Association of PARK-2 Non-synonyms Polymorphisms and Their In Silico Validation Among North Indian Colorectal Cancer Patients.

PURPOSE: PARK2 is a potential tumour suppressor gene and its genetic alterations (regionic loss) are common across many human cancers. The association of PARK2 germline variations (SNPs) with Parkinson's has been shown, but their association in development and progression of cancer remains elusive. The aim of this study was to identify association of PARK2 polymorphisms (rs1801474, rs1801334) with colorectal cancer in a case control study design. METHODS: This case control study included a total of 650 genetically unrelated subjects comprising 300 colorectal cancer cases and 350 healthy controls belonging to North Indian. Both SNPs were analyzed using the PCR-RFLP assay. Statistical analysis for describing risk and association was performed using SPSS-17 software. Structural deviations due to non- synonymous substitutions (S167N and D394N) were analyzed using MD simulations. RESULTS: The genotype distributions of both the SNPs were in Hardy-Weinberg equilibrium. For both the polymorphisms, the allelic model showed statistically significant risk with OR ~ 1.3. Many of the associations remained significant even after Bonferroni correction (P < 0.00125). The result suggested that both S167N and D394N were deviated from wild type and structures and were stable after 5 ns. The average value of RMSD for backbone atoms was calculated from 5 to 10 ns molecular dynamics simulation data. CONCLUSION: In conclusion, our study revealed a significant association of PARK2 SNPs with colorectal cancer as well as their relations with other clinical parameters highlighting their contribution towards colorectal cancer susceptibility in North Indian population.

Coenzyme Q10 ameliorates cadmium induced reproductive toxicity in male rats.

This study aimed at investigating the protective role of CoQ10 against cadmium (Cd)-induced reproductive toxicity in male rats. Adult male Wistar rats were exposed to an acute dose of Cd (25 mg/kg bwt; Cd group), Cd+CoQ10 (25 mg/kg bwt Cd+10 mg CoQ10; Cd-Q10 group) and distilled water (control) in vivo for 15 consecutive days and semen quality was assessed. A significant reduction was noted in sperm concentration, progressive motility, morphology and DNA integrity in both Cd- and Cd-Q10 groups in comparison to control indicating Cd-induced testicular lipid per oxidation (LPO) and decline in indigenous antioxidant defense system as measured by total antioxidant capacity (TAC) (p<0.05). However, simultaneous co-administration of CoQ10 along with Cd (Cd-Q10 group) was able to improve sperm concentration, motility, progressive motility, morphology, DNA integrity, and testicular TAC as well as lower LPO compared to Cd group (p<0.05). Results indicate that used dose of CoQ10 is capable of moderately ameliorating reproductive toxicity of Cd by improving semen quality and reducing testicular oxidative stress.

Association of PARK2 promoter polymorphisms and methylation with colorectal cancer in North Indian population.

Different diseases have been associated with PARK2/PACRG overlapping promoter polymorphisms (rs2276201 and rs9347683) in the recent past. However association of these polymorphisms with cancer remains elusive till date. Thus in this study we evaluated association between these polymorphisms and colorectal cancer (CRC) incidences among North Indians. Genomic DNA was isolated using venous blood of 400 unrelated subjects (200 CRC cases and 200 healthy controls) of North Indian origin. Both SNPs were genotyped using PCR-RFLP method. Promoter methylation status in tumor DNA was checked using MS-PCR. Statistical analysis was performed using SPSS-17 software. In-silico predictions for transcription factor binding were performed using "PROMO" a freely available online tool. SNP rs2276201 showed statistically significant difference (P = 0.047) among cases and controls while rs9347683 did not (P = 0.113). The TC genotype (OR: 1.855, 95% CI: 1.021-3.369, P = 0.043), CC genotype (OR: 1.617, 95% CI: 1.042-2.510, P = 0.032), TT vs CT+CC genetic model (OR: 1.60, P = 0.0158) and allelic model (OR: 1.3931, 95% CI: 1.0498-1.8485, P = 0.0214) of rs2276201 showed significant risk for CRC. For rs9347683 AC genotype (OR: 1.604, 95% CI: 1.019-2.523, P = 0.041) and AA vs AC+CC genetic model (OR: 1.57, P = 0.039) showed significant risk. Haplotype CC provided significant risk (OR: 1.618, 95% CI: 1.112-2.352, P = 0.011) whereas haplotype TA provided significant protection (OR: 0.732, 95% CI: 0.543-0.987, P = 0.040) against CRC. Promoter methylation was significantly higher in tumor grade III + IV (OR: 2.37, P = 0.019), while PARK2 expression was lower in cancer tissues compared to normal tissue. Here we provide the first report where PARK2 promoter SNP's rs2276201 and rs9347683 are shown to be significantly associated with the risk of CRC development.

