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Gamma ray shielding ability of WO3 borate glasses is analyzed by using the Phy-X/PSD software. Mass attenuation coefficient of glasses gets enhanced with addition of tungsten oxide resulting in lowering of the values of MFP, HVL, TVL and EBF at 10 mol % of tungsten as compared to many commercial and radiation shielding glasses/concretes. The higher value of FNRCS (∑R) in studied glasses than concretes shows their neutron shielding ability. The sample with highest value of tungsten is most suitable for making radiation shielding materials. The OPD, OMV, n ¯ c , nb and dbb values indicate the rigid and stable glass structure due to the formations of stable BO4 groups. Poisson ratio confirms high cross density and stability of prepared glasses as its value decreases from 0.233 to 0.226. The increased values of elastic constants and VHN are also in the favour of higher stability and rigidity of the glasses due to addition of WO3. All of these parameters are in good relation with each other and support the shielding power of the studied glasses.

Single-mode, air-cladded optical waveguides have wavelength scale diameters, making them very fragile and difficult to handle and yet highly desirable for sensing and inter-chip photonic interconnects. These contradictory qualities are resolved in this work by supporting the optical waveguide with a nano-fin structure attached to a substrate, narrow enough and sufficiently tall to minimally impact the wave-guiding metrics of the solid core while providing structural mechanical integrity. The design considerations for the nano-fin-supported waveguide and its realization using a commercial direct laser writing system based on two-photon activation of a photopolymer is reported herein. The 3D printed waveguides are characterized and experimentally assessed, demonstrating low birefringence and an estimated propagation loss for LP01x and LP01y of 2.9 dB/mm and 3.4 dB/mm, respectively, attributed to surface roughness and the relatively high refractive index contrast with air.

Aim of present study was to estimate quantitative changes in nutraceutical properties of cookies. Refined wheat flour and raw/roasted flaxseed flour blends (100:00, 90:10, 80:20, and 70:30) were prepared and subjected for baking to prepare cookies. Effect of addition of raw/roasted flaxseed flour at different proportions on nutritional, physicochemical (weight, diameter, thickness and spread ratio) and phytochemical (total phenolic content and total flavonoids content) properties were studied. Antioxidant capacity was measured by using TEAC assay. Colour and texture measurement was undertaken with the help of HunterLab colorimeter and Texture Analyzer (TA-XT2) respectively. Refined wheat flour was found to have 4.26% protein and 0.04% fiber which were further increased to about 9.25% and 2.37% respectively after addition of raw flaxseed flour in 70:30 proportions. Baking process at higher temperature resulted in decrease in TPC and TFC while increase in antioxidant capacity. Hardness, resilience, chewiness and springiness of cookies decreased and cohesiveness, gumminess and fracturability increased with increasing amount of flaxseed flour in cookies. Keywords: Flaxseed flour, Baking, Cookies characteristics, Phytochemicals

Tuberculosis (TB) is a potentially fatal contagious disease and is a second leading infectious cause of death in the world. Osteoarticular TB is treated using standard regimen of 1st and 2nd line anti-tubercular drugs (ATDs) for extensive period of 8-20 months. These drugs are commonly administered in high doses by oral route or by intravenous route, because of their compromised bioavailability. The common drawbacks associated with conventional therapy are poor patient compliance due to long treatment period, frequent and high dosing, and toxicity. This aspect marks for the need of formulations to eliminate these drawbacks. MTB is an intracellular pathogen of mononuclear phagocyte. This attribute makes nanotherapeutics an ideal approach for MTB treatment as macrophages capture nano forms. Polymeric nanoparticles are removed from the body by opsonization and phagocytosis, which forms an ideal strategy to target macrophage containing mycobacteria. To further improve targetability, the nanoparticles are conjugated with ligand, which serves as an easy substrate for the receptors present on the macrophage surface. The purpose of present work was to develop intra-articular injectable in situ gelling system containing polymeric nanoparticles, which would have promising advantages over conventional method of treatment. The rationale behind formulating nanoparticle incorporated in situ gel-based system was to ensure localization of the formulation in intra-articular cavity along with sustained release and conjugation of nanoparticles with mannose as ligand to improve uptake by macrophages. Rifampicin standard ATD was formulated into chitosan nanoparticles. Chitosan with 85% degree of deacetylation (DDA) and sodium tripolyphosphate (TPP) as the crosslinking agent was used for preparing nanoparticles. The percent entrapment was found to be about 71%. The prepared nanoparticles were conjugated with mannose. Conjugation of ligand was ascertained by performing Fourier transformed infrared spectroscopy. The particle size was found to be in the range of 130-140 nm and zeta potential of 38.5 mV. Additionally, we performed scanning electron microscopy to characterize the surface morphology of ligand-conjugated nanoparticles. The conjugated chitosan nanoparticles were incorporated into in situ gelling system comprising Poloxamer 407 and HPMC K4M. The gelling system was evaluated for viscosity, gelling characteristics, and syringeability. The drug release from conjugated nanoparticles incorporated in in situ gel was found to be about 70.3% at the end of 40 h in simulated synovial fluid following zero-order release kinetics. Based on the initial encouraging results obtained, the nanoparticles are being envisaged for ex vivo cellular uptake study using TB-infected macrophages.

