bluuebunny/crossref_metadata_2025_split huggingface dataset:
UnveilingCrocosphaeraresponses to phosphorus depletion: insights from genome analysis and functional characterization
Authors: Caille Chloé , Rabouille Sophie , Ortega-Retuerta Eva , Denis Yann , Crispi Olivier , Marie Barbara , Pujo-Pay Mireille , Daric Vladimir , Talla Emmanuel , Latifi Amel 
Published: October 2024

AbstractUnicellular, nitrogen-fixing cyanobacteria (UCYN) thrive and support primary production in oligotrophic oceans, playing a significant role in the marine nitrogen cycle.Crocosphaerasp, a model for studying marine nitrogen fixation, is adapted to low phosphate (Pi) conditions. Yet, howCrocosphaeracopes with Pidepletion is rather poorly understood. We present genomics analysis of Pistress-responsive genes in this genus, encompassing sixC. watsoniigenomes and two strains isolated in coastal environments,C. subtropicaandC. chwakensis. We identified genes involved in Pisignaling, uptake, and dissolved organic phosphorus (DOP) hydrolysis. Results showed different genetic potentials to cope with Piscarcity between theCrocosphaerastrains. Physiological monitoring of cultures ofC. watsoniiWH8501 exposed to Pidepletion highlighted a capacity to divide several times and survive for a few more days, albeit with a skewed C:N:P stoichiometry. Upon addition of DOP, cultures efficiently recovered to a growth rate and cell composition equivalent to those observed under favorable conditions. The concomitant transcription analysis revealed diel expression patterns of Pi-related genes and endogenous clock genes, suggesting a possible circadian regulation. Our data deepen our understanding of the growth strategiesCrocosphaeraemploys in Pi-limited environments, offering broader insights into microbial resilience in marine ecosystems.
Skeletal muscle ribosome analysis: a comparison of common assay methods and utilization of a novel RiboAb antibody cocktail
Authors: Godwin Joshua S. , Michel J. Max , Mobley C. Brooks , Nader Gustavo A. , Roberts Michael D. 
Published: October 2024

ABSTRACTCellular and tissue total RNA concentrations have been widely reported to represent ribosome content, a metric that reflects the trophic state of skeletal muscle. Although various assays are used to assess total RNA concentrations, there is a need to homologize the various quantification approaches. Thus, we analyzed C2C12 myotubes and mouse skeletal muscle to determine if total RNA concentrations provided through UV-Vis spectroscopy (UV), fluorometry only (Fluor), and fluorometry-based microfluidic chip electrophoresis (MFGE) were representative of cellular and muscle tissue rRNA concentrations (i.e., MFGE 18S+28S rRNA, criterion metric of ribosome content). We also sought to determine whether a novel ribosomal protein antibody cocktail (termedRiboAb) corresponded with 18S+28S rRNA concentrations. Compared to non-treated C2C12 myotubes, 24-hour insulin-like growth factor-1 (IGF-1) treatments increased 18S+28S rRNA concentrations (∼2.0-fold; p<0.001) and total RNA concentrations based on UV (∼1.9-fold; p<0.001), Fluor (∼2.3 fold; p=0.001), and MFGE (∼2.1-fold, p<0.001). In C57BL/6 mice, 10 days of mechanical overload (MOV) via synergist ablation elevated plantaris 18S+28S rRNA concentrations (∼1.7-fold; p=0.017) and total RNA concentrations according to UV (∼1.5-fold; p=0.033), Fluor (∼1.6-fold; p=0.001), and MFGE (∼1.8-fold, p=0.017). In both experiments, total RNA concentration data yielded from all three techniques exhibited significant positive correlations to 18S+28S rRNA concentrations. Ribosome pelleting experiments indicated that the proteins assayed with the RiboAb cocktail (rps3/6 and rpl5/11) were exclusively associated with the ribosome pellet. Additionally, C2C12 myotube and mouse plantaris RiboAb levels were higher with IGF-1 treatments and MOV, respectively, relative to controls (1.3-fold and 1.7-fold, respectively, p<0.017), and values correlated with rRNA concentrations (r=0.637 and r=0.853, respectively, p<0.005). These data confirm that total RNA concentrations yielded from the UV, Fluor, MFGE techniques are valid surrogates of cell/tissue ribosome content. We also propose that the RiboAb cocktail may serve as a surrogate for changes in ribosome content in these models, although future research is needed to examine the feasibility of the RiboAb cocktail in humans as well as utility with other applications (e.g., immunohistochemistry and/or tissue fractionation experiments).
A FAN1 point mutation associated with accelerated Huntington’s disease progression alters its PCNA-mediated assembly on DNA
Authors: Aretz Jonas , Jeyasankar Gayathri , Salerno-Kochan Anna , Thomsen Maren , Thieulin-Pardo Gabriel , Haque Tasir , Monteagudo Edith , Felsenfeld Dan , Finley Michael , Vogt Thomas F. , Boudet Julien , Prasad Brinda C. 
Published: October 2024

