bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biallelic variants inARHGAP19cause a motor-predominant neuropathy with asymmetry and conduction slowing
Authors: Dominik Natalia , Efthymiou Stephanie , Record Christopher J. , Miao Xinyu , Lin Renee , Parmar Jevin , Scardamaglia Annarita , Maroofian Reza , Aughey Gabriel , Wilson Abigail , Lowe Simon , Curro Riccardo , Schnekenberg Ricardo P. , Alavi Shahryar , Leclaire Leif , He Yi , Zhelchenska Kristina , Bellaiche Yohanns , Gaugué Isabelle , Skorupinska Mariola , Van de Vondel Liedewei , Da’as Sahar I. , Turchetti Valentina , Güngör Serdal , Karimiani Ehsan Ghayoor , Ricaurte Camila Armirola , Topaloglu Haluk , Jordanova Albena , Zaman Mashaya , Banu Selina H. , Marques Wilson , Tomaselli Pedro José , Aynekin Busra , Cansu Ali , Per Huseyin , Güleç Ayten , Alvi Javeria Raza , Sultan Tipu , Khan Arif , Zifarelli Giovanni , Ibrahim Shahnaz , Mancini Grazia M.S. , Motazacker M. Mahdi , Brusse Esther , Lupo Vincenzo , Sevilla Teresa , Başak A Nazlı , Tekgul Seyma , Palvadeau Robin , Baets Jonathan , Parman Yesim , Çakar Arman , Horvath Rita , Haack Tobias B. , Stahl Jan-Hendrik , Grundmann-Hauser Kathrin , Park Joohyun , Züchner Stephan , Laing Nigel G. , Wilson Lindsay , Rossor Alexander M. , Polke James , Figueiredo Fernanda Barbosa , Pessoa André Luiz , Kok Fernando , Coimbra-Neto Antônio Rodrigues , França Marcondes C. , Jamshidi Yalda , Ravenscroft Gianina , Hamed Sherifa Ahmed , Chung Wendy K. , Osborn Daniel P. , Hanna Michael , Cortese Andrea , Reilly Mary M. , Jepson James E. C. , Lamarche-Vane Nathalie , Houlden Henry 
Published: May 2024

AbstractCharcot-Marie-Tooth Disease is a clinically and genetically heterogeneous group of hereditary neuropathies, with over 100 causative genes identified to date. Despite progress in genetic sequencing, around a quarter of patients remain unsolved. Through international collaborations, we identified 16 recessive variants in Rho GTPase activating protein 19 (ARHGAP19) causing motor-predominant neuropathy with conduction slowing in 25 individuals from 20 unrelated multi-ancestry families. ARHGAP19 is a GTPase-activating protein with activity towards RhoA.In vitrobiochemical assays revealed that variants located within the GAP domain cause loss of GAP activity. iPSc-derived motor neurons exhibited 50% knockdown of ARHGAP19 protein.In vivogenetic perturbations of theDrosophila melanogaster ARHGAP19orthologRhoGAP54Dreduced self-driven locomotor activity and startle responses to visual stimuli. Zebrafish loss-of-function models similarly exhibited movement deficits, coupled with increased motor neuron axonal branching but shorter caudal primary motor neurons. Together, these findings establishARHGAP19as a novel cause of early-onset neuropathy through a loss-of-function mechanism.
Effects of goldenrod (Solidago giganteaAiton and S.canadensisL.) invasion on the wet meadow vegetation composition of Somogyfajsz wood pasture
Authors: Szitár Katalin , Kabai Melinda , Zimmermann Zita , Szabó Gábor , Reis Bruna Paolinelli , Somay László 
Published: May 2024