Antibiotic stewardship in a tertiary care hospital of a developing country: establishment of a system and its application in a unit-GASP Initiative.

PURPOSE: Despite the proven benefits of antimicrobial stewardship, models for executing the same in the developing countries are sparse. The present study highlights the approaches undertaken by our group in initiating one such program in a public sector tertiary level health care setting of a developing country. METHODS: The study focussed on development of a system after evaluation of existing issues and case study of implementation of the program in a unit within the hospital. The system building exercise included (1) development of generic data capture form for prospective audit and feedback; (2) development of an electronic system for data capture; (3) identification of key intervention points for strategy decision for stewardship in a particular unit; (4) application of the stewardship method and (5) evaluation of outcomes. RESULTS: A digital system for prospective audit was constructed after a background study. In the study unit, there was a significant decline in double anaerobic coverage. There was a significant decline in the average number of antimicrobials used per patients and a decrease in Defined Daily Dose of designated antimicrobials was noted. Additionally, there was an increase in the use of optimized doses. CONCLUSION: A system for undertaking antimicrobial stewardship with a mechanism for prospective audit was put in place. The system may be adopted by other public sector hospitals of the developing country.

New low bandgap near-IR conjugated D-A copolymers for BHJ polymer solar cell applications.

We synthesized two novel ultra low bandgap donor-acceptor (D-A) copolymers (E(g) ≤ 1.2 eV), containing the thiadiazoloquinoxaline unit as the main electron accepting unit (A) and benzodithiophene (BDT) and dithienosilole (DTS) as different donor units (D), denoted as P1 and P2, respectively, using the cross-coupling Stille reaction. The copolymers possess light absorption ranging from UV (350 nm) to near-IR (1300 nm) with optical bandgaps of 1.16 eV and 1.08 eV, respectively. Quantum-chemical calculations and experimental data were compared for proposing a more detailed concept for the optical and electronic properties of these copolymers which can be used as donors for polymer solar cells (PSCs). The PSCs based on optimized P1:PC71BM and P2:PC71BM showed overall power conversion efficiencies (PCEs) of 4.32% and 3.48%, respectively. Although P2 possesses a broad absorption coverage of up to 1300 nm, the lower PCE may be attributed to the low J(sc), due to the poor driving force for exciton dissociation, since the LUMO offset with PC71BM is less than 0.3 eV. The PCE has been significantly increased to 7.27% and 6.68% for solvent vapor annealing (SVA) treated P1:PC71BM and P2:PC71BM active layers, respectively. This improvement arises from the appropriate nanoscale morphology and an increase in hole mobility, induced by the SVA treatment of the active layers.

A triazine di(carboxy)porphyrin dyad versus a triazine di(carboxy)porphyrin triad for sensitizers in DSSCs.

