bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nucleosome dynamics render heterochromatin accessible in living human cells
Authors: Prajapati Hemant K. , Xu Zhuwei , Eriksson Peter R. , Clark David J. 
Published: December 2024

ABSTRACTThe eukaryotic genome is packaged into chromatin, which is composed of a nucleosomal filament that coils up to form more compact structures. Chromatin exists in two main forms: euchromatin, which is relatively decondensed and enriched in transcriptionally active genes, and heterochromatin, which is condensed and transcriptionally repressed1–10. It is widely accepted that chromatin architecture modulates DNA accessibility, restricting the access of sequence-specific, gene-regulatory, transcription factors to the genome. Here, we measure genome accessibility at all GATC sites in living human MCF7 and MCF10A cells, using an adenovirus vector to express the sequence-specificdamDNA adenine methyltransferase. We find that the human genome is globally accessible in living cells, unlike in isolated nuclei. Active promoters are methylated somewhat faster than gene bodies and inactive promoters. Remarkably, both constitutive and facultative heterochromatic sites are methylated only marginally more slowly than euchromatic sites. In contrast, sites in centromeric chromatin are methylated slowly and are partly inaccessible. We conclude thatallnucleosomes in euchromatin and heterochromatin are highly dynamic in living cells, whereas nucleosomes in centromeric α-satellite chromatin are static. A dynamic architecture implies that simple occlusion of transcription factor binding sites by chromatin is unlikely to be critical for gene regulation.
A conserved role for ALG10/ALG10B and theN-glycosylation pathway in the sleep-epilepsy axis
Authors: Gill Shubhroz , Mandigo Torrey R. , Elmali Ayse Deniz , Leger Brittany S. , Yang Bo , Tran Steven , Laosuntisuk Kanjana , Lane Jacqueline M. , Bannister Dalton , Aonbangkhen Chanat , Ormerod Kiel G. , Mahama Belinda , Schuch Kelsey N. , Elya Carolyn , Akhund-Zade Jamilla , Math Suraj R. , LoRocco Nicholas C. , Seo Soobin , Maher Matthew , Kanca Oguz , Bebek Nerses , Karadeniz Derya , Senel Gulcin Benbir , Courage Carolina , Lehesjoki Anna-Elina , Winkelman John W. , Bellen Hugo J. , de Bivort Benjamin , Hart Anne C. , Littleton J. Troy , Baykan Betul , Doherty Colleen J. , Melkani Girish C. , Prober David A. , Woo Christina M. , Saxena Richa , Schreiber Stuart L. , Walker James A. 
Published: December 2024

ABSTRACTCongenital disorders of glycosylation (CDG) comprise a class of inborn errors of metabolism resulting from pathogenic variants in genes coding for enzymes involved in the asparagine-linked glycosylation of proteins. Unexpectedly to date, no CDG has been described forALG10, encoding the alpha-1,2-glucosyltransferase catalyzing the final step of lipid-linked oligosaccharide biosynthesis. Genome-wide association studies (GWAS) of human traits in the UK Biobank revealed significant SNP associations with short sleep duration, reduced napping frequency, later sleep timing and evening diurnal preference as well as cardiac traits at a genomic locus containing a pair of paralogous enzymesALG10andALG10B. Modeling Alg10 loss inDrosophila,we identify an essential role for theN-glycosylation pathway in maintaining appropriate neuronal firing activity, healthy sleep, preventing seizures, and cardiovascular homeostasis. We further confirm the broader relevance of neurological findings associated with Alg10 from humans and flies using zebrafish and nematodes and demonstrate conserved biochemical roles forN-glycosylation inArabidopsis. We report a human subject homozygous for variants in bothALG10andALG10Barising from a consanguineous marriage, with epilepsy, brain atrophy, and sleep abnormalities as predicted by the fly phenotype. Quantitative glycoproteomic analysis in ourDrosophilamodel identifies potential key molecular targets for neurological symptoms of CDGs.
Palliative Care in Geriatric Trauma: Quantitative Insight From 64 Trauma Surgeon Survey Respondent on Utilizing Specialty Palliative Care in Geriatric Trauma
Authors: Hopp Morgan J. , Comrie Cameron E. , Kang Paul T , Strand Jacob J. , Santivasi Wil L. , Hollingworth Alexzandra K. , Iskander Gaby , Weinberg Jordan , Wu Kelly L. 
Published: December 2024

