bluuebunny/crossref_metadata_2025_split huggingface dataset:
ExonViz: A website and Python package to visualize transcripts and genetic variants
Authors: van den Berg Redmar R. , Lauffer Marlen C. , Laros Jeroen F.J. 
Published: September 2024

AbstractSummaryExonViz is an application and website that creates biologically accurate transcript figures, including features such as coding regions, genetic variants and exon reading frames. Transcript definitions are automatically retrieved from Ensembl and RefSeq. We illustrate the full functionality of ExonViz by generating a figure for all ClinVar variants reported inCYLD.Alvailability and ImplementationExonViz is available online viaDutch Center for RNA Therapeuticsand can be installed locally viaPyPI.ContactRedmar R. van den BergSupplementary informationExtensive documentation on ExonViz is available onRead the Docs.
Involvement of 5’ and 3’ UTRs on SARS-CoV-2 Genome Packaging
Authors: Zhang Zhang , Yang Kun , Shao Fangze , Shen Wenlong , Li Ping , Zhang Yue , Xu Junjie , Yu Guoying , Zhang Jun , Zhao Zhihu , Zhang Yan 
Published: September 2024

AbstractThe SARS-CoV-2 virus, responsible for the COVID-19 pandemic, packages its large single-stranded RNA genome through a precise yet enigmatic mechanism. A packaging signal (PS) within its genome was proposed to facilitate the assembly of new viral particles. Here in this study, we report the role of the 5’ and 3’ untranslated regions (UTRs) in PS-mediated genome packaging. Utilizing proximity ligation data, we demonstrate direct interactions between the UTRs and the PS9 element, a key packaging signal within the SARS-CoV-2 genome. Multiple evidence confirmed that the presence of UTRs enhance the packaging efficiency of infectious virus-like particles (iVLPs) and recruits more nucleocapsid (N) protein, suggesting a critical role in genome compaction and packaging. These insights into the regulatory mechanisms of SARS-CoV-2 genome packaging provide novel targets for antiviral therapeutics and contribute to the broader understanding of coronavirus assembly.
Integrating collecting systems in kidney organoids through fusion of distal nephron to ureteric bud
Authors: Shi Min , Crouse Brittney , Sundaram Nambirajan , Shakked Naomi Pode , Ester Lioba , Zhang Weitao , Janakiram Vinothini , Kopan Raphael , Helmrath Michael A. , Bonventre Joseph V. , McCracken Kyle W. 
Published: September 2024

AbstractThe kidney maintains homeostasis through an array of parallel nephrons, which all originate in development as isolated epithelial structures that later fuse through their distal poles to a system of collecting ducts (CD). This connection is required to generate functional nephrons by providing a pathway for excretion of metabolic waste and byproducts. Currently, methods for differentiating human pluripotent stem cells into kidney organoids generate nephrons that lack CDs and instead terminate as blind-ended tubules. Here we describe a developmentally inspired system that addresses this deficiency through assembly of induced nephrogenic mesenchyme with ureteric bud (UB) tissues, the embryonic building blocks of the kidney’s collecting system. The UB progenitors grow and develop into a network of CDs within the organoid, and importantly, they functionally integrate with the nephrons through recapitulating fusion between the distal tubule and CD to create a continuous epithelial lumen. We further showed that proximal-distal nephron specification, fusion frequency, and maturation of the CD can be augmented through temporal manipulation of developmental signaling pathways. This work provides a platform for interrogating the principles and mechanisms underlying nephron-UB fusion and a framework for engineering unobstructed nephrons with patterned collecting systems, an important step toward the de novo generation of functional kidney tissue.
Efficient production of functional proaerolysin fromE.coli
Authors: Pham Quynh Thi-Huong , Tagawa Ayako , Iwata Narumi , Miyanari Yusuke 
Published: September 2024

