Next generation sequencing reveals the antibiotic resistant variants in the genome of Pseudomonas aeruginosa

Rapid progress in next generation sequencing and allied computational tools have aided in identification of single nucleotide variants in genomes of several organisms. In the present study, we have investigated single nucleotide polymorphism (SNP) in ten multi-antibiotic resistant Pseudomonas aeruginosa clinical isolates. All the draft genomes were submitted to Rapid Annotations using Subsystems Technology (RAST) web server and the predicted protein sequences were used for comparison. Non-synonymous single nucleotide polymorphism (nsSNP) found in the clinical isolates compared to the reference genome (PAO1), and the comparison of nsSNPs between antibiotic resistant and susceptible clinical isolates revealed insights into the genome variation. These nsSNPs identified in the multi-drug resistant clinical isolates were found to be altering a single amino acid in several antibiotic resistant genes. We found mutations in genes encoding efflux pump systems, cell wall, DNA replication and genes involved in repair mechanism. In addition, nucleotide deletions in the genome and mutations leading to generation of stop codons were also observed in the antibiotic resistant clinical isolates. Next generation sequencing is a powerful tool to compare the whole genomes and analyse the single base pair variations found within the antibiotic resistant genes. We identified specific mutations within antibiotic resistant genes compared to the susceptible strain of the same bacterial species and these findings may provide insights to understand the role of single nucleotide variants in antibiotic resistance

THE EVOLVING COMPETITIVE DYNAMICS IN THE RETAIL BANKING SECTOR IN INDIA: A CASE STUDY OF KARNATAKA BANK

The banking industry in India is going through a unique competitive situation: on the one hand, the proliferation of new banks has increased competition multi-fold; on the other hand, given the rigid regulatory environment, banks have very little liberty to innovate products. The entry of multinational banking giants with superior service operations has further amplified the competition for customers. This paper examines the business performance of Karnataka bank during the period between 2006 and 2014 in order to bring home some of these challenges. Based on feedback from the branch managers, savings and current accounts - two classic banking products – suffered the most in the onslaught. Practicing managers as well as customers that we interviewed held that banking services in terms of customer experience ought to be improved and that various value added services could be introduced. Customers also expected reduced penalty for minimum balance and enhanced insurance cover for their accounts

Effect of pullulanase debranching and storage temperatures on structural characteristics and digestibility of sweet potato starch

AbstractThe effect of autoclaving (120°C/30min), debranching (2% pullulanase/1h) and storage at 4°C (DS4) or 32°C (DS32) or 60°C (DS60) for 24h on starch fractions, functional, pasting, thermal and structural properties of sweet potato starch was investigated. Results showed that DS4 sample displayed the lower functional properties than other modified starches. Debranching showed a significant increase in the apparent amylose content of native starch from 18.56% to 25%. A higher yield of RS (28.76%) was observed in debranched starch stored at 4°C (DS4) due to the higher degree of retrogradation. All debranched starches showed a substantial decrease in pasting profile and higher gelatinization temperatures than in native starch. B+V X-ray diffraction pattern was observed in debranched starches with increased crystallinity value. The scanning electron micrographs of debranched starches showed rough plate-like surfaces with irregularly shaped structures were observed due to debranching and retrogradation during storage. The study concludes that a combination of autoclaving, debranching and subsequent storage at 4°C is best technique to produce a higher amount of resistant starch in the sweet potato starch

Search-ability A Domain Quality Factor for Web Software Applications

As organizations become aware of the strategic importance of e-commerce they will also become aware of the need of quality Web sites. In early years the World Wide Web was originally designed to present information to Web surfers using simple sites that consists of hyper linked text. But, Modern Web applications run large-scale software applications for e-commerce, information distribution, entertainment, and numerous other activities. The factors that constitute software quality in traditional data processing are well defined. However, it is necessary to have a full understanding about the quality in the context of World Wide Web. This paper identifies a new quality factor, searchability for the World Wide Web with the checklist of enablers. This factor enables the Web site developers and evaluators to create quality Web sites

