Host Type Research Articles

RKKY-type in-plane ferromagnetism in layered Mn1/4NbS2 single crystals

Placing the layers of the $3d$ magnetic elements in the van der Waals gap pulls the Nb/Ta-based transition metal dichalcogenides family from a nonmagnetic to a magnetic zone. However, the magnetic spectrum is strongly sensitive to the specific combination of host lattice and type of intercalated magnetic element and thus each combination needs a proper explicit study. In this context, we systematically investigate the magnetization of the Mn-intercalated layered ferromagnet ${\mathrm{Mn}}_{1/4}{\mathrm{NbS}}_{2}$ single crystal. Magnetization measurement revealed paramagnetic to ferromagnetic phase transition at around 105 K and an easy in-plane ($H\ensuremath{\perp}c$) significantly high magnetic anisotropy. The in-plane magnetic anisotropic energy (MAE) evaluated via the noncollinear first-principle approach is $\ensuremath{\sim}\ensuremath{-}600 \ensuremath{\mu}\mathrm{eV}$ per unit cell. The position of the Fermi level in between the spin-up and spin-down Mn states suppresses the positive contribution in the overall MAE, which lifts the overall MAE negative (in plane) with a larger size in ${\mathrm{Mn}}_{1/4}{\mathrm{NbS}}_{2}$. The comprehensive analysis of magnetization isotherms measured in the vicinity of ${T}_{c}$ with magnetic field $H$ applied parallel to the $ab$ plane ($H\ensuremath{\perp}c$) yields the asymptotic critical exponents $\ensuremath{\beta}=0.3251(2)$ and $\ensuremath{\gamma}=1.2(1)$, and $\ensuremath{\delta}=4.691(1)$. These critical exponents fulfill the scaling relation and scaling equation of the magnetic state predicted by the scaling theory. The determined critical exponents agree well with those obtained from the results of the renormalization group theory approach for a three-dimensional Ising system coupled with a long-range interaction between spins decaying as $J(r)\ensuremath{\approx}{r}^{\ensuremath{-}(d+\ensuremath{\sigma})}$ with $\ensuremath{\sigma}$ = 1.84. The Ising-type spin state in ${\mathrm{Mn}}_{1/4}{\mathrm{NbS}}_{2}$ is attributed to the higher size of MAE. Our theoretical analysis shows that indirect exchange interaction between Mn-Mn along the $c$ axis, mediated via spins' polarized conduction electrons of Nb atoms, a Ruderman-Kittel-Kasuya-Yoshida (RKKY) type ferromagnetic interaction, dominates over the direct in-plane Mn-Mn exchange interaction (less favorable due to large ${d}_{\text{Mn-Mn}}\ensuremath{\sim}6.67\phantom{\rule{4pt}{0ex}}\stackrel{\ifmmode \mathring{}\else \r{}\fi{}}{\mathrm{A}}$) and is thus responsible for the macroscopic magnetization in ${\mathrm{Mn}}_{1/4}{\mathrm{NbS}}_{2}$. The RKKY-type ferromagnetic interaction in ${\mathrm{Mn}}_{1/4}{\mathrm{NbS}}_{2}$ arises due to the large spin polarization of the conduction electrons associated with the Nb atoms at the Fermi energy and existence of unoccupied Mn $3d$ states well above the Fermi level.

Sirt6-mediated epigenetic modification of DNA accessibility is essential for Pou2f3-induced thymic tuft cell development

Thymic epithelial cells (TECs) are essential for the production of self-tolerant T cells. The newly identified thymic tuft cells are regulated by Pou2f3 and represent important elements for host type 2 immunity. However, epigenetic involvement in thymic tuft cell development remains unclear. We performed single-cell ATAC-seq of medullary TEC (mTEC) and established single-cell chromatin accessibility profiling of mTECs. The results showed that mTEC III cells can be further divided into three groups (Late Aire 1, 2, and 3) and that thymic tuft cells may be derived from Late Aire 2 cells. Pou2f3 is expressed in both Late Aire 2 cells and thymic tuft cells, while Pou2f3-regulated genes are specifically expressed in thymic tuft cells with simultaneous opening of chromatin accessibility, indicating the involvement of epigenetic modification in this process. Using the epigenetic regulator Sirt6-defect mouse model, we found that Sirt6 deletion increased Late Aire 2 cells and decreased thymic tuft cells and Late Aire 3 cells without affecting Pou2f3 expression. However, Sirt6 deletion reduced the chromatin accessibility of Pou2f3-regulated genes in thymic tuft cells, which may be caused by Sirt6–mediated regulation of Hdac9 expression. These data indicate that epigenetic regulation is indispensable for Pou2f3-mediated thymic tuft cell development.

