bluuebunny/crossref_metadata_2025_split huggingface dataset:
The phenotype of SMC6_G514R hinge mutant ofPhyscomitrium patents
Authors: Angelis Karel J. , Holá Marcela , Vágnerová Radka , Vaculíková Jitka , Paleček Jan J. 
Published: July 2024

ABSTRACTThe Structural Maintenance of Chromosomes (SMC) complexes play roles in cohesion, condensation, replication, transcription, and DNA repair. Their cores are composed of SMC proteins with a unique structure consisting of an ATPase head, long arm, and hinge. The direct interaction of hinges leads to the formation of SMC heterodimer. A critical SMC6 mutation G551R interrupting the interaction of SMC5 and SMC6 hinges have been previously identified inSchizosaccharomyces pombewithin a conserved motif. Using CRISPR/Cas9 directed oligonucleotide replacement, we have introduced this G to R point mutation in SMC6 ofPhyscomitrium patens(P. patens) at position 514 and also at position 517 of the same hinge domain. It turned out that both mutations are not toxic and do not affect the viability of establishedPpsmc6_G514RandPpsmc6_G517Rlines.SinceP. patensmutants with entire or partial deletion of theSMC6gene are not viable, we compare hinge mutants with previously established mutant line with attenuated transcription by targeted binding of deactivated Cas9 nuclease (Ppsmc6_dCas). We show that mutation of G to R at position 514 fully prevents the interaction of SMC6 not only with SMC5, but also NSE5 and NSE6. Surprisingly, mutation of close residue 517 has no effect at all. ThePpsmc6_G514Rline has aberrant morphology quite similar toPpsmc6_dCas, though the absence of protonemata branching and formation of gametophores is incomplete. On the contrary, thePpsmc6_G517Rline is morphologically more or less similar to WT. Spontaneous and bleomycin-induced mutagenesis and maintenance of the number of rDNA copies in thePpsmc6_G514Rline is also similar toPpsmc6_dCas, whilePpsmc6_G517Rmore or less mimics WT. The sensitivity of thePpsmc6_G514Rline to bleomycin is not as severe as that ofPpsmc6_dCas, and surprisingly, thePpsmc6_G517Rline is even less sensitive to bleomycin than WT. Moreover, both hinge mutations have no direct effect on the rate of DSB repair in dividing and differentiated cells.The most unique feature of the hinge mutants is interference with gene targeting (GT). Whilst GT efficiency ofPpsmc6_G517RandPpsmc6_dCaswhen compared to WT is only slightly or moderately reduced, it is completely abolished inPpsmc6_G514R.Based on these results, we conclude that sufficient amounts of SMC6 and its interactions are necessary for normal moss development and genome stability, such as DNA repair and rDNA maintenance. The reduced levels of SMC6 subunit, and therefore low levels of complete SMC5/6 complex, are insufficient for acute DSB repair, however, the acute DSB repair is not affected by impaired SMC6 interactions inPpsmc6_G514R. In contrast, SMC6 inability to interact with SMC5 and other partners like NSE5 and NSE6 results in abolished GT, while low levels of SMC6 have only mild effect. These data underline importance of different aspects of SMC5/6, such as its levels or interactions.
Chronic Tinnitus is Associated with Aging but not Dementia
Authors: Reisinger Lisa , Weisz Nathan 
Published: July 2024

