bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular dynamics simulations and functional studies reveal that hBD-2 binds SARS-CoV-2 spike RBD and blocks viral entry into ACE2 expressing cells
Authors: Zhang Liqun , Ghosh Santosh K. , Basavarajappa Shrikanth C. , Muller-Greven Jeannine , Penfield Jackson , Brewer Ann , Ramakrishnan Parameswaran , Buck Matthias , Weinberg Aaron 
Published: January 2021

ABSTRACTNew approaches to complement vaccination are needed to combat the spread of SARS-CoV-2 and stop COVID-19 related deaths and long-term medical complications. Human beta defensin 2 (hBD-2) is a naturally occurring epithelial cell derived host defense peptide that has antiviral properties. Our comprehensivein-silicostudies demonstrate that hBD-2 binds the site on the CoV-2-RBD that docks with the ACE2 receptor. Biophysical and biochemical assays confirm that hBD-2 indeed binds to the CoV-2-receptor binding domain (RBD) (KD∼ 300 nM), preventing it from binding to ACE2 expressing cells. Importantly, hBD-2 shows specificity by blocking CoV-2/spike pseudoviral infection, but not VSV-G mediated infection, of ACE2 expressing human cells with an IC50of 2.4± 0.1 μM. These promising findings offer opportunities to develop hBD-2 and/or its derivatives and mimetics to safely and effectively use as novel agents to prevent SARS-CoV-2 infection.
ANTIMICROBIAL RESISTANCE AND VIRULENCE GENES PROFILING OFPROTEUSSPECIES FROM POULTRY FARMS IN LAFIA, NIGERIA
Authors: Owoseni Mojisola Christiana , Oyigye Odula , Sani Bashiru , Lamin Jebes , Chere Amara 
Published: January 2021

AbstractThe poultry industry is important in boosting food sustainability of a population; however, the poultry environment and products are susceptible to pathogen contamination arising from poor farm hygienic conditions. This study investigated the prevalence, antimicrobial resistance and virulence profile ofProteusspecies from the environment and products of four selected poultry farms in Lafia, Nasarawa State. Farm samples (n =216) comprising feed (64), drinking water (64) and swabs from eggshells (88) were collected and analysed for detection ofProteusspecies using cultural, biochemical and microscopic techniques. Antibiotics susceptibilities of isolates were also determined, and virulence genes were confirmed using Polymerase Chain Reaction. Of the total studied samples, 34.26% (74/216) were positive forProteusspecies.Proteusspecies were more prevalent in drinking water samples (37.84%) and feed samples (33.78%) and least prevalent in eggshells (28.38%).Proteusspecies (n= 74) comprisedP. mirabilis78% (58/74) andProteus vulgaris22% (16/74).P. mirabiliswas markedly higher thanP. vulgarisin all the four farms sampled. Farms A and D had the highest prevalence ofProteusspecies, while Farms A and C (80%), and Farm D (25) has the highest prevalence ofP. mirabilisandP. vulgarisrespectively. The isolates’ prevalence rate within and between farms, sample type, and species was not statistically significantly different (p≥0.05) from the other farms. Isolates were 100% susceptible to Amikacin and showed the highest resistance (25.7%) to tetracycline. Molecular analysis of the virulence genes ofProteusspecies revealed the presence ofrsbA,ureCandluxSvirulent genes in all the test isolates. Data generated indicates a high level of multidrug-resistant pathogenic strains ofProteuscirculating in poultry farms in Lafia, Nigeria, which potentiates a significant risk of transmission of pathogenicProteusvia the food chain.
Mass spectrometry-basedde novosequencing of the anti-FLAG-M2 antibody using multiple proteases and a dual fragmentation scheme
Authors: Peng Weiwei , Pronker Matti F. , Snijder Joost 
Published: January 2021

