bluuebunny/crossref_metadata_2025_split huggingface dataset:
The C-type Lectin Receptor Dectin-2 is a receptor for Aspergillus fumigatus galactomannan
Authors: Reedy Jennifer L. , Crossen Arianne J. , Negoro Paige E. , Brown Hannah E. , Ward Rebecca A. , Blanco Diego A. Vargas , Timmer Kyle D. , Mansour Michael K. , Wüthrich Marcel , Fontaine Thierry , Latgé Jean-Paul , Vyas Jatin M. 
Published: April 2022

ABSTRACTAspergillus fumigatus is a ubiquitous environmental mold that causes significant mortality particularly amongst immunocompromised patients. The detection of the Aspergillus-derived carbohydrate galactomannan in patient sera and bronchoalveolar lavage fluid is the major biomarker used to detect A. fumigatus infection in clinical medicine. Despite the clinical relevance of this carbohydrate, we lack a fundamental understanding of how galactomannan is recognized by the immune system and its consequences. Galactomannan is composed of a linear mannan backbone with galactofuranose sidechains and is found both attached to the cell surface of Aspergillus and as a soluble carbohydrate in the extracellular milieu. In this study, we utilized fungal-like particles composed of highly purified Aspergillus galactomannan to identify a C-type lectin host receptor for this fungal carbohydrate. We identified a novel and specific interaction between Aspergillus galactomannan and the C-type lectin receptor Dectin-2. We demonstrate that galactomannan bound to Dectin-2 and induced Dectin-2 dependent signaling including activation of spleen tyrosine kinase and potent TNFα production. Deficiency of Dectin-2 increased immune cell recruitment to the lungs but was dispensable for survival in a mouse model of pulmonary aspergillosis. Our results identify a novel interaction between galactomannan and Dectin-2 and demonstrate that Dectin-2 is a receptor for galactomannan which leads to a pro-inflammatory immune response in the lung.IMPORTANCEAspergillus fumigatus is a fungal pathogen that causes serious and often fatal disease in humans. The surface of Aspergillus is composed of complex sugar molecules. Recognition of these carbohydrates by immune cells by carbohydrate lectin receptos can lead to clearance of the infection or, in some cases, benefit the fungus by dampening the host response. Galactomannan is a carbohydrate that is part of the cell surface of Aspergillus but is also released during infection and is found in patient lungs as well as their bloodstreams. The significance of our research is that we have identified a mammalian immune cell receptor that recognizes, binds, and signals in response to galactomannan. These results enhance our understanding of how this carbohydrate interacts with the immune system at the site of infection and will lead to broader understanding of how release of galactomannan by Aspergillus effects the immune response in infected patients.
Karyorelict ciliates use an ambiguous genetic code with context-dependent stop/sense codons
Authors: Seah Brandon Kwee Boon , Singh Aditi , Swart Estienne Carl 
Published: April 2022

AbstractIn ambiguous stop/sense genetic codes, the stop codon(s) not only terminate translation but can also encode amino acids. Such codes have evolved at least four times in eukaryotes, twice among ciliates (Condylostoma magnum and Parduczia sp.). These have appeared to be isolated cases whose next closest relatives use conventional stop codons. However, little genomic data have been published for the Karyorelictea, the ciliate class that contains Parduczia sp., and previous studies may have overlooked ambiguous codes because of their apparent rarity. We therefore analyzed single-cell transcriptomes from four of the six karyorelict families to determine their genetic codes. Reassignment of canonical stops to sense codons was inferred from codon frequencies in conserved protein domains, while the actual stop codon was predicted from full-length transcripts with intact 3’-untranslated regions (3’-UTRs). We found that all available karyorelicts use the Parduczia code, where canonical stops UAA and UAG are reassigned to glutamine, and UGA encodes either tryptophan or stop. Furthermore, a small minority of transcripts may use an ambiguous stop-UAA instead of stop-UGA. Given the ubiquity of karyorelicts in marine coastal sediments, ambiguous genetic codes are not mere marginal curiosities but a defining feature of a globally distributed and diverse group of eukaryotes.
Tuning aromatic contributions by site-specific encoding of fluorinated phenylalanine residues in bacterial and mammalian cells
Authors: Galles Grace D. , Infield Daniel T. , Clark Colin J. , Hemshorn Marcus L. , Manikandan Shivani , Fazan Frederico , Rasouli Ali , Tajkhorshid Emad , Galpin Jason D. , Cooley Richard B. , Mehl Ryan A. , Ahern Christopher A. 
Published: April 2022

