Small Molecular Antimicrobial Ligands of YspD are Potential Therapeutic Agents Against Yersinia enterocolitica Infection.

YspD is a hydrophilic translocator forming the platform for assemblage of functional translocon. Exposure to the extra-cellular milieu makes YspD a potential therapeutic target. DoGSiteScorer predicted best druggable pocket (P0) within YspD, encompassing predominantly the C-terminal helical bundles and the long helices-9 & 5. COACH metaserver also identified ligand binding residues within the aforementioned druggable pocket mapping to helix-9. Amino acids of helix-9 are involved in oligomerization of YspD. Interaction of helix-9 and parts of C-terminal of YspD with hydrophobic translocator protein (YspB), is essential for translocation of bacterial effectors to initiate an infection. Helices-9 & 5 form an intramolecular coiled-coil structure, required for protein-protein interaction. Targeting intramolecular coiled-coil and parts of C-terminal would be important for functional inactivation of YspD. Solvent exposed surface in YspD, particularly in P0, enhances its accessibility to ligands. Nine small molecular inhibitors of TIIISS were identified and retrieved from ZINC15 database (drug-library) as putative drug candidates. Molecular docking of potential ligands with P0 was done using SwissDock server and Achilles Blind Docking server. Considering the "Significance" threshold of binding score and region of interaction, Salicylidene Acyl Hydrazide derivatives (INP0400) and Phenoxyacetamide derivative (MBX1641) were found to bind effectively with YspD. These potential ligands interact with functional domains of YspD including parts of C-terminal and the intramolecular coiled-coil, which may affect the oligomerization of YspD and disrupt the interaction of YspD with YspB, inhibiting formation of functional translocon. The identified small molecular antimicrobial ligands of YspD could be tested in vivo to attenuate Y. enterocolitica infection by deregulation of Ysa-Ysp TIIISS. Supplementary Information: The online version contains supplementary material available at 10.1007/s40011-022-01443-2.

The knowledge of pressure ulcer among nursing students and related factors

Pressure ulcer has been recognized as one of the major causes of morbidity, mortality and a burden to healthcare. Our aim is to compare the level of knowledge regarding pressure ulcer prevention among final year nursing students in one of the Health Campus in Kelantan. This is a cross-sectional study aimed to determine and compare the knowledge of pressure ulcer prevention among the nursing students. The total sample for this study is 108 students. The sampling methods used are purposive sampling methods, i.e. the sample was chosen based on the potentially knowledge about the phenomena studied. Self-administered questionnaire is used to measure the characteristic and knowledge level of sample towards pressure ulcer prevention. Data including descriptive statistic and statistical tests was analyzed using the SPSS version 22.0. Finding of this study was significant with p < 0.001 (significant at p < 0.05). This indicates the significant differences of pressure ulcer knowledge between both programmes. The degree students have higher knowledge than the diploma students. Therefore, it is evident from this study that higher the level of education, the higher is the knowledge regarding pressure ulcer

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PcrG protects the two long helical oligomerization domains of PcrV, by an interaction mediated by the intramolecular coiled-coil region of PcrG.

BACKGROUND: PcrV is a hydrophilic translocator of type three secretion system (TTSS) and a structural component of the functional translocon. C-terminal helix of PcrV is essential for its oligomerization at the needle tip. Conformational changes within PcrV regulate the effector translocation. PcrG is a cytoplasmic regulator of TTSS and forms a high affinity complex with PcrV. C-terminal residues of PcrG control the effector secretion. RESULT: Both PcrV and PcrG-PcrV complex exhibit elongated conformation like their close homologs LcrV and LcrG-LcrV complex. The homology model of PcrV depicts a dumbbell shaped structure with N and C-terminal globular domains. The grip of the dumbbell is formed by two long helices (helix-7 and 12), which show high level of conservation both structurally and evolutionary. PcrG specifically protects a region of PcrV extending from helix-12 to helix-7, and encompassing the C-terminal globular domain. This fragment ∆PcrV(128-294) interacts with PcrG with high affinity, comparable to the wild type interaction. Deletion of N-terminal globular domain leads to the oligomerization of PcrV, but PcrG restores the monomeric state of PcrV by forming a heterodimeric complex. The N-terminal globular domain (∆PcrV(1-127)) does not interact with PcrG but maintains its monomeric state. Interaction affinities of various domains of PcrV with PcrG illustrates that helix-12 is the key mediator of PcrG-PcrV interaction, supported by helix-7. Bioinformatic analysis and study with our deletion mutant ∆PcrG(13-72) revealed that the first predicted intramolecular coiled-coil domain of PcrG contains the PcrV interaction site. However, 12 N-terminal amino acids of PcrG play an indirect role in PcrG-PcrV interaction, as their deletion causes 40-fold reduction in binding affinity and changes the kinetic parameters of interaction. ∆PcrG(13-72) fits within the groove formed between the two globular domains of PcrV, through hydrophobic interaction. CONCLUSION: PcrG interacts with PcrV through its intramolecular coiled-coil region and masks the domains responsible for oligomerization of PcrV at the needle tip. Also, PcrG could restore the monomeric state of oligomeric PcrV. Therefore, PcrG prevents the premature oligomerization of PcrV and maintains its functional state within the bacterial cytoplasm, which is a pre-requisite for formation of the functional translocon.

Incidence of anemia and effect of nutritional supplementation on women in rural and tribal populations of eastern and northeastern India.

Screening of women of child bearing age among the tribal and rural population of different north eastern and eastern states of India was performed. More than 50% of women in some areas were found to have anemia. As part of the study nutritional supplementation was given to a proportion of the anemic population, comparing the effects of Spirulina, a compound containing vitamins and micronutrients and an iron-folic acid-B12 supplement. Follow-up of the cases was done over a period of one year and the impact of supplementation and a comparison of the two compounds made.

Anemia and hemoglobinopathies in tribal population of Eastern and North-eastern India.

It is estimated that out of approximately 31.4 million people living in North-eastern India, about 8.1 million are tribal people of the hills and plains. Among four of the seven north-eastern states, tribal people are in majority. Arunachal Pradesh is made of approximately 24 major tribal groups, which constitute about 70% of the total population, Tripura 29% and in Assam constitutes 11%. A total of 1726 cases were randomly selected in this study, out of which 1263 cases were from North-east India, namely from Arunachal Pradesh, Assam, Tripura and the rest were from West Bengal. Hematological parameters were estimated and agarose gel electrophoresis for identification of the Hb variants was performed. DNA was isolated, amplified and analysed by PCR-ARMS technology. The incidence of anemia among the tribal people of Assam was 59.82%, in Arunachal Pradesh 53.77% and Tripura 57.45%. The presence of hemoglobinopathies and thalassemia account for anemia in a sizeable population of the north-eastern states in certain tribes and urgent health resources are needed to deal with this. HbE appears to be the commonest hemoglobin among the different tribes of north-east.