bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cortical tracking of speech is reduced in adults who stutter when listening for speaking
Authors: Gastaldon Simone , Busan Pierpaolo , Molinaro Nicola , Lizarazu Mikel 
Published: February 2024

AbstractPurposeInvestigate cortical tracking of speech (CTS) in adults who stutter (AWS) compared to typically fluent adults (TFA) to test the involvement of the speech-motor network in tracking auditory information.MethodParticipants’ EEG was recorded while they either had to simply listen to sentences (listening only) or complete them by naming a picture (listening-for-speaking), thus manipulating the upcoming involvement of speech production. We analyzed speech-brain coherence and brain connectivity during listening.ResultsDuring the listening-for-speaking task, AWS exhibited reduced CTS in the 3-5 Hz range (theta), corresponding to the syllabic rhythm. The effect was localized in left inferior parietal and right pre-/supplementary motor regions. Connectivity analyses revealed that TFA had stronger information transfer in the theta range in both tasks in fronto-temporo-parietal regions. When considering the whole sample of participants, increased connectivity from the right superior temporal cortex to the left sensorimotor cortex was correlated with faster naming times in the listening-for-speaking task.ConclusionsAtypical speech-motor functioning in stuttering also impacts speech perception, especially in situations requiring articulatory alertness. The involvement of frontal and (pre-) motor regions in CTS in typically fluent adults is highlighted. Speech perception in individuals with speech-motor deficits should be further investigated, especially when smooth transitioning between listening and speaking is required, such as in real-life conversational settings.
Rhodoquinone-dependent electron transport chain is essential forC. eleganssurvival in hydrogen sulfide environments
Authors: Romanelli-Cedrez Laura , vairoletti Franco , Salinas Gustavo 
Published: February 2024

AbstractHydrogen sulfide (H2S) has traditionally been considered as an environmental toxin for animal lineages; yet, it plays a signaling role in various processes at low concentrations. Mechanisms controlling H2S in animals, especially in sulfide-rich environments, are not fully understood. The main detoxification pathway involves the conversion of H2S into less harmful forms, through a mitochondrial oxidation pathway. The first step of this pathway oxidizes sulfide and reduces ubiquinone (UQ) through sulfide-quinone oxidoreductase (SQRD/SQOR). Because H2S inhibits cytochrome oxidase and hence UQ regeneration, this pathway becomes compromised at high H2S concentrations. The free-living nematodeC. elegansfeeds on bacteria and can face high sulfide concentrations in its natural environment. This organism has an alternative ETC that uses rhodoquinone (RQ) as the lipidic electron transporter and fumarate as the final electron acceptor. In this study, we demonstrate that RQ is essential for survival in sulfide. RQ-less animals (kynu-1andcoq-2eKO) cannot survive high H2S concentrations, while UQ-less animals (clk-1andcoq-2aKO) exhibit recovery, even when provided with a UQ-deficient diet. Our findings highlight thatsqrd-1uses both benzoquinones and that RQ-dependent ETC confers a key advantage (RQ regeneration) over UQ in sulfide conditions.C. elegansalso faces cyanide, another cytochrome oxidase inhibitor, whose detoxification leads to H2S production, viacysl-2. Our study reveals that RQ delays killing by the HCN-producing bacteriaPseudomonas aeruginosaPAO1. These results underscore the fundamental role that RQ-dependent ETC serves as a biochemical adaptation to H2S environments, and to pathogenic bacteria producing cyanide and H2S toxins.
Neuroimmune changes underscore pain-associated behaviors and disc herniations in SM/J mice
Authors: Novais Emanuel J. , Ottone Olivia K. , Brown Eric V. , Madhu Vedavathi , Tran Victoria A. , Dighe Abhijit S. , Solga Michael D. , Manchel Alexandra , Lepore Angelo C. , Risbud Makarand V. 
Published: February 2024

