bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exercise-induced extracellular vesicles mediate apoptosis in human colon cancer cells in an exercise intensity-dependent manner
Authors: Ozerklig Berkay , Turkel Ibrahim , Yılmaz Merve , Vaizoglu Refika Dilara , Akan Handan Sevim , Dikmen Z. Gunnur , Saleem Ayesha , Kosar Sukran N. 
Published: September 2024

AbstractRegular exercise is known to reduce incidence rates and improve the prognosis of all cancers, but the underlying mechanisms remain elusive. Ample evidence suggests that exercise exerts therapeutic effects through extracellular vesicles (EVs), essential for cellular communication. Here, we hypothesized that exercise-induced EVs from serum of healthy young male participants will exert anti-tumorigenic effects on human colon cancer HT-29 cells, in an exercise intensity-dependent manner. 10 healthy young active males (25.4±6.2yrs, with maximal oxygen consumption (VO2max) = 45±3.7 ml.min-1.kg-1 participated in a randomized crossover trial. Participants underwent two different workload-matched, acute bouts of exercise: (1) moderate-intensity continuous exercise (MICE) at 50-55% V02max, and (2) high-intensity interval exercise (HIIE) at 90% V02max on a cycle ergometer. A control session of rest (PRE) was included. EVs were isolated from serum samples collected during PRE and immediately after each exercise session. EVs were co-incubated with colon cancer HT-29 cells (100 µg EVs/ml, 48-72h), and effect on cell viability, migration, and apoptosis measured. EV treatment reduced cell viability in all groups (PRE, MICE, HIIE) by 35%, 43% and 47% respectively, vs. PBS. EVs from HIIE group showed a significantly greater reduction in cell viability vs. PRE, therefore further analysis used these groups only. PRE-EVs reduced migration by 27%, and HIIE-EVs by 39%. EV from HIIE group increased expression of pro-apoptotic markers: Bax/Bcl-2 ratio by 56% and Caspase-3 by 30% vs. PBS, with no change observed in the PRE group. Further, 16% of cells in PRE, and 28% of cells in HIIE were TUNEL-positive, indicating DNA fragmentation, a hallmark feature of apoptosis. Our data show that exercise-induced EVs reduced cell viability, in an exercise intensity-dependent manner. HIIE-derived EVs exerted the most anti-tumorigenic effects: decreased cell viability, reduced cell migration, increase in pro-apoptotic protein expression, and elevated DNA fragmentation. It is likely these changes were mediated by altered EV Cargo induced by exercise, as the amount of EVs was the same in each treatment group. To our knowledge, this is the first human study that illustrates the therapeutic potential of exercise-induced EVs in cancer treatment.
Calculating and interpretingFSTin the genomics era
Authors: de Jong Menno J. , van Oosterhout Cock , Hoelzel A. Rus , Janke Axel 
Published: September 2024

ABSTRACTThe relative genetic distance between populations is commonly measured using the fixation index (FST). Traditionally inferred from allele frequency differences, the question arises howFSTcan be estimated and interpreted when analysing genomic datasets with low sample sizes. Here, we advocate an elegant solution first put forward by Hudson et al. (1992):FST= (Dxy–πxy)/Dxy, whereDxyandπxydenote mean sequence dissimilaritybetweenandwithinpopulations, respectively. This multi-locusFST-metric can be derived from allele frequency data, but also from sequence alignment data alone, even when sample sizes are low and/or unequal. As with otherFST-metrices, the numerator denotes net divergence (Da), which is equivalent to thef2-statistic and Nei’sD(for realistic estimates ofDxyandπxy). In terms of demographic inference, net divergence measures the difference in increase ofDxyandπxysince the population split, owing to a reduction of coalescence times within populations as a result of genetic drift. Because different combinations ofΔDxyandΔπxycan produce identicalFST-estimates, no universal relationship exists betweenFSTand population split time. Still, in case of recent population splits, when novel mutations are negligible,FST-estimates can be accurately converted into coalescent units (τ. i.e., split time in multiples of 2Ne). This then allows to quantify gene tree discordance, without the need for multispecies coalescent based analyses, using the formula:Pdiscordance= ⅔·(1 –FST). To facilitate the use of the HudsonFST-metric, we implemented new utilities in the R package SambaR.
First record ofCulex pipiens(Diptera: Culicidae) in Alberta: Expanding distributions and ecotype patterns in a western Canadian province
Authors: Pan Ty , Seal Michaela , Shaw Hailey , Mohanaraj Shahaanaa , Morinaga Gen , Hogaboam Brittany , Jenkins Michael , Coker Alexandra , Soghigian John 
Published: September 2024