Two porphyrin-chromophores, i.e. triad PorZn-(PorCOOH)(2)-(piper)2 (GZ-T1) and dyad (PorZn)(2)-NMe2 (GZ-T1), have been synthesized and their photophysical and electrochemical properties have been investigated. The optical properties together with the appropriate electronic energy levels, i.e. the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) energy levels, revealed that both porphyrin assemblies can function as sensitizers for dye sensitized solar cells (DSSCs). The and -based DSSCs have been prepared and studied using 20 mM CDCA as coadsorbent and were found to exhibit an overall power conversion efficiency (PCE) of 5.88% and 4.56%, respectively (under an illumination intensity of 100 mW cm(-2) with TiO(2) films of 12 µm). The higher PCE of the -sensitized DSSC, as revealed from the current-voltage characteristic under illumination and the incident photon to current conversion efficiency (IPCE) spectra of the two DSSCs, is mainly attributed to its enhanced short circuit current (J(sc)), although both the open circuit voltage (V(oc)) and the fill factor are improved too. The electrochemical impedance spectra (EIS) demonstrated a shorter electron transport time, longer electron lifetime and higher charge recombination resistance for the DSSC sensitized with the dye as well as a larger dye loading onto the TiO(2) surface.

Synthesis and characterization of π-conjugated copolymers with thieno-imidazole units in the main chain: application for bulk heterojunction polymer solar cells.

In this paper the three new narrow bandgap D­A conjugated copolymers P1, P2 and P3 based on different weak donor fused thiophene-imidazole containing derivatives and the same benzothiadiazole acceptor unit were synthesized by Stille cross-coupling polymerization and characterized by 1H NMR, elemental analysis, GPC, TGA, DSC. These copolymers exhibit intensive absorbance in the range 350­900 nm and the optical bandgap lies in the range of 1.50­1.61 eV, which corresponds to the maximum photon flux of the solar spectrum. The electrochemical bandgap derived from cyclic voltammetry varies within the limits 1.47­1.65 eV and is approximately very close to the optical bandgap. The highest occupied molecular orbital (HOMO) energy level of all copolymers is deep lying (−5.24 eV and −5.37 eV and −5.25 eV for P1, P2 and P2, respectively) which shows that copolymers have good stability in the air and assured a higher open circuit voltage (Voc) for polymer BHJ solar cells. These copolymers were used as donors along with PC71BM and the BHJ polymer solar cells based on P1:PC71BM, P2:PC71BM and P3:PC71BM processed from chloroform (CF) solvent with 3 v% DIO as an additive showed an overall PCE of 4.55%, 6.76% and 5.16%, respectively.

Near infrared organic semiconducting materials for bulk heterojunction and dye-sensitized solar cells.

Dye sensitized solar cells (DSSCs) and bulk heterojunction (BHJ) solar cells have been the subject of intensive academic interest over the past two decades, and significant commercial effort has been directed towards this area with the vison of developing the next generation of low cost solar cells. Materials development has played a vital role in the dramatic improvement of both DSSC and BHJ solar cell performance in the recent years. Organic conjugated polymers and small molecules that absorb solar light in the visible and near infrared (NIR) regions represent a class of emering materials and show a great potential for the use of different optoelectronic devices such as DSSCs and BHJ solar cells. This account describes the emering class of near infrared (NIR) organic polymers and small molecules having donor and acceptors units, and explores their potential applications in the DSSCs and BHJ solar cells.

Effect of ethylene carbonate as a plasticizer on CuI/PVA nanocomposite: Structure, optical and electrical properties.

Layers of ethylene carbonate (EC) modified CuI/PVA polymer composites were prepared by growth of CuI nano-particles in an aqueous solution of PVA followed by casting at room temperature. The structural, thermal, optical, electrical and di-electrical characterization of polymer composites was investigated using different techniques. These investigations confirm the growth of CuI nano-particles and reduction of PVA crystallinity by increasing ethylene carbonate concentration. These results show that energy band gap and bulk conductivity increase while activation energy reduces with the increase of EC concentration in the composite. Moreover, the variation of the dielectric permittivity and dielectric loss with EC content are found to obey Debye dispersion relations.