AbstractIn recent decades, restoring abandoned wood pastures are being rediscovered as an effective way to preserve biodiversity. Their restoration include the control of invasive plant species. In our study, we compared the vegetation composition of wet meadow patches uninvaded and invaded by giant and Canadian goldenrod in a wood pasture located in Somogyfajsz, Hungary. We sampled the vegetation of the wet meadows of the pasture in 16 pairs of 1 x 1 m invaded and uninvaded quadrats in June 2020. We studied the effect of goldenrod invasion on nature conservation value in terms of species diversity, origin of species, and Social Behaviour Types, and forage quality and quantity. The study revealed that goldenrod invasion had negative effects on species richness and community-level biomass in wet meadows, leading to a significant reduction in species diversity and total cover. Goldenrod invasion also impacted the richness and cover of both native and exotic species, with a decrease in richness but not cover, highlighting the competitive ability of goldenrods and their potential to alter vegetation composition.
GENE THERAPY PREVENTS HEPATIC MITOCHONDRIAL DYSFUNCTION IN MURINE DEOXYGUANOSINE KINASE DEFICIENCY
Authors: Keshavan Nandaki , Greenwood Miriam , Prunty Helen , Diaz Juan Antinao , Privolizzi Riccardo , Counsell John , Karlsson Anna , Waddington Simon , Karda Rajvinder , Rahman Shamima 
Published: May 2024

AbstractPrimary mitochondrial disorders are an uncommon cause of neonatal hepatic failure. Biallelic pathogenic variants of the gene encoding the mitochondrial localising enzyme deoxyguanosine kinase (DGUOK) cause hepatocerebral mitochondrial DNA depletion syndrome leading to acute neonatal liver failure and early mortality. There are currently no effective disease-modifying therapies. In this study, we developed an adeno-associated virus 9 (AAV9) gene therapy approach to treat a mouse model of DGUOK deficiency that recapitulates human disease. We delivered AAV9-hDGUOKgene therapy intravenously to newbornDguokknock-out mice and showed that liver dysfunction was prevented in a dose dependent manner. Unexpectedly for neonatal delivery, durable and long-lasting liver transduction and RNA expression were demonstrated. Liver mitochondrial DNA depletion, deficiencies of oxidative phosphorylation complexes I, III and IV and liver transaminitis and survival were ameliorated in a dose-dependent manner.
Insights into Ligand-Mediated Activation of an Oligomeric Ring-Shaped Gene-Regulatory Protein from Solution- and Solid-State NMR
Authors: Muzquiz Rodrigo , Jamshidi Cameron , Conroy Daniel W. , Jaroniec Christopher P. , Foster Mark P. 
Published: May 2024

AbstractThe 91 kDa oligomeric ring-shaped ligand binding protein TRAP (trpRNA binding attenuation protein) regulates the expression of a series of genes involved in tryptophan (Trp) biosynthesis in bacilli. When cellular Trp levels rise, the free amino acid binds to sites buried in the interfaces between each of the 11 (or 12, depending on the species) protomers in the ring. Crystal structures of Trp-bound TRAP show the Trp ligands are sequestered from solvent by a pair of loops from adjacent protomers that bury the bound ligand via polar contacts to several threonine residues. Binding of the Trp ligands occurs cooperatively, such that successive binding events occur with higher apparent affinity but the structural basis for this cooperativity is poorly understood. We used solution methyl-TROSY NMR relaxation experiments focused on threonine and isoleucine sidechains, as well as magic angle spinning solid-state NMR13C-13C and15N-13C chemical shift correlation spectra on uniformly labeled samples recorded at 800 and 1200 MHz, to characterize the structure and dynamics of the protein. Methyl13C relaxation dispersion experiments on ligand-free apo TRAP revealed concerted exchange dynamics on the µs-ms time scale, consistent with transient sampling of conformations that could allow ligand binding. Cross-correlated relaxation experiments revealed widespread disorder on fast timescales. Chemical shifts for methyl-bearing side chains in apo- and Trp-bound TRAP revealed subtle changes in the distribution of sampled sidechain rotameric states. These observations reveal a pathway and mechanism for induced conformational changes to generate homotropic Trp-Trp binding cooperativity.
Unravelling the Impact of miR-21 Overexpression on the MicroRNA Network and Cancer Pathways
Authors: Hill Meredith , Stapleton Sarah , Nguyen Phuong Thao , Sais Dayna , Deutsch Fiona , Gay Valarie , Marsh Deborah , Tran Nham 
Published: May 2024

