bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating the association between oral health behaviours and risk behaviours of university students – a quantitative study utilising online questionnaires
Authors: Azam Tanzeelah , Kitsaras George , Gomez Juliana , Goodwin Michaela 
Published: August 2024

AbstractBackgroundYoung adults are exposed to a variety of risk-related behaviours such as alcohol, smoking, and changes in dietary habits, which may result in unknown outcomes in their oral health. There is limited evidence on whether different risk behaviours are associated with oral health behaviours in the university student population. This study gathers data on the behaviours of students in their first year of university, which will inform the future development of oral health behaviour change interventions for this population.MethodThis longitudinal quantitative survey involved 205 first-year university students, aged 18-24. They completed questionnaires at baseline and a 6-month follow-up interval providing information regarding self-reported oral health status, hygiene routines, risk behaviours (e.g., diet, smoking, alcohol) and attitudes towards digital health.ResultsThe findings show associations between oral health behaviours with risk behaviours including links with oral care routines, bleeding gums, brushing frequency, with exercise, vaping, and unhealthy food and drink intake. Significant changes over the two-time points were also observed, such as the worsening of the self-reported condition of the teeth (p<0.001), reduction in the self-reported condition of the gums (p=0.004), reduced brushing frequency (p=0.003), less regular dental visits (p=0.013), more students intending to visit their previous dentist rather than finding a new dentist at university (p=0.026), and increased consumption of unhealthy non-alcoholic drinks (p=0.003). Positive changes over time include reduced alcohol consumption frequency and units (p=0.030 and p=0.001), fewer instances of binge drinking (p=0.014), and less frequent consumption of unhealthy foods (p=0.034).ConclusionThe findings highlight the complex relationship between oral heal and risk behaviours in this demographic. Poorer oral health behaviours are linked to engagement in risk behaviours. Therefore, oral health behaviours should be targeted alongside other risk behaviours. Tailored interventions should be developed to improve oral health and behaviour among university students.
Prospective Analysis of urINe LAM to Eliminate NTM Sputum Screening (PAINLESS) study: Rationale and trial design for testing urine lipoarabinomannan as a marker of NTM lung infection in cystic fibrosis
Authors: Calhoun Kara M. , Armantrout Emily , Poch Katie , Caceres Silvia , Lovell Valerie K. , Jones Marion , Malcolm Kenneth C. , Vestal Brian , Wheeler Emily , Rysavy Noel , Manzer Jordan , Aboellail Ibrahim , Chatterjee Delphi , Nick Jerry A. 
Published: August 2024

AbstractBackgroundRoutine screening for nontuberculous mycobacterial (NTM) lung disease is dependent on sputum cultures. This is particularly challenging in the cystic fibrosis (CF) population due to reduced sputum production and low culture sensitivity. Biomarkers of infection that do not rely on sputum may lead to earlier diagnosis, but validation trials require a unique prospective design.PurposeThe rationale of this trial is to investigate the utility of urine lipoarabinomannan (LAM) as a test to identify people with CF with a new positive NTM culture. We hypothesize that urine LAM is a sensitive, non-invasive screening test with a high negative predictive value to identify individuals with a relatively low risk of having positive NTM sputum culture.Study designThis is a prospective, single-center, non-randomized observational study in adults with CF, 3 years of negative NTM cultures, and no known history of NTM positive cultures. Patients are followed for two year-long observational periods with the primary endpoint being a positive NTM sputum culture within a year of a positive urine LAM result and a secondary endpoint of a positive NTM sputum culture within 3 years of a positive urine LAM result. Study implementation includes remote consent and sample collection to accommodate changes from the COVID-19 pandemic.ConclusionsThis report describes the study design of an observational study aimed at using a urine biomarker to assist in the diagnosis of NTM lung infection in pwCF. If successful, urine LAM could be used as an adjunct to traditional sputum cultures for routine NTM screening.
Adenomas from individuals with pathogenic biallelic variants in theMUTYHandNTHL1genes demonstrate base excision repair tumour mutational signature profiles similar to colorectal cancers, expanding potential diagnostic and variant classification applications
Authors: Walker Romy , Joo Jihoon E. , Mahmood Khalid , Clendenning Mark , Como Julia , Preston Susan G. , Joseland Sharelle , Pope Bernard J. , Medeiros Ana B. D. , Murillo Brenely V. , Pachter Nicholas , Sweet Kevin , Spigelman Allan D. , Groves Alexandra , Gleeson Margaret , Bernatowicz Krzysztof , Poplawski Nicola , Andrews Lesley , Healey Emma , Gallinger Steven , Grant Robert C. , Win Aung K. , Hopper John L. , Jenkins Mark A. , Torrezan Giovana T. , Rosty Christophe , Macrae Finlay A. , Winship Ingrid M. , Buchanan Daniel D. , Georgeson Peter 
Published: August 2024

