bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of aging and hearing impairment on listening in noise
Authors: Boncz Ádám , Szalárdy Orsolya , Velősy Péter Kristóf , Béres Luca , Winkler István , Tóth Brigitta 
Published: January 2023

AbstractListening in a noisy environment (e.g., speech in noise) relies on the fundamental ability to extract coherence from the variable sensory input. This allows the detection active sound sources and their segregation of them from the rest of the scene (figure-ground segregation). Peripheral and central causes of age-related decline of listening in noise were assessed by a tone-cloud-based figure detection task. In two conditions differing in the amount of noise, figure detection performance was equalized between young, normal-hearing, and hearing-impaired elderly listeners by adapting the stimulation separately to the abilities of each person. Based on behavioral measures and event-related brain potentials (ERP), in the absence of cognitive deficits, aging alone does not appear to significantly deteriorate the ability to detect sound sources in noise, although ERPs show delayed perceptual processes and some expected deterioration in attention and/or executive functions. However, even mild hearing impairment substantially reduces the ability to segregate individual sound sources within a complex auditory scene, and susceptibility to masking noise increases together with the severity of the hearing deficit.Significance StatementThis work provides new information about the contributions of central and peripheral causes to the typical age-related decline of listening in a noisy environment. Behavioral and neurophysiological data collected in a well-controlled model of listening in noise suggest that aging alone does not significantly reduce the ability to detect sound sources in a complex auditory scene. However, even mild hearing impairment significantly reduces this ability. The stimulus paradigm used appears to be quite sensitive to hearing loss, making it potentially useful for the early detection of hearing problems.
Accurate age prediction from blood using of small set of DNA methylation sites and a cohort-based machine learning algorithm
Authors: Varshavsky Miri , Harari Gil , Glaser Benjamin , Dor Yuval , Shemer Ruth , Kaplan Tommy 
Published: January 2023

SummaryChronological age prediction from DNA methylation sheds light on human aging, indicates poor health and predicts lifespan. Current clocks are mostly based on linear models from hundreds of methylation sites, and are not suitable for sequencing-based data.We present GP-age, an epigenetic clock for blood, that uses a non-linear cohort-based model of 11,910 blood methylomes. Using 30 CpG sites alone, GP-age outperforms state-of-the-art models, with a median accuracy of ~2 years on held-out blood samples, for both array and sequencing-based data. We show that aging-related changes occur at multiple neighboring CpGs, with far-reaching implications on aging research at the cellular level. By training three independent clocks, we show consistent deviations between predicted and actual age, suggesting individual rates of biological aging.Overall, we provide a compact yet accurate alternative to array-based clocks for blood, with future applications in longitudinal aging research, forensic profiling, and monitoring epigenetic processes in transplantation medicine and cancer.Graphical abstractMachine learning analysis of a large cohort (~12K) of DNA methylomes from bloodA 30-CpG regression model achieves a 2.1-year median error in predicting ageImproved accuracy (≥1.75 years) from sequencing data, using neighboring CpGsPaves the way for easy and accurate age prediction from blood, using NGS dataMotivationEpigenetic clocks that predict age from DNA methylation are a valuable tool in the research of human aging, with additional applications in forensic profiling, disease monitoring, and lifespan prediction. Most existing epigenetic clocks are based on linear models and require hundreds of methylation sites. Here, we present a compact epigenetic clock for blood, which outperforms state-of-the-art models using only 30 CpG sites. Finally, we demonstrate the applicability of our clock to sequencing-based data, with far reaching implications for a better understanding of epigenetic aging.
Complex organic matter degradation by secondary consumers in chemolithoautotrophy-based subsurface geothermal ecosystems
Authors: Paul Raegan , Rogers Timothy J. , Fullerton Kate M. , Selci Matteo , Cascone Martina , Stokes Murray H. , Steen Andrew D. , de Moor J. Maarten , Chiodi Agostina , Stefánsson Andri , Halldórsson Sæmundur A. , Ramirez Carlos J. , Jessen Gerdhard L. , Barry Peter H. , Cordone Angelina , Giovannelli Donato , Lloyd Karen G. 
Published: January 2023