AbstractProaerolysin is a bacterial toxin produced byAeromonas hydrophilathat specifically binds to GPI-anchored proteins on the plasma membrane, creating transmembrane pores that lead to cell death within a few hours. Leveraging this unique property, proaerolysin is widely used in diagnostic tests for paroxysmal nocturnal hemoglobinuria (PNH), a disease caused by somatic mutations in thePIGAgene, which is involved in the biosynthesis of GPI anchors. Additionally, proaerolysin serves as a counter-selection agent in genetic manipulations. Although bacterial expression and purification of proaerolysin have been previously reported, yields were low due to the absence of internal disulfide bonds, which are crucial for protein stability. Here, we demonstrate that using the ShuffleE. colistrain, which facilitates the formation of disulfide bonds in the cytoplasm, significantly improves the solubility and proper folding of proaerolysin. We achieved a high yield of proaerolysin, approximately 3 mg from a 50 ml bacterial culture, with a purity of over 99%. The functionality of recombinant proaerolysin was confirmed by testing in mouse embryonic stem cells (mESCs), demonstrating that this high-yield production method offers a reliable and cost-effective source of functional proaerolysin for a wide range of biotechnological applications.
Qualitative EEG abnormalities signal a shift towards inhibition-dominated brain networks. Results from the EU-AIMS LEAP studies
Authors: Juarez-Martinez Erika L. , Avramiea Arthur-Ervin , Garcés Pilar , Hipp Joerg F. , Poil Simon-Shlomo , Diachenko Marina , Mansvelder Huibert D. , Jones Emily , Mason Luke , Murphy Declan , Loth Eva , Oakley Bethany , Charman Tony , Banaschewski Tobias , Oranje Bob , Buitelaar Jan , Bruining Hilgo , Linkenkaer-Hansen Klaus 
Published: September 2024

AbstractQualitative EEG abnormalities are common in Autism Spectrum Disorder (ASD) and hypothesized to reflect disrupted excitation/inhibition balance. To test this, we recently introduced a functional measure of network-level E/I ratio (fE/I). Here, we applied fE/I and other quantitative EEG measures to alpha oscillations from source-reconstructed data in the EU-AIMS compilation of 267 EEG recordings from children-adolescents and adults with ASD and 209 controls. We analyzed these quantitative measures alongside evaluating for qualitative EEG abnormalities ranging from slowing of activity to epileptiform patterns aiming to replicate the findings from the SPACE-BAMBI study (Bruining et al., 2020). EEG abnormalities were only identified in a few adults and could not be statistically assessed. ASD children-adolescents with EEG abnormalities exhibited lower relative alpha power and lower fE/I compared to children-adolescents without abnormalities; however, the EEG-abnormality scoring did not stratify the behavioral heterogeneity of ASD using clinical measures. Surprisingly, several controls presented with qualitative EEG abnormalities and showed a strikingly similar anatomical distribution of lower fE/I to the one observed in the ASD group, suggesting a shift towards inhibition-dominated network dynamics, in regions associated with altered sensory processing. The robustness of this association between EEG abnormalities and reduced fE/I was further supported by re-analysis of the SPACE-BAMBI study in source space. Stratification by the presence of EEG abnormalities and their associated effects on network activity may help understand neurodevelopmental physiological heterogeneity and the difficulties in implementing E/I targeting treatments in unselected cohorts.
Designing and bioengineering of CDRs with higher affinity against receptor-binding domain (RBD) of SARS-CoV-2 Omicron variant
Authors: Singh Vishakha , Choudhary Shweta , Bhutkar Mandar , Nehul Sanketkumar , Ali Sabika , Singla Jitin , Kumar Pravindra , Tomar Shailly 
Published: September 2024

AbstractThe emergence of the SARS-CoV-2 Omicron variant highlights the need for innovative strategies to address evolving viral threats. This study bioengineered three nanobodies H11-H4, C5, and H3 originally targeting the Wuhan RBD, to bind more effectively to the Omicron RBD. A structure-basedin silicoaffinity maturation pipeline was developed to enhance their binding affinities. The pipeline consists of three key steps: high-throughputin silicomutagenesis of complementarity-determining regions (CDRs), protein-protein docking for screening, and molecular dynamics (MD) simulations for assessment of the complex stability. A total of 741, 551, and 684 mutations were introduced in H11-H4, C5, and H3 nanobodies, respectively. Protein-protein docking and MD simulations shortlisted high-affinity mutants for H11-H4(6), C5(5), and H3(6). Further, recombinant production of H11-H4 mutants and Omicron RBD enabled experimental validation through Isothermal Titration Calorimetry (ITC). The H11-H4 mutants R27E, S57D, S107K, D108W, and A110I exhibited improved binding affinities with dissociation constant (KD) values ranging from ∼8.8 to ∼27 µM, compared to the H11-H4 nanobody KDof ∼32 µM, representing a three-fold enhancement. This study demonstrates the potential of the developedin silicoaffinity maturation pipeline as a rapid, cost-effective method for repurposing nanobodies, aiding the development of robust prophylactic strategies against evolving SARS-CoV-2 variants and other pathogens.Graphical Abstract
Low maternal plasma apelin in the second trimester is associated with adverse pregnancy outcome in severe, early-onset fetal growth restriction
Authors: Braun N. , Bethell K. , Chaloner L. , Maksym K. , Spencer R.N. , Maguire J.J. , Davenport A.P. ,   EVERREST consortium, David A.L. , Vaughan O.R. 
Published: September 2024