Towards a spatial understanding of identity play: coworking spaces as playgrounds for identity

ABSTRACT Based on thirty interviews conducted in ten coworking spaces in Amsterdam and Paris, we ask whether and how members of coworking spaces engage in identity play, and what mechanisms related to space seem to enable such identity play. We identify four types of spatial mechanisms members and hosts of coworking spaces claim to create or engage in, and show how these relate to experimentation with professional identity. In so doing, we highlight possible material and spatial aspects of identity play. This paper contributes to the literature on identity play by drawing attention to the physicality and constitutive nature of the holding spaces necessary for identity play, and to research on coworking spaces by drawing attention to their possible identity effects.

Structural, Optical, Luminescence, and Electrical Properties of Eu/Li- and Eu/Na-Codoped Magnesium Bismuth Niobate Pyrochlores.

Eu-doped bismuth-based Bi1.5M0.4Mg0.5Nb1.5O7-δ (M = Li and Na) pyrochlores were synthesized by the organic-inorganic precursor combustion technique. The study examined the effect of rare earth element Eu3+ doping on the structural, dielectric, optical, and luminescence properties of synthesized materials. The analysis showed that the substitution of Bi3+ cations with Eu3+ leads to dielectric permittivity decreasing due to the structural distortion for the Eu-concentrated compositions and low polarizability of Eu3+. The band gap values predicted by electronic band structure calculation using DFT-HSE03 are in line with the experimental ones and tended to increase with the decrease in the unit cell parameters with Eu concentration changing. By the optical and luminescence measurements, the specific roles of Li- and Na-containing host types, additional phases, and dopant concentration in bismuth niobate pyrochlores are shown concerning the dielectric, structural, and Eu3+ emission properties. All Eu-doped bismuth-based pyrochlore ceramics behave as high-frequency dielectrics up to 200 °C and have mixed conductivity (electronic, proton, and oxygen) at T > 200 °C. The obtained dielectric parameters make them suitable for high-frequency ceramic capacitors.

The spatial distribution of Airbnb providers in Brussels: different drivers for different types of hosts?

PurposeThe purpose of this study is to compare the spatial distribution of different types of Airbnb hosts – based on a novel typology – and to investigate their association with neighbourhood characteristics in Brussels.Design/methodology/approachThis study describes the location of Airbnb dwellings across the types of hosts and use spatial tests to compare their distributions to the traditional hospitality industry. With regression models, this study examines the relationship between the provision of Airbnb listings and neighbourhood indicators.FindingsWhile different types of hosts offer their listings in the same urban space, they also cover different areas and exhibit different clustering processes. Their locations are associated with structural, socio-economic and demographic neighbourhood characteristics that vary across the types and provide support for the new typology.Research limitations/implicationsThis study focuses on the type of Airbnb hosts and their listings in one year, 2019. It would be worthwhile to apply the typology to other cities and to observe how the distributions change over time, including the period of the COVID-19 pandemic.Originality/valueTo the best of the authors’ knowledge, this paper is the first to suggest a finer typology of Airbnb hosts than the regular distinction into professional and non-professional types and reveals how hosts differ in the location of their Airbnbs.

Host type 2 immune response to xenogeneic serum components impairs biomaterial-directed osteo-regenerative therapies

