bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel Pan-viral prophylaxis strategy using vaccine adjuvant CAF09b protects against influenza virus infection
Authors: Zimmermann Julie , Schmidt Signe Tandrup , Trebbien Ramona , Cox Rebecca Jane , Zhou Fan , Follmann Frank , Pedersen Gabriel Kristian , Christensen Dennis 
Published: October 2021

ABSTRACTThe SARS-CoV-2 pandemic caused a massive health and societal crisis, although the fast development of effective vaccines reduced some of the impact. To prepare for future pandemics, a pan-viral prophylaxis could be used to control the initial virus outbreak in the period prior to vaccine approval. The liposomal vaccine adjuvant CAF®09b contains the TLR3 agonist polyinosinic:polycytidylic acid, which induces a type I interferon (IFN-I) response and an antiviral state in the affected tissues. When testing CAF09b as a potential pan-viral prophylaxis, we observed that intranasal administration of CAF09b to mice resulted in an influx of innate immune cells into the nose and lungs and upregulation of IFN-I related gene expression. When CAF09b was administered prior to challenge with mouse-adapted influenza A/Puerto Rico/8/1934 virus, it protected from severe disease, although virus was still detectable in the lungs. However, when CAF09b was administered after influenza challenge, the mice had a similar disease course to controls. In conclusion, CAF09b may be a suitable candidate as a pan-viral prophylactic treatment for epidemic viruses, but must be administered prior to virus exposure to be effective.
Roosting ecology and the evolution of bat landing maneuvers
Authors: Boerma David B. , Swartz Sharon M. 
Published: October 2021

AbstractBiomechanics is poised at the intersection of organismal form, function, and ecology, and forms a practical lens through which to investigate evolutionary linkages among these factors. We conducted the first evolutionary analysis of bat flight dynamics by examining the phylogenetic patterning of landing mechanics. We discovered that bats perform stereotyped maneuvers that are correlated with landing performance quantified as impact force, and that these are linked with roosting ecology, a critical aspect of bat biology. Our findings suggest that bat ancestors performed simple, four-limbed landings, similar to those performed by gliding mammals, and that more complex landings evolved in association with novel roost types. This explicit connection between ecology and biomechanics presents the opportunity to identify traits that are associated with a locomotor behavior of known ecological relevance, thus laying the foundation for a broader understanding of the evolution of flight and wing architecture in this extraordinarily successful mammalian lineage.
Mitochondrial fission process 1 (MTFP1) controls bioenergetic efficiency and prevents inflammatory cardiomyopathy and heart failure in mice
Authors: Donnarumma Erminia , Kohlhaas Michael , Vimont Elodie , Kornobis Etienne , Chaze Thibault , Giai Gianetto Quentin , Matondo Mariette , Moya-Nilges Maryse , Maack Christoph , Wai Timothy 
Published: October 2021

AbstractMitochondria are paramount to the metabolism and survival of cardiomyocytes. Here we show that Mitochondrial Fission Process 1 (MTFP1) is essential for cardiac structure and function. Constitutive knockout of cardiomyocyte MTFP1 in mice resulted in adult-onset dilated cardiomyopathy (DCM) characterized by sterile inflammation and cardiac fibrosis that progressed to heart failure and middle-aged death. Failing hearts from cardiomyocyte-restricted knockout mice displayed a general decline in mitochondrial gene expression and oxidative phosphorylation (OXPHOS) activity. Pre-DCM, we observed no defects in mitochondrial morphology, content, gene expression, OXPHOS assembly nor phosphorylation dependent respiration. However, knockout cardiac mitochondria displayed reduced membrane potential and increased non-phosphorylation dependent respiration, which could be rescued by pharmacological inhibition of the adenine nucleotide translocase ANT. Primary cardiomyocytes from pre-symptomatic knockout mice exhibited normal excitation-contraction coupling but increased sensitivity to programmed cell death (PCD), which was accompanied by an opening of the mitochondrial permeability transition pore (mPTP). Intriguingly, mouse embryonic fibroblasts deleted for Mtfp1 recapitulated PCD sensitivity and mPTP opening, both of which could be rescued by pharmacological or genetic inhibition of the mPTP regulator Cyclophilin D. Collectively, our data demonstrate that contrary to previous in vitro studies, the loss of the MTFP1 promotes mitochondrial uncoupling and increases cell death sensitivity, causally mediating pathogenic cardiac remodeling.
An in-vivo digital atlas of the spatially reliable cerebral vasculature in mice
Authors: Hinz Rukun , Malekzadeh Meriam , Peeters Lore M. , Vanreusel Verdi , Verhoye Marleen , Van der Linden Annemie , Keliris Georgios A. 
Published: October 2021

