bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulating the Human Gut Microbiome and Health Markers through Kombucha Consumption: A Controlled Clinical Study
Authors: Ecklu-Mensah Gertrude , Miller Rachel , Maseng Maria Gjerstad , Hawes Vienna , Hinz Denise , Kim Cheryl , Gilbert Jack 
Published: July 2024

AbstractFermented foods are surging in popularity globally due to their links to metabolic health and the gut microbiome. However, direct clinical evidence for the health claims is lacking. Here, we describe an eight-week clinical trial that explored the effects of a kombucha supplement in healthy individuals consuming a Western diet, randomized into the kombucha (n= 16) or control (n= 8) group. We collected longitudinal stool and blood samples to profile the human microbiome and inflammation markers. Paired analysis between baseline and end of intervention time points within kombucha or control groups revealed increases in fasting insulin and in HOMA-IR in the kombucha group whereas reductions in HDL cholesterol were associated with the control group. Shotgun metagenomic analysis revealed the relative abundance ofWeizmannia, a kombucha-associated probiotic to be overrepresented in consumers at the end of the intervention. Short-term kombucha intervention induced modest impacts on human gut microbiome composition and biochemical parameters.HighlightsThere is a global rise in popularity of fermented foods due to their links to metabolic health. However, empirical evidence supporting the health conferring benefits is lacking.This eight-week randomized controlled clinical trial tested the effect of kombucha on gut microbiome and inflammation in healthy participants consuming a Western diet.Biochemical indicators and inflammation markers were not different between the control and intervention groups at the end of the intervention.Kombucha-associated probiotic,Weizmanniaand short chain fatty acids synthesizing microbes were enriched in consumers after 4 weeks of kombucha intervention.Graphical abstract
Structure of a novel α-synuclein filament fold from multiple system atrophy
Authors: Yan Nicholas L. , Candido Francisco , Tse Eric , Melo Arthur A. , Prusiner Stanley B. , Mordes Daniel A. , Southworth Daniel R. , Paras Nick A. , Merz Gregory E. 
Published: July 2024

AbstractMultiple system atrophy (MSA) is a synucleinopathy, a group of related diseases characterized by the accumulation of α-synuclein aggregates in the brain. In MSA, these aggregates form glial cytoplasmic inclusions, which contain abundant cross-β amyloid filaments. Structures of α-synuclein filaments isolated from MSA patient tissue were determined by cryo–electron microscopy (cryo-EM), revealing three discrete folds that are distinct from α-synuclein filaments associated with other synucleinopathies. Here, we use cryo-EM classification methods to characterize filaments from one individual with MSA and identify a novel, low-populated MSA filament fold (designated Type I2) in addition to a predominant class comprising MSA Type II2. The 3.3-Å resolution structure of the Type I2filament reveals a fold consisting of two asymmetric protofilaments. One is identical to a previously solved Type I protofilament, while the second adopts a novel fold that is chimeric between two previously reported Type I and II protofilaments. These results further define disease-specific folds of α-synuclein filaments that develop in MSA and have implications for the design of therapeutic and diagnostic molecules that target disease.
Wolbachiaincompatible insect technique program optimization over large spatial scales using a process-based model of mosquito metapopulation dynamics
Authors: Lim Preston , Cook Alex R , Bansal Somya , Chow Jo Yi , Lim Jue Tao 
Published: July 2024

AbstractBackgroundWolbachiaincompatible insect technique (IIT) programs have been shown in field trials to be highly effective in suppressing populations of mosquitoes that carry diseases such as dengue, chikungunya and Zika. However, the frequent and repeated release ofWolbachia-infected male mosquitoes makes such programs resource-intensive. While the need for optimization is recognized, potential strategies to optimize releases and reduce resource utilization have not been fully explored.MethodsWe developed a process-based model to study the spatial-temporal metapopulation dynamics of mosquitoes in aWolbachiaIIT program, which explicitly incorporates climatic influence in mosquito life-history traits. We then used the model to simulate various scale-down and redistribution strategies to optimize the existing program in Singapore. Specifically, the model was used to study the trade-offs between the intervention efficacy outcomes and resource requirements of various release program strategies, such as the total number of release events and the number of mosquitoes released.ResultsWe found that scaling down releases in existing sites from twice a week to only once a week yielded minimal changes in suppression efficacy (from 91% to 85%), while requiring 45% fewer mosquitoes and release events. Additionally, redistributing mosquitoes from already suppressed areas and releasing them in new areas once a week led to a greater total suppressive efficacy (88% compared to 65%) while also yielding a 16% and 14% reduction in the number of mosquitoes and release events required respectively.ConclusionsBoth scale-down and redistribution strategies can be implemented to significantly reduce program resource requirements without compromising the suppressive efficacy of IIT. These findings will inform planners on ways to optimize existing and future IIT programs, potentially allowing for the wider adoption of this method for mosquito-borne disease control.
Opto-Myomatrix: μLED integrated microelectrode arrays for optogenetic activation and electrical recording in muscle tissue
Authors: Lu Jiaao , Zia Muneeb , Baig Danish A. , Yan Geyu , Kim Jeong Jun , Nagapudi Kailash , Anschutz Philip , Oh Shane , O’Connor Daniel , Sober Samuel J. , Bakir Muhannad S. 
Published: July 2024

