bluuebunny/crossref_metadata_2025_split huggingface dataset:
Urine tenofovir and dried blood spot tenofovir diphosphate concentrations and viraemia in people taking efavirenz and dolutegravir based antiretroviral therapy
Authors: Dorward Jienchi , Govender Katya , Moodley Pravikrishnen , Lessells Richard , Samsunder Natasha , Sookrajh Yukteshwar , Fanshawe Thomas R. , Turner Philip J. , Butler Christopher C. , Drain Paul K. , Hayward Gail N. , Garrett Nigel 
Published: September 2023

ABSTRACTObjectiveWe aimed to determine whether urine tenofovir (TFV) and dried blood spot (DBS) tenofovir diphosphate (TFV-DP) concentrations are associated with concurrent HIV viraemia.DesignCross-sectional study among people with HIV (PWH) receiving tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy (ART).MethodsWe used dual tandem liquid chromatography and mass spectrometry to measure urine TFV and DBS TFV-DP concentrations, and evaluated their associations with concurrent viraemia ≥ 1000 copies/mL using logistic regression models. In exploratory analyses, we used receiver operating curves to estimate optimal urine TFV and DBS TFV-DP thresholds to predict concurrent viraemia.ResultsAmong 124 participants, 68 (54.8%) were women, median age was 39 years (interquartile range [IQR] 34-45) and 74 (59.7%) were receiving efavirenz versus 50 (40.3%) receiving dolutegravir. Higher concentrations of urine TFV (1000 ng/mL increase, odds ratio [OR] 0.97 95%CI 0.94-0.99, p=0.005) and DBS TFV-DP (100 fmol/punch increase, OR 0.76, 95%CI 0.67-0.86, p<0.001) were associated with lower odds of viraemia. There was evidence that these associations were stronger among people receiving dolutegravir than among people receiving efavirenz (urine TFV p=0.072, DBS TFV-DP p=0.003). Nagelkerke Pseudo-R2for the DBS TFV-DP models was higher than for the urine TFV models, demonstrating a stronger relationship between DBS TFV-DP and viraemia. Among people receiving dolutegravir, a DBS TFV-DP concentration of 483 fmol/punch had 88% sensitivity and 85% specificity to predict concurrent viraemia ≥ 1000 copies/ml.ConclusionsAmong PWH receiving TDF-based ART, urine TFV concentrations, and in particular DBS TFV-DP concentrations, were strongly associated with concurrent viraemia, especially among people receiving dolutegravir.
Sex-specific socioeconomic inequalities in trajectories of anthropometry, blood pressure and blood-based biomarkers from birth to 18 years: a prospective cohort study
Authors: O’Neill Kate N , Ahmed Minhal , O’Keeffe Linda M 
Published: September 2023

AbstractBackgroundEvidence on when socioeconomic inequalities in conventional cardiometabolic risk factors emerge and how these change over time is sparse but important in identifying pathways leading to socioeconomic inequalities in cardiovascular disease (CVD). We examine socioeconomic inequalities in trajectories of cardiometabolic risk factors across childhood and adolescence.MethodsData were from offspring of the Avon Longitudinal Study of Parents and Children (ALSPAC), born in 1991/1992. Socioeconomic position (SEP) was measured using maternal education from questionnaires administered to mothers at 32-weeks’ gestation. Cardiometabolic risk factors were measured from birth/mid-childhood to age 18 years (y) and included fat and lean mass (9y–18y), systolic and diastolic blood pressure (SBP, DBP), pulse rate and glucose (7y-18y), high-density lipoprotein cholesterol (HDL-c), non-HDL-c and triglycerides (birth-18y). We examined the sex-specific associations between SEP and trajectories of risk factors using linear spline multilevel models.ResultsAmong 6,517-8,952 participants with 11,948-42,607 repeated measures, socioeconomic inequalities in fat mass were evident at age 9y and persisted throughout adolescence, with graded associations across levels of SEP among females only. By 18y, fat mass was 12.32% (95% Confidence Interval (CI):6.96,17.68) lower among females and 7.94% (95% CI:1.91,13.97) lower among males with the highest SEP compared to the lowest. Socioeconomic inequalities in SBP and DBP trajectories were evident at 7y, narrowed in early adolescence and re-emerged between ages 16y-18y, particularly among females. Socioeconomic inequalities in lipid trajectories emerged, among females only, between birth and 9y in non-HDL-c, 7y and 18y in HDL-c and 9y and 18y in triglycerides while inequalities in glucose emerged among males only between ages 15y-18y.ConclusionPrevention targeting the early life course may be beneficial for reducing socioeconomic inequalities in CVD especially among females who have greater socioeconomic inequalities in cardiometabolic risk factors than males at the end of adolescence.
Smartphone Apps for Cannabis Cessation: Quality Assessment and Content Analysis
Authors: Seth Siddharth , Kushwaha Sumedha , Prashad Reshma , Chaiton Michael 
Published: September 2023

