bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-molecule Mapping of Amyloid-β Oligomer Insertion into Lipid Bilayers
Authors: Dey Arpan , Patil Abhsihek , Arumugam Senthil , Maiti Sudipta 
Published: February 2024

AbstractThe interaction of disease-causing amyloid oligomers with lipid membranes is implicated in their toxicity. However, understanding the membrane interaction of different oligomers, and each constituent monomer in a given oligomer, has remained a challenge. Here we employed a recently developed single-molecule technique, called QSLIP, which can simultaneously determine the stoichiometry and membrane location of individual fluorescent labels on oligomeric membrane proteins. Using QSLIP, we measured the membrane insertion of small amyloid-beta (Aβ) oligomers of three different isoforms at the single-molecule level, and found that their toxicity is correlated with the depth of penetration of their amino-terminal into the bilayer. Such single-molecule maps provide a detailed assay for measuring the effect of any drug candidate on oligomer-membrane interactions.
Salivary metabolomics in the family environment: A large-scale study investigating oral metabolomes in children and their parental caregivers
Authors: Rothman Jason A. , Piccerillo Hillary L. , Riis Jenna L. , Granger Douglas A. , Thomas Elizabeth A. , Whiteson Katrine L. 
Published: February 2024

AbstractHuman metabolism is complex and dynamic, and is impacted by genetics, diet, health, and countless inputs from the environment. Beyond the genetics shared by family members, cohabitation leads to shared microbial and environmental exposures. Furthermore, metabolism is affected by factors such as inflammation, environmental tobacco smoke (ETS) exposure, metabolic regulation, and exposure to heavy metals.Metabolomics represents a useful analytical method to assay the metabolism of individuals to find potential biomarkers for metabolic conditions that may not be phenotypically obvious or represent unknown physiological processes. As such, we applied untargeted LC-MS metabolomics to archived saliva samples from a racially diverse group of elementary school-aged children and their caregivers collected during the “90-month” assessment of the Family Life Project. We assayed a total of 1,425 saliva samples of which 1,344 were paired into 672 caregiver/child dyads. We compared the metabolomes of children (N = 719) and caregivers (N = 706) within and between homes, performed population-wide “metabotype” analyses, and measured associations between metabolites and salivary biomeasures of inflammation, antioxidant potential, ETS exposure, metabolic regulation, and heavy metals.Dyadic analyses revealed that children and their caregivers have largely similar salivary metabolomes. Although there were differences between the dyads at the individual levels of analysis, dyad explained most (62%) of the metabolome variation. At a population level of analysis, our data clustered into two large groups, indicating that people likely share most of their metabolomes, but that there are distinct “metabotypes” across large sample sets. Lastly, individual differences in several metabolites – which were putative oxidative damage-associated or pathological markers – were significantly correlated with salivary measures indexing inflammation, antioxidant potential, ETS exposure, metabolic regulation, and heavy metals. Implications of the effects of family environment on metabolomic variation at the population, dyadic, and individual levels of analyses for health and human development are discussed.
Improving 3D-CINE tTV-regularized whole-heart MRI reconstruction
Authors: Milani Bastien , Roy Christopher , Ledoux Jean-Baptiste , Rotzinger David C. , Masi Ambra , Troxler Renaud , Si-mohamed Salim , Yerly Jerome , Romanin Ludovica , Rutz Tobias , Tenisch Estelle , Prsa Milan , Schwitter Juerg , Stuber Matthias 
Published: February 2024

