bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacological elevation of cellular dihydrosphingomyelin provides a novel antiviral strategy against West Nile virus infection
Authors: Jiménez de Oya Nereida , San-Félix Ana , Casasampere Mireia , Blázquez Ana-Belén , Mingo-Casas Patricia , Escribano-Romero Estela , Calvo-Pinilla Eva , Poderoso Teresa , Casas Josefina , Saiz Juan-Carlos , Pérez-Pérez María-Jesús , Martín-Acebes Miguel A. 
Published: December 2022

ABSTRACTFlavivirus life cycle is strictly dependent on cellular lipid metabolism. Polyphenols like gallic acid and its derivatives are promising lead compounds for new therapeutic agents as they can exert multiple pharmacological activities, including the alteration of lipid metabolism. The evaluation of our own collection of polyphenols against West Nile virus, a representative medically relevant flavivirus, led to the identification ofN,N′-(dodecane-1,12-diyl)bis(3,4,5-trihydroxybenzamide) and its 2,3,4-trihydroxybenzamide regioisomer as selective antivirals with low cytotoxicity and high antiviral activity (EC50of 2.2 and 0.24 μM, respectively in Vero cells; EC50of 2.2 and 1.9 μM, respectively in SH-SY5Y cells). These polyphenols also inhibited the multiplication of other flaviviruses, namely Usutu, dengue, and Zika viruses, exhibiting lower antiviral or negligible antiviral activity against other RNA viruses. The mechanism underlying their antiviral activity against WNV involved the alteration of sphingolipid metabolism. These compounds inhibited ceramide desaturase (Des1) promoting the accumulation of dihydrosphingomyelin (dhSM), a minor component of cellular sphingolipids with important roles on membrane properties. Addition of exogenous dhSM, or Des1 blockage by using the reference inhibitor GT-11, confirmed the involvement of this pathway in WNV infection. These results unveil the potential of novel antiviral strategies based on the modulation of the cellular levels of dhSM and Des1 activity for the control of flavivirus infection.
Self-reported and measured anthropometric variables in association with cardiometabolic markers: a Danish cohort study
Authors: Zhang Jie , Olsen Anja , Halkjær Jytte , Petersen Kristina Elin Nielsen , Tjønneland Anne , Overvad Kim , Dahm Christina C 
Published: December 2022

AbstractSelf-reported measures of height and weight are widely used in epidemiological studies. However, misreporting may bias estimates of associations between anthropometry and health outcomes. Further, few validation studies have compared self-reported and measured waist circumference (WC). This study aimed to quantify the agreement between self-reported and measured height, weight, body mass index (BMI), WC, and waist-to-height ratio (WHtR), and to investigate associations of these anthropometric measures with cardiometabolic biomarkers.Self-reported and measured anthropometric variables, as well as cardiometabolic biomarkers, were obtained from participants aged above 18 years at recruitment into the Diet, Cancer, and Health-Next Generation Cohort in 2015-19 (N=39,514). Pearson correlations (r) and Lin’s concordance correlations were applied to evaluate misreporting. Misreporting by age, sex and smoking status was investigated in linear regression models. Multivariable regression models and Receiver Operating Characteristic analyses assessed associations of self-reported and measured anthropometry with cardiometabolic biomarkers. Self-reported height was overreported by 1.07 cm, and weight was underreported by 0.32 kg on average. Self-reported BMI and WC were 0.42 kg/m2and 0.2 cm lower than measured, respectively. Self-reported and measured height, weight, BMI, WC and WtHR were strongly correlated (r=0.98, 0.99, 0.98, 0.88, 0.86, respectively). Age, sex, smoking, and BMI contributed to misreporting of all anthropometric measures. Associations between self-reported or measured anthropometric measures and cardiometabolic biomarkers were similar in direction and strength. Concordance between self-reported and measured anthropometric measures, including WC, was very high. Self-reported anthropometric measures were reliable when estimating associations with cardiometabolic biomarkers.
Target height influences shoulder and elbow non-use after stroke during reaching with the hand : A brief communication
Authors: Faity Germain , Mottet Denis , Froger Jérôme 
Published: December 2022