AbstractAntibody sequence information is crucial to understanding the structural basis for antigen binding and enables the use of antibodies as therapeutics and research tools. Here we demonstrate a method for directde novosequencing of monoclonal IgG from the purified antibody products. The method uses a panel of multiple complementary proteases to generate suitable peptides forde novosequencing by LC-MS/MS in a bottom-up fashion. Furthermore, we apply a dual fragmentation scheme, using both stepped high-energy collision dissociation (stepped HCD) and electron transfer high-energy collision dissociation (EThcD) on all peptide precursors. The method achieves full sequence coverage of the monoclonal antibody Herceptin, with an accuracy of 99% in the variable regions. We applied the method to sequence the widely used anti-FLAG™-M2 mouse monoclonal antibody, which we successfully validated by remodeling a high-resolution crystal structure of the Fab and demonstrating binding to a FLAG™-tagged target protein in Western blot analysis. The method thus offers robust and reliable sequences of monoclonal antibodies.
Colonization of dermal arterioles byNeisseria meningitidisprovides a safe haven from neutrophils
Authors: Manriquez Valeria , Nivoit Pierre , Urbina Tomas , Echenique-Rivera Hebert , Melican Keira , Flamant Patricia , Schmitt Taliah , Bruneval Patrick , Obino Dorian , Duménil Guillaume 
Published: January 2021

AbstractNeisseria meningitidis,a human-specific bacterium, is responsible for meningitis and fatal fulminant systemic disease. Bacteria colonize blood vessels, rapidly causing devastating vascular damage despite a neutrophil-rich inflammatory infiltrate. How this pathogen escapes the neutrophil response is unknown. Using a humanized mouse model, we show that vascular colonization leads to the recruitment of neutrophils, partially reducing bacterial burden and vascular damage. This partial effect is due to the ability of bacteria to indiscriminately colonize capillaries, venules and arterioles, as observed in human samples. In venules, potent neutrophil recruitment allows efficient bacterial phagocytosis. In contrast, in infected capillaries and arterioles adhesion molecules such as E-Selectin are not expressed on the endothelium and intravascular neutrophil recruitment is minimal. These results show that colonization of capillaries and arterioles byN. meningitidiscreate an intravascular niche that preclude the action of neutrophils, resulting in immune escape and subsequent fulminant progression of the infection.
Hydroxynonenal causes Langerhans cell degeneration in the pancreas of Japanese macaque monkeys
Authors: Boontem Piyakarn , Yamashima Tetsumori 
Published: January 2021

AbstractBackgroundFor their functions of insulin biosynthesis and glucose- and fatty acid- induced insulin secretion, the Langerhans β-cells require an intracellular milieu rich in oxygen. This requirement makes β-cells, with their constitutively low antioxidative defense, susceptible to the oxidative stress. Although much progress has been made in identifying its molecular basis in the experimental systems, whether the oxidative stress due to excessive fatty acids plays a crucial role in the Langerhans degeneration in primates is still debated.MethodsFocusing on Hsp70.1, which has dual functions as a molecular chaperone and lysosomal stabilizer, the mechanism of lipotoxicity to the Langerhans islet cells was studied using Japanese macaque monkeys (Macaca fuscata) after the consecutive injections of the lipid peroxidation product hydroxynonenal. Based on the ‘calpain-cathepsin hypothesis’ of ischemic neuronal death formulated in 1998, calpain activation, Hsp70.1 cleavage, and lysosomal integrity were studied by immunofluorescence histochemistry, electron microscopy and Western blotting.ResultsLight microscopy showed higher vacuole formation in the treated islet cells than in the control cells. Electron microscopy showed that vacuolar changes that were identified as enlarged rough endoplasmic reticula occurred mainly in β-cells followed by δ-cells. Intriguingly, both cell types showed a marked decrease in insulin and somatostatin granules. Furthermore, they exhibited marked increases in peroxisomes, autophagosomes/autolysosomes, lysosomal and peroxisomal membrane rupture/permeabilization, and mitochondrial degeneration. Disrupted peroxisomes were often localized in the close vicinity of degenerating mitochondria or autolysosomes. Immunofluorescence histochemical analysis showed an increased colocalization of activated μ-calpain and Hsp70.1 with the extralysosomal release of cathepsin B. Western blotting showed increases in μ-calpain activation, Hsp70.1 cleavage, and hydroxynonenal receptor GPR109A expression.ConclusionsTaken together, these data implicate hydroxynonenal in both the carbonylation of Hsp70.1 and the activation of μ-calpain. The calpain-mediated cleavage of the carbonyl group on Hsp70.1 after the hydroxynonenal-mediated carbonylation of Hsp70.1, may cause lysosomal membrane rupture/permeabilization. The low defense of primate Langerhans cells against exogenous hydroxynonenal and peroxisomally-generated hydrogen peroxide, was presumably overwhelmed to facilitate cell degeneration.
Genetic composition of queen conch (Lobatus gigas) population on Pedro Bank, Jamaica and its use in fisheries management
Authors: Blythe-Mallett Azra , Aiken Karl A. , Segura-Garcia Iris , Truelove Nathan K. , Webber Mona K. , Roye Marcia E. , Box Stephen J. 
Published: January 2021