AbstractMicrobial communities in terrestrial geothermal systems often contain chemolithoautotrophs with well-characterized distributions and metabolic capabilities. However, the extent to which organic matter produced by these chemolithoautotrophs supports heterotrophs remains largely unknown. Here we compared the abundance and activity of peptidases and carbohydrate active enzymes (CAZymes) that are predicted to be extracellular identified in metagenomic assemblies from 63 springs in the Central American and the Andean convergent margin (Argentinian backarc of the Central Volcanic Zone), as well as the plume-influenced spreading center in Iceland. All assemblies contain two orders of magnitude more peptidases than CAZymes, suggesting that the microorganisms more often use proteins for their carbon and/or nitrogen acquisition instead of complex sugars. The CAZy families in highest abundance are GH23 and CBM50, and the most abundant peptidase families are M23 and C26, all four of which degrade peptidoglycan found in bacterial cells. This implies that the heterotrophic community relies on autochthonous dead cell biomass, rather than allochthonous plant matter, for organic material. Enzymes involved in the degradation of cyanobacterial- and algal-derived compounds are in lower abundance at every site, with volcanic sites having more enzymes degrading cyanobacterial compounds and non-volcanic sites having more enzymes degrading algal compounds. Activity assays showed that many of these enzyme classes are active in these samples. High temperature sites (> 80°C) had similar extracellular carbon-degrading enzymes regardless of their province, suggesting a less well-developed population of secondary consumers at these sites, possibly connected with the limited extent of the subsurface biosphere in these high temperature sites. We conclude that in < 80°C springs, chemolithoautotrophic production supports heterotrophs capable of degrading a wide range of organic compounds that do not vary by geological province, even though the taxonomic and respiratory repertoire of chemolithoautotrophs and heterotrophs differ greatly across these regions.
HumanVDACpseudogenes: an emerging role forVDAC1P8pseudogene in acute myeloid leukemia
Authors: Pappalardo Xena Giada , Risiglione Pierpaolo , Zinghirino Federica , Ostuni Angela , Luciano Daniela , Bisaccia Faustino , De Pinto Vito , Guarino Francesca , Messina Angela 
Published: January 2023

AbstractBackgroundVoltage-dependent anion selective channels (VDACs) are the most abundant mitochondrial outer membrane proteins, encoded in mammals by three genes,VDAC1,2and3, mostly ubiquitously expressed. As ‘mitochondrial gatekeepers’,VDACscontrol organelle and cell metabolism and are involved in many diseases. Despite the presence of numerousVDACpseudogenes in the human genome, their significance and possible role in VDAC protein expression has not yet been considered.ResultsWe investigated the relevance of processed pseudogenes of humanVDACgenes, both in physiological and in pathological contexts. Using high-throughput tools and querying many genomic and transcriptomic databases, we show that someVDACpseudogenes are transcribed in specific tissues and pathological contexts. The obtained experimental data confirm an association of theVDAC1P8pseudogene with acute myeloid leukemia (AML).ConclusionsOurin-silicocomparative analysis between theVDAC1gene and itsVDAC1P8pseudogene, together with experimental data produced in AML cellular models, indicate a specific over-expression of theVDAC1P8pseudogene in AML, correlated with a downregulation of the parentalVDAC1gene.
Identification of novel sex determination loci in Japanese weedy melon
Authors: Nashiki Akito , Matsuo Hiroki , Takano Kota , Fitriyah Fauziatul , Isobe Sachiko , Shirasawa Kenta , Yoshioka Yosuke 
Published: January 2023

AbstractSex expression contributes to fruit quality and yield in the Cucurbitaceae. In melon, orchestrated regulation by sex determination genes explains the mechanism of sex expression, resulting in a great variety of sexual morphologies. In this study, we examined the Japanese weedy melon UT1, which does not follow the reported model of sex expression. We conducted QTL analysis using F2plants for flower sex on the main stem and the lateral branch and mapped a “femaleness” locus on Chr. 3 (Fem3.1) and a “type of flower femaleness” (female or bisexual) locus on Chr. 8 (tff8.1).Fem3.1included the known sex determination geneCmACS11. Sequence comparison ofCmACS11between parental lines revealed three nonsynonymous SNPs. A CAPS marker developed from one of the SNPs was closely linked to femaleness in two F2populations with different genetic backgrounds. The femaleness allele was dominant in F1lines from crosses between UT1 and diverse cultivars and breeding lines. This study suggests that the identity oftff8.1isCmCPR5, a recently reported bisexual flower control gene. We found that the Japanese weedy melon UT1 does not follow the conventional sex expression model because of the interaction of the lociFem3.1andtff8.1with the previously reported sex determination genes. The results of this study provide new insights into the molecular mechanisms of sex determination in melons and considerations for the application of femaleness in melon breeding.Key messageJapanese weedy melon exhibits unique sex expression with interactions between previously reported sex determination genes and two novel loci.
Improved Isolation of Extracellular Vesicles by Removal of Both Free Proteins and Lipoproteins
Authors: Ter-Ovanesyan Dmitry , Gilboa Tal , Budnik Bogdan , Nikitina Adele , Whiteman Sara , Lazarovits Roey , Trieu Wendy , Kalish David , Church George M , Walt David R 
Published: January 2023