AbstractThe aromatic side-chains of phenylalanine, tyrosine, and tryptophan interact with their environments via both hydrophobic and electrostatic interactions. Determining the extent to which these contribute to protein function and stability is not possible with conventional mutagenesis. Serial fluorination of a given aromatic is a validated method in vitro and in silico to specifically alter electrostatic characteristics, but this approach is restricted to a select few experimental systems. Here, we report a new group of pyrrolysine-based aminoacyl-tRNA synthetase/tRNA pairs that enable the site-specific encoding of a varied spectrum of fluorinated phenylalanine amino acids in E. coli and mammalian (HEK 293T) cells. By allowing the cross-kingdom expression of proteins bearing these unnatural amino acids at biochemical scale, these tools will enable deconstruction of biological mechanisms which utilize aromatic-pi interactions in structural and cellular contexts.Statement of SignificanceThe aromatic side-chains of phenylalanine, tyrosine, and tryptophan are crucial for protein function and pharmacology due to their hydrophobic and electrostatic contributions to catalytic centers and ligand-binding pockets. However, few experimental approaches can chemically assess the functional roles of aromatics in cellular environments. The accepted computational method for aromatic interrogation is via serial fluorination, which lacks an experimental correlate in bacterial or mammalian cell systems. We have identified a family of synthetases to encode multiple different types of fluorinated phenylalanine residues in E. coli and HEK cells via nonsense suppression. The efficiency of these synthetases is sufficient to support biochemical characterization and structural determination of proteins with site-specific incorporation of unnatural phenylalanine analogs.
Physiological insight into the conserved properties ofCaenorhabditis elegansacid-sensing DEG/ENaCs
Authors: Kaulich Eva , McCubbin Patrick T. N. , Schafer William R. , Walker Denise S. 
Published: April 2022

AbstractAcid sensing ion channels (ASICs) are members of the diverse family of degenerin/epithelial sodium channels (DEG/ENaCs). They perform a wide range of physiological roles in healthy organisms, including in gut function and synaptic transmission, but also play important roles in disease, as acidosis is a hallmark of painful inflammatory and ischaemic conditions. We performed a screen for acid-sensitivity on all 30 subunits of theC. elegansDEG/ENaC family using Two-Electrode Voltage Clamp (TEVC) inXenopusoocytes. We found two groups of acid-sensing DEG/ENaCs characterised by being inhibited or activated by increasing proton concentrations. Three of these acid-sensitiveC. elegansDEG/ENaCs were activated by acidic pH, making them functionally similar to the vertebrate ASICs. We also identified four new members of the acid-inhibited DEG/ENaC group, giving a total of seven additional acid-sensitive channels. We observed sensitivity to the anti-hypertensive drug amiloride as well as modulation by the trace element zinc. Acid-sensitive DEG/ENaCs were found to be expressed in both neurons and non-neuronal tissue, highlighting the likely functional diversity of these channels. Our findings provide a framework to exploit theC. eleganschannels as models to study the function of these acid-sensing channelsin vivo, as well as to study them as potential targets for anti-helminthic drugs.
A Joint Subspace Mapping Between Structural and Functional Brain Connectomes
Authors: Ghosh Sanjay , Raj Ashish , Nagarajan Srikantan S. 
Published: April 2022

AbstractUnderstanding the connection between the brain’s structural connectivity and its functional connectivity is of immense interest in computational neuroscience. Although some studies have suggested that whole brain functional connectivity is shaped by the underlying structure, the rule by which anatomy constraints brain dynamics remains an open question. In this work, we introduce a computational framework that identifies a joint subspace of eigenmodes for both functional and structural connectomes. We found that a small number of those eigenmodes are sufficient to reconstruct functional connectivity from the structural connectome, thus serving as low-dimensional basis function set. We then develop an algorithm that can estimate the functional eigen spectrum in this joint space from the structural eigen spectrum. By concurrently estimating the joint eigenmodes and the functional eigen spectrum, we can reconstruct a given subject’s functional connectivity from their structural connectome. We perform elaborate experiments and demonstrate that the proposed algorithm for estimating functional connectivity from the structural connectome using joint space eigenmodes gives competitive performance as compared to the existing benchmark methods with better interpretability.
3D-equivariant graph neural networks for protein model quality assessment
Authors: Chen Chen , Chen Xiao , Morehead Alex , Wu Tianqi , Cheng Jianlin 
Published: April 2022

