CYTB: A HOT SPOT FOR PATHOGENIC MUTATIONS IN MITOCHONDRIAL GENOME OF BREAST CANCER AND OVARIAN CANCER PATIENTS

Objective: Out of various cancer types, Breast and ovarian cancers are the most commonly occurring malignancies in women. As per literature, a large number of mutations are reported in various mitochondrial genome encoded subunits of respiratory chain complexes in breast and ovarian cancer patients. However, a very few of them are functionally validated till now. Our study is an attempt to highlight the pathogenic potential of all these reported mutations in breast and ovarian cancer patients.Methods: In order to achieve so, total 109mitochondrial gene mutations of breast cancer and 11 mitochondrial gene mutations of ovarian cancer patients were selected from MITOMAP database as well as various literatures. All these mutations were analyzed using various in silico tools such as MUSCLE, PolyPhen-2, SIFT, Mut Pred, Mu Pro, PANTHER, GOR4 and MUSCLE.Results: As a result of our analysis, 28 out 95 mutations in CytB gene are most pathogenic in the case of breast cancer patients. On the other hand 2 out of 3 mutations of the same gene were predicted to be potentially pathogenic in case of ovarian cancer patients. Mutations in other mitochondrial subunit was also predicted pathogenic but with the low score.Conclusion: Out of different mitochondrial subunits, CytB seems to most important site for mutations in these two groups of patients. Hence, mutations of CytB subunit, which are predicted to be highly pathogenic as per our analysis, should be functionally validated in future.Â

BSMI AND TAQI POLYMORPHISMS IN VITAMIN D RECEPTOR GENE OF TYPE 2 DIABETES MELLITUS PATIENTS FROM NORTH INDIA

ABSTRACTObjective: Polymorphisms in vitamin D receptor (VDR) genes are known to be linked with different metabolic diseases including Type 2 diabetesmellitus (T2DM) also. However, the association of these polymorphisms is not much explored for the Indian population. To determine the prevalenceof BsmI and TaqI polymorphism in VDR gene of T2DM patients from North India.Methods: Blood samples were obtained from 100 well-characterized T2DM patients and 100 healthy controls. Genomic DNA was isolated from bloodsamples and using polymerase chain reaction/restriction fragment length polymorphism based method, the presence of these polymorphisms wasinvestigated in these samples. The data were statistically analyzed using SPSS 21.0 software.Results: For TaqI polymorphism, both the wild type (TT) and heterozygous (TC) genotype showed a significant difference between patients andcontrols (p=0.023 and p<0.001, respectively). Whereas, the frequency of CC genotype was not significantly different among these groups (p=0.506).For BsmI polymorphism also, the frequency of wild type (GG) and heterozygous (GA) genotype was significantly different in patients and controls(p=0.027 and p=0.001), respectively. However, the frequency of AA genotype was not of statistical significance in patients (p=0.071).Conclusions: The mutant alleles of TaqI and BsmI polymorphisms are known to be associated with different metabolic diseases, including diabetestoo. In our study also, there is a significant difference between the frequency of wild type and heterozygous genotype for these polymorphisms. Thissuggests that BsmI and TaqI polymorphisms may be associated with T2DM patients.Keywords: Type 2 diabetes mellitus, Polymorphism, Vitamin D receptor, Patient, Control, Restriction fragment length polymorphism

VITAMIN D RECEPTOR GENE POLYMORPHISMS AND HAPLOTYPE ANALYSIS IN TYPE 2 DIABETES MELLITUS PATIENTS FROM NORTH INDIA

  Objective: Vitamin D receptor (VDR) mediated Vitamin D signaling is important for expression of insulin gene and glucose transporters, which help in glucose uptake by cells. Current evidence suggests that four common polymorphisms (FokI, BsmI, ApaI, TaqI) of VDR gene are associated with Type 2 diabetes mellitus (T2DM) in different populations. However, there is a scarcity of data on VDR polymorphisms from Indian population.Methods: In the current study, total genomic DNA was isolated from 100 well-characterized T2DM patients and 100 healthy controls. We investigated the prevalence of FokI and ApaI polymorphisms in VDR gene of these patients by polymerase chain reaction-restriction fragment length polymorphism-based method. Taking help of our previous published data on TaqI and BsmI polymorphisms in same patients, the haplotype study was also conducted. Statistical analysis of data was performed using SPSS 21.0 software. Haplotype and linkage disequilibrium analysis was performed by Haploview software.Results: Both the wild (TT) and mutant (CC) genotype of FokI polymorphism showed a significant difference between patients and controls (p<0.001 and p<0.001, respectively). The frequency of mutant allele (C) was also significantly higher in T2DM patients than the controls (p<0.001). In case of ApaI, frequency of wild (GG) and mutant (CC) genotype was significantly different in patients and controls (p=0.017 and p=0.034). As per haplotype analysis, the CACT haplotype was predicted to be of significance in patients and consists of mutant alleles of three polymorphisms (FokI, BsmI, ApaI). Conclusion: Our study supports the association of FokI and ApaI polymorphism in T2DM. The haplotype analysis also indicates that the combinations of mutant allele of different VDR polymorphisms are probably responsible for increased susceptibility of these individuals toward T2DM

