bluuebunny/crossref_metadata_2025_split huggingface dataset:
MAPK signaling modulates the partition of DCP1 between P-bodies and stress granules in plant cells
Authors: He Siou-Luan , Wang Ying , Shan Libo , He Ping , Jang Jyan-Chyun 
Published: November 2024

AbstractProcessing bodies (PBs) and stress granules (SGs) are membrane-less cellular compartments consisting of ribonucleoprotein complexes. Whereas PBs are more ubiquitous, SGs are assembled mainly in response to stress. PBs and SGs are known to physically interact and molecules exchange between the two have been documented in mammals. However, the molecular mechanisms underpinning these processes are virtually unknown in plants. We have reported recently that tandem CCCH zinc finger 1 (TZF1) protein can recruit MAPK signaling components to SGs. Here we have found that TZF1-MPK3/6-MKK4/5 form a protein-protein interacting network in SGs. The mRNA decapping factor 1 (DCP1) is a core component of PBs. MAPK signaling mediated phosphorylation triggers a rapid reduction of DCP1 partition into PBs, concomitantly associated with an increase of DCP1 assembly into SGs. Furthermore, we have found that plant SG marker protein UBP1b (oligouridylate binding protein 1b) plays a role in maintaining DCP1 in PBs by suppressing the accumulation of MAPK signaling components. Together, we propose that MAPK signaling and UBP1b mediate the dynamics of PBs and SGs in plant cells.
Brain functional connectivity, but not neuroanatomy, captures the interrelationship between sex and gender in preadolescents
Authors: Metoki Athanasia , Chauvin Roselyne J. , Gordon Evan M. , Laumann Timothy O. , Kay Benjamin P. , Krimmel Samuel R. , Marek Scott , Wang Anxu , Van Andrew N. , Baden Noah J. , Suljic Vahdeta , Scheidter Kristen M. , Monk Julia , Whiting Forrest I. , Ramirez-Perez Nadeshka J. , Barch Deanna M. , Sotiras Aristeidis , Dosenbach Nico U.F. 
Published: November 2024

AbstractUnderstanding sex differences in the adolescent brain is crucial, as these differences are linked to neurological and psychiatric conditions that vary between males and females. Predicting sex from adolescent brain data may offer valuable insights into how these variations shape neurodevelopment. Recently, attention has shifted toward exploring socially-identified gender, distinct from sex assigned at birth, recognizing its additional explanatory power. This study evaluates whether resting-state functional connectivity (rsFC) or cortical thickness more effectively predicts sex and sex/gender alignment (the congruence between sex and gender) and investigates their interrelationship in preadolescents. Using data from the Adolescent Brain Cognitive Development (ABCD) Study, we employed machine learning to predict both sex (assigned at birth) and sex/gender alignment from rsFC and cortical thickness. rsFC predicted sex with significantly higher accuracy (86%) than cortical thickness (75%) and combining both did not improve the rsFC model’s accuracy. Brain regions most effective in predicting sex belonged to association (default mode, dorsal attention, and parietal memory) and visual (visual and medial visual) networks. The rsFC sex classifier trained on sex/gender aligned youth was significantly more effective in classifying unseen youth with sex/gender alignment than in classifying unseen youth with sex/gender unalignment. In females, the degree to which their brains’ rsFC matched a sex profile (female or male), was positively associated with the degree of sex/gender alignment. Lastly, neither rsFC nor cortical thickness predicted sex/gender alignment. These findings highlight rsFC’s predictive power in capturing the relationship between sex and gender and the complexity of the interplay between sex, gender, and the brain’s functional connectivity and neuroanatomy.
Bias-accounting meta-analyses overcome cerebellar neglect to refine the cerebellar behavioral topography
Authors: Magielse Neville , Manoli Aikaterina , Eickhoff Simon B. , Fox Peter T. , Saberi Amin , Valk Sofie L. 
Published: November 2024

