Efficacy of Inclisiran in patients having familial hypercholesterolemia: heterozygous compared to homozygous trait, a systematic review and meta analysis.

OBJECTIVE: To find out whether Inclisiran sodium has different efficacy in heterozygous familial hypercholesterolemia (HeFH) and homozygous familial hypercholesterolemia (HoFH) patient groups. METHODS: We conducted the systematic review and meta analysis of ORION Clinical Trials Pubmed, Embase and Clinicaltrials.gov databases were searched for the relevant studies.Atheroscalerotic parameters considered for our objective were LDL-C,Total cholesterol,PCSK9, Apolipoportien-B, and Non HDL-C. Primary outcomes were the percentage difference in atheroscalerotic parameters at followup relative to baseline values. Our study examined these primary outcomes in order to determine whether there is a statistically significant difference between the HeFH and HoFH groups. Risk of bias was assessed by Cochrane risk of bias tool. Meta-analysis was performed when at least two studies reported on the same variable. RESULTS: Four ORION Clinical Trials provided the data related to the mean difference in the atheroscalerotic parameters at followup relative to baseline, of HeFH and HoFH patient populations, after administration of 300mg inclisiran subcutaneously. We pooled together these mean difference for each group and applied a statistical test to analyse if the values were significantly different between the groups. The results of our study unveiled the significant difference in pooled mean differences in LDL-C (HeFH:-48.62% HoFH:-9.12% p<0.05) Total cholesterol (HeFH:-30.31% HoFH:-11.50% p<0.05),Apolipoprotein(HeFH:-39.97% HoFH:-14.68% p<0.05), non HDL(HeFH:-44.51% HoFH:-12.22% p<0.05) between HeFH and HoFH groups. However the difference in pooled mean difference in PCSK9 values (HeFH:-68.41% HoFH:-56.25% p=0.2)between HeFH and HoFH groups, was statistically insignificant. Studies were of high quality. CONCLUSION: There was significant difference in the reductions in atherosclerotic lipid parameters in heterozygous and homozygous populations after the administration of Inclisiran except for PCSK9 parameter. Further studies are needed to support this conclusion.

Exposure to urban particulate matter alters responses of olfactory mucosal cells to SARS-CoV-2 infection.

Respiratory viruses have a significant impact on health, as highlighted by the COVID-19 pandemic. Exposure to air pollution can contribute to viral susceptibility and be associated with severe outcomes, as suggested by recent epidemiological studies. Furthermore, exposure to particulate matter (PM), an important constituent of air pollution, is linked to adverse effects on the brain, including cognitive decline and Alzheimer's disease (AD). The olfactory mucosa (OM), a tissue located at the rooftop of the nasal cavity, is directly exposed to inhaled air and in direct contact with the brain. Increasing evidence of OM dysfunction related to neuropathogenesis and viral infection demonstrates the importance of elucidating the interplay between viruses and air pollutants at the OM. This study examined the effects of subacute exposure to urban PM 0.2 and PM 10-2.5 on SARS-CoV-2 infection using primary human OM cells obtained from cognitively healthy individuals and individuals diagnosed with AD. OM cells were exposed to PM and subsequently infected with the SARS-CoV-2 virus in the presence of pollutants. SARS-CoV-2 entry receptors and replication, toxicological endpoints, cytokine release, oxidative stress markers, and amyloid beta levels were measured. Exposure to PM did not enhance the expression of viral entry receptors or cellular viral load in human OM cells. However, PM-exposed and SARS-CoV-2-infected cells showed alterations in cellular and immune responses when compared to cells infected only with the virus or pollutants. These changes are highly pronounced in AD OM cells. These results suggest that exposure of human OM cells to PM does not increase susceptibility to SARS-CoV-2 infection in vitro, but it can alter cellular immune responses to the virus, particularly in AD. Understanding the interplay of air pollutants and COVID-19 can provide important insight for the development of public health policies and interventions to reduce the negative influences of air pollution exposure.