AbstractFAN1 is an endo- and exo-nuclease involved in DNA and interstrand crosslink repair. Genome-wide association studies of people with Huntington’s disease revealed a strong association between the FAN1 R507H mutation and early disease onset, however the underlying mechanism(s) remains unclear. FAN1 has previously been implicated in modulating triplet repeat expansion in a PCNA dependent manner. To examine the role of PCNA on FAN1 activation, we solved the cryo-EM structures of a PCNA–FAN1–DNA complex. Our findings reveal that the FAN1 R507 residue directly interacts with PCNA D232. Biophysical interaction studies demonstrated that FAN1 enhances the binding affinity of PCNA for DNA, a synergistic effect disrupted in mutants carrying the R507H mutation. In contrast, PCNA does not affect the affinity of FAN1 for DNA but does modulate FAN1 activity upon ternary complex formation. The weakened and functionally altered FAN1 R507H-PCNA-DNA complex may partly impair the FAN1-mediated repair of CAG extrahelical extrusions, providing a potential explanation for the mutation’s role in accelerating disease progression.
Mapping multiple RNA modifications simultaneously by proximity barcode sequencing
Authors: Sendinc Erdem , Yu Hua , Hwang Fu Yu Hsien , Santos Jerome , Johnson Zachary , Kirstein Justin R. , Niu Jiani , Chabot Michael B. , Cantu Vito Adrian , Džakula Željko , Lam Quan , Anmangandla Ananya , Burcham Timothy S. , Davis Eric M. , Miles Zachary D. , Price Andrew D. , Purse Byron W. , Gregory Richard I. , Stengel Gudrun 
Published: October 2024

AbstractRNA is subject to a multitude of different chemical modifications that collectively represent the epitranscriptome. Individual RNA modifications including N6-methyladenosine (m6A) on mRNA play essential roles in the posttranscriptional control of gene expression. Recent technological advances have enabled the transcriptome-wide mapping of certain RNA modifications, to reveal their broad relevance and characteristic distribution patterns. However, convenient methods that enable the simultaneous mapping of multiple different RNA marks within the same sample are generally lacking. Here we present EpiPlex RNA modification profiling, a bead-based proximity barcoding assay with sequencing readout that expands the scope of molecular recognition-based RNA modification detection to multiple targets, while providing relative quantification and enabling low RNA input. Measuring signal intensity against spike-in controls provides relative quantification, indicative of the RNA mod abundance at each locus. We report on changes in the modification status of HEK293T cells upon treatment with pharmacological inhibitors separately targeting METTL3, the dominant m6A writer enzyme, and the EIF4A3 component of the exon junction complex (EJC). The treatments resulted in decreased or increased m6A levels, respectively, without effect on inosine levels. Inhibiting the helicase activity of EIF4A3 and EIF4A3 knockdown both cause a significant increase of m6A sites near exon junctions, consistent with the previously reported role of EIF4A3 in shaping the m6A landscape. Thus, EpiPlex offers a reliable and convenient method for simultaneous mapping of multiple RNA modifications to facilitate epitranscriptome studies.
Performance of and preference for saliva sampling for detection of SARS-COV-2 in the Bahamas
Authors: Martin Indira , McMillan Pearl 
Published: October 2024