AbstractBackgroundEarly specialty palliative care (SPC) involvement in geriatric trauma care improves outcomes, quality of life and healthcare utilization. However, SPC usage is inconsistent and imprecise. A knowledge gap persists in understanding surgeons’ perspectives towards SPC and barriers in geriatric trauma.MethodsThe 38-question survey was distributed through a prestigious surgical society’s membership. Subsequently, comparative analysis of responses was completed based on demographic features.Results64 surgeons responded (2.8%). 87.5% of respondents identified a potentially life-limiting diagnosis/prognosis and 76.6% conflicting goals of care as consult triggers. 59.4% reported comfort in addressing the palliative needs without SPC consult. The perception of limited SPC availability (54.7%) was a common barrier. 28.1% felt that patient/family resistance was the most common reason not to consult SPC.ConclusionsSurgeons reported comfort with goals of care discussions, perceived limited SPC availability, and the perception of patient/family resistance as limitation to consultation. These data provide previously unexplored insight from trauma surgeons.
An endogenous cluster of target-directed microRNA degradation sites induces decay of distinct microRNA families
Authors: Hiers Nicholas M. , Li Lu , Li Tianqi , Sheng Peike , Wang Yuzhi , Traugot Conner M. , Yao Michael , Xie Mingyi 
Published: December 2024

SUMMARYWhile much is known about miRNA biogenesis and canonical miRNA targeting, relatively less is understood about miRNA decay. The major miRNA decay pathway in metazoans is mediated through target-directed miRNA degradation (TDMD), in which certain RNAs can “trigger” miRNA decay. All known triggers for TDMD base pair with the miRNA seed, and extensively base pair on the miRNA 3′ end, a pattern that supposedly induces a TDMD-competent conformational change of Argonaute (Ago), allowing for miRNA turnover. Here, we utilized Ago1-CLASH to find that theDrosophilatranscriptKahcontains at least two triggers, a “trigger cluster”, against miR-9b and the miR-279 family. One of these triggers contains minimal/non-canonical 3′ end base pairing but is still sufficient to induce TDMD of the entire miR-279 family. We found that these clustered triggers likely lack cooperativity, the minimal 3′ pairing is required for miR-279 family turnover, and probed the in-cell RNA structure of theKahtrigger cluster. Overall, this study expands the list of endogenous triggers and the unexpectedly complex regulatory network governing miRNA degradation.
A novel and robust method for assessing mitochondrial (dys)function in healthy and diseased frozen cardiac tissue
Authors: Hu Liangyu , van Rinsum Alexia , Caliandro Rocco , Qi Xi , Fan Shuxiu , Jiang Xinyi , Massop Jur , Bekkenkamp-Grovenstein Melissa , Ott Christiane , Grune Tilman , van de Wal Melissa A.E. , Koopman Werner J.H. , Giesbers Marcel , Gladka Monika , Keijer Jaap , Zhang Deli 
Published: December 2024

AbstractCardiovascular diseases are often associated with impairment in mitochondrial function detected by reduced mitochondrial oxygen consumption using high-resolution respirometry. However, existing respirometry protocols are limited by the necessity for fresh tissue samples. This study developed a method with tailored substrate-inhibitor titration (TSIT) of mitochondrial electron transport complexes (ETC) to measure mitochondrial function in frozen cardiac samples using high-resolution respirometry. Briefly, acetyl-CoA was added to fuel the tricarboxylic acid (TCA) cycle for NADH production, enabling complex I (CI)-linked respiratory assessment. NADH was then added to measure maximum CI-linked respiratory capacity, followed by rotenone and succinate to assess complex II (CII)-linked respiratory capacity. TSIT detected mitochondrial functional differences between frozen atrial and ventricular tissue, with comparable results as measured in fresh samples. It also detected cardiac mitochondrial dysfunction across various (patho)physiological mouse models (including aging, ischemia reperfusion, obesity, and CI deficiency) as well as in frozen human donor samples, highlighting its clinical potential. Furthermore, we showed the first evidence for supercomplexes (SCs) formation between ETC-SCs and the TCA cycle metabolon, underpinning TSIT feasibility. In conclusion, we established a novel, robust, sensitive and translational method (TSIT) for assessing mitochondrial (dys)function in frozen cardiac samples from various species, enabling flexible analysis of mitochondrial function in both laboratory and clinical settings.
Male Mice Have no Sugar-preference Behavior
Authors: Pan Tao , Huang Jia-Fu , Wu Qi-Ci , Chen Yi-Xuan , Li Xiu-Min , Zhang San-Guo , Pan Yu-Tian 
Published: December 2024