AbstractThe cerebellum plays important roles in motor, cognitive, and emotional behaviors. Previous cerebellar coordinate-based meta-analyses and mappings have attributed different behaviors to cerebellar subareas, but an accurate behavioral topography is lacking. Here, we show overrepresentation of superior activation foci, which may be exacerbated by historical cerebellar neglect. Unequal foci distributions render the null hypothesis of standard activation likelihood estimation unsuitable. Our new method, cerebellum-specific activation-likelihood estimation (C-SALE), finds behavioral convergence beyond baseline activation rates. It does this by testing experimental foci versus null models sampled from a data-driven, biased probability distribution of finding foci at any cerebellar location. Cerebellar mappings were made across five BrainMap task domains and thirty-five subdomains, illustrating improved specificity of the new method. Twelve of forty (sub)domains reached convergence in specific cerebellar subregions, supporting dual motor representations and placing cognition in posterior-lateral regions. Repeated subsampling revealed that whereas action, language and working memory were relatively stable, other behaviors produced unstable meta-analytic maps. Lastly, meta-analytic connectivity modeling in the same debiased framework was used to reveal coactivation networks of cerebellar behavioral clusters. In sum, we created a new method for cerebellar meta-analysis that accounts for data biases and can be flexibly adapted to any part of the brain. Our findings provide a refined understanding of cerebellar involvement in human behaviors, highlighting regions for future investigation in both basic and clinical applications.
Speech in noise performance in adults with cochlear implants using a combined channel deactivation strategy with a variable number of dynamic focused channels
Authors: Wohlbauer Dietmar M. , Hem Charles , McCallick Caylin , Arenberg Julie G. 
Published: November 2024

AbstractObjectives and MethodsCochlear implant listeners show difficulties in understanding speech in noise. Channel interactions from activating overlapping neural populations reduce the signal accuracy necessary to interpret complex signals. Optimizing programming strategies based on focused detection thresholds to reduce channel interactions has led to improved performance. In the current study, two previously suggested methods, channel deactivation and focused dynamic tripolar stimulation, were combined to create three cochlear implant programs. Utilizing an au-tomatic channel selection algorithm from focused detection threshold profiles, three programs were created with the same deactivated channels but varying proportions of channels employing focused stimulation, monopolar, dynamic focused and a mixed program. Thirteen ears in eleven adult cochlear implant listeners with Advanced Bionics HiRes90k devices were tested. Vowel identification and sentence perception in quiet and noise served as outcome measures, and the influences of listening experience, age, clinical consonant-nucleus-consonant performance, and perceptual thresholds on speech performance were assessed.ResultsAcross subjects, different degrees of focusing showed individual performance improvements for vowels and sentences over the monopolar program. However, only slight trends and no significant group improvements were observed. Focused listening benefits were shown for individuals with less cochlear implant experience, and clinically poor performers seem to benefit more from focusing than good per-formers.ConclusionThe current findings suggest that deactivating and focusing subsets of channels improves speech performance for some individuals, especially poor performers, a possi-ble effect of reduced channel interactions. The findings also show that individual performance is largely variable, possibly due to listening experience, age or the underlying detection threshold.
Fitness trade-off and the discovery of a novel missense mutation in the PmrB sensor kinase of a colistin-resistantPseudomonas aeruginosastrain developed by adaptive laboratory evolution
Authors: Padhy Indira , Dwibedy Sambit K. , Mohapatra Saswat S. 
Published: November 2024

