bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic and neurodevelopmental markers in schizophrenia-spectrum disorders: analysis of the combined role of the Cannabinoid Receptor 1 gene (CNR1) and dermatoglyphics
Authors: Guardiola-Ripoll Maria , Sotero-Moreno Alejandro , Chaumette Boris , Kebir Oussama , Hostalet Noemí , Almodóvar-Payá Carmen , Moreira Mónica , Giralt-López Maria , Odile-Krebs Marie , Fatjó-Vilas Mar 
Published: January 2024

ABSTRACTThe aetiology of schizophrenia-spectrum disorders (SSD) involves genetic and environmental factors impacting neurodevelopmental trajectories. Dermatoglyphic pattern deviances have been associated with SSD and considered vulnerability markers for these disorders based on the shared ectodermal origin of the epidermis and the central nervous system. The endocannabinoid system participates in epidermal differentiation, is sensitive to the prenatal environment and is associated with SSD. We assessed whether theCannabinoid receptor 1(CNR1) gene is a common denominator in dermatoglyphic pattern configurations and SSD risk and whether it modulates the dermatoglyphics-SSD association.In a sample of 112 controls and 97 SSD patients, three dermatoglyphic markers were assessed: the total palmar a-b ridge count (TABRC), the a-b ridge count fluctuating asymmetry (ABRC-FA), and the pattern intensity index (PII). TwoCNR1polymorphisms were genotyped: rs2023239-A/G and rs806379-A/T. We tested theCNR1association with SSD and with the dermatoglyphic variability within diagnostic groups. Secondly, we assessed theCNR1x dermatoglyphic measures interaction on SSD susceptibility.Both polymorphisms were associated with the risk for SSD, and within controls, rs2023239 and rs806379 modulated the PII and TABRC, respectively. Lastly, our data showed that rs2023239 modulated the relationship between PII and SSD: a high PII score was associated with a lower SSD risk within G-allele-carriers and a higher SSD risk within AA-homozygotes.These novel results highlight the endocannabinoid system’s role in the development and variability of dermatoglyphic patterns. The identified interaction encourages combining genetic and dermatoglyphics to assess neurodevelopmental alterations predisposing to SSD.
Patients with end-stage kidney disease and COVID-19 are commonly hospitalized early during COVID-19 illness: an opportunity for early intervention
Authors: Seethapathy Rituvanthikaa , Wang Qiyu , Katz-Agranov Nurit , Strohbehn Ian , Moreno Daiana , Harden Destiny , Bhattacharyya Roby P. , Sise Meghan E. 
Published: January 2024

AbstractAntiviral medications such as remdesivir, molnupiravir, and nirmatrelvir/ritonavir are most effective when used early in the course of coronavirus disease 2019 (COVID-19). These medications are mainly authorized for outpatient use in high risk populations. End-stage kidney disease (ESKD) is among the strongest risk factors for mortality from COVID-19, however, therapeutic options have been lacking in this patient population given exclusion of ESKD in the registrational trials of antiviral therapy leading to limited FDA approval. In our retrospective study of patients with ESKD on dialysis admitted for symptomatic COVID-19 from March 2020 to January 2020, we found that majority of patients (>80%) were admitted to the hospital early during their disease course (within 5 days of symptom onset). Despite this pattern of early admission, there was a high risk of respiratory failure within 90 days since admission (30%) among this population. We argue that this unique pattern of early presentation and high risk of progression to respiratory failure of the ESKD patients suggests an opportunity for further research to determine if outpatient antiviral therapies should be expanded to patients with ESKD to address the huge unmet need of therapeutic intervention in this vulnerable population.
Estimating effects of serum vitamin B12 levels on psychiatric disorders and cognitive impairment: a Mendelian randomization study
Authors: Lu Tianyuan , Paterson Andrew D. 
Published: January 2024