Structure-based design of antivirals against Envelope Glycoprotein of dengue virus

Dengue virus (DENV) presents a significant threat to global public health with more than 500,000 hospitalizations and 25,000 deaths annually. Currently, there is no clinically approved antiviral drug to treat DENV infection. The envelope (E) glycoprotein of DENV is a promising target for drug discovery as the E protein is important for viral attachment and fusion. Understanding the structure and function of DENV E protein has led to the exploration of structure-based drug discovery of antiviral compounds and peptides against DENV infections. This review summarizes the structural information of the DENV E protein with regards to DENV attachment and fusion. The information enables the development of antiviral agents through structure-based approaches. In addition, this review compares the potency of antivirals targeting the E protein with the antivirals targeting DENV multifunctional enzymes, repurposed drugs and clinically approved antiviral drugs. None of the current DENV antiviral candidates possess potency similar to the approved antiviral drugs which indicates that more efforts and resources must be invested before an effective DENV drug materializes

Search-ability A Domain Quality Factor for Web Software Applications

As organizations become aware of the strategic importance of e-commerce they will also become aware of the need of quality Web sites. In early years the World Wide Web was originally designed to present information to Web surfers using simple sites that consists of hyper linked text. But, Modern Web applications run large-scale software applications for e-commerce, information distribution, entertainment, and numerous other activities. The factors that constitute software quality in traditional data processing are well defined. However, it is necessary to have a full understanding about the quality in the context of World Wide Web. This paper identifies a new quality factor, searchability for the World Wide Web with the checklist of enablers. This factor enables the Web site developers and evaluators to create quality Web sites

Broad and potent cross clade neutralizing antibodies with multiple specificities in the plasma of HIV-1 subtype C infected individuals.

Broadly Cross clade Neutralizing (BCN) antibodies are recognized as potential therapeutic tools and leads for the design of a vaccine that can protect human beings against various clades of Human Immunodeficiency Virus (HIV). In the present study, we screened plasma of 88 HIV-1 infected ART naïve individuals for their neutralization potential using a standard panel of 18 pseudoviruses belonging to different subtypes and different levels of neutralization. We identified 12 samples with good breadth of neutralization (neutralized >90% of the viruses). Four of these samples neutralized even the difficult-to-neutralize tier-3 pseudoviruses with great potency (GMT > 600). Analysis of neutralization specificities indicated that four samples had antibodies with multiple epitope binding specificities, viz. CD4-binding site (CD4BS), glycans in the V1/V2 and V3 regions and membrane proximal external region (MPER). Our findings indicate the strong possibility of identifying highly potent bNAbs with known or novel specificities from HIV-1 subtype C infected individuals from India that can be exploited as therapeutic tools or lead molecules for the identification of potential epitopes for design of a protective HIV-1 vaccine

Związek między polimorfizmem rs7903146 genu TCF7L2 a nefropatią cukrzycową nie jest niezależny od cukrzycy typu 2 — badanie populacji Indii Południowych i metaanaliza