AbstractExtracellular vesicles (EVs) are released by all cells into biofluids such as plasma. The separation of EVs from highly abundant free proteins and similarly-sized lipoproteins remains technically challenging. We developed a digital ELISA assay based on Single Molecule Array (Simoa) technology for ApoB-100, the protein component of several lipoproteins. Combining this ApoB-100 assay with previously developed Simoa assays for albumin and three tetraspanin proteins found on EVs (Ter-Ovanesyan*, Norman* et al., 2021), we were able to measure the separation of EVs from both lipoproteins and free proteins. We used these five assays to compare EV separation from lipoproteins using size exclusion chromatography (SEC) with resins containing different pore sizes. We also developed improved methods for EV isolation based on combining several types of chromatography resins in the same column. We present a simple approach to quantitatively measure the main contaminants of EV isolation in plasma and apply this approach to develop novel methods for isolating highly-pure EVs from human plasma. These methods will enable applications where high purity EVs are required to both understand EV biology and profile EVs for biomarker discovery.
Effect of caffeine and other xanthines on liver sinusoidal endothelial cell ultrastructure
Authors: Mao Hong , Szafranska Karolina , Kruse Larissa , Holte Christopher , Wolfson Deanna L. , Ahluwalia Balpreet Singh , Whitchurch Cynthia B. , Cole Louise , Lockwood Glen P. , Diekmann Robin , Le Couteur David , Cogger Victoria C. , McCourt Peter A.G. 
Published: January 2023

AbstractXanthines such as caffeine and theobromine are among the most consumed psychoactive stimulants in the world, either as natural components of coffee, tea and chocolate, or as food additives. The present study assessed if xanthines affect liver sinusoidal endothelial cells (LSEC). Cultured primary rat LSEC were challenged with xanthines at concentrations typically obtained from normal consumption of xanthine-containing beverages, food or medicines; and at higher concentrations below thein vitrotoxic limit. The fenestrated morphology of LSEC were examined with scanning electron and structured illumination microscopy. All xanthine challenges had no toxic effects on LSEC ultrastructure as judged by LSEC fenestration morphology, or function as determined by endocytosis studies. All xanthines in high concentrations (150 μg/mL) increased fenestration frequency but at physiologically relevant concentrations, only theobromine (8 μg/mL) showed an effect. LSEC porosity was influenced only by high caffeine doses which also shifted the fenestration distribution towards smaller pores. Moreover, a dose-dependent increase in fenestration number was observed after caffeine treatment. If these compounds induce similar changesin vivo, age-related reduction of LSEC porosity can be reversed by oral treatment with theobromine or with other xanthines using targeted delivery.
mRNA decay can be uncoupled from deadenylation during stress response
Authors: Czarnocka-Cieciura Agnieszka , Turtola Matti , Tomecki Rafał , Krawczyk Paweł , Mroczek Seweryn , Orzeł Wiktora , Saha Upasana , Jensen Torben Heick , Dziembowski Andrzej , Tudek Agnieszka 
Published: January 2023