ABSTRACTBackgroundColorectal cancers (CRCs) from people with biallelic germline likely pathogenic/pathogenic variants inMUTYHorNTHL1exhibit specific single base substitution (SBS) mutational signatures, namely combined SBS18 and SBS36 (SBS18+SBS36), and SBS30, respectively. The aim was to determine if adenomas from biallelic cases demonstrated these mutational signatures at diagnostic levels.MethodsWhole-exome sequencing of FFPE tissue and matched blood-derived DNA was performed on 9 adenomas and 15 CRCs from 13 biallelicMUTYHcases, on 7 adenomas and 2 CRCs from 5 biallelicNTHL1cases and on 27 adenomas and 26 CRCs from 46 non-hereditary (sporadic) participants. All samples were assessed for COSMIC v3.2 SBS mutational signatures.ResultsIn biallelicMUTYHcases, SBS18+SBS36 signature proportions in adenomas (mean±standard deviation, 65.6%±29.6%) were not significantly different to those observed in CRCs (76.2%±20.5%,p-value=0.37), but were significantly higher compared with non-hereditary adenomas (7.6%±7.0%,p-value=3.4x10-4). Similarly, in biallelicNTHL1cases, SBS30 signature proportions in adenomas (74.5%±9.4%) were similar to those in CRCs (78.8%±2.4%) but significantly higher compared with non-hereditary adenomas (2.8%±3.6%,p-value=5.1x10-7). Additionally, a compound heterozygote with the c.1187G>A p.(Gly396Asp) pathogenic variant and the c.533G>C p.(Gly178Ala) variant of unknown significance (VUS) inMUTYHdemonstrated high levels of SBS18+SBS36 in four adenomas and one CRC, providing evidence for reclassification of the VUS to pathogenic.ConclusionsSBS18+SBS36 and SBS30 were enriched in adenomas at comparable proportions observed in CRCs from biallelicMUTYHand biallelicNTHL1cases, respectively. Therefore, testing adenomas may improve the identification of biallelic cases and facilitate variant classification, ultimately enabling opportunities for CRC prevention.
Biallelic Loss of Molecular Chaperone Molecule AIP Results in a Novel Severe Multisystem Disease Defined by Defective Proteostasis
Authors: Korbonits Márta , Wang Xian , Barry Sayka , Lim Chung Thong , Suleyman Oniz , Tito Stefano De , Uddin Nazia , Vignola Maria Lillina , Hall Charlotte , Perna Laura , Chapple J. Paul , Czbik Gabor , Henson Sian M , Morales Valle , Bianchi Katiuscia , Eðvarðsson Viðar Örn , Ragnarsson Kristján Ari , Kristinsdóttir Viktoría Eir , Debeer Anne , Sleyp Yoeri , Zinchenko Rena , Anderson Glenn , Duchen Michael , Singh Kritarth , Chung Chih Yao , Yuan Yu , Patel Sandip , Aksoy Ezra , Borovikov Artem O. , Björnsson Hans Tómas , Esch Hilde Van , Tooze Sharon , Brennan Caroline , Haworth Oliver 
Published: August 2024

AbstractChildren born with deleterious biallelic variants of the chaperone aryl hydrocarbon receptor interacting protein (AIP) have a novel pediatric metabolic disease presenting a severe, complex clinical phenotype characterized by failure to develop following birth. Analysis ofAipknockout mouse embryonic fibroblasts and patient-derived dermal fibroblasts revealed that AIP was required to support proteostasis; including proteasome activity, induction of autophagy and lysosome function. aip knockout zebrafish, recapitulated the phenotype of the children; dying at an early stage of development when autophagy is required to adapt to periods of starvation. Our results demonstrate that AIP plays a crucial role in initiating autophagy and maintaining proteostasisin vitroandin vivo.One Sentence SummaryHomozygous loss of the chaperone AIP results in a novel pediatric disease exhibiting multiple features of a lysosomal storage disease.
SILAC-based quantification reveals modulation of the immunopeptidome in BRAF and MEK inhibitor sensitive and resistant tumor cells
Authors: Bernhardt Melissa , Rech Anne , Berthold Marion , Lappe Melina , Herbel Jan-Niklas , Erhard Florian , Paschen Anette , Schilling Bastian , Schlosser Andreas 
Published: August 2024