AbstractOptogenetics is a valuable and widely-used technique that allows precise perturbations of selected groups of cells with high temporal and spatial resolution by using optical systems and genetic engineering technologies. Although numerous studies have been done to investigate optogenetic tools used in the brain and central nervous system (CNS), there has been limited progress in developing similar tools for optogenetic muscle stimulation. This paper introduces Opto-Myomatrix, a novel optogenetic tool designed for precise muscle fiber control and high-resolution recording. Based on a flexible and biocompatible polymer substrate, the device incorporates an integrated µLED that delivers light at 465 nm for optogenetic stimulation and 32 low-impedance electrodes for electromyography (EMG) recording. A reflector is also added to the device to improve optical power output by nearly 100% in the direction of interest. Compared to uncoated electrical contacts, the PEDOT:PSS-coated recording electrodes possess an average impedance that is 85% lower, ensuring high signal-to-noise EMG acquisition. To evaluate the potential risk of thermal tissue damage, we measured and simulated the heat dissipation characteristics of the µLED. This analysis aimed to ensure that the maximum temperature change remains within a safe range. The Opto-Myomatrix device was implanted in transgenetic mice and successfully stimulated targeted jaw muscles, inducing movement while simultaneously capturing EMG signals.
Metabolic Profiles of Encapsulated Chondrocytes Exposed to Short-Term Simulated Microgravity
Authors: Bergstrom Annika R. , Glimm Matthew G. , Houske Eden A. , Cooper Gwendolyn , Viles Ethan , Chapman Marrin , Bourekis Katherine , Welhaven Hope D. , Brahmachary Priyanka P. , Hahn Alyssa K. , June Ronald K. 
Published: July 2024

AbstractThe mechanism by which chondrocytes respond to reduced mechanical loading environments and the subsequent risk of developing osteoarthritis remains unclear. This is of particular concern for astronauts. In space the reduced joint loading forces during prolonged microgravity (10-6g) exposure could lead to osteoarthritis (OA), compromising quality of life post-spaceflight. In this study, we encapsulated human chondrocytes in an agarose gel of similar stiffness to the pericellular matrix to mimic the cartilage microenvironment. We then exposed agarose-chondrocyte constructs to simulated microgravity (SM) using a rotating wall vessel (RWV) bioreactor to better assess the cartilage health risks associated with spaceflight. Global metabolomic profiling detected a total of 1205 metabolite features across all samples, with 497 significant metabolite features identified by ANOVA (FDR-corrected p-value < 0.05). Specific metabolic shifts detected in response to SM exposure resulted in clusters of co-regulated metabolites, as well as key metabolites identified by variable importance in projection scores. Microgravity-induced metabolic shifts in gel constructs and media were indicative of protein synthesis, energy metabolism, nucleotide metabolism, and oxidative catabolism. The microgravity associated-metabolic shifts were consistent with early osteoarthritic metabolomic profiles in human synovial fluid, which suggests that even short-term exposure to microgravity (or other reduced mechanical loading environments) may lead to the development of OA.
Phenotypically wild barley shows evidence of introgression from cultivated barley
Authors: Liu Chaochih , Lei Li , Shao Mingqin , Franckowiak Jerome D. , Pacheco Jacob B. , Scott Jeness C. , Gavin Ryan T. , Roy Joy K. , Sallam Ahmad H. , Steffenson Brian J. , Morrell Peter L. 
Published: July 2024