The transformative potential of cells as therapeutic agents is being realized in a wide range of applications, from regenerative medicine to cancer therapy to autoimmune disorders. The majority of these therapies require ex vivo expansion of the cellular product, often utilizing fetal bovine serum (FBS) in the culture media. However, the impact of residual FBS on immune responses to cell therapies and the resulting cell therapy outcomes remains unclear. Here, we show that hydrogel-delivered FBS elicits a robust type 2 immune response characterized by infiltration of eosinophils and CD4+ T cells. Host secretion of cytokines associated with type 2 immunity, including IL-4, IL-5, and IL-13, is also increased in FBS-containing hydrogels. We demonstrate that the immune response to xenogeneic serum components dominates the local environment and masks the immunomodulatory effects of biomaterial-delivered mesenchymal stromal/stem cells. Importantly, delivery of relatively small amounts of FBS (3.2% by volume) within BMP-2-containing biomaterial constructs dramatically reduces the ability of these constructs to promote de novo bone formation in a radial defect model in immunocompetent mice. These results urge caution when interpreting the immunological and tissue repair outcomes in immunocompetent pre-clinical models from cells and biomaterial constructs that have come in contact with xenogeneic serum components.

FACTORS INFLUENCING THE BIOLOGICAL AND MORPHOMETRIC PARAMETERS OF HETERAKIS GALLINARUM EGGS (GMELIN, 1790)

The article presents the results of the research on the peculiarities of embryo and morphometric development
 of the eggs isolated from the gonads of female nematodes Heterakis gallinarum that parasitize turkeys and hens at different
 intensities of invasion in case of mono-and mixed forms of helminth infections. It was established that the eggs of H. gallinarum became invasive at 30 °C for 7 days, their survival rate in the laboratory conditions was: 80,67±2,08 % (turkeys), 84±3 % (chickens). The morphometric parameters of eggs excreted by mature H. gallinarum females are objectively influenced by such factors as the stage of biological cycle, the intensity of invasion, the type of host.

The Gentrification of Airbnb: Closing Rent Gaps Through the Professionalization of Hosting

In this article, we argue that it is analytically productive to think about the professionalization of hosting on Airbnb in terms of (commercial) gentrification. More precisely, we believe that rent gap theory is helpful to advance our understanding of why and how professionalized hosting has become an increasingly salient phenomenon and for centering the active role of Airbnb as a platform operator. We develop the notion of platform-scale rent gaps to explain the economic logic that drives Airbnb to professionalize its hosts and gentrify its platform. We then discuss Airbnb’s professionalization programs and tools, showing how some of its most substantial resources primarily cater to large-scale property managers who, like Airbnb itself, seek to identify and close rent gaps on the platform. This consequently creates the conditions for uneven business development opportunities among hosts, which we illustrate by focusing on how two different types of hosts have sought to professionalize their business in Berlin. Finally, we conclude by speculating on the relationship between the gentrification of the Airbnb platform and urban gentrification.

Oral dysbiosis and its linkage with SARS-CoV-2 infection

The human oral cavity harbours complex microbial communities with various commensal microorganisms that play pivotal roles in maintaining host health and immunity but can elicit local and systemic diseases. The role of commensal microorganisms in SARS-CoV-2 infection and disease susceptibility and enrichment of opportunistic pathobionts in the oral cavity is poorly understood. The present study aims to understand the altered landscape of the oral microbiome and mycobiome in SARS-CoV-2 infected patients (n = 30) and its correlation with risk factors compared to non-infected individuals (n = 24) using targeted amplicon sequencing. Diminution of species richness, an elevated abundance of opportunistic pathogens (Veillonella, Acinetobacter, Klebsiella, Prevotella, Gemella, and Streptococcus) and impaired metabolic pathways were observed in the COVID-19 patients. Similarly, altered oral mycobiome with enrichment of known respiratory disease causing pathogenic fungi were observed in the infected individuals. The data further suggested that reduction in immunomodulatory microorganisms lowers the protection of individuals from SARS-CoV-2. Linear discriminant analysis identified several differentially abundant taxa associated with risk factors (ageing and co-morbidities). We also observed distinct bacterial and fungal community structures of elderly infected patients compared to the younger age group members making them highly vulnerable to SARS-CoV-2 infection and disease severity. Furthermore, we also assessed the dynamics of the oral microbiome and mycobiome in symptomatic and asymptomatic patients, host types, co-morbidities, and viral load in the augmentation of specific pathobionts. Overall, the present study demonstrates the microbiome and mycobiome profiling of the COVID-19 infected individuals, the data further suggests that the SARS-CoV-2 infection triggers the prevalence of specific pathobiont.

Mycobacterium tuberculosis Induces Irg1 in Murine Macrophages by a Pathway Involving Both TLR-2 and STING/IFNAR Signaling and Requiring Bacterial Phagocytosis.

