Comparison of Modules of Wild Type and Mutant Huntingtin and TP53 Protein Interaction Networks: Implications in Biological Processes and Functions

Disease-causing mutations usually change the interacting partners of mutant proteins. In this article, we propose that the biological consequences of mutation are directly related to the alteration of corresponding protein protein interaction networks (PPIN). Mutation of Huntingtin (HTT) which causes Huntington's disease (HD) and mutations to TP53 which is associated with different cancers are studied as two example cases. We construct the PPIN of wild type and mutant proteins separately and identify the structural modules of each of the networks. The functional role of these modules are then assessed by Gene Ontology (GO) enrichment analysis for biological processes (BPs). We find that a large number of significantly enriched (p<0.0001) GO terms in mutant PPIN were absent in the wild type PPIN indicating the gain of BPs due to mutation. Similarly some of the GO terms enriched in wild type PPIN cease to exist in the modules of mutant PPIN, representing the loss. GO terms common in modules of mutant and wild type networks indicate both loss and gain of BPs. We further assign relevant biological function(s) to each module by classifying the enriched GO terms associated with it. It turns out that most of these biological functions in HTT networks are already known to be altered in HD and those of TP53 networks are altered in cancers. We argue that gain of BPs, and the corresponding biological functions, are due to new interacting partners acquired by mutant proteins. The methodology we adopt here could be applied to genetic diseases where mutations alter the ability of the protein to interact with other proteins.Comment: 35 pages, 10 eps figures, (Supplementary material and Datasets are available on request

Transporte autorregulador de fármacos: un sistema inteligente de administración de fármacos

Introduction: Main objective of any pharmaceutical scientist is to develop drug delivery system that is safe, effective, stable, having good patient compliance and fulfill the requirements of customers. Lead to a great interest of research to develop the drug delivery system that will enable to supply drug «on-demand » basis. These «stimuli-responsive and intelligent» systems have been designed to deliver the drug on various times or at various sites in the body, according to a stimulus that is either endogenous or externally applied. Objectives: This paper aim to review various researches in the field of self regulatory drug delivery systems in tabular form so one can utilize these finding for further development of in intelligent drug delivery systems. Method: Various physicochemical principles and chemical schemes have been applied by researchers to get release pattern of drug as per requirement of body. Such devices can be used for intelligent drug delivery needed for the treatment of many diseases like diabetes. Results & Discussion: This type of intelligent system firstly sense the signals caused by diseaseà judge the magnitude of signalsà and then release the drug in direct response. Conclusion: In this article we have discuss various innovations in the field of self regulatory drug delivery Systems and suggest that here is a lot of research scope in this field.Introducción: El objetivo principal de cualquier científico farmacéutico es desarrollar un sistema de administración de fármacos que sea seguro, efectivo, estable, que cumpla con los requisitos del paciente y cumpla con los requisitos de los clientes. Llevar a un gran interés de investigación para desarrollar el sistema de entrega de medicamentos que permitirá suministrar medicamentos «a demanda». Estos sistemas «sensibles a estímulos e inteligentes» han sido diseñados para administrar el farmaco en varios momentos o en varios sitios en el cuerpo, de acuerdo con un estímulo endógeno o aplicado externamente. Objetivos: Este artículo tiene como objetivo revisar diversas investigaciones en el campo de los sistemas autorreguladores de administración de fármacos en forma tabular para que uno pueda utilizar estos hallazgos para un mayor desarrollo de sistemas inteligentes de administración de fármacos. Método: Los investigadores han aplicado varios principios fisicoquímicos y esquemas químicos para obtener el patrón de liberación del fármaco según las necesidades del cuerpo. Dichos dispositivos se pueden usar para la administración inteligente de medicamentos necesarios para el tratamiento de muchas enfermedades, como la diabetes. Resultados y discusión: Este tipo de sistema inteligente primero detecta las señales causadas por la enfermedad, juzga la magnitud de las señales y luego libera la droga en respuesta directa. Conclusión: En este artículo, hemos discutido varias innovaciones en el campo de los sistemas autorreguladores de administración de fármacos y sugerimos que aquí hay mucho campo de investigación en este campo

Correlation of spirometry and six minute walk test in patients with chronic obstructive pulmonary disease from Sundargarh, Odisha, India

