bluuebunny/crossref_metadata_2025_split huggingface dataset:
Guanine crystals discovered in bacteria
Authors: Pavan María Elisa , Movilla Federico , Pavan Esteban E. , Di Salvo Florencia , López Nancy I. , Pettinari M. Julia 
Published: December 2022

AbstractGuanine crystals are organic biogenic crystals found in many organisms. Due to their exceptionally high refractive index, they contribute to structural color and are responsible for the reflective effect in the skin and visual organs in animals such as fish, reptiles and spiders. Occurrence of these crystals in animals has been known for many years, and they have also been observed in eukaryotic microorganisms, but not in prokaryotes. In this work we report the discovery of extracellular crystals in bacteria, and reveal that they are composed of guanine, and particularly the unusual monohydrate form. We demonstrate the occurrence of these crystals inAeromonasand other bacteria, and investigate the metabolic traits related to their synthesis. In all cases studied the presence of the guanine crystals in bacteria correlate with the absence of guanine deaminase, which could lead to guanine accumulation providing the substrate for crystal formation. Our finding of the hitherto unknown guanine crystal occurrence in prokaryotes extends the range of guanine crystal producing organisms to a new domain of life. Bacteria constitute a new and more accessible model to study the process of guanine crystal formation and assembly. This discovery opens countless chemical and biological questions, including those about the functional and adaptive significance of their production in these microorganisms. It also paves the road for the development of simple and convenient processes to obtain biogenic guanine crystals for diverse applications.SignificanceGuanine crystal formation is well known in animals such as fish, reptiles and arthropods (among other eukaryotic organisms), but its occurrence has never been reported in prokaryotes. This manuscript describes the discovery of extracellular guanine crystals in bacteria, and reveals that they are composed of the unusual monohydrate form of guanine. Knowledge of guanine crystal biosynthesis in bacteria could lead to a better understanding of their synthesis in other organisms. It also paves the road for the development of simple and convenient processes to obtain biogenic guanine crystals for diverse applications. Our finding extends the range of guanine crystal producing organisms to a new domain of life.
Disease-Associated Non-Coding Variants Alter NKX2-5 DNA-Binding Affinity
Authors: Peña-Martínez Edwin G. , Rivera-Madera Alejandro , Pomales-Matos Diego A. , Sanabria-Alberto Leandro , Rosario-Cañuelas Brittany M. , Rodríguez-Ríos Jessica M. , Carrasquillo-Dones Emmanuel A. , Rodríguez-Martínez José A. 
Published: December 2022

1.AbstractGenome-wide association studies (GWAS) have mapped over 90% of disease- or trait-associated variants within the non-coding genome, likecis-regulatory elements (CREs). Non-coding single nucleotide polymorphisms (SNPs) are genomic variants that can change how DNA-binding regulatory proteins, like transcription factors (TFs), interact with the genome and regulate gene expression. NKX2-5 is a TF essential for proper heart development, and mutations affecting its function have been associated with congenital heart diseases (CHDs). However, establishing a causal mechanism between non-coding genomic variants and human disease remains challenging. To address this challenge, we identified 8,475 SNPs predicted to alter NKX2-5 DNA- binding using a position weight matrix (PWM)-based predictive model. Five variants were prioritized for in vitro validation; four of them are associated with traits and diseases that impact cardiovascular health. The impact of these variants on NKX2-5 binding was evaluated with electrophoretic mobility shift assay (EMSA) using recombinantly expressed and purified human NKX2-5 homeodomain. Binding curves were constructed to determine changes in binding between variant and reference alleles. Variants rs7350789, rs7719885, rs747334, and rs3892630 increased binding affinity, whereas rs61216514 decreased binding by NKX2-5 when compared to the reference genome. Our findings suggest that differential TF-DNA binding affinity can be key in establishing a causal mechanism of pathogenic variants.Abstract Figure
Annotation-agnostic discovery of associations between novel gene isoforms and phenotypes
Authors: Hjörleifsson Kristján Eldjárn , Pachter Lior , Melsted Páll 
Published: December 2022