AbstractPlant conservation hinges on preserving biodiversity, which is crucial for long-term adaptation. Multiple studies have reported genetic evidence of crop-to-wild introgression in phenotypically wild accessions of wild barley (Hordeum vulgaressp.spontaneum). We examined 318 Wild Barley Diversity Collection (WBDC) accessions for evidence of introgression from cultivated barley. Using SNP genotype and exome capture data, we performed local ancestry inference between the 318 WBDC accessions and cultivated barley to identify genomic regions with evidence of introgression. Using the genomic intervals for well-characterized genes involved in domestication and improvement, we examined the evidence for introgression at genomic regions potentially important for maintaining a wild phenotype. Our analysis revealed that nearly 16% (48 of 318) of WBDC accessions showed evidence of introgression from cultivated barley, and up to 16.6% of the genome has been introgressed. All accessions identified as introgressed based on domestication-related phenotypes show clear genetic evidence of introgression. The size of runs of identity by state and local ancestry inference suggests that most introgression did not occur recently. This study suggests a long history of genetic exchange between wild and cultivated barley, highlighting the potential for introgression to influence the genetic makeup and future adaptation of wild populations, with implications for plant conservation strategies.
Epilepsy protein myoclonin1 interacts with inositol 1,4,5–trisphosphate (IP3) receptor and reduces Ca2+store in endoplasmic reticulum
Authors: Suzuki Toshimitsu , Aguan Kripamoy , Mizuno Hideaki , Nakamura Takeshi , Inoue Ikuyo , Mikoshiba Katsuhiko , Miyawaki Atsushi , Yamakawa Kazuhiro 
Published: July 2024

AbstractMutations ofEFHC1gene have been identified in patients with epilepsies including juvenile myoclonic epilepsy (JME), and mice withEfhc1deficiency exhibit epileptic phenotypes. Myoclonin1 protein encoded byEFHC1is not expressed in neurons but in cells with motile cilia including those of choroid plexus and ependymal cells which form an epithelial layer lining brain ventricles. Detailed molecular basis of epilepsies caused byEFHC1mutations, however, remain unclear. Here we report that myoclonin1 is well co–expressed with inositol 1,4,5–trisphosphate receptor type 1 (IP3R1) at choroid plexus and ependymal cells and these two proteins bind each other. Endoplasmic reticulum (ER) ofEfhc1–deficient mouse (Efhc1-/–) cells contains larger levels of calcium ions (Ca2+) than that of wild–type (WT) mice, and IP3–induced Ca2+release (IICR) from ER is higher inEfhc1-/–cells than that of WT. Furthermore, myoclonin1 revealed to interact with PRKCSH, also known as a protein kinase C substrate 80K–H which interacts with IP3R1. Myoclonin1 further binds to IP3R2 and IP3R3. Thus, our results indicate that myoclonin1 modulates ER–Ca2+homeostasis through interactions with IP3Rs and PRKCSH, and suggest that myoclonin1 dysfunctions cause impaired intracellular Ca2+mobilization. It’s relevance to the epileptic phenotypes of patients withEFHC1mutations is now of interest.
Estimates of the eligible population for Australia’s targeted National Lung Cancer Screening Program, 2025-2030
Authors: Wade Stephen , Ngo Preston , He Yue , Caruana Michael , Steinberg Julia , Luo Qingwei , David Michael , McWilliams Annette , Fong Kwun M , Canfell Karen , Weber Marianne 
Published: July 2024

AbstractAustralia’s National Lung Cancer Screening Program will commence in July 2025, targeted at individuals aged 50-70 years with a 30 pack-year smoking history, who either currently smoke or have quit within the last 10 years. We forecasted the number of screening-eligible individuals over the first 5 years of the program using data from the 2019 National Drug Strategy Household Survey, and the 2022 Australian Bureau of Statistics population projections. Multiple imputation integrated with predictive modelling of future or unmeasured smoking characteristics was used to address missing data and simultaneously, to project individuals’ smoking histories to 2030. In 2025, 930,500 (95% prediction interval 852,200-1,019,000) individuals were estimated to be eligible, with the number meeting the criteria declining slightly over the years 2025-2030 in all Australian jurisdictions. Overall, 26-30% of those eligible will have quit smoking, and 70-74% will currently smoke. These estimates can be used in resource planning and as an indicative denominator to track participation rates for the program over time.
Integrated analysis of high-throughput sequencing-based lncRNA-mediated ceRNA network in Hepatic Alveolar Echinococcosis
Authors: Liu Zhen , Shang Chang-zhen , Wang Jin-peng , Gai Zhi-gang , Ma Fu-cai , Xia Pan , Wang Yan , Yang Xiao , Zhu Hai-hong 
Published: July 2024