AbstractThere are no appropriate mouse models to study the pathophysiology of spontaneous disc herniations and associated pain pathology. We demonstrate that SM/J mice show a high incidence of age-associated lumbar disc herniations with neurovascular innervations. Transcriptomic comparisons of the SM/J annulus fibrosus with human tissues showed shared pathways related to immune cell activation and inflammation. Notably, aged SM/J mice showed increased pain sensitization and neuroinflammatory signatures associated with altered extracellular matrix regulation in the DRGs and spinal cord. There were increased T cells in the vertebral marrow, and CyTOF analysis showed increased splenic CD8+T cells, nonspecific activation of CD8+memory T cells, and enhanced IFN-γ production in the myeloid compartment. ScRNA-seq of PBMCs in SM/J showed more B cells, with lower proportions of T cells, monocytes, and granulocytes. This study identifies SM/J mice as a clinically-relevant model to study the pathophysiology of spontaneous disc herniations and highlights a causative axis for chronic discogenic pain with novel contributors from the primary lymphoid organs (spleen and vertebral marrow), circulation, and the nervous system.One-Sentence SummaryThe novel SM/J mouse model shows a neuroimmune axis drives chronic back pain, a leading cause of years lived with disability.
PPTC7 antagonizes mitophagy by promoting BNIP3 and NIX degradation via SCFFBXL4
Authors: Nguyen-Dien Giang Thanh , Townsend Brendan , Kulkarni Prajakta , Kozul Keri-Lyn , Ooi Soo Siang , Eldershaw Denaye , Weeratunga Saroja , Liu Meihan , Jones Mathew JK , Millard S Sean , Ng Dominic CH , Pagano Michele , Komander David , Lazarou Michael , Collins Brett M , Pagan Julia K 
Published: February 2024

AbstractMitophagy must be carefully regulated to ensure that cells maintain appropriate numbers of functional mitochondria. The SCFFBXL4ubiquitin ligase complex suppresses mitophagy by controlling the degradation of BNIP3 and NIX mitophagy receptors, andFBXL4mutations result in mitochondrial disease as a consequence of elevated mitophagy. Here, we reveal that the mitochondrial phosphatase PPTC7 is an essential cofactor for SCFFBXL4-mediated destruction of BNIP3 and NIX, suppressing both basal and induced mitophagy. Disruption of the phosphatase activity of PPTC7 is not required for BNIP3 and NIX turnover. Rather, a pool of PPTC7 on the mitochondrial outer membrane acts as an adaptor linking BNIP3 and NIX to FBXL4, facilitating the turnover of these mitophagy receptors. PPTC7 accumulates on the outer mitochondrial membrane in response to mitophagy induction or the absence of FBXL4, suggesting a homeostatic feedback mechanism that attenuates high levels of mitophagy. We mapped critical residues required for PPTC7-NIX/BNIP3 and PPTC7-FBXL4 interactions and their disruption interferes with both NIX/BNIP3 degradation and mitophagy suppression. Collectively, these findings delineate a complex regulatory mechanism that restricts NIX/BNIP3-induced mitophagy.
Large herbivores link plant phenology and abundance in arctic tundra
Authors: Post Eric , Higgins R. Conor , Bøving Pernille Sporon , John Christian , Post Mason , Kerby Jeff 
Published: February 2024

AbstractPlant phenology has been well studied in relation to abiotic conditions and climate change, but poorly studied in relation to herbivory. In contrast, plant abundance dynamics have been well studied in relation to abiotic conditions and herbivory, but poorly studied in relation to phenology. Consequently, the contribution of herbivory to plant phenological dynamics and therefrom to plant abundance dynamics remains obscure. We conducted a nine-year herbivore exclusion experiment to investigate whether herbivory might link plant phenological and abundance dynamics in arctic tundra. From 2009 - 2017 we monitored annual green-up timing and abundance of nine plant taxa, including deciduous shrubs, forbs, and graminoids, on plots that were either grazed or experimentally exclosed from herbivory by caribou (Rangifer tarandus) and muskoxen (Ovibos moschatus). In 62% of cases, green-up occurred earlier under herbivory, and in 75% of cases abundance was greater under herbivory, compared to green-up and abundance under herbivore exclusion. Moreover, taxa that responded to herbivory with earlier green-up also had comparatively greater abundance later in the growing season. Conversely, taxa that responded to herbivory with delayed green-up exhibited comparatively lower abundance later in the growing season. Hence, well-documented influences of large herbivores on plant abundance and community composition in arctic tundra may, at least to some extent, relate to influences of herbivory on plant phenology. We recommend that ongoing and future assessments of the contribution of herbivores to plant abundance and community responses to climate change, especially in the Arctic, should also consider impacts of herbivores on plant phenology.
Toxoplasmatype II effector GRA15 has limited influencein vivo
Authors: Merritt Emily F. , Kochanowsky Joshua A. , Hervé Perrine , Watson Alison A. , Koshy Anita A. 
Published: February 2024