Diabetic nephropathy (DN) is a chronic microangiopathic complication of both type 1 (T1DM) and type 2 diabetes mellitus (T2DM). The TCF7L2 gene has been reported to be associated with type 2 diabetes risk. We aimed to investigate the impact of TCF7L2 gene on the susceptibility of T2DM and DN in a south Indian population. Plus to evaluate the association of rs7903146 in the TCF7L2 gene with T2DM in the Indian population. The subjects recruited for this included 55 diabetic cases with diabetic nephropathy, 68 diabetic cases without nephropathy, and 82 non-diabetic healthy controls. Genomic DNA was isolated from blood and genotyping of TCF7L2 rs7903146 was performed by PCR-RFLP analysis. A literature survey was carried out into the effect of rs7903146 on genetic susceptibility to T2DM in Indian populations and we then performed a meta-analysis in order to evaluate its association with T2DM. Analysis of TCF7L2 rs7903146 in normal controls and diabetics with or without nephropathy demonstrated that the ‘T’ allele is associated with both diabetes (p = 0.049) and DN (p = 0.024), but this association is not independent of T2DM. Meta-analysis showed that the mutant allele and genotypes are associated with T2DM in Indian populations. In summary, a significant association exists between the ‘T’ allele and DN, but this association is not independent of T2DM. Pooled meta-analysis of studies on rs7903146 and T2DM confirmed that rs7903146 is significantly associated with susceptibility to T2DM in Indian populations. (Endokrynol Pol 2014; 65 (4): 298–305)Nefropatia cukrzycowa (DN, diabetic nephropathy) jest przewlekłym powikłaniem o charakterze mikroangiopatii występującym zarówno w cukrzycy typu 1 (T1DM, type 1 diabetes mellitus), jak i typu 2 (T2DM, type 2 diabetes mellitus). Gen TCF7L2 jest związany z ryzykiem cukrzycy typu 2. Badanie przeprowadzono w celu dokonania oceny wpływu genu TCF7L2 na podatność na zachorowanie na T2DM i DN w populacji Indii Południowych oraz oceny związku między występowaniem polimorfizmu rs7903146 genu TCF7L2 i T2DM w populacji południowej części Indii. Do badania włączono 55 przypadków chorych na cukrzycę z nefropatią cukrzycową, 68 przypadków cukrzycy bez nefropatii i 82 osoby niechorujące na cukrzycę jako grupę kontrolną. Genomowe DNA izolowano z krwi i przeprowadzono genotypowanie polimorfizmu rs7903146 genu TCF7L2 metodą analizy PCR-RFLP. Przeprowadzono również przegląd literatury pod kątem danych dotyczących wpływu występowania polimorfizmu rs7903146 na genetyczną podatność na T2DM w populacji hinduskiej, a następnie przeprowadzono metaanalizę w celu oceny jego związku z T2DM. Analiza polimorfizmu rs7903146 genu TCF7L2 u zdrowych osób z grupy kontrolnej oraz u chorych na cukrzycę z nefropatią i bez nefropatii wykazała, że allel T jest związany zarówno z cukrzycą (p = 0,049), jak i DN (p = 0,024), jednak ten związek nie jest niezależny od T2DM. Metaanaliza wykazała, że zmutowane allele i genotypy są związane z T2DM w populacji hinduskiej. Podsumowując, istnieje istotny związek między allelem T i DN, jednak związek ten nie jest niezależny od T2DM. Metaanaliza danych z badań dotyczących polimorfizmu rs7903146 i T2DM potwierdziła, że obecność polimorfizmu rs7903146 jest istotnie związana z podatnością na zachorowanie na T2DM w populacji hinduskiej. (Endokrynol Pol 2014; 65 (4): 298–305

Enhancement of tetravalent immune responses to highly conserved epitopes of a dengue peptide vaccine conjugated to polystyrene nanoparticles

Vaccination remains the major approach to the prevention of dengue. Since the only licensed live attenuated vaccine (LAV) lacked efficacy against all four serotypes, other vaccine platforms, such as synthetic peptide vaccines, should be explored. In this study, four multi-epitope peptides (P1–P4)were designed by linking a universal T-helper epitope (PADREorTpD) to the highly conserved CD8 T cell epitope and B cell epitope (B1 or B2) against all four DENV serotypes. The multi-epitope peptides were conjugated to polystyrene nanoparticles (PSNPs) and four nanovaccines (NP1–NP4) were constructed. Mice immunized with NP1–NP4 elicited significantly higher titers of IgG and neutralizing antibodies when compared to immunization with naked P1–P4. The immune responses in mice immunized with peptide vaccines were compared with nanovaccines using ELISA, ELISPOT, and a neutralization test based on FRNT50. Among the four conjugated peptide nanovaccines, NP3comprisingtheTpDT-helper epitope linked to the highly conserved B1 epitope derived from the E protein was able to elicit significant levels of IFN-γ and neutralizing antibodies to all four dengue serotypes. NP3 is a promising tetravalent synthetic peptide vaccine, but the selection of a more effective CD8+ T cell epitope and adjuvants to further improve the immunogenicity is warranted