bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Massively Parallel Screen of 5′UTR Mutations Identifies Variants Impacting Translation and Protein Production in Neurodevelopmental Disorder Genes
Authors: Plassmeyer Stephen P. , Florian Colin P. , Kasper Michael J. , Chase Rebecca , Mueller Shayna , Liu Yating , White Kelli McFarland , Jungers Courtney F. , Djuranovic Slavica Pavlovic , Djuranovic Sergej , Dougherty Joseph D. 
Published: November 2023

AbstractDe novomutations cause a variety of neurodevelopmental disorders including autism. Recent whole genome sequencing from individuals with autism has shown that manyde novomutations also occur in untranslated regions (UTRs) of genes, but it is difficult to predict from sequence alone which mutations are functional, let alone causal. Therefore, we developed a high throughput assay to screen the transcriptional and translational effects of 997 variants from 5′UTR patient mutations. This assay successfully enriched for elements that alter reporter translation, identifying over 100 potentially functional mutations from probands. Studies in patient-derived cell lines further confirmed that these mutations can alter protein production in individuals with autism, and some variants fall in genes known to cause syndromic forms of autism, suggesting a diagnosis for these individual patients. Since UTR function varies by cell type, we further optimized this high throughput assay to enable assessment of mutations in neuronsin vivo. First, comparingin cellulotoin vivoresults, we demonstrate neurons have different principles of regulation by 5′UTRs, consistent with a more robust mechanism for reducing the impact of RNA secondary structure. Finally, we discovered patient mutations specifically altering the translational activity of additional known syndromic genesLRRC4andZNF644in neurons of the brain. Overall our results highlight a new approach for assessing the impact of 5′UTR mutations across cell types and suggest that some cases of neurodevelopmental disorder may be caused by such variants.
Strong Effect of Demographic Changes on Tuberculosis Susceptibility in South Africa
Authors: Oyageshio Oshiomah P. , Myrick Justin W. , Saayman Jamie , van der Westhuizen Lena , Al-Hindi Dana , Reynolds Austin W. , Zaitlen Noah , Uren Caitlin , Möller Marlo , Henn Brenna M. 
Published: November 2023

AbstractSouth Africa is among the world’s top eight TB burden countries, and despite a focus on HIV-TB co-infection, most of the population living with TB are not HIV co-infected. The disease is endemic across the country with 80-90% exposure by adulthood. We investigated epidemiological risk factors for tuberculosis (TB) in the Northern Cape Province, South Africa: an understudied TB endemic region with extreme TB incidence (645/100,000) and the lowest provincial population density. We leveraged the population’s high TB incidence and community transmission to design a case-control study with population-based controls, reflecting similar mechanisms of exposure between the groups. We recruited 1,126 participants with suspected TB from 12 community health clinics, and generated a cohort of 878 individuals (cases =374, controls =504) after implementing our enrollment criteria. All participants were GeneXpert Ultra tested for active TB by a local clinic. We assessed important risk factors for active TB using logistic regression and random forest modeling. Additionally, a subset of individuals were genotyped to determine genome-wide ancestry components. Male gender had the strongest effect on TB risk (OR: 2.87 [95% CI: 2.1-3.8]); smoking and alcohol consumption did not significantly increase TB risk. We identified two interactions: age by socioeconomic status (SES) and birthplace by residence locality on TB risk (OR = 3.05, p = 0.016) – where rural birthplace but town residence was the highest risk category. Finally, participants had a majority Khoe-San ancestry, typically greater than 50%. Epidemiological risk factors for this cohort differ from other global populations. The significant interaction effects reflect rapid changes in SES and mobility over recent generations and strongly impact TB risk in the Northern Cape of South Africa. Our models show that such risk factors combined explain 16% of the variance (r2) in case/control status.
Multicellular growth as a dynamic network of cells
Authors: Nanda Piyush , Barrere Julien , LaBar Thomas , Murray Andrew W. 
Published: November 2023

