecules that can transform between different conformational states when exerting physiological functions, which is difficult to simulate by using all-atom methods. Coarse-grained Gō-like models are widely-used to investigate large-scale conformational transitions, which usually adopt implicit solvent models and therefore cannot explicitly capture the interaction between proteins and surrounding molecules, such as water and lipid molecules. Here, we present a new method, namedSwitching Gō-Martini, to simulate large-scale protein conformational transitions between different states, based on the switching Gō method and the coarse-grained Martini 3 force field. The method is straight-forward and efficient, as demonstrated by the benchmarking applications for multiple protein systems, including glutamine binding protein (GlnBP), adenylate kinase (AdK), andβ2-adrenergic receptor (β2AR). Moreover, by employing theSwitching Gō-Martinimethod, we can not only unveil the conformational transition from the E2Pi-PL state to E1 state of the Type 4 P-type ATPase (P4-ATPase) flippase ATP8A1-CDC50, but also provide insights into the intricate details of lipid transport.
Improved taxonomic annotation of Archaea communities using LotuS2, the Genome Taxonomy Database and RNAseq data
Authors: Grant Alastair , Aleidan Abdullah , Davies Charli S. , Udochi Solomon C. , Fritscher Joachim , Bahram Mohammad , Hildebrand Falk 
Published: August 2023

AbstractMetabarcoding is increasingly used to uncover diversity and characterise communities of Archaea In various habitats, but taxonomic annotation of their sequences remains more challenging than for bacteria. Fewer reference sequences are available; widely used databases do not reflect recent revisions of higher level archaeal taxonomy and a substantial fraction of their phylogenetic diversity remains to be fully characterised. We address these gaps with a systematic and tractable approach based around the Genome Taxonomy Database (GTDB). GTDB provides a standardized taxonomy with normalized ranks based on protein coding genes, allowing us to identify and remove incongruent SSU sequences. We then use this in combination with the eukaryote PR2 database to annotate a collection of near full length rRNA sequences and the Archaea SSU sequences in SILVA, creating a new reference database, KSGP (Karst,Silva,GTDB andPR2). GTDB SSUs alone provides a small improvement in annotation of an example marine Archaea OTU data set over standardized SSU databases such as SILVA and Greengenes2, while KSGP increases Class and Order assignments by 145% and 280% respectively and is likely to provide some improvement in annotation of bacterial sequences too.We make the KSGP database and a cleaned and deduplicated subset of GTDB SSU sequences available at ksgp.earlham.ac.uk; integrate them into a metabarcoding pipeline, LotuS2 and outline rapid and robust strategies to generate a set of annotated Archaea OTUs and to determine the proportion of Archaea sequences in metatranscriptomic data. We also demonstrate simple tools to visualise the completeness of database coverage and outline strategies to further understand poorly characterised components of the archaeal community which will be equally applicable to bacteria.
Timing the Evolution of Phosphorus-Cycling Enzymes Through Geological Time
Authors: Boden Joanne S. , Zhong Juntao , Anderson Rika E. , Stüeken Eva E. 
Published: August 2023

SUMMARY PARAGRAPHPhosphorus plays a crucial role in controlling biological productivity, but geological estimates of phosphate concentrations in the Precambrian ocean, during life’s origin and early evolution, vary over several orders of magnitude1-10. While reduced phosphorus species may have served as alternative substrates to phosphate11, their bioavailability on the early Earth remains unknown. Here, we reconstruct the phylogenomic record of life on Earth and find that phosphate transporting genes (pnas) evolved in the mid-Archean (ca. 3.2 Ga) and are consistent with phosphate concentrations above modern levels (>3 μM). The first gene optimized for low phosphate levels (pstS; <1 μM) appeared around 2.9 Ga. Most enzymatic pathways for metabolising reduced phosphorus emerged and expanded across the tree of life in the Neoarchean to Paleoproterozoic (ca. 2.6 to 1.8 Ga). This includes phosphonate-catabolising CP-lyases, phosphite-oxidising pathways and hypophosphite-oxidising pathways. CP-lyases are particularly abundant in dissolved phosphate concentrations below 0.1 μM. Our results thus indicate declining phosphate levels through the Archean, possibly linked to increasing deposition of phosphate-scavenging iron oxides, which may have limited productivity. However, reduced phosphorus species did not become widely used until after the Paleoproterozoic Great Oxidation Event (2.3 Ga), possibly linked to an expansion of the biosphere at that time.
Synaptopodin is required for long-term depression at Schaffer collateral-CA1 synapses
Authors: Inglebert Yanis , Wu Pei You , Tourbina-Kolomiets Julia , Dang Cong Loc , McKinney R. Anne 
Published: August 2023