ABSTRACTContextFetal growth restriction increases adverse pregnancy outcomes such as preterm birth and intrauterine fetal death. Apelin is a secreted peptide expressed in placental syncytiotrophoblast and downregulated in fetal growth restriction.ObjectivesWe tested the hypothesis that adverse pregnancy outcome is associated with low maternal plasma apelin at diagnosis of early-onset fetal growth restriction.MethodsPlasma samples and fetomaternal blood flow Doppler velocimetry measurements were obtained from pregnant women (n=59) at diagnosis of early-onset fetal growth restriction in the second trimester. Plasma apelin was determined by ELISA and pregnancy outcome was recorded. Placental gene expression was analysed after birth by qRT-PCR, compared to term placentas from women with late-onset fetal growth restriction or with appropriate-for-gestational age infants.ResultsAt diagnosis of early-onset fetal growth restriction, plasma apelin concentration was significantly lower in women who delivered extremely preterm (<28 weeks gestation) or had an intrauterine fetal death, compared to women who had a livebirth≥28 weeks (P<0.05). Plasma apelin correlated directly with uterine artery volume flow rate and inversely with pulsatility index. Placental gene expression of apelin, but not the apelin receptor or elabela, was lower in women with early-onset fetal growth restriction delivering preterm than in appropriate-for-gestational-age, term control women.ConclusionLow maternal circulating apelin during the second trimester is associated with impaired uteroplacental perfusion and subsequent adverse pregnancy outcome in severe, early-onset fetal growth restriction. Placental apelin deficiency may contribute mechanistically to the pathogenesis of early-onset fetal growth restriction.
Chromatin remodeler BRG1 recruits huntingtin to repair DNA double-strand breaks in neurons
Authors: Pradhan Subrata , Bush Keegan , Zhang Nan , Pandita Raj K. , Tsai Chi-Lin , Smith Charlene , Pandlebury Devon F. , Gaikwad Sagar , Leonard Francis , Nie Linghui , Tao Annie , Russell William , Yuan Subo , Choudhary Sanjeev , Ramos Kenneth S. , Elferink Cornelis , Wairkar Yogesh P. , Tainer John A. , Thompson Leslie M. , Pandita Tej K. , Sarkar Partha S. 
Published: September 2024

SUMMARYPersistent DNA double-strand breaks (DSBs) are enigmatically implicated in neurodegenerative diseases including Huntington’s disease (HD), the inherited late-onset disorder caused by CAG repeat elongations in Huntingtin (HTT). Here we combine biochemistry, computation and molecular cell biology to unveil a mechanism whereby HTT coordinates a Transcription-Coupled Non-Homologous End-Joining (TC-NHEJ) complex. HTT joins TC-NHEJ proteins PNKP, Ku70/80, and XRCC4 with chromatin remodeler Brahma-related Gene 1 (BRG1) to resolve transcription-associated DSBs in brain. HTT recruitment to DSBs in transcriptionally active gene- rich regions is BRG1-dependent while efficient TC-NHEJ protein recruitment is HTT-dependent. Notably, mHTT compromises TC-NHEJ interactions and repair activity, promoting DSB accumulation in HD tissues. Importantly, HTT or PNKP overexpression restores TC-NHEJ in aDrosophilaHD model dramatically improving genome integrity, motor defects, and lifespan. Collective results uncover HTT stimulation of DSB repair by organizing a TC-NHEJ complex that is impaired by mHTT thereby implicating dysregulation of transcription-coupled DSB repair in mHTT pathophysiology.Highlights•BRG1 recruits HTT and NHEJ components to transcriptionally active DSBs.•HTT joins BRG1 and PNKP to efficiently repair transcription related DSBs in brain.•Mutant HTT impairs the functional integrity of TC-NHEJ complex for DSB repair.•HTT expression improves DSB repair, genome integrity and phenotypes in HD flies.
Mpox mRNA-1769 Vaccine Inhibits Orthopoxvirus Replication at Intranasal, Intrarectal, and Cutaneous Sites of Inoculation
Authors: Cotter Catherine A. , Ignacio Maxinne A. , Americo Jeffrey L. , Earl Patricia L. , Mucker Eric M. , Hooper Jay W. , Frey Tiffany R. , Carfi Andrea , Freyn Alec W. , Moss Bernard 
Published: September 2024