CURRENT TREATMENTS FOR TYPE 2 DIABETES, THEIR SIDE EFFECTS AND POSSIBLE COMPLEMENTARY TREATMENTS

Diabetes mellitus is a chronic metabolic disorder in the endocrine system and characterized by a varied and complex pathophysiology. World-wide there is a dramatic increase in the number of patients for type 2 diabetes, and hence it is becoming a serious threat to the health of mankind. Commercially a large number of drugs belonging to different classes such as biguanides, sulfonylureas, meglitinides and thiazolidinediones are available to control and treat the type 2 diabetic patients. However, none of these drugs are known to completely cure the diabetic phenotype. On the other hand, a long term usage of these drugs exhibits several side effects and complications to different organs of the body which ultimately lead to cardiovascular problems, liver disease, kidney disease and weight gain too. Like many other drugs, these anti-diabetic drugs are also known to interfere and interact with other non anti-diabetic drugs, if the patient is taking them for a long time. To combat the side effects of these drugs, complementary treatments may be found as a preventive measure and more promising in the management of disease phenotypes in these patients. As per reports available from a large number of studies, these complementary therapies may include physical exercise, dietary supplements and Nutraceuticals.Â

EFFECT OF FUCITHALMIC AND SOFINOX EYE DROPS ON EXPERIMENTAL ALLERGIC CONJUNCTIVITIS IN RATS

Objective: To investigate the therapeutic effect of Fucithalmic 1%, Sofinox 0.5% and 1% eye drops against an IgE-mediated allergic conjunctivitis model in Wistar rats. Methods: IgE-mediated allergic conjunctivitis was induced by ovalbumin antigen challenge. Allergic conjunctivitis induced control rats (Group I) received normal saline (0.9% NaCl; 10 µl/eye) whereas Fucithalmic 1% (Group II), Sofinox 0.5% (Group III) and 1% (Group IV) were administered as 10, 20 and 10 µl/eye respectively to the treatment group animals (n=6) for 15 days. Eye scratching behavior, hypothermia and edema was evaluated after topical antigen challenge. Results: Sofinox 1% eye drops (10 µl/eye) significantly attenuated eye scratching behavior, hyperemia and edema in comparison with allergic conjunctivitis induced control (p < 0.001) and Fucithalmic 1% treated rats (p < 0.05). Eye scratching behavior and edema was also significantly decreased in Sofinox 0.5% eye drops (20 µl/eye) treatment group as compared to allergic conjunctivitis induced control rats (p < 0.05). Conclusion: The present study revealed that the Sofinox eye drop is the potential agent that could offer a novel therapeutic opportunity against IgE-mediated allergic conjunctivitis in Wistar rats

The Preterm Clinical Network (PCN) Database: a web-based systematic method of collecting data on the care of women at risk of preterm birth

Background: Despite much research effort, there is a paucity of conclusive evidence in the field of preterm birth prediction and prevention. The methods of monitoring and prevention strategies offered to women at risk vary considerably around the UK and depend on local maternity care provision. It is becoming increasingly recognised that this experience and knowledge, if captured on a larger scale, could be a utilized as a valuable source of evidence for others. The UK Preterm Clinical Network (UKPCN) was established with the aim of improving care and outcomes for women at risk of preterm birth through the sharing of a wealth of experience and knowledge, as well as the building of clinical and research collaboration. The design and development of a bespoke internet-based database was fundamental to achieving this aim. Method: Following consultation with UKPCN members and agreement on a minimal dataset, the Preterm Clinical Network (PCN) Database was constructed to collect data from women at risk of preterm birth and their children. Information Governance and research ethics committee approval was given for the storage of historical as well as prospectively collected data. Collaborating centres have instant access to their own records, while use of pooled data is governed by the PCN Database Access Committee. Applications are welcomed from UKPCN members and other established research groups. The results of investigations using the data are expected to provide insights into the effectiveness of current surveillance practices and preterm birth interventions on a national and international scale, as well as the generation of ideas for innovation and research. To date, 31 sites are registered as Data Collection Centres, four of which are outside the UK. Conclusion: This paper outlines the aims of the PCN Database along with the development process undertaken from the initial idea to live launch