ABSTRACTBackgroundDuring hand reaching movements in people with stroke, the coordination of trunk, shoulder, and elbow muscles changes as a function of target height. However, it is not known whether target height also influences non-use, defined as the difference between two coordinations aiming at the same target.MethodsTwenty-two individuals with stroke (> 1 month) completed the Proximal Arm Non-Use (PANU) test in two conditions: high target (80 cm) and low target (67 cm). Elbow, shoulder, and trunk use was recorded using motion capture.ResultsTrunk compensation and non-use of the shoulder and elbow joints were found to depend on target height.ConclusionsBecause trunk bending forward goes against the need to elevate the hand, a sufficiently low target is necessary to unmask the presence of shoulder-elbow non-use. We provide novel recommendations for assessing compensations and non-use during hand reaching. Clinical Trial:NCT04747587.
Adherence to Pre-exposure Prophylaxis intervention by transgender women: A systematic review
Authors: Moncayo-Quevedo Jorge Eduardo , Mar Pérez-Arizabaleta María Del , María Villegas-Trujillo Lina , Rodríguez-Ortiz Alejandra 
Published: December 2022

AbstractBackgroundThe prevalence of HIV is higher in the transgender population. Recently, the preexposure prophylaxis (PrEP) intervention has been proven successful in reducing HIV acquisition in trials among men who have sex with men (MSM), and heterosexual couples. This research aims to investigate the adherence to PrEP by HIV-negative transgender women (TW).MethodsWere followed the Cochrane Handbook for Systematic Reviews of Interventions and the PRISMA Statement. Research in WoS, Ovid, Scopus, MEDLINE, and the Cochrane Central Register of Controlled Trials (CENTRAL) electronic databases for studies that involved HIV-negative TW population and focused on their adherence to PrEP intervention and condom use after the treatment.Results11 studies were included. TW sample sizes were low in comparison to the total sample, which often included men who have sex with men (MSM) population. The participation and adherence to the intervention was low compared to MSM, and it was measured mainly by self-report (72.7%) or by Tenofovir-diphosphate (TFV-DP)/ Emtricitabine triphosphate (FTC-TP) dried blood spot (DBS) (45.5%).ConclusionsIt is important to increase awareness and explain the effect of PrEP on feminizing hormone therapy at the beginning of the trials. Nevertheless, the low adherence may be affected by the interaction between drugs and the barriers faced to use the health services.
Nucleosome repositioning in chronic lymphocytic leukaemia
Authors: Piroeva Kristan V. , McDonald Charlotte , Xanthopoulos Charalampos , Fox Chelsea , Clarkson Christopher T. , Mallm Jan-Philipp , Vainshtein Yevhen , Ruje Luminita , Klett Lara C. , Stilgenbauer Stephan , Mertens Daniel , Kostareli Efterpi , Rippe Karsten , Teif Vladimir B. 
Published: December 2022

AbstractThe location of nucleosomes in the human genome determines the primary chromatin structure and regulates access to regulatory regions. However, genome-wide information on deregulated nucleosome occupancy and its implications in primary cancer cells is scarce. Here, we performed a systematic comparison of high-resolution nucleosome maps in peripheral-blood B-cells from patients with chronic lymphocytic leukaemia (CLL) and healthy individuals at single base pair resolution. Our investigation uncovered significant changes of both nucleosome positioning and packing in CLL. Globally, the spacing between nucleosomes (the nucleosome repeat length, NRL) was shortened in CLL. This effect was stronger in the more aggressive IGHV-unmutated than IGHV-mutated CLL subtype. Changes in nucleosome occupancy at specific sites were linked to active chromatin remodelling and reduced DNA methylation. Nucleosomes lost or gained in CLL in comparison with non-malignant B-cells marked differential binding of 3D chromatin organisers such as CTCF as well as immune response-related transcription factors, allowing delineating epigenetic mechanisms affected in CLL. Furthermore, patients could be better assigned to CLL subtypes according to nucleosome occupancy at cancer-specific sites than based on DNA methylation or gene expression. Thus, nucleosome positioning constitutes a novel readout to dissect molecular mechanisms of disease progression and to stratify patients. Furthermore, we anticipate that the global nucleosome positioning changes detected in our study, like the reduced NRL, can be exploited for liquid biopsy applications based on cell-free DNA to monitor disease progression.
Metabolism is correlative not causative for age-related auditory decline in an insect model
Authors: Austin Thomas T , Thomas Christian , Clifton Lewis , Blockley Alix , Warren Ben 
Published: December 2022