AbstractWe present a novel method for associating phenotypes with RNA expression, that can identify expression associations resulting from a wide variety of underlying transcriptional and post-transcriptional events, without relying on annotations of these events. We show that we can reliably detect,de novo, phenotypically relevant transcriptional structures
Unveiling the anti-glioma potential of a marine derivative, Fucoidan: its synergistic cytotoxicity with Temozolomide-anin vitroandin silicoexperimental study
Authors: Biswas Indrani , Precilla Daisy S , Kuduvalli Shreyas S , Ramachandran Muralidharan Arumugam , Akshaya S , Raman Venkat , Prabhu Dhamodharan , Anitha T. S 
Published: December 2022

AbstractIntroductionGlioma, coined as a “butterfly” tumor associated with a dismal prognosis. Marine algal compounds with the richest sources of bioactive components, act as significant anti-tumor therapeutics. However, there is a paucity of studies conducted on Fucoidan to enhance the anti-glioma efficacy of Temozolomide. Therefore, the present study aimed to evaluate the synergistic anti-proliferative, anti-inflammatory and pro-apoptotic effects of Fucoidan with Temozolomide inin vitroandin silicoexperimental setup.MethodologyThe anti-proliferative effects of Temozolomide and Fucoidan was evaluated on C6 glioma cells by MTT and migration assay. Modulation of inflammatory markers and apoptosis induction was affirmed at the morphological and transcriptional level, by dual staining and gene expression. Molecular docking (MD) and molecular dynamics simulation (MDS) studies were performed against the targets to rationalize the inhibitory effect.ResultsThe dual-drug combination significantly reduced the cell viability and migration of glioma cells in a synergistic dose-dependent manner. At the molecular level, the dual-drug combination significantly down-regulated inflammatory genes with a concomitant upregulation of pro-apoptotic marker. In consensus with our in vitro findings, molecular docking and simulation studies revealed that the anti-tumor ligands: Temozolomide, Fucoidan with 5-(3-Methy1-trizeno)-imidazole-4-carboxamide (MTIC), and 4-amino-5-imidazole-carboxamide (AIC) had the potency to bind to the inflammatory proteins at their active sites, mediated by H-bonds and other non-covalent interactions.Discussion and ConclusionThe dual-drug combinatorial treatment synergistically inhibited the proliferation, migration of glioma cells and promoted apoptosis; conversely with the down-regulation of inflammatory genes. However, pre-clinical experimental evidence is warranted for the possible translation of this combination.
Complex spatiotemporal oscillations emerge from transverse instabilities in large-scale brain networks
Authors: Clusella Pau , Deco Gustavo , Kringelbach Morten L. , Ruffini Giulio , Garcia-Ojalvo Jordi 
Published: December 2022

AbstractSpatiotemporal oscillations underlie all cognitive brain functions. Large-scale brain models, constrained by neuroimaging data, aim to trace the principles underlying such macroscopic neural activity from the intricate and multi-scale structure of the brain. Despite substantial progress in the field, many aspects about the mechanisms behind the onset of spatiotemporal neural dynamics are still unknown. In this work we establish a simple framework for the emergence of complex brain dynamics, including high-dimensional chaos and travelling waves. The model consists of a complex network of 90 brain regions, whose structural connectivity is obtained from tractography data. The activity of each brain area is governed by a Jansen neural mass model and we normalize the total input received by each node so it amounts the same across all brain areas. This assumption allows for the existence of an homogeneous invariant manifold, i.e., a set of different stationary and oscillatory states in which all nodes behave identically. Stability analysis of these homogeneous solutions unveils a transverse instability of the synchronized state, which gives rise to different types of spatiotemporal dynamics, such as chaotic alpha activity. Additionally, we illustrate the ubiquity of this route towards complex spatiotemporal activity in a network of next-generation neural mass models. Altogehter, our results unveil the bifurcation landscape that underlies the emergence of function from structure in the brain.Author summaryMonitoring brain activity with techniques such as EEG and fMRI has revealed that normal brain function is characterized by complex spatiotemporal dynamics. This behavior is well captured by large-scale brain models that incorporate structural connectivity data obtained with MRI-based tractography methods. Nonetheless, it is not yet clear how these complex dynamics emerges from the interplay of the different brain regions. In this paper we show that complex spatiotemporal dynamics, including travelling waves and high-dimensional chaos can arise in simple large-scale brain models through the destabilization of a synchronized oscillatory state. Such transverse instabilities are akin to those observed in chemical reactions and turbulence, and allow for a semi-analytical treatment that uncovers the overall dynamical landscape of the system. Overall, our work establishes and characterizes a general route towards spatiotemporal oscillations in large-scale brain models.
Biomechanical characterisation of thoracic ascending aorta with preserved pre-stresses
Authors: Parikh Shaiv , Moerman Kevin M. , Ramaekers Mitch J.F.G. , Schalla Simon , Bidar Elham , Delhaas Tammo , Reesink Koen , Huberts Wouter 
Published: December 2022

