bluuebunny/crossref_metadata_2025_split huggingface dataset:
Losartan promotes cell survival following SARS-CoV-2 infectionin vitro
Authors: Nejat Reza , Sadr Ahmad Shahir , Freitas Brendan T. , Crabtree Jackelyn , Pegan Scott D. , Tripp Ralph A. , Najafi David J. 
Published: December 2020

AbstractIntroductionCoronavirus disease 2019 (COVID-19) can be associated with mortality and high morbidity worldwide. There is an extensive effort to control infection and disease caused by SARS-CoV-2. This study addressed the hypothesis that angiotensin II type I receptor blocker, Losartan, may restrict pathogenesis caused by SARS-CoV-2 by decreasing viral-induced cytopathological changes by blocking angiotensin II type 1 receptor (AT1R), thus reducing the affinity of the virus for ACE2, and inhibiting papain-like protease of the virus.MethodLosartan inhibitory effect on deubiquitination and deISGylation properties of papain-like protease was investigated using a fluorescence method and gel shift analysis determining its inhibitory effects.The inhibitory effect of Losartan on SARS-CoV-2 cell replication was investigated both when losartan was added to the cell culture 1 hour before (pre-infection group) and 1 hour after (post-infection group) SARS-CoV-2 infection of Vero E6 cells.ResultsLosartan treatment of Vero E6 cells prior to and after SARS-CoV-2 infection reduced SARS-CoV-2 replication by 80% and 70% respectively. Losartan was not a strong deubiquitinase and deISGylase inhibitor of PLpro.ConclusionLosartan added pre- and post-infection to the Vero E6 cell culture significantly prevents cell destruction and replication by SARS-CoV2. Losartan has low side-effects, is readily available, and can be produced at high levels globally, all features of a promising drug in treatment of COVID-19 if validated by clinical trials.
Ribosome collision sensor Hel2 recognizes mistargeting secretory ribosome-nascent chain complexes
Authors: Matsuo Yoshitaka , Inada Toshifumi 
Published: December 2020

SummaryRibosome collision due to translational stalling is recognized as a problematic event in translation by E3 ubiquitin ligase Hel2, leading to non-canonical subunit dissociation followed by targeting of the faulty nascent peptides for degradation. Although Hel2-mediated quality control greatly contributes to maintaining cellular protein homeostasis, its physiological role in dealing with endogenous substrates remains unclear. This study utilized genome-wide analysis, based on selective ribosome profiling, to survey the endogenous substrates for Hel2. This survey revealed that Hel2 preferentially binds to the pre-engaged secretory ribosome-nascent-chain complexes (RNCs), which translate upstream of targeting signals. Notably, Hel2 recruitment into secretory RNCs was elevated under signal recognition particle (SRP)-deficient conditions. Moreover, the mitochondrial defects caused by insufficient SRP were enhanced byhel2deletion, along with the mistargeting of secretory proteins into mitochondria. Collectively, these findings provide novel insights into risk management in the secretory pathway that maintains cellular protein homeostasis.
Effect of Stapling on the Thermodynamics of mdm2-p53 Binding
Authors: Maity Atanu , Choudhury Asha Rani , Chakrabarti Rajarshi 
Published: December 2020

AbstractProtein-protein interaction (PPI) is one of the key regulatory features to drive biomolecular processes and hence is targeted for designing therapeutics against diseases. Small peptides are a new and emerging class of therapeutics owing to their high specificity and low toxicity. For achieving efficient targeting of the PPI, amino acid side chains are often stapled together resulting in the rigidification of these peptides. Exploring the scope of these peptides demands a comprehensive understanding of their working principle. In this work, two stapled p53 peptides have been considered to delineate their binding mechanism with mdm2 using computational approaches. Addition of stapling protects the secondary structure of the peptides even in the case of thermal and chemical denaturation. Although the introduction of a stapling agent increases the hydrophobicity of the peptide, the enthalpic stabilization decreases. This is overcome by the lowering of the entropic penalty and the overall binding affinity improves. The mechanistic insights into the benefit of peptide stapling can be adopted for further improvement of peptide therapeutics.
The N-terminal Tail ofC. elegansCENP-A Interacts with KNL-2 and is Essential for Centromeric Chromatin Assembly
Authors: de Groot Christian , Houston Jack , Davis Bethany , Gerson-Gurwitz Adina , Monen Joost , Oegema Karen , Shiau Andrew K. , Desai Arshad 
Published: December 2020