ABSTRACTThe queen conch fishery in Jamaica is sustained by Pedro Bank, which is the main harvesting site located approximately 80 km south-west from Kingston. Due to its relative size, Pedro Bank has been subdivided into zones for management purposes by the Fisheries Division and the Veterinary Services Division. Understanding whether these sub-divisions reflect different sub-populations is critical for managing exploitation levels because fisheries management must demonstrate that harvesting does not endanger the future viability of the population as queen conch are on Appendix II of the Convention in Trade in Endangered Species of Wild Fauna and Flora (CITES). This determination is essential for the continued export to international markets such as the European Union. Two hundred and eight samples were collected across the entire Pedro Bank and were genetically characterized using nine polymorphic microsatellite loci. Population structure analysis forLobatus gigasfrom Pedro Bank yielded low but significant values (FST= 0.009: p = 0.006) and suggested a high magnitude of gene flow indicative of a fit and viable population throughout the bank. Analysis of molecular variance (AMOVA) indicated a 100% variation within individual samples with little variation (0.9%) between populations. In contrast pairwise genetic comparisons identified significant differences between populations located to the south eastern and eastern region of the bank to those in the central and western locations. Bayesian clustering analysis also indicated the likelihood of two population sub-divisions (K=2) on Pedro Bank. The results provided evidence of a weak but significant population structure which has crucial implications for the fishing industry as it suggests the use of ecosystem based management (EBM) in setting quotas to promote sustainable harvesting ofL. gigaswithin each monitoring zone on Pedro Bank.
Population Status and Habitat Association of Swayne’s Hartebeest (Alcelaphus Buselaphus Swaynei(Sclater, 1892)) in Maze National Park, Southern Ethiopia
Authors: Tolcha Abraham , Shibru Simon , Ayechew Belayneh 
Published: January 2021

AbstractWe investigated the population status and habitat association of the endemic Swayne’s Hartebeest (Alcelaphus buselaphus swaynei(Sclater, 1892)) in Maze National Park, Southern Ethiopia, in 2018 and 2019. Sample count method line-transect was used for the population estimation, while habitat association was made based on the abundance of individuals counted in each habitat. Data were analyzed using descriptive statistics and compared with χ2 test. The total estimated populations of Swayne’s Hartebeest (SHB) in the study period were 1456 and 1492 during wet and dry seasons, respectively showing no seasonal variation. Among the total estimated population, 31% were adult males, 38.46% adult females, 13.97% sub adult males, 15.94% sub adult females and 1.07% young. The number of adult females was higher than the other age groups followed by adult males in both seasons. Significant differences were reported among age and sex structure of population size during both seasons (wet season: χ2= 58.423, df =3, P < 0.05; dry season: χ2=534.079, df= 4, P < 0.05). The maximum group size was 36 and the minimum was 1. The ratio of adult males to adult females was 1:1.24 and 1:1.24, sub-adult males to sub adult females was 1:1.16 and 1:1.12, adult males to sub-adult males was 1:0.36 and 1:0.56, adult females to sub-adult females was 1:0.33 and 1:0.49 in the wet and dry seasons, respectively. The male to female ratio was 1:1.22 and 1:1.19 during wet and dry seasons as well. The population trend among ten years were significantly differed (χ2= 1.708, df= 9, P< 0.05). The SHB was distributed into three types of habitat (riverine forest, open grassland and scattered tree) with significant differences (χ2=1109.937, df = 3, P < 0.05). The savannah grass land was most preferable habitat followed by scattered tree habitat. Maintaining its critical habitat was highly recommended for sustainability of current population status.
Preprocessing of general stenotic vascular flow data for topological data analysis
Authors: Bresten Christopher L. , Kweon Jihoon , Chen Xinjuan , Kim Young-Hak , Jung Jae-Hun 
Published: January 2021