AbstractBackgroundAging is related to deterioration of bodily and neural functions, leading to various disorders and symptoms, including the development of dementia, hearing loss, or tinnitus. Understanding how these phenomena are intertwined and how aging affects those is crucial for prevention and the future development of interventions.MethodsWe utilized the UK Biobank which includes a total of 502,382 participants between 40 and 70 years old. We used logistic regression models and cox proportional hazard models and compared hazard ratios.ResultsThe odds of reporting tinnitus in the older age group (i.e., older than 58 years) were increased by 43.3% and a one decibel increase in the SRT enhanced the odds for tinnitus by 13.5%. For our second analysis regarding hearing loss, the risk of dementia increased by 9.2% with an increase by one decibel in the SRT score. In terms of aging, each additional year increased the risk by 19.2%. Tinnitus alone showed a significant influence with a hazard ratio of 52.1%, however, when adding hearing loss, age and various covariates, the effect vanished.ConclusionFindings confirm that tinnitus is indeed related to aging, but presumably independent of the aging processes accompanying the development of dementia. This highlights the urge to further investigate the impact of aging on neural processes that are relevant for alterations in the auditory systems (e.g., leading to the development of tinnitus or hearing loss) as well as for increased vulnerability in terms of neurodegenerative diseases.Key PointsQuestionAging and hearing loss have been linked to dementia and tinnitus respectively. But is there a direct influence of tinnitus on dementia risk?FindingsIn this case-control study, data derived from the UK Biobank was used to first replicate previous findings establishing aging as a risk factor for tinnitus and hearing loss as a risk factor for dementia. Tinnitus was not found to increase the risk of dementia.MeaningAging is related to tinnitus, however, since tinnitus does not influence the risk of dementia, we conclude that the aging processes that determine tinnitus are independent of neural processes facilitating the development of dementia.
Therapy Without Borders: A Systematic Review on Telehealth’s Role in Expanding Mental Health Access
Authors: Swint Jennifer , Fischer Margaret , Zhang Wei , Zhang Xi 
Published: July 2024

AbstractBackgroundThe COVID-19 pandemic has accelerated the adoption of telehealth services in mental healthcare. This systematic review aims to evaluate the effectiveness of telehealth interventions for mental health conditions compared to traditional face-to-face treatment.MethodsWe searched major electronic databases (PubMed, PsycINFO, CINAHL, and Cochrane Library) for randomized controlled trials published between 2010 and 2023. Studies comparing telehealth interventions to face-to-face treatment for adults with mental health disorders were included. Two independent reviewers assessed study quality and extracted data. Meta-analyses were conducted where appropriate.ResultsThirty-five studies met the inclusion criteria, encompassing 4,827 participants across various mental health conditions. Telehealth interventions demonstrated non-inferiority to face-to-face treatment for depression (standardized mean difference [SMD] = -0.03, 95% CI [-0.15, 0.09]) and anxiety disorders (SMD = -0.06, 95% CI [-0.19, 0.07]). For post-traumatic stress disorder, telehealth showed a small but significant advantage (SMD = -0.21, 95% CI [-0.37, -0.05]). Patient satisfaction and therapeutic alliance were comparable between telehealth and face-to-face interventions. However, dropout rates were slightly higher in telehealth conditions (risk ratio = 1.27, 95% CI [1.11, 1.46]).ConclusionThis review suggests that telehealth interventions are generally as effective as face-to-face treatment for common mental health disorders. While promising, these findings should be interpreted cautiously due to heterogeneity in study designs and interventions. Future research should focus on long-term outcomes, cost-effectiveness, and strategies to improve engagement in telehealth settings.
Bacteria combine polar- and dispersed-growth to power cell elongation and wall width dynamics
Authors: Zambri Matthew P. , Baglio Christine R. , Irazoki Oihane , Jones Stephanie E. , Garner Ethan C. , Cava Felipe , Elliot Marie A. 
Published: July 2024

AbstractThe cell wall is a complex structure. For most bacteria, peptidoglycan is an essential component of their cell wall, with different bacteria having evolved distinct biosynthetic strategies. The mechanisms driving bacterial growth can be divided into three, mutually-exclusive categories: (i) dispersed growth, mediated by MreB and employed by many rod-shaped bacteria; (ii) polar growth, driven by distinct proteins in the actinobacteria and rhizobiales; and (iii) septal growth, fueled by FtsZ in many coccoid bacteria. Here, we show that under conditions of rapid growth, the actinobacterial representativeStreptomyces venezuelaetranscends these categories, simultaneously employing both canonical polar growth, and MreB-mediated dispersed growth. Our results indicate that MreB is essential for cell wall integrity and culture viability under these growth conditions, promotes dynamic cell wall changes over the course of a growth cycle, and contributes to a wall that is structurally distinct from that of conventionally growing streptomycetes.
Id2 levels determine the development of effector vs. exhausted tissue-resident memory CD8+T cells during CNS chronic infection
Authors: Coulibaly Aboubacar Sidiki K. , Nozeran Lucie , Thomann Céline , Alis Marine , Bassot Emilie , Hassan Ali , Porte Rémi , Belloy Marcy , Blanchard Nicolas , Masson Frederick 
Published: July 2024