AbstractToxoplasma gondiiis an intracellular parasite that establishes a long-term infection in the brain of many warm-blooded hosts, including humans and rodents. Like all obligate intracellular microbes,Toxoplasmauses many effector proteins to manipulate the host cell to ensure parasite survival. While some of these effector proteins are universal to allToxoplasmastrains, some are polymorphic betweenToxoplasmastrains. One such polymorphic effector is GRA15. Thegra15allele carried by type II strains activates host NF-κB signaling, leading to the release of cytokines such as IL-12, TNF, and IL-1β from immune cells infected with type II parasites. Prior work also suggested that GRA15 promotes early host control of parasitesin vivo, but the effect of GRA15 on parasite persistence in the brain and the peripheral immune response has not been well defined. For this reason, we sought to address this gap by generating a new IIΔgra15strain and comparing outcomes at 3 weeks post infection between WT and IIΔgra15infected mice. We found that the brain parasite burden and the number of macrophages/microglia and T cells in the brain did not differ between WT and IIΔgra15infected mice. In addition, while IIΔgra15infected mice had a lower number and frequency of splenic M1-like macrophages and frequency of PD-1+ CTLA-4+ CD4+ T cells and NK cells compared to WT infected mice, the IFN-γ+ CD4 and CD8 T cell populations were equivalent. In summary, our results suggest thatin vivoGRA15 may have a subtle effect on the peripheral immune response, but this effect is not strong enough to alter brain parasite burden or parenchymal immune cell number at 3 weeks post infection.
Cryptic genetic variation shapes the fate of gene duplicates in a protein interaction network
Authors: Dibyachintan Soham , Dube Alexandre K , Bradley David , Lemieux Pascale , Dionne Ugo , Landry Christian R 
Published: February 2024

AbstractParalogous genes are often redundant for long periods of time before they diverge in function. While their functions are preserved, paralogous proteins can accumulate mutations that, through epistasis, could impact their fate in the future. By quantifying the impact of all single-amino acid substitutions on the binding of two myosin proteins to their interaction partners, we find that the future evolution of these proteins is highly contingent on their regulatory divergence and the mutations that have silently accumulated in their protein binding domains. Differences in the promoter strength of the two paralogs amplify the impact of mutations on binding in the lowly expressed one. While some mutations would be sufficient to non-functionalize one paralog, they would have minimal impact on the other. Our results reveal how functionally equivalent protein domains could be destined to specific fates by regulatory and cryptic coding sequence changes that currently have little to no functional impact.
Engineering oncogenic hotspot mutations onSF3B1via CRISPR-directed PRECIS mutagenesis
Authors: Fernandez Mike , Jia Qiong , Yu Lei , Wang Xuesong , Hart Kevyn , Jia Zhenyu , Lin Ren-Jang , Wang Lili 
Published: February 2024

AbstractSF3B1is the most recurrently mutated RNA splicing factor in cancer; However, its study has been hindered by a lack of disease-relevant cell line models. Here, we compared four genome engineering platforms to establishSF3B1mutant cell lines: CRISPR-Cas9 editing, AAV HDR editing, base editing (ABEmax, ABE8e), and prime editing (PE2, PE3, PE5Max). We showed that prime editing via PE5max achieved the most efficientSF3B1K700E editing across a wide range of cell lines. We further refined our approach by coupling prime editing with a with a fluorescent reporter that leverages aSF3B1mutation-responsive synthetic intron to mark prime edited cells. Calling this approach prime editing coupled intron-assisted selection (PRECIS), we then introduced the K700E hotspot mutation into two chronic lymphocytic leukemia (CLL) cell lines, HG-3 and MEC-1, and demonstrated that our PRECIS-engineered cells faithfully recapitulate the altered splicing and copy number variation (CNV) events frequently found in CLL patients withSF3B1mutation. Our results showcase PRECIS as an efficient and generalizable method for engineering genetically faithfulSF3B1mutant models, shed new light on the role ofSF3B1mutation in cancer biology, and enables generation of novelSF3B1mutant cell lines in any cellular context.
Digital divide is amplifying cognitive disparities among the older population: a community-based cohort study in China
Authors: Li Yumeng , Liu Chen , Sun Jiaqing , Zhang Junying , Li Xin , Zhang Zhanjun 
Published: February 2024