AbstractAging is due to a complex decline of multiple biological processes. Some of the causes include oxidative damage, mitochondrial and proteostatic dysfunction, and DNA damage. The result is that as biological systems age their performance deteriorates. This age-related decline is well quantified, and experienced, for human hearing and is presumed to be due to a decrease in the ear’s metabolism – specifically a decrease in ability to maintain an electrochemical gradient, the endocochlear potential. However, direct measurements of metabolism across a lifespan in an auditory system are lacking. Even if metabolism does decrease with age, the question remains is it a cause of age-related auditory decline or simply correlative? All auditory systems across the animal kingdom share functional principles including ion pumping cells, auditory receptors, spiking auditory nerves and multiple supporting cells. Therefore, we used an insect, the desert locust,Schistocerca gregaria, as a physiologically versatile model to understand how cellular metabolism correlates with age and impacts on age-related auditory decline. We found that although metabolism correlates with age-related auditory decline it is not causative.
Chromatin accessibility is a two-tier process regulated by transcription factor pioneering and enhancer activation
Authors: Brennan Kaelan J. , Weilert Melanie , Krueger Sabrina , Pampari Anusri , Liu Hsiao-Yun , Yang Ally W.H. , Hughes Timothy R. , Rushlow Christine A. , Kundaje Anshul , Zeitlinger Julia 
Published: December 2022

SummaryChromatin accessibility is integral to the process by which transcription factors (TFs) read out cis-regulatory DNA sequences, but it is difficult to differentiate between TFs that drive accessibility and those that do not. Deep learning models that learn complex sequence rules provide an unprecedented opportunity to dissect this problem. Using zygotic genome activation in theDrosophilaembryo as a model, we generated high-resolution TF binding and chromatin accessibility data, analyzed the data with interpretable deep learning, and performed genetic experiments for validation. We uncover a clear hierarchical relationship between the pioneer TF Zelda and the TFs involved in axis patterning. Zelda consistently pioneers chromatin accessibility proportional to motif affinity, while patterning TFs augment chromatin accessibility in sequence contexts in which they mediate enhancer activation. We conclude that chromatin accessibility occurs in two phases: one through pioneering, which makes enhancers accessible but not necessarily active, and a second when the correct combination of transcription factors leads to enhancer activation.
Shared neural codes of recognition memory
Authors: Ambrus Géza Gergely 
Published: December 2022

AbstractRecognition memory research has identified several electrophysiological indicators of successful memory retrieval, known as old-new effects. These effects have been observed in different sensory domains using various stimulus types, but little attention has been given to their similarity or distinctiveness and the underlying processes they may share. Here, a data-driven approach was taken to investigate the temporal evolution of shared information content between different memory conditions using openly available EEG data from healthy human participants of both sexes, taken from six experiments. A test dataset involving personally highly familiar and unfamiliar faces was used. The results show that neural signals of recognition memory for face stimuli were highly generalized starting from around 200 ms following stimulus onset. When training was performed on non-face datasets, an early (around 200-300 ms) to late (post-400 ms) differentiation was observed over most regions of interest. Successful cross-classification for non-face stimuli (music and object/scene associations) was most pronounced in late period. Additionally, a striking dissociation was observed between familiar and remembered objects, with shared signals present only in the late window for correctly remembered objects, while cross-classification for familiar objects was successful in the early period as well. These findings suggest that late neural signals of memory retrieval generalize across sensory modalities and stimulus types, and the dissociation between familiar and remembered objects may provide insight into the underlying processes.
Structural basis of odorant recognition by a human odorant receptor
Authors: Billesbølle Christian B. , de March Claire A. , van der Velden Wijnand J. C. , Ma Ning , Tewari Jeevan , del Torrent Claudia Llinas , Li Linus , Faust Bryan , Vaidehi Nagarajan , Matsunami Hiroaki , Manglik Aashish 
Published: December 2022