ABSTRACTTissue-resident memory T cells (Trm) are essential for regional immunity in non-lymphoid tissues. Although single-cell transcriptomics have revealed Trm heterogeneity in various diseases, the molecular mechanisms behind this diversity are unclear. To investigate this, we usedToxoplasma gondii(T. gondii) infection, which persists in the central nervous system (CNS) and is controlled by brain CD8+Trm. Our single-cell transcriptomic analysis of brain CD8+T cells fromT. gondii-infected mice showed heterogeneous expression of the transcriptional regulator Id2, correlating with different functional states. Using mixed bone marrow chimeras, we found that Id2-deficiency in T cells caused parasite-specific Trm to develop an altered phenotype with diminished effector functions and reduced expression of CD49a. Furthermore, loss of Id2 in brain-infiltrating CD8+T cells led to the accumulation of exhausted PD1+Tox+CD8+Trm cells, while Id2 overexpression repressed T cell exhaustion. Overall, our study shows that Id2 levels dictate the acquisition of effectorvs.exhausted phenotypes in CD8+Trm during chronic CNS infection.One sentence SummaryId2 expression level regulates the functional heterogeneity of brain Trm during CNS chronic infection
Rapid neutralizing assay for circulating H5N1 influenza virus in dairy cows
Authors: Miyakawa Kei , Ota Makoto , Sano Kaori , Momose Fumitaka , Okura Takashi , Kishida Noriko , Arita Tomoko , Suzuki Yasushi , Shirakura Masayuki , Asanuma Hideki , Watanabe Shinji , Ryo Akihide , Hasegawa Hideki 
Published: July 2024

AbstractA rapid and safe neutralization assay is required for emerging highly pathogenic avian influenza viruses, including the H5N1 subtype, which was recently found in cows. Herein, we report a novel neutralization assay using HiBiT-tagged virus-like particles (hiVLPs). Our hiVLP-based neutralization test demonstrated a higher quantitative value and shorter assay time than conventional methods. We used this assay to evaluate whether the neutralizing antibodies induced by the candidate vaccine virus (NIID-002) were cross-reactive with cow-derived H5N1. Our results suggest that the circulating H5N1 virus in cows shares antigenic characteristics with NIID-002, providing significant implications for the development and preparation of vaccines.
Regulatory Subfunctionalization drives OXPHOS evolution in teleosts
Authors: Tsipourlianos A , Cardoso JCR , Angelakopoulos R , Kotoula A , Power DM , Mamuris Z , Moutou KA 
Published: July 2024

AbstractOxidative phosphorylation (OXPHOS) supplies over 90% of the cellular ATP requirements through the orchestrated function of five multiprotein complexes located in the inner mitochondrial membrane. The study explores how the evolutionary constraints imposed by the indispensable function of OXPHOS guide the outcome of Whole Genome Duplication (WGD) events. Two teleosts, the gilthead seabream (Sparus aurata) and the European seabass (Dicentrarchus labrax), which have undergone three rounds of WGDs were used as models and OXPHOS gene expression was assessed during the highly plastic and energy-demanding period of early development. Fish ontogeny is a unique period in fish life marked with dramatic changes in morphology, physiology, metabolism and behavior. The tightly regulated landscape of cell divisions, migrations and differentiation driving these dramatic changes demands high energy supplies. The discovery of 24 and 22 OXPHOS gene families in gilthead seabream and European seabass genome, respectively, and the subsequent phylogenetic analysis showed in most cases divergence from a common ancestor at the base of the teleost lineage, a process attributed to teleost-specific WGD. Overall results indicate that the WGD events have resulted in early retention of OXPHOS paralogue genes and subsequent species- or lineage-specific losses. OXPHOS paralogue gene expression levels were compared following RNA sequencing within and between distinct developmental stages in gilthead seabream and European seabass. Different expression patterns between paralogs were revealed; some were in dosage balance, others were expressed only in particular stage(s) and a lot of them were differentially expressed between stages. Differences in both the number and location of SNPs were revealed between paralogs, after merging the RNA sequencing data with whole genome sequencing data. A considerable number of mutations were mapped in the UTRs and mostly synonymous substitutions were identified in the CDS. The ratio of non-synonymous to synonymous substitutions when comparing the CDS variants revealed neutral positions while others are subject to purifying selection, safeguarding protein structural integrity and/or function. Overall, regulatory subfunctionalization of OXPHOS paralogs appeared as the evolutionary mechanism behind the retention of the paralogs in gilthead seabream and European seabass genomes in favor of ontogenetic plasticity.
Charting Taxa inAmanitaSectionAmidella(Basidiomycota:Amanitaceae)
Authors: Oliveira Paulo , Arraiano-Castilho Ricardo 
Published: July 2024