2,6-Bis(1-methylbenzimidazol-2-yl)pyridine: a new ancillary ligand for efficient thiocyanate-free ruthenium sensitizer in dye-sensitized solar cell applications.

We have designed and synthesized a new thiocyante-free ruthenium complex containing 2,6-bis(1-methylbenzimidazol-2-yl)pyridine, coded as SPS-G3, and it has been used as an efficient photosensitizer for dye-sensitized solar cells (DSSCs). Upon sensitization of SPS-G3 on nanocrystalline TiO2 film, the DSSC test cell yielded a large short-circuit photocurrent (16.15 mA cm(-2)), an open circuit voltage of 0.52 V, and a fill factor (FF) of 0.72, resulting in an overall power conversion efficiency (PCE) of 6.04% under simulated AM 1.5 solar irradiation (100 mW cm(-2)). DSSCs were prepared by adding various concentrations of multiwall carbon nanotubes (MWCNTs) (up to 0.5 wt %) into the TiO2 nanoparticles. Optimization of MWCNT concentration (0.3 wt %) lead to PCE values as high as 7.76%, while the test cells employing pure TiO2 photoanode obtained an efficiency of 6.04%. The results indicate that the PCE of MWCNTs/TiO2 composite DSSCs are dependent on the quantity of MWCNTs loading on the photoanodes. A small amount (0.3 wt %) clearly enhances the PCE of DSSC, while the excessive MWCNT loading lowers the photovoltaic performance of the DSSC. The increase in the PCE has been attributed to the decrease in charge-transport resistance, charge-transport time, and electron lifetime, which are estimated from electrochemical impedance spectra.

Application of solution processable squaraine dyes as electron donors for organic bulk-heterojunction solar cells.

New low bandgap small molecules based on a squaraine (SQ) chromophore, bis[4-(2,6-di-tert-butyl)vinylpyrylium]squaraine (TBU-SQ), bis[2,6-di-tert-butyl-4-(prop-1-en-2-yl)pyrylium]squaraine (MeTBU-SQ) and bis[4-(but-1-en-2-yl)-2,6-di-tert-butylpyrylium]squaraine (EtTBU-SQ), were synthesized and used as electron donors along with PC70BM for their application in solution processed organic bulk-heterojunction (OBHJ) solar cell (SC). The long wavelength of these SQ dyes are located in between 650-750 nm in thin films and the optical bandgaps are about 1.64, 1.52 and 1.48 eV, respectively. The electrochemical properties of these SQ dyes indicate that they are well suited for the fabrication of OBHJSCs as electron donors along with fullerene derivatives as electron acceptors. The OBHJ photovoltaic (PV) devices fabricated with the blend of TBU-SQ:PC70BM, MeTBU-SQ:PC70BM and EtTBU-SQ:PC70BM cast from chloroform (CF) solvent exhibited a power conversion efficiency (PCE) of 1.71%, 2.15%, and 1.89%, respectively. The PCE of the OBHJSCs based on MeTBU-SQ:PC70BM blends cast from DIO-THF (DIO = 1,8-diiodooctane) additive solvent and cast from DIO-THF with subsequent thermal annealing have been further improved up to 2.73% and 3.14%, respectively. This enhancement in the PCE is attributed to the improvement in the crystalline nature of the blend and more balanced charge transport resulting from the higher hole mobility. All these results have been supported by the quantum chemical calculations.

MicroRNAs: a new ray of hope for diabetes mellitus.