AbstractSugar-preference behavior is considered to be universally innate among humans and animals. Current research on the detection and mechanisms of sugar-preference behavior largely adopts the “two-bottle choice assay”, and most experiments use male mice as the model, which has serious methodological flaws, leading to questionable conclusions. As expected, through adopting our improved experimental method, we discovered distinct sugar preferences between male and female mice: females possess an innate preference, while males do not. However, the innate sugar preference in female mice can be lost due to their long-term normal diet. Even after “training” with high-sugar food for a long time, the results still show differences between males and females. Female mice retain a significant preference for sugar, while male mice are not influenced by the training of high-sugar food and still do not evolve a sugar preference. From this, we conclude that gender determines the emergence and development of sugar preference in mice. Our results can provide researchers with a new understanding of sugar preference, which will help them fill in or even correct the gaps in the original experimental design methods to obtain more reliable conclusions.
Sex-allocation trade-offs and their genetic architecture revealed by experimental evolution
Authors: Gerchen Jörn F. , Villamil-Buenrostro Nora , Li Xinji , Le Faou Ehouarn , Pannell John R. 
Published: December 2024

AbstractThe theory of sex-allocation is hailed as one of evolutionary biology’s great successes. But while it has successfully predicted strategies of resource allocation to sons versus daughters under a wide range of conditions in species with separate sexes, it has been difficult to apply to hermaphroditic species because of the repeated failure to verify the fundamental assumption of a direct genetic trade-off between male and female allocations made by hermaphrodites. This assumption supposes that mutations that increase an individual’s male allocation reduce its female allocation in equal measure, yet there is almost no evidence for such ‘trade-off’ loci in hermaphroditic populations. Here, we use experimental evolution to generate wide variation in hermaphroditic sex allocation in an annual plant and demonstrate a clear trade-off between the two sexual functions within populations as well as over time, with populations evolving both increased male and reduced female allocation. Quantitative trait locus (QTL) analysis performed on multiple crosses further reveals the segregation of allelic variation at trade-off loci. Taken together, our results demonstrate a phenotypic trade-off in sex allocation in hermaphrodites and provide compelling evidence for sex-allocation trade-off loci, verifying the fundamental assumption of sex-allocation theory and securing its general applicability to both dioecious and hermaphroditic species.
Simultaneous Overexpression of Three Enzymes of Chloroplast Metabolism Fails to Improve CO2Assimilation or Biomass
Authors: Lemonnier Pauline , Wall Shellie , Gherli Hussein , Moreno-Garcia Beatriz , Afamefule Chidi , Lawson Tracy , Raines Christine A. , Lopez-Calcagno Patricia E. 
Published: December 2024

AbstractEnsuring an adequate food supply amidst a growing global population and climate change challenges, necessitates innovative strategies to enhance crop productivity. Previous studies have demonstrated that the simultaneous stimulation of different photosynthesis-related processes can increase the rate of photosynthetic carbon assimilation and plant biomass. This study evaluates an approach based on modelling aimed at simultaneously increasing photosynthetic and sink capacities inNicotiana tabacumby overexpressing three key enzymes: Sedoheptulose-1,7-bisphosphatase (SBPase), Fructose-1,6-bisphosphate aldolase (FBP Aldolase), and ADP-glucose pyrophosphorylase (AGPase). Our results showed that this strategy does not significantly improve growth or carbon assimilation inNicotiana tabacumunder the tested conditions. This suggests that while the model informing our work offers a valuable framework, its application may require adjustments based on species and environmental conditions. Future research should explore these genetic modifications in species with larger sink capacities and under a range of growth conditions to fully realize the potential of photosynthetic optimization.
Exploring the help-seeking journeys for Long Covid from a health inequalities perspective: a qualitative study in England
Authors: Clutterbuck Donna , Ramasawmy Mel , Pantelic Marija , Allsopp Gail , Gabbay Mark , Hayer Jasmine , Heightman Melissa , Mu Yi , Sunkersing David , Wootton Dan , Banerjee Amitava , Alwan Nisreen A ,   STIMULATE-ICP Consortium
Published: December 2024