AbstractPseudomonas aeruginosais a prominent bacterial pathogen that causes several nosocomial infections and is notorious for its environmental resilience and rapid development of resistance to frontline antibiotics. A major cause of mortality and morbidity among cystic fibrosis patients, multidrug-resistantP. aeruginosais often targeted with the antibiotic colistin as a last option. However, increasing reports of colistin resistance amongP. aeruginosais a matter of significant concern. Though the molecular mechanisms responsible for the development of colistin resistance are well known, the evolutionary trajectory to colistin resistance is an important area of investigation. In this work, using the adaptive laboratory evolution (ALE) approach we have evolved a colistin-sensitiveP. aeruginosaancestral strain to a resistant one. During the process of laboratory evolution in 106 generations, colistin MIC was increased 32-fold. The evolved strain had lower fitness than the ancestral strain as evidenced by a lower growth rate and higher doubling time. Moreover, the evolved strain produced more biofilm and less pyocyanin. Interestingly, the evolved strain showed collateral sensitivity to several antibiotics such as co-trimoxazole, rifampicin, kanamycin, tigecycline, penicillin, ampicillin, and teicoplanin. On analysing various TCS modules involved in the development of colistin resistance a novel missense mutation (V136G) was detected in the PmrB sensor kinase. Bioinformatics prediction indicated that the mutation could be deleterious, though the functionality of the PmrB mutant remains to be validated experimentally.
Early life adversity increases risk for chronic posttraumatic pain, data from humans and rodents
Authors: McKibben Lauren A. , Woolard Alice , McLean Samuel A. , Zhao Ying , Verma Taanvii , Mickelson Jacqueline , Lu Hongxia , Lobo Jarred , House Stacey L. , Beaudoin Francesca L. , An Xinming , Stevens Jennifer S. , Neylan Thomas C. , Jovanovic Tanja , Germine Laura T. , Rauch Scott L. , Haran John P. , Storrow Alan B. , Lewandowski Christopher , Hendry Phyllis L. , Sheikh Sophia , Jones Christopher W. , Punches Brittany E. , Hudak Lauren A. , Pascual Jose L. , Seamon Mark J. , Pearson Claire , Peak David A. , Merchant Roland C. , Domeier Robert M. , Rathlev Niels K. , O’Neil Brian J. , Sanchez Leon D. , Bruce Steven E. , Sheridan John F. , Kessler Ronald C. , Koenen Karestan C. , Ressler Kerry J. , Linnstaedt Sarah D. 
Published: November 2024

ABSTRACTTraumatic stress exposures (TSE) are common in life. While most individuals recover following a TSE, a substantial subset develop adverse posttraumatic neuropsychiatric sequelae such as chronic posttraumatic musculoskeletal pain (CPMP). Vulnerability factors for CPMP are poorly understood, which hinders identification of high-risk individuals for targeted interventions. One known vulnerability factor for many pain types is exposure to early life adversity (ELA), but few studies have assessed whether ELA increases risk for CPMP. This study used data from the AURORA study, a prospective human cohort study of TSE survivors, to test the hypothesis that ELA increases risk for CPMP. In addition, in secondary analyses, we assessed which subtypes of ELA (including childhood bullying) were most predictive of CPMP and whether a rat ELA model consisting of neonatal limited bedding (NLB), combined with single prolonged stress (SPS) in adulthood, would accurately model human findings. In AURORA study participants (n=2,480), using multinomial logistic regression modeling of four identified latent pain classes, we found that ELA increased vulnerability to the high unremitting pain class (OR=1.047,p<0.001), the moderate pain class (OR=1.031,p<0.001), and the moderate recovery pain class (OR=1.018,p=0.004), with physical abuse, emotional abuse, and bullying being the strongest predictors of high pain class assignment. Similarly, in male and female Sprague Dawley rats, in comparison to SPS alone NLB combined with SPS caused increased baseline sensitivity and prolonged mechanical hypersensitivity (F(11,197)=3.22,p<0.001). Further studies in animals and humans are needed to understand mechanisms by which ELA confers vulnerability to CPMP.SummaryIn humans and rats, early life adversity is associated with a greater duration of musculoskeletal pain and mechanical hypersensitivity following traumatic stress exposures during adulthood.
Does frequency or diversity of leisure activity matter more for epigenetic ageing? Analyses of arts engagement and physical activity in the UK Household Longitudinal Study
Authors: Fancourt Daisy , Masebo Lehané , Finn Saoirse , Mak Hei Wan , Bu Feifei 
Published: November 2024