Diabetes mellitus has become one of the most common chronic diseases, thereby posing a major challenge to global health. Characterized by high levels of blood glucose (hyperglycemia), diabetes usually results from a loss of insulin-producing ß-cells in the pancreas, leading to a deficiency of insulin (type 1 diabetes), or loss of insulin sensitivity (type 2 diabetes). Both types of diabetes have serious secondary complications, such as microvascular abnormalities, cardiovascular dysfunction, and kidney failure. Various complex factors, such as genetic and environmental factors, are associated with the pathophysiology of diabetes. Over the past two decades, the role of small, single-stranded noncoding microRNAs in various metabolic disorders, especially diabetes mellitus and its complications, has gained widespread attention in the scientific community. Discovered first as an endogenous regulator of development in the nematode Caenorhabditis elegans, these small RNAs post-transcriptionally suppress mRNA target expression. In this review, we discuss the potential roles of different microRNAs in diabetes and diabetes-related complications.

Efficient thiocyanate-free sensitizer: a viable alternative to N719 dye for dye-sensitized solar cells.

We have designed and synthesized a new thiocyanate-free sensitizer coded as SPS-01 and used it as the sensitizer in a TiO(2) based nanocrystalline dye-sensitized solar cell (DSSC). SPS-01 exhibits strong visible absorption properties with maximum peak around at 532 nm. The overall power conversion efficiency (PCE) of a DSSC sensitized with SPS-01 (7.96%) is higher than that of N719 (7.30%) under identical experimental conditions. This high PCE is attributed mainly due to the improvement in the short circuit current.

Isolation and characterization of heavy metal resistant bacteria from Barak River contaminated with pulp paper mill effluent, South Assam.

A group of 15 heavy metal resistant bacteria were isolated from Barak River contaminated with paper and pulp effluents. These isolates displayed different degrees of chromium tolerance. Four isolates showed 34 %-49 % of growth at a concentration of 4.0 mM of Cr(6+) and subjected to chromium reduction assay under aerobic condition. The isolate E (4) showed highest reduction (34.38 %) followed by E (3) and K(6)PA6, both showed 28.75 % reduction and then D (2) (27.5 %) after 72 h of incubation. These 4 isolates also showed different degrees of resistance to other heavy metals like Ni, Cu, Co and Cd. Antibiotic sensitivity profile of these selected bacterial strains was determined against 10 different antibiotics. Isolate E (4) appeared to be most susceptible being inhibited by eight antibiotics and resistant to penicillin G and ampicillin. The isolate E (3) was resistant to as many as five antibiotics and showed susceptible responses to the rest of the antibiotics. Both the isolates K(6)PA6 and D (2) were resistant to four antibiotics and showed intermediate to susceptible responses to the rest of the antibiotics.

Excess copper induced oxidative stress and response of antioxidants in rice.

To investigate the effects of copper (Cu), rice plant (Oryza sativa. L. var. MSE-9) was treated with different Cu concentrations (0, 10, 50 and 100 µM) for 5 days in hydroponic condition. Gradual decrease in shoot and root growth was observed with the increase of Cu concentration and duration of treatment where maximum inhibition was recorded in root growth. Cu was readily absorbed by the plant though the maximum accumulation was found in root than shoot. Hydrogen peroxide (H(2)O(2)) production and lipid peroxidation were found increased with the elevated Cu concentration indicating excess Cu induced oxidative stress. Antioxidant enzymes superoxide dismutase (SOD), guaiacol peroxidase (GPX) and ascorbate peroxidase (APX) and glutathione reductase (GR) were effectively generated at the elevated concentrations of Cu though catalase (CAT) did not show significant variation with respect to control. Ascorbate (ASH), glutathione (GSH) and proline contents were also increased in all the Cu treated plants compared with the control. SOD isoenzyme was greatly affected by higher concentration of Cu and it was consistent with the changes of the activity assayed in solution. The present study confirmed that excess Cu inhibits growth, induced oxidative stress by inducing ROS formation while the stimulated antioxidative system appears adaptive response of rice plant against Cu induced oxidative stress. Moreover proline accumulation in Cu stress plant seems to provide additional defense against the oxidative stress.

Effect of predator stress and malathion on tadpoles of Indian skittering frog.