AbstractObjectivesTo investigate the potential impact of the digital divide on individuals’ cognitive function and its association with the development and reversion of mild cognitive impairment (MCI).MethodsThis cohort study used data from Beijing Aging Brain Rejuvenation (BABRI) study applying a multistage cluster sampling design in 2008-2020. Analysis of Covariance (ANCOVA), mixed linear models, and Cox proportional hazards models were used to model the association of digital divide and multi-domain cognition.ResultsAmong the 10098 participants, nearly half of them (48.9%) failed to overcome the digital divide, resulting in the worse performance in processing speed (F=10.67,p<0.001). The causal model indicated that individuals’ physical and mental health joint educational and occupational prestige affected the resource they achieved ultimately caused the digital divide. Moreover, longitudinal data revealed that both the elderly who successfully crossed the digital divide during the tracking process and those who had already done so prior to tracking showed significantly slower rates of decline in processing speed (B=-1.98,p<0.05; B=-2.62,p<0.01) and general cognitive function (B=3.50,p<0.001; B=3.13,p<0.01). Additionally, overcoming the digital divide also exhibited a lower risk of developing into MCI (HR, 0.5; 95% CI, 0.34-0.74; HR, 0.43; 95% CI, 0.29-0.62) and a greater probability of reversion from MCI to normal cognition (HR, 6.00; 95% CI, 3.77-9.56; HR, 9.22; 95% CI, 5.63-15.11).ConclusionsOvercoming the digital divide was significantly associated with better performance and lower aging rate of cognitive function, as well as a lower risk of developing into MCI and a higher probability of reversion from MCI into NC.
mTOR controls growth and internal architecture of human breast cancer spheroids
Authors: Hötte Katharina , Fischer Sabine C. , Schmitz Alexander , Koch Michael , Saeifar Sanam , Stelzer Ernst H.K. , Pampaloni Francesco 
Published: February 2024

AbstractmTOR is a serine/threonine kinase participating in two distinct functional complexes: mTORC1 and mTORC2. mTORC1 regulates protein translation, cell cycle progression and autophagy. mTORC2 controls cell survival, proliferation and actin cytoskeleton reorganization. mTOR signaling is often deregulated during breast cancer. We investigated how mTOR and its downstream process autophagy determine the inner architecture of solid tumor aggregates at multiple levels. We focused on structures, which are morphologically altered during progression of cancer, including: nuclei number and volume, cell density, number, shape and volume of polarized structures. We developed a breast cancer spheroid model, in which the effects of mTOR and autophagy modulation were investigated by pharmacological inhibition mTOR signaling and induction autophagy, as well as using ATG7 KO spheroids. Spheroids were imaged with light sheet-based fluorescence microscopy and data were quantitatively analyzed. Our data suggest that mTORC1 regulates the spheroid volume, cell number and size. mTORC2 controls nuclei volume and determines growth and elongation of polarized acini inside a spheroid.
Genetic diversity within a tree and alternative indexes for different evolutionary effects
Authors: Iwasa Yoh , Tomimoto Sou , Satake Akiko 
Published: February 2024