AbstractA new analysis and classification method of vascular disease based on topological data analysis (TDA) has been proposed in [1]. The proposed method utilizes the application of persistent homology to hemodynamic variables. Particularly, 2D homology is obtained from the velocity field of the flow projected onto the unit sphere, known as so-called theS2projection. It was shown that such homology is closely related to the degree of vascular disease. The original method was developed based on the computational fluid dynamic (CFD) solutions of the straight stenotic vessels.In this paper, we develop a preprocessing method that enables the proposed TDA method to be applied to general stenotic vessels of irregular geometry. The velocity field is subject to a coordinate transformation correcting for orientation and curved geometry. The preprocessed data is projected ontoS2and the corresponding homology is calculated. We show that this preprocessing is necessary for the proposed TDA method to be successfully applied to general types of stenotic vessels. Validation was performed on a set of clinical data including reconstructed vascular geometry with corresponding diagnostic indices.
Colistin resistance inAcinetobacter baumanniiis driven by multiple genomic traits: Evaluating the role of ISAba1-driveneptAoverexpression among Indian isolates
Authors: Vijayakumar Saranya , Jacob Jobin John , Vasudevan Karthick , Shankar Baby Abirami , Francis Maria Lincy , Kirubananthan Agilandeeswari , Anandan Shalini , Gunasekaran Karthik , Walia Kamini , Biswas Indranil , Kaye Keith S , Veeraraghavan Balaji 
Published: January 2021

AbstractColistin resistance inAcinetobacter baumanniiis mediated by multiple mechanisms. Recently, mutations withinpmrABtwo component system and overexpression ofeptAdue to upstream insertion of ISAba1play a major role.To characterize colistin resistance mechanisms among the clinical isolates ofA. baumanniiin India. A total of 224 clinical isolates ofA. baumanniicollected from 2016 to 2019 were included in this study. Mutations within lipid A biosynthesis andpmrABgenes were characterized by Whole Genome Shotgun sequencing. Twenty eight complete genomes were further characterized for insertional inactivation oflpxgenes and the association of ISAba1-eptAusing hybrid assembly approach. Non-sysnonymous mutations like M12I inpmrA, A138T and A444V inpmrBand E117K inlpxDwere identified. Four of the five colistin resistantA.baumanniiisolates had insertion of ISAba1upstreameptA. Nomcrgenes were identified.Overall, the present study highlights the diversity of colistin resistance mechanisms inA. baumannii. ISAba1-driveneptAoverexpression could be responsible for colistin resistance among Indian isolates of colistin resistantA. baumannii.
Mycobacteria tuberculosisPPE36 modulates host inflammation by promoting E3 ligase Smurf1-mediated MyD88 degradation
Authors: Peng Zhangli , Yue Yan , Xiong Sidong 
Published: January 2021