AbstractBackgroundNumerous studies have indicated that long non-coding RNAs (lncRNAs) can modulate the expression of target gene mRNAs by adsorbing microRNAs (miRNAs). The lncRNA–miRNA–mRNA ceRNA network has been theorized to play an indispensable role in many types of tumors, and has been garnering increasing attention. However, the role of the lncRNA-associated ceRNA regulatory network in Hepatic Alveolar Echinococcosis (HAE) remains unclear and requires further exploration.MethodsIn this study, high-throughput sequencing was performed on lesion tissues and adjacent tissues from three patients with Hepatic Alveolar Echinococcosis (HAE) to identify differentially expressed RNAs. We utilized Cytoscape (version 3.10.1) to construct the lncRNA-miRNA-mRNA ceRNA network based on the interactions from the miRcode, miRTarBase, miRDB, and TargetScan databases, and identified hub lncRNAs from within the ceRNA network. Through the use of the “clusterProfiler” package in R, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotations for the DEGs (Differentially Expressed Genes) within the ceRNA network. Concurrently, we utilized these DEGs to construct a protein-protein interaction network (PPI). Finally, an analysis was conducted on the PCBP1-AS1-miR-20b-5p/CAPRIN2 axis within the ceRNA network.ResultsIn HAE, a total of 979 differentially expressed lncRNAs (DELncRNAs) and 870 differentially expressed mRNAs (DEmRNAs) were identified. An HAE-specific ceRNA network comprising 11 lncRNAs, 21 miRNAs, and 56 mRNAs was established, and analysis of this network led to the construction of a sub-network associated with hub lncRNAs. GO and KEGG pathway analyses indicated that the HAE-specific ceRNA network is related to molecular functions and pathways associated with cancer. Subsequent experiments using qPCR and dual-luciferase assays validated the interactions between PCBP1-AS1 and miR-20b-5p, as well as between miR-20b-5p and CAPRIN2. Analysis of the target gene in relation to clinical characteristics of HAE patients suggested that the PCBP1-AS1-miR-20b-5p/CAPRIN2 axis may influence the development of HAE.ConclusionIn this study, we described the gene regulation within the lncRNA-miRNA-mRNA ceRNA network during the development of Hepatic Alveolar Echinococcosis (HAE), which contributes to a deeper exploration of the molecular mechanisms underlying HAE. Additionally, we discovered that PCBP1-AS1 may regulate the expression of CAPRIN2 by adsorbing miR-20b-5p, affecting the onset and progression of HAE. PCBP1-AS1 could potentially serve as a useful target for the diagnosis and treatment of HAE.
Discrepancies in readouts between Infinium MethylationEPIC v2.0 and v1.0 reflected in DNA methylation-based tools: implications and considerations for human population epigenetic studies
Authors: Zhuang Beryl C. , Jude Marcia Smiti , Konwar Chaini , Yusupov Natan , Ryan Calen P. , Engelbrecht Hannah-Ruth , Whitehead Joanne , Halberstam Alexandra A. , MacIsaac Julia L. , Dever Kristy , Tran Toan Khanh , Korinek Kim , Zimmer Zachary , Lee Nanette R. , McDade Thomas W. , Kuzawa Christopher W. , Huffman Kim M. , Belsky Daniel W. , Binder Elisabeth B. , Czamara Darina , Korthauer Keegan , Kobor Michael S. 
Published: July 2024

AbstractBackgroundThe recently launched DNA methylation profiling platform, Illumina MethylationEPIC BeadChip Infinium microarray v2.0 (EPICv2), is highly correlated with measurements obtained from its predecessor MethylationEPIC BeadChip Infinium microarray v1.0 (EPICv1). However, the concordance between the two versions in the context of DNA methylation-based tools, including cell type deconvolution algorithms, epigenetic clocks, and inflammation and lifestyle biomarkers has not yet been investigated. To address this, we profiled DNA methylation on both EPIC versions using matched venous blood samples from individuals spanning early to late adulthood across four cohorts.FindingsWithin each cohort, samples primarily clustered by the EPIC version they were measured on. High concordance between EPIC versions at the array level, but variable concordance at the individual probe level was noted. Significant differences between versions in estimates from DNA methylation-based tools were observed, irrespective of the normalization method, with some nuanced differences across cohorts and tools. Adjusting for EPIC version or calculating estimates separately for each version largely mitigated these version-specific discordances.ConclusionsOur work illustrates the importance of accounting for EPIC version differences in research scenarios, especially in meta-analyses and longitudinal studies, when samples profiled across different versions are harmonized. Alongside DNA methylation-based tools, our observations also have implications in interpretation of epigenome-wide association studies (EWAS) findings, when results obtained from one version are compared to another, particularly for probes that are poorly concordant between versions.
Differential Aging Effects on Implicit and Explicit Sensorimotor Learning
Authors: Cisneros Elizabeth , Karny Sheer , Ivry Richard B. , Tsay Jonathan S. 
Published: July 2024