AbstractImplementing public health diagnostic modalities that are simultaneously accurate and acceptable is integral to effective pandemic response. In this regard, saliva has proven to be a reliable alternative to nasopharyngeal swabs (NPS) for the detection of SARS-COV-2 infections. In particular, the SalivaDirect protocol utilises untreated saliva as its sample type, and removes the need for RNA extraction, thereby decreasing the time and cost of diagnosis by RT-PCR. IN the current study we piloted SalivaDirect in the context of The Bahamas archipelago, where it demonstrated acceptable performance, with 95.2% concordance with NPS. However, there was discordance in 3 of the 8 total SARS-COV-2 positive samples,all of which were above Ct 30 and therefore presumably of low infectivity. Furthermore, a significant majority of survey respondents chose saliva as their preferred sample type and this was associated with citing ‘discomfort’ of NPS sampling as the reason for their choice. These results support the practical use of SalivaDirect in the Bahamas as a mass testing tool.
TikTok: Empowering Hidradenitis Suppurativa Patients through Social Media Education - A Cross-Sectional Content Analysis
Authors: Decker Paulina M. , Ezaldein Harib H. 
Published: October 2024

AbstractHidradenitis suppurativa (HS) is a chronic condition characterized by painful, inflamed lumps under the skin in intertriginous areas. While social media platforms like TikTok are increasingly raising public awareness about HS, the quality of the information presented remains challenging to assess. Our study aims to analyze the top one hundred TikTok videos focusing on HS clinical information, treatment options, and patient experiences from 2020 to 2024. We evaluate user engagement data, content characteristics, and assess the quality of health information using a validated DISCERN score. Overall, our study suggests that while TikTok serves as a valuable resource for raising awareness and accessing new information about HS, content from healthcare professionals and scientific research garners higher user engagement and contributes to greater awareness of HS.
Whole-genome sequencing reveals contribution of rare and common variation to structural kidney and urinary tract malformations
Authors: Chan Melanie MY , Sadeghi-Alavijeh Omid , Voinescu Catalin D , van der Zanden Loes FM , Groen in ’t Woud Sander , Schreuder Michiel F , Feitz Wout , Mingardo Enrico , Hilger Alina C , Reutter Heiko , Vendrig Lisanne M , Westland Rik , Stanescu Horia C , Levine Adam P , Böckenhauer Detlef , Gale Daniel P 
Published: October 2024

AbstractCongenital anomalies of the kidneys and urinary tract (CAKUT) are the commonest cause of kidney failure in children and young adults with over 50 monogenic causes identified, largely in cohorts enriched for familial, syndromic, or consanguineous disease. We sought to better characterise the genomic architecture of these conditions using whole genome sequencing data from 992 unrelated individuals recruited to the UK’s 100,000 Genomes Project. The overall diagnostic yield was 4.3% with family history (P=7.4×10−3; OR 2.7; 95% CI 1.3-5.4) and extra-renal features (P=2.0×10−4; OR 3.4; 95% CI 1.8-6.6) independently predicting a monogenic diagnosis. Diagnostic yield was highest in cystic kidney dysplasia (10.7%) and kidney agenesis/hypodysplasia (5.9%). Exome-wide rare variant and genome-wide common variant (minor allele frequency ≥ 0.1%) testing was performed in a subset of 813 patients and 25,205 ancestry-matched controls with significant association detected at rs117473527 (P=3.93×10−8; OR 3.17; 95% CI 2.10-4.78; MAF 0.02). Heritability analysis estimated common variants explain 23% (standard error 11%) of phenotypic variance in those with European ancestry. Comparison of phenotype-specific genomic risk scores (GRS) demonstrated shared polygenic aetiology between upper urinary tract phenotypes but distinct patterns for both posterior urethral valves (PUV) and bladder exstrophy. A PUV-GRS consisting of 36,106 variants was validated in an independent European cohort of 77 cases and 2,746 controls (P=1×10−4) accounting for 37% of phenotypic variance. Together, these data demonstrate the importance of non-Mendelian genomic factors in the pathogenesis of CAKUT, evidenced by the fact that only a minority of patients in this large, unselected cohort received a monogenic diagnosis and that a substantial proportion of heritability can be attributed to common variation.Lay SummaryThis study looks at the DNA of patients with congenital anomalies of the kidneys and urinary tract (CAKUT), the most common cause of kidney failure in children. It finds that single gene (monogenic) causes are uncommon, and that genetic testing is more likely to find a cause in people with kidneys that have not formed properly (especially those with cysts), those with affected family members or with involvement of other organ systems. The study also supports the idea that many different common DNA changes (polygenic) together contribute to these conditions, particularly in posterior urethral valves, which is the leading cause of kidney failure in boys. Larger studies are needed to better understand the DNA changes and biological processes involved in kidney and urinary tract development and malformations.
Omega-3 & Aspirin Boost in Periodontal Therapy for Type II Diabetes: A Systematic Review
Authors: Walker Emma , Franklin John , Robinson Jonathan 
Published: October 2024