SummaryCell division without cell separation produces multicellular clusters in budding yeast. Two fundamental characteristics of these clusters are their size (the number of cells per cluster) and cellular composition: the fractions of cells with different phenotypes. However, we do not understand how different cellular features quantitatively influence these two phenotypes. Using cells as nodes and links between mother and daughter cells as edges, we model cluster growth and breakage by varying three parameters: the cell division rate, the rate at which intercellular connections break, and the kissing number (the maximum number of connections to one cell). We find that the kissing number sets the maximum possible cluster size. Below this limit, the ratio of the cell division rate to the connection breaking rate determines the cluster size. If links have a constant probability of breaking per unit time, the probability that a link survives decreases exponentially with its age. Modeling this behavior recapitulates experimental data. We then use this framework to examine synthetic, differentiating clusters with two cell types, faster-growing germ cells and their somatic derivatives. The fraction of clusters that contain both cell types increases as either of two parameters increase: the kissing number and difference between the growth rate of germ and somatic cells. In a population of clusters, the variation in cellular composition is inversely correlated (r2=0.87) with the average fraction of somatic cells in clusters. Our results show how a small number of cellular features can control the phenotypes of multicellular clusters that were potentially the ancestors of more complex forms of multicellular development, organization, and reproduction.
A diet-dependent host metabolite shapes the gut microbiota to protect from autoimmunity
Authors: Alexander Margaret , Upadhyay Vaibhav , Rock Rachel , Ramirez Lorenzo , Trepka Kai , Puchalska Patrycja , Orellana Diego , Ang Qi Yan , Whitty Caroline , Turnbaugh Jessie A. , Tian Yuan , Dumlao Darren , Nayak Renuka , Patterson Andrew , Newman John C. , Crawford Peter A. , Turnbaugh Peter J. 
Published: November 2023

SUMMARYDiet can protect from autoimmune disease; however, whether diet acts via the host and/or microbiome remains unclear. Here, we use a ketogenic diet (KD) as a model to dissect these complex interactions. A KD rescued the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis in a microbiota-dependent fashion. Dietary supplementation with a single KD-dependent host metabolite (β-hydroxybutyrate, βHB) rescued EAE whereas transgenic mice unable to produce βHB in the intestine developed more severe disease. Transplantation of the βHB-shaped gut microbiota was protective.Lactobacillussequence variants were associated with decreased T helper 17 (Th17) cell activationin vitro. Finally, we isolated aL. murinusstrain that protected from EAE, which was phenocopied by theLactobacillusmetabolite indole lactic acid. Thus, diet alters the immunomodulatory potential of the gut microbiota by shifting host metabolism, emphasizing the utility of taking a more integrative approach to study diet-host-microbiome interactions.
Sex and Education Modify the Association Between Subjective Cognitive Decline and Amyloid Pathology
Authors: Bolton Corey J. , Khan Omair A. , Liu Dandan , Wilhoite Sydney , Dumitrescu Logan , Peterson Amalia , Blennow Kaj , Zetterberg Henrik , Hohman Timothy J. , Jefferson Angela L. , Gifford Katherine A. 
Published: November 2023

AbstractBackgroundSubjective cognitive decline (SCD) may be an early risk factor for dementia, particularly in highly educated individuals and women. This study examined the effect of education and sex on the association between SCD and Alzheimer’s disease (AD) biomarkers in non-demented older adults.MethodVanderbilt Memory and Aging Project participants free of clinical dementia or stroke (n=156, 72±6 years, 37% mild cognitive impairment, 33% female) completed fasting lumbar puncture, SCD assessment, and Wide Range Achievement Test-III Reading subtest to assess reading level at baseline as a a proxy for educational quality. Cerebrospinal fluid (CSF) biomarkers for AD (β-amyloid42(Aβ42), Aβ42/40 ratio, phosphorylated tau (p-tau), tau, and neurofilament light (NfL)) were analyzed in batch. Linear mixed effects models related SCD to CSF AD biomarkers and follow-up models assessedSCD x sex, SCD x reading level, andSCD x educationinteractions on AD biomarkers.ResultIn main effect models, higher SCD was associated with lower Aβ42 and Aβ42/40 ratio (p-values<0.004). SCD was not associated with tau, p-tau, or NfL levels (p-values>0.38). SCD score interacted with sex on Aβ42/40 ratio (p=0.03) but no other biomarkers (p-values>0.10). In stratified models, higher SCD was associated with lower Aβ42/40 ratio in men (p=0.0003) but not in women (p=0.48). SCD score interacted with education on Aβ42 (p=0.005) and Aβ42/40 ratio (p=0.001) such that higher education was associated with a stronger negative association between SCD and amyloid levels. NoSCD score x reading levelinteraction was found (p-values> 0.51) though significant associations between SCD and amyloid markers were seen in the higher reading level group (p-values<0.004) but not the lower reading level group (p-values>0.12) when stratified by a median split in reading level.ConclusionAmong community-dwelling older adults free of clinical dementia, higher SCD was associated with greater cerebral amyloid accumulation, one of the earliest pathological AD changes. SCD appears most useful in detecting early AD-related brain changes in men and individuals with higher quantity and quality of education. SCD was not associated with CSF markers of tau pathology or neurodegeneration. These findings suggest that considering sex and education is important when assessing SCD in older adults.
Prognostic Implications of Changes in Total Physiological Atherosclerotic Burden in Patients With Coronary Artery Disease –A Serial Quantitative Flow Ratio Study
Authors: Chu Jiapeng , Yuan Deqiang , Lai Yan , Ye Wen , Liu Lei , Lin Hao , Ping Fan , Zhu Guoqi , Chen Fei , Yao Yian , Yan Wenwen , Liu Xuebo 
Published: November 2023