AbstractThe immunopeptidome is constantly monitored by T cells to detect foreign or aberrant HLA peptides. It is highly dynamic and reflects the current cellular state, enabling the immune system to recognize abnormal cellular conditions, such as those present in cancer cells. To precisely determine how changes in cellular processes, such as those induced by drug treatment, affect the immunopeptidome, quantitative immunopeptidomics approaches are essential. To meet this need, we developed a pulsed SILAC-based method for quantitative immunopeptidomics. Metabolic labeling with lysine, arginine, and leucine enabled isotopic labeling of nearly all HLA peptides across all allotypes (> 90% on average). We established a data analysis workflow that integrates thede novosequencing-based tool Peptide-PRISM for comprehensive HLA peptide identification with MaxQuant for accurate quantification. We employed this strategy to explore the modulation of the immunopeptidome upon MAPK pathway inhibition (MAPKi) and to investigate alterations associated with early cellular responses to inhibitor treatment and acquired resistance to MAPKi. Our analyses demonstrated significant changes in the immunopeptidome early during MAPKi treatment and in the resistant state. Moreover, we identified putative tumor-specific cryptic HLA peptides linked to these processes that might represent exploitable targets for cancer immunotherapy.SynopsisWe have developed a mass spectrometric method that allowed us to investigate the effects of common MAPK inhibitors on the immunopeptidome of melanoma cells. This approach has led to the discovery of new potential targets for cancer immunotherapy.
Neurofibromin deficiency alters the patterning and prioritization of motor behaviors in a state-dependent manner
Authors: Suarez Genesis Omana , Kumar Divya S. , Brunner Hannah , Emel Jalen , Teel Jensen , Knauss Anneke , Botero Valentina , Broyles Connor N. , Stahl Aaron , Bidaye Salil S. , Tomchik Seth M. 
Published: August 2024

AbstractGenetic disorders such as neurofibromatosis type 1 increase vulnerability to cognitive and behavioral disorders, such as autism spectrum disorder and attention-deficit/hyperactivity disorder. Neurofibromatosis type 1 results from loss-of-function mutations in the neurofibromin gene and subsequent reduction in the neurofibromin protein (Nf1). While the mechanisms have yet to be fully elucidated, loss of Nf1 may alter neuronal circuit activity leading to changes in behavior and susceptibility to cognitive and behavioral comorbidities. Here we show that mutations decreasing Nf1 expression alter motor behaviors, impacting the patterning, prioritization, and behavioral state dependence in aDrosophilamodel of neurofibromatosis type 1. Loss of Nf1 increases spontaneous grooming in a nonlinear spatial and temporal pattern, differentially increasing grooming of certain body parts, including the abdomen, head, and wings. This increase in grooming could be overridden by hunger in food-deprived foraging animals, demonstrating that the Nf1 effect is plastic and internal state-dependent. Stimulus-evoked grooming patterns were altered as well, withnf1mutants exhibiting reductions in wing grooming when coated with dust, suggesting that hierarchical recruitment of grooming command circuits was altered. Yet loss of Nf1 in sensory neurons and/or grooming command neurons did not alter grooming frequency, suggesting that Nf1 affects grooming via higher-order circuit alterations. Changes in grooming coincided with alterations in walking. Flies lacking Nf1 walked with increased forward velocity on a spherical treadmill, yet there was no detectable change in leg kinematics or gait. Thus, loss of Nf1 alters motor function without affecting overall motor coordination, in contrast to other genetic disorders that impair coordination. Overall, these results demonstrate that loss of Nf1 alters the patterning and prioritization of repetitive behaviors, in a state-dependent manner, without affecting motor coordination.
DMT1 knockout abolishes ferroptosis induced mitochondrial dysfunction inC. elegansamyloid β proteotoxicity
Authors: Peng Wilson , Chung Kaitlin B , Lawrence B Paige , O’Banion M Kerry , Dirksen Robert T , Wojtovich Andrew P , Onukwufor John O 
Published: August 2024