ABSTRACTCentromeres are epigenetically defined by the presence of the centromere-specific histone H3 variant CENP-A. A specialized loading machinery, including the histone chaperone HJURP/Scm3, participates in CENP-A nucleosome assembly. However, Scm3/HJURP is missing from multiple lineages, including nematodes, which rely on a CENP-A-dependent centromere. Here, we show that the extended N-terminal tail ofC. elegansCENP-A contains a predicted structured region that is essential for centromeric chromatin assembly. Removal of this region of the CENP-A N-Tail prevents loading, resulting in failure of kinetochore assembly and defective chromosome condensation. By contrast, the N-Tail mutant CENP-A localizes normally in the presence of endogenous CENP-A. The portion of the N-Tail containing the predicted structured region binds to KNL-2, a conserved SANTA and Myb domain-containing protein (referred to as M18BP1 in vertebrates), that is specifically involved in CENP-A chromatin assembly. This direct interaction is conserved in the related nematodeC. briggsae,despite divergence of the N-Tail and KNL-2 primary sequences. Thus, the extended N-Tail of CENP-A is essential for CENP-A chromatin assembly inC. elegansand partially substitutes for the function of Scm3/HJURP, in that it mediates an interaction of the specialized histone fold of CENP-A with KNL-2. These results highlight an evolutionary variation on centromeric chromatin assembly in the absence of a dedicated CENP-A-specific chaperone/targeting factor of the Scm3/HJURP family.
Haplotype and Population Structure Inference using Neural Networks in Whole-Genome Sequencing Data
Authors: Meisner Jonas , Albrechtsen Anders 
Published: December 2020

AbstractAccurate inference of population structure is important in many studies of population genetics. Here we present,HaploNet, a method for performing dimensionality reduction and clustering of genetic data. The method is based on local clustering of phased haplotypes using neural networks from whole-genome sequencing or dense genotype data. By utilizing Gaussian mixtures in a variational autoencoder framework, we are able to learn a low-dimensional latent space in which we cluster haplotypes along the genome in a highly scalable manner. We demonstrate that we can use haplotype clusters in the latent space to infer global population structure utilizing haplotype information by exploiting the generative properties of our framework. Based on fitted neural networks and its latent haplotype clusters, we can perform principal component analysis and estimate ancestry proportions based on a maximum likelihood framework. Using sequencing data from simulations and closely related human populations, we demonstrate that our approach is better at distinguishing closely related populations than standard admixture and principal component analysis software. We further show thatHaploNetis fast and highly scalable by applying it to genotype array data of the UK Biobank.
PARprolink: a photoaffinity probe for identifying poly(ADP-ribose)-binding proteins
Authors: Dasovich Morgan , Beckett Morgan Q. , Bailey Scott , Ong Shao-En , Greenberg Marc M. , Leung Anthony K. L. 
Published: December 2020

ABSTRACTPost-translational modification of proteins with poly(ADP-ribose) (PAR) is an important component of the DNA damage response. Four PAR synthesis inhibitors have recently been approved for the treatment of breast, ovarian, and prostate cancers. Despite its clinical significance, a molecular understanding of PAR function, including its binding partners, remains incomplete. In this work, we synthesize a PAR photoaffinity probe that captures and isolates endogenous PAR binders. Our method identified dozens of known PAR-binding proteins and hundreds of novel binders involved in DNA repair, RNA processing, and metabolism. PAR binding by eight candidates was confirmed using pull-down and/or electrophoretic mobility shift assays. Using PAR probes of defined lengths, we detected proteins that preferentially bind to 40-mer over 8-mer PAR, indicating that polymer length may regulate the outcome and timing of PAR signaling pathways. This investigation produces the first census of PAR-binding proteins, provides a proteome-wide view of length-selective PAR binding, and associates PAR binding with RNA metabolism and the formation of biomolecular condensates.
The replication of the human respiratory syncytial virus in a T cell line has multiple ineffective steps
Authors: de Souza Cardoso Ricardo , Coelho Ana Carolina Lunardello , de Jesus Bruna Laís Santos , Vitti Brenda Cristina , de Paula Souza Juliano , Viana Rosa Maria Mendes , Pontelli Marjorie C. , Murakami Tomoyuki , Ventura Armando Moraes , Ono Akira , Arruda Eurico 
Published: December 2020