AbstractMotivationQuality assessment of predicted protein tertiary structure models plays an important role in ranking and using them. With the recent development of deep learning end-to-end protein structure prediction techniques of generating highly confident tertiary structures for most proteins, it is important to explore corresponding quality assessment strategies to evaluate and select the structural models predicted by them since these models have better quality and different properties than the models predicted by traditional tertiary structure prediction methods.ResultsWe develop EnQA, a novel graph-based 3D-equivariant neural network method that is equivariant to rotation and translation of 3D objects to estimate the accuracy of protein structural models by leveraging the structural features acquired from the state-of-the-art tertiary structure prediction method - AlphaFold2. We train and test the method on both traditional model datasets (e.g., the datasets of the Critical Assessment of Techniques for Protein Structure Prediction (CASP)) and a new dataset of high-quality structural models predicted only by AlphaFold2 for the proteins whose experimental structures were released recently. Our approach achieves state-of-the-art performance on protein structural models predicted by both traditional protein structure prediction methods and the latest end-to-end deep learning method - AlphaFold2. It performs even better than the model quality assessment scores provided by AlphaFold2 itself. The results illustrate the 3D-equivariant graph neural network is a promising approach to the evaluation of protein structural models. AlphaFold2 features are important for improving protein model quality assessment and are complimentary with the geometric property features extracted from structural models.AvailabilityThe source code is available at https://github.com/BioinfoMachineLearning/EnQA.Contactchengji@missouri.eduSupplementary informationSupplementary data are available.
Mutation of Arabidopsis SME1 and Sm core assembly improves oxidative stress resilience
Authors: Willems Patrick , Van Ruyskensvelde Valerie , Maruta Takanori , Pottie Robin , Fernández-Fernández Álvaro Daniel , Pauwels Jarne , Hannah Matthew A. , Gevaert Kris , Van Breusegem Frank , Van der Kelen Katrien 
Published: April 2022

AbstractAlternative splicing is a key posttranscriptional gene regulatory process, acting in diverse adaptive and basal plant processes. Splicing of precursor-messenger RNA (pre-mRNA) is catalyzed by a dynamic ribonucleoprotein complex, designated the spliceosome. In a suppressor screen, we identified a nonsense mutation in the Sm protein SME1 to alleviate photorespiratory H2O2-dependent cell death in catalase deficient plants. Similar attenuation of cell death was observed upon chemical inhibition of the spliceosome, suggesting pre-mRNA splicing inhibition to be responsible for the observed cell death alleviation. Furthermore, the sme1-2 mutants showed increased tolerance to the reactive oxygen species inducing herbicide methyl viologen. Both an mRNA-seq and shotgun proteomic analysis in sme1-2 mutants displayed a constitutive molecular stress response, together with extensive alterations in pre-mRNA splicing of transcripts encoding metabolic enzymes and RNA binding proteins, even under unstressed conditions. Using SME1 as a bait to identify protein interactors, we provide experimental evidence for almost 50 homologs of mammalian spliceosome-associated protein to reside in the Arabidopsis thaliana spliceosome complexes and propose roles in pre-mRNA splicing for four uncharacterized plant proteins. Furthermore, like in sme1-2, a mutant in the Sm core assembly protein ICLN resulted in a decreased sensitivity to methyl viologen. Taken together, these data show that both a perturbed Sm core composition and assembly results in the activation of a defense response and enhanced resilience to oxidative stress.
Integration of Xeno-Free Single-cell Cloning in CRISPR-mediated DNA Editing of Human iPSCs Improves Homogeneity and Methodological Efficiency of Cellular Disease Modelling
Authors: Namipashaki Atefeh , Pugsley Kealan , Liu Xiaodong , Abrehart Kirra , Lim Sue Mei , Sun Guizhi , Herold Marco J. , Polo Jose M. , Bellgrove Mark A. , Hawi Ziarih 
Published: April 2022