AbstractCulex pipiensis an invasive mosquito found in temperate regions globally. It is considered among the most important disease vectors worldwide and is responsible for transmission of a range of pathogens, including West Nile virus, avian malaria, Saint Louis encephalitis, and filarial worms. Throughout its northern temperate range, this mosquito is found in two ecotypes: formpipiensand formmolestus. In Canada, this mosquito was previously thought restricted to the Pacific coast of British Columbia and the eastern provinces of Ontario, Quebec, and the Maritimes. Through routine mosquito surveillance and targeted trapping forCx. pipiens, we detected this mosquito in two Albertan municipalities earlier than suggested by species distribution modelling based on climate change data. We confirmed the identity of putativeCx. pipiensspecimens using DNA sequencing and found that formpipienswas the most common ecotype found in Alberta. Further, we compared the frequency of ecotypes in Alberta to elsewhere in North America and found a general trend of increased formpipiensin more northern latitudes, similar to previously reported results. We discuss our findings in context of vector-borne disease activity in Canada, particularly West Nile virus.
Degradation of PET plastic with engineered environmental bacteria
Authors: Banks Alice M. , Abdulmutalib Umar , Sonnendecker Christian , Kim Juhyun , Bosomworth Charlotte , Brown Stuart , Wei Ren , Álvarez-Ortega Carolina , Pomposiello Pablo , Avignone-Rossa Claudio , Larrouy-Maumus Gerald , Zimmermann Wolfgang , Jiménez José I. 
Published: September 2024

AbstractPolyethylene terephthalate (PET) is one of the most widely used plastic materials in the food and textile industry. Consequently, post-consumer PET waste is a common environmental pollutant that leaks into the environment in the form of macro and microplastics with concerning health impacts. There is a pressing need to identify novel and sustainable solutions to process the abundance of PET waste contributing to this pollution. While there is extensive research into enzymes able to hydrolyse PETin vitro, a similar solution for discarded or difficult-to-collect PET based on whole-cell microbial catalysts is missing. In this work we report the engineering of environmental bacteria to use PET as a growth substrate. This was achieved by isolating a strain ofPseudomonas umsongensisable to use the PET monomer terephthalate as carbon source, engineering the strain to effectively secrete the high-activity PET hydrolase PHL7 through the addition of a recombinant TAT secretion leader sequence, and enhancing the bioavailability of PET by transforming it into an amorphous and macroporous structure by pre-treatment with an organic solvent. Our findings demonstrate the direct microbial consumption of PET, which could lead to improved and more sustainable upcycling strategies for this plastic.
Systemic extracellular acidification is a hallmark of aging
Authors: dos Santos Eliano , Xie Yining , Cao Enyuan , Foley Andrea , Taylor Max E. , Andrew Ivan , Young George , Trevaskis Natalie L. , Cochemé Helena M. 
Published: September 2024

AbstractUnderstanding the critical pathophysiological processes that promote age-related disease is needed to uncover effective targets for preventive medicine. Here, we investigate how extracellular pH changes with age and its impact on longevity, using fly and mouse models. We find that extracellular acidification occurs in flies during aging and correlates to mortality rate. With age, flies also become more susceptible to die from acidotic stress, which can be prevented by alkalotic treatment. Acidification is caused by insufficient acid elimination, linked to downregulation of genes in the fly excretory tract that control pH and ATP production, essential for active secretion initiation. In mice, we show that lymph-drained interstitial fluids acidify with age. Expression of genes, whose pathogenic loss-of-function variants cause tubular acidosis in humans, is decreased in the kidneys of aging mice. Overall, this study sheds light on dysregulated systemic acid-base balance as a conserved pathophysiological mechanism of aging.
Interplay of YEATS2 and GCDH mediates histone crotonylation and drives EMT in head and neck cancer
Authors: Pant Deepak , Kakani Parik , Joshi Rushikesh , Agrawal Shruti , Samaiya Atul , Shukla Sanjeev 
Published: September 2024

