bluuebunny/crossref_metadata_2025_split huggingface dataset:
gExcite - A start-to-end framework for single-cell gene expression, hashing, and antibody analysis
Authors: Grob Linda , Bertolini Anne , Carrara Matteo , Menzel Ulrike , Tastanova Aizhan , Beisel Christian , Levesque Mitchell P. , Stekhoven Daniel J. , Singer Franziska 
Published: May 2022

AbstractSummarySingle-cell RNA sequencing (scRNA-seq) based gene expression analysis is now an established powerful technique to decipher tissues at a single-cell level. Recently, CITE-seq emerged as a multimodal single-cell technology capturing gene expression and surface protein information from the same single-cells, which allows unprecedented insights into disease mechanisms and heterogeneity, as well as immune cell profiling. Multiple single-cell profiling methods exist, but they are typically focussed on either gene expression or antibody analysis, not their combination. Moreover, existing software suites are not easily scalable to a multitude of samples. To this end, we designed gExcite, a start-to-end workflow that provides both gene expression and CITE-seq analysis, as well as hashing deconvolution. Embedded in the Snakemake workflow manager, gExcite facilitates reproducible and scalable analyses. We showcase the output of gExcite on a study of different dissociation protocols on PBMC samples.AvailabilitygExcite is open source available on github at https://github.com/ETH-NEXUS/gExcite_pipeline The software is distributed under the GNU General Public License 3 (GPL3).Contactsinger@nexus.ethz.chSupplementary InformationSupplementary information is available at the journal’s web site.
Identification of novel basil downy mildew resistance genes using de novo comparative transcriptomics
Authors: Allen Kelly S. , DeIulio Gregory A. , Pyne Robert , Maman Jacob , Guo Li , Wick Robert L. , Simon James , Gershenson Anne , Ma Li-Jun 
Published: May 2022

SummarySweet basil (Ocimum basilicum L.) production is threatened by the oomycete pathogen Peronospora belbahrii causing basil downy mildew (BDM); BDM resistant cultivar ‘Mrihani’ (MRI) was identified in a germplasm screen, and fertile progeny were produced through a breeding program with BDM-susceptible ‘Newton’ (SB22), but the molecular mechanisms conferring resistance in MRI and progeny remained unknownComparative transcriptomics was performed to identify candidate resistance genes and potential mechanisms for BDM resistance; RNA samples from BDM-infected MRI and SB22 plants were harvested at 4 time points during the first 3 days of infection to differentiate interactions in resistant and susceptible plants.Three categories of genes uniquely induced in resistant MRI upon pathogen challenge were identified: nucleotide-binding leucine rich repeat proteins (NLRs), multi-functional receptor-like kinases (RLKs), and secondary metabolic enzymes; validation of the top resistance candidate NLR gene confirmed its unique presence in MRI as well as in two of four resistant MRIxSB22 F2 progeny.In MRI, pathogen challenge also upregulated transcripts in the salicylic acid synthesis pathway, suggesting its role in BDM resistance, and demonstrating the application of using comparative transcriptomics to identify resistance genes and mechanisms in non-model crops for marker-assisted breeding approaches.
The electric field generated by cationic TiO2 nanoparticles can be their key antimicrobial factor
Authors: Zhukova Lyudmila V. 
Published: May 2022

ABSTRACTThe antimicrobial effect of TiO2 nanoparticles (TiO2 NPs) has been reliably established. However, the mechanism of this action remains unclear. Currently, according to the dominant hypothesis, it is assumed that the key destructive mechanism is the photocatalytic oxidation of cell components, and the key antimicrobial factor is the reactive oxygen species (ROS) formed on the surface of TiO2 NPs as a result of photocatalysis. In this communication, for the first time, the influence of the electric field created by cationic TiO2 NPs is suggested as a key killing factor, and the key antimicrobial mechanism - the electrical breakdown of the cell membranes and the destruction of the DNA molecule under the action of this field. Here, it was shown by mathematical calculation that TiO2 NPs are able to generate an electric field with a strength sufficient for an electrical breakdown of bilayer lipid membranes, which can lead to a violation of the structure and vital functions of the cytoplasmic membrane (CPM) and to collapse of DNA molecule.GRAPHICAL ABSTRACT
Whole-Genome RNA Sequencing of Femoral Head Impingement Cartilage Identifies FGF18 As A Biomarker in Hip Osteoarthritis Progression
Authors: Kuhns Benjamin D. , Reuter John M. , Hansen Victoria L. , Soles Gillian , Jonason Jennifer H. , Ackert-Bicknell Cheryl , Wu Chia-Lung , Giordano Brian D. 
Published: May 2022