AbstractOur sense of smell enables us to navigate a vast space of chemically diverse odor molecules. This task is accomplished by the combinatorial activation of approximately 400 olfactory G protein-coupled receptors (GPCRs) encoded in the human genome1–3. How odorants are recognized by olfactory receptors (ORs) remains mysterious. Here we provide mechanistic insight into how an odorant binds a human olfactory receptor. Using cryogenic electron microscopy (cryo-EM), we determined the structure of active human OR51E2 bound to the fatty acid propionate. Propionate is bound within an occluded pocket in OR51E2 and makes specific contacts critical to receptor activation. Mutation of the odorant binding pocket in OR51E2 alters the recognition spectrum for fatty acids of varying chain length, suggesting that odorant selectivity is controlled by tight packing interactions between an odorant and an olfactory receptor. Molecular dynamics simulations demonstrate propionate-induced conformational changes in extracellular loop 3 to activate OR51E2. Together, our studies provide a high-resolution view of chemical recognition of an odorant by a vertebrate OR, providing insight into how this large family of GPCRs enables our olfactory sense.
T cell development is regulated by high fidelity replication of mitochondrial DNA
Authors: Limper Candice B. , Bondah Narda , Zhu Daphne , Villanueva Alanis N. , Chukwukere Uchenna K. , Huang Weishan , August Avery 
Published: December 2022

AbstractOne of the most proliferative periods for T cells occurs during their development in the thymus. Increased DNA replication can result in increased DNA mutations in the nuclear genome, but also in mitochondrial genomes. A high frequency of mitochondrial DNA mutations can lead to abnormal mitochondrial function and have negative implications on human health. Furthermore, aging is accompanied by an increase in such mutations through oxidative damage and replication errors. Increased mitochondrial DNA mutations cause loss of mitochondrial protein function, and decrease energy production, substrates, and metabolites. Here we have evaluated the effect of increased mitochondrial DNA mutations on T cell development in the thymus. Using mice carrying a mutant mitochondrial DNA polymerase γ (PolG) that causes increased mitochondrial DNA mutations, we show that high fidelity replication of mitochondrial DNA is pivotal for proper T cell development. Reducing the fidelity of mitochondrial DNA replication results in a premature age-dependent reduction in the total number of CD4/CD8 double negative and double positive thymocytes. Analysis of mitochondrial density in thymocyte subpopulations suggests that this may be due to reduced proliferation in specific double negative stages. Taken together, this work suggests that T cell development is regulated by the ability of mitochondria to faithfully replicate their DNA.
The hippocampus binds movements to their temporal position in a motor sequence
Authors: Dolfen Nina , Reverberi Serena , Op de beeck Hans , King Bradley R. , Albouy Genevieve 
Published: December 2022

AbstractA plethora of daily motor tasks consist of sequences of movements or steps that need to be performed in a specific order. Yet, it remains unclear how the brain represents sequential motor actions in a way that preserves their temporal order. Here, we used multivoxel pattern similarity analysis of functional Magnetic Resonance Imaging (fMRI) data acquired during motor sequence practice to investigate whether the hippocampus, a brain region known to support temporal order in the non-motor memory domain, represents information about the temporal order of sequential motor actions. We also examined such representation in other regions of the motor network (i.e., the premotor cortex (PMC), supplementary motor area (SMA), anterior superior parietal lobule (aSPL) and striatum) known for their critical role in motor sequence learning. Our results show that hippocampal activation patterns carried information about movements in their learned temporal position in the sequence (i.e., movement-position binding), but not about movements or positions in random movement patterns. In contrast, other ROIs showed evidence of binding in the sequence as well as movement (M1, SMA, PMC, putamen and aSPL) and position (aSPL and PMC) coding in random movement patterns. Importantly, movement coding contributed to sequence learning patterns in M1, SMA and PMC but not in the putamen and aSPL, suggesting a specific involvement of these regions in movement-position binding. Altogether, our findings provide novel insight into the role of the hippocampus in the motor memory domain and point to its capacity to bind movements to their temporal position in a motor sequence. Our results also deepen our understanding of how striatal and cortical regions contribute to motor sequence learning via movement coding or movement-position binding.Significance StatementConsistent evidence collected over the last two decades indicates that the hippocampus - a brain structure traditionally associated to declarative memory - is critically involved in motor memory. Yet, the functional role and representational contribution of the hippocampus during motor learning remains to be elucidated. Using a multivariate functional MRI approach, we show here that the hippocampus binds movements to their temporal position in a learned sequence of actions. These results point towards the involvement of the hippocampus in preserving information about temporal order in motor memory - a process well described for declarative memories. We suggest that the ability of the hippocampus to encode temporal order during sequence learning is common across declarative and non-declarative memory systems.
Nanopore sequencing for real-time genomic surveillance ofPlasmodium falciparum
Authors: Girgis Sophia T. , Adika Edem , Nenyewodey Felix E. , Senoo Jnr Dodzi K. , Ngoi Joyce M. , Bandoh Kukua , Lorenz Oliver , van de Steeg Guus , Harrott Alexandria J. R. , Nsoh Sebastian , Judge Kim , Pearson Richard D. , Almagro-Garcia Jacob , Saiid Samirah , Atampah Solomon , Amoako Enock K. , Morang’a Collins M. , Asoala Victor , Adjei Elrmion S. , Burden William , Roberts-Sengier William , Drury Eleanor , Pierce Megan L. , Gonçalves Sónia , Awandare Gordon A. , Kwiatkowski Dominic P. , Amenga-Etego Lucas N. , Hamilton William L. 
Published: December 2022