AbstractCerebral vascular abnormalities can have a large impact on brain function and have been frequently detected as a comorbidity in various neuropathologies. The mouse is the most common pre-clinical animal model used to investigate neuropathologies and thus cerebral vascular atlases of this species are indispensable. In particular, an atlas derived from multiple animals and that can address inter-subject variability is still absent. The current study presents a mouse cerebral vascular atlas developed from MR 2D-TOF angiograms acquired from a relatively high number (N=21) of 12 weeks old male C57BL/6 mice. The vascular atlas we present depicts large arteries, veins and sinuses that are more spatially reliable across animals than smaller vessels. The atlas is available for download and contains multiple datasets: i) a cerebral vascular atlas; ii) a digital segmentation of large vessels (arteries and veins); iii) a high resolution T2 anatomical background aligned to the atlas; iv) a skeletonized vascular atlas; and v) a vascular graph model. We suggest that these components provide a very potent analysis tool for mouse fMRI data and that the atlas can be used as a template for multimodal brain imaging studies. To this end, we also demonstrate an explicit application of the atlas for the investigation of vascular influences in resting-state fMRI.
Incorporating Target-Specific Pharmacophoric Information Into Deep Generative Models For Fragment Elaboration
Authors: Hadfield Thomas E. , Imrie Fergus , Merritt Andy , Birchall Kristian , Deane Charlotte M. 
Published: October 2021

AbstractDespite recent interest in deep generative models for scaffold elaboration, their applicability to fragment-to-lead campaigns has so far been limited. This is primarily due to their inability to account for local protein structure or a user’s design hypothesis. We propose a novel method for fragment elaboration, STRIFE that overcomes these issues. STRIFE takes as input Fragment Hotspot Maps (FHMs) extracted from a protein target, and processes them to provide meaningful and interpretable structural information to its generative model, which in turn is able to rapidly generate elaborations with complementary pharmacophores to the protein. In a large-scale evaluation, STRIFE outperforms existing, structure-unaware, fragment elaboration methods in proposing highly ligand efficient elaborations. In addition to automatically extracting pharmacophoric information from a protein target’s FHM, STRIFE optionally allows the user to specify their own design hypotheses.
Diversification of multipotential postmitotic mouse retinal ganglion cell precursors into discrete types
Authors: Shekhar Karthik , Whitney Irene E. , Butrus Salwan , Peng Yi-Rong , Sanes Joshua R. 
Published: October 2021

AbstractThe genesis of broad neuronal classes from multipotential neural progenitor cells has been extensively studied, but less is known about the diversification of a single neuronal class into multiple types. We used single-cell RNA-seq to study how newly-born (postmitotic) mouse retinal ganglion cell (RGC) precursors diversify into ~45 discrete types. Computational analysis provides evidence that RGC type identity is not specified at mitotic exit, but acquired by gradual, asynchronous fate restriction of postmitotic multipotential precursors. Some types are not identifiable until a week after they are generated. Immature RGCs may be specified to project ipsilaterally or contralaterally to the rest of the brain before their type identity has been determined. Optimal transport inference identifies groups of RGC precursors with largely non-overlapping fates, distinguished by selectively expressed transcription factors that could act as fate determinants. Our study provides a framework for investigating the molecular diversification of discrete types within a neuronal class.
Impact of various preservation and storage methods on the viability of mycoplasma field strains isolated in Mali
Authors: Sery Amadou , Sidibe Cheick Abou Kounta , Kone Mamadou , Sacko Bekaye , Awuni Joseph , Amafu William , Niang Mamadou 
Published: October 2021