AbstractBackgroundThe rising rates of cannabis use, cannabis-related problems, and hospitalization rates related to cannabis usage warrant further research into better treatment methods and interventions.PurposeThis study aims to identify the quality of free cannabis cessation applications available on both the Apple App Store and the Google Play Store and analyse their features, content, and adherence to evidence-based practices.MethodsA systematic search was conducted in April 2023 using a variety of keywords. The applications were deemed eligible if they were free, in English, available on both the Apple App Store and the Google Play Store and were related to cannabis cessation. Each application was used for at least one month and were rated on the Mobile App Rating Scale by two users. There was excellent agreement determined between the two reviewers (≤2 points on all categories).ResultsA total of 4 applications were included in the overall quality and content analysis. The mean total quality scores of applications were determined to be 3.36 out of 5 indicating a poor to acceptable quality of applications. It was determined that there was a very limited number of available applications for users and those that were available were not of high quality with few applications incorporating evidence-based practices.ConclusionsThere are a very limited number of cannabis cessation applications available, and the currently available products have poor to acceptable quality.
Macrophage-expressed Neuropilin 2 promotes plaque formation in ApoE knockout mice and is essential for pro-inflammatory macrophage polarisation and gene expression
Authors: Fernando-Sayers Jacob , Harman Jennifer L. , Gage Matthew C. , Zachary Ian C. , Pellet-Many Caroline 
Published: September 2023

AbstractAimsAtherosclerosis is a chronic inflammatory disease causing the narrowing of arteries, leading to ischaemic heart disease. It is characterised by the subendothelial retention, and modification, of lipoproteins by macrophages, highly plastic cells which undergo polarisation to a pro-inflammatory phenotype in response to cytokines and other environmental stimuli.Neuropilin-2 (NRP2) is a cell-surface co-receptor with essential roles in angiogenesis and axonal guidance, that is also expressed by macrophages. However, the role of NRP2 in macrophage function in the development of atherosclerosis has not been studied.Methods and resultsThe role of NRP2 in modulating macrophage polarisation and signalling was assessed using functional assays and transcriptome analysis in macrophages obtained from mice with macrophage-specific deletion ofNrp2(Nrp2-KOMac,EYFP). These mice were further crossed with pro-atherogenic Apolipoprotein E-deficient mice to produceNrp2-KOMac,Apoe-/-,EYFPmice, which were fed a high-fat diet (HFD) for 16 weeks. Plaque formation and composition were characterised using chemical and immuno-staining.NRP2 was significantly upregulated upon differentiation of bone marrow progenitors into bone marrow derived macrophages (BMDM), and further upregulated by pro-inflammatory polarisation. Transcriptome analysis revealed that inflammatory signalling pathway genes, and genes regulating monocyte chemotaxis, were downregulated inNrp2-KOMac,EYFPBMDMs. HFD-induced plaque development was significantly reduced inNrp2-KOMac,Apoe-/-,EYFPmice. Additionally, plaques from those mice displayed features consistent with increased plaque stability, including reduced necrotic core area, plaque lipid content and increased cap thickness.ConclusionsMacrophage-derived NRP2 is proatherogenic, likely resulting from its ability to positively regulate pro-inflammatory pathways and macrophage migration. Targeting NRP2 expressed on the surface of macrophages could therefore offer a novel therapeutic approach for reducing the disease burden associated with atherosclerosis.
Proteome profiling of brain vessels in a mouse model of cerebrovascular pathology
Authors: Haqqani Arsalan S. , Mianoor Zainab , Star Alexandra T. , Detcheverry Flavie , Stanimirovic Danica B. , Hamel Edith , Badhwar AmanPreet 
Published: September 2023