AbstractMechanical properties of an aneurysmatic thoracic aorta are potential markers of future growth and remodeling and can help to estimate risk of rupture. Aortic geometries obtained from routine medical imaging do not display wall stress distribution and mechanical properties. Mechanical properties for a given vessel may be determined from medical images at different physiological pressures using inverse finite element analysis. However, without considering pre-stresses, the estimation of mechanical properties will lack accuracy. In the present paper, we propose and evaluate a mechanical parameter identification technique, which recovers pre-stresses by determining the zero-pressure configuration of the aortic geometry. We first validated the method on a cylindrical geometry and subsequently applied it to a realistic aortic geometry. Verification of the assessed parameters was performed using synthetically generated reference data for both geometries. The method was able to estimate the true mechanical properties with an accuracy ranging from 98% to 99%.Author summaryCurrent clinical guidelines recommend to perform surgical intervention on thoracic ascending aortas with diameters greater than 55 mm. However, diameter sizes solely are not indicative of the degenerative changes in the vessel wall. Patient-specific tissue mechanical properties give better insight into the degenerative changes caused due to the variations in mass densities of the vessel wall constituents. Inverse finite element analysis can be performed on aortic geometries derived from medical images to determine tissue mechanical properties. Performing inverse finite element analysis on geometries obtained directly from medical images leads to incorrect estimation of vessel wall stresses and therefore, mechanical properties. Mechanical properties estimation is incorrect because inverse analysis does not take into account the pre-stressed nature of the geometry. In this study, we propose a novel approach to non-invasively estimatein vivomechanical properties of the thoracic ascending aorta by performing inverse finite element analysis, which considers the vessel wall pre-stresses.
Isolation of strains and their genome sequencing to analyze the mating system ofOphiocordyceps robertsii
Authors: Xu Melvin , Ashley Nathan A. , Vaghefi Niloofar , Wilkinson Ian , Idnurm Alexander 
Published: December 2022

ABSTRACTThe fungal genusOphiocordycepscontains a number of insect pathogens. One of the best known of these isOphiocordyceps sinensis, which is used in Chinese medicine and its overharvesting threatens sustainability; hence, alternative sources are being sought.Ophiocordyceps robertsii, found in Australia and New Zealand, has been proposed to be a close relative toO. sinensis, but little is known about this species despite being also of historical significance. Here,O. robertsiistrains were isolated into culture and high coverage draft genome sequences obtained and analyzed. This species has a large genome expansion, as also occurred inO. sinensis. The mating type locus was characterized, indicating a heterothallic arrangement whereby each strain has an idiomorphic region of two (MAT1-2-1, MAT1-2-2) or three (MAT1-1-1, MAT1-1-2, MAT1-1-3) genes flanked by the conservedAPN2andSLA2genes. These resources provide a new opportunity for understanding the evolution of the expanded genome in the homothallic speciesO. sinensis, as well as capabilities to explore the pharmaceutical potential in a species endemic to Australia and New Zealand.One sentence summaryOphiocordyceps robertsiiis a close relative ofO. sinensisand has a large genome but with a heterothallic mating system.
BBmix: a Bayesian Beta-Binomial mixture model for accurate genotyping from RNA-sequencing
Authors: Vigorito Elena , Barton Anne , Pitzalis Costantino , Lewis Myles J. , Wallace Chris 
Published: December 2022