SUMMARYThe capability to generate induced pluripotent stem cell (iPSC) lines, in tandem with CRISPR-Cas9 DNA editing, offers great promise to understand the underlying genetic mechanisms of human disease. The low efficiency of available methods for homogeneous expansion of singularised CRISPR-transfected iPSCs necessitates the coculture of transfected cells in mixed populations and/or on feeder layers. Consequently, edited cells must be purified using labour-intensive screening and selection, culminating in inefficient editing. Here, we provide a xeno-free method for single-cell cloning of CRISPRed iPSCs achieving a clonal survival of up to 70% within 7-10 days. This was accomplished through improved viability of the transfected cells, paralleled with provision of enriched environment for the robust establishment and proliferation of singularised iPSC clones. Enhanced cell survival was accompanied by a high transfection efficiency exceeding 97%, and editing efficiencies of 50-65% for NHEJ and 10% for HDR, indicative of the method’s utility in stem cell disease modelling.
DNA damage response signaling is crucial for effective Chikungunya virus replication
Authors: Chatterjee Sanchari , Kumar Sameer , Mamidi Prabhudutta , Datey Ankita , Sengupta Soumya , Mahish Chandan , Laha Eshna , De Saikat , Keshry Supriya Suman , Nayak Tapas Kumar , Ghosh Soumyajit , Singh Sharad , Subudhi Bharat Bhusan , Chattopadhyay Subhasis , Chattopadhyaya Soma 
Published: April 2022

AbstractViruses utilize a plethora of strategies to manipulate the host pathways and hijack its machineries for efficient replication. Several DNA as well as handful of RNA viruses are reported to interact with proteins involved in DNA damage responses (DDR). As the DDR pathways have never been explored in Alphaviruses, this investigation intended to determine the importance of the DDR pathways in CHIKV infection through in vitro,in vivoandex vivomodels. The study reveals that CHIKV infection activates the Chk2 and Chk1 proteins associated with DDR signaling pathways and increases DNA damage by 95%. Inhibition of both ATM-ATR kinases by ATM/ATR kinase inhibitor (AAKi) shows drastic reduction in viral particle formation in vitro. Next, the treatment of mice with this drug has been shown to reduce the disease score substantially in CHIKV-infected C57BL/6 mice with 71% decrement in the viral copy and the same has been established in hPBMC-derived monocyte-macrophage populations. Additionally, gene silencing of Chk2 and Chk1 reduces viral progeny formation around 73.7% and 78% respectively. Moreover, it has been demonstrated that CHIKV-nsP2 interacts with Chk2 and Chk1 during CHIKV infection and docking analysis depicts the specific amino acids responsible for these interactions. Further, the data suggests that CHIKV infection induces cell cycle arrest in G1 and G2 phases.In conclusion, this work demonstrated for the first time the mechanistic insight of the induction of DDR pathways by CHIKV that might contribute to the designing of effective therapeutics for the control of this virus infection in future.IMPORTANCEViruses being intra-cellular parasite, need several host cell machineries so as to achieve effective replication of their own genome, along with virus-encoded enzymes. One of the strategies is to hijack the DDR pathways. Several DNA as well as handful of RNA viruses interact with the cellular proteins involved in DDR pathways, however, reports with respect to the association of Chk2 and Chk1 in alphavirus infection are scanty. Hence, this study is amongst the first to report that modulation of DDR pathways is crucial for effective CHIKV infection. This work also shows that there is interaction of CHIKV-nsP2 with two crucial host factors, Chk2 and Chk1 for efficient viral infection. Interestingly, CHIKV infection was found to cause DNA damage and arrest cell cycle in G1 and G2 phases to facilitate viral infection. This information might facilitate to develop effective therapeutics for the control of the CHIKV infection in future.
Associations of genetic and infectious risk factors with coronary heart disease
Authors: Hodel Flavia , Xu Zhi Ming , Thorball Christian W. , de La Harpe Roxane , Letang-Mathieu Prunelle , Brenner Nicole , Butt Julia , Bender Noemi , Waterboer Tim , Marques-Vidal Pedro , Vollenweider Peter , Vaucher Julien , Fellay Jacques 
Published: April 2022