AbstractThe association between coronary physiological progression and clinical outcomes has not been investigated. A total of 421 patients who underwent serial coronary angiography at least 6 months apart were included. Total physiological atherosclerotic burden was characterized by sum of quantitative flow ratio in 3 epicardial vessels (3V-QFR). The relationships of the 3V-QFR and its longitudinal change (Δ3V-QFR) with major adverse cardiovascular events (MACE) were explored. 3V-QFR values derived from follow-up angiograms were slightly lower compared to baseline (2.85 [2.77, 2.90] vs. 2.86 [2.80, 2.90],p< 0.001). The median Δ3V-QFR value was −0.01 (−0.05, 0.02). The multivariable models demonstrated follow-up 3V-QFR or Δ3V-QFR were independently associated with MACE (bothp< 0.05). Patients with both low follow-up 3V-QFR (≤ 2.78) and low Δ3V-QFR (≤ −0.05) presented 3 times higher risk of MACE than those without (hazard ratio: 2.953, 95% confidence interval 1.428-6.104,p= 0.003). Furthermore, adding patient-level 3V-QFR and Δ3V-QFR to clinical model significantly improved the predictability for MACE. In conclusion, total physiological atherosclerotic burden and its progression can provide incremental prognostic value over clinical characteristics, supporting the use of coronary physiology in the evaluation of disease progression and for the identification of vulnerable patients.
Reprogramming early cortical astroglia into neurons with hallmarks of fast-spiking parvalbumin-positive interneurons by phospho-site deficient Ascl1
Authors: Marichal Nicolás , Péron Sophie , Beltran Arranz Ana , Galante Chiara , Scarante Franciele Franco , Wiffen Rebecca , Schuurmans Carol , Karow Marisa , Gascón Sergio , Berninger Benedikt 
Published: November 2023

AbstractCellular reprogramming of mammalian glia to an induced neuronal fate holds potential for restoring diseased brain circuits. While the proneural factor Ascl1 is widely used for neuronal reprogramming, in the early postnatal mouse cortex Ascl1 fails to induce glia-to-neuron conversion, instead promoting proliferation of oligodendrocyte progenitor cells (OPC). Since Ascl1 activity is post-translationally regulated, here we investigated the consequences of mutating six serine phospho-acceptor sites to alanine (Ascl1SA6) on lineage reprogrammingin vivo. Ascl1SA6 exhibited increased neurogenic activity in glia of the early postnatal mouse cortex, an effect enhanced by co-expression of Bcl2. Genetic fate-mapping revealed that most induced neurons originated from astrocytes while only a few derived from OPCs. Intriguingly, many Ascl1SA6/Bcl2-induced neurons expressed parvalbumin and were capable of high-frequency action potential firing. Our study demonstrates authentic conversion of astroglia into neurons featuring subclass hallmarks of cortical interneurons, advancing our scope of engineering neuronal fates in the brain.
Decellularized Banana Leaves: Eco-Friendly Scaffolds for Cell-Based Seafood
Authors: Sarkarat Reyhaneh , Banavar Amiti , Amirvaresi Arian , Li Xinxin , Nguyen Cuong , Kaplan David L. , Nitin Nitin , Ovissipour Reza 
Published: November 2023