AbstractThe polyadenosine tail (pA-tail) regulates mRNA nuclear export, stability, and translatability. Based on reporter constructs, the prevailing model suggests that pA-tail removal mediated by Ccr4-NOT or PAN2/3 deadenylases is required for mRNA decapping and degradation. Here, we use direct RNA sequencing to track mRNA deadenylation and decay at steady-state and in stress conditions to show a global correlation between deadenylation and decay. Interestingly, codon optimality, previously postulated to dictate mRNA stability, only strongly affects decay of conserved and abundant transcripts, such as coding for ribosomal protein subunits. Degradation of those mRNAs is also accelerated in response to stress. Still, the in-depth analysis revealed that deadenylation is a factor that contributes to degradation but is not indispensable for decapping. We further demonstrate that deadenylation is the fastest for newly made tails depending on polyA-binding protein Pab1. Unexpectedly, decapping initiates on mRNAs of pA-tails of 20-35 adenosines presumably bound by Pab1.
TCGAnalyzeR: a web application for integrative visualization of molecular and clinical data of cancer patients for cohort and associated gene discovery
Authors: Zengin Talip , Masud Başak Abak , Önal-Süzek Tuğba 
Published: January 2023

AbstractMotivationThe vast size and complexity of The Cancer Genome Atlas (TCGA) database with multidimensional molecular and clinical data of ~11,000 cancer patients of 33 cancer types challenge the effective utilization of this valuable resource. Therefore, we built a web application named TCGAnalyzeR with the main idea of presenting an integrative visualization of mutations, transcriptome profile, copy number variation and clinical data allowing researchers to facilitate the identification of customized patient cohorts and gene sets for better decision-making for oncologists and cancer researchers.ResultsWe present TCGAnalyzeR for integrative visualization of pre-analyzed TCGA data with the several novel modules: (i) Simple nucleotide variations with driver prediction; (ii) Recurrent copy number alterations; (iii) Differential expression in tumor versus normal, with pathway enrichment and the survival analysis; (iii) TCGA clinical data and survival analysis; (iv) External subcohorts from literature, curatedTCGAData and BiocOncoTK R packages; (v) Internal patient clusters determined using iClusterPlus R package or signature-based expression analysis. TCGAnalyzeR provides clinical oncologists and cancer researchers interactive and integrative representations of these multi-omic, pan-cancer TCGA data with availability of subcohort analysis and visualization. TCGAnalyzeR can be used to create their own custom gene sets for pan-cancer comparisons, to create custom patient subcohorts comparing external subcohorts (MSI, Immune, PAM50, Triple Negative, IDH1, miRNA, etc) along with our internal patient clusters, to visualize cohort-centric or gene-centric results along with pathway enrichment and survival analysis graphically on an interactive web tool.AvailabilityTCGAnalyzeR is freely available on the web athttp://tcganalyzer.mu.edu.tr.Contacttugbasuzek@mu.edu.trSupplementary informationSupplementary data are available atBioinformaticsonline.
Variable effects ofWolbachiaon alphavirus infection inAedes aegypti
Authors: Dodson Brittany L. , Pujhari Sujit , Brustolin Marco , Metz Hillery C. , Rasgon Jason L. 
Published: January 2023

2.AbstractWolbachia pipientis(=Wolbachia) has promise as a tool to suppress virus transmission byAedes aegyptimosquitoes. However,Wolbachiacan have variable effects on mosquito-borne viruses. This variation remains poorly characterized, yet the multimodal effects ofWolbachiaon diverse pathogens could have important implications for public health. Here, we examine the effects of somatic infection with two strains ofWolbachia(wAlbB andwMel) on the alphaviruses Sindbis virus (SINV), O’nyong-nyong virus (ONNV), and Mayaro virus (MAYV) inAe. aegypti. We found variable effects ofWolbachiaincluding enhancement and suppression of viral infections, with some effects depending onWolbachiastrain. BothwAlbB- andwMel-infected mosquitoes showed enhancement of SINV infection rates one week post-infection, withwAlbB-infected mosquitoes also having higher viral titers than controls. Infection rates with ONNV were low across all treatments and no significant effects ofWolbachiawere observed. The effects ofWolbachiaon MAYV infections were strikingly strain-specific;wMel strongly blocked MAYV infections and suppressed viral titers, whilewAlbB did not influence MAYV infection. The variable effects ofWolbachiaon vector competence underscore the importance of further research into how this bacterium impacts the virome of wild mosquitoes including the emergent human pathogens they transmit.Impact statementIn recent years, wild populations ofAedes aegyptimosquitoes have been deliberately infected withWolbachia—a bacterium that helps to curb the spread of some pathogens including dengue virus. But how doesWolbachiaaffect the ability of mosquitoes to become infected with and spread the many different viruses they encounter in nature? Here, we characterize the effects ofWolbachiaon three alphaviruses that cause illness in humans— Sindbis virus, O’nyong-nyong virus, and Mayaro virus. We findWolbachiahas variable effects on these pathogens, including significant enhancement of Sindbis virus infections. Our research has important implications for the design of vector control strategies, and suggests further research is needed to understand howWolbachiashapes the replication and transmission of diverse viruses.3.Data SummaryAll data in the study are available in the Figures and supplementary material.
Microglia Proliferation Underlies Synaptic Dysfunction in the Prefrontal Cortex: Implications for the Pathogenesis of HIV-1-Associated Neurocognitive and Affective Alterations
Authors: Li Hailong , McLaurin Kristen A. , Mactutus Charles F. , Booze Rosemarie M. 
Published: January 2023