AbstractIntroductionThe natural history of Femoroacetabular Impingement (FAI) has been clinically associated with the development of hip osteoarthritis (OA); however, the pathobiological mechanisms underlying the transition from focal impingement to global joint degeneration remain unclear. The goal of the study was to investigate differences in transcriptomic profiles of the cartilage from FAI and hip OA patients using whole-genome RNA sequencing.MethodsThirty-seven patients were included in the study with 20 diagnosed with FAI undergoing arthroscopic treatment and 15 diagnosed with hip OA undergoing total hip arthroplasty (THA). Cartilage samples were obtained intraoperatively over the femoral head-neck junction for both FAI and OA cohorts. Whole-genome RNA sequencing was performed on 10 gender-matched patients in the FAI and OA cohorts with the remaining samples used for histopathologic analysis using the Osteoarthritis Research Society International (OARSI) grading system and qRT-PCR validation. Target validation was further confirmed with immunohistochemical staining for FGF18 on FAI and OA cartilage samples.ResultsWe identified a total of 3,531 Differentially Expressed Genes (DEGs) between the FAI and OA cohorts with multiple targets for genes implicated in canonical OA pathways. qRT-PCR validation confirmed increased expression of FGF18 and WNT16 in the FAI samples, while there was increased expression of MMP13 and ADAMTS4 in the OA samples. Expression levels of FGF18 and WNT16 were also higher in FAI samples with mild cartilage damage (OARSI grades 1-2) compared to FAI samples with severe cartilage damage or OA cartilage (OARSI grade 4-6). Immunohistochemical evaluation identified increased FGF18 staining in OARSI grade 1-2 FAI samples compared to OARSI grade 5-6 FAI and OA samples.ConclusionsRNA sequencing of cartilage of FAI and hip OA patients identified a negative association of FGF18 expression levels with cartilage damage severity, suggesting that FGF18 may be used as a marker for hip OA progression. Future evaluation of FGF18 signaling as well as other markers in early OA may yield further insight into disease prevention and treatment.
Rapid, in-patient adaptations of Legionella pneumophila to the human host
Authors: Leenheer Daniël , Moreno Anaísa B. , Murray Susan , Jarraud Sophie , Ginevra Christophe , Guy Lionel 
Published: May 2022

AbstractLegionella pneumophila are host-adapted bacteria that infect and reproduce primarily in amoeboid protists. Using similar infection mechanisms, they infect human macrophages, and cause Legionnaires’ disease, an atypical pneumonia, and the milder Pontiac fever. We hypothesized that, despite these similarities, the hosts are different enough so that there exist high-selective value mutations that would dramatically increase the fitness of Legionella inside the human host. By comparing a large number of isolates from independent infections, we identified two genes, mutated in three unrelated patients, despite the short duration of the incubation period (2-14 days). One is a gene coding for an outer membrane protein (OMP) belonging to the OmpP1/FadL family. The clinical strain, carrying the mutated OMP homolog, grows faster in macrophages than the wild type strain, and thus appears to be better adapted to the human host. The other is a gene coding for a protein involved in cyclic-di-GMP regulation, which in turn modulates flagellar activity. As human-to-human transmission is very rare, fixation of these mutations into the population and spread into the environment is unlikely. Therefore, convergent evolution – here mutations in the same genes observed in independent human infections – could point to adaptations to the accidental human host. These results suggest that despite its ability to infect, replicate, and disperse from amoebae, L. pneumophila is not well adapted to the human host.Impact statementLegionella pneumophila is primarily infecting amoeboid protists, but occasionally infects human lung macrophages, causing Legionnaires’ disease, an atypical pneumonia. By comparing 171 isolates from patients to their probable environmental source, we identified 119 mutations that presumably occurred in-patient. Among these, several mutations occurred in the gene. In particular, two genes were mutated thrice, significantly more often than expected by chance alone, and are likely to represent adaptations to the human host. We experimentally show that, for one mutation at least, the mutated strain grows faster in human macrophages than in amoebae. By specifically investigating in-patient mutations, we were able to identify two genes that might be involved in human host-specific adaptations of L. pneumophila. This result suggests that L. pneumophila is not particularly well adapted to the human host, as mutations get fixed in-patient, during the short course of an infection (2-14 days), indicating a very high selective value.Data SummaryThe sequencing data generated in this study are available in the NCBI database under the BioProject accession number: PRJEB52976.
A protocol for the use of cold plasma treatment to inhibit in vitro growth of Fusarium graminearum
Authors: Kaur M. , Hüberli D. , Bayliss K. L. 
Published: May 2022