ABSTRACTA cerebrovascular pathology that involves altered protein levels or signaling of the transforming growth factor beta (TGFβ) family has been associated with various forms of dementia, including Alzheimer disease (AD) and vascular cognitive impairment and dementia (VCID). Transgenic mice overexpressing TGFβ1 in the brain (TGF mice) recap VCID-associated cerebrovascular pathology and develop cognitive deficits in old age or when submitted to comorbid cardiovascular risk-factors for dementia. Here, we characterized the cerebrovascular proteome of TGF mice using mass-spectrometry (MS) based quantitative proteomics. Cerebral arteries were surgically removed from 6-month-old-TGF and wild-type mice, proteins extracted and analyzed by gel-free nanoLC-MS/MS. We identified 3,602 proteins in brain vessels, with 20 demonstrating robust altered levels in TGF mice. For total and/or differentially-expressed proteins (p≤0.01, ≥2-fold change), using multiple databases, we performed protein characterization, and identified proteins demonstrating RNA-transcripts in both mouse and human cerebrovascular cells, and known to be present in human-extracellular-vesicles (EVs). Dysregulated proteins point to perturbed brain vessel vasomotricity, remodeling, and inflammation. Given that blood-isolated EVs are novel, attractive and a minimally invasive biomarker discovery platform for the age-related dementias, several proteins identified in this study can potentially serve as VCID markers in humans.
Avoidance, confusion or solitude? Modelling how noise pollution affects whale migration
Authors: Johnston Stuart T. , Painter Kevin J. 
Published: September 2023

AbstractMany baleen whales are renowned for their acoustic communication. Under pristine conditions, this communication can plausibly occur across hundreds of kilometres. Frequent vocalisations may allow a dispersed migrating group to maintain contact, and therefore benefit from improved navigation via the “wis-dom of the crowd.” Human activities have considerably inflated ocean noise levels. Here we develop a data-driven mathematical model to investigate how ambient noise levels may inhibit whale migration. Mathematical models allow us to simul-taneously simulate collective whale migration behaviour, auditory cue detection, and noise propagation. Rising ambient noise levels are hypothesised to influence navigation through three mechanisms: (i) diminished communication space; (ii) reduced ability to hear external sound cues and; (iii) triggering noise avoidance behaviour. Comparing pristine and current soundscapes, we observe navigation impairment that ranges from mild (increased journey time) to extreme (failed navigation). Notably, the three mechanisms induce qualitatively different impacts on migration behaviour. We demonstrate the model’s potential predictive power, exploring the extent to which migration may be altered under future shipping and construction scenarios.
Cytoplasmic fluidization triggers breaking spore dormancy in fission yeast
Authors: Sakai Keiichiro , Kondo Yohei , Goto Yuhei , Aoki Kazuhiro 
Published: September 2023

AbstractThe cytoplasm is a complex, crowded environment that influences myriad cellular processes including protein folding and metabolic reactions. Recent studies have suggested that changes in the biophysical properties of the cytoplasm play a key role in cellular homeostasis and adaptation. However, it still remains unclear how cells control their cytoplasmic properties in response to environmental cues. Here, we used fission yeast spores as a model system of dormant cells to elucidate the mechanisms underlying regulation of the cytoplasmic properties. By tracking fluorescent tracer particles, we found that particle mobility decreased in spores compared to vegetative cells, and rapidly increased at the onset of dormancy breaking upon glucose addition. This cytoplasmic fluidization depended on glucose sensing via the cAMP-PKA pathway. PKA activation led to trehalose degradation through trehalase Ntp1, thereby increasing particle mobility as the amount of trehalose decreased. In contrast, the rapid cytoplasmic fluidization did not requirede novoprotein synthesis, cytoskeletal dynamics, or cell volume increase. Furthermore, the measurement of diffusion coefficients with tracer particles of different sizes suggests that the spore cytoplasm impedes the movement of larger protein complexes (40–150 nm) such as ribosomes, while allowing free diffusion of smaller molecules (∼3 nm) such as second messengers and signaling proteins. Our experiments have thus uncovered a series of signaling events that enable cells to quickly fluidize the cytoplasm at the onset of dormancy breaking.Significance statementCellular processes are influenced by the biophysical properties of the cytoplasm such as crowding and viscoelasticity. Although it has been suggested that cells tune the cytoplasmic properties in response to environmental changes, the molecular mechanisms remain unclear. Here, we used the dormant fission yeast spores and uncovered signaling pathways that facilitate cytoplasmic fluidization during dormancy breaking. Furthermore, we tracked the mobility of intracellular tracer particles, and found that the spore cytoplasm impedes the mobility of larger protein complexes, while allowing free diffusion of smaller molecules. These results suggest that small signaling proteins can diffuse relatively freely in the spore cytoplasm and have the ability to transmit dormancy breaking signals, while the motion of large complexes, such as ribosomes, is restricted.
Mapping the task-general and task-specific neural correlates of speech production: meta-analysis and fMRI direct comparisons of category fluency and picture naming
Authors: Humphreys Gina F. , Ralph Matthew A. Lambon 
Published: September 2023