AbstractVitamin B12 deficiency can lead to pernicious anemia, various neuropsychiatric diseases, and cognitive decline. However, it is unclear whether increasing vitamin B12 levels can help to prevent the onset of psychiatric disorders and cognitive impairment in the general population. Leveraging large-scale genome-wide association studies (GWASs), we conducted Mendelian randomization (MR) analyses to estimate the potential effects of serum vitamin B12 levels on eight psychiatric disorders, as well as educational attainment and cognitive performance. We performed sensitivity analyses by excluding genetic instruments that demonstrated potential horizontal pleiotropy. We conducted additional MR analyses utilizing within-sibship studies for depressive symptoms, educational attainment, and cognitive performance to mitigate bias due to potential residual confounding in GWASs. As a positive control, we confirmed that a one standard deviation increase in genetically increased vitamin B12 levels was strongly associated with a decreased odds of developing pernicious anemia (odds ratio, OR = 0.24; 95% confidence interval, CI: 0.15-0.40; p-value = 2.1x10-8). In contrast, MR estimates of vitamin B12 effects on all eight psychiatric disorders, educational attainment and cognitive performance largely overlapped with the null. In particular, based on the three most well-powered GWASs, a one standard deviation increase in genetically predicted vitamin B12 levels was associated with an OR of 1.01 for depression (95% CI: 0.97-1.04; p-value = 0.74), a 7.7x10-3standard deviation increase in educational attainment (95% CI: -1.0x10-2-2.5x10-2; p-value = 0.39) and a 1.3x10-2standard deviation increase in cognitive performance (95% CI: -8.8x10-3-3.5x10-2; p-value = 0.24). No significant associations between genetically predicted vitamin B12 levels and any of the outcomes were identified in sensitivity analyses excluding pleiotropic genetic instruments or MR analyses based on within-sibship studies. In summary, our findings suggest that increasing serum vitamin B12 levels may not protect against the investigated psychiatric disorders or cognitive impairment in the general population.
Evolution of glucuronoxylan side chain variability in vascular plants and the counter-adaptation of pathogenic cell-wall-degrading hydrolases
Authors: Yu Li , Wilson Louis F.L. , Terrett Oliver M. , Wurman-Rodrich Joel , Lyczakowski Jan J. , Yu Xiaolan , Krogh Kristian B.R.M. , Dupree Paul 
Published: January 2024

Summary• Polysaccharide structural complexity not only influences cell wall strength and extensibility, but also hinders pathogenic and biotechnological attempts to saccharify the wall. In certain species and tissues, glucuronic acid side chains on xylan exhibit arabinopyranose or galactose decorations whose genetic and evolutionary basis is completely unknown, impeding efforts to understand their function and engineer wall digestibility.• Genetics and polysaccharide profiling were used to identify the responsible loci in Arabidopsis and Eucalyptus from proposed candidates, while phylogenies uncovered a shared evolutionary origin. GH30-familyendo-glucuronoxylanase activities were analysed by electrophoresis and their differing specificities were rationalised by phylogeny and structural analysis.• The newly identified xylan arabinopyranosyltransferases comprise an overlooked subfamily in the GT47-A family of Golgi glycosyltransferases, previously assumed to comprise mainly xyloglucan galactosyltransferases, highlighting an unanticipated adaptation of both donor and acceptor specificities. Further neofunctionalisation has produced a Myrtaceae-specific xylan galactosyltransferase. Simultaneously, GH30 endo-glucuronoxylanases have convergently adapted to overcome these decorations, suggesting a role for these structures in defence. The differential expression of glucuronoxylan-modifying genes across Eucalyptus tissues, however, hints at further functions.• Our results demonstrate the rapid adaptability of biosynthetic and degradative carbohydrate-active enzyme activities, providing insight into a plant-pathogen arms race and facilitating plant cell wall biotechnological utilisation.
Genome data artifacts and functional studies of deletion repair in the BA.1 SARS-CoV-2 spike protein
Authors: Álvarez-Herrera Miguel , Ruiz-Rodriguez Paula , Navarro-Domínguez Beatriz , Zulaica Joao , Grau Brayan , Bracho María Alma , Guerreiro Manuel , Aguilar-Gallardo Cristóbal , González-Candelas Fernando , Comas Iñaki , Geller Ron , Coscollá Mireia 
Published: January 2024