AbstractAimOmega-3 polyunsaturated fatty acids and aspirin are increasingly explored as adjuncts in periodontal therapy for patients with type II diabetes, owing to their anti-inflammatory properties. Despite preliminary evidence suggesting their effectiveness in reducing periodontal inflammation and improving metabolic control, comprehensive evaluations at the clinical level remain limited. This systematic review seeks to critically assess the existing evidence to determine the efficacy of these agents in modifying clinical, biochemical, and metabolic parameters in this high-risk patient group.MethodsA comprehensive search was conducted across electronic databases, including CINAHL, MEDLINE, PubMed, Embase, Dentistry & Oral Sciences Source, and Cochrane Library, to identify relevant studies from inception to January 22, 2024. Included studies were required to be randomised controlled trials and comprise both omega-3 and aspirin as an adjunct to non-surgical treatment. Data extraction was completed independently, and accuracy confirmed by a second reviewer. Data were synthesised using the revised Cochrane risk of bias tool for randomised trials.ResultsA total of 76 records were identified, and three studies met the inclusion criteria. One demonstrated a statistically significant difference in pocket depth, clinical attachment gain and inflammatory markers compared to the control group, and two showed a significant improvement in glycated haemoglobin levels.ConclusionOmega-3 and aspirin combined have the potential to improve clinical parameters and reduce inflammatory markers in the gingival crevicular fluid. Following non-surgical periodontal treatment, this combination may enhance glycemic control and aid in managing type II diabetes. This systematic review offers insights into the potential effectiveness of omega-3 polyunsaturated fatty acids and aspirin as adjuncts to non-surgical periodontal therapy in patients with type II diabetes and periodontitis. However, current research is limited by small sample sizes and varied study designs. Consequently, there is insufficient evidence to integrate this approach into clinical practice at present.
Effects of Exertion on PLR; A study of pupillary light reflex in rugby players before and after exercise
Authors: Davies W , Middleton PM , Buzytsky I , Ryan Martha 
Published: October 2024

AbstractAimTo investigate the effects of physical exertion on pupillary light reflex (PLR) metrics in sports participants, with the aim of determining whether exercise-induced changes could potentially confound concussion assessment using PLR.Materials and methodsTwenty-five adult rugby players underwent PLR assessment, using the MindMirror™ smartphone application, before and after a 30-55 minute rugby practice session or game. PLR metrics included latency, maximum and minimum pupil diameters, maximum constriction velocity, and pupil size correlation. Paired t-tests were used to compare pre- and post-exertion PLR metrics.ResultsNo statistically significant differences were observed between pre- and post-exertion assessments in any of the measured PLR metrics (p > 0.05 for all metrics). The most notable, though still non-significant, change was in maximum constriction velocity (mean difference: 1.47 mm/s, p = 0.08 for pupil 1; 1.09 mm/s, p = 0.27 for pupil 2).ConclusionThis study suggests that PLR metrics, as measured by a smartphone-based pupillometer, do not appear to be affected by rugby-related exertion. These findings support the potential use of PLR assessment in concussion screening protocols without the need to account for exercise-induced changes. However, further research with larger sample sizes and in full-contact situations is needed to confirm these results and their applicability in concussion assessment.Plain language summaryPupil size and reactivity have been critical components of the clinical assessment of patients with head injury and concussion for decades. Pupillary examination may provide critical information related to new or worsening intracranial pathology, and quantitative PLR examination is increasingly used outside of the hospital setting, particularly for concussion assessment in sports medicine. Exertion-dependent changes could confound valid measurement, however, and compromise the detection of concussion, so we investigated PLR assessment with the MindMirror™smartphone application. We found no systematic differences in PLR variables between exertion and non-exertion groups.Tweetable abstractA novel smartphone-based AI tool did not reveal exertion-related differences in pupillary light reflex measurement in rugby players.
Consensus for Integrating the Point-of-Care Genital InFlammation Test (GIFT) into Sexually Transmitted Infection Management Guidelines: Results from a Two-Round Modified Delphi Survey
Authors: Kpokiri Eneyi E. , Mackworth-Young Constance , Francis Suzanna , Crucitti Tania , van de Wijgert Janneke HHM , Masson Lindi , Passmore Jo-Ann , Harding-Esch Emma M. 
Published: October 2024