Cyclic extraction of phosphate from soybean meal using immobilized Aspergillus oryzae SBS50 phytase.

Phytase enzyme found in plants, animals, and microorganisms is mainly involved in catalyzing the systematic removal of a phosphate group from phytic acid. Enzyme immobilization is one of the cost-effective methods for the wide usage of enzymes in the industrial sector. This paper reports the covalent immobilization of phytase on glutaraldehyde-activated aluminum oxide beads. The immobilization yield, efficiency, and activation energy were found to be 47.8%, 71.5%, and 15.78 J/mol, respectively. The bound enzyme displayed a shift in pH optima from 5.5 to 4.5, which is more beneficial to increase digestibility in comparison with the free enzyme. Immobilized phytase retained 42.60% of its activity after 1.0 h incubation at 80 °C, whereas free enzyme retained only 4.20% of its activity. Thermodynami increase in half-lives, D-values, enthalpy and free energy change after covalent immobilization could be credited to the enhanced stability. Immobilized phytase could be reused for five consecutive cycles retaining 51% of its initial activity with sodium phytate. The immobilized phytase was also found effective to hydrolyze the soybean meal, thus increasing the digestibility of poultry feed. The hydrolyzing reaction of soybean meal was carried out for six consecutive cycles and immobilized phytase retained nearly 50% of activity till the fifth cycle. The amount of phosphorus released after treatment with immobilized phytase was far higher than that from free phytase. Immobilization on this support is significant, as this support can sustain high mechanical resistance at high pH and temperature. This considerable stability and reusability of the bound enzyme may be advantageous for its industrial application.

Naphthyl bearing 1,3,4-thiadiazoleacetamides targeting the parasitic folate pathway as anti-infectious agents: in silico, synthesis, and biological approach.

Malaria is still a complex and lethal parasitic infectious disease, despite the availability of effective antimalarial drugs. Resistance of malaria parasites to current treatments necessitates new antimalarials targeting P. falciparum proteins. The present study reported the design and synthesis of a series of a 2-(4-substituted piperazin-1-yl)-N-(5-((naphthalen-2-yloxy)methyl)-1,3,4-thiadiazol-2-yl)acetamide hybrids for the inhibition of Plasmodium falciparum dihydrofolate reductase (PfDHFR) using computational biology tools followed by chemical synthesis, structural characterization, and functional analysis. The synthesized compounds were evaluated for their in vitro antimalarial activity against CQ-sensitive PfNF54 and CQ-resistant PfW2 strain. Compounds T5 and T6 are the most active compounds having anti-plasmodial activity against PfNF54 with IC50 values of 0.94 and 3.46 µM respectively. Compound T8 is the most active against the PfW2 strain having an IC50 of 3.91 µM. Further, these active hybrids (T5, T6, and T8) were also evaluated for enzyme inhibition assay against PfDHFR. All the tested compounds were non-toxic against the Hek293 cell line with good selectivity indices. Hemolysis assay also showed non-toxicity of these compounds on normal uninfected human RBCs. In silico molecular docking studies were carried out in the binding pocket of both the wild-type and quadruple mutant Pf-DHFR-TS to gain further insights into probable modes of action of active compounds. ADME prediction and physiochemical properties support their drug-likeness. Additionally, they were screened for antileishmanial activity against L. donovani promastigotes to explore broader applications. Thus, this study provides molecular frameworks for developing potent antimalarials and antileishmanial agents.

Production, Characterization and Prebiotic Potential of Xylooligosaccharides Produced from Wheat Bran using Enterobacter hormaechei KS1 Xylanase.