AbstractMicroRNAs (miRNA, miRs) are small noncoding RNAs that are ubiquitously expressed in all mammalian cells. Their primary function is the regulation of nascent RNA transcripts by direct binding to regions on the target. There is now exciting data to suggest that these miRNAs can bind to other miRNAs, and this may have a broader impact on gene regulation in disease states. The oncomiR miR-21 is one of the highest-expressing miRNAs in cancer cells, and in this study, we characterise which miRNAs could be potential targets of miR-21. In cancer cells delivered with a miR-21 mimic, there was an observable shift of the miRNA milieu. We demonstrate that the miR-17-92a cluster, which harbours six miRNA members, may be a target of miR-21 regulation. Additionally, the primary transcript of miR-17-92a was reduced in the presence of miR-21. In the broader context of gene regulation, overexpression of miR-21 shifted the expression of more than 150 miRNAs, including those known to regulate genes encoding proteins in cancer pathways such as the MAPK signalling and FoxO pathways. This study expands upon our limited understanding of miR:miR regulatory network and reinforces the concept that miRNAs can regulate each other, thereby influencing broader gene regulatory networks.
Novel Neuromuscular Controllers with Simplified Muscle Model and Enhanced Reflex Modulation: A Comparative Study in Hip Exoskeletons
Authors: Manzoori Ali Reza , Messara Sara , Di Russo Andrea , Ijspeert Auke , Bouri Mohamed 
Published: May 2024

AbstractNeuromuscular controllers (NMCs) offer a promising approach to adaptive and task-invariant control of exoskeletons for walking assistance, leveraging the bioinspired models based on the peripheral nervous system. This article expands on our previous development of a novel structure for NMCs with modifications to the virtual muscle model and reflex modulation strategy. The modifications consist firstly of simplifications to the Hill-type virtual muscle model, resulting in a more straightforward formulation and reduced number of parameters; and secondly, using a finer division of gait subphases in the reflex modulation state machine, allowing for a higher degree of control over the shape of the assistive profile. Based on the proposed general structure, we present two controller variants for hip exoskeletons, with four- and five-state reflex modulations (NMC-4 and NMC-5). We used an iterative data-driven approach with two tuning stages (i.e., muscle parameters and reflex gains) to determine the controller parameters. Biological joint torque profiles and optimal torque profiles for metabolic cost reduction were used as references for the final tuning outcome. Experimental testing under various walking conditions demonstrated the capability of both variants for adapting to the locomotion task with minimal parameter adjustments, mostly in terms of timing. Furthermore, NMC-5 exhibited better alignment with biological and optimized torque profiles in terms of timing characteristics and relative magnitudes, resulting in less negative mechanical work. These findings firstly validate the adequacy of the simplified muscle model for assistive controllers, and demonstrate the utility of a more nuanced reflex modulation in improving the assistance quality.
Leveraging the genetic diversity of trout in the rivers of the British Isles and northern France to understand the movements of sea trout (Salmo truttaL.) around the English Channel
Authors: King R. Andrew , Ellis Charlie D. , Bekkevold Dorte , Ensing Dennis , Lecointre Thomas , Osmond Daniel R. , Piper Adam , Roberts Dylan E. , Launey Sophie , Stevens Jamie R. 
Published: May 2024

AbstractPopulations of anadromous brown trout, also known as sea trout, have suffered recent marked declines in abundance due to multiple factors, including climate change and human activities. While much is known about their freshwater phase, less is known about the species’ marine feeding migrations. This situation is hindering the effective management and conservation of anadromous trout in the marine environment. Using a panel of 95 single nucleotide polymorphism markers we developed a genetic baseline, which demonstrated strong regional structuring of genetic diversity in trout populations around the English Channel and adjacent waters. Extensive baseline testing showed this structuring allowed high-confidence assignment of known-origin individuals to region of origin. This study presents new data on the movements of anadromous trout in the English Channel and southern North Sea. Assignment of anadromous trout sampled from 12 marine and estuarine localities highlighted contrasting results for these areas. The majority of these fisheries are composed predominately of stocks local to the sampling location. However, there were multiple cases of long-distance movements of anadromous trout, with several individuals originating from rivers in northeast England being caught in the English Channel and southern North Sea, in some cases more than 1000 km from their natal region. These results have implications for the management of sea trout in inshore waters around the English Channel and southern North Sea.
sangerFlow, a Sanger sequencing-based bioinformatics pipeline for pests and pathogens identification
Authors: Prodhan M. Asaduzzaman , Power Matthew , Kehoe Monica 
Published: May 2024