AbstractSpecies determination in theAmidellaclade is notoriously difficult, because of the relative dearth of diagnostic characters and the rather common occurrence of homoplasies. This results in a substantial number of misnamed and unnamed collections, a misapprehension of the geographic range of known species, and a gross underestimation of the number of species it contains. To assess the diversity that should be considered as part ofAmidella, DNA sequences available for this group were retrieved in public nucleotide databases, using a combination of approaches to achieve a comprehensive representation. Phylogenetic analysis based on the aligned ITS sequences, consistently with the results from other molecular markers (ncLSU,RPB2,TEF1,BTUB), suggests five major clades: one containing the type speciesAmanita volvata, another forAmanita ponderosaand allies, a third one (roughly half of all species) withAmanita lepiotoides, and two others without valid species yet. At species level, around 81 clades were delimited, of which only 16–17 can be assigned a valid name, with a few more corresponding to provisional taxa listed in the amanitaceae.org website. Up to three further species without assigned sequences might correspond to the proposed clades. The current evidence suggests a rather narrow geographic range for most of these clades. This study provides a phylogeny-arranged outlook of the worldwide distribution ofAmidellaspecies, and an infrasectional framework for optimizing taxonomic sampling and designing clade-specific molecular markers to assist in identification.
Single cell data enables dissecting cell types present in bulk transcriptome data
Authors: Wruck Wasco , Adjaye James 
Published: July 2024

SummaryThe quality of organoid models can be assessed by single-cell-RNA-sequencing (scRNA-seq) but often only bulk transcriptome data is available. Here we present a pipeline for the analysis of scRNA-seq data and subsequent “deconvolution”, which is a method for estimating cell type fractions in bulk transcriptome data based on expression profiles and cell types found in scRNA-seq data derived from biopsies. We applied this pipeline on bulk iPSC-derived kidney and brain organoid transcriptome data to identify cell types employing two scRNA-seq kidney datasets and one brain dataset. Relevant cells present in kidney (eg. proximal tubules, distal convoluted tubules and podocytes) and brain (eg. neurons, astrocytes, oligodendrocytes and microglia) with obligatory endothelial and immune-related cells were identified. We anticipate that this pipeline will also enable estimation of cell type fractions in organoids of other tissues.
Central activation of catecholamine-independent lipolysis drives the end-stage catabolism of all adipose tissues
Authors: Zhang Xiao , Majumdar Anurag , Kim Clara , Kleiboeker Brian , Magee Kristann L , Learman Brian S , Thomas Steven A , Lodhi Irfan J , MacDougald Ormond A , Scheller Erica L 
Published: July 2024

AbstractSeveral adipose depots, including constitutive bone marrow adipose tissue (cBMAT), resist conventional lipolytic cues, making them metabolically non-responsive. However, under starvation, wasting, or cachexia, the body can eventually catabolize these stable adipocytes through unknown mechanisms. To study this, we developed a mouse model of brain-evoked depletion of all fat, including cBMAT, independent of food intake. Genetic, surgical, and chemical approaches demonstrated that depletion of stable fat required adipose triglyceride lipase-dependent lipolysis but was independent of local nerves, the sympathetic nervous system, and catecholamines. Instead, concurrent hypoglycemia and hypoinsulinemia activated a potent catabolic state by suppressing lipid storage and increasing catecholamine-independent lipolysis via downregulation of cell-autonomous lipolytic inhibitorsAcvr1c, G0s2, and Npr3. This was also sufficient to delipidate classical adipose depots. Overall, this work defines unique adaptations of stable adipocytes to resist lipolysis in healthy states while isolating a potentin vivoneurosystemic pathway by which the body can rapidly catabolize all adipose tissues.
Embryological insights into the evolution of genome regulation using haploid and diploid whiteflies,Bemisia tabaci
Authors: Shelby Emily A. , McKinney Elizabeth C. , Simmons Alvin M. , Moore Allen J. , Moore Patricia J. 
Published: July 2024

