Antigen-specific acquired immunity in human brucellosis: implications for diagnosis, prognosis, and vaccine development.

Brucella spp., are Gram negative bacteria that cause disease by growing within monocyte/macrophage lineage cells. Clinical manifestations of brucellosis are immune mediated, not due to bacterial virulence factors. Acquired immunity to brucellosis has been studied through observations of naturally infected hosts (cattle, goats), mouse models (mice), and human infection. Even though Brucella spp. are known for producing mechanisms that evade the immune system, cell-mediated immune responses drive the clinical manifestations of human disease after exposure to Brucella species, as high antibody responses are not associated with protective immunity. The precise mechanisms by which cell-mediated immune responses confer protection or lead to disease manifestations remain undefined. Descriptive studies of immune responses in human brucellosis show that TH(1) (interferon-γ-producing T cells) are associated with dominant immune responses, findings consistent with animal studies. Whether these T cell responses are protective, or determine the different clinical responses associated with brucellosis is unknown, especially with regard to undulant fever manifestations, relapsing disease, or are associated with responses to distinct sets of Brucella spp. antigens are unknown. Few data regarding T cell responses in terms of specific recognition of Brucella spp. protein antigens and peptidic epitopes, either by CD4+ or CD8+ T cells, have been identified in human brucellosis patients. Additionally because current attenuated Brucella vaccines used in animals cause human disease, there is a true need for a recombinant protein subunit vaccine for human brucellosis, as well as for improved diagnostics in terms of prognosis and identification of unusual forms of brucellosis. This review will focus on current understandings of antigen-specific immune responses induced Brucella peptidic epitopes that has promise for yielding new insights into vaccine and diagnostics development, and for understanding pathogenetic mechanisms of human brucellosis

Herpes simplex keratitis: Challenges in diagnosis and clinical management

Herpes simplex virus is responsible for numerous ocular diseases, the most common of which is herpetic stromal keratitis. This is a recurrent infection of the cornea that typically begins with a subclinical infection of the cornea that establishes a latent infection of sensory ganglia, most often the trigeminal ganglia. Recurring infections occur when the virus is reactivated from latency and travels back to the cornea, where it restimulates an inflammatory response. This inflammatory response can lead to decreased corneal sensation, scarring, and blindness. The diagnosis of these lesions as the result of a recurrent herpes simplex virus infection can at times be problematic. Currently, herpetic stromal keratitis is diagnosed by its clinical presentation on the slit-lamp examination, but the literature does not always support the accuracy of these clinical findings. Other diagnostic tests such as polymerase chain reaction assay, enzyme-linked immunosorbent assay, immunofluorescent antibody, and viral cultures have provided more definitive diagnosis, but also have some limitations. That said, accurate diagnosis is necessary for proper treatment, in order to prevent serious consequences. Current treatment reduces the severity of lesions and controls further viral spread, but does not provide a cure

Trends and oscillations in the Indian summer monsoon rainfall over the last two millennia

Observations show that summer rainfall over large parts of South Asia has declined over the past five to six decades. It remains unclear, however, whether this trend is due to natural variability or increased anthropogenic aerosol loading over South Asia. Here we use stable oxygen isotopes in speleothems from northern India to reconstruct variations in Indian monsoon rainfall over the last two millennia. We find that within the long-term context of our record, the current drying trend is not outside the envelope of monsoon’s oscillatory variability, albeit at the lower edge of this variance. Furthermore, the magnitude of multi-decadal oscillatory variability in monsoon rainfall inferred from our proxy record is comparable to model estimates of anthropogenic-forced trends of mean monsoon rainfall in the 21st century under various emission scenarios. Our results suggest that anthropogenic forced changes in monsoon rainfall will remain difficult to detect against a backdrop of large natural variability

Humoral and cytokine response elicited during immunisation with recombinant Immune Mapped protein-1 (EtIMP-1) and oocysts of Eimeria tenella

Eimeria tenella, the causative agent of caecal coccidiosis, is a pathogenic gut dwelling protozoan which can cause severe morbidity and mortality in farmed chickens. Immune mapped protein-1 (IMP-1) has been identified as an anticoccidial vaccine candidate; in the present study allelic polymorphism was assessed across the IMP-1 coding sequence in E. tenella isolates from four countries and compared with the UK reference Houghton strain. Nucleotide diversity was low, limited to expansion/contraction of a CAG triplet repeat and five substitutions, three of which were non-synonymous. The EtIMP-1 coding sequence from a cloned Indian E. tenella isolate was expressed in E. coli and purified as a His-tagged thioredoxin fusion protein. An in-vivo vaccination and challenge trial was conducted to test the vaccine potential of recombinant EtIMP-1 (rEtIMP-1) and to compare post-vaccination immune responses of chickens to those stimulated by live oocyst infection. Following challenge, parasite replication measured using quantitative PCR was significantly reduced in chickens that had been vaccinated with rEtIMP-1 (rIC group; 67% reduction compared to UC or unimmunised controls; 79% reduction compared to rTC group or recombinant thioredoxin mock-immunised controls, p < 0.05), or the birds vaccinated by infection with oocysts (OC group, 90% compared to unimmunised controls). Chickens vaccinated with oocysts (OC) had significantly higher levels of interferon gamma in their serum post-challenge, compared to rEtIMP-1 vaccinated birds (rIC). Conversely rEtIMP-1 (rIC) vaccinated birds had significantly higher antigen specific serum IgY responses, correlating with higher serum IL-4 (both p < 0.05)