AbstractCold plasma is an ionised gas that can be used to control a range of microorganisms. In this study, a protocol was developed for cold plasma treatment of in vitro growth of Fusarium graminearum, a global mycotoxic species generally associated with cereal grain. Four F. graminearum isolates on potato dextrose agar (PDA) were treated with cold plasma for 70 s from a distance of 21 cm in a closed environment, and their radial colony growth was measured. To consider whether cold plasma modified the culture media, non-inoculated half-strength PDA plates were also treated with cold plasma prior to inoculation with the F. graminearum isolates. Similarly, to determine if a rise in temperature during the treatment impacted the growth of the isolates or the culture media itself, the plates were treated with dry heat before and after inoculation with the isolates. Treatment of F. graminearum isolates with cold plasma inhibited their growth and was not associated with the culture media or the rise in temperature during the treatment. Optical emission spectroscopy of cold plasma identified reactive (ionised) species of argon, nitrogen, hydrogen, oxygen, copper, and carbon with the highest number of peaks produced for argon. These results demonstrate that cold plasma can significantly reduce the in vitro growth of F. graminearum isolates when treated in a closed environment and suggest there is potential to control the in vivo growth of F. graminearum.
The Cancermuts software package for the prioritization of missense cancer variants: a case study of AMBRA1 in melanoma
Authors: Tiberti Matteo , Di Leo Luca , Vistesen Mette Vixø , Kuhre Rikke , Cecconi Francesco , De Zio Daniela , Papaleo Elena 
Published: May 2022

AbstractCancer genomics and cancer mutation databases have made a wealth of information about missense mutations found in cancer patient samples. Contextualizing by means of annotation and predicting the effect of amino acid change help identify which ones are more likely to have a pathogenic impact. Those can be validated by means of experimental approaches that assess the impact of protein mutations on the cellular functions or their tumorigenic potential. Here, we propose the integrative bioinformatic approach Cancermuts, implemented as a Python package. Cancermuts is able to gather known missense cancer mutations from databases such as cBioPortal and COSMIC, and annotate them with the pathogenicity score REVEL as well as information on their source. It is also able to add annotations about the protein context these mutations are found in, such as post-translational modification sites, structured/ustructured regions, presence of short linear motifs and more. We applied Cancermuts to the intrinsically disordered protein AMBRA1, a key regulator of many cellular processes tightly (de)regulated in cancer. By these means, we classified mutations of AMBRA1 in melanoma, where AMBRA1 is highly mutated and displays a tumor-suppressive role. Next, based on REVEL score, position along the sequence and their local context, we applied cellular and molecular approaches to validate the predicted pathogenicity of a subset of mutations in an in vitro melanoma model. By doing so, we have identified two AMBRA1 mutations which show enhanced tumorigenic potential and are worth further investigation, highlighting the usefulness of the tool. Cancermuts can be used on any protein targets starting from minimal information, and it is available at https://www.github.com/ELELAB/cancermuts as free software.
Engineering aSinorhizobium melilotichassis with monopartite, single replicon genome configuration
Authors: Wagner Marcel , Döhlemann Johannes , Geisel David , Sobetzko Patrick , Serrania Javier , Lenz Peter , Becker Anke 
Published: May 2022

