Background: ZyCoV-D is a DNA vaccine candidate, which comprises a plasmid DNA carrying spike-S gene of SARS-CoV-2 virus along with gene coding for signal peptide. The spike(S) region includes the receptor-binding domain (RBD), which binds to the human angiotensin converting Enzyme (ACE)-2 receptor and mediates the entry of virus inside the cell. Methods: We conducted a single-center, open-label, non-randomized, Phase 1 trial in India between July 2020 and October 2020. Healthy adults aged between 18 and 55 years were sequentially enrolled and allocated to one of four treatment arms in a dose escalation manner. Three doses of vaccine were administered 28 days apart and each subject was followed up for 28 days post third dose to evaluate safety and immunogenicity. Findings: Out of 126 individuals screened for eligibility. Forty-eight subjects (mean age 34¢9 years) were enrolled and vaccinated in the Phase 1 study Overall, 12/48 (25%) subjects reported at least one AE (i.e. combined solicited and unsolicited) during the study. There were no deaths or serious adverse events reported in Phase 1 of the study. The proportion of subjects who seroconverted based on IgG titers on day 84 was 4/11 (36¢36%), 4/12 (33¢33%), 10/10 (100¢00%) and 8/10 (80¢00%) in the treatment Arm 1 (1 mg: Needle), Arm 2 (1 mg: NFIS), Arm 3 (2 mg: Needle) and Arm 4 (2 mg: NFIS), respectively. Interpretation: ZyCoV-D vaccine is found to be safe, well-tolerated and immunogenic in the Phase 1 trial. Our findings suggest that the DNA vaccine warrants further investigation.

ALV003 is an orally active protease that appears to be stable in the fed stomach and degrades dietary gluten in this compartment. Single doses of oral ALV003 were not associated with serious adverse reactions.

Infection by Leptospira interrogans has been causally associated with human and equine uveitis. Studies in our laboratories have demonstrated that leptospiral lipoprotein LruA and LruB are expressed in the eyes of uveitic horses, and that antibodies directed against LruA and LruB react with equine lenticular and retinal extracts, respectively. These reactivities were investigated further by performing immunofluorescent assays on lenticular and retinal tissue sections. Incubation of lens tissue sections with LruA-antiserum and retinal sections with LruB-antiserum resulted in positive fluorescence. By employing two-dimensional gel analyses followed by immunoblotting and mass spectrometry, lens proteins cross-reacting with LruA antiserum were identified to be α-crystallin B and vimentin. Similarly, mass spectrometric analyses identified β-crystallin B2 as the retinal protein cross-reacting with LruB-antiserum. Purified recombinant human α-crystallin B and vimentin were recognized by LruA-directed antiserum, but not by control pre-immune serum. Recombinant β-crystallin B2 was likewise recognized by LruB-directed antiserum, but not by pre-immune serum. Moreover, uveitic eye fluids contained significantly higher levels of antiibodies that recognized α-crystallin B, β-crystallin B2 and vimentin than did normal eye fluids. Our results indicate that LruA and LruB share immuno-relevant epitopes with eye proteins, suggesting that cross-reactive antibody interactions with eye antigens may contribute to immunopathogenesis of Leptospira-associated recurrent uveitis.

The impact of variation in the relative fractions of the ferromagnetic metallic and antiferromagnetic/charge ordered insulator phases on the supercooling/superheating transition in strongly phase separated system, La5/8−yPryCa3/8MnO3 (y ≈ 0.4), has been studied employing magnetotransport measurements. Our study clearly shows that the supercooling transition temperature is non-unique and strongly depends on the magneto-thermodynamic path through which the low temperature state is accessed. In contrast, the superheating transition temperature remains constant. The thermo-magnetic hysteresis, the separation of the two transitions and the associated resistivity, all are functions of the relative fraction of the coexisting phases.

Mesenchymal stem cells (MSCs) isolated from umbilical cord blood (UCB) in equines have not been well characterized with respect to the expression of pluripotency and mesenchymal markers and for tenogenic differentiation potential in vitro. The plastic adherent fibroblast-like cells isolated from 13 out of 20 UCB samples could proliferate till passage 20. The cells expressed pluripotency markers (OCT4, NANOG, and SOX2) and MSC surface markers (CD90, CD73, and CD105) by RT-PCR, but did not express CD34, CD45, and CD14. On immunocytochemistry, the isolated cells showed expression of CD90 and CD73 proteins, but tested negative for CD34 and CD45. In flow cytometry, CD29, CD44, CD73, and CD90 were expressed by 96.36 ± 1.28%, 93.40 ± 0.70%, 73.23 ± 1.29% and 46.75 ± 3.95% cells, respectively. The UCB-MSCs could be differentiated to tenocytes by culturing in growth medium supplemented with 50 ng/ml of BMP-12 by day 10. The differentiated cells showed the expression of mohawk homeobox (Mkx), collagen type I alpha 1 (Col1α1), scleraxis (Scx), tenomodulin (Tnmd) and decorin (Dcn) by RT-PCR. In addition, flow cytometry detected tenomodulin and decorin protein in 95.65 ± 2.15% and 96.30 ± 1.00% of differentiated cells in comparison to 11.30 ± 0.10% and 19.45 ± 0.55% cells, respect vely in undifferentiated control cells. The findings support the observation that these cells may be suitable for therapeutic applications, including ruptured tendons in racehorses.