AbstractIron is critical for neuronal activity and metabolism, and iron dysregulation alters these functions in age-related neurodegenerative disorders, such as Alzheimer’s disease (AD). AD is a chronic neurodegenerative disease characterized by progressive neuronal dysfunction, memory loss and decreased cognitive function. AD patients exhibit elevated iron levels in the brain compared to age-matched non-AD individuals. However, the degree to which iron overload contributes to AD pathogenesis is unclear. Here, we evaluated the involvement of ferroptosis, an iron-dependent cell death process, in mediating AD-like pathologies inC. elegans. Results showed that iron accumulation occurred prior to the loss of neuronal function as worms age. In addition, energetic imbalance was an early event in iron-induced loss of neuronal function. Furthermore, the loss of neuronal function was, in part, due to increased mitochondrial reactive oxygen species mediated oxidative damage, ultimately resulting in ferroptotic cell death. The mitochondrial redox environment and ferroptosis were modulated by pharmacologic processes that exacerbate or abolish iron accumulation both in wild-type worms and worms with increased levels of neuronal amyloid beta (Aβ). However, neuronal Aβ worms were more sensitive to ferroptosis-mediated neuronal loss, and this increased toxicity was ameliorated by limiting the uptake of ferrous iron through knockout of divalent metal transporter 1 (DMT1). In addition, DMT1 knockout completely suppressed phenotypic measures of Aβ toxicity with age. Overall, our findings suggest that iron-induced ferroptosis alters the mitochondrial redox environment to drive oxidative damage when neuronal Aβ is overexpressed. DMT1 knockout abolishes neuronal Aβ−associated pathologies by reducing neuronal iron uptake.HighlightsEnergetic imbalance is an early event in iron-induced loss of neuronal functionNeuronal Aβ increases susceptibility to ferroptosis mediated oxidative damageDivalent metal transporter 1 knockout protects against iron-induced oxidative damage and ferroptosisGraphical Abstract
Reduced gene dosage of the psychiatric risk geneCacna1cis associated with impairments in hypothalamic-pituitary-adrenal axis activity in rats
Authors: Moon Anna L. , Mawson Elle , Gasalla Canto Patricia , Wilkinson Lawrence , Dwyer Dominic , Thomas Kerrie L. , Hall Jeremy 
Published: August 2024

AbstractCommon and rare variation inCACNA1Cgene expression has been consistently associated with neuropsychiatric disorders such as schizophrenia, bipolar disorder, and major depression, however the underlying biological pathways that cause this association have yet to be fully determined. In this study, we present evidence that rats with a reduced gene dosage ofCacna1chave increased basal corticosterone levels in the periphery and reducedNr3c1gene expression in the hippocampus and hypothalamus. These results are consistent with an effect ofCacna1cdosage on hypothalamus-pituitary-adrenal (HPA) axis function. We also show that the reduction ofNr3c1in the hippocampus may be caused by epigenetic modification of exon 17ofNr3c1, including the reduced interaction with the histone modifying markers H3K4me3 and H3K27ac. HeterozygousCacna1crats additionally show increased anxiety behaviours. These results support an association ofCacna1cheterozygosity with the altered activity of the HPA axis and function in the resting state and this may be a predisposing mechanism that contributes to the increased risk of psychiatric disorders with stress.
Sequencing of historical plastid genomes reveal exceptional genetic diversity in early domesticated rye plants
Authors: Komluski Jovan , Filatova Sofia , Schlütz Frank , Claaßen Benjamin , Rösch Manfred , Krause-Kyora Ben , Kirleis Wiebke , Stukenbrock Eva H. 
Published: August 2024