AbstractMycobacterium tuberculosis(Mtb) PPE36, a cell-wall associated protein is highly specific and conserved for the Mtb complex group. Although it has been proven essential for iron utilization, little is known about the role of PPE36 in regulating host immune responses. Here we exhibited that PPE36 preferentially enriched in Mtb virulent strains, and could efficiently inhibit host inflammatory responses and increase bacterial loads both in mycobacterium-infected macrophages and mice. In exploring the underlying mechanisms, we found that PPE36 could robustly inhibit the activation of inflammatory NF-κB and MAPK (ERK, p38 and JNK) pathways by promoting E3 ligase Smurf1-mediated ubiquitination and proteasomal degradation of MyD88 protein. Our research revealed a previously unknown function of PPE36 on modulating host immune responses, and provided some clues to the development of novel tuberculosis treatment strategies based on immune regulation.Author SummaryMycobacterium tuberculosis (Mtb) has developed diverse immune evasion strategies to successfully establish infection in host. Identifying the important Mtb immune regulatory proteins and elucidating the underlying mechanisms are critical for tuberculosis control. Here we demonstrated that PPE36, a Mtb cell-wall associated protein, was predominantly enriched in virulent mycobacterial strains, and obviously inhibited inflammatory responses and facilitated bacterial survival in infected macrophages. Compared with the wild-type BCG, BCG lacking PPE36 (BCGΔPPE36) induced more inflammation, lower bacterial loads as well as the improved histopathological changes in the lungs of infected mice. We further found that PPE36 significantly reduced host MyD88 abundance, and inhibited the activation of subsequunt inflammatory NF-κB and MAPK pathways. In addition, this direct inhibition effect of PPE36 on MyD88 was mediated by the promoted E3 ligase Smurf1 ubiquitin -protesome pathway. This study identified PPE36 as a immune regulatory protein of Mtb, and showed it played an important role in the Mtb immune evasion.
Morphological variability in the mucosal attachment site ofTrichuris murisrevealed by X-ray microcomputed tomography
Authors: O’Sullivan James D. B. , Cruickshank Sheena M. , Withers Philip J. , Else Kathryn J. 
Published: January 2021

AbstractParasitic infections can be challenging to study, because light and electron microscopy are often limited in visualising complex and inaccessible attachment sites. Exemplifying this,Trichurisspp. inhabits a tunnel of epithelial cells within the host caecum and colon. A significant global burden of this infection persists partly because available anthelminthics lack efficacy, although the mechanisms underlying this remain unknown. Consequently, there is a need to pioneer new approaches to better characterize the parasite niche within the host and investigate how variation in its morphology and integrity may contribute to resistance to therapeutic intervention. To address these aims, we exploited 3D X-ray micro-computed tomography (microCT) to image the mouse whipwormT. murisin caeca of wild-type C57BL/6 and SCID miceex vivo. Using osmium tetroxide staining to effectively enhance contrast of worms, we found that a subset exhibited preferential positioning towards the bases of the intestinal crypts. Moreover, in one rare event, we demonstrate whipworm traversal of the lamina propria. This morphological variability contradicts widely accepted conclusions from conventional microscopy of the parasite niche, showingTrichurisin close contact with the host proliferative and immune compartments that may facilitate immunomodulation. Furthermore, by using a skeletonization-based approach we demonstrate considerable variation in tunnel length and integrity which may represent an indicator of tunnel “health”. The qualitative and quantitative observations provide a new morphological point of reference for futurein vitrostudy ofTrichuris-host interactions and highlight the potential of microCT to more accurately characterise enigmatic host-parasite interactions.Author SummaryParasites are often difficult to observe once established within host tissues, presenting a barrier to biological understanding and therapeutic innovation. Whipworms (Trichurisspp.) affect 500 million people worldwide, causing significant disability, and appear partially resistant to widely used “deworming” drugs. However, the inaccessibility of worms within the cells of the host intestine makes them highly challenging to image and study. By investigatingTrichurisattachment sites in 3D, using X-ray micro-computed tomography, we found that the niche is highly variable in size and, contrary to reports in all previous studies, can also penetrate different layers of intestinal tissue. By showing that worms are positioned much closer to host immune cells that previously appreciated, we provide a morphological reference point for future studies on howTrichuriseffectively avoids clearance by the host. The non-invasive imaging approach used represents an excellent opportunity to clarify the lifecycles of other difficult-to-study parasites.