HIV-1 reverse transcriptase mutations that confer decreased in vitro susceptibility to anti-RT DNA aptamer RT1t49 confer cross resistance to other anti-RT aptamers but not to standard RT inhibitors

RNA and DNA aptamers specific for HIV-1 reverse transcriptase (RT) can inhibit reverse transcription in vitro. RNA aptamers have been shown to potently block HIV-1 replication in culture. We previously reported mutants of HIV-1 RT with substitutions N255D or N265D that display resistance to the DNA aptamer RT1t49. Variant viruses bearing these mutations singly or in combination were compromised for replication. In order to address the wider applicability of such aptamers, HIV-1 RT variants containing the N255D, N265D or both (Dbl) were tested for the extent of their cross-resistance to other DNA/RNA aptamers as well as to other RT inhibitors. Both N265D and Dbl RTs were resistant to most aptamers tested. N255D mutant displayed mild resistance to two of the DNA aptamers, little change in sensitivity to three and hypersensitivity to one. Although all mutants displayed wild type-like ribonuclease H activity, their activity was compromised under conditions that prevent re-binding. This suggests that the processivity defect caused by these mutations can also affect RNase H function thus contributing further to the replication defect in mutant viruses. These results indicate that mutants conferring resistance to anti-RT aptamers significantly affect many HIV-1 RT enzymatic activities, which could contribute to preventing the development of resistance in vivo. If such mutations were to arise in vivo, our results suggest that variant viruses should remain susceptible to many existing anti-RT inhibitors. This result was tempered by the observation that NRTI-resistance mutations such as K65R can confer resistance to some anti-RT aptamers

Identification of critical residues in loop E in the 5-HT(3AS)R binding site

BACKGROUND: The serotonin type 3 receptor (5-HT(3)R) is a member of a superfamily of ligand gated ion channels. All members of this family share a large degree of sequence homology and presumably significant structural similarity. A large number of studies have explored the structure-function relationships of members of this family, particularly the nicotinic and GABA receptors. This information can be utilized to gain additional insights into specific structural and functional features of other receptors in this family. RESULTS: Thirteen amino acids in the mouse 5-HT(3AS)R that correspond to the putative E binding loop of the nicotinic α7 receptor were chosen for mutagenesis. Due to the presence of a highly conserved glycine in this region, it has been suggested that this binding loop is comprised of a hairpin turn and may form a portion of the ligand-binding site in this ion channel family. Mutation of the conserved glycine (G147) to alanine eliminated binding of the 5-HT(3)R antagonist [(3)H]granisetron. Three tyrosine residues (Y140, Y142 and Y152) also significantly altered the binding of 5-HT(3)R ligands. Mutations in neighboring residues had little or no effect on binding of these ligands to the 5-HT(3AS)R. CONCLUSION: Our data supports a role for the putative E-loop region of the 5-HT(3)R in the binding of 5-HT, mCPBG, d-tc and lerisetron. 5-HT and mCPBG interact with Y142, d-tc with Y140 and lerisetron with both Y142 and Y152. Our data also provides support for the hypothesis that this region of the receptor is present in a loop structure

The observational, cross sectional study to assess quality of life on patient suffering from chronic obstructive pulmonary disease in tertiary care hospital

Background: Chronic obstructive pulmonary disease (COPD) patients often present considerable individual medical burden in their symptoms, limitations, and well-being that complicate medical treatment. Quality of life (QOL) is an important aspect for measuring the impact of chronic diseases. HRQOL measurement facilitates the evaluation of efficacy of medical interventions and also the detection of groups at risk of psychological or behavioural problems.Methods: COPD patient attending the OPD/IPD are screened as per inclusion and exclusion criteria. After obtaining a written informed consent of eligible patient, they were enrolled in the study. QOL of patient is assessed based on a set of questionnaire i.e. COPD Assessment Test™ (CAT). The questionnaire was translated to Hindi and Marathi. Socio demographic variable like age, sex, education occupation and income are also collected. All 8 questions related to health-improvement and management of COPD. CAT scores were given to each question according to the level of impact.Results: In the total score of CAT we observed that there were 2.04% patients with very good QOL, 25.51% with good QOL, 61.22% with moderate QOL and 11.22% with poor QOL.Conclusions: We conclude that the quality of life is moderate in larger number of patient’s population. The most affected domain was the patient’s energy level. The patients enrolled had COPD from long period of time which might have affected their answer because they have been habitual with the difficulties arising from COPD

Potential impact and controversy of stem cells in public health

Stem cells are versatile in the bodies which are able to both reproduce themselves and to produce more specialized cells. As such, they are of great potential values in repairing and regenerating damaged cells and tissues. Many different kinds of stem cells have been discovered. The most common are embryonic, foetal and adult stem cells. Stem cell research has the potential to provide an increased understanding of development and differentiation, as well as leading to treatments and cures for many diseases. They are important to the future of medicine and public health because with adequate research, stem cells have the potential to treat degenerative conditions through transplanting human stem cells into patients. With sufficient development of stem cell medicine, chronic diseases such as diabetes, heart disease, and Parkinson’s disease will be effectively managed. Embryonic stem cell (ESC) research has been a source of ethical, legal, and social controversy which has slowed the pace of stem cell science and shaped many aspects of its subsequent development

Unknown System Identification using LMS Algorithm

An adaptive filter is a digital filter that self adjusts its transfer function according to an optimizing algorithm which is most frequently Least Mean Square (LMS) algorithm. Due to the complexity of adaptive filtering most digital filters are FIR filter. There are numerous applications of adaptive filters like noise cancellations, echo cancellation, system modelling and identification, inverse system modelling, adaptive beam-forming etc. In this research article, adaptive LMS algorithm has been used for unknown system identification. The system identification is a category of adaptive filtering which find its numerous applications in diverse field like communication, image processing, speech processing etc

Off-Grid Single Phase Micro-Inverter System

In most of the households appliances, AC electricity are mostly used. This electricity are easily available but renewable energy is increasing now a days as there is shortage of traditional fissile fuel and it also hazardous to the environment. Such form of electricity can be obtained by converting the DC electricity generated by the solar panels using power electronics devices. There are so many types of inverter configuration are available which can be used for such purpose. Dealing with hundreds of watts of energy, micro-Photovoltaic (PV) type inverters can convert solar energy of each PV panel to the utility individually, with significant improvement of overall system reliability and also have a several advantages over the other topology like tuning the output of each panel, less sensitive to overheating problems etc. This paper presents a case study of a single-phase micro-PV inverter. Circuit analysis and its parameters calculation are carried out in details and demonstrated through simulation based on MATLAB/Simulink. The result proves the analysis of the circuit and provides theoretical validation for further work in research. DOI: 10.17762/ijritcc2321-8169.15085