Elucidating the molecular interaction of Zebrafish (Danio rerio) peptidoglycan recognition protein 2 with diaminopimelic acid and lysine type peptidoglycans using in silico approaches

Abstract

Peptidoglycan recognition proteins (PGRPs) belong to the family of pattern recognition receptor, represent the major constituent of innate immunity. Although PGRPs are structurally conserved through evolution, their involvement in innate immunity is different in vertebrates and invertebrates. They are highly specific towards recognition of ligands and can hydrolyze bacterial peptidoglycans (PGNs). Zebrafish PGRPs (zPGRPs) have both peptidoglycans lytic amidase activity and broad-spectrum bactericidal activity, but far less is known about how these receptors recognize these microbial ligands. Such studies are hindered due to lack of structural and functional configuration of zPGRPs. Therefore, in this study, we predicted the three-dimensional structure of zPGRP2 through theoretical modeling, investigated the conformational and dynamic properties through molecular dynamics simulations. Molecular docking study revealed the microbial ligands, that is, muramyl pentapeptide–DAP , muramyl pentapeptide–LYS, muramyl tripeptide–DAP, muramyl tripeptide–Lys, muramyl tetrapeptide–DAP, muramyl tetrapeptide–LYS and tracheal cytotoxin interacts with the conserved amino acids of the ligand recognition site comprised of β1, α2, α4, β4 and loops connecting β1 ? α2, α2 ? β2, β3 ? β4 and α4 ? α5. Conserved His31, His32, Ala34, Ile35, Pro36, Lys38, Asp60, Trp61, Trp63, Ala89, His90, Asp106, His143 and Arg144 are predicted to essential for binding and provides stability to these zPGRP–PGN complexes. Our study provides basic molecular information for further research on the immune mechanisms of PGRP’s in Zebrafish. The plasticity of the zPGRP’s binding site revealed by these microbial ligands suggests an intrinsic capacity of the innate immune system to rapidly evolve specificities to meet new microbial challenges in the future.

Communicated by Ramaswamy H. Sarma     

Fused lobed anther and hooked stigma affect pollination,fertilization and fruit set in mango: A scanning electron microscopy study

Mango malformation is the most threaten disease that limits mango production, worldwide. For a long time, due to its complex nature, the cause and causal agents were strongly disputed. Diverse Fusaria, including Fusarium mangiferae, are known to be associated with the disease. There are indications that augmented level of endogenous ethylene in response to various abiotic and biotic stresses alters the morphology of reproductive organs. Here, scanning electron microscopy (SEM) of healthy and malformed reproductive organs of mango cv. Baramasi was performed to compare the functional morphology. The SEM study revealed that anthers of hermaphrodite healthy flowers were bilobed with large number of turgid pollen grains whereas malformed flowers showed fused lobed anthers with scanty deformed pollen grains. Furthermore, the stigma of healthy flowers exhibited a broad landing pad as compared to malformed stigma which showed hooked and pointed tip. All these impaired morphology of male and female reproductive organs lead to failure of sexual reproduction. This is the first evidence to show fused lobed anther with impaired pollen grains and hooked stigma with poor stigmatic receptivity are mainly responsible for restricting the pollen germination and pollen tube growth. Here we suggest that abnormal development of anthers and pistils is due to endogenously produced stress ethylene. Further, added load of cyanide, a byproduct of ethylene biosynthesis, may also contribute to the development of necrosis which lead to desiccation of anther and pistil during hypersensitive response of plants.     

Efficacy of live attenuated and inactivated influenza vaccines among children in rural India: A 2-year,randomized, triple-blind,placebo-controlled trial

BackgroundInfluenza is a cause of febrile acute respiratory infection (FARI) in India; however, few influenza vaccine trials have been conducted in India. We assessed absolute and relative efficacy of live attenuated influenza vaccine (LAIV) and inactivated influenza vaccine (IIV) among children aged 2 to 10 years in rural India through a randomized, triple-blind, placebo-controlled trial conducted over 2 years.Methods and findingsIn June 2015, children were randomly allocated to LAIV, IIV, intranasal placebo, or inactivated polio vaccine (IPV) in a 2:2:1:1 ratio. In June 2016, vaccination was repeated per original allocation. Overall, 3,041 children received LAIV (n = 1,015), IIV (n = 1,010), nasal placebo (n = 507), or IPV (n = 509). Mean age of children was 6.5 years with 20% aged 9 to 10 years.Through weekly home visits, nasal and throat swabs were collected from children with FARI and tested for influenza virus by polymerase chain reaction. The primary outcome was laboratory-confirmed influenza-associated FARI; vaccine efficacy (VE) was calculated using modified intention-to-treat (mITT) analysis by Cox proportional hazards model (PH) for each year.In Year 1, VE was 40.0% (95% confidence interval (CI) 25.2 to 51.9) for LAIV and 59.0% (95% CI 47.8 to 67.9) for IIV compared with controls; relative efficacy of LAIV compared with IIV was −46.2% (95% CI −88.9 to −13.1). In Year 2, VE was 51.9% (95% CI 42.0 to 60.1) for LAIV and 49.9% (95% CI 39.2 to 58.7) for IIV; relative efficacy of LAIV compared with IIV was 4.2% (95% CI −19.9 to 23.5). No serious adverse vaccine-attributable events were reported. Study limitations include differing dosage requirements for children between nasal and injectable vaccines (single dose of LAIV versus 2 doses of IIV) in Year 1 and the fact that immunogenicity studies were not conducted.ConclusionsIn this study, we found that LAIV and IIV vaccines were safe and moderately efficacious against influenza virus infection among Indian children.Trial registrationClinical Trials Registry of India CTRI/2015/06/005902.

Anand Krishnan and co-workers study the efficacy and safety of influenza vaccines for children in India.     

Pseudomonas aeruginosa Induced Lung Injury Model

In order to study human acute lung injury and pneumonia, it is important to develop animal models to mimic various pathological features of this disease. Here we have developed a mouse lung injury model by intra-tracheal injection of bacteria Pseudomonas aeruginosa (P. aeruginosa or PA). Using this model, we were able to show lung inflammation at the early phase of injury. In addition, alveolar epithelial barrier leakiness was observed by analyzing bronchoalveolar lavage (BAL); and alveolar cell death was observed by Tunel assay using tissue prepared from injured lungs. At a later phase following injury, we observed cell proliferation required for the repair process. The injury was resolved 7 days from the initiation of P. aeruginosa injection. This model mimics the sequential course of lung inflammation, injury and repair during pneumonia. This clinically relevant animal model is suitable for studying pathology, mechanism of repair, following acute lung injury, and also can be used to test potential therapeutic agents for this disease.     

Isolation and comparative mapping of a human chromosome 20-specific alpha-satellite DNA clone.

We have isolated and characterized a human genomic DNA clone (PZ20, locus D20Z2) that identifies, under high-stringency hybridization conditions, an alphoid DNA subset specific for chromosome 20. The specificity was determined using fluorescence in situ hybridization. Sequence analysis confirmed our previously reported data on the great similarity between the chromosome 20 and chromosome 2 alphoid subsets. Comparative mapping of pZ20 on chimpanzee and gorilla chromosomes, also performed under high-stringency conditions, indicates that the alphoid subset has ancestral sequences on chimpanzee chromosome 11 and gorilla chromosome 19. However, no hybridization was observed to chromosomes 21 in the great apes, the homolog of human chromosome 20.