AbstractSequencing of a Polymerase Chain Reaction product (amplicon) is called amplicon sequencing. Amplicon sequencing allows for reliable identification of an organism by amplifying, sequencing, and analysing a single conserved marker gene or DNA barcode. As this approach generally involves a single gene, it is a light-weight protocol compared to multi-locus or whole genome sequencing for diagnostic purposes; yet considerably reliable. Therefore, Sanger-based high-quality amplicon sequencing is widely deployed for species identification and high-throughput biosecurity surveillance. However, keeping up with the data analysis in a large-scale surveillance or diagnostic settings could be a limiting factor because it involves manual quality control of the raw sequencing data, alignment of the forward and reverse reads, and finally web-based Blastn search of all the amplicons. Here, we present a bioinformatics pipeline that automates the entire analysis. As a result, the pipeline is scalable with high-volume of samples and reproducible. Furthermore, the pipeline leverages the modern open-source Nextflow and Singularity concept, thus it does not require software installation except Nextflow and Singularity, software subscription, or programming expertise from the end users making it widely adaptable.Availability and implementationsangerFlow source code and documentation are freely available for download at GitHub, implemented in Nextflow and Singularity.
Parallel maximal common subgraphs with labels for molecular biology
Authors: Agbeto Wilfried , Coti Camille , Reinharz Vladimir 
Published: May 2024

AbstractAdvances in graph algorithmics have allowed in-depth study of many natural objects from molecular biology or chemistry to social networks. Particularly in molecular biology and cheminformatics, understanding complex structures by identifying conserved sub-structures is a key milestone towards the artificial design of novel components with specific functions. Given a dataset of structures, we are interested in identifying all maximum common connected partial subgraphs between each pair of graphs, a task notoriously NP-Hard.In this work, we present parallel algorithms over shared and distributed memory to enumerate all maximal connected common sub-graphs between pairs of arbitrary multi-directed graphs with labels on their edges. We offer an implementation of these methods and evaluate their performance on the non-redundant dataset of all known RNA 3D structures. We show that we can compute the exact results in a reasonable time for each pairwise comparison while taking into account a much more diverse set of interactions—resulting in much denser graphs—resulting in an order of magnitude more conserved modules. All code is available athttps://gitlab.info.uqam.ca/cbe/pasigraphand results in the branchresults.
Inferred Developmental Origins of Brain Tumors from Single Cell RNA-Sequencing Data
Authors: Wang Su , Curry Rachel Naomi , Erickson Anders W , Kleinman Claudia , Taylor Michael D. , Rao Ganesh , Deneen Benjamin , Harmanci Arif O. , Harmanci Akdes Serin 
Published: May 2024

AbstractThe reactivation of neurodevelopmental programs in cancer highlights parallel biological processes that occur in both normal development and brain tumors. Achieving a deeper understanding of how dysregulated developmental factors play a role in the progression of brain tumors is therefore crucial for identifying potential targets for therapeutic interventions. Single-cell RNA sequencing (scRNA-Seq) provides an opportunity to understand how developmental programs are dysregulated and reinitiated in brain tumors at single-cell resolution. Here, we introduce COORS (Cell Of ORigin like CellS), as a computational tool trained on developmental human brain single-cell datasets that enables annotation of “developmental-like” cell states in brain tumor cells. Applying COORS to various brain cancer datasets, including medulloblastoma (MB), glioma, and diffuse midline glioma (DMG), we identified developmental-like cells that represent putative cells of origin in these tumors. Our work adds to our cumulative understanding of brain tumor heterogeneity and helps pave the way for tailored treatment strategies.
Adverse pregnancy outcomes and coronary artery disease risk: A negative control Mendelian randomization study
Authors: Rogne Tormod , Gill Dipender 
Published: May 2024