AbstractThe survival of five mycoplasma strains was studied in different storage media (Mycoplasma complet media without cryopreservative agent, Mycoplasma complete media with addition of horse serum, Mycoplasma complete media with addition of glycerol and lyophilized cultures without stabilizer) under different temperatures (+37°C, +4°C, −20°C, −85°C) during 24 months. Five Mycoplasma strains, Mycoplasma mycoides subsp mycoides (Mmm), Mycoplasma bovis (Mb), Mycoplasma agalactiae (Ma), Mycoplasma gallisepticum (Mg) and Mycoplasma synoviae (Ms) were isolated from various parts of the country. The initial titers of the strains determined by the agar plate count before storage were 42.4×107 UFC/ml (8.6 log UFC/ml) for Mmm strain; 32.4×108 UFC/ml (9.51 log UFC/ml) for M.bovis strain; 12.4×109 UFC/ml (10.09 log UFC/ml) for Ma strain; 2.4×109 UFC/ml (9.38 log UFC/ml) for Mg and 2.8×109 UFC/ml (9.45 log UFC/ml) for Ms strain. After 3 weeks of storage, no viable mycoplasmas were detected in all the conservation media at +37°C and after 3 months of storage at +4°C except for the lyophilized cultures in which an average viability rate of 17.81% was observed. Overall, the mycoplasma strains remained viable at freezing temperatures after 24 months regardless of the storage medium, but with decreasing titers, which was noticeable with mycoplasma complete media, and mycoplasma media with horse serum. Conversely, at −20°C the average viability rates after 24 months of storage were 84.36% (with glycerol) and 90.04% (lyophilized cultures). At −85°C after 24 months of storage, this was 87.98% (with glycerol) and 91.44% (lyophilized cultures). These findings suggest that, in the absence of the lysophylisation process, the addition of glycerol may be recommended for long-term storage of frozen mycoplasma isolates.
Mining transcriptomic data to identifySaccharomyces cerevisiaesignatures related to improved and repressed ethanol production under fermentation
Authors: Sazegari Sima , Niazi Ali , Zinati Zahra , Eskandari Mohammad Hadi 
Published: October 2021

AbstractSaccharomyces cerevisiaeis known for its outstanding ability to produce ethanol in industry. Identifying the dynamic of gene expression inS. cerevisiaein response to fermentation is required for the establishment of any ethanol production improvement program. The goal of this study was to identify the discriminative genes between improved and repressed ethanol production as well as clarifying the molecular responses to this process through mining the transcriptomic data. Through 11 machine learning based algorithms from RapidMiner employed on available microarray datasets related to yeast fermentation performance under Mg2+and Cu2+supplementation, 172 probe sets were identified by at least 5 AWAs. Some have been identified as being involved in carbohydrate metabolism, oxidative phosphorylation, and ethanol fermentation. Principal component analysis (PCA) and heatmap clustering were also validated the top-ranked selective probe sets. According to decision tree models, 17 roots with 100% performance were identified.OLI1andCYC3were identified as the roots with the best performance, demonstrated by the most weighting algorithms and linked to top two significant enriched pathways including porphyrin biosynthesis and oxidative phosphorylation.ADH5andPDA1are also recognized as differential top-ranked genes that contribute to ethanol production. According to the regulatory clustering analysis,Tup1has a significant effect on the top-ranked target genesCYC3andADH5genes. This study provides a basic understanding of theS. cerevisiaecell molecular mechanism and responses to two different medium conditions (Mg2+and Cu2+) during the fermentation process.
Hybridisation and chloroplast capture between ancient Themeda triandra ecotypes in Australia
Authors: Dunning Luke T. , Oloffson Jill K. , Papadopulos Alexander S.T. , Baleeiro Paulo C. , Ntshangase Sinethemba , Barker Nigel , Jobson Richard W. 
Published: October 2021

AbstractEcotypes are distinct populations within a species which are adapted to specific environmental conditions. Understanding how these ecotypes become established, and how they interact when reunited, is fundamental to elucidating how ecological adaptations are maintained. This study focuses on Themeda triandra, a dominant grassland species across Asia, Africa and Australia. It is the most widespread plant in Australia, where it has distinct ecotypes that are usually restricted to either wetter and cooler coastal regions or the drier and hotter interior. We use whole genome sequencing for over 80 Themeda accessions to reconstruct the evolutionary history of T. triandra and related taxa. A chloroplast phylogeny confirms that Australia was colonised by T. triandra twice, with the division between ecotypes predating their arrival in Australia. The nuclear genome provides evidence of gene-flow among the ecotypes, largely restricted to two geographic areas. In northern Queensland there appears to be a hybrid zone with admixed nuclear genomes and shared plastid haplotypes. Conversely, in the cracking claypans of Western Australia, there is cytonuclear discordance with individuals possessing the coastal plastid and interior clade nuclear genomes. This chloroplast capture is potentially a result of adaptive introgression, with selection detected in the rpoC2 gene which is associated with water use efficiency. A stable hybrid zone in the east, and the displacement of one ecotype in the west, highlights the unpredictable nature of hybrid zones, with repeated contacts between the same ecotypes producing different outcomes.
Unlocking the functional potential of polyploid yeasts
Authors: Mozzachiodi Simone , Krogerus Kristoffer , Gibson Brian , Nicolas Alain , Liti Gianni 
Published: October 2021