AbstractPurposeTo improve the image quality of 3D radial free-running MRI data of the heart through a deliberate and stepwise extension of the XD-GRASP reconstruction.MethodsFerumoxytol-enhanced cardiac free-running 3D-radial data were reconstructed using an XD-GRASP reconstruction improved by 4 new developments: motion-compensated temporal-Total-Variation (MC-tTV) regularization for 3D images, a new coil-sensitivity, a new k-space density compensation and a revisited conjugate-gradient-descent (with exact line search) for solving the least-square sub-problem of ADMM. The resulting images were compared quantitatively and qualitatively to reconstructions lacking some of the newly implemented measures. Also, the measurement of ejection-fraction by a threshold-based method on the new reconstruction was compared to a reference standard.ResultsThe new reconstruction significantly increased the sharpness of the right coronary artery (4% to 6%, p < 0.05) and the left anterior descending coronary artery (4% to 5% p < 0.05). It also increased blood-myocardium interface sharpness (between 20% and 25%, p < 0.05) and decreases spatial-Total-Variation in the blood-pool (13%, p < 0.05). The qualitative evaluation suggests better anatomical depiction of small structures using the new reconstruction. As compared to a reference standard method, ejection fraction could also be correctly evaluated.ConclusionCompressed sensing image reconstruction for 3D-radial free-running cardiac acquisition was successfully improved by including MC-tTV regularization, a new density compensation, a new coil-sensitivity and a revisited conjugate-gradient-descent with exact line search. Quantitative and qualitative quality metrics demonstrated significant improvement in image quality when using the new reconstruction, while extracted dynamic information compared favorably with the gold standard.
Perceptions of barriers and facilitators for cervical cancer screening from women and healthcare workers in Ghana: Applying the Dynamic Sustainability Framework
Authors: Boamah Mensah Adwoa Bemah , Konney Thomas Okpoti , Adankwah Ernest , Amuasi John , Nones Madalyn , Okyere Joshua , Boadu Kwame Ofori , Efua Eduah Felicia Maame , Xiong Serena , Moon J. Robin , Virnig Beth , Kulasingam Shalini 
Published: February 2024

AbstractCervical cancer screening has reduced cervical cancer-related mortality by over 70% in countries that have achieved high coverage. However, there are significant geographic disparities in access to screening. In Ghana, although cervical cancer is the second most common cancer in women, there is no national-level cervical cancer screening program, and only 2 to 4% of eligible Ghanaian women have ever been screened for cervical cancer. This study used an exploratory, sequential mixed-methods approach to examine barriers and facilitators to cervical cancer screening from women and healthcare workers perspectives, guided by the Dynamic Sustainability Framework. Two convenience samples of 215 women and 17 healthcare personnel were recruited for this study. All participants were from one of three selected clinics (Ejisu Government Hospital, Kumasi South Hospital, and the Suntreso Government Hospital) in the Ashanti region of Ghana. Descriptive analyses were used to group the data by practice setting and ecological system. Statistical differences in means and proportions were used to evaluate women’s barriers to cervical cancer screening. Quantitative findings from the women’s survey informed qualitative, in-depth interviews with the healthcare workers and analyzed using an inductive thematic analysis. The median age of women and healthcare workers was 37.0 years and 38.0 years respectively. Most women (n=194, 90.2%) reported never having been screened. Women who had not been screened were more likely to have no college or university education. Ecologic factors identified were lack of knowledge about available services, distance to a clinic and requiring a spouse’s permission prior to scheduling. Practice setting barriers included long clinic wait times and culturally sensitive issue. The quantitative and qualitative data were integrated in the data collection stage, results, and subsequent discussion. These findings highlight the need for non-clinician-based culturally sensitive tool options for screening such as self-collected HPV tests to increase screening participation in Ghana.
Efficient cloning of genes for wheat yield component traits from QTLs via sequencing of the RIL population
Authors: Zhang Mingxia , Han Xu , Wang Hui , Sun Junsheng , Guo Baojin , Gao Minggang , Xu Huiyan , Zhang Guizhi , Li Hongna , Cao Xiaofeng , Li Nannan , Xu Yiru , Wu Qun , Wang Chunyang , Zhang Guohua , Yuan Yapei , Man Junxia , Pu Yanyan , Lv Guangde , Qu Chunyan , Sun Jinjie , Cheng Xiyong , Dong Xinjuan , Kong Fanmei , Zhao Yan , An Yanrong , Yuan Yuanyuan , Guo Ying , Li Sishen 
Published: February 2024