In the present investigation, xylooligosaccharides were produced from wheat bran and wheat bran extracted xylan through enzymatic hydrolysis using xylanase from novel Enterobacter hormaechei KS1. Xylooligosaccharides/reducing sugars production from wheat bran was found maximum (374 mg/g) when 4.0% of wheat bran was treated with 375 units (IU/mL) of Enterobacter hormaechei KS1 xylanase at pH 6.0 and incubated at 50 °C for 24 h of incubation. In case of wheat bran extracted xylan 419 mg/g of xylooligosaccharides were produced when 3% of extracted xylan was incubate for 8 h. Analysis of the enzymatic hydrolysate through high performance liquid chromatography equipped with refractive index detector showed the presence of xylose, xylopentose and xylohexose. The decrease in pH with 1.0% dose of xylooligosacchaides produced from extracted xylan hydrolysis using E. hormaechei KS1 xylanase showed more decrease with L. rhamnosus (6.72 to 5.94) followed by L. brevis (6.71 to 6.15) and L. plantarum (6.71 to 6.41). In case of increase in optical density both wheat bran and wheat bran extracted xylan generated xylooligosaccharides exhibited similar pattern i.e., L. rhamnosus > L. plantarum > L. brevis.

Divergent Responses of Hydrophilic CdSe and CdSe@CdS Core-Shell Nanocrystals in Apoptosis and In Vitro Cancer Cell Imaging: A Comparative Analysis.

With their distinctive core-shell design, core-shell nanocrystals have drawn interest in catalysis, medicinal research, and nanotechnology. These nanocrystals have a variety of characteristics and possible uses. The application of core-shell nanocrystals offers significant potential in increasing diagnostic and therapeutic approaches for cancer research in apoptosis and in vitro cancer cell imaging. In the present study, we investigated the fluorescence behavior of hydrophilic CdSe (core-only) and CdSe@CdS (core-shell) nanocrystals (NCs) and their potential in cancer cell imaging. The addition of a CdS coating to CdSe NCs increased the fluorescence intensity tenfold. The successful fabrication of core-shell CdSe@CdS nanocrystals was proven by a larger particle size (evaluated via DLS and TEM) and their XRD pattern and surface morphology compared to CdSe (core-only) NCs. When these NCs were used for bioimaging in MCF-7 and HEK-293 cell lines, they demonstrated excellent cellular uptake due to higher fluorescence intensity within cancerous cells than normal cells. Comparative cytotoxicity studies revealed that CdSe NCs were more toxic to all three cell lines (HEK-293, MCF-7, and HeLa) than CdSe@CdS core-shell structures. Furthermore, a decrease in mitochondrial membrane potential and intracellular ROS production supported NCs inducing oxidative stress, which led to apoptosis via the mitochondria-mediated pathway. Increased cytochrome c levels, regulation of pro-apoptotic gene expression (e.g., p53, Bax), and down-regulation of Bcl-2 all suggested cellular apoptosis occurred via the intrinsic pathway. Significantly, at an equivalent dose of core-shell NCs, core-only NCs induced more oxidative stress, resulting in increased apoptosis. These findings shed light on the role of a CdS surface coating in reducing free radical release, decreasing cytotoxicity, and improving fluorescence, advancing the field of cell imaging.

Gamma radiation detector selection for CT scanner.

Three types of gamma radiation detectors associated with distributed electronics namely, NaI (Tl), HPGe and LaBr3(Ce) are compared primarily focusing on electronic noise and scattering noise. Additionally, detectors of same make, material, size and electronics are also compared. A methodology is proposed to select the most suitable detector for computed tomography (CT) among the available options. Standard deviation parameter is employed to estimate electronic noise without performing CT experiment. Kanpur theorem-1(KT-1) is used to estimate the scattering noise quantitatively after verifying its sensitivity to scattering noise. The impact of scattering noise on CT profiles is evaluated using dice similarity dice coefficient. A good resemblance between KT-1 and dice coefficient is observed. A maximum difference of 56% in scattering noise is observed when five detectors used simultaneously instead of single detector whereas a discrepancy of 85% is observed between different types of radiation detectors. As far as ease of handling, operational and capital cost is concern one has to compromise minimum 12% of accuracy in CT reconstruction if NaI (Tl) detector is used with respect to best alternative available. The proposed methodology can be applied to measurement that require minimal scattering interference data other than CT experiments. The manufacturer can add noise level of detector as a characteristic parameter in the data sheet.