Celiac Sprue is an inflammatory disease of the small intestine triggered by ingestion of dietary gluten, a family of glutamine and proline rich proteins found in common foodgrains such as wheat, rye, and barley. One potential therapy for this lifelong disease anticipates using an oral protease to detoxify gluten in vivo. Recent studies have shown that EP-B2 (endoprotease B, isoform 2) from barley is a promising example of such a glutenase, thus warranting its large-scale production for animal safety and human clinical studies. Here we describe a scaleable fermentation, refolding and purification process for the production of gram to kilogram quantities of pro-EP-B2 (zymogen form of EP-B2) in a lyophilized form. A fed-batch E. coli fermentation system was developed that yields 0.3-0.5 g purified recombinant protein per liter culture volume. Intracellular degradation of pro-EP-B2 during the fermentation was overcome by manipulating the fermentation temperature and duration of protein expression. A simple refolding protocol was developed using a fast dilution method to refold the enzyme at concentrations greater than 0.5 mg/mL. Kinetic analysis showed that pro-EP-B2 refolding is a first-order reaction with an estimated rate constant of 0.15 h(-1). A lyophilization procedure was developed that yielded protein with 85% recoverable activity after 7 weeks of storage at room temperature. The process was successfully scaled up to 100 L with comparable purity and recovery.

The discovery of Weyl semimetals (WSM) has brought forth the condensed matter realization of Weyl fermions, which were previously theorized as low energy excitations in high energy particle physics. Recently, transition metal mono-pnictides are under intense investigation for understanding properties of inversion-symmetry broken Weyl semimetals. Non-trivial Berry phase and chirality are important markers for characterizing topological aspects of Weyl semimetals. Most recently, theoretical calculations predict strong influence of the position of Weyl nodes with respect to Fermi surface and weak disorder that can drive WSMs into chirally symmetric Dirac semimetals. Using magneto-transport measurements in single crystals of WSM NbP, we observe an exceptionally large magnetoresistance at low temperature, which is non-saturating and linear at high fields. The origin of linear transverse magnetoresistance is assigned to charge carrier mobility fluctuations. Negative longitudinal magnetoresistance is not seen, suggesting lack of well-defined chiral anomaly in NbP. Unambiguous Shubnikov-de Haas oscillations are observed at low temperatures that are correlated to a trivial Berry phase corresponding to Fermi surface extrema at 30.5 Tesla. Our results are important towards identifying topological characteristics of Weyl semimetals and their experimental manifestations in the presence of weak disorder.

The present study was planned to investigate the molecular prevalence of canine monocytic ehrlichiosis (CME) in dogs in and around Hisar and to evaluate the haemato-biochemical profile for its better management. A total of 60 dogs presented to Medicine Section, TVCC, LUVAS, Hisar with the history of naturally acquired tick infestation and clinical signs consistent with CME were screened on the basis of blood smear examination, followed by molecular detection by nested PCR assay targeting a portion of 16S rRNA gene of . Nested PCR detected 18 cases positive for with estimated 30% percent positivity as compared to 8.33% (5 out of 60) by blood smear examination. These 18 dogs confirmed for CME by nested PCR were assessed for clinical and haemato-biochemical profile. Breed-wise prevalence indicated maximum number of cases in Labrador retriever, followed by Pug, Rottweiler and German shepherd dog with more number of cases in male dogs. Age-wise prevalence revealed highest number of cases in more than 1 year age group, followed by 6 months to 1 year age group and least in less than 6 months aged dogs. Pyrexia, anorexia and pale to congested mucous membranes were the main clinical signs observed, followed by lethargy, vomiting. Less common clinical signs were epistaxis, lymphadenomegaly, hind limb weakness, malena, ocular discharge, followed by haematuria, corneal opacity, nasal discharge and coughing, icterus, dermal petechiae and ecchymoses. The haematological profile revealed macrocytic hypochromic anaemia, thrombocytopenia, normal leucocyte count with relative lymphocytosis, monocytosis and neutropenia. Serum biochemistry revealed significant rise in values of ALT, AST, GGT, bilirubin total, bilirubin indirect, alkaline phosphatase and A/G ratio in affected dogs as compared to healthy control, suggesting the hepatic dysfunction. The lipid metabolites and kidney function parameters were non-significantly altered from those of healthy control. A high positivity for detected by nested PCR in dogs in and around Hisar suggests the endemicity of the disease in dogs' population in this region and warrants the screening for the disease in suspected dogs by this technique as compared to routine blood smear examination. The presented haemato-biochemical profile may be useful in presumptive diagnosis of the disease in dogs and their better clinical management.