ABSTRACTMultipartite bacterial genomes pose challenges for genome engineering and establishment of additional replicons. We simplified the tripartite genome structure (3.65 Mbp chromosome, 1.35 Mbp megaplasmid pSymA, 1.68 Mbp chromid pSymB) ofSinorhizobium meliloti. Strains with bi- and monopartite genome configurations were generated by targeted replicon fusions. Our design preserved key genomic features, such as replichore ratios, GC skew, and KOPS and coding sequence distribution. Under standard culture conditions, growth rates of these strains and the wild type were nearly comparable. Spatiotemporal replicon organization and segregation were maintained in the triple replicon fusion strain. Deletion of the replication initiator-encoding genes including theoriVsof pSymA and pSymB from this strain resulted in a monopartite genome withoriCas the sole origin of replication, a strongly unbalanced replichore ratio, slow growth and an aberrant cellular localization oforiC. Suppressor mutation R436H in the cell cycle histidine kinase CckA and a 3.2 Mbp inversion, both individually, largely restored growth. These strains will facilitate integration of secondary replicons inS. meliloti,and thus be useful for genome engineering applications, such as generating hybrid genomes.Graphical Abstract
On Weighted K-Mer Dictionaries
Authors: Pibiri Giulio Ermanno 
Published: May 2022

AbstractWe consider the problem of representing a set of k-mers and their abundance counts, or weights, in compressed space so that assessing membership and retrieving the weight of a k-mer is efficient. The representation is called a weighted dictionary of k-mers and finds application in numerous tasks in Bioinformatics that usually count k-mers as a pre-processing step. In fact, k-mer counting tools produce very large outputs that may result in a severe bottleneck for subsequent processing.In this work we extend the recently introduced SSHash dictionary (Pibiri, Bioinformatics 2022) to also store compactly the weights of the k-mers. From a technical perspective, we exploit the order of the k-mers represented in SSHash to encode runs of weights, hence allowing (several times) better compression than the empirical entropy of the weights. We also study the problem of reducing the number of runs in the weights to improve compression even further and illustrate a lower bound for this problem. We propose an efficient, greedy, algorithm to reduce the number of runs and show empirically that it performs well, i.e., very similarly to the lower bound. Lastly, we corroborate our findings with experiments on real-world datasets and comparison with competitive alternatives. Up to date, SSHash is the only k-mer dictionary that is exact, weighted, associative, fast, and small.
Sustainable elk harvests in Alberta with increasing predator populations
Authors: Trump Tyler , Knopff Kyle , Morehouse Andrea , Boyce Mark S. 
Published: May 2022

AbstractLarge predators often are believed to cause declines in hunter harvests of ungulates due to direct competition for prey with hunters. In Alberta, predators of elk (Cervus elaphus), including grizzly bear (Ursus arctos), cougar (Puma concolor), and wolf (Canis lupus), have increased in recent years. We used trend analysis replicated by Wildlife Management Unit (WMU) to examine regional trends in elk harvest and hunter success. Over a 26-year period, average harvest of elk increased for both unrestricted bull (5.46% yr-1) and limited-quota (6.64% yr-1) hunting seasons. Average hunter success also increased for both unrestricted bull (0.2% yr-1) and limited-quota (0.3% yr-1) seasons, but no trend was detected in hunter effort (P> 0.05). Our results show that increasing large-predator populations do not necessarily reduce hunter harvest of elk, and we only found evidence for this in Alberta’s mountain WMUs where predation on elk calves has reduced recruitment. Furthermore, data indicate that Alberta’s elk harvest management has been sustainable, i.e., hunting has continued while populations of elk have increased throughout most of the province. Wildlife agencies can justify commitments to long-term population monitoring because data allow adaptive management and can inform stakeholders on the status of populations.
Fission yeast Smi1p participates in the synthesis of the primary septum by regulating β-1,3-glucan synthase Bgs1p function
Authors: Sethi Kriti , Cortés Juan C. G. , Sato Mamiko , Osumi Masako , Naqvi Naweed I. , Ribas Juan Carlos , Balasubramanian Mohan 
Published: May 2022