AbstractHuman respiratory syncytial virus is the most frequent cause of severe respiratory disease in children. The main targets of HRSV infection are epithelial cells of the respiratory tract and the great majority of the studies regarding HRSV infection are done in respiratory cells. Recently, the interest on respiratory virus infection of lymphoid cells has been growing, but details of the interaction of HRSV with lymphoid cells remain unknown. Therefore, this study was done to assess the relationship of HRSV with A3.01 cells, a CD4+T cell line. We found by flow cytometry and fluorescent focus assay that A3.01 cells are susceptible but virtually not permissive to HRSV infection. De-quenching experiments revealed that the fusion process of HRSV in A3.01 cells is reduced in comparison to HEp-2 cells, an epithelial cell lineage. Quantification of viral RNA by qPCR determined that the replication of HRSV in A3.01 cells was modest. Western blot and quantitative flow cytometry analyses demonstrated that the production of HRSV proteins in A3.01 was significantly lower than in HEp-2 cells. Additionally, we found by fluorescence in situ hybridization that the inclusion body-associated granules (IBAG’s) are almost absent in HRSV inclusion bodies in A3.01 cells. We also assessed the intracellular trafficking of HRSV proteins and found that HRSV proteins co-localized partially with the secretory pathway in A3.01 cells, but these HRSV proteins and viral filaments are present only scarcely at the plasma membrane. HRSV infection of A3.01 CD4+T cells is virtually unproductive as compared to HEp-2 cells, with virion production hampered by low fusion, hypofunctional inclusion bodies, altered trafficking of viral proteins to the plasma membrane.
The Diversity and Evolution of Microbial Dissimilatory Phosphite Oxidation
Authors: Ewens Sophia D. , Gomberg Alexa F. S. , Barnum Tyler P. , Borton Mikayla A. , Carlson Hans K. , Wrighton Kelly C. , Coates John D. 
Published: December 2020

AbstractPhosphite is the most energetically favorable chemotrophic electron donor known, with a half-cell potential (E°’) of −650 mV for the PO43-/PO33-couple. Since the discovery of microbial dissimilatory phosphite oxidation (DPO) in 2000, the environmental distribution, evolution, and diversity of DPO microorganisms (DPOM) has remained enigmatic and only two species have been identified. Here metagenomic sequencing of phosphite enriched microbial communities enabled the reconstruction and metabolic characterization of 21 novel DPOM. These DPOM spanned six classes of bacteria, including theNegativicutes, Desulfotomaculia, Synergistia, Syntrophia, DesulfobacteriaandDesulfomonilia_A. Comparing the DPO genes from the genomes of enriched organisms to over 17,000 publicly available metagenomes revealed the global existence of this metabolism in diverse anoxic environments, including wastewaters, sediments, and subsurface aquifers. Despite their newfound environmental and taxonomic diversity, metagenomic analyses suggested that the typical DPOM is a chemolithoautotroph that occupies low-oxygen environments and specializes in phosphite oxidation coupled to CO2reduction. Phylogenetic analyses indicated that the DPO genes form a highly conserved cluster that likely has ancient origins predating the split of monoderm and diderm bacteria. By coupling microbial cultivation strategies with metagenomics, these studies highlighted the unsampled metabolic versatility latent in microbial communities. We have uncovered the unexpected prevalence, diversity, biochemical specialization, and ancient origins of a unique metabolism central to the redox cycling of phosphorus, a primary nutrient on earth.Significance StatementGeochemical models of the phosphorus (P) cycle uniquely ignore microbial redox transformations. Yet phosphite is a reduced P source that has been detected in several environments at concentrations that suggest a contemporary P redox cycle. Microbial dissimilatory phosphite oxidation (DPO) converts soluble phosphite into phosphate, and a false notion of rarity has limited our understanding of its diversity and environmental distribution. Here we demonstrate that DPO is an ancient energy metabolism hosted by taxonomically diverse, autotrophic bacteria that exist globally throughout anoxic environments. DPO microorganisms are therefore likely to have provided bioavailable phosphate and fixed carbon to anoxic ecosystems throughout Earth’s history and continue to do so in contemporary environments.
Mitochondrial introgression by ancient admixture between two distant lacustrine fishes in Sulawesi Island
Authors: Horoiwa Mizuki , Mandagi Ixchel F. , Sutra Nobu , Montenegro Javier , Tantu Fadly Y. , Masengi Kawilarang W. A. , Nagano Atsushi J. , Kusumi Junko , Yasuda Nina , Yamahira Kazunori 
Published: December 2020