AbstractIn wheat (Triticum aestivumL.), yield component traits (YCTs) are the most important yield traits. Only several genes for YCTs have been originally cloned. The efficient cloning of genes for YCTs directly from wheat remains a challenge. Here, we proposed a strategy for cloning genes from quantitative trait loci (QTLs) by sequencing of recombinant inbred lines (RILs) (QTL-Seq-RIL). Using the ‘TN18 × LM6’ RIL population as an example, we identified 138 candidate unigenes (CUGs) for YCTs from 77 stable QTLs. The average of CUGs per QTL was 1.8, which enabled us to confirm the CUGs directly. We have confirmed seven CUGs,TaIFABPL, TaDdRp, TaRLK, TaTD, TaTFC3, TaKMTandTaSPL17, via the CRISPR/Cas9 system. Of these, six genes were found firstly to regulate YCTs in crops except forTaSPL17. Five CUGs (includeTaSPL17) for which orthologous genes have been cloned previously with the same or similar agronomic functions. It is to say, 11 CUGs were preliminarily validated using a single RIL population. QTL-Seq-RIL provides an efficient method for rapid gene cloning using existing RIL populations.
Molecular confirmation ofAnopheles stephensiin the Al Hudaydah Governorate, Yemen, 2021-2022
Authors: Assada Methaq , Al-Hadi Mohammed , Esmail Mohammed A. , Al-Jurban Jamil , Alkawri Abdulsamad , Shamsan Arif , Gomein Payton , Samake Jeanne N. , Aljasari Adel , Awash Abdullah A. , Al Eryani Samira M. , Carter Tamar E. 
Published: February 2024

AbstractAnopheles stephensiis an invasive malaria vector in Africa. To determine the status of the mosquito in Yemen,An. stephensivector surveillance and molecular confirmation was conducted in Al Hudaydah Governorate in 2021 and 2022. Mosquito larvae were collected in suspected man-made breeding habitats in Ah Dahi and Zabid city in 2021 and 2022, respectively. Mosquitoes morphologically identified asAn. stephensiunderwent molecular confirmation through PCR assays, sequencing, and phylogenetic analysis of the cytochrome oxidase subunit I (COI) gene and internal transcribed spacer 2 locus (ITS2). Analysis confirmedAn. stephensiidentification for the majority of samples (39/41), with two COI haplotypes detected: one newly reported haplotype and one haplotype common to Northeast Ethiopia and Somaliland. No clustering withAn. stephensifrom the Arabian Peninsula was observed. These findings provide preliminary insight into the diversity ofAn. stephensi in Yemen and the connection betweenAn. stephensiin Yemen and East Africa.
Arabidopsis Gluconolactonase, the First Enzyme Involved in Ascorbate Biosynthesis Localized in the Chloroplast Protects Plants from Light Stress
Authors: Yactayo-Chang Jessica P. , Nepal Nirman , Aboobucker Siddique I. , Medina-Jiménez Karina , Wilkie Austin , Teoh Thomas K. , Wilson Gwendolyn A. , Lorence Argelia 
Published: February 2024

AbstractVitamin C (L-ascorbic acid, AsA) is the most abundant water-soluble antioxidant in plants. Ascorbate scavenges free radicals, is an enzyme cofactor, and a donor and acceptor of electrons in the chloroplast. Ascorbate protects tissues against damage caused by reactive oxygen species (ROS) produced through normal metabolism or generated from stress. The inositol route to AsA involves four enzymes:myo-inositol oxygenase, glucuronate reductase, gluconolactonase (GNL), and L-gulono-1,4-lactone oxidase. The third enzyme, GNL, has been characterized in rat and bacteria but not in plants. Eighteen putative GNLs were identified in Arabidopsis, one of which,AtGNL,is interesting because it possesses a chloroplastic signal peptide. Plastids can accumulate up to 50 m M As A but until now no chloroplastic AsA biosynthetic genes have been described. This study includes the characterization of the first plant GNL enzymein vitroandin planta. A knockout on this gene had lower foliar As A and stunted growth compared to controls. The functional gene restored the phenotype of the knockout, and those restored plants had higher AsA content, enhanced photosynthetic capacity, and higher seed yield. These results highlight the importance ofAtGNL in As A formation and in maintaining a healthy redox balance in the leaves particularly under low light stress.
Career Navigator: An online platform to streamline professional development and career education for graduate bioscientists
Authors: Rudlaff Rachel M. , Adhikary Utsarga , Khairani Candrika D. , Emmans Daniel S. , Gutlerner Johanna L. , Heustis Ronald J. 
Published: February 2024