ABSTRACTBackgroundAdverse pregnancy outcomes are predictive for future cardiovascular disease risk, but it is unclear whether they play a causal role. We conducted a Mendelian randomization study with males as a negative control population to estimate the associations between genetic liability to adverse pregnancy outcomes and risk of coronary artery disease.MethodsWe extracted uncorrelated (R2<0.01) single-nucleotide polymorphisms strongly associated (p-value<5e-8) with miscarriage, gestational diabetes, hypertensive disorders of pregnancy, preeclampsia, placental abruption, poor fetal growth and preterm birth from relevant genome-wide association studies. Genetic associations with risk of coronary artery disease were extracted separately for females and males. The main analysis was the inverse-variance weighted analysis, while MR Egger, weighted median and weighted mode regression, bidirectional analyses, and the negative control population with males were sensitivity analyses to evaluate bias due to genetic pleiotropy.ResultsThe number of cases for the adverse pregnancy outcomes ranged from 691 (182,824 controls) for placental abruption to 49,996 (174,109 controls) for miscarriage, and there were 22,997 (310,499 controls) and 54,083 (240,453 controls) cases of coronary artery disease for females and males, respectively. We observed an association between genetic liability to hypertensive disorders of pregnancy and preeclampsia, and to some extent gestational diabetes, poor fetal growth and preterm birth, with an increased risk of coronary artery disease among females, which was supported by the MR Egger, weighted median and weighted mode regressions. However, in the negative control population of males, we observed largely the same associations as for females.ConclusionsThe associations between adverse pregnancy outcomes and coronary artery disease risk were likely driven by confounding (e.g., shared genetic liability). Thus, our study does not support the hypothesis that adverse pregnancy outcomes are causal risk factors for cardiovascular diseases.
Novel mark recapture surveys reveal stable pigmentation patterns but age-related melanism in the common frogRana temporaria
Authors: Petrovan Silviu O. , Sivakumar Sharvani , Li Carissa , Christie Alec 
Published: May 2024

AbstractVariations in melanin-based pigmentation patterns are frequent evolutionary adaptations in vertebrates and allow the study of phenotypic diversity across populations as well as individual recognition. Age-related changes in such pigmentation patterns have been demonstrated for several species but remain rarely explored in adult amphibians. For the wide-ranging European common frog (Rana temporaria) dorsal melanism was discussed in the context of UV protection at high altitude or as thermal adaptation at high latitude, yet patterns remain unquantified across most of its range or in terms of individual variation over time. We investigated dorsal pigmentation patterns in a wild population ofR. temporariain a lowland site in England which was the focus of a 7 year high-intensity mark recapture programme. We collected dorsal photographs using phone cameras and analysed pigmentation patterns using visual classifications and ImageJ image processing software. Pigmentation was highly variable between individuals but overall: (i) the number of melanin-based spots was largely stable or decreased over time as enlarging spots sometimes merged but never disappeared; (ii) the total melanin-based pigmented area increased significantly over time on average, albeit not for all individuals; and (iii) pigmentation was similar in males compared to females although the darkest individuals tended to be males. Our analysis reveals important patterns in pigmentation change and stability in this widespread species but the mechanisms and specific drivers remain unknown.
Association between depression and the prevalence and prognosis of prediabetes: a population-based study
Authors: Zhou Jin , Yang Xiaojiao 
Published: May 2024

AbstractBackgroundDiagnosis and intervention of prediabetes is an emerging approach to preventing the progression and complications of diabetes. It has been reported that inflammatory factors and dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis may be potential pathogenesis mechanisms of diabetes and depression. However, the relationship between depression levels and the prevalence of prediabetes and its prognosis remains elusive. This study aimed to explore the relationship between depression and the prevalence of prediabetes and to further explore the all-cause mortality of different levels of depression in patients with prediabetes.MethodsOur study used a data set from the National Health and Nutrition Examination Survey (NHANES). Participants were divided into two groups (with or without depression) and further divided into subgroups based on different levels of depression status to analyze the relationship between depression and prediabetes prevalence. We then analyzed the relationship between all-cause mortality and depressive status in patients with prediabetes. This study used a weighted multiple logistic/Cox regression model.ResultsA total of 4384 participants were included, divided into depression group (n=1379) and non-depression group (n=3005). Results showed that people with depression were at higher risk of developing prediabetes. After adjusting for covariates, moderate to severe depression was positively associated with prediabetes (moderate to severe depression vs no depression: OR=1.834, 95%CI: 0.713–4.721; severe depression vs no depression: OR= 1.004, 95% CI 0.429–2.351). In addition, we explored the relationship between all-cause mortality and depressive status in patients diagnosed with prediabetes (n=2240) and found that moderate to severe depression (HR=2.109, 95%CI 0.952-4.670) was associated with higher mortality in patients with prediabetes. Associated with increased all-cause mortality.ConclusionsOverall, findings suggest that depression is positively associated with prediabetes prevalence and mortality. These results suggest that good management of mental health conditions may be a potential strategy to reduce the occurrence and progression of prediabetes.