ABSTRACTThe increasing incidence of mpox in Africa and the recent global outbreak with evidence of sexual transmission have stimulated interest in new vaccines and therapeutics. Our previous study demonstrated that mice immunized twice with a quadrivalent lipid nanoparticle vaccine comprising four monkeypox virus mRNAs raised neutralizing antibodies and antigen-specific T cells and were protected against a lethal intranasal challenge with vaccinia virus. Here we extended these findings by using live animal imaging to demonstrate that the mRNA vaccine greatly reduced virus replication and spread from an intranasal site of inoculation and prevented detectable replication at intrarectal and cutaneous inoculation sites. Moreover, considerable protection was achieved with a single vaccination and a booster vaccination enhanced protection for at least 4 months. Protection was related to the amount of mRNA inoculated, which correlated with neutralizing antibody levels. The role of antibody in protection was demonstrated by passive transfer of immune serum pre- or post-challenge to immunocompetent and immunodeficient mice lacking mature B and T cells and therefore unable to mount an adaptive response. These findings provide insights into the mechanism and extent of mRNA vaccine induced protection of orthopoxviruses and support clinical testing.
Organ-specific Sympathetic Innervation Defines Visceral Functions
Authors: Wang Tongtong , Teng Bochuan , Yao Dickson R. , Gao Wei , Oka Yuki 
Published: September 2024

AbstractThe autonomic nervous system orchestrates the brain and body functions through the sympathetic and parasympathetic pathways. However, our understanding of the autonomic system, especially the sympathetic system, at the cellular and molecular levels is severely limited. Here, we show unique topological representations of individual visceral organs in the major abdominal sympathetic ganglion complex. Using multi-modal transcriptomic analyses, we identified distinct sympathetic populations that are both molecularly and spatially separable in the celiac-superior mesenteric ganglia (CG-SMG). Notably, individual CG-SMG populations exhibit selective and mutually exclusive axonal projections to visceral organs, targeting either the gastrointestinal (GI) tract or secretory areas including the pancreas and bile tract. This combinatorial innervation pattern suggests functional segregation between different CG-SMG populations. Indeed, our neural perturbation experiments demonstrated that one class of neurons selectively regulates GI food transit. Another class of neurons controls digestion and glucagon secretion independent of gut motility. These results reveal the molecularly diverse sympathetic system and suggest modular regulations of visceral organ functions through distinct sympathetic populations.
Ecophysiological behaviour of majorFusariumspecies in response to combinations of temperature and water activity constraints
Authors: Garcia Marie-Anne , Mahmoud Rémi , Bancal Marie-Odile , Bancal Pierre , Bernillon Stéphane , Pinson-Gadais Laetitia , Richard-Forget Florence , Foulongne-Oriol Marie 
Published: September 2024