Irg1 is an enzyme that generates itaconate, a metabolite that plays a key role in the regulation of inflammatory responses. Previous studies have implicated Irg1 as an important mediator in preventing excessive inflammation and tissue damage in Mycobacterium tuberculosis (Mtb) infection. Here, we investigated the pattern recognition receptors and signaling pathways by which Mtb triggers Irg1 gene expression by comparing the responses of control and genetically deficient BMDMs. Using this approach, we demonstrated partial roles for TLR-2 (but not TLR-4 or -9), MyD88 and NFκB signaling in Irg1 induction by Mtb bacilli. In addition, drug inhibition studies revealed major requirements for phagocytosis and endosomal acidification in Irg1 expression triggered by Mtb but not LPS or PAM3CSK4. Importantly, the Mtb-induced Irg1 response was highly dependent on the presence of the bacterial ESX-1 secretion system, as well as host STING and Type I IFN receptor (IFNAR) signaling with Type II IFN (IFN-γ) signaling playing only a minimal role. Based on these findings we hypothesize that Mtb induces Irg1 expression in macrophages via the combination of two independent triggers both dependent on bacterial phagocytosis: 1) a major signal stimulated by phagocytized Mtb products released by an ESX-1-dependent mechanism into the cytosol where they activate the STING pathway leading to Type I-IFN production, and 2) a secondary TLR-2, MyD88 and NFκB dependent signal that enhances Irg1 production independently of Type I IFN induction.

Abstract 514: High-density Lipoproteins Mediate Bidirectional Flux Of Extracellular Small RNAs In Macrophages

HDL are a class of dynamic particles that play critical roles in lipid metabolism, inflammation, and cell signaling. HDL are small, highly-mobile carriers of diverse molecular cargo, that include many types of host and non-host small RNAs (sRNA), as observed by sequencing. We have previously reported that HDL can accept host sRNAs from macrophages and transfer functional miRNAs to recipient endothelial cells; however, HDL’s ability to transfer sRNAs, host or non-host, to macrophages or mediate intercellular communication between immune cells are unknown. Based on preliminary results, we hypothesize that HDL mediates bidirectional flux of extracellular sRNA between macrophages. To demonstrate that HDL accepts sRNAs from macrophages and determine if macrophages have the capacity to export non-host sRNAs to HDL in vitro , macrophages were loaded with a synthetic microbial sRNA (ssRNA40-Cy5) and allowed to efflux to accepting HDL in the media. Macrophage HDL-sRNA acceptance was assessed by size-exclusion chromatography and fluorometry; and macrophages were found to export microbial sRNAs to HDL in a process inhibited by monensin, an ionophore and small molecule inhibitor of the endo-lysosomal pathway. Previous studies of HDL-sRNA flux required targeted candidate approaches based on prior knowledge. To overcome this barrier, sRNAs on intact native HDL particles were labeled (stained) with SYTO RNASelect dye and incubated with macrophages. This approach facilitated the quantification of all sRNAs on HDL using a standard curve and traced sRNA uptake and storage in recipient macrophages. After confirming specificity, SYTO quantification of total sRNAs showed that human HDL transport >14 μg sRNA/ mg total protein, a value far greater than previously recognized. HDL was found to transfer sRNAs to recipient macrophages based on fluorescence quantification and confocal microscopy live-cell imaging of HDL-delivered sRNAs in macrophage organelles. These results support that HDL mediates the bidirectional import and export of extracellular sRNAs from macrophages.

Automated Identification of Immunocompromised Status in Critically Ill Children.