AbstractBreeding and domestication have generated widely exploited crops, animals and microbes. However, many Saccharomyces cerevisiae industrial strains have complex polyploid genomes and are sterile, preventing genetic improvement strategies based on breeding. Here, we present a novel strain improvement approach based on the budding yeasts’ property to promote genetic recombination when meiosis is interrupted and cells return-to-mitotic-growth (RTG). We demonstrated that two unrelated sterile industrial strains with complex triploid and tetraploid genomes were RTG-competent and developed a visual screening for easy and high-throughput identification of recombined RTG clones based on colony phenotypes. Sequencing of the evolved clones revealed unprecedented levels of RTG-induced genome-wide recombination. We generated and extensively phenotyped a RTG library and identified clones with superior biotechnological traits. Thus, we propose the RTG-framework as a fully non-GMO workflow to rapidly improve industrial yeasts that can be easily brought to the market.
Effects of Oncohistone Mutations and PTM Crosstalk on the N-terminal Acetylation Activities of NatD
Authors: Ho Yi-Hsun , Huang Rong 
Published: October 2021

ABSTRACTAcetylation at the α-N-terminus (Nα) is one of the most abundant modifications detected on histone H4 and H2A, which is catalyzed by N-terminal acetyltransferase D (NatD). NatD substrate recognition motif, N-terminal SGRGK, is enriched with frequent oncohistone mutations and post-translational modifications (PTMs). However, there is no information on how oncohistone mutations and other PTMs affect NatD-catalyzed acetylation. Herein, we determined how changes of local chemical environment on the N-terminal SGRGK sequence regulate NatD-catalyzed Nα acetylation on histone H4/H2A. Our studies indicate that all oncohistone mutations at SGRG suppressed the catalytic efficiency of NatD. Meanwhile, H4 serine 1 phosphorylation and arginine 3 methylation also negatively affect the NatD activity, but the lysine 5 acetylation has a marginal effect on NatD. This work reveals the impacts of oncohistone mutations on NatD activity and unravels the crosstalk between NatD and PTMs. To our knowledge, this is the first report on the potential regulatory mechanism of NatD, highlighting different revenues to interrogate the NatD-mediated pathway in the future.
Structural analysis of the lncRNA SChLAP1 reveals protein binding interfaces and a conformationally heterogenous retroviral insertion
Authors: Falese James P. , McFadden Emily J. , D’Inzeo Christopher A. , Hargrove Amanda E. 
Published: October 2021

ABSTRACTThe lncRNA Second Chromosome Locus Associated with Prostate 1 (SChLAP1) was previously identified as a predictive biomarker and potential driver of aggressive prostate cancer. Recent work suggests that SChLAP1 may bind the SWI/SNF chromatin remodeling complex to promote prostate cancer metastasis, though the exact role of SWI/SNF recognition is debated. To date, there are no detailed biochemical studies ofapoSChLAP1 or SChLAP1:protein complexes. Herein, we report the first secondary structure model of SChLAP1 using SHAPE-MaPinvitro,in cellulo, andex cellulo(protein-free). Comparison of theex celluloandin cellulodata via ΔSHAPE identified putative protein binding sites within SChLAP1. In addition, we identified primate conserved exons of SChLAP1 as well as regions that appear to have been incorporated through retroviral insertion. In particular, we characterized a complex structural landscape in a protein binding region at the 3′—end of SChLAP1 derived from a THE1B-type retroviral insertion, suggesting a role for an exapted RNA structure in SChLAP1:protein recognition and prostate cancer progression. This work lays the foundation for future efforts to selectively target and disrupt the SChLAP1:protein interface and to develop new therapeutic avenues in prostate cancer treatment.
Non-monotonic fibril surface occlusion by GFP tags from coarse-grained molecular simulations
Authors: Shillcock Julian C. , Hastings Janna , Riguet Nathan , Lashuel Hilal 
Published: October 2021

