Dharam Pal Singh Anhal
Ontology highlight
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PROVIDER: S-EPMC524610 | biostudies-literature | 2004 Oct
REPOSITORIES: biostudies-literature
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Project description:The Tol-peptidoglycan-associated lipoprotein (PAL) system of Escherichia coli is a multiprotein complex of the envelope involved in maintaining outer membrane integrity. PAL and the periplasmic protein TolB, two components of this complex, are interacting with each other, and they have also been reported to interact with OmpA and the major lipoprotein, two proteins interacting with the peptidoglycan. All these interactions suggest a role of the Tol-PAL system in anchoring the outer membrane to the peptidoglycan. Therefore, we were interested in better understanding the interaction between PAL and the peptidoglycan. We designed an in vitro interaction assay based on the property of purified peptidoglycan to be pelleted by ultracentrifugation. Using this assay, we showed that a purified PAL protein interacted in vitro with pure peptidoglycan. A peptide competition experiment further demonstrated that the region from residues 89 to 130 of PAL was sufficient to bind the peptidoglycan. Moreover, the fact that this same region of PAL was also binding to TolB suggested that these two interactions were exclusive. Indeed, the TolB-PAL complex appeared not to be associated with the peptidoglycan. This led us to the conclusion that PAL may exist in two forms in the cell envelope, one bound to TolB and the other bound to the peptidoglycan.
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Project description:Palliative patients require several types of care to improve their quality of life as much as possible, and valid and reliable assessment instruments are essential. The objective of this study is the Spanish validation of the Functional Assessment Chronic Illness Therapy-Palliative Care (FACIT-PAL) and its abbreviated version, FACIT-PAL-14, in palliative care patients. FACIT-PAL and FACIT-PAL-14 were translated into Spanish and administered to 131 terminal oncology patients in home palliative care units, hospital palliative care units, health center teams, and social health centers. The European Organization for Research and Treatment of Cancer questionnaire, EORTC-QLQ-C15-PAL version, was used to evaluate the criterion validity. The EORTC-QLQ-C15-PAL was employed as a "gold standard", and it obtained significant results with FACIT scales. FACIT-PAL-14, FACIT-PAL, and its subscales reported high internal consistency, from 0.640 to 0.816. The exploratory factor analysis for FACIT-PAL-14 found a structure in three factors that explained the 70.10% variance, and the FACIT-PAL scale found a structure of five factors. Physical wellbeing from FACIT-PAL highly correlated to the EORTC-QLQ-C15-PAL (r = 0.700), but social and family wellbeing was correlated to a lesser extent (r = -0.323). FACIT-PAL and the TOI (Toi Outcome Index) were also highly correlated with the EORTC-QLQ-C15-PAL, with values of r = -0.708 and r = -0.709, respectively. The Spanish versions of FACIT-PAL and FACIT-PAL-14 were demonstrated to be valid and reliable scales in palliative care patients.
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Project description:Bacteriolytic enzymes are promising antibacterial agents, but they can cause a typical immune response in vivo. In this study, we used a targeted modification method for two antibacterial endolysins, Pal and Cpl-1. We identified the key immunogenic amino acids, and designed and tested new, bacteriolytic variants with altered immunogenicity. One new variant of Pal (257-259 MKS → TFG) demonstrated decreased immunogenicity while a similar mutant (257-259 MKS → TFK) demonstrated increased immunogenicity. A third variant (280-282 DKP → GGA) demonstrated significantly increased antibacterial activity and it was not cross-neutralized by antibodies induced by the wild-type enzyme. We propose this variant as a new engineered endolysin with increased antibacterial activity that is capable of escaping cross-neutralization by antibodies induced by wild-type Pal. We show that efficient antibacterial enzymes that avoid cross-neutralization by IgG can be developed by epitope scanning, in silico design, and substitutions of identified key amino acids with a high rate of success. Importantly, this universal approach can be applied to many proteins beyond endolysins and has the potential for design of numerous biological drugs.
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Project description:In previous studies, beta-k distribution and distribution functions strongly related to that, have played important roles in representing extreme events. Among these distributions, the Beta-Singh-Maddala turned out to be adequate for modelling hydrological extreme events. Starting from this distribution, the aim of the paper is to express the model as a function of indexes of hydrological interest and simultaneously investigate on their dependence with a set of explanatory variables in such a way to explore on possible determinants of extreme hydrologic events. Finally, an application to a real hydrologic dataset is considered in order to show the potentiality of the proposed model in describing data and in understanding effects of covariates on frequently adopted hydrological indicators.
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