ABSTRACTMicroglia, which are productively infected by HIV-1, are critical for brain development and maturation, as well as synaptic plasticity. The pathophysiology of HIV-infected microglia and their role in the pathogenesis of HIV-1-associated neurocognitive and affective alterations, however, remains understudied. Three complementary aims were undertaken to critically address this knowledge gap. First, the predominant cell type expressing HIV-1 mRNA in the dorsolateral prefrontal cortex of postmortem HIV-1 seropositive individuals with HAND was investigated. Utilization of a combined RNAscope multiplex fluorescent and immunostaining assay revealed prominent HIV-1 mRNA in microglia of postmortem HIV-1 seropositive individuals with HAND. Second, measures of microglia proliferation and neuronal damage were evaluated in chimeric HIV (EcoHIV) rats. Eight weeks after EcoHIV innoculation, enhanced microglial proliferation was observed in the medial prefrontal cortex (mPFC) of EcoHIV rats, evidenced by an increased number of cells co-localized with both Iba1+ and Ki67+ relative to control animals. Neuronal damage in EcoHIV infected rats was evidenced by pronounced decreases in both synaptophysin and post synaptic density protein 95 (PSD-95), markers of pre-synaptic and post-synaptic damage, respectively. Third, regression analyses were conducted to evaluate whether microglia proliferation mechanistically underlies neuronal damage in EcoHIV and control animals. Indeed, microglia proliferation accounts for 42-68.6% of the variance in synaptic dysfunction. Collectively, microglia proliferation induced by chronic HIV-1 viral protein exposure may underlie the profound synaptodendritic alterations in HIV-1. Understanding how microglia are involved in the pathogenesis of HAND and HIV-1-associated affective disorders affords a key target for the development of novel therapeutics.
Neuroimmune cortical organoids overexpressing C4A exhibit multiple schizophrenia endophenotypes
Authors: Stanton Morgan M. , Modan Sara , Taylor Patrick M. , Hariani Harsh N. , Sorokin Jordan , Rash Brian G. , Rao Sneha B. , López-Tobón Alejandro , Enriquez Luigi , Dang Brenda , Owango Dorah , O’Neill Shannon , Castrillo Carlos , Nicola Justin , Ye Kathy , Blattner Robert M. , Gonzalez Federico , Antonio Dexter , Ramkumar Pavan , Lash Andy , Flanzer Douglas , Bardehle Sophia , Gyoneva Stefka , Shah Kevan , Kato Saul , Skibinski Gaia 
Published: January 2023

AbstractElevated expression of the complement component 4A (C4A) protein has been linked to an increased risk of schizophrenia (SCZ). However, there are few human models available to study the mechanisms by which C4A contributes to the development of SCZ. In this study, we established a C4A overexpressing neuroimmune cortical organoid (NICO) model, which includes mature neuronal cells, astrocytes, and functional microglia. The C4A NICO model recapitulated several neuroimmune endophenotypes observed in SCZ patients, including modulation of inflammatory genes and increased cytokine secretion. C4A expression also increased microglia-mediated synaptic uptake in the NICO model, supporting the hypothesis that synapse and brain volume loss in SCZ patients may be due to excessive microglial pruning. Our results highlight the role of C4A in the immunogenetic risk factors for SCZ and provide a human model for phenotypic discovery and validation of immunomodulating therapies.