Background: Six‑Minute Walk Test (6MWT) is a simple, objective, reproducible test which correlated well with different spirometric indices, and thus able to predict severity of Chronic Obstructive Pulmonary Disease (COPD) and can replace spirometry in resource poor set‑up. Here, author evaluated the correlation of 6 minute walk distance (6MWD) with spirometric indices in COPD patients and the potential of 6MWT as an alternative to the assessment of severity of COPD.Methods: This cross-sectional observational study included a total of 80 COPD patients, diagnosed by GOLD criteria (Post bronchodilator FEV1/ FVC ratio <0.7). Modified Medical Research Council (mMRC) grading was used (age, weight, height, body mass index- BMI and breathlessness) and all the patients underwent spirometric measurement of FEV1, FVC and FEV1/ FVC ratio and tests were repeated after bronchodilation using 200-400 μg of salbutamol. 6MWT was performed following American Thoracic Society (ATS) protocol of 6MWT and distance was measured in meters.Results: Author found significant negative correlation of 6MWT with age (r=-0.384, p=0.00) and mMRC grading of dyspnea (r=-0.559, p=0.00) and significant positive correlation with height (r=0.267, p=0.019) and weight (r=0.293, p=0.008). Significant positive correlation of 6MWD was noted with post bronchodilator FEV1(r=0.608, p=0.00), FEV1% (r=0.429, p=0.00), FVC (r=0.514 p=0.00), FVC% (r=0.313 p=0.005), FEV1/FVC % (r=0.336, p=0.001). Positive correlation was also observed between 6MWT and BMI but statistically insignificant (r=0.177, p=0.116). There was significant negative correlation between 6MWT and GOLD staging (r=-0.536, p=0.00).Conclusions: This finding concludes that 6MWT can be used for the assessment of severity of disease in COPD patients in places where spirometry is not available

BACTERIOLOGICAL PROFILE AND ANTIBIOTIC SENSITIVITY PATTERN OF HOSPITALACQUIRED SEPTICEMIA IN A TERTIARY CARE HOSPITAL IN NORTH EAST INDIA

Objective: The objective of this study was to determine the bacterial agents responsible for hospital acquired septicaemia and to determine the antibiotic sensitivity profile of the bacterial isolates.Methods:  Three hundred fifty hospitalized clinically suspect septicaemia cases were included in this cross sectional observational study during a period of one year. Blood samples were collected with aseptic precautions for culture following universal precautions. Anti-microbial susceptibility test of the bacterial isolates was performed according to Clinical and Laboratory Standards Institute (CLSI, USA) guidelines.    Results: Over two-thirds of cultures showed gram positive organism. The most frequently identified Gram positive bacteria were coagulase negative staphylococci and Staphylococcus aureus. Among gram negative bacteria Escherichia coli, Klebsiella spp and Salmonella typhi were isolated. In our study, coagulase negative staphylococci showed maximum resistance to penicillin and erythromycin. Enterobactereciae had maximum sensitivity to carbapenems, tigecycline and aminoglycosides.Conclusion: Gram positive pathogens predominated in the blood stream infections. Résistance to fluoroquinolones, especially in Gram negative bacteria was significantly high. Therefore, rapid microbiological diagnosis and the determinants of antimicrobial susceptibility become relevant for early initiation of antimicrobial therapy.    Â

Clinical profile and lipid abnormalities in subclinical and overt primary hypothyroidism

Background: Overt and subclinical hypothyroidism, affects metabolism of lipids particularly that of cholesterol, low density lipoprotein and triglyceride. Hypercholesterolemia predisposes to atherosclerosis and thereby increases cardiovascular risks.Methods: Hundred patients of primary  hypothyroidism of age more than 15 yrs were included. Five milliliters of venous blood was drawn in fasting state and serum obtained; thyroid function test (TFT) and fasting lipid profile were performed. Based on the TFT, patients were categorized as sub clinical or overt hypothyroidism. Clinical data, thyroid and lipid profiles obtained were analyzed and compared using statistical methods.Results: Seventy patients were females and thirty were males in the ratio of 2.3:1. Most common age group was 51-60years followed by 41-50years. Most common symptom was generalised weakness followed by weight gain, cold intolerance, constipation, hair loss, paraesthesia’s. Most common signs were myxoedema, delayed ankle reflex relaxation, dry and  coarse skin, bradycardia, non-pitting peripheral edema, madarosis, pallor, goiter. Patients with Overt hypothyroidism had significantly higher serum levels of total cholesterol(249.1±31.7 mg/dl), Triglycerides (191.5±68.5 mg/dl) and LDL cholesterol(167.7±31 mg/dl) than the Subclinical hypothyroidism with total cholesterol(202±19.8),triglycerides(155.6±35) and LDL cholesterol(129±21.1) but HDL cholesterol  level remains normal in both overt  (44.0±4.7) and subclinical  (43.1±4.4)hypothyroidism respectively.Conclusions: Patients with Overt hypothyroidism had significantly higher levels of Total cholesterol, Triglycerides (TG) and LDL cholesterol than the Subclinical hypothyroidism but HDL cholesterol level remains normal in both. So, concomitant estimation of lipid profile in hypothyroidism patients is needed for early intervention and prevention of cardiovascular morbidity and mortality