AbstractSulawesi, an island located in a biogeographical transition zone between Indomalaya and Australasia, is famous for its high levels of endemism. Ricefishes (family Adrianichthyidae) are an example of taxa that have uniquely diversified on this island. It was demonstrated that habitat fragmentation due to the Pliocene juxtaposition among tectonic subdivisions of this island was the primary factor that promoted their divergence; however, it is also equally probable that habitat fusions and resultant admixtures between phylogenetically distant species may have frequently occurred. Previous studies revealed that some individuals ofOryzias sarasinorumendemic to a tectonic lake in central Sulawesi have mitochondrial haplotypes that are similar to the haplotypes ofO. eversi, which is a phylogenetically related but geologically distant (ca. 190 km apart) adrianichthyid endemic to a small lake. In this study, we tested if this reflects ancient admixture ofO. eversiandO. sarasinorum. Population genomic analyses of genome-wide single-nucleotide polymorphisms revealed thatO. eversiandO. sarasinorumare substantially reproductively isolated from each other. Comparison of demographic models revealed that the models assuming ancient admixture fromO. eversitoO. sarasinorumwas more supported than the models assuming no admixture; this supported the idea that theO. eversi-likemitochondrial haplotype inO. sarasinorumwas introgressed fromO. eversi. This study is the first to demonstrate ancient admixture of lacustrine organisms in Sulawesi beyond 100 km. The complex geological history of this island enabled such island-wide admixture of lacustrine organisms, which usually experience limited migration.
Business valuation strategy for new hydroponic farm development – a proposal towards sustainable agriculture development in United Arab Emirates
Authors: Sisodia Gyanendra Singh , Alshamsi Raweya , Sergi Bruno S. 
Published: December 2020

PurposeThis study aims to evaluate a hydroponic farm (through nutrient film technique) while considering uncertainty, sustainability and the system's utility in the dominant desert geography. The idea of the hydroponic farm is to allow individuals/businesses to grow plants. Given the geographical condition, the hydroponic system may be useful in the Gulf context and may lead to food security and sustainability. Additionally, the UAE government has initiated several support schemes that can be availed for investing in such businesses that can contribute to the nation's food security.Design/methodology/approachThe hydroponic farm is evaluated using the net present value and real options approach. The authors studied five scenarios: 1. business as usual, 2. 50% subsidy on initial investment through Khalifa funding, 3. 4% premium, 4. Subsidy plus premium and 5. solar panel installation with bore well.FindingsAs per the assumptions and data usage, all the scenarios shows a positive net present value (NPV); Nevertheless, scenarios 4 and 5 report the significant highest net present and delay value.Research limitations/implicationsThis study has environmental, economic and social implications. Lower imports indirectly lead to lower carbon footprints. The local production of food ensures higher employability in the sector and increase in local consumption. Additionally, fresh food consumption is directly associated to good health.Practical implicationsSupportive policies such as subsidies through Khalifa funding may accelerate the expansion of such projects through domestic and foreign investments. One of the important takeaway from the study is to invest in the training of the workforce.Social implicationsGiven the geographical condition, the UAE usually depends on food imports. If the hydroponic farms become popular, the residents will have access to fresh vegetables and fruits. Higher engagement in agriculture activities also ensures a significant increase in agriculture-related businesses and higher employability.Originality/valueThe study adds novelty to the literature because the effect of Khalifa funding and investment analysis on solar (wells) has not been evaluated in any hydroponic studies. We presented the results with tornado graphs using NPV risk and real options approach in the Gulf context. The study represents functional scenarios that were previously not found in the literature.
A computational analysis of heat transport irreversibility phenomenon in a magnetized porous channel
Authors: Marzougui Souad , Bouabid M. , Mebarek-Oudina Fateh , Abu-Hamdeh Nidal , Magherbi Mourad , Ramesh K. 
Published: December 2020