AbstractImproving our understanding of the neural network engaged by different forms of speech production is a crucial step for both cognitive and clinical neuroscience. We achieved this aim by exploring two of the most commonly utilised speech production paradigms in research and the clinic, which have been rarely, if ever, compared directly: picture naming and category fluency. This goal was achieved in this two study investigation through a full ALE meta-analysis as well as a targeted fMRI study. Harnessing the similarities and differences between the two tasks offers a powerful methodology to delineate the core systems recruited for speech production, as well as revealing task-specific processes. The results showed that both tasks engaged a bilateral fronto-temporal speech production network, including executive and motor frontal areas, as well as semantic representational regions in the ATL, bilaterally. In addition, it was found that the extent of relative frontal lateralisation was task-dependent with the more executively-demanding category fluency task showing augmented left hemisphere activation. The results have implications for neurocomputational speech production models and the clinical assessment of speech production impairments.Open access: For the purpose of open access, the UKRI-funded authors have applied a Creative Commons Attribution (CC BY) licence to any Author Accepted Manuscript version arising from this submission.
53BP1 interacts with the RNA primer from Okazaki fragments to support their processing during unperturbed DNA replication
Authors: Leriche Melissa , Bonnet Clara , Jana Jagannath , Chhetri Gita , Mennour Sabrina , Martineau Sylvain , Pennaneach Vincent , Busso Didier , Veaute Xavier , Bertrand Pascale , Lambert Sarah , Somyajit Kumar , Uguen Patricia , Vagner Stéphan 
Published: September 2023

ABSTRACTRNA-binding proteins are found at replication forks, but their direct interaction with DNA-embedded RNA species that inevitably shape physiological DNA replication remains unexplored. Here we report that 53BP1, involved in the DNA damage and replication stress response, is an RNA-binding protein that directly interacts with Okazaki fragments, in the absence of any external stress. The bulk chromatin association of 53BP1 shows dramatic dependence on PRIM1, which synthesizes the RNA primer of Okazaki fragments. The direct recruitment of 53BP1 to nascent DNA shows susceptibility toin situribonuclease A treatment. Conversely, depletion of FEN1, which results in the accumulation of uncleaved RNA primers, leads to an upregulation of 53BP1 levels at the replication forks, suggesting that RNA primers contribute to the recruitment of 53BP1 at the lagging DNA strand. 53BP1 depletion induces an accumulation of S phase poly(ADP-ribose), which constitutes a sensor of unligated Okazaki fragments. Collectively, our data indicate that 53BP1, distinct from its canonical mode of chromatin-binding, is anchored at the replication fork through its RNA-binding activity, highlighting the role of an RNA-protein interaction at DNA replication forks.
Transcriptional reactivation of the tRNASer/tRNATyrgene cluster inArabidopsis thalianaroot tip (V2)
Authors: Hummel Guillaume , Kumari Priyanka , Hua Chenlei , Wang Long , Mai Yan-Xia , Wang Nan , Shala Negjmedin , Kaya Emir Can , Molinier Jean , Wang Jia-Wei , Liu Chang 
Published: September 2023

ABSTRACTPlants retain a repetitious tRNA gene content in their nuclear genome. How important are these individuals, how exactly plants orchestrate their usage, and for what purposes, is poorly understood.Arabidopsis thalianachromosome 1 holds a cluster of tandemly repeated serine– and tyrosine-decoding tRNA genes (SYY cluster). They intersect with constitutive heterochromatin and are silenced in most parts of the plant. Yet, the natural conditions leading to their transcription remain unknown. Here, we resolve the tissular expression pattern of this cluster along seedling establishment. We show that the root cap columella and few adjacent lateral root cap cells are the main sources of SYY cluster tRNAs. The transcriptional reactivation of the SYY cluster occurs in these tissues although elevated DNA methylation levels. Furthermore, we evidence that these cells are able to accumulate high levels of a transgenic glycoprotein rich in serine, tyrosine, and proline, and that the CRISPR/Cas9 deletion of the SYY cluster alters the phenomenon. Altogether, our work sheds light on pioneering evidence of a developmental and cell-specific expression program for a plant tRNA gene. We provide new perspectives on the role of peculiar tRNA genes in conferring a potential for the high synthesis of glycoproteins in protective tissues of the meristem.
Dairy practices select for thermostable endolysins in phages
Authors: Oechslin Frank , Zhu Xiaojun , Morency Carlee , Somerville Vincent , Shi Rong , Moineau Sylvain 
Published: September 2023