Validation of Participatory Farming Situation Identification: Case of Rainfed Rice Cultivation in Selected Area of West Bengal, India

Paper Presented at the 4th World Congress on Conservation Agriculture, 2009 at New Delhi, Indiamicro-farming situation, farmers’ classification, validation of indigenous classification, rainfed rice, appropriate technology, Community/Rural/Urban Development, Farm Management, Research Methods/ Statistical Methods, Teaching/Communication/Extension/Profession,

HIGH-THROUGHPUT SCREENING AND DYNAMIC STUDIES OF SELECTED COMPOUNDS AGAINST SARS-COV-2

Objective: This study was aimed to analyze the inhibitory effect of the drugs used in nanocarrier as well as nanoparticles formulation based drug delivery system selected from PubChem database literature against 3CLpro (3C-like protease) receptor of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) by implementing several in silico analysis techniques. Methods: This paper detailed a molecular docking-based virtual screening of 5240 compounds previously utilized in nanoparticle and nanocarrier drug delivery systems utilizing AutoDock Vina software on 3CL protease to discover potential inhibitors using a molecular docking technique. Results: According to the results of the screening, the top two compounds, PubChem Id 58823276 and PubChem Id 60838 exhibited a high affinity for the 3CL protease binding region. Their binding affinities were-9.6 and-8.5 kJ/mol, indicating that they were tightly bound to the target receptor, respectively. These results outperformed those obtained using the co-crystallized native ligand, which exhibited a binding affinity of-7.4 kJ/mol. PubChem Id 60838, the main hit compound in terms of both binding affinity and ADMET analysis, displayed substantial deformability after MD simulation. As a result of the VS and molecular docking techniques, novel 3CL protease inhibitors from the PubChem database were discovered using the Lipinski rule of five and functional molecular contacts with the target protein, as evidenced by the findings of this work. Conclusion: The findings suggest that the compounds discovered may represent attractive opportunities for the development of COVID-19 3CLpro inhibitors and that they need further evaluation and investigation

Genetics and genomics studies of rice disease resistance and development of alternative disease management methods for bacterial panicle blight and sheath blight

Bacterial panicle blight (BPB) and sheath blight (SB), caused by the bacteria Burkholderia glumae and B. gladioli, and the fungus Rhizoctonia solani, respectively, are two major rice diseases in southern rice growing regions of US. No completely resistant rice cultivars have been identified for these diseases. However, a medium-grain cultivar, Jupiter, showed partial resistance to BPB. In order to understand the mechanisms of rice resistance against BPB and SB, rice genetics and genomics studies have been conducted. Alternative methods to suppress BPB and SB were also studied. Broad-sense heritability and correlations were calculated for the traits, BPB and SB disease ratings, days to heading, and plant height, with recombinant inbred lines generated from a cross between Trenasse and Jupiter in replicated trials for two years. Days to heading and plant height had high heritability, and were negatively correlated with BPB and SB disease ratings. The traits with high heritability will not have environmental influence, and can be used as indirect selection tools. Study on genomic characteristics of five rice genotypes grown in Louisiana using their whole genome sequence data provides genome-wide DNA polymorphisms among them. These information will enable us to understand genetic elements for phenotypic variations among these genotypes, which will help to enhance the genetic studies of US rice cultivars. The sequence data were also used to develop microsatellites and single nucleotide polymorphism markers, which can be used for genetic mapping studies. Previous microarray studies showed that the gene encoding a NAC4-like transcription factor, named bacterial panicle blight response gene 1 (BPR1), was highly up-regulated in Jupiter upon B. glumae inoculation. Expression of BPR1 in response to B. glumae was not detected in both Jupiter and Trenasse at seedling and tillering stages. However, rapid induction of BPR1 expression was observed in Jupiter, but not in Trenasse, when it was treated with B. glumae or chemicals, such as ascorbic acid and jasmonic acid, at its heading stage, suggesting that BPR1 expression is tissue-specific, and might be involved in rice defense response against B. gluame. Several rice-associated bacteria (RAB) isolated from healthy rice leaves were tested for their ability to suppress BPB and SB in rice. Those RAB were able to suppress bacterial cell growth and sclerotia germination in vitro, and were able to reduce the BPB and SB symptoms in rice in the field. Based on the 16S rDNA sequencing analysis, those RABs were identified as Bacillus and Lysinibacillus spp., and are potential candidates for biological control agents