AbstractCellular agriculture, as an emerging food production system, holds potential to address sustainability, food security, and agricultural resilience. Within the cell-based meat supply chain, one of the key steps is scaffolding. In this study, we assessed decellularized banana leaves, various coating materials, and different cell seeding strategies to determine their effects on cell viability, cell growth, cell alignment, and the response of the materials to thermal processing. The efficiency of decellularization was verified through DNA quantification, which decreased from 445 ng/mg in fresh banana leaves to non-detectable levels in the decellularized samples. This was further confirmed by FTIR and PCA modeling. Cell viability exceeded 98% on uncoated, soy-coated, and gelatin-coated samples of the decellularized banana leaves. Alignment of cells on gelatin-coated samples was the highest among the samples, with a dominant orientation of 65.8°, compared to soy-coated and uncoated samples with dominant orientations of 9.2° and −6.3°, respectively. In terms of quality attributes, the kinetics of shrinkage indicated that coating with soy and the presence of cells increased the activation energy due to the higher energy required for protein denaturation. Moreover, the kinetics of area changes in plain scaffolds without cells followed a first-order pattern, while with seeded cells a second-order pattern was followed. In summary, decellularized banana leaves present a sustainable and suitable biomaterial to support cells towards future needs related to meat production.
Robust dense‐field based copy‐move forgery localization using generic radial harmonic Fourier moment invariants
Authors: Atallah Asmaa M. , Mahmoud Imbaby I. , Ali Hanaa S. 
Published: November 2023

AbstractAs the importance of reliable multimedia content increases in today's society, image forensics is a growing field of research. The act of copying and pasting specific parts of an image, known as copy‐move forgery, may be utilized for illegal or unethical purposes. Just as with other vision‐related technologies, the accuracy of forensic analysis depends on having an appropriate image representation. Most existing feature extraction techniques do not accurately reflect the underlying image content leading to reduced performance. In this article, to detect the copy‐move forgery attack, the Generic Radial Harmonic Fourier Moment (GRHFM) is proposed for reliable and distinctive image representation. The algorithm has the ability to effectively manipulate the distribution of zeros to emphasize certain image regions. Additionally, the relationships between complex exponentials and trigonometric functions are exploited to efficiently compute and easily implement the transform kernels. The efficacy of the algorithm is illustrated through experiments on dense‐domain‐based matching patterns. Experimental results on five benchmarking databases prove the effectiveness of the proposed approach compared with the state‐of‐the‐art methods. According to the average scores, the proposed method demonstrates superior accuracy in overall localization performance. The F1 score, precision, and recall percentage values obtained are 92.5, 95.44, and 91.96, respectively. Robustness experiments on more challenging attacks are also conducted on FAU dataset. Results show that the proposed framework satisfies invariance to the various image variations, and thus an enhanced robustness compared to the previous methods. Moreover, the advantage of reasonable computational cost implies its potential use in real‐world forensic applications.
Synaptotagmin‐11 regulates immune functions of microglia in vivo
Authors: Zhang Feifan , Yang Dong , Li Jingchen , Du Cuilian , Sun Xinran , Li Wanru , Liu Fengwei , Yang Yiwei , Li Yuhong , Fu Lei , Li Rena , Zhang Claire Xi 
Published: November 2023

AbstractMembrane trafficking pathways mediate key microglial activities such as cell migration, cytokine secretion, and phagocytosis. However, the underlying molecular mechanism remains poorly understood. Previously, we found that synaptotagmin‐11 (Syt11), a non‐Ca2+‐binding Syt associated with Parkinson's disease (PD) and schizophrenia, inhibits cytokine release and phagocytosis in primary microglia. Here we reported the in vivo function of Syt11 in microglial immune responses using an inducible microglia‐specific Syt11‐conditional‐knockout (cKO) mouse strain. Syt11‐cKO resulted in activation of microglia and elevated mRNA levels of IL‐6, TNF‐α, IL‐1β, and iNOS in various brain regions under both resting state and LPS‐induced acute inflammation state in adult mice. In a PD mouse model generated by microinjection of preformed α‐synuclein fibrils into the striatum, a reduced number of microglia migrated toward the injection sites and an enhanced phagocytosis of α‐synuclein fibrils by microglia were found in Syt11‐cKO mice. To understand the molecular mechanism of Syt11 function, we identified its direct binding proteins vps10p‐tail‐interactor‐1a (vti1a) and vti1b. The linker domain of Syt11 interacted with both proteins and a peptide derived from it competitively inhibited the interaction of Syt11 with vti1a/vti1b in vitro and in cells. Importantly, application of this peptide induced more cytokine secretion in wild‐type microglia upon LPS treatment, phenocopying defects in Syt11 knockdown cells. Altogether, we propose that Syt11 inhibits microglial activation in vivo and regulates cytokine secretion through interactions with vti1a and vti1b.
How accurate are self‐evaluations of singing ability?
Authors: Yeom Daniel , Stead Kendall S. , Tan Yi Ting , McPherson Gary E. , Wilson Sarah J. 
Published: November 2023