AbstractOver the past decade, ageing clocks have become widely adopted as important tools for understanding biological ageing and have been redefining notions of “pro-longevity” lifestyles. However, this work is still at an early stage. Some leisure activities, such as arts and cultural engagement (ACEng) have never been studied at all, while others such as physical activity (PA) have only received scant attention. In particular, there is little understanding of whether frequency of engagement or diversity (which provides access to more active ingredients) is more important. This study used 3,354 adults in the UK Household Longitudinal Study - a large, nationally-representative cohort study, which includes six derived epigenetic clocks. We used a doubly robust estimation using the inverse-probability-weighted regression adjustment estimator adjusted for demographic, socioeconomic, behavioural and health covariates, data collection gaps and technical covariates of epigenetic clocks. ACEng and PA were related to slower biological ageing in the PhenoAge and DunedinPoAm clocks, although not to the other measured clocks, with comparable effect sizes between ACEng and PA (Lin, Horvath2018, Horvath2013 and Hannum). For ACEng, diversity and frequency of engagement were related to DunedinPoAm, while for PhenoAge, there was a slightly clearer relationship for frequency than diversity. For PA, higher levels of frequency, diversity, and activeness were related to DunedinPoAm, while only the highest diversity and activeness were related to PhenoAge. These findings were all stronger amongst middle-aged and older adults. This was the first study to show a relationship between ACEng and epigenetic ageing, with comparable effect sizes to PA, suggesting the value of its exploration alongside other lifestyle factors. Decelerations in ageing clocks, including those within our study, have been demonstrated to have clinical (as well as statistical) importance, supporting future exploration as to whether lifestyle changes have any value to slowing or potentially reversing epigenetic ageing.
Positive and negative affect, related mental health traits, and cognitive performance: shared genetic architecture and potential causality
Authors: Slaney Chloe , Mac Giollabhui Naoise , van der Most Peter J. , Palacios Ensor R. , Snieder Harold , Nivard Michel , Hemani Gibran , Hartman Catharina A. , Khandaker Golam M. 
Published: November 2024

AbstractAltered affect and cognitive dysfunction are transdiagnostic, burdensome, and pervasive features of many psychiatric conditions which remain poorly understood and have few efficacious treatments. Research on the genetic architecture of these phenotypes and causal relationships between them may provide insight into their aetiology and comorbidity. Using data from the Lifelines Cohort Study, we conducted genome-wide association studies (GWAS) on positive and negative affect and four cognitive domains (working memory, reaction time, visual learning and memory, executive function). Using publicly available large GWAS on related - albeit distinct-phenotypes (depression, anxiety, wellbeing, general cognitive ability [GCA]) we conducted genetic correlation and Mendelian randomization (MR) analyses to examine genetic overlap and causal relationships. We identified one genome-wide hit (p<5×10-8) for reaction time, and many loci with suggestive associations (p<5×10-6; N range= 11-20 independent hits) for other phenotypes. For most phenotypes, gene mapping and tissue expression analysis of suggestive hits from the GWAS showed increased gene expression in brain tissue compared to other tissues. As predicted, negative affect is genetically correlated with mental health phenotypes (depressionrg=0.51; anxietyrg=0.70; wellbeingrg= −0.71) and cognitive domains are genetically correlated with GCA and brain volume (rg≤ 0.66). Genetic correlations between negative and positive affect suggest that they are dissociable constructs (rg= −0.18) with negative affect having higher genetic overlap with GCA than positive affect (rg=-0.19 vs −0.06). This could indicate that negative affect has a higher shared neural basis with GCA than positive affect and/or GCA and negative affect may exhibit causal relationships. MR analyses suggest potential causal effects of higher GCA on reduced negative affect, reduced risk of depression and anxiety, and higher wellbeing, but little impact on positive affect. We also report evidence for potential causal effects of depression and lower wellbeing on reduced GCA. Taken together, these results suggests that GCA may be a valid target for negative affect (but not positive affect) and depression and wellbeing may be valid targets for GCA.
Interplay between polygenic effects and polypharmacy on dementia: An investigation in an elderly Scottish cohort
Authors: Raptis Vasilis , Mullin Donncha , Syed Sumbul , Deary Ian J , Cox Simon R , Russ Tom C , Luciano Michelle 
Published: November 2024

ABSTRACTINTRODUCTIONPolygenic Risk Scores for Alzheimer dementia (AD-PRS), a measure of aggregate AD genetic risk and polypharmacy have been associated with dementia. Here, we test their interaction’s association with future dementia among older adults without baseline neurodegenerative diagnoses.METHODSUsing Cox proportional hazards and mortality-adjusted competing risk regression models we analysed up to 17.5 years all-cause incident dementia in the Lothian Birth Cohort 1936 (n=759, 105 dementia patients). We used polypharmacy (total or nervous-system-acting medications count), AD-PRS, and their interaction as main predictors.RESULTSA non-significant interaction was found between AD-PRS and total polypharmacy (HR=1.06; p=0.15) or nervous-system-acting polypharmacy (HR=0.98; p=0.86) in shaping dementia risk. Omitting interaction, mortality-adjusted models showed significant AD-PRS prediction of dementia (HR ∼1.40; p<0.001), non-significant total (HR=1.03; p=0.49), and nervous-system-acting polypharmacy effects (HR=1.27; p=0.069).DISCUSSIONElucidating the complex interplay between polypharmacy and genetics could improve management of inappropriate medication in older adults genetically prone to dementia/AD.
Nanophysiology Approach Reveals Diversity in Calcium Microdomains across Zebrafish Retinal Bipolar Ribbon Synapses
Authors: Rameshkumar Nirujan , Shrestha Abhishek P , Boff Johane M. , Hoon Mrinalini , Matveev Victor , Zenisek David , Vaithianathan Thirumalini 
Published: November 2024