Environmental hazard assessment and metal contamination in coastal sediments.

In order to reduce contamination levels from diverse sources, it is important to understand the factors affecting the natural ecosystems that are impacted by coastal and marine pollution. In this study, we used GIS and remote sensing techniques to investigate and evaluate the distribution of heavy metals (Fe, Mn, Zn, Cr, Pb, Co, and Cu) in surface sediments along Tamil Nadu's East Coast (from Besant Nagar to Sathurangapattinam). The CF and Igeo of metals indicate that sediments contain no evidence of Fe, Mn, or Zn metal pollution in the sediments, with only mild contamination from Co, Cu, and Pb. In contrast, the sediment samples were found to be significantly contaminated with Cr. Heavy metal contamination occurs in the following order, according to our research: Cr > Pb > Cu > Co > Mn > Zn > Fe. Except for sites 8, 10, 11, and 13, where PLI>1 implies that there is no pollution in this area, the PLI values show that most of the locations are contaminated. The ecological risk index (ERI) values for five metals in the study areas are as follows: Cr > Pb > Cu > Mn > Zn. The sediment samples fall into the low-risk and highly polluted to dangerous sediment categories for SPI, according to the Risk index (RI). Based on the Mean Effect Range-Median Quotient (M-ERM-Q), Cu, Pb, Zn, and Cr metals in the research region have a 9-21% probability of being harmful. Statistical approaches show that the majority of heavy metals in sediments are of natural origin. The spatial distribution of heavy metals in surface sediments provides the conceptual framework for practical strategies to protect coastal areas. Many shreds of evidence indicate that anthropogenic inputs from the surrounding land area are primarily responsible for the deposition of these heavy metals in the coastal zone.

Synthesis and Spectral Characterisation of Fabricated Cerium-Doped Magnesium Oxide Nanoparticles: Evaluation of the Antimicrobial Potential and Its Membranolytic Activity through Large Unilamellar Vesicles.

Considerable attention has been given to Magnesium oxide nanoparticles lately due to their antimicrobial potential, low toxicity to humans, high thermal stability, biocompatibility, and low cost of production. However, their successful transformation into sustainable drugs is limited due to their low membrane permeability, which reduces their bioavailability in target cells. Herein we propose Cerium-doped magnesium oxide nanoparticles (MgOCeNPs) as a powerful solution to above mentioned limitations and are compared with MgO NPs for their membrane permeability and antimicrobial activity. Both pure and Ce-doped were characterized by various spectroscopic and microscopic techniques, in which an X-ray diffraction (XRD) examination reveals the lattice patterns for doped nanoparticles. Furthermore, Atomic Force Microscopy (AFM) revealed the three-dimensional (3D) structure and height of the nanoparticle. The crystal structure (FCC) of MgO did not change with Ce doping. However, microstructural properties like lattice parameter, crystallite size and biological activity of MgO significantly changed with Ce doping. In order to evaluate the antimicrobial potential of MgOCeNPs in comparison to MgO NPs and to understand the underlying mechanisms, the antibacterial activity was investigated against human pathogenic bacteria E. coli and P. aeruginosa, and antifungal activity against THY-1, a fungal strain. MgOCeNPs were studied by several methods, which resulted in a strong antibacterial and antifungal activity in the form of an elevated zone of inhibition, reduced growth curve, lower minimum inhibitory concentration (MIC80) and enhanced cytotoxicity in both bacterial and fungal strain as compared to MgO nanoparticles. The study of the growth curve showed early and prolonged stationary phase and early decline log phase. Both bacterial and fungal strains showed dose-dependent cytotoxicity with enhancement in intracellular reactive oxygen species (ROS) generation and formation of pores in the membrane when interacting with egg-phosphatidylcholine model Large Unilamellar Vesicles (LUVs). The proposed mechanism of MgOCeNPs toxicity evidently is membranolytic activity and induction of ROS production, which may cause oxidative stress-mediated cytotoxicity. These results confirmed that MgOCeNPs are a novel and very potent antimicrobial agent with a great promise of controlling and treating other microbes.