AbstractBackground and aimLong Covid is a health condition that continues to be challenging in terms of obtaining care and support, even in the fourth year following its emergence. This study, which forms part of the STIMULATE-ICP study in England, explores the barriers and facilitators people with Long Covid face when trying to access care, as well as experiences in relation to stigma, discrimination, and inequitable treatment.MethodsThe study was co-designed with people with lived experience of Long Covid. People attending three post-covid services in England were invited to participate by clinic staff. Twenty-three participants were interviewed about their experiences in relation to barriers and facilitators of accessing adequate care, including experiences of being treated unfairly. Interviews were analysed thematically.FindingsParticipants experienced difficulties in accessing and receiving appropriate support from primary and secondary care but generally care and support improved once participants were under the care of a Long Covid service. Positive interactions with clinicians who were knowledgeable and supportive helped to foster good patient experiences when accessing Long Covid care. Inequalities in accessing care were reported in the form of experiences of gender and race discrimination. People with previous and existing conditions reported further stigmatisation. Financial barriers to care existed and there were also difficulties faced by those who got infected with COVID-19 early in the pandemic. The impact of Long Covid on mental health was evident, as was the stigma related to mental health and the inadequacy of mental health service provision for people with Long Covid.Some participants who worked within the National Health Service (NHS) perceived their professional position as a facilitator to accessing Long Covid care. However, some NHS employees also reported the negative impact of Long Covid on their work, the lack of employment support available, mistreatment from colleagues, and dismissal of professional knowledge.ConclusionOur findings highlight a range of barriers to accessing adequate Long Covid care, with women, ethnic minorities and people with co-occurring conditions experiencing intersectional stigma. We recommend a move towards a healthcare system that is sensitive to intersectional disparities in access to care and is mindful of how stigma can reinforce these inequalities. This would speak to removing barriers to care and foster a more positive experience for people living with Long Covid already disadvantaged by structural and systemic discrimination.
Anopheles mosquito exposure is associated with age, gender and bed net use in areas in Uganda experiencing varying malaria transmission intensity
Authors: Blanken Sara Lynn , Kilama Maxwell , Ramjith Jordache , Musiime Alex K. , Lanke Kjerstin , Ayo Daniel , Huijbers Kristiaan , Hofste Tom , Conrad Melissa , Krezanoski Paul , Dorsey Grant , Kamya Moses R. , Arinaitwe Emmanuel , Bousema Teun 
Published: December 2024

AbstractObjectivesThe number ofAnophelesmosquito bites a person receives determines the risk of acquiring malaria and the likelihood of transmitting infections to mosquitoes. We assessed heterogeneity inAnophelesbiting and associated factors in two settings in Uganda with different endemicity.MethodsPlasmodium falciparumparasites in blood-fed indoor caughtAnophelesmosquitoes were quantified using qPCR targeting the Pf18S rRNA gene. Human DNA in dried blood spots from household occupants and mosquito blood meals was profiled using 15 short-tandem repeats (STRs) and analysed using a log-likelihood approach for matching of both single and multi-sourced blood meals and incomplete DNA profiles.ResultsThe distribution of mosquito bites was non-random; school-age children (5-15 years) and adults (≥16 years) had a mosquito biting rate ratio (BRR) 1.76 (95%CI 1.27-2.44, P < 0.001) and 1.96 (95%CI 1.41-2.73, P < 0.0001) times that of children under 5 years, respectively. Biting rates were lower in bed net users (BRR: 0.80, 95%CI 0.65-0.99, P = 0.042), and higher in males (BRR: 1.30, 95%CI 1.01-1.66, P = 0.043) and individuals infected withP. falciparum(BRR: 1.42, 95%CI 1.03-1.96, P = 0.030), though the latter effect lost statistical significance in sensitivity analyses.ConclusionsAdults and school-age children are at higher risk for receiving mosquito bites and this has implications for the relative importance of demographic populations to onward malaria transmission to mosquitoes.HighlightsA novel statistical approach allowed us to match multi-sourced mosquito bloodmeals and partially digested mosquito bloodmeals to human individualsParticipant age consistently related to mosquito biting: adults and school-age children had a mosquito biting rate ratio that was ∼2 and ∼1.8 times that of children below 5 years, respectivelyMen received more mosquito bites than women and self-reported bed net use was associated with lower mosquito exposure.Higher mosquito biting rates were observed in individuals infected withPlasmodium falciparum
Pallidal and motor cortical interactions determine gait initiation dynamics in Parkinson’s disease
Authors: Bath Jessica E. , Louie Kenneth H. , Azgomi Hamid Fekri , Balakid Jannine P. , Presbrey Kara N. , Marks Jacob H. , Wozny Thomas A. , Wang Doris D. 
Published: December 2024