AbstractMutations within the N-terminal domain (NTD) of the spike (S) protein are critical for the emergence of successful SARS-CoV-2 viral lineages. The NTD has been repeatedly impacted by deletions, often exhibiting complex and dynamic patterns, such as the recurrent emergence and disappearance of deletions in dominant variants. This study investigates the influence of repair of NTD lineage-defining deletions found in the BA.1 lineage (Omicron variant) on viral success. We performed comparative genomic analyses of more than 10 million SARS-CoV-2 genomes from GISAID to decipher the transmission success of viruses lacking S:ΔH69/V70, S:ΔV143/Y145, or both. These findings were contrasted against a screening of publicly available raw sequencing data, revealing substantial discrepancies between data repositories, suggesting that spurious deletion repair observations in GISAID may result from systematic artifacts. Specifically, deletion repair events were approximately an order of magnitude less frequent in the read-run survey. Our results suggest that deletion repair events are rare, isolated events with limited direct influence on SARS-CoV-2 evolution or transmission. Nevertheless, such events could facilitate the emergence of fitness-enhancing mutations. To explore potential drivers of NTD deletion repair patterns, we characterized the viral phenotype of such markers in a surrogatein vitrosystem. Repair of the S:ΔH69/V70 deletion reduced viral infectivity, while simultaneous repair with S:ΔV143/Y145 led to lower fusogenicity. In contrast, individual S:ΔV143/Y145 repair enhanced both fusogenicity and susceptibility to neutralization by sera from vaccinated individuals. This work underscores the complex genotype-phenotype landscape of the spike NTD in SARS-CoV-2, which impacts viral biology, transmission efficiency, and immune escape potential, offering insights with direct relevance to public health, viral surveillance, and the adaptive mechanisms driving emerging variants.
Novel sensor-integrated proteome on chip (SPOC) platform with thousands of folded proteins on a 1.5 sq-cm biosensor chip to enable high-throughput real-time label-free screening for kinetic analysis
Authors: Agu Chidozie Victor , Cook Rebecca L , Martelly William , Gushgari Lydia R , Mohan Mukilan , Takulapalli Bharath 
Published: January 2024

AbstractAn automated proteomic platform for producing and screening an array of functional proteins on biosensor surfaces was developed to address the challenges of measuring proteomic interaction kinetics in high throughput (HTP). This technology is termed Sensor-Integrated Proteome On Chip (SPOC®) which involvesin-situcell-free protein expression in nano-liter volume wells (nanowells) directly from rapidly customizable arrays of plasmid DNA, facilitating simultaneous capture-purification of up to 2400 unique full-length folded proteins onto a 1.5 sq-cm surface of a single gold biosensor chip. Arrayed SPOC sensors can then be screened by real-time label-free analysis, including surface plasmon resonance (SPR) to generate kinetic affinity, avidity data. Fluorescent and SPR assays were used to demonstrate zero crosstalk between protein spots. The functionality of the SPOC protein array was validated by antibody binding assay, post-translational modification, mutation-mediated differential binding kinetics, and catalytic activity screening on model SPOC protein arrays containing p53, Src, Jun, Fos, HIST1H3A, and SARS-CoV-2 receptor binding domain (RBD) protein variants of interest, among others. Monoclonal antibodies were found to selectively bind their target proteins on the SPOC array. A commercial anti-RBD antibody was used to demonstrate discriminatory binding to numerous SARS-CoV-2 RBD variants of concern with comprehensive kinetic information. With advantages of HTP, flexibility, low-cost, quick turnaround time, and real-time kinetic affinity profiling, the SPOC proteomic platform addresses the challenges of interrogating protein interactions at scale and can be deployed in various research and clinical applications.
Regulatory T cells and IFN-γ-producing Th1 cells play a critical role in the pathogenesis of Sjögren’s Syndrome
Authors: Wang Yin-Hu , Li Wenyi , McDermott Maxwell , Son Ga-Yeon , Maiti George , Zhou Fang , Tao Anthony , Raphael Dimitrius , Moreira Andre L. , Shen Boheng , Vaeth Martin , Nadorp Bettina , Chakravarti Shukti , Lacruz Rodrigo S. , Feske Stefan 
Published: January 2024