Approaches to Address PK-PD Challenges of Conventional Liposome Formulation with Special Reference to Cancer, Alzheimer's, Diabetes, and Glaucoma: An Update on Modified Liposomal Drug Delivery System.

Liposomes nowadays have become a preferential drug delivery system since they provide facilitating properties to drugs, such as improved therapeutic index of encapsulated drug, target and controlled drug delivery, and less toxicity. However, conventional liposomes have shown some disadvantages, such as less drug loading capacity, poor retention, clearance by kidney or reticuloendothelial system, and less release of hydrophilic drugs. Thus, to overcome these disadvantages recently, scientists have explored new approaches and methods, viz., ligand conjugation, polymer coating, and liposome hybrids, including surface-modified liposomes, biopolymer-incorporated liposomes, guest-in-cyclodextrin-in-liposome, liposome-in-hydrogel, liposome-in-film, liposome-in-nanofiber, etc. These approaches have been shown to improve the physiochemical and pharmacokinetic properties of encapsulated drugs. Lately, pharmacokinetic-pharmacodynamic (PK-PD) computational modeling has emerged as a beneficial tool for analyzing the impact of formulation and system-specific factors on the target disposition and therapeutic efficacy of liposomal drugs. There has been an increasing number of liposome-based therapeutic drugs, both FDA approved and those undergoing clinical trials, having application in cancer, Alzheimer's, diabetes, and glaucoma. To meet the continuous demand of health sectors and to produce the desired product, it is important to perform pharmacokinetic studies. This review focuses on the physical, physicochemical, and chemical factors of drugs that influence the target delivery of drugs. It also explains various physiological barriers, such as systemic clearance and extravasation. A novel approach, liposomal-hybrid complex, an innovative approach as a vesicular drug delivery system to overcome limited membrane permeability and bioavailability, has been discussed in the review. Moreover, this review highlights the pharmacokinetic considerations and challenges of poorly absorbed drugs along with the applications of a liposomal delivery system in improving PKPD in various diseases, such as cancer, Alzheimer's, diabetes, and glaucoma.

Natural Products: Potential Source of DPP-IV Inhibitors.

Out of multiple therapeutic targets, DPP-IV is the lead target for the treatment of type 2 diabetes. Natural products have always been available for the possible lead generation against various diseases and disorders. In the present review, we have covered various natural sources which have experimentally validated anti-diabetic activity for type 2 diabetic patients with specific focus on the DPP-IV inhibition. Out of all, the most potent DPP-IV inhibitors were found to be resveratrol, luteolin, apigenin and flavone having activity in nanomolar range. Standard drugs like sitagliptin, saxagliptin, and diprotin A have complex structures as compared to these phenolic compounds. Flavonoids and phenolic compounds have their added advantages in being present in a number of functional foods and carry antioxidant properties as well. So, the scientists working on the new chemical entity hunting for the type 2 diabetes treatment can also explore these natural sources for lead generation.

Dynamic colour change and the confusion effect against predation.

The confusion effect - the decreased attack-to-kill ratio of a predator with increase in prey group size - is thought to be one of the main reasons for the evolution of group living in animals. Despite much interest, the influence of prey coloration on the confusion effect is not well understood. We hypothesized that dynamic colour change in motion (due to interference coloration or flash marks), seen widely in many group living animals, enhances the confusion effect. Utilizing a virtual tracking task with humans, we found targets that dynamically changed colour during motion were more difficult to track than targets with background matching patterns, and this effect was stronger at larger group sizes. The current study thus provides the first empirical evidence for the idea that dynamic colour change can benefit animals in a group and may explain the widespread occurrence of dynamic colorations in group-living animals.

Clinical safety profile of ticagrelor compared to clopidogrel in 1208 patients: Real world evidence.