AbstractTrees, living for centuries, accumulate somatic mutations in their growing trunks and branches, causing genetic divergence within a single tree. Stem cell lineages in a shoot apical meristem accumulate mutations independently and diverge from each other. In plants, somatic mutations can alter the genetic composition of reproductive organs and gametes, impacting future generations. To evaluate the genetic variation among a tree’s reproductive organs, we consider three indexes: mean pairwise phylogenetic distance, phylogenetic diversity (PD; sum of branch lengths in molecular phylogeny), and parent-offspring phylogenetic distance (DPO). The tissue architecture of trees facilitated the accumulation of somatic mutations, which have various evolutionary effects, including enhancing fitness under strong sib competition and intense host-pathogen interactions, efficiently eliminating deleterious mutations through epistasis, and increasing genetic variance in the population. Choosing appropriate indexes for the genetic diversity of somatic mutations depends on the specific aspect of evolutionary influence being assessed.
Mechanism of phage sensing and abortion by toxin-antitoxin-chaperone systems
Authors: Mets Toomas , Kurata Tatsuaki , Ernits Karin , Johansson Marcus J. O. , Craig Sophie Z. , Evora Gabriel Medina , Buttress Jessica A. , Odai Roni , Coppieters‘t Wallant Kyo , Nakamoto Jose A. , Shyrokova Lena , Egorov Artyom A. , Doering Christopher Ross , Brodiazhenko Tetiana , Laub Michael T. , Tenson Tanel , Strahl Henrik , Martens Chloe , Harms Alexander , Garcia-Pino Abel , Atkinson Gemma C. , Hauryliuk Vasili 
Published: February 2024

SummaryToxin-antitoxins (TAs) are prokaryotic two-gene systems comprised of a toxin neutralised by an antitoxin. Toxin-antitoxin-chaperone (TAC) systems additionally include a SecB-like chaperone that stabilises the antitoxin by recognising its chaperone addiction (ChAD) element. TACs have been shown to mediate antiphage defence, but the mechanisms of viral sensing and restriction are unexplored. We identify and characterise twoEscherichia coliantiphage TAC systems containing HigBA and CmdTA TA units, HigBAC and CmdTAC. The HigBAC is triggered through recognition of the gpV major tail protein of phage λ. Both the ChAD and gpV are recognised by the HigC chaperone through analogous aromatic molecular patterns, explaining the mechanism of activation. We show that the CmdT ADP-ribosyltransferase toxin modifies mRNA to shut down protein synthesis. We establish the modularity of TACs by creating a hybrid broad-spectrum antiphage system combining the CmdTA TA warhead with the HigC chaperone phage sensor.HighlightsE. coliHigBAC and CmdTAC are translation-targeting phage immunity TAC systems HigC chaperone recognises phage λ major tail protein to trigger HigBAC toxicityCmdT ADP-ribosyltransferase toxin abrogates translation through modification of mRNA HigC combined with CmdTA yields hybrid broad-spectrum antiphage defence system
Roles of C/EBPα, GATA2, TGF-β-signaling, and epigenetic regulation in the expression of basophil-specific protease genes
Authors: Tojima Ryotaro , Nagata Kazuki , Ito Naoto , Arai Takahiro , Ishii Kenta , Ito Tomoka , Kasakura Kazumi , Nishiyama Chiharu 
Published: February 2024

AbstractIn the present study, we analyzed the transcriptional regulation of genes encoding basophil-specific proteases Mcpt8 and Mcpt11 to clarify the molecular mechanisms by which the commitment between basophil and mast cell (MC) is determined. We used bone marrow-derived (BM) cells maintained in the presence of IL-3, in which basophil-like cells and MC-like cells exist. Knock down (KD) and overexpression of a transcription factor C/EBPα showed thatCebpamRNA levels were associated with those ofMcpt8andPrss34(a gene symbol of Mcpt11). Treatment with trichostatin A (TSA), a histone deacetylase inhibitor, decreased mRNA levels ofCebpa,Mcpt8, andPrss34in BM cells, whereas these mRNA levels were increased by the treatment with an inhibitor of DNA methyltransferase. TSA treatment upregulated mRNA levels ofGata1andMitfin BM cells, andMitfKD but notGata1KD increased mRNA levels ofCebpaandPrss34. Furthermore,Gata2KD significantly decreased mRNA levels ofMcpt8andPrss34without affectingCebpamRNA level. In addition, mRNA levels ofGata1andMitfwere increased in BM cells transfected withCebpasiRNA, and decreased inCebpa-overexpressing BM cells. We also found the TGF-β treatment increased mRNA levels ofMcpt8,Prss34, along with upregulation ofGata2andCebpatranscription.Taken together, we conclude that the transcription of basophil-specific protease genes was positively regulated by C/EBPα, GATA2, and TGF-β signaling with modification of epigenetic regulation.