AbstractDeterioration in motor control is a hallmark of aging, significantly contributing to a decline in quality of life. More controversial is the question of whether and how aging impacts sensorimotor learning. We hypothesized that the inconsistent picture observed in the current literature can be attributed to at least two factors. First, aging studies tend to be underpowered. Second, the learning assays used in these experiments tend to reflect, to varying degrees, the operation of multiple learning processes, making it difficult to make inferences across studies. We took a two-pronged approach to address these issues. We first performed a meta-analysis of the sensorimotor adaptation literature focusing on outcome measures that provide estimates of explicit and implicit components of adaptation. We then conducted two well-powered experiments to re-examine the effect of aging on sensorimotor adaptation, using behavioral tasks designed to isolate explicit and implicit processes. Convergently, both approaches revealed a striking dissociation: Older individuals exhibited a marked impairment in their ability to discover an explicit strategy to counteract a visuomotor perturbation. However, they exhibited enhanced implicit recalibration. We hypothesize that the effect of aging on explicit learning reflects an age-related decline in reasoning and problem solving, and the effect of aging on implicit learning reflects age-related changes in multisensory integration. Taken together, these findings deepen our understanding of the impact of aging on sensorimotor learning.
Large shifts in diatom and dinoflagellate biomass in the North Atlantic over six decades
Authors: Mutshinda Crispin M. , Finkel Zoe V. , Irwin Andrew J. 
Published: July 2024

AbstractThe North Atlantic Ocean has large seasonal blooms rich in diatoms and dinoflagellates which can contribute disproportionately relative to other primary producers to export production and transfer of resources up the food web. Here we analyze data from the Continuous Plankton Recorder to reconstruct variation in the diatom and dinoflagellate community biomass over 6 decades across the North Atlantic. We find: 1) diatom and dinoflagellate biomass has decreased up to 2% per year throughout the North Atlantic except in the eastern and western shelf regions, and 2) there has been a 1-2% per year increase in diatom biomass relative to total diatom and dinoflagellate biomass throughout the North Atlantic, except the Arctic province, from 1960-2017. Our results confirm the widely reported relationship where diatoms are displaced by dinoflagellates as waters warm on short time scales, but we did not observe a coherent effect of sea surface temperature.
Specialized signaling centers direct cell fate and spatial organization in a limb organoid model
Authors: Skoufa Evangelia , Zhong Jixing , Kahre Oliver , Hu Kelly , Tsissios Georgios , Carrau Louise , Herrera Antonio , Dominguez Mantes Albert , Castilla-Ibeas Alejandro , Jang Hwanseok , Weigert Martin , Manno Gioele La , Lutolf Matthias , Ros Marian , Aztekin Can 
Published: July 2024

AbstractSpecialized signaling centers orchestrate robust development and regeneration. Limb morphogenesis, for instance, requires interactions between the mesoderm and the signaling center apical-ectodermal ridge (AER), whose properties and role in cell fate decisions have remained challenging to dissect. To tackle this, we developed mouse embryonic stem cells (mESCs)-based heterogeneous cultures and a limb organoid model, termed budoids, comprising cells with AER, surface ectoderm, and mesoderm properties. mESCs were first induced into heterogeneous cultures that self-organized into domes in 2D. Aggregating these cultures resulted in formation of limb bud-like structures in 3D, exhibiting chondrogenesis-based symmetry breaking and elongation. Using our organoids and quantitative in situ expression profiling, we uncovered that AER-like cells support nearby limb mesoderm and fibroblast identities while enhancing tissue polarization that permits distant cartilage formation. Together, our findings provide a powerful model to study aspects of limb morphogenesis, and reveal the ability of signaling center AER cells to concurrently modulate cell fate and spatial organization.