AbstractSynaptopodin (SP), an actin-associated protein found in telencephalic neurons, affects synaptic and structural plasticity. While being required for longterm depression (LTD) mediated by metabotropic glutamate receptor (mGluR-LTD), little is known about its role in other forms of LTD induced by low frequency stimulation (LFS-LTD) or spike-timing dependent plasticity (STDP). Using SP-deficient mice (SPKO), we have here demonstrated that the presence of SP is mandatory for normal LTD expression. On the contrary, long-term potentiation (LTP), albeit diminished in SPKO, is still present and can be easily recovered by increasing the stimulation frequency. Our study shows, for the first time, the role of SP in a more physiological form of induction of synaptic plasticity.
Soft-metal(loid)s induce protein aggregation inEscherichia coli
Authors: Cornejo Fabián A. , Muñoz-Villagrán Claudia M. , Luraschi Roberto A. , Sandoval-Díaz María P. , Cancino Camila A. , Pugin Benoit , Morales Eduardo H. , Piotrowski Jeff S. , Sandoval Juan M. , Vásquez Claudio C. , Arenas Felipe A. 
Published: August 2023

AbstractMetal(loid) salts have been used to treat infectious diseases due to their exceptional biocidal properties at low concentrations. However, the mechanism of their toxicity has yet to be fully elucidated. The production of reactive oxygen species (ROS) has been linked to the toxicity of soft metal(loid)s such as Ag(I), Au(III), As(III), Cd(II), Hg(II), and Te(IV). Nevertheless, few reports have described the direct, or ROS-independent, effects of some of these soft-metal(loid)s on bacteria, including the dismantling of iron-sulphur clusters [4Fe-4S] and the accumulation of porphyrin IX. Here, we used genome-wide genetic, proteomic, and biochemical approaches under anaerobic conditions to evaluate the direct mechanisms of toxicity of these metal(loid)s inEscherichia coli. We found that certain soft-metal(loid)s promote protein aggregation in a ROS-independent manner. This aggregation occurs during translation in the presence of Ag(I), Au(III), Hg(II), or Te(IV) and post-translationally in cells exposed to Cd(II) or As(III). We determined that aggregated proteins were involved in several essential biological processes that could lead to cell death. For instance, several enzymes involved in amino acid biosynthesis were aggregated after soft-metal(loid) exposure, disrupting intracellular amino acid concentration. We also propose a possible mechanism to explain how soft-metal(loid)s act as proteotoxic agents.
Moderate Endurance Exercise Increases Arrhythmia Susceptibility and modulates Cardiac Structure and Function in a Sexually Dimorphic manner
Authors: George Sharon A , Trampel Katy Anne , Brunner Kelsey , Efimov Igor R 
Published: August 2023

ABSTRACTBackgroundWhile moderate endurance exercise has been reported to improve cardiovascular health, its effects on cardiac structure and function are not fully characterized, especially with respect to sexual dimorphism. We aimed to assess the effects of moderate endurance exercise on cardiac physiology in male versus female mice.MethodsC57BL/6J mice of both sexes were run on a treadmill for six weeks. ECG and echocardiography were performed every two weeks. After six weeks of exercise, mice were euthanized, and triple parametric optical mapping was performed on Langendorff perfused hearts to assess cardiac electrophysiology. Arrhythmia inducibility was tested by programmed electrical stimulation. Left ventricular (LV) tissue was fixed, and RNA sequencing was performed to determine exercise-induced transcriptional changes.ResultsExercise-induced LV dilatation was observed in female mice alone, as evidenced by increased LV diameter and reduced LV wall thickness. Increased cardiac output was also observed in female exercised mice but not males. Optical mapping revealed further sexual dimorphism in exercise-induced modulation of cardiac electrophysiology. In female mice, exercise prolonged action potential duration and reduced voltage-calcium influx delay. In male mice, exercise reduced the calcium decay constant, suggesting faster calcium reuptake. Exercise increased arrhythmia inducibility in both male and female mice, however, arrhythmia duration was increased only in females. Lastly, exercise-induced transcriptional changes were sex-dependent: females and males exhibited the most significant changes in contractile versus metabolism-related genes, respectively.ConclusionsOur data suggest that moderate endurance exercise can significantly alter multiple aspects of cardiac physiology in a sex-dependent manner. While some of these effects are beneficial, like improved cardiac mechanical function, others are potentially pro-arrhythmic.
A data-driven approach for timescale decomposition of biochemical reaction networks
Authors: Akbari Amir , Haiman Zachary B. , Palsson Bernhard O. 
Published: August 2023

AbstractUnderstanding the dynamics of biological systems in evolving environments is a challenge due to their scale and complexity. Here, we present a computational framework for timescale decomposition of biochemical reaction networks to distill essential patterns from their intricate dynamics. This approach identifies timescale hierarchies, concentration pools, and coherent structures from time-series data, providing a system-level description of reaction networks at physiologically important timescales. We apply this technique to kinetic models of hypothetical and biological pathways, validating it by reproducing analytically characterized or previously known concentration pools of these pathways. Moreover, by analyzing the timescale hierarchy of the glycolytic pathway, we elucidate the connections between the stoichiometric and dissipative structures of reaction networks and the temporal organization of coherent structures. Specifically, we show that glycolysis is a cofactor driven pathway, the slowest dynamics of which are described by a balance between high-energy phosphate bond and redox trafficking. Overall, this approach provides more biologically interpretable characterizations of network dynamics than large-scale kinetic models, thus facilitating model reduction and personalized medicine applications.