The impact of pesticides on amphibians is of particular concern because their populations appear to be declining on a global scale. We examined the toxic and genotoxic effects of malathion, a commonly used organophosphorus pesticide, in the larvae of Indian skittering frog (Euflictis cyanophlyctis). The different concentrations of malathion (0, 0.5, 1.0, 2.0, 4.0 and 8.0mg/L) tested in a 2×6 factorial design, induced concentration-dependent lethality in tadpoles in the presence and absence of predator cues. The 96 h LC50 for malathion in the presence and absence of predator stress were 3.523 mg/L and 3.588 mg/L, respectively. The 15-day LC50 value for malathion was estimated to be 2.452 mg/L. Lower concentrations of malathion extending into the sublethal range (0.5, 1.0 and 2.0 mg/L) induced micronuclei (MN) in the erythrocytes of tadpoles at 24 h (F3,56=70.291, p<0.001), 48 h (F3,56=78.423, p<0.001), 72 h (F3,56=88.817, p<0.001) and 96 h (F3,56=64.770, p<0.001) in a concentration-dependent manner. Predator stress significantly enhanced the MN frequency at 48 h following 1.0mg/L malathion treatment (p<0.001). The present report is the first one to analyze genotoxic effect of malathion in the presence of predator stress. These results suggest that predator stress may potentiate the genotoxic effect of lower concentrations of malathion in E. cyanophlyctis tadpoles. These effects may have long-term fitness consequence to the population as a whole.

Transformation of pWWO in Rhizobium leguminosarum DPT to Engineer Toluene Degrading Ability for Rhizoremediation.

Rhizoremediation of organic xenobiotics is based on interactions between plants and their associated micro-organisms. The present work was designed to engineer a bacterial system having toluene degradation ability along with plant growth promoting characteristics for effective rhizoremediation. pWWO harboring the genes responsible for toluene breakdown was isolated from Pseudomonas putida MTCC 979 and successfully transformed in Rhizobium DPT. This resulted in a bacterial strain (DPT(T)) which had the ability to degrade toluene as well as enhance growth of host plant. The frequency of transformation was recorded 5.7 × 10(-6). DPT produced IAA, siderophore, chitinase, HCN, ACC deaminase, solubilized inorganic phosphate, fixed atmospheric nitrogen and inhibited the growth of Fusarium oxysporum and Macrophomina phaseolina in vitro. During pot assay, 50 ppm toluene in soil was found to inhibit the germination of Cajanus cajan seeds. However when the seeds bacterized with toluene degrading P. putida or R. leguminosarum DPT were sown in pots, again no germination was observed. Non-bacterized as well as bacterized seeds germinated successfully in toluene free soil as control. The results forced for an alternative mode of application of bacteria for rhizoremediation purpose. Hence bacterial suspension was mixed with soil having 50 ppm of toluene. Germination index in DPT treated soil was 100% while in P. putida it was 50%. Untreated soil with toluene restricted the seeds to germinate.

Value addition to bamboo shoots: a review.

Bamboo shoot forms a traditional delicacy in many countries. Being low in fat content and high in potassium, carbohydrate, dietary fibres, Vitamins and active materials, bamboo shoots are consumed in raw, canned, boiled, marinated, fermented, frozen, liquid and medicinal forms. Although the fresh bamboo shoots of species like Dendraocalamus giganteus are healthier and nutritionally rich, the young shoots, after fortification, can be consumed by processing into a wide range of food products with longer shelf-life and better organoleptic qualities. However, the consumption pattern of bamboo shoots in most of the countries is traditional, non-standardized, seasonal and region-specific with little value addition. Therefore, there exists a great opportunity, especially for the organized food processing sectors to take up the processing of bamboo shoot-based food products in an organized manner. The present article gives an insight into the global scenario of bamboo shoot-based food products and their consumption pattern, the quality attributes, and the opportunities for value addition along with future prospects in view of international food safety, security and nutrition.