AbstractRapid and high local calcium (Ca2+) signals are essential for triggering neurotransmitter release from presynaptic terminals. In specialized bipolar ribbon synapses of the retina, these local Ca2+signals control multiple processes, including the priming, docking, and translocation of vesicles on the ribbon before exocytosis, endocytosis, and the replenishment of release-ready vesicles to the fusion sites for sustained neurotransmission. However, our knowledge about Ca2+signals along the axis of the ribbon active zone is limited. Here, we used fast confocal quantitative dual-color ratiometric line-scan imaging of a fluorescently labeled ribbon binding peptide and Ca2+indicators to monitor the spatial and temporal aspects of Ca2+transients of individual ribbon active zones in zebrafish retinal rod bipolar cells (RBCs). We observed that a Ca2+transient elicited a much greater fluorescence amplitude when the Ca2+indicator was conjugated to a ribeye-binding peptide than when using a soluble Ca2+indicator, and the estimated Ca2+levels at the ribbon active zone exceeded 26 μM in response to a 10-millisecond stimulus, as measured by a ribbon-bound low-affinity Ca2+indicator. Our quantitative modeling of Ca2+diffusion and buffering is consistent with this estimate and provides a detailed view of the spatiotemporal [Ca2+] dynamics near the ribbon. Importantly, our data demonstrates that the local Ca2+levels may vary between ribbons of different RBCs and within the same cells. The variation in local Ca2+signals is correlated to ribbon size, which in turn correlates with active zone extent, as serial electron microscopy provides new information about the heterogeneity in ribbon size, shape, and area of the ribbon in contact with the plasma membrane.
Single-cell profiling of trabecular meshwork identifies mitochondrial dysfunction in a glaucoma model that is protected by vitamin B3 treatment
Authors: Tolman Nicholas , Li Taibo , Balasubramanian Revathi , Li Guorong , Bupp-Chickering Violet , Kelly Ruth A. , Simón Marina , Peregrin John , Montgomery Christa , Stamer W. Daniel , Qian Jiang , John Simon W.M. 
Published: November 2024

AbstractSince the trabecular meshwork (TM) is central to intraocular pressure (IOP) regulation and glaucoma, a deeper understanding of its genomic landscape is needed. We present a multimodal, single-cell resolution analysis of mouse limbal cells (includes TM). In total, we sequenced 9,394 wild-type TM cell transcriptomes. We discovered three TM cell subtypes with characteristic signature genes validated by immunofluorescence on tissue sections and whole-mounts. The subtypes are robust, being detected in datasets for two diverse mouse strains and in independent data from two institutions. Results show compartmentalized enrichment of critical pathways in specific TM cell subtypes. Distinctive signatures include increased expression of genes responsible for 1) extracellular matrix structure and metabolism (TM1 subtype), 2) secreted ligand signaling to support Schlemm’s canal cells (TM2), and 3) contractile and mitochondrial/metabolic activity (TM3). ATAC-sequencing data identified active transcription factors in TM cells, including LMX1B. Mutations inLMX1Bcause high IOP and glaucoma. LMX1B is emerging as a key transcription factor for normal mitochondrial function and its expression is much higher in TM3 cells than other limbal cells. To understand the role of LMX1B in TM function and glaucoma, we single-cell sequenced limbal cells fromLmx1bV265D/+mutant mice. InV265D/+mice, TM3 cells were uniquely affected by pronounced mitochondrial pathway changes. This supports a primary role of mitochondrial dysfunction within TM3 cells in initiating the IOP elevation that causes glaucoma in these mice. Importantly, treatment with vitamin B3(nicotinamide), to enhance mitochondrial function and metabolic resilience, significantly protectedLmx1bmutant mice from IOP elevation.