AbstractThe regulation of gene expression is an integral cellular process orchestrated by epigenetic marks like histone modifications. Perturbations in the activity or abundance of epigenetic factors can lead to tumorigenesis. Remarkably, several metabolites influence the epigenetic landscape in cells. Here, we investigated the interplay between a highly expressed epigenetic factor, YEATS2, and a metabolic enzyme, GCDH, in regulating epithelial-to-mesenchymal transition in head and neck cancer. We report that the histone reader YEATS2 is responsible for increased invasive potential in head and neck cancer in an SP1-dependent manner. YEATS2 functions by maintaining histone crotonylation, and its abrogation leads to a global decrease in the H3K27Cr mark. Mechanistically, we report that YEATS2 maintains high H3K27Cr levels at the promoter of the EMT-promoting geneSPARC. Further, we found that the addition of the H3K27Cr mark is also dependent on the crotonyl-CoA-producing enzyme GCDH. Overall, we describe a novel mechanism of interplay between epigenetics and metabolism in head and neck tumorigenesis, which results in the enhanced expression of EMT-related genes in a histone crotonylation-dependent manner.
Integrating spatial profiles and cancer genomics to identify immune-infiltrated mismatch repair proficient colorectal cancers
Authors: Wala Jeremiah , de Bruijn Ino , Coy Shannon , Gagné Andréanne , Chan Sabrina , Chen Yu-An , Hoffer John , Muhlich Jeremy , Schultz Nikolaus , Santagata Sandro , Sorger Peter K 
Published: September 2024

ABSTRACTPredicting the progression of solid cancers based solely on genetics is challenging due to the influence of the tumor microenvironment (TME). For colorectal cancer (CRC), tumors deficient in mismatch repair (dMMR) are more immune infiltrated than mismatch repair proficient (pMMR) tumors and have better prognosis following resection. Here we quantify features of the CRC TME by combining spatial profiling with genetic analysis and release our findings via a spatially enhanced version of cBioPortal that facilitates multi-modal data exploration and analysis. We find that ∼20% of pMMR tumors exhibit similar levels of T cell infiltration as dMMR tumors and that this is associated with better survival but not any specific somatic mutation. These T cell-infiltrated pMMR (tipMMR) tumors contain abundant cells expressing PD1 and PDL1 as well as T regulatory cells, consistent with a suppressed immune response. Thus, like dMMR CRC, tipMMR CRC may benefit from immune checkpoint inhibitor therapy.SIGNIFICANCEpMMR tumors with high T cell infiltration and active immunosuppression are identifiable with a mid-plex imaging assay whose clinical deployment might double the number of treatment-naïve CRCs eligible for ICIs. Moreover, the low tumor mutational burden in tipMMR CRC shows that MMR status is not the only factor promoting immune infiltration.
Analytical Assessment of Metagenomic Workflows for Pathogen Detection with NIST RM 8376 and Two Sample Matrices
Authors: Kralj Jason G. , Servetas Stephanie L. , Forry Samuel P. , Hunter Monique E. , Dootz Jennifer N. , Jackson Scott A. 
Published: September 2024