Easy identification of immunocompromised hosts (ICHs) would allow for stratification of culture results based on host type. We utilized antimicrobial stewardship program (ASP) team notes written during handshake stewardship rounds in the pediatric intensive care unit (PICU) as the gold standard for host status; clinical notes from the primary team, medication orders during the encounter, problem list, and billing diagnoses documented prior to the ASP documentation were extracted to develop models that predict host status. We calculated performance for three models based on diagnoses/medications, with and without natural language processing from clinical notes. The susceptibility of pathogens causing bacteremia to commonly used empiric antibiotic regimens was then stratified by host status. We identified 844 antimicrobial episodes from 666 unique patients; 160 (18.9%) were identified as ICHs. We randomly selected 675 initiations (80%) for model training and 169 initiations (20%) for testing. A rule-based model using diagnoses and medications alone yielded a sensitivity of 0.87 (08.6-0.88), specificity of 0.93 (0.92-0.93), and positive predictive value (PPV) of 0.74 (0.73-0.75). Adding clinical notes into XGBoost model led to improved specificity of 0.98 (0.98-0.98) and PPV of 0.9 (0.88-0.91), but with decreased sensitivity 0.77 (0.76-0.79). There were 77 bacteremia episodes during the study period identified and a host-specific visualization was created. An electronic health record-based phenotype based on notes, diagnoses, and medications identifies ICH in the PICU with high specificity.

LL-37 transports immunoreactive cGAMP to activate STING signaling and enhance interferon-mediated host antiviral immunity.

Cyclic 2',3'-GMP-AMP (cGAMP) binds to and activates stimulator of interferon genes (STING), which then induces interferons to drive immune responses against tumors and pathogens. Exogenous cGAMP produced by infected and malignant cells and synthetic cGAMP used in immunotherapy must traverse the cell membrane to activate STING in target cells. However, as an anionic hydrophilic molecule, cGAMP is not inherently membrane permeable. Here, we show that LL-37, a human host defense peptide, can function as a transporter of cGAMP. LL-37 specifically binds cGAMP and efficiently delivers cGAMP into target cells. cGAMP transferred by LL-37 activates robust interferon responses and host antiviral immunity in a STING-dependent manner. Furthermore, we report that LL-37 inducers vitamin D3 and sodium butyrate promote host immunity by enhancing endogenous LL-37 expression and its mediated cGAMP immune response. Collectively, our data uncover an essential role of LL-37 in innate immune activation and suggest new strategies for immunotherapy.

New molecular markers for distinguishing the main phylogenetic lineages within Alternaria section Alternaria

Several members of Alternaria section Alternaria are economically important plant-pathogenic fungi that cause disease on a wide range of host types and plant tissues. The production of Alternaria-derived mycotoxins can lead to significant post-harvest losses due to contamination of agricultural products. Multiple Alternaria species are listed as regulated organisms, which are monitored by international plant protection programmes. These taxa often share high levels of both morphological and phylogenetic similarity, and the establishment of molecular markers that are able to distinguish among them unambiguously has proven to be quite challenging. Previously, we examined fine-scale genome-wide phylogenetic patterns and proposed a list of candidate genes for development into informative markers that are diagnostic for the main section Alternaria lineages. Here, we design primer sets and sequence three new markers (ASA-05, ASA-10, ASA-19) in order to evaluate their diagnostic performance. Sequence data for 49 new independent test taxa were combined with existing data for 38 taxa, and phylogenetic analyses revealed that, in general, the new molecular markers consistently classified section Alternaria strains into one of the main lineages. A discrepancy among the three markers for lineage assignment was observed only for one strain. We also sequenced a commonly used marker in molecular phylogenetics of fungi (rpb2, RNA polymerase II second largest subunit) and found it was outperformed by all three of the new markers. We suggest that an ASA marker presented here could form the basis of a convenient one-locus test for rapid and routine diagnostic screening of unknown section Alternaria strains.

Effect of host preference and micro habitats on the survival of Tetranychus urticae Koch (Acari: Tetranychidae) in Saudi Arabia

ObjectiveControl of pests is essential to save the loss of economically important plants. Biological and environmental control became the most important interventions of choice. The two-spotted spider mite Tetranychus urticae is a herbivorous mite which is considered to be a harmful pest. The objective of the study was to investigate the effect of host preference on the survival and distribution of Tetranychus urticae. MethodsSpecimens of T. urtica were collected from Solanum melongena plants grown at Al Qaseem University. Eggs were transferred individually to the bottom surface of leaves of certain plants namely: Phasoelus vulgaris (beans), Solanum melongena (eggplant), Fragaria ananasa (Strawberry), Citrus sinensis (Orange), and Cucumis sativus (Cucumber) and reared on those plants under optimum conditions. The effect of climatic conditions and the type of the plant host on the survival of mature and immature stages of T. urtica has been observed. ResultsThe total growth period length of the immature stage of the male mites was found to be shorter than the growth period of the female immature stages. The peak of this period was recorded in Citrus sinensis followed by Cucumis sativus then Solanum melongena, Phasoelus vulgaris, and Fragaria ananasa. ConclusionThese results may lead to the screening process of comparatively resistant herbal species to be used in the management of T. urticae.