Purpose
The purpose of this paper is to evaluate the temperature, the Dirichlet conditions have been considered to the parallel horizontal plates. The model of generalized Brinkman-extended Darcy with the Boussinesq approximation is considered and the governing equations are computed by COMSOL multiphysics.

Design/methodology/approach
In the current study, the thermodynamic irreversible principle is applied to study the unsteady Poiseuille–Rayleigh–Bénard (PRB) mixed convection in a channel (aspect ratio A = 5), with the effect of a uniform transverse magnetic field.

Findings
The effects of various flow parameters on the fluid flow, Hartmann number (Ha), Darcy number (Da), Brinkman number (Br) and porosity (ε), are presented graphically and discussed. Numerical results for temperature and velocity profiles, entropy generation variations and contour maps of streamlines, are presented as functions of the governing parameter mentioned above. Basing on the generalized Brinkman-extended Darcy formulation, which allows the satisfaction of the no-slip boundary condition on a solid wall, it is found that the flow field and then entropy generation is notably influenced by the considering control parameters. The results demonstrate that the flow tends toward the steady-state with four various regimes, which strongly depends on the Hartman and Darcy numbers variations. Local thermodynamic irreversibilities are more confined near the active top and bottom horizontal walls of the channel when increasing the Da and decreasing the Hartmann number. Entropy generation is also found to be considerably affected by Brinkman number variation.

Originality/value
In the present work, we are presenting our investigations on the influence of a transverse applied external magnetohydrodynamic on entropy generation at the unsteady laminar PRB flow of an incompressible, Newtonian, viscous electrically conducting binary gas mixture fluid in porous channel of two horizontal heated plates. The numerical solutions for the liquid velocity, the temperature distribution and the rates of heat transport and entropy generation are obtained and are plotted graphically.
Numerical analysis of jet airflow impact inclined flat plate under electrohydrodynamics force in a porous medium
Authors: Ayuttaya Suwimon Saneewong Na 
Published: December 2020

Purpose
This study aims to present a numerical analysis of the behavior of the electric field and flow field characteristics under electrohydrodynamics (EHD) force. The influence of the jet airflow under the EHD force is investigated when it impacts the inclined flat plate.

Design/methodology/approach
The high electrical voltage and angle of an inclined flat plate are tested in a range of 0–30 kV and 0–90°, respectively. In this condition, the air is set in a porous medium and the inlet jet airflow is varied from 0–2 m/s.

Findings
The results of this study show that the electric field line patterns increase with increasing the electrical voltage and it affects the electric force increasing. The angle of inclined flat plate and the boundary of the computational model are influenced by the electric field line patterns and electrical voltage surface. The electric field pattern is the difference in the fluid flow pattern. The fluid flow is more expanded and more concentrated with increasing the angle of an inclined flat plate, the electrical voltage and the inlet jet airflow. The velocity field ratio is increased with increasing the electrical voltage but it is decreased with increasing the angle of the inclined flat plate and the inlet jet airflow.

Originality/value
The maximum Reynolds number, the maximum velocity field and the maximum cell Reynolds number are increased with increasing the electrical voltage, the inlet jet airflow and the angle of the inclined flat plate. In addition, the cell Reynolds number characteristics are more concentrated and more expanded with increasing the electrical voltage. The pattern of numerical results from the cell Reynolds number characteristics is similar to the pattern of the fluid flow characteristics. Finally, a similar trend of the maximum velocity field has appeared for experimental and numerical results so both techniques are in good agreement.