AbstractWe assessed the analytical performance of metagenomic workflows using NIST Reference Material 8376 DNA from bacterial pathogens spiked into two simulated clinical samples: cerebral spinal fluid (CSF) and stool. Sequencing and taxonomic classification were used to generate signals for each sample and taxa of interest, and to estimate the limit of detection (LOD), the response function, and linear dynamic range. We found that the LODs for taxa spiked into CSF ranged from approximately (0.1 to 0.3) copy/μL, with a linearity of 0.96 to 0.99. For stool, the LODs ranged from (10 to 221) copy/μL, with a linearity of 0.99 to 1.01. Further, discriminating differentE. colistrains proved to be workflow-dependent, as only one classifier:database combination of the three tested showed the ability to differentiate the two pathogenic and commensal strains. Surprisingly, when we compared the response functions of the same taxa in the two different sample types, we found those functions to be the same, despite large differences in LODs. This suggests that the “agnostic diagnostic” theory for metagenomics may apply to different target organismsanddifferent sample types. Using RMs, we were able to generate quantitative analytical performance metrics for each workflow and sample set, enabling relatively rapid workflow screening before employing clinical samples. This makes these RMs a useful tool that will generate data needed to support translation of metagenomics into regulated use.ImportanceAssessing the analytical performance of metagenomic workflows, especially when developing clinical diagnostics, is foundational for ensuring that the measurements underlying a diagnosis are supported by rigorous characterization. To facilitate the translation of metagenomics into clinical practice, workflows must be tested using control samples designed to probe the analytical limitations (e.g. limit of detection). Spike-ins allow developers to generate fit-for-purpose control samples for initial workflow assessments and inform decisions about further development. However, clinical sample types include a wide range of compositions and concentrations, each presenting different detection challenges. In this work, we demonstrate how spike-ins elucidate workflow performance in two highly dissimilar sample types (stool and CSF); and we provide evidence that detection of individual organisms is unaffected by background sample composition, making detection sample agnostic within a workflow. These demonstrations and performance insights will facilitate translation of the technology to the clinic.
Nucleoprotein phase-separation affinities revealed via atomistic simulations of short peptide and RNA fragments
Authors: Ramachandran Vysakh , Brown William , Potoyan Davit A 
Published: September 2024

AbstractLiquid-liquid phase separation of proteins and nucleic acids into condensate phases is a versatile mechanism for ensuring compartmentalization of cellular biochemistry. RNA molecules play critical roles in these condensates, particularly in transcriptional regulation and stress responses, exhibiting a wide range of thermodynamic and dynamic behaviors. However, deciphering the molecular grammar that governs the stability and dynamics of protein-RNA condensates remains challenging due to the multicomponent and heterogeneous nature of these biomolecular mixtures. In this study, we employ atomistic simulations of twenty distinct mixtures containing minimal RNA and peptide fragments to dissect the phase-separating affinities of all twenty amino acids in the presence of RNA. Our findings elucidate chemically specific interactions, hydration profiles, and ionic effects that synergistically promote or suppress protein-RNA phase separation. We map a ternary phase diagram of interactions, identifying four distinct groups of residues that promote, maintain, suppress, or disrupt protein-RNA clusters.
Germinated brown rice research: bibliometric analysis of progress, hotspots and trends
Authors: Zhang Wenyang , Niu Hao , Zhao Yewang , Zhang Qiang , Yang Fuxue , Zhang Hong 
Published: September 2024

AbstractTo gain a deeper understanding of global research trends and focal points in germinated brown rice, this article takes the relevant literature on germinated brown rice in the core database of Web of Science as the research object. By using bibliometric analysis, the literature on germinated brown rice published from 2003 to 2023 is deeply analyzed, and the global research progress, hotspots and future development trend of germinated brown rice are summarized. Since 2018, research on germinated brown rice has been rapidly developing, with a significant surge in interest since 2020. China leads in the number of publications, institutions, and core authors in this research area. The primary research topics include the nutritional value, physiological active components, and industrial applications of germinated brown rice. Current research frontiers involve identifying, evaluating, and enhancing bioactive substances in germinated brown rice for food applications. Research in this field remains active, and application scenarios are becoming increasingly diverse. Future studies may explore new directions in related equipment and ingredients.
Differential participation of the corticospinal and corticorubral neurons during motor execution in the rat
Authors: Rodriguez-Moreno Paola , Loza-Vaqueiro Juliana , Olivares-Moreno Rafael , Rojas-Piloni Gerardo 
Published: September 2024