ABSTRACTObjectivesSjögren’s Disease (SjD) is an autoimmune disorder characterized by progressive dysfunction, inflammation and destruction of salivary and lacrimal glands, and by extraglandular manifestations. Its etiology and pathophysiology remain incompletely understood, though a role for autoreactive B cells has been considered key. Here, we investigated the role of effector and regulatory T cells in the pathogenesis of SjD.MethodsHistological analysis, RNA-sequencing and flow cytometry were conducted on glands, lungs, eyes and lymphoid tissues of mice with regulatory T cell-specific deletion of stromal interaction proteins (STIM) 1 and 2 (Stim1/2Foxp3), which play key roles in calcium signaling and T cell function. The pathogenicity of T cells fromStim1/2Foxp3mice was investigated through adoptively transfer into lymphopenic host mice. Additionally, single-cell transcriptomic analysis was performed on peripheral blood mononuclear cells (PBMCs) of patients with SjD and control subjects.ResultsStim1/2Foxp3mice develop a severe SjD-like disorder including salivary gland (SG) and lacrimal gland (LG) inflammation and dysfunction, autoantibodies and extraglandular symptoms. SG inflammation inStim1/2Foxp3mice is characterized by T and B cell infiltration, and transcriptionally by a Th1 immune response that correlates strongly with the dysregulation observed in patients with SjD. Adoptive transfer of effector T cells fromStim1/2Foxp3mice demonstrates that the SjD-like disease is driven by interferon (IFN)-γ producing autoreactive CD4+T cells independently of B cells and autoantiboodies. scRNA-seq analysis identifies increased Th1 responses and attenuated memory Treg function in PBMCs of patients with SjD.ConclusionsWe report a more accurate mouse model of SjD while providing evidence for a critical role of Treg cells and IFN-γ producing Th1 cells in the pathogenesis of SjD, which may be effective targets for therapy.
Self-inspired learning to denoise for live-cell super-resolution microscopy
Authors: Qu Liying , Zhao Shiqun , Huang Yuanyuan , Ye Xianxin , Wang Kunhao , Liu Yuzhen , Liu Xianming , Mao Heng , Hu Guangwei , Chen Wei , Guo Changliang , He Jiaye , Tan Jiubin , Li Haoyu , Chen Liangyi , Zhao Weisong 
Published: January 2024

ABSTRACTEvery collected photon is precious in live-cell super-resolution (SR) fluorescence microscopy for contributing to breaking the diffraction limit with the preservation of temporal resolvability. Here, to maximize the utilization of accumulated photons, we propose SN2N, aSelf-inspiredNoise2Noise engine with self-supervised data generation and self-constrained learning process, which is an effective and data-efficient learning-based denoising solution for high-quality SR imaging in general. Through simulations and experiments, we show that the SN2N’s performance is fully competitive to the supervised learning methods but circumventing the need for large training-set and clean ground-truth, in which a single noisy frame is feasible for training. By one-to-two orders of magnitude increased photon efficiency, the direct applications on various confocal-based SR systems highlight the versatility of SN2N for allowing fast and gentle 5D SR imaging. We also integrated SN2N into the prevailing SR reconstructions for artifacts removal, enabling efficient reconstructions from limited photons. Together, we anticipate our SN2N and its integrations could inspire further advances in the rapidly developing field of fluorescence imaging and benefit subsequent precise structure segmentation irrespective of noise conditions.
High response diversity and conspecific density-dependence, not species interactions, drive dynamics of coral reef fish communities
Authors: Ruiz-Moreno Alfonso , Emslie Michael J. , Connolly Sean R. 
Published: January 2024

AbstractSpecies-to-species and species-to-environment interactions are key drivers of community dynamics. Disentangling these drivers in species-rich assemblages is challenging due to the high number of potentially interacting species (the “curse of dimensionality”). We develop a process-based model that quantifies how intraspecific and interspecific interactions, and species’ covarying responses to environmental fluctuations, jointly drive community dynamics. We fit the model to reef fish abundance time series from 41 reefs of Australia’s Great Barrier Reef. We found that fluctuating relative abundances are driven by species’ heterogenous responses to environmental fluctuations, whereas interspecific interactions are negligible. Species differences in long-term average abundances are driven by interspecific variation in the magnitudes of both conspecific density-dependence and density-independent growth rates. This study introduces a novel approach to overcoming the curse of dimensionality, which reveals highly individualistic dynamics in coral reef fish communities that imply a high level of niche structure.
Alterations of genomic imprinting appear during the reprogramming of adult neural stem cells
Authors: Montalbán-Loro Raquel , Lozano-Ureña Anna , Lázaro-Carot Laura , Jiménez-Villalba Esteban , Planells Jordi , Lleches-Padilla Adela , Ito Mitsu , Radford Elisabeth J. , Ferrón Sacri R. 
Published: January 2024