AbstractThe pathological growth of amyloid fibrils in neurons underlies the progression of neurodegenerative diseases including Alzheimer’s and Parkinson’s disease. Fibrils form when soluble monomers oligomerise in the cytoplasm. Their subsequent growth occurs via nucleated polymerization mechanisms involving the free ends of the fibrils augmented by secondary nucleation of new oligomers at their surface. Amyloid fibrils possess a complex interactome with diffusing cytoplasmic proteins that regulates many aspects of their growth, seeding capacity, biochemical activity and transition to pathological inclusions in diseased brains. Changes to their surface are also expected to modify their interactome, pathogenicity and spreading in the brain. Many assays visualise fibril formation, growth and inclusion formation by decorating monomeric proteins with fluorescent tags such as GFP. Recent studies from our group suggest that tags with sizes comparable to the fibril radius may modify the fibril surface accessibility and thus their PTM pattern, interactome and ability to form inclusions. Using coarse-grained molecular simulations of a single alpha synuclein fibril tagged with GFP we find that thermal fluctuations of the tags create a non-monotonic, size-dependent sieve around the fibril that perturbs its interactome with diffusing species. Our results indicate that experiments using tagged and untagged monomers to study the growth and interactome of fibrils should be compared with caution, and the confounding effects of the tags are more complex than a reduction in surface accessibility. The prevalence of fluorescent tags in amyloid fibril growth experiments suggests this has implications beyond the specific alpha synuclein fibrils we model here.
Defining cellular complexity in human autosomal dominant polycystic kidney disease by multimodal single cell analysis
Authors: Muto Yoshiharu , Dixon Eryn E. , Yoshimura Yasuhiro , Wu Haojia , Omachi Kohei , King Andrew J. , Olson Eric N. , Gunawan Marvin G. , Kuo Jay J. , Cox Jennifer , Miner Jeffrey H. , Seliger Stephen L. , Woodward Owen M. , Welling Paul A. , Watnick Terry J. , Humphreys Benjamin D. 
Published: October 2021

AbstractAutosomal dominant polycystic kidney disease (ADPKD) is the leading genetic cause of end stage renal disease and is characterized by the formation and progressive expansion of kidney cysts. Most ADPKD cases arise from mutations in either the PKD1 or PKD2 gene but the precise downstream signaling pathways driving cyst growth are not well understood, and relatively few studies investigate human cystic kidney due to sample scarcity. In order to better understand the cell types and states driving human ADPKD progression, we analyzed eight ADPKD and five healthy human kidney samples, generating a single cell multiomic atlas consisting of ~100,000 single nucleus transcriptomes and ~50,000 single nucleus epigenomes. The integrated datasets identified 11 primary cell clusters including most epithelial cell types as well as large endothelial and fibroblast cell clusters. Proximal tubular cells from ADPKD kidneys expressed a failed repair transcriptomic signature characterized by profibrotic and proinflammatory transcripts. We identified the G protein-coupled receptor GPRC5A as specifically upregulated in cyst lining cells derived from collecting duct. The principal cell subpopulation enriched for GPRC5A expression also exhibited increased transcription factor binding motif availability for NF-κB, TEAD, CREB and retinoic acid receptor families and we identified and validated a distal enhancer regulating GPRC5A expression containing these transcription factor binding motifs. This study establishes the single cell transcriptomic and epigenomic landscape of ADPKD, revealing previously unrecognized cellular heterogeneity.
A pathogenic fungus uses volatiles to entice male flies into fatal matings with infected female cadavers
Authors: Naundrup Andreas , Bohman Björn , Kwadha Charles A. , Jensen Annette B. , Becher Paul G. , De Fine Licht Henrik H. 
Published: October 2021

AbstractTo ensure dispersal, many parasites and pathogens behaviourally manipulate infected hosts. Other pathogens and certain insect-pollinated flowers use sexual mimicry and release deceptive mating signals. However, it is unusual for pathogens to rely on both behavioural host manipulation and sexual mimicry. Here, we show that the host-specific and behaviourally manipulating pathogenic fungus, Entomophthora muscae, generates a chemical blend of volatile sesquiterpenes and alters the level of natural host cuticular hydrocarbons in dead infected female house fly (Musca domestica) cadavers. Healthy male house flies respond to the fungal compounds and are enticed into mating with dead female cadavers. This is advantageous for the fungus as close proximity between host individuals leads to an increased probability of infection. The fungus-emitted volatiles thus represent the evolution of an extended phenotypic trait that exploit male flies’ willingness to mate and benefit the fungus by altering the behavioural phenotype of uninfected healthy male host flies.