ABSTRACTFusariumHead Blight (FHB) is a devastating fungal disease affecting cereals, caused byFusariumspecies that can produce harmful mycotoxins.Fusariumspecies share the same ecological niche, and their population dynamic and associated mycotoxin patterns are driven by the environment. The aim of the present study was to investigate ecophysiological characteristics of the majorFusariumspecies causing FHB under abiotic factors. Growth and mycotoxin production of different strains ofFusarium avenaceum, Fusarium graminearum,Fusarium langsethiae, Fusarium poaeandFusarium tricinctumwere characterized under a combined effect of temperature (ϴ = 15, 20, 25 and 30°C) and water activity (aw= 0.99, 0.98, 0.97, 0.96, 0.95 and 0.94). Using innovative statistical analyses, we demonstrated that thoseFusariumspecies greatly differ in their responses to the studied environmental constraints. Our findings indicated that ϴ, aw, and their interaction were the major factors with a significant impact on the species behaviour. The intraspecific variation was demonstrated as less pronounced than the interspecific one. Understanding the ecophysiological requirements ofFusariumspecies is crucial in the context of climate change that is predicted to worsen disease outbreaks. Our data constitute a valuable knowledge base for improving the reliability and robustness of FHB prediction models and anticipating the associated mycotoxin risk.IMPORTANCEFusariumspecies pose a significant threat to major cereal crops, including wheat. These fungi not only reduce yield but also produce mycotoxins harmful to animals and humans. The prevalence of eachFusariumspecies is influenced by environmental conditions and shifts in pathogen populations, leading to changes in mycotoxin patterns have already been observed in relation to climate changes. This study revealed distinct ecophysiological behaviours, including mycelium growth and mycotoxin production, among the five majorFusariumspecies when exposed to varying temperature and water activity conditions. Our findings provide a valuable foundation for a more comprehensive understanding of the challenge of mycotoxin contamination and for the development of more effective mitigation strategies in the near future.
Extremely distinct microbial communities in closely related leafhopper subfamilies: Typhlocybinae and Eurymelinae (Cicadellidae, Hemiptera)
Authors: Kobiałka Michał , Świerczewski Dariusz , Walczak Marcin , Urbańczyk Weronika 
Published: September 2024

AbstractAmong the Hemiptera insects, a widespread way of feeding is sucking sap from host plants. Due to diet poor in nutrients, these insects enter into obligate symbiosis with their microorganisms. However, within the Cicadellidae family, there is a relatively large group of mesophyll feeders – Typhlocybinae that is considered to be devoid of symbiotic companions. In this work, we examine the composition of microorganisms in this subfamily and compare the results with their close relatives – the Eurymelinae subfamily. To study the microbiome, we used high-throughput next-generation sequencing (NGS, Illumina) and advanced microscopic techniques such as transmission electron microscopy (TEM) and fluorescencein situhybridization (FISH) in a confocal microscope. The Typhlocybinae insects have very poor microbial communities in their bodies, these are mainly facultative microorganisms, such as alphaproteobacteria of the genusWolbachiaorRickettsia. We detected also the presence of bacteria that can be considered as facultative symbionts e.g.Spiroplasma, Acidocella, Arsenophonus, Sodalis, Lariskella, Serratia, CardiniumandAsaia.On the other hand, the Eurymelinae group is characterized by a large diversity of the microbial communities, similar to those described in other Cicadomorpha. We find obligate co-symbionts involved in the synthesis of essential amino acids such asSulcia,betaproteobacteria related to genusNasuiaor gammaproteobacteriaSodalis. In other representatives, we observed symbiotic yeast-like fungi from the family Ophiocordycipitaceae and within some genera we discoveredArsenophonusbacteria inhabiting the interior ofSulciabacteria. Additionally, we investigated the transovarial transmission of obligate symbionts, which occurs via infection of the ovaries of females.ImportanceThe Typhlocybinae and Eurymelinae leafhoppers differ significantly in their symbiotic communities. This is undoubtedly due to their different diets, as Typhlocybinae insects feed on parenchyma, richer in nutrients, while Eurymelinae, like most representatives of Auchenorrhyncha, consume sap from the phloem fibers of plants. Our work presents comprehensive studies of 42 species belonging to two above-mentioned, so far poorly known Cicadomorpha subfamilies. Phylogenetic studies we conducted confirm that the insects from the groups studied have a common ancestor. Since obligate symbionts, having a reduced genome, may affect the reduction of their host’s adaptation to changing environmental conditions, e.g. temperature, and facultative microbiomes may influence the increase in such adaptation and expansion of host niche space. Therefore, Typhlocybinae species may show greater resistance to future climate change than representatives of the Eurymelinae. The research that considers the role of ecological niches in microbiome composition is essential in the era of climate change.