AbstractIn medieval central Europe, rye was one of the most important agricultural crops. It’s properties of frost resistance, general resilience and resistance to many pathogens made it invaluable for medieval farmers. Rye has a distinct domestication history compared to other cereal crops and was not domesticated directly from its wild ancestors, like barley and wheat. Rye is considered to be a “secondary domesticate”, i.e. a crop with domestication traits that initially evolved as an arable weed but eventually was intentionally sown and propagated as a crop. To study the history of rye domestication, genetic sequences of present-day plant populations as well as material from historical samples can provide insights into the temporal and spatial signatures of domestication. In this study we combined archaeobotanical methods and ancient DNA sequencing of well-preserved, historical rye material to study patterns of genetic diversity across four centuries. We first applied archaeobotanical methods to characterize rye material acquired from construction material ranging from the 14thto 18thcentury from different locations in Germany. Next, we extracted DNA to sequence complete chloroplast genomes of six individual samples. We compared the 115,000 bp chloroplast genomes of historical rye samples to chloroplast genomes of other cereal crops and identified 217 single nucleotide variants exclusive to historical samples. By comparing the aDNA chloroplast samples with modern rye chloroplasts, we show that the genetic variation in ancient rye populations was exceptionally high compared to samples from contemporary rye cultivars. This confirms that late domestication and selective breeding have reduced genetic variation in this important crop species only in the last few centuries.HighlightsHistorical plant material covering four centuries was obtained from half-timbered houses from five locations in GermanyIntegrative archaeobotanical analyses and ancient DNA sequencing provided insights into genetic diversity of rye plants from historical farmland fields.Sequence analyses of complete assembled chloroplast genomes reveal expectational diversity in rye populations.Late domestication of rye preserved genetic diversity over centuries. The more recent intensification of rye breeding has however conferred a considerable loss of genetic diversity in this important crop.
Subcellular context-specific tuning of actomyosin ring contractility within a common cytoplasm
Authors: Linehan John B. , Zampetaki Alexandra , Werner Michael E. , Heck Bryan , Maddox Paul S. , Fürthauer Sebastian , Maddox Amy S. 
Published: August 2024

SummaryThe non-muscle actomyosin cytoskeleton generates contractile force through the dynamic rearrangement of its constituent parts. Actomyosin rings are a specialization of the non-muscle actomyosin cytoskeleton that drive cell shape changes during division, wound healing, and other events. Contractile rings throughout phylogeny and in a range of cellular contexts are built from conserved components including non-muscle myosin II (NMMII), actin filaments (F-actin), and crosslinking proteins. However, it is unknown whether diverse actomyosin rings close via a single unifying mechanism. To explore how contractile forces are generated by actomyosin rings, we studied three instances of ring closure within the common cytoplasm of theC. elegansoogenic germline: mitotic cytokinesis of germline stem cells (GSCs), apoptosis of meiotic compartments, and cellularization of oocytes. We found that each ring type closed with unique kinetics, protein density and abundance dynamics. These measurements suggested that the mechanism of contractile force generation varied across the subcellular contexts. Next, we formulated a physical model that related the forces generated by filament-filament interactions to the material properties of these rings that dictate the kinetics of their closure. Using this framework, we related the density of conserved cytoskeletal proteins anillin and NMMII to the kinematics of ring closure. We fitted model rings to in situ measurements to estimate parameters that are currently experimentally inaccessible, such as the asymmetric distribution of protein along the length of F-actin, which occurs naturally due to differences in the dimensions of the crosslinker and NMMII filaments. Our work predicted that the role of NMMII varies across these ring types, due in part to its distribution along F-actin and motoring. Our model also predicted that the degree of contractility and the impact of ring material properties on contractility differs among ring types.
Mechanism of ASF1 Inhibition by CDAN1
Authors: Sedor Samantha F. , Shao Sichen 
Published: August 2024

AbstractCodanin-1 (CDAN1) is an essential and ubiquitous protein named after congenital dyserythropoietic anemia type I (CDA-I), an autosomal recessive disease that manifests from mutations in theCDAN1orCDIN1(CDAN1 interactingnuclease 1) gene. CDAN1 interacts with CDIN1 and the paralogous histone H3-H4 chaperones ASF1A (Anti-SilencingFunction 1A) and ASF1B, but its function remains unclear. Here, we biochemically and structurally analyze CDAN1 complexes. We find that CDAN1 dimerizes and assembles into cytosolic complexes with CDIN1 and multiple copies of ASF1A/B. Single-particle cryogenic electron microscopy (cryo-EM) structures of CDAN1 complexes identify interactions with ASF1 mediated by two CDAN1 B-domains commonly found in ASF1 binding partners and two helices that mimic histone H3 binding. We additionally observe that one CDAN1 can recruit two ASF1 molecules and that ASF1A and ASF1B have different requirements for CDAN1 engagement. Our findings explain how CDAN1 sequesters and inhibits the chaperone function of ASF1A/B and provide new molecular-level insights into this enigmatic complex.