AbstractMotivationWhile many pipelines have been developed for calling genotypes using RNA-sequencing data, they all have adapted DNA genotype callers that do not model biases specific to RNA-sequencing such as reference panel bias or allele specific expression.ResultsHere, we present BBmix, a Bayesian Beta-Binomial mixture model that first learns the expected distribution of read counts for each genotype, and then deploys those learned parameters to call genotypes probabilistically. We benchmarked our model on a wide variety of datasets and showed that our method generally performed better than competitors, mainly due to an increase of up to 1.4% in the accuracy of heterozygous calls. Moreover, BBmix can be easily incorporated into standard pipelines for calling genotypes. We further show that parameters are generally transferable within datasets, such that a single learning run of less than one hour is sufficient to call genotypes in a large number of samples.AvailabilityWe implemented BBmix as an R package that is available for free under a GPL-2 licence athttps://gitlab.com/evigorito/bbmixand accompanying pipeline athttps://gitlab.com/evigorito/bbmix_pipeline.
MHC class II transactivator effects on local and systemic immune responses in an α-synuclein seeded rat model for Parkinson’s disease
Authors: Fredlund Filip , Jimenez-Ferrer Itzia , Grabert Kathleen , Belfiori Lautaro , Luk Kelvin C. , Swanberg Maria 
Published: December 2022

AbstractBACKGROUNDParkinson’s disease (PD) is characterized by alpha-synuclein (α-Syn) pathology, neurodegeneration and neuroinflammation. HLA variants associated with PD and α-Syn specific circulating CD4+ T lymphocytes in PD patients highlight the importance of antigen presentation in PD etiology. The class II transactivator (CIITA) is the major regulator of MHCII expression. ReducedCiitalevels significantly increase α-Syn pathology, nigrostriatal neurodegeneration and behavioral deficits in α-Syn seed-induced rat PD models.OBJECTIVETo characterize immune profiles associated with enhanced PD-like pathology observed in rats expressing lowerCiitalevels (DA.VRA4) compared to the background (DA) strain.METHODSTo model PD, we combined rAAV-mediated α-Syn overexpression in the substantia nigra with striatal injection of α-Syn pre-formed fibrils (PFF). Immune profiles in brain and blood were analyzed by flow cytometry and multiplexed ELISA in naïve rats, 4- and 8 weeks post rAAV injection.RESULTSFlow cytometry showedCiita-dependent regulation of MHCII on microglia, brain macrophages and circulating myeloid cells. The MHCII-dependent microglial response peaked at 4 weeks post rAAV injection, whereas the MHCII levels in circulating myeloid cells peaked at 8 weeks. There was no major infiltration of macrophages or T lymphocytes into the CNS in response to α-Syn and only subtleCiita- and/or α-Syn-dependent changes in the T lymphocyte compartment. LowerCiitalevels were consistently associated with higher TNF levels in serum.CONCLUSIONSThese results suggest thatCiitaregulates susceptibility to PD-like pathology through minor but detectable changes in resident and peripheral immune cells and TNF levels, and indicate that mild immunomodulatory therapies could have therapeutic effects in PD.
cazy_webscraper: local compilation and interrogation of comprehensive CAZyme datasets
Authors: Hobbs Emma E. M. , Gloster Tracey M. , Pritchard Leighton 
Published: December 2022

AbstractCarbohydrate Active enZymes (CAZymes) are pivotal in biological processes including energy metabolism, cell structure maintenance, signalling and pathogen recognition. Bioinformatic prediction and mining of CAZymes improves our understanding of these activities, and enables discovery of candidates of interest for industrial biotechnology, particularly the processing of organic waste for biofuel production. CAZy (www.cazy.org) is a high-quality, manually-curated and authoritative database of CAZymes that is often the starting point for these analyses. Automated querying, and integration of CAZy data with other public datasets would constitute a powerful resource for mining and exploring CAZyme diversity. However, CAZy does not itself provide methods to automate queries, or integrate annotation data from other sources (except by following hyperlinks) to support further analysis.To overcome these limitations we developedcazy_webscraper, a command-line tool that retrieves data from CAZy and other online resources to build a local, shareable, and reproducible database that augments and extends the authoritative CAZy database.cazy_webscraper’s integration of curated CAZyme annotations with their corresponding protein sequences, up to date taxonomy assignments, and protein structure data facilitates automated large-scale and targeted bioinformatic CAZyme family analysis and candidate screening. This tool has found widespread uptake in the community, with over 20,000 downloads.We demonstrate the use and application ofcazy_webscraperto: (i) augment, update and correct CAZy database accessions; (ii) explore taxonomic distribution of CAZymes recorded in CAZy, identifying underrepresented taxa and unusual CAZy class distributions; and (iii) investigate three CAZymes having potential biotechnological application for degradation of biomass, but lacking a representative structure in the PDB database. We describe in general howcazy_webscraperfacilitates functional, structural and evolutionary studies to aid identification of candidate enzymes for further characterisation, and specifically note that CAZy provides supporting evidence for recent expansion of the Auxiliary Activities (AA) CAZy family in eukaryotes, consistent with functions potentially specific to eukaryotic lifestyles.Supplementary informationcazy_webscrapersource code is available athttps://github.com/HobnobMancer/cazy_webscraper, and online documentation is provided athttps://cazywebscraper.readthedocs.io.
Selective volumetric excitation and imaging for single molecule localization microscopy in multicellular systems
Authors: Galgani Tommaso , Fedala Yasmina , Zapata Romeo , Caccianini Laura , Viasnoff Virgile , Sibarita Jean-Baptiste , Galland Rémi , Dahan Maxime , Hajj Bassam 
Published: December 2022