INTRODUCTION: Dual antiplatelet treatment is recommended by current clinical practice guidelines for patients undergoing PCI. The PLATO trial showed superiority of ticagrelor to clopidogrel in reducing the rate of death from vascular causes, myocardial infarction and stroke without increase in the rate of overall major bleeding in ACS patients. However, real world evidence in Indian patients is limited. The objective of this study is to compare safety profile of ticagrelor with clopidogrel in real world settings. METHODOLOGY: In this single centered retrospective observational study, a total of 1208 serial patient records undergoing PCI (ACS and stable angina patients as well) treated with Ticagrelor or Clopidogrel were collected and analyzed to look into in hospital outcomes. We excluded the patient's data that were incomplete. RESULTS: In total of 1208 patients, 604 patients received ticagrelor and similarly 604 patient received clopidogrel. No significant differences in the rates of major life threatening bleeding and any major bleeding were observed between ticagrelor and clopidogrel group (0.2% (n = 1) vs. 0.7% (n = 4), p = 0.18 and 2.8% (n = 17) vs. 3% (n = 18), p = 0.86 respectively). There was increase in minor bleeding rate with ticagrelor compared to clopidogrel (21.4% & 13.6%, p = 0.00). CONCLUSION: In the real world settings, patients undergoing PCI treated with ticagrelor showed similar safety profile compared to clopidogrel but with increase in minor bleeding rate. The observed results were in alignment with PLATO clinical trial.

Genotoxicity of intermediate frequency magnetic fields in vitro and in vivo.

We assessed genotoxic effects of intermediate frequency magnetic fields (MF) in vitro and in vivo. Rat primary astrocytes were exposed for 24 h to a 7.5 kHz MF at a magnetic flux density of 30 or 300 µT. Male C57BL/6 J mice were exposed continuously for 5 weeks to a 7.5 kHz MF at 12 or 120 µT, and blood samples were collected for the genotoxicity assays. To evaluate possible co-genotoxicity, the in vitro experiments included combined exposure with menadione (an agent that induces mitochondrial superoxide production and DNA damage) and methyl methanesulfonate (an alkylating agent). DNA damage and DNA repair (in vitro) were measured using the alkaline Comet assay and formation of micronuclei was assessed microscopically (in vivo) or using flow cytometry (in vitro). The results did not support genotoxicity or co-genotoxicity of 7.5 kHz MFs at magnetic flux densities up to 300 µT in vitro or in vivo. On the contrary, there was some evidence that exposure to 7.5 kHz MFs might reduce the level of genetic damage. Strongest indication of any biological effects was obtained from measurements of relative cell number, which was significantly and consistently increased after MF exposure in all in vitro experiments. Health implications of this finding are unclear, but it suggests that 7.5 kHz MFs may stimulate cell proliferation or suppress cell death.

Behavioural phenotypes in mice after prenatal and early postnatal exposure to intermediate frequency magnetic fields.

Electromagnetic fields are ubiquitous in the environment. Human exposure to intermediate frequency (IF) fields is increasing due to applications like electronic article surveillance systems, wireless power transfer, and induction heating cooking hobs. However, there are limited data on possible health effects of exposure to IF magnetic fields (MF). In the present study, we set out to assess cognitive and behavioural effects of IF MF in mice exposed during prenatal and early postnatal periods. Pregnant female mice were exposed continuously to 7.5kHz MFs at 12 and 120µT, from mating until weaning of pups. Sham exposed pregnant mice were used as a control group. A behavioural teratology study was conducted on the male offspring at two months of age to detect possible effects on the developing nervous system. Body weight development did not differ between the exposure groups. The exposure did not alter spontaneous motor activity when exploring a novel cage or anxiety in novelty-suppressed feeding or marble burying tests. Improved performance in the Rotarod task was observed in the 12µT group, while the 120µT exposure group swam more slowly than the sham exposed group in the Morris swim navigation task. However, indices of learning and memory (path length and escape latency during task acquisition and search bias during the probe test) did not differ between the exposure groups. Furthermore, the passive avoidance task did not indicate any impairment of long-term memory over a 48h interval in the exposed groups. In a post-mortem histopathological analysis, there was no evidence for an effect of IF MF exposure on astroglial reactivity or hippocampal neurogenesis. The results suggest that the IF MF used did not have detrimental effects on spatial learning and memory or histological markers of tissue reaction. The two statistically significant findings that were observed (improved performance in the Rotarod task in the 12µT group and decreased swimming speed in the 120µT group) are likely to be chance findings, as they do not form an internally consistent, dose-dependent pattern indicative of specific developmental effects.