Approaches in biotechnological applications of natural polymers

Natural polymers, such as gums and mucilage, are biocompatible, cheap, easily available and non-toxic materials of native origin. These polymers are increasingly preferred over synthetic materials for industrial applications due to their intrinsic properties, as well as they are considered alternative sources of raw materials since they present characteristics of sustainability, biodegradability and biosafety. As definition, gums and mucilages are polysaccharides or complex carbohydrates consisting of one or more monosaccharides or their derivatives linked in bewildering variety of linkages and structures. Natural gums are considered polysaccharides naturally occurring in varieties of plant seeds and exudates, tree or shrub exudates, seaweed extracts, fungi, bacteria, and animal sources. Water-soluble gums, also known as hydrocolloids, are considered exudates and are pathological products; therefore, they do not form a part of cell wall. On the other hand, mucilages are part of cell and physiological products. It is important to highlight that gums represent the largest amounts of polymer materials derived from plants. Gums have enormously large and broad applications in both food and non-food industries, being commonly used as thickening, binding, emulsifying, suspending, stabilizing agents and matrices for drug release in pharmaceutical and cosmetic industries. In the food industry, their gelling properties and the ability to mold edible films and coatings are extensively studied. The use of gums depends on the intrinsic properties that they provide, often at costs below those of synthetic polymers. For upgrading the value of gums, they are being processed into various forms, including the most recent nanomaterials, for various biotechnological applications. Thus, the main natural polymers including galactomannans, cellulose, chitin, agar, carrageenan, alginate, cashew gum, pectin and starch, in addition to the current researches about them are reviewed in this article.. }To the Conselho Nacional de Desenvolvimento Cientfíico e Tecnológico (CNPq) for fellowships (LCBBC and MGCC) and the Coordenação de Aperfeiçoamento de Pessoal de Nvíel Superior (CAPES) (PBSA). This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit, the Project RECI/BBB-EBI/0179/2012 (FCOMP-01-0124-FEDER-027462) and COMPETE 2020 (POCI-01-0145-FEDER-006684) (JAT)

Optimasi Portofolio Resiko Menggunakan Model Markowitz MVO Dikaitkan dengan Keterbatasan Manusia dalam Memprediksi Masa Depan dalam Perspektif Al-Qur`an

Risk portfolio on modern finance has become increasingly technical, requiring the use of sophisticated mathematical tools in both research and practice. Since companies cannot insure themselves completely against risk, as human incompetence in predicting the future precisely that written in Al-Quran surah Luqman verse 34, they have to manage it to yield an optimal portfolio. The objective here is to minimize the variance among all portfolios, or alternatively, to maximize expected return among all portfolios that has at least a certain expected return. Furthermore, this study focuses on optimizing risk portfolio so called Markowitz MVO (Mean-Variance Optimization). Some theoretical frameworks for analysis are arithmetic mean, geometric mean, variance, covariance, linear programming, and quadratic programming. Moreover, finding a minimum variance portfolio produces a convex quadratic programming, that is minimizing the objective function ðð¥with constraintsð ð 𥠥 ðandð´ð¥ = ð. The outcome of this research is the solution of optimal risk portofolio in some investments that could be finished smoothly using MATLAB R2007b software together with its graphic analysis

Search for supersymmetry in events with one lepton and multiple jets in proton-proton collisions at root s=13 TeV

Peer reviewe

Measurement of the top quark forward-backward production asymmetry and the anomalous chromoelectric and chromomagnetic moments in pp collisions at √s = 13 TeV

Abstract The parton-level top quark (t) forward-backward asymmetry and the anomalous chromoelectric (d̂ t) and chromomagnetic (μ̂ t) moments have been measured using LHC pp collisions at a center-of-mass energy of 13 TeV, collected in the CMS detector in a data sample corresponding to an integrated luminosity of 35.9 fb−1. The linearized variable AFB(1) is used to approximate the asymmetry. Candidate t t ¯ events decaying to a muon or electron and jets in final states with low and high Lorentz boosts are selected and reconstructed using a fit of the kinematic distributions of the decay products to those expected for t t ¯ final states. The values found for the parameters are AFB(1)=0.048−0.087+0.095(stat)−0.029+0.020(syst),μ̂t=−0.024−0.009+0.013(stat)−0.011+0.016(syst), and a limit is placed on the magnitude of | d̂ t| < 0.03 at 95% confidence level. [Figure not available: see fulltext.