AbstractBackgroundSexually transmitted infections (STIs) and bacterial vaginosis (BV) are frequently asymptomatic in women. They cause genital inflammation and can increase transmission and acquisition of HIV. GIFT (Genital InFlammation Test) is a novel, point-of-care (POC) device under development for detecting genital inflammation in women. We aimed to obtain consensus to inform the development of GIFT and its integration into management guidelines.MethodsWe employed a Delphi technique through two rounds of online surveys. Respondents included service providers, health programmers, researchers, and policy makers. Round one questions generated ideas, and round two built consensus on the strategies from round one. Survey sections included demographics, implementation of the test, integration into current guidelines and purpose. Round two survey employed a five-point Likert scale from strongly agree to strongly disagree. Consensus was reached if ≥70% of participants selected strongly agree or agree.ResultsWe received 28 to the first and 68 to the second round. From both rounds, participants were healthcare providers (41%) or researchers (26%), residing in Africa (57%), Europe (21%) and America (10%). Most participants agreed that GIFT should be used as a screening tool to be followed by confirmatory STI testing before treatment: 75% (round 1), 69% (round 2). There was consensus that populations to benefit most from GIFT were young asymptomatic women (16-24 years) in high HIV prevalence settings, and high-risk women like female sex workers and those with multiple partners of any age. Attributes of GIFT ranked as most important included ease-of-use, stability at room temperature, high diagnostic accuracy and barriers were test stock-outs, complexity of use and high cost,ConclusionWhile the Delphi process suggests the purpose of GIFT is as a POC screening tool, factors like supply chain, storage and stakeholder engagement are crucial for its integration into management guidelines.Key messagesThere is a need to identify BV and STIs in asymptomatic women, however, laboratory diagnostics services are severely limited in most low- and middle-income countriesIf the GIFT test has high diagnostic accuracy, it promises to be a valuable point-of-care screening tool for detecting genital inflammation in asymptomatic women and may be useful to inform the management of women with symptoms.It is important to obtain feedback from a variety of stakeholders when considering test design and implementation to increase the test’s utility and likely adoption in policy and routine care.
Functional diversification of the BBSome: Insights from honey bee trypanosomatid parasite,Lotmaria passim
Authors: Yuan Xuye , Kadowaki Tatsuhiko 
Published: October 2024

AbstractThe BBSome is an octameric protein complex crucial for ciliary transport, though it also participates in multiple other cellular processes. These diverse functions may result from the co-option of its ancestral roles. Studying the BBSome in flagellated protists can provide insights into these ancestral functions and their subsequent adaptations. Here, we examine the function of the BBSome inLotmaria passim, a monoxenous trypanosomatid parasite infecting honey bee. Parasites deficient in LpBBS2 are smaller and less motile compared to wild-type. Although intraflagellar transport of a marker membrane protein is only mildly impaired, its association with lipid rafts is significantly disrupted in the mutants. This suggests that the BBSome is essential for maintaining lipid raft integrity inL. passim. Transcriptomic comparisons between wild-type and LpBBS2-deficient parasites reveal that the BBSome may also influence processes related to metabolism, membrane localization of specific proteins, DNA repair, microtubules, and mitochondria. In contrast toLeishmania mexicana, the BBSome inL. passimis crucial for efficient infection of the honey bee gut, demonstrating that its cellular functions vary between related trypanosomatid species. The BBSome is likely an adaptor that links multiple proteins in a species-specific manner under various cellular contexts.