Behavioral testing of mice exposed to intermediate frequency magnetic fields indicates mild memory impairment.

Human exposure to intermediate frequency magnetic fields (MF) is increasing due to applications like electronic article surveillance systems and induction heating cooking hobs. However, limited data is available on their possible health effects. The present study assessed behavioral and histopathological consequences of exposing mice to 7.5 kHz MF at 12 or 120 µT for 5 weeks. No effects were observed on body weight, spontaneous activity, motor coordination, level of anxiety or aggression. In the Morris swim task, mice in the 120 µT group showed less steep learning curve than the other groups, but did not differ from controls in their search bias in the probe test. The passive avoidance task indicated a clear impairment of memory over 48 h in the 120 µT group. No effects on astroglial activation or neurogenesis were observed in the hippocampus. The mRNA expression of brain-derived neurotrophic factor did not change but expression of the proinflammatory cytokine tumor necrosis factor alpha mRNA was significantly increased in the 120 µT group. These findings suggest that 7.5 kHz MF exposure may lead to mild learning and memory impairment, possibly through an inflammatory reaction in the hippocampus.

Population structure and association mapping of yield contributing agronomic traits in foxtail millet.

Association analyses accounting for population structure and relative kinship identified eight SSR markers ( p < 0.01) showing significant association ( R (2) = 18 %) with nine agronomic traits in foxtail millet. Association mapping is an efficient tool for identifying genes regulating complex traits. Although association mapping using genomic simple sequence repeat (SSR) markers has been successfully demonstrated in many agronomically important crops, very few reports are available on marker-trait association analysis in foxtail millet. In the present study, 184 foxtail millet accessions from diverse geographical locations were genotyped using 50 SSR markers representing the nine chromosomes of foxtail millet. The genetic diversity within these accessions was examined using a genetic distance-based and a general model-based clustering method. The model-based analysis using 50 SSR markers identified an underlying population structure comprising five sub-populations which corresponded well with distance-based groupings. The phenotyping of plants was carried out in the field for three consecutive years for 20 yield contributing agronomic traits. The linkage disequilibrium analysis considering population structure and relative kinship identified eight SSR markers (p < 0.01) on different chromosomes showing significant association (R (2) = 18 %) with nine agronomic traits. Four of these markers were associated with multiple traits. The integration of genetic and physical map information of eight SSR markers with their functional annotation revealed strong association of two markers encoding for phospholipid acyltransferase and ubiquitin carboxyl-terminal hydrolase located on the same chromosome (5) with flag leaf width and grain yield, respectively. Our findings on association mapping is the first report on Indian foxtail millet germplasm and this could be effectively applied in foxtail millet breeding to further uncover marker-trait associations with a large number of markers.

Therapeutic approaches of melatonin in microwave radiations-induced oxidative stress-mediated toxicity on male fertility pattern of Wistar rats.