ISOLATION, CLONING AND PHYLOGENETIC ANALYSIS OF pld AND cp40, VIRULENCE FACTORS OF A MEXICAN ISOLATE OF Corynebacterium pseudotuberculosis ovis

<p><strong>Background. </strong>Caseous lymphadenitis is a worldwide distribute disease that affects the sheep and goat industry. <em>Corynebacterium pseudotuberculosis</em> <em>ovis</em> is a facultative intracellular Gram-positive bacterium, considered the etiologic agent of the disease. Complete genome sequences of Mexican isolates have been obtained and different strain has been previously characterized. The study of virulence factors allows establishing potential candidates for the development of vaccines and diagnostic tools. <strong>Objective.</strong> To identify the complete <em>pld </em>and <em>cp40</em> genes sequence from a Mexican isolate of <em>Corynebacterium pseudotuberculosis ovis</em>, principal virulence factors. <strong>Methodology</strong>. <em>Corynebacterium pseudotube</em>rculosis isolate 2J-L was obtained from an abscess of a sheep of the State of Jalisco. The complete <em>pld </em>and <em>cp40</em> genes were amplified by PCR, cloned into a replicative vector and sequenced by Sanger automatic sequencing. Gene sequences conservancy was established, analyzing homology across previously reported genes of Mexican strains MEX1, MEX2, MEX9, MEX25 and MEX29. <strong>Results</strong>. Sequences of <em>pld</em> and <em>cp40</em> genes from isolate 2J-L presented high percentages of similarity (99%) in comparison with the sequences of other isolates of <em>Corynebacterium pseudotuberculosis</em>, reported in the GenBank database. The analysis of nucleotide sequence homology and phylogenetic tree based on <em>pld</em> and <em>cp40</em> directed the observation that 2J-L is related to Mexican strain MEX29 and MEX25. Phylogenetic results agreed on the idea that strains biovar <em>ovis</em> and biovar <em>equi</em> are groupings on different clades. Finally, results indicate that Mexican strains are more similar among strains isolated from the same host type, without geography distance influence. <strong>Implications.</strong> The analysis pointed out that both genes conserve their sequences in comparison with Mexican and international strains, which encourages the research continuity for vaccine and diagnostic tools development using proteins PLD and CP40 as antigen targets. <strong>Conclusions.</strong> The complete <em>pld</em> and <em>cp40</em> genes from Mexican isolate 2J-L were amplified, cloned and analyzed; important virulence factors from <em>Corynebacterium pseudotuberculosis</em>.</p>

Human land use impacts viral diversity and abundance in a New Zealand river.

Although water-borne viruses have important implications for the health of humans and other animals, little is known about the impact of human land use on viral diversity and evolution in water systems such as rivers. We used metatranscriptomic sequencing to compare the diversity and abundance of viruses at sampling sites along a single river in New Zealand that differed in human land-use impacts, ranging from pristine to urban. From this, we identified 504 putative virus species, of which 97 per cent were novel. Many of the novel viruses were highly divergent and likely included a new subfamily within the Parvoviridae. We identified at least sixty-three virus species that may infect vertebrates—most likely fish and water birds—from the Astroviridae, Birnaviridae, Parvoviridae, and Picornaviridae. No putative human viruses were detected. Importantly, we observed differences in the composition of viral communities at sites impacted by human land use (farming and urban) compared to native forest sites (pristine). At the viral species level, the urban sites had higher diversity (327 virus species) than the farming (n = 150) and pristine sites (n = 119), and more viruses were shared between the urban and farming sites (n = 76) than between the pristine and farming or urban sites (n = 24). The two farming sites had a lower viral abundance across all host types, while the pristine sites had a higher abundance of viruses associated with animals, plants, and fungi. We also identified viruses linked to agriculture and human impact at the river sampling sites in farming and urban areas that were not present at the native forest sites. Although based on a small sample size, our study suggests that human land use can impact viral communities in rivers, such that further work is needed to reduce the impact of intensive farming and urbanisation on water systems.