AbstractEndolysins are phage lytic enzymes that degrade the bacterial cell wall to release phage progeny. We found that the diversity of endolysins is unsuspectedly low and dominated by a single structural type in distinct phages that infectStreptococcus thermophilus. Through X-ray crystallography, we discovered that this type of endolysin contains a highly conserved calcium-binding motif in its cell wall binding domain. Inactivation of the motif in the purified endolysin or in the phage genome revealed its key role in stabilizing the enzyme under conditions that mimic the cheesemaking process, including at elevated temperatures. Fermented dairy products such as yogurt and cheeses are incubated or cooked at higher temperatures and require the addition of thermophilic lactic acid bacteria such asS. thermophilusto drive milk fermentation. It appears that dairy practices have influenced the genetic signatures of streptococcal phages by selecting for thermostable endolysins, which in turn have limited their diversity.
RlmQ: A Newly Discovered rRNA Modification Enzyme Bridging RNA Modification and Virulence Traits inStaphylococcus aureus
Authors: Bahena-Ceron Roberto , Teixeira Chloe , Jaramillo Ponce Jose R , Wolff Philippe , Couzon Florence , François Pauline , Klaholz Bruno , Vandenesch François , Romby Pascale , Moreau Karen , Marzi Stefano 
Published: September 2023

ABSTRACTrRNA modifications play crucial roles in fine-tuning the delicate balance between translation speed and accuracy, yet the underlying mechanisms remain elusive. Comparative analysis of the ribosomal RNA modifications in taxonomically distant bacteria could help define their general as well as species-specific roles. In this study, we identified a new methyltransferase, RlmQ, inStaphylococcus aureusresponsible for the Gram-positive specific m7G2601, which is not modified inE. coli(G2574). We also demonstrate the absence of methylation on C1989, equivalent toE. coliC1962, which is methylated at position 5 by the Gram-negative specific RlmI methyltransferase, a paralogue of RlmQ. Both modifications (S. aureusm7G2601 andE. colim5C1962) are situated within the same tRNA accommodation corridor, hinting at a potential shared function in translation. Inactivation ofS. aureus rlmQcauses the loss of methylation at G2601 and significantly impacts growth, cytotoxicity, and biofilm formation. These findings unravel the intricate connections between rRNA modifications, translation, and virulence in pathogenic Gram-positive bacteria.
Transient states during the annealing of mismatched and bulged oligonucleotides
Authors: Todisco Marco , Ding Dian , Szostak Jack W. 
Published: September 2023

ABSTRACTOligonucleotide hybridization is crucial in various biological, prebiotic and nanotechnological processes, including gene regulation, non-enzymatic primer extension and DNA nanodevice assembly. Although extensive research has focused on the thermodynamics and kinetics of nucleic acid hybridization, the behavior of complex mixtures and the outcome of competition for target binding remain less well understood. In this study, we investigate the impact of mismatches and bulges in a 12bp DNA or RNA duplex on its association (kon) and dissociation (koff) kinetics. We find that such defects have relatively small effects on the association kinetics, while the dissociation kinetics vary in a position-dependent manner by up to 6 orders of magnitude. Building upon this observation, we explored a competition scenario involving multiple oligonucleotides, and observed a transient low specificity of probe hybridization to fully vs. partially complementary targets in solution. We characterize these long-lived metastable states and their evolution toward equilibrium, and show that sufficiently long-lived mis-paired duplexes can serve as substrates for prebiotically relevant chemical copying reactions. Our results suggest that transient low accuracy states may spontaneously emerge within all complex nucleic acid systems comprising a large enough number of competing strands, with potential repercussions for gene regulation in the realm of modern biology and the prebiotic preservation of genetic information.