Microwave (MW) radiation produced by wireless telecommunications and a number of electrical devices used in household or in healthcare institutions may adversely affects the reproductive pattern. Present study aimed to investigate the protective effects of melatonin (is well known antioxidant that protects DNA, lipids and proteins from free radical damage) against oxidative stress-mediated testicular impairment due to long-term exposure of MWs. For this, 70-day-old male Wistar rats were divided into four groups (n = 6/group): Sham exposed, Melatonin (Mel) treated (2 mg/kg), 2.45 GHz MWs exposed and MWs + Mel treated. Exposure took place in Plexiglas cages for 2 h a day for 45 days where, power density (0.21 mW/cm(2)) and specific absorption rate (SAR 0.14 W/Kg) were estimated. After the completion of exposure period, rats were sacrificed and various stress related parameters, that is LDH-X (lactate dehydrogenase isoenzyme) activity, xanthine oxidase (XO), ROS (reactive oxygen species), protein carbonyl content, DNA damage and MDA (malondialdehyde) were performed. Result shows that melatonin prevent oxidative damage biochemically by significant increase (p < 0.001) in the levels of testicular LDH-X, decreased (p < 0.001) levels of MDA and ROS in testis (p < 0.01). Meanwhile, it reversed the effects of MWs on XO, protein carbonyl content, sperm count, testosterone level and DNA fragmentation in testicular cells. These results concluded that the melatonin has strong antioxidative potential against MW induced oxidative stress mediated DNA damage in testicular cells.

Development of 5123 intron-length polymorphic markers for large-scale genotyping applications in foxtail millet.

Generating genomic resources in terms of molecular markers is imperative in molecular breeding for crop improvement. Though development and application of microsatellite markers in large-scale was reported in the model crop foxtail millet, no such large-scale study was conducted for intron-length polymorphic (ILP) markers. Considering this, we developed 5123 ILP markers, of which 4049 were physically mapped onto 9 chromosomes of foxtail millet. BLAST analysis of 5123 expressed sequence tags (ESTs) suggested the function for ∼71.5% ESTs and grouped them into 5 different functional categories. About 440 selected primer pairs representing the foxtail millet genome and the different functional groups showed high-level of cross-genera amplification at an average of ∼85% in eight millets and five non-millet species. The efficacy of the ILP markers for distinguishing the foxtail millet is demonstrated by observed heterozygosity (0.20) and Nei's average gene diversity (0.22). In silico comparative mapping of physically mapped ILP markers demonstrated substantial percentage of sequence-based orthology and syntenic relationship between foxtail millet chromosomes and sorghum (∼50%), maize (∼46%), rice (∼21%) and Brachypodium (∼21%) chromosomes. Hence, for the first time, we developed large-scale ILP markers in foxtail millet and demonstrated their utility in germplasm characterization, transferability, phylogenetics and comparative mapping studies in millets and bioenergy grass species.

Development of eSSR-Markers in Setaria italica and Their Applicability in Studying Genetic Diversity, Cross-Transferability and Comparative Mapping in Millet and Non-Millet Species.

Foxtail millet (Setariaitalica L.) is a tractable experimental model crop for studying functional genomics of millets and bioenergy grasses. But the limited availability of genomic resources, particularly expressed sequence-based genic markers is significantly impeding its genetic improvement. Considering this, we attempted to develop EST-derived-SSR (eSSR) markers and utilize them in germplasm characterization, cross-genera transferability and in silico comparative mapping. From 66,027 foxtail millet EST sequences 24,828 non-redundant ESTs were deduced, representing ~16 Mb, which revealed 534 (~2%) eSSRs in 495 SSR containing ESTs at a frequency of 1/30 kb. A total of 447 pp were successfully designed, of which 327 were mapped physically onto nine chromosomes. About 106 selected primer pairs representing the foxtail millet genome showed high-level of cross-genera amplification at an average of ~88% in eight millets and four non-millet species. Broad range of genetic diversity (0.02-0.65) obtained in constructed phylogenetic tree using 40 eSSR markers demonstrated its utility in germplasm characterizations and phylogenetics. Comparative mapping of physically mapped eSSR markers showed considerable proportion of sequence-based orthology and syntenic relationship between foxtail millet chromosomes and sorghum (~68%), maize (~61%) and rice (~42%) chromosomes. Synteny analysis of eSSRs of foxtail millet, rice, maize and sorghum suggested the nested chromosome fusion frequently observed in grass genomes. Thus, for the first time we had generated large-scale eSSR markers in foxtail millet and demonstrated their utility in germplasm characterization, transferability, phylogenetics and comparative mapping studies in millets and bioenergy grass species.