AbstractMalaria is a global public health priority causing over 600,000 deaths annually, mostly young children living in Sub-Saharan Africa. Molecular surveillance can provide key information for malaria control, such as the prevalence and distribution of antimalarial drug resistance. However, genome sequencing capacity in endemic countries can be limited. Here, we have implemented an end-to-end workflow forP. falciparumgenomic surveillance in Ghana using Oxford Nanopore Technologies, targeting antimalarial resistance markers and the leading vaccine antigencircumsporozoite protein(csp). The workflow was rapid, robust, accurate, affordable and straightforward to implement, and could be deployed using readily collected dried blood spot samples. We found thatP. falciparumparasites in Ghana had become largely susceptible to chloroquine, with persistent sulfadoxine-pyrimethamine (SP) resistance, and no evidence of artemisinin resistance. Multiple Single Nucleotide Polymorphism (SNP) differences from the vaccinecspsequence were identified, though their significance is uncertain. This study demonstrates the potential utility and feasibility of malaria genomic surveillance in endemic settings using Nanopore sequencing.
Early Seasonal Increases and Persistence in Relative Abundance of Potentially Toxic Cyanobacteria: Concerning Impacts of Extended Ice-Free Periods in Northern Temperate Lakes
Authors: Cameron Ellen S. , Müller Kirsten M. , Stone Mike , Buttle Jim , Leach Jason , Webster Kara , Emelko Monica B. 
Published: December 2022

AbstractCyanobacteria threaten public and ecosystem health globally through the production of secondary metabolites including potent toxins, and disruption of water treatment processes. Warmer water temperatures and high nutrient availability are key characteristics associated with the occurrence of cyanobacteria. There is typically concern of cyanobacteria blooms (e.g., visible biomass accumulations) occurring in the summer season of eutrophic systems. However, in this study, the proliferation of cyanobacteria in lakes across all seasons and in absence of visual biomass indicators of bloom condition was observed in three oligotrophic lakes of the Turkey Lakes Watershed (TLW) in Ontario, located within a sugar maple dominated forest on the Canadian Shield. Almost 40 years of ice phenology data showed that rising temperatures have led to significantly longer ice-free periods and aquatic growing seasons in TLW. Warming is especially evident in the autumn, with the onset of ice-on periods commencing significantly later in the year. Cyanobacterial communities in three interconnected temperate, oligotrophic lakes were characterized over an 18-month period from July 2018 to January 2020 (across 10 synoptic sampling events) using amplicon sequencing of the V4 region of the 16S rRNA gene. During the winter, there was low abundance or occasional absence of cyanobacteria; however, a non-photosynthetic basal lineage of cyanobacteria (Melainabacteria) was present during periods of ice cover. Notably, photosynthetic populations reappeared in the water column immediately following the loss of ice-cover—they were especially abundant in lakes with surficial geology and lake morphometry that favor greater availability of fine sediment and associated nutrients. Thus, this collective analysis demonstrates that the convergence of key abiotic and biotic factors—climate forcing of hydrological and biogeochemical processes, and intrinsic landscape features—enable increases in the relative abundance of potentially toxic cyanobacteria within the temperate forest biome of Canada over increasingly longer periods of time.