ABSTRACTGraduate professional development is a highly dynamic enterprise that prepares graduate students for personal and career success in a variety of fields, including the biosciences. National policies, funding awards, and institutional programs have generated myriad tools and services for graduate bioscience students, including new learning resources, events, connections to prospective employers, and opportunities to strengthen academic and professional portfolios. These interventions are welcome and have done much to enhance graduate bioscience training, but they may also be overwhelming for trainees. To streamline professional development and career education information for the bioscience graduate students at our institution, we tested a model where we built a centralized web portal of career development resources. Here we present our strategy and best practices for website design. We show data that students preferred a centralized online portal over other forms of resource communication; that programming, paired communication and environmental factors (e.g. remote learning and work as in the COVID-19 pandemic) combined to increase sustained engagement with the site; and that harnessing website analytics is an effective way to measure site utilization and generate insights on programming and resource development. This data, in turn, fits into broader priorities to evaluate interventions in graduate bioscience education.
Interpretable deep learning reveals the sequence rules of Hippo signaling
Authors: Dalal Khyati , McAnany Charles , Weilert Melanie , McKinney Mary Cathleen , Krueger Sabrina , Zeitlinger Julia 
Published: February 2024

SummaryThe response to signaling pathways is highly context-specific, and identifying the transcription factors and mechanisms that are responsible is very challenging. Using the Hippo pathway in mouse trophoblast stem cells as a model, we show here that this information is encoded incis-regulatory sequences and can be learned from high-resolution binding data of signaling transcription factors. Using interpretable deep learning, we show that the binding levels of TEAD4 and YAP1 are enhanced in a distance-dependent manner by cell type-specific transcription factors, including TFAP2C. We also discovered that strictly spacedTead doublemotifs are widespread highly active canonical response elements that mediate cooperativity by promoting labile TEAD4 protein-protein interactions on DNA. These syntax rules and mechanisms apply genome-wide and allow us to predict how small sequence changes alter the activity of enhancersin vivo. This illustrates the power of interpretable deep learning to decode canonical and cell type-specific sequence rules of signaling pathways.Graphical abstract
Electron-Activated Dissociation and Collision-Induced Dissociation Glycopeptide Fragmentation for Improved Glycoproteomics
Authors: Macauslane Kyle L. , Pegg Cassandra L. , Nouwens Amanda S. , Kerr Edward D. , Seitanidou Joy , Schulz Benjamin L. 
Published: February 2024

AbstractTandem mass spectrometry coupled with liquid chromatography (LC-MS/MS) has proven a versatile tool for the identification and quantification of proteins and their post-translational modifications (PTMs). Protein glycosylation is a critical PTM for the stability and biological function of many proteins, but full characterisation of site-specific glycosylation of proteins remains analytically challenging. Collision induced dissociation (CID) is the most common fragmentation method used in LC-MS/MS workflows, but loss of labile modifications render CID inappropriate for detailed characterisation of site-specific glycosylation. Electron-based dissociation (ExD) methods provide alternatives that retain intact glycopeptide fragments for unambiguous site localisation, but these methods often underperform CID due to increased reaction times and reduced efficiency. Electron activated dissociation (EAD) is another strategy for glycopeptide fragmentation. Here, we use a ZenoTOF 7600 SCIEX instrument to compare the performance of various fragmentation techniques for the analysis of a complex mixture of mammalianO- andN-glycopeptides. We found CID fragmentation identified the most glycopeptides and generally produced higher quality spectra, but EAD provided improved confidence in glycosylation site localisation. Supplementing EAD with CID fragmentation (EAciD) further increased the number and quality of glycopeptide identifications, while retaining localisation confidence. These methods will be useful for glycoproteomics workflows for either optimal glycopeptide identification or characterisation.
Loss of the scavenger receptor MARCO results in uncontrolled vomocytosis of fungi from macrophages
Authors: Onyishi Chinaemerem U. , Fejer Gyorgy , Mukhopadhyay Subhankar , Gordon Siamon , May Robin C. 
Published: February 2024

AbstractVomocytosis, also known as nonlytic exocytosis, is a process whereby fully phagocytosed microbes are expelled from phagocytes without discernible damage to either the phagocyte or microbe. Although this phenomenon was first described in the opportunistic fungal pathogenCryptococcus neoformansin 2006, to date, mechanistic studies have been hampered by an inability to reliably stimulate or inhibit vomocytosis. Here we present the fortuitous discovery that macrophages lacking the scavenger receptor MAcrophage Receptor with COllagenous domain (MARCO), exhibit near-total vomocytosis of internalised cryptococci within a few hours of infection. Our findings suggest that MARCO’s role in modulating vomocytosis is independent of its role as a phagocytic receptor and instead may be driven by variation in cytoskeletal arrangement between wildtype and MARCO-deficient macrophages.
RhizoBindingSites v2.0 is a bioinformatic database of DNA motifs potentially involved in transcriptional regulation deduced from sites of the itself genome
Authors: Taboada-Castro Hermenegildo , Hernández-Álvarez Alfredo José , Castro-Mondragón Jaime A. , Encarnación Guevara Sergio M. 
Published: February 2024