ABSTRACTThe whitefly,Bemisia tabaci, is a hemipteran with a haplodiploid sex determination system, which provides a natural experiment for examining genome function in haploid and diploid embryos. Yet the embryogenesis ofB. tabaciremains understudied. Our previous work has established a possible role ofDNA methyltransferase 1(Dnmt1) in genome stability. In this study we used maternal RNA interference (RNAi) and immunohistochemistry to study the complex dynamics between DNMT1 and ploidy during embryogenesis. We found that both haploid and diploidB. tabacihave a similar developmental timeline to other holometabolous insects. We also found that, like other obligatory haploid insects, ploidy does not affect developmental timing, suggesting that maternal factors play a greater role than ploidy in developmental timing. For embryos with reduced expression ofDnmt1, we found that the loss of DNMT1 disrupts blastoderm development and affects nuclei morphology in both haploid and diploid embryos. Our results suggest that DNMT1 is required for blastoderm development.
A computational model of altered neuronal activity in altered gravity
Authors: Gontier Camille , Kalinski Laura , Striebel Johannes , Sturm Maximilian , Meerholz Zoe , Schunk Sarah , Lichterfeld Yannick , Liemersdorf Christian 
Published: July 2024

AbstractElectrophysiological experiments have shown that neuronal activity changes upon exposure to altered gravity. More specifically, the firing rate increases during microgravity and decreases during centrifugal-induced hypergravity. However, the mechanism by which altered gravity impacts neuronal activity is still unknown. Different explanations have been proposed: a first hypothesis states that microgravity increases the fluidity of the cell membrane and modifies the properties of the neurons’ ion channels. Another hypothesis suggests the role of mechano-gated (MG) ion channels depolarizing the cells during microgravity exposure. Although intuitive, these models have not been backed by quantitative analyses nor simulations. Here, we developed computational models of the impact of altered gravity, both on single cell activity and on population dynamics. Firstly, in line with previous electrophysiological experiments, we suggest that microgravity could be modelled as an increase of the voltage-dependent channel transition rates, which are assumed to be the result of higher membrane fluidity and can be readily implemented into the Hodgkin-Huxley model. Using in-silico simulations of single neurons, we show that this model of the influence of gravity on neuronal activity allows to reproduce the increased firing and burst rates observed in microgravity. Secondly, we explore the role of MG ion channels on population activity. We show that recordings can be fitted by a network of connected excitatory neurons, whose activity is balanced by firing rate adaptation. Adding a small depolarizing current to account for the activation of mechano-gated channels also reproduces the observed increased firing and burst rates. Overall, our results fill an important gap in the literature, by providing a computational link between altered gravity and neuronal activity.
Cell-type-specific striatal modulation of amygdalar acetylcholine in salience assignment
Authors: Chen Aixiao , Li Yunjing , Zhu Hangfei , Gu Hanmei , Weng Yanhong , Ye Qinyong , Guan Wuqiang , Sun Qingtao , Li Bo , Xu Fuqiang , Deng Hanfei , Xiao Xiong 
Published: July 2024

ABSTRACTThe salience assignment is pivotal for both natural and artificial intelligence. Pioneering studies established that basal forebrain cholinergic neurons process behaviorally relevant salient information. However, the neural circuit mechanism underlying salience assignment remains poorly understood. Here we show that the acetylcholine (ACh) level in the basolateral amygdala (BLA) dynamically represented behavioral salience. Distinct neuronal subpopulations in the nucleus accumbens (NAc), D1- and D2-expressing medium spiny neurons (MSNs), antagonistically and specifically promote and suppress ACh release in the BLA, but not the cortex and hippocampus. These striatal D1 and D2 MSNs regulate BLA ACh by disinhibiting and inhibiting cholinergic neurons in the basal forebrain subregion substantia innominata (SI), respectively. Optogenetic manipulations of the pathway from striatal D1 and D2 MSNs to the SI opposingly affect associative learning. Our findings uncover an unconventional role of striatal MSNs in salience assignment via regulating the salience-representing amygdalar ACh activity.