AbstractGait initiation is a fundamental human task, requiring one or more anticipatory postural adjustments (APA) prior to stepping. Deviations in amplitude and timing of APAs exist in Parkinson’s disease (PD), causing dysfunctional postural control which increases the risk of falls. The motor cortex and basal ganglia have been implicated in the regulation of postural control, however, their dynamics during gait initiation, relationship to APA metrics, and response to pharmacotherapy such as levodopa are unknown.To address these questions, we streamed electrocorticography (ECoG) potentials from the premotor and primary motor cortices, as well as local field potentials (LFPs) from the globus pallidus in five people with PD exhibiting gait and balance dysfunction during a cued gait initiation task. Amplitude and timing of APA were evaluated with force plates and synchronized to the neural data. Subjects performed gait initiation trials under ON and LOW levodopa conditions to assess effects of medication on APA metrics and underlying neural dynamics.All subjects demonstrated pallidal and cortical oscillatory changes during different phases of gait initiation. Grouped analysis revealed that from quiet standing to the first foot step, pallidal beta power showed stepwise decrease and broadband gamma power increases, whereas cortical potentials showed low frequency (theta, alpha, beta) power decrease during gait initiation, regardless of medication state. The pallidum and motor cortices also became increasingly coherent during gait initiation compared to quiet standing prior to APA onset. Using linear mixed models, we found that while pallidal gamma powers are predictive of APA scaling, pallidal-cortical coherence (theta, alpha, beta) and premotor-M1 gamma coherence are predictive of APA timing.Our study is the first detailed characterization of basal-ganglia cortical circuit dynamics during human gait initiation. We identified significant pallidal motor cortical power and coherence changes that underlie the amplitude and timing of APA which appear to be independent of medication states of the study subjects. Our results provide evidence for a model where synchronized premotor and motor cortical activities transiently couple with the globus pallidus to regulate the timing of postural responses, and local pallidal activity regulate the amplitude of postural changes during gait initiation. It suggests that abnormal pallidal outflow and synchronization between the pallidum and motor cortices may be a pathophysiological mechanism underlying disordered postural response in Parkinson’s disease.
Digital healthcare in public libraries 2002-2025: a scoping review protocol
Authors: Chan Xavier , Flowers Paul , Crawford Megan 
Published: December 2024

AbstractObjectiveThe objective of this scoping review is to explore the use of digital healthcare in public libraries within the literature.IntroductionAccelerated by the COVID-19 pandemic, reliance on digital healthcare has grown in the past decade and will continue to play an increasingly important role in health service provision in the future, including treatment and management of health conditions. An increasing reliance on these digital technologies may exacerbate longstanding inequalities in healthcare access and socioeconomic disparities more widely. Public libraries offer an opportunity to bridge this divide to improve access to digital healthcare. A scoping review will be conducted to explore existing digital health technologies used in public libraries to inform future research.Inclusion criteriaPublished studies with adolescents and adults, focusing on digital healthcare in public libraries and conducted in any geographical location will be included in this review. Additional limiters include being published in English and conducted and published between 2002 and 2024. Grey literature sources, including theses, posters and preprints will be included in the review, where relevant.MethodsJBI methodology for Scoping Reviews has been employed for this review. Searches will be conducted using Web of Science, SCOPUS, Pubmed, Library Information and Technology Abstracts (LISTA), Library and Information Science Abstracts(LISA), OpenDisserations and advanced Google search. Sources will be screened by two independent reviewers through 1) title and abstract screening and 2) full text screening. Data will then be charted and presented.