AbstractRhizoBindingSites is ade novodepurified database of conserved DNA motifs potentially involved in the transcriptional regulation of theRhizobium,Sinorhizobium,Bradyrhizobium,Azorhizobium,andMesorhizobiumrepresentative symbiotic species, deduced from the upstream regulatory sequences of orthologous genes (O-matrices) from the Rhizobiales taxon. The sites collected with O-matrices per gene per genome from RhizoBindingSites were used to deduce matrices using the dyad-Regulatory Sequence Analysis Tool (RSAT) method, giving rise to novel S-matrices for the construction of the RizoBindingSites v2.0 database. A comparison of the S-matrix logos showed a greater frequency and/or re-definition of specific-position nucleotides found in the O-matrices. Moreover, S-matrices were better at detecting genes in the genome and there was a greater number of transcription factors (TFs) in the vicinity than O-matrices, corresponding to a more significant genomic coverage for S-matrices. The homology between the matrices of TFs from a genome showed inter-regulation between the clustered TFs. In addition, matrices of AraC, ArsR, GntR, and LysR ortholog TFs showed different motifs, suggesting distinct regulation. Benchmarking showed 72%, 68%, and 81% of common genes per regulon for O-matrices and approximately 14% less common genes with S-matrices ofRhizobium etliCFN42,R. leguminosarumbv.viciae3841, andSinorhizobium meliloti1021. These data were deposited in RhizoBindingSites and the RhizoBindingSites v2.0 database (http://rhizobindingsites.ccg.unam.mx/).
Senataxin modulates resistance to cisplatin through an R-loop mediated mechanism in HPV-associated Head and Neck Squamous Cell Carcinoma
Authors: Crane Hannah , Carr Ian , Hunter Keith D , El-Khamisy Sherif F. 
Published: February 2024

AbstractIntroductionOropharyngeal Squamous Cell Carcinoma (OPSCC) is a site defined subtype of head and neck cancer with two distinct clinical subtypes: HPV-associated (HPV+) and HPV-independent (HPV-); both of which are commonly treated with chemoradiotherapy involving cisplatin. Cisplatin creates DNA crosslinks, which lead to eventual cell death via apoptosis. Clinical outcomes in HPV-OPSCC are poor and although HPV+ has an improved response to therapy, a subset of patients suffer from distant metastases, with a poor prognosis. Therefore, there is a need to understand the molecular basis underlying treatment resistance. A common mechanism of chemotherapy resistance is upregulation of DNA repair, and a major source of endogenous DNA damage are DNA/RNA hybrids, known as R-loops. R-loops are three stranded DNA/RNA hybrids formed in the genome as a by- product of transcription and are normally transient; however, they can persist and become a source of genomic instability. The contribution of R-loops to the development of cisplatin resistance in OPSCC is unknown.MethodsHPV+ and HPV- cisplatin resistant cell lines were developed, and RNA-sequencing was used to investigate changes in gene expression. Changes in R-loop dynamics were explored using slot blots and DRIP-qPCR. The effect of depleting known R-loop regulators on cisplatin sensitivity was assessed using siRNA. R-loop burden in a cohort of HPV+ and HPV- OPSCC tumours was explored using S9.6 immunohistochemistry.ResultsDevelopment of cisplatin resistant clones led to changes in gene expression consistent with resistance, alongside alterations in the expression of known R-loop regulators. Both HPV+ and HPV- resistant cells had elevated global R-loop levels and in HPV+ resistant cells there was a corresponding upregulation of the R-loop resolving protein, senataxin, which was not observed in HPV- resistant cells. Depletion of senataxin led to increased sensitivity to cisplatin in both HPV+ and HPV- resistant cells, however, the effect was greater in HPV+ cells. Quantification of R-loop levels by S9.6 immunohistochemistry revealed that HPV+ tumours and tumours with bone metastases had a higher R-loop burden.ConclusionR-loops are involved in modulating sensitivity to cisplatin and may represent a potential therapeutic target.