Background and PurposeCoronary heart disease (CHD) is one of the most pressing health problems of our time and a major cause of preventable death. CHD results from complex interactions between genetic and environmental factors. Using multiplex serological testing for persistent or frequently recurring infections and genome-wide analysis in a prospective population study, we delineate the respective and combined influences of genetic variation, infections, and low-grade inflammation on the risk of incident CHD.Participants and MethodsStudy participants are enrolled in the CoLaus|PsyCoLaus study, a longitudinal, population-based cohort with baseline assessments from 2003 through 2008 and follow-up visits every five years. We analyzed a subgroup of 3’459 individuals with available genome-wide genotyping data and immunoglobulin G levels for 22 persistent or frequently recurring pathogens. All reported CHD events were evaluated by a panel of specialists. We identified independent associations with incident CHD using univariable and multivariable stepwise Cox proportional hazards regression analyses.ResultsOf the 3’459 study participants, 210 (6.07%) had at least one CHD event during the 12 years of follow-up. Multivariable stepwise Cox regression analysis, adjusted for known cardiovascular risk factors, socioeconomic status and statin intake, revealed that high polygenic risk (hazard ratio (HR) 1.31, 95% CI 1.10–156, P = 2.64e-03) and infection withFusobacterium nucleatum(HR 1.63, 95% CI 1.08–2.45, P = 1.99e-02) were independently associated with incident CHD.ConclusionIn a prospective, population-based cohort, high polygenic risk and infection withFusobacterium nucleatumhave a small, yet independent impact on CHD risk.
Proteomic study of differentially expressed proteins in seeds between parents and offspring of castor bean (Ricinus communis L.)
Authors: Liang Xiaotian , Luo Rui , Zhang Yanxin , Yin Mingda , Wen Yanpeng , Hu Xuemei , Wang Zhiyan , Huo Yumiao , Huang Fenglan 
Published: April 2022

AbstractCastor bean (Ricinus communis L.), one of the top 10 oilseed crops in the world, has high economic value. Hybridization is the most direct and effective method to breed new varieties with high yield, high oil content, and strong stress resistance. Therefore, prediction of desired traits in castor hybrid offspring is particularly important. In this study, proteomic analysis was performed to identify differentially expressed proteins (DEPs) in seeds between castor hybrid offspring and their female (Lm female line aLmAB2) and male parents (CSR•181). Among the DEPs upregulated in the seeds of hybrid offspring, the majority were related to seed yield and stress resistance, while some were related to oil synthesis and fatty acid synthesis and metabolism in seeds. In other words, the hybrid offspring showed heterosis for seed yield, stress resistance, oil synthesis, and fatty acid synthesis and metabolism when compared with their parents. Further, real-time quantitative polymerase chain reaction assays were performed on 12 genes encoding DEPs involved in oil synthesis, pollen abortion, yield, and stress resistance of seeds. The results showed that the expression levels of the 12 genes were consistent with those of the DEPs.
Islamic banking and economic growth: fresh insights from Nigeria using autoregressive distributed lags (ARDL) approach
Authors: Tabash Mosab I. , Abdulkarim Fatima Muhammad , Akinlaso Mustapha Ishaq , Dhankar Raj S. 
Published: April 2022

PurposeThe paper examines the relationship between Islamic banking and the growth of the economy in Nigeria in both the short run and long run.Design/methodology/approachThe study employs quarterly secondary time series data for Islamic banking as well as major macroeconomic variables to study the contribution of Islamic banking to the economy of Nigeria. It employs autoregressive distributed lags (ARDL) and error correction model (ECM) approaches from 2013 quarter 1 up to 2020 quarter 2.FindingsThe results show that Islamic banking has a positive contribution to Nigeria's economy in both short run and long run, but this contribution is insignificant.Practical implicationsPolicymakers should endeavor to redesign the country's financial architecture and come up with policies that can support the growth of Islamic finance sector. This will significantly strengthen Nigeria's position as one of the leading Islamic finance hubs in Africa.Originality/valueThis is the first study to examine the contribution of Islamic banking to the Nigerian economy according to the best knowledge of the authors.