Diagnostic potential of 36-55 kDa somatic antigens of Fasciola gigantica for bovine fasciolosis

Fascioliasis causes huge economic losses in livestock industry by reducing the growth, fertility rate, meat and milk yield. In the present study, somatic antigens isolated from Fasciola gigantica were assessed for the early detection of infection by developing antibody detection enzyme immunoassay. The somatic antigens extracted from adult F. gigantica worms was separated on SDS-PAGE and immunogenicity was determined by Western blot (WB). The results showed polypeptides bands between 15 to 95 kDa, and most prominent bands were 15, 28, 36, 38, 55, 72 and 95 kDa polypeptides. The WB revealed a single polypeptide of size between 36 to 55 kDa as antigenic. The sensitivity and specificity of ELISA test established for 36 to 55 kDa somatic antigens was 95.45% (95% CI: 77.16% to 99.88%) and 87.1% (95% CI: 70.17% to 96.37%), respectively. Kappa value revealed that the strength of agreement is considered to be very ‘good’. In house established ELISA was implemented in the field and 12.1% (31/256) large ruminants were found positive, while 4.68% (12/256) with postmortem examination. The fasciolosis did not show significant (P>0.05) association with host type, breed and age groups, while significant (P<0.01) association with host sexes. The result confirmed that in-house established ELISA test had good value for serodiagnosis of fasciolosis in cattle and buffaloes for large scale epidemiological studies.

Identification of novel TMPRSS2 inhibitors against SARS-CoV-2 infection: a structure-based virtual screening and molecular dynamics study.

The scientific insights gained from the severe acute respiratory syndrome (SARS) and the middle east respiratory syndrome (MERS) outbreaks are helping scientists to fast-track the antiviral drug discovery process against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Coronaviruses, as well as influenza viruses, depend on host type 2 transmembrane serine protease, TMPRSS2, for entry and propagation in the human cell. Recent studies show that SARS-CoV-2 also uses TMPRSS2 for its cell entry. In the present study, a structure-based virtual screening of 52,337, protease ligands downloaded from the Zinc database was carried out against the homology model of TMPRSS2 protein followed by the molecular dynamics-based simulation to identify potential TMPRSS2 hits. The virtual screening has identified 13 hits with a docking score range of −10.447 to −9.863 and glide energy range of −60.737 to −40.479 kcal/mol. The binding mode analysis shows that the hit molecules form H-bond (Asp180, Gly184 & Gly209), Pi-Pi stacking (His41), and salt bridge (Asp180) type of contacts with the active site residues of TMPRSS2. In the MD simulation of ZINC000013444414, ZINC000137976768, and ZINC000143375720 hits show that these molecules form a stable complex with TMPRSS2. The complex equilibrates well with a minimal RMSD and RMSF fluctuation. All three structures, as predicted in Glide XP docking, show a prominent interaction with the Asp180, Gly184, Gly209, and His41. Further, MD simulation also identifies a notable H-bond interaction with Ser181 for all three hits. Among these hits, ZINC000143375720 shows the most stable binding interaction with TMPRSS2. The present study is successful in identifying TMPRSS2 ligands from zinc data base for a possible application in the treatment of COVID-19.

Population genomics of Escherichia coli in livestock-keeping households across a rapidly developing urban landscape

Quantitative evidence for the risk of zoonoses and the spread of antimicrobial resistance remains lacking. Here, as part of the UrbanZoo project, we sampled Escherichia coli from humans, livestock and peri-domestic wildlife in 99 households across Nairobi, Kenya, to investigate its distribution among host species in this rapidly developing urban landscape. We performed whole-genome sequencing of 1,338 E. coli isolates and found that the diversity and sharing patterns of E. coli were heavily structured by household and strongly shaped by host type. We also found evidence for inter-household and inter-host sharing and, importantly, between humans and animals, although this occurs much less frequently. Resistome similarity was differently distributed across host and household, consistent with being driven by shared exposure to antimicrobials. Our results indicate that a large, epidemiologically structured sampling framework combined with WGS is needed to uncover strain-sharing events among different host populations in complex environments and the major contributing pathways that could ultimately drive the emergence of zoonoses and the spread of antimicrobial resistance.