FAST DISSOLVING ORAL FILMS: A TABULAR UPDATE

Fast-dissolving oral films have emerged as alternative dosage forms for the patients who experience difficulties in swallowing traditional oral solid dosage forms such as tablets, capsules, and syrups etc.   These dosage forms disintegrate or dissolve very quickly within seconds when placed in the mouth cavity without need of water or chewing. Due to fast dissolution it provide faster onset of action, bypassing the first pass metabolism, reducing gastric degradation and metabolism of drugs and thus enhance their oral bioavailability. These properties of oral films with patient convenience and compliance made popular and accepted dosage form for pediatric and geriatric as well as adult population. These formulations are suitable for cough, cold, sore throat, allergenic conditions, nausea, pain, hypertension and CNS disorders, epilepsy and many more diseases. The present review provides up to date review in fast dissolving oral films in tabular form so researches can easily track various technologies/research in design and development of oral fast dissolving film. Keywords: Mouth dissolving films, Oral dispersible film, Oral dissolving film, Oral disintegrating film

Genetic diversity and population structure of Indian golden silkmoth (Antheraea assama)

Background The Indian golden saturniid silkmoth (Antheraea assama), popularly known as muga silkmoth, is a semi-domesticated silk producing insect confined to a narrow habitat range of the northeastern region of India. Owing to the prevailing socio-political problems, the muga silkworm habitats in the northeastern region have not been accessible hampering the phylogeography studies of this rare silkmoth. Recently, we have been successful in our attempt to collect muga cocoon samples, although to a limited extent, from their natural habitats. Out of 87 microsatellite markers developed previously for A. assama, 13 informative markers were employed to genotype 97 individuals from six populations and analyzed their population structure and genetic variation. Methodology/Principal Findings We observed highly significant genetic diversity in one of the populations (WWS-1, a population derived from West Garo Hills region of Meghalaya state). Further analysis with and without WWS-1 population revealed that dramatic genetic differentiation (global FST = 0.301) was due to high genetic diversity contributed by WWS-1 population. Analysis of the remaining five populations (excluding WWS-1) showed a marked reduction in the number of alleles at all the employed loci. Structure analysis showed the presence of only two clusters: one formed by WWS-1 population and the other included the remaining five populations, inferring that there is no significant genetic diversity within and between these five populations, and suggesting that these five populations are probably derived from a single population. Patterns of recent population bottlenecks were not evident in any of the six populations studied. Conclusions/Significance A. assama inhabiting the WWS-1 region revealed very high genetic diversity, and was genetically divergent from the five populations studied. The efforts should be continued to identify and study such populations from this region as well as other muga silkworm habitats. The information generated will be very useful in conservation of dwindling muga culture in Northeast India

Evaluating air quality and criteria pollutants prediction disparities by data mining along a stretch of urban-rural agglomeration includes coal-mine belts and thermal power plants

Air pollution has become a threat to human life around the world since researchers have demonstrated several effects of air pollution to the environment, climate, and society. The proposed research was organized in terms of National Air Quality Index (NAQI) and air pollutants prediction using data mining algorithms for particular timeframe dataset (01 January 2019, to 01 June 2021) in the industrial eastern coastal state of India. Over half of the study period, concentrations of PM2.5, PM10 and CO were several times higher than the NAQI standard limit. NAQI, in terms of consistency and frequency analysis, revealed that moderate level (ranges 101–200) has the maximum frequency of occurrence (26–158 days), and consistency was 36%–73% throughout the study period. The satisfactory level NAQI (ranges 51–100) frequency occurrence was 4–43 days with a consistency of 13%–67%. Poor to very poor level of air quality was found 13–50 days of the year, with a consistency of 9%–25%. Random Forest (RF), Support Vector Machine (SVM), Bagged Multivariate Adaptive Regression Splines (MARS) and Bayesian Regularized Neural Networks (BRNN) are the data mining algorithms, that showed higher efficiency for the prediction of PM2.5, PM10, NO2 and SO2 except for CO and O3 at Talcher and CO at Brajrajnagar. The Root Mean Square Error (RMSE) between observed and predicted values of PM2.5 (ranges 12.40–17.90) and correlation coefficient (r) (ranges 0.83–0.92) for training and testing data indicate about slightly better prediction of PM2.5 by RF, SVM, bagged MARS, and BRNN models at Talcher in comparison to PM2.5 RMSE (ranges 13.06–21.66) and r (ranges 0.64–0.91) at Brajrajnagar. However, PM10 (RMSE: 25.80–43.41; r: 0.57–0.90), NO2 (RMSE: 3.00–4.95; r: 0.42–0.88) and SO2 (RMSE: 2.78–5.46; r: 0.31–0.88) at Brajrajnagar are better than PM10 (RMSE: 35.40–55.33; r: 0.68–0.91), NO2 (RMSE: 4.99–9.11; r: 0.48–0.92), and SO2 (RMSE: 4.91–9.47; r: 0.20–0.93) between observed and predicted values of training and testing data at Talcher using RF, SVM, bagged MARS and BRNN models, respectively. Taylor plots demonstrated that these algorithms showed promising accuracy for predicting air quality. The findings will help scientific community and policymakers to understand the distribution of air pollutants to strategize reduction in air pollution and enhance air quality in the study region