AbstractCytokinesis is the concluding step of the cell cycle. Coordination between multiple cellular processes is essential for the success of cytokinesis. The fission yeast, Schizosaccharomyces pombe, like other fungal cells is contained within a cell wall. During cell division, the external cell wall is extended inwards to form a special septum wall structure in continuity with the cell wall. The primary septum, the central component of the three-layered division septum, is enriched with linear β-1,3-glucan formed by Bgs1p, a β-1,3-glucan synthase. In this study we uncover a novel essential protein, Smi1p, that functions as a suppressor of the Bgs1p temperature-sensitive mutant, cps1-191. We observe a rescue in the cell wall composition and ultrastructure and also in actomyosin ring dynamics. Further, we identify a colocalization and physical association between Bgs1p and Smi1p. Altogether, our results indicate that Smi1p regulates the function of Bgs1p during cytokinesis.
NetBCE: An Interpretable Deep Neural Network for Accurate Prediction of Linear B-Cell Epitopes
Authors: Xu Haodong , Zhao Zhongming 
Published: May 2022

AbstractIdentification of B-cell epitopes (BCEs) plays an essential role in the development of peptide vaccines, immuno-diagnostic reagents, and antibody design and production. In this work, we generated a large benchmark dataset comprising 126,779 experimentally-supported, linear epitope-containing regions in 3567 protein clusters from over 1.3 million B cell assays. Analysis of this curated dataset showed large pathogen diversity covering 176 different families. The accuracy in linear BCE prediction was found to strongly vary with different features, while the performance by sequence features was superior to that by structural features. To search more efficient and interpretive feature representations, a ten-layer deep learning framework for linear BCE prediction, namely NetBCE, was developed. NetBCE achieved high accuracy and robust performance with the average area under the curve (AUC) value of 0.846 in five-fold cross validation through automatically learning the informative classification features. NetBCE substantially outperformed the conventional machine learning algorithms and other tools, with an over 22.06% improvement of AUC value compared to other tools using an independent dataset. Through investigating the output of important network modules in NetBCE, epitopes and non-epitopes tended to present in distinct regions with efficient feature representation along the network layer hierarchy. The NetBCE tool will be useful for linear B-cell epitopes identification and more generally, immunological and computational biology research.
Self-assembly and structure of a clathrin-independent AP-1:Arf1 tubular membrane coat
Authors: Hooy Richard M. , Iwamoto Yuichiro , Tudorica Daniel , Ren Xuefeng , Hurley James H. 
Published: May 2022

AbstractThe AP adaptor complexes are best known for forming the inner layer of clathrin coats on spherical vesicles. AP complexes also have many clathrin-independent roles in tubulovesicular membrane traffic, whose structural and mechanistic basis has been a mystery. HIV-1 Nef hijacks the AP-1 complex to sequester MHC-I internally, evading immune detection. We found that AP-1:Arf1:Nef:MHC-I forms a coat on tubulated membranes in the absence of clathrin, and determined its structure by cryo-ET. The coat assembles both laterally and axially via an Arf1 dimer interface not seen before. Nef recruits MHC-I, but is not essential for the underlying AP-1:Arf1 lattice. Consistent with a role for AP-1:Arf1 coated tubules as intermediates in clathrin coated vesicle formation, AP-1 positive tubules are enriched in cells upon clathrin knockdown, with or without Nef. Nef localizes preferentially to AP-1 tubules in cells, explaining how Nef can sequester MHC-I. The coat contact residues are conserved across Arf isoforms and across the Arf-dependent AP adaptors AP-1, 3, and 4. These findings reveal that AP complexes can self-assemble with Arf1 into tubular coats in the absence of clathrin or other scaffolding factors. The AP-1:Arf1 coat defines the structural basis of a broader class of tubulovesicular membrane coats, as an intermediate in clathrin vesicle formation from internal membranes, and as a MHC-I sequestration mechanism in HIV-1 infection.