AbstractLight sheet fluorescence microscopy (LSFM) has become a leading standard in high-resolution imaging of living samples in 2- and 3-dimensions. Biological samples are however not restricted to a single observation plane and several molecular processes evolve rapidly in 3D. The conventional mechanical scanning required in LSFM limits the range of observable dynamics and are usually restricted in resolution. Here we introduce a new strategy for instantaneous volumetric excitation and volumetric imaging of single-molecules in cell aggregates. The technique combines, for the first time, the use of light sheet microscopy and multifocus microscopy (MFM) and enables a volumetric 4D imaging of biological samples with single-molecule resolution. We engineered the excitation beam to yield a modular and uniform excitation matching the observable detection range of MFM. The strength of the method is highlighted with examples of single-molecule 3D tracking and 3D super-resolution imaging in multicellular samples.
Development of non-alcoholic steatohepatitis is associated with gut microbiota but not oxysterol synthesis
Authors: Wyss Jacqueline , Raselli Tina , Wyss Annika , Telzerov Anja , Rogler Gerhard , Krupka Niklas , Yilmaz Bahtiyar , Schmidt Thomas SB , Misselwitz Benjamin 
Published: December 2022

AbstractLiver steatosis is the most frequent liver disorder and its advanced stage, non-alcoholic steatohepatitis (NASH), will soon become the main reason for liver fibrosis and cirrhosis. The “multiple hits hypothesis” suggests that progression from simple steatosis to NASH is triggered by multiple factors including the gut microbiota composition. The Epstein Barr virus induced gene 2 (EBI2) is a receptor for the oxysterol 7a, 25-dihydroxycholesterol synthesized by the enzymes CH25H and CYP7B1. EBI2 and its ligand control activation of immune cells in secondary lymphoid organs and the gut. Here we show a concurrent study of the microbial dysregulation and perturbation of the EBI2 axis in a mice model of NASH.We used mice with wildtype, or littermates with CH25H-/-, EBI2-/-, or CYP7B1-/-genotypes fed with a high-fat diet (HFD) containing high amounts of fat, cholesterol, and fructose for 20 weeks to induce liver steatosis and NASH. Fecal and small intestinal microbiota samples were collected, and microbiota signatures were compared according to genotype and NASH disease state.We found pronounced differences in microbiota composition of mice with HFD developing NASH compared to mice did not developing NASH. In mice with NASH, we identified significantly increased 33 taxa mainly belonging to the Clostridiales order and/ or the family, and significantly decreased 17 taxa. Using an Elastic Net algorithm, we suggest a microbiota signature that predicts NASH in animals with a HFD from the microbiota composition with moderate accuracy (area under the receiver operator characteristics curve=0.64). In contrast, no microbiota differences regarding the studied genotypes (wildtype vs knock-out CH25H-/-, EBI2-/-, or CYP7B1-/-) were observed.In conclusion, our data confirm previous studies identifying the intestinal microbiota composition as a relevant marker for NASH pathogenesis. Further, no link of the EBI2 – oxysterol axis to the intestinal microbiota was detectable in the current study.