AbstractGenomic imprinting is an epigenetic mechanism that causes monoallelic expression of genes depending on their parental origin. Loss of imprinting (LOI) is associated with cancer progression and human imprinting disorders (IDs), impacting foetal development, metabolism and cognition. Imprinted genes, organized in clusters, rely on methylation at imprint control regions (ICRs), which are differentially methylated regions (DMRs) on both parental chromosomes. Somatic cell reprogramming into induced pluripotent stem cells (iPSCs) is a valuable tool to understand the mechanisms associated with pluripotency and holds promise for generating patient-specific stem cells for therapeutical applications to treat different pathologies such as IDs. Here, we conduct genome-wide RNA-seq and MeDIP-seq analysis on mouse iPSCs derived from adult neural stem cells (NSCs). Our findings reveal a comprehensive alteration in iPSCs transcriptome profile, aligning with DNA hypomethylation. This correlation is pivotal in discerning which modifications in genomic imprinting during the reprogramming process represent undesirable epigenetic abnormalities that could compromiise the quality of iPSCs. Simultaneously, it helps identify genuine epigenetic modifications that are inherently linked to pluripotency, thus ensuring a clearer understanding of the factors influencing iPSC quality and pluripotent potential.
A functional interaction between TDP-43 and USP10 reveals USP10 dysfunction in TDP-43 proteinopathies
Authors: Marrero-Gagliardi A , Noda J , Zanovello M , Brito Armas JM , Bampton A , Torres P , Pérez Hernández C , Fumagallo F , Taoro L , Muñoz de Bustillo Alfaro R , Brown AL , Quinet G , Andrés-Benito P , Ferrer I , Acebes A , Freire R , Smits VAJ , Keuss M , Portero-Otin M , Lashley T , Fratta P , Acevedo-Arozena A 
Published: January 2024

ABSTRACTAmyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterised by the progressive degeneration of motor neurons in the cerebral cortex and spinal cord, with a rapid progression from diagnosis to death. The great majority of ALS cases and around 50% of FTD cases present with TDP-43 pathology, leading to mislocalization and cytoplasmic aggregation of TDP-43, which can result in both its loss of nuclear functions and a gain of toxicity in the cytoplasm. TDP-43 and other RNA-binding proteins accumulate in stress granules (SGs) under stress conditions. The ubiquitin-specific protease 10 (USP10) is an inhibitor of SGs assembly that has been recently linked to neurodegeneration. Here, we identified a new functional interaction between TDP-43 and USP10, in which USP10 can control multiple aspects of TDP-43 biology that are thought to play important roles in its involvement in disease pathogenesis, such as its cytoplasmic and nuclear aggregation, expression and splicing functionality. In turn, TDP-43 is also able to control diverse aspects of USP10 biology, such as its expression levels, aggregation and function. Critically, we found USP10 dysregulation in ALS and FTD patients, overall suggesting a possible role for USP10 in ALS/FTD pathogenesis.
Establishing a straightforward I-SceI mediated recombination one plasmid system for efficient genome editing inP. putidaKT2440
Authors: Meng Hao , Köbbing Sebastian , Blank Lars M. 
Published: January 2024

AbstractPseudomonas putidahas become an increasingly important chassis for the production of valuable bioproducts. This development is not at least due to the ever-improving genetic toolbox, including gene and genome editing techniques. Here, we present a novel, one plasmid design of a key genetic tool, the pEMG/pSW system, guaranteeing one engineering cycle to be finalized in three days. The pEMG/pSW system proved in the last decade to be valuable for targeted gensome engineering inPseudomonas, as it enables the deletion of large regions of the genome, the integration of heterologous gene clusters or targeted generation of point mutations. Here, to expedite genetic engineering, two alternative plasmids were constructed: 1) thesacBgene fromBacillus subtiliswas integrated into the I-SceI expressing plasmid pSW-2 as counterselection marker to accelerated plasmid curing; 2) double strand break introducing gene I-SceI and SacB counterselection marker were integrated into the backbone of the original pEMG vector, named pEMG-RIS. The single plasmid of pEMG-RIS allows rapid genome editing despite the low transcriptional activity of a single copy of the I-SceI encoding gene. Here, the usability of the pEMG-RIS is shown inP. putidaKT2440 by integrating an expression cassette including amsfGFPgene in three days. In addition, a large fragment of almost 16 kb was also integrated. In summary, an updated pEMG/pSW genome editing system is presented that allows efficient and rapid genome editing inP. putida. The pEMG-RIS will be available via the Addgene platform.