AbstractResearch has shown that people inaccurately assess their own abilities on self‐report measures, including academic, athletic, and music ability. Evidence suggests this is also true for singing, with individuals either overestimating or underestimating their level of singing competency. In this paper, we present the Melbourne Singing Tool Questionnaire (MST‐Q), a brief 16‐item measure exploring people's self‐perceptions of singing ability and engagement with singing. Using a large sample of Australian twins (n = 996), we identified three latent factors underlying MST‐Q items and examined whether these factors were related to an objective phenotypic measure of singing ability. The three factors were identified as Personal Engagement, Social Engagement, and Self‐Evaluation. All factors were positively associated with objective singing performance, with the Self‐Evaluation factor yielding the strongest correlation (r = 0.66). Both the Self‐Evaluation factor and a single self‐report item of singing ability shared the same predictive strength. Contrary to expectations, our findings suggest that self‐evaluation strongly predicts singing ability, and this self‐evaluation is of higher predictive value than self‐reported engagement with music and singing.
Guide to the cultural geology of Youngstown, Ohio, USA
Authors: Hannibal Joseph T. , Petras Brigitte , Holstein Ann L. , McLean Colleen E. 
Published: November 2023

ABSTRACT
The city of Youngstown, the county seat of Mahoning County, is situated along the Mahoning River in northeastern Ohio, USA. Its early industrial growth was due to the ready availability of iron ore, limestone, abundant forests, and coal, all used for production of iron and then steel during the last two centuries. Local Massillon sandstone and Vanport limestone from Ohio and western Pennsylvania were used to construct mansions and other structures in the nineteenth century. By the early 1900s, other stones including Berea sandstone from Ohio, and sedimentary, metamorphic, and intrusive igneous stones quarried at other sites in North America and Europe, were being utilized as dimension stone in Youngstown. This guide briefly reviews the geological and cultural setting of Youngstown, and describes the building, decorative, and monumental stones used for a variety of structures in downtown Youngstown, with emphasis on stone used for the exterior and interior of major structures. Sites include the Butler Institute of American Art, which is clad with marble and incorporates an assortment of other stone inside and outside of the complex, and St. Columba Cathedral, whose limestone is known commercially as Mankato (Kasota) stone and is full of fossil burrows, as well as a sampling of stones used in beautiful Oak Hill Cemetery.
Some cosmological consequences of higher dimensional Klein–Gordon–Rastall theory
Authors: Widianto Tegar Ari , Falah Ahmad Khoirul , Suroso Agus , Alatas Husin , Gunara Bobby Eka 
Published: November 2023

AbstractUsing dynamical system analysis, we investigate some cosmological consequences of Rastall gravity coupled to a scalar field (called the Klein–Gordon–Rastall theory) with exponential scalar potential turned on in higher dimensions. From the critical points of the autonomous equations, we can determine the dominant components of the energy density in different cosmic eras. We obtain a fixed point representing a scalar field-matter-dominated era which corresponds to either a late-time or past-time attractor depending on the parameters used. According to this point, the inflationary phase, corresponding to past-time attractors, is given by unstable nodes, whilst the dark energy era, corresponding to late-time attractors, is represented by stable nodes. In the inflationary sector, power-law inflation can still occur in this Klein–Gordon–Rastall cosmological model. On the other hand, in the late-time sector, we find a nontrivial interplay between a scalar field with an exponential potential and the non-conservative energy-momentum tensor of the non-relativistic matter field (baryonic-dark matter) in curved spacetime plays a role as the dark energy. Based on such features, the Klein–Gordon–Rastall cosmology could be a promising candidate for describing both the early and late-time universe.