ABSTRACTThe sensorimotor cortex is crucial for learning and executing new movements with precision (Nudo & Frost, 2007). It selectively modulates sensory information flow and represents motor information in a spatially organized manner (Canedo, 1997; Chen et al., 2017). The pyramidal system is made up layer 5 pyramidal tract neurons (PTNs), which are organized into populations with distinct morphological, genetic and functional properties. These subpopulations project to different subcortical structures in a segregated manner (Nudo & Frost, 2007).To understand whether PTNs projecting to different structures play distinct functional roles in motor control, we characterized two types of layer 5 neurons in the motor cortex: corticorubral (CR) neurons, which project to the red nucleus, and corticospinal (CS) neurons, which project to the spinal cord.To analyze movement performance in rats, we compared the selective optogenetic inhibition of motor cortex CS or CR neurons during lever movement execution in response to a light stimulus. As the animals progressed through the training sessions, the variability of lever trajectories decreased, and the movements became more stereotyped. Photoinhibition of CS or CR neurons increased the performance variability of learned movements but differentially affected kinematic parameters. CR neuron inhibition affected amplitude, duration, reaction times, speed, and acceleration of the movement. In contrast, inhibition of CS neurons mainly altered the duration, speed, and acceleration of the movement. We conclude that CS and CR are complementary pathways for transmitting information rather than copies of the same motor command.
Development of Machine Learning-Based Mpox Surveillance Models in a Learning Health System
Authors: Reyes Nieva Harry , Zucker Jason , Tucker Emma , McLean Jacob , DeLaurentis Clare , Gunaratne Shauna , Elhadad Noémie 
Published: September 2024

ABSTRACTWe developed machine learning and deep learning models to identify mpox cases from clinical notes as part of a learning health system initiative. Lasso regression outperformed deep learning models, excelled in minimizing false positives, and may prove helpful for flagging missed or delayed diagnoses as part of continuous quality improvement.
Functional Connectivity Alterations in Asymptomatic Familial Early-Onset Alzheimer’s Disease Caused by APP Duplication
Authors: Paz Rotem , Kalfon Limor , Bergmann Eyal , Eran Ayelet , Aharon-Peretz Judith , Falik Zaccai Tzipora C , Kahn Itamar 
Published: September 2024

ABSTRACTBACKGROUND AND OBJECTIVESAutosomal dominant mutations of Alzheimer’s Disease (AD) are highly penetrant allowing to characterize the asymptomatic phase of this devastating condition. We investigated brain-wide functional alterations in the asymptomatic phase of autosomal dominant early-onset AD (ADEOAD) and explored whether a functional brain fingerprint of the disease can be found prior to clinical manifestation.METHODSIn this cross-sectional study fourteen asymptomaticAPP-dup carriers and eightAPP-dup non-carriers from the same kindred underwent neurological and neuropsychological examination and resting-state fMRI scanning. The functional connectome of each participant was constructed based on 264 pre-defined brain regions, which were classified into seven different sensory (Visual and Somatomotor) and association (Default, Frontoparietal, Ventral Attention, Dorsal Attention, Limbic) cortical networks. Time courses were extracted from all regions in each participant and brain-wide Fisher’sz-transformed Pearson correlation (z(r)) from each region to all other regions was calculated, resulting in a 264 × 264 connectivity matrix per participant. These matrices were used for network similarity and connectome-based predictive modelling (CPM) analyses aimed to characterize age-dependent functional connectivity alterations within the carriers group that reflect their position along the neurodegeneration trajectory.RESULTSComparing individual connectomes within the carriers group to the average connectome in the non-carrier group, we found that network similarity between groups decreased in an age-dependent manner. With age the APP-dup connectome diverged from the non-carriers connectome, with this difference being driven primarily by alterations in association networks and specifically involving the Default and Frontoparietal networks. Moreover, decreases in network similarity of association networks correlated with decreased performance on a visuospatial memory task. Using CPM, we found that in this family, carriers’ age can be predicted independent of the non-carriers control group and that this prediction is based mainly on connections within and between association networks.DISCUSSIONFunctional connectivity was used to assess the progress of AD pathology in asymptomatic carriers of an autosomal-dominant deterministic gene. Our results show that in asymptomaticAPP-dup carriers, aging is associated with functional connectivity alterations that preferentially involve association networks. Understanding these alterations might lay the foundation for development of novel diagnostic markers and assist in determining the appropriate timing of therapeutic interventions in ADEOAD.