Single-mode polymer optical waveguides with air cladding, supported only by a narrow fin, were designed and fabricated by direct laser writing technique. The waveguides offer low bending losses and high confinement with increasing core diameter.

Wastewater flowing in streams and nallahs across India carries several trace metals, including metalloid arsenic (As), which are considered serious environmental contaminants due to their toxicity, and recalcitrant nature. In this study, we determined the phytoremediation of As by Eichhornia crassipes (Mart.) Solms either alone or in association with plant growth-promoting rhizobacteria. Pseudomonas and Azotobacter inoculation to E. crassipes resulted in enhanced As removal compared to uninoculated control. Co-inoculation with a consortium of Pseudomonas, Azotobacter, Azospirillum, Actinomyces, and Bacillus resulted in a higher As (p < 0.05) phytoaccumulation efficiency. P. aeruginosa strain jogii was found particularly effective in augmenting As removal by E. crassipes. Our findings indicate that the synergistic association of E. crassipes and various rhizobacteria is an effective strategy to enhance removal of As and thus may be utilized as an efficient biological alternative for the removal of this metalloid from wastewaters.

In present work, Ce 3+ activated Sm 3+ doped lead alumino borate glasses have been synthesized by melt quench method. Photoluminescence spectra were measured under different excitation wavelengths. The co-doped samples show enhanced Sm 3+ ions emission at the cost of Ce 3+ emission with the increasing Ce 3 + ions concentration which shows that Ce 3+ is acting as a sensitizer. This kind of luminescent behavior is discussed with respect to energy transfer process. The investigation based on excitation spectra and decay curves demonstrated that the energy transfer is nonradiative in nature taking place between Ce 3+ and Sm 3+ clusters. It is governed by dipole–dipole interactions as explained in terms of donor lifetime. The results showed that the white light has been achieved under excitation at 400 nm when concentration of Ce 3+ is in the range of 0.5–1.0 mol%. An efficient energy transfer from Ce 3+ to Sm 3+ ions (up to around 42%) with decay times approaching 22 ns has been observed at 400 nm excitation. The UV–Vis absorption spectra shows an increase in intensity and a significant red-shift of the optical absorption edge with increasing rare earth ions concentration in lead alumino borate glass and the FTIR study depicts the conversion of trigonal BO 3 units into more stable tetrahedral BO 4 units.

The success of bedaquiline as an anti-tubercular agent for the treatment of multidrug-resistant tuberculosis has validated the ATP synthesis pathway and in particular ATP synthase as an attractive target. However, limitations associated with its use in the clinic and the drug–drug interactions with rifampicin have prompted research efforts towards identifying alternative ATP synthesis inhibitors with differentiated mechanisms of action. A biochemical assay was employed to screen AstraZeneca's corporate compound collection to identify the inhibitors of mycobacterial ATP synthesis. The high-throughput screening resulted in the identification of 2,4-diaminoquinazolines as inhibitors of the ATP synthesis pathway. A structure–activity relationship for the quinazolines was established and the knowledge was utilized to morph the quinazoline core into quinoline and pyrazolopyrimidine to expand the scope of chemical diversity. The morphed scaffolds exhibited a 10-fold improvement in enzyme potency and over 100-fold improvement in selectivity against inhibition of mammalian mitochondrial ATP synthesis. These novel compounds were bactericidal and demonstrated growth retardation of Mycobacterium tuberculosis in the acute mouse model of tuberculosis infection.

This study focuses on alkali oxide (lithium and sodium) glasses with an aim to explore suitable host for cerium ions which will enhance the optical properties like UV blocking efficiency. Conventional melt quench method was employed for making these glasses. FTIR results show conversion of BO3 to BO4 units and development of CeO4 groups with addition of CeO2. The increase in density values (2.10 to 2.67 g/cm3 for sodium glasses and 2.04 to 2.75 g/cm3 for Lithium glasses) and decrease in band gap values (3.16 to 2.40 eV for sodium glasses and 3.28 to 2.08 eV for Lithium glasses) in both glass systems confirm the modifier role of CeO2. Hardness of lithium-based glasses (1366.91 Kg/mm2) at 4 mol% of CeO2 is higher than the glasses containing sodium (1007.21 Kg/mm2). The obtained values of refractive index and transmittance show better suitability of CeO2 incorporated lithium glasses in some optical applications.

We report the discovery of benzothiazoles, a novel anti-mycobacterial series, identified from a whole cell based screening campaign. Benzothiazoles exert their bactericidal activity against Mycobacterium tuberculosis (Mtb) through potent inhibition of decaprenylphosphoryl-β-d-ribose 2'-oxidase (DprE1), the key enzyme involved in arabinogalactan synthesis. Specific target linkage and mode of binding were established using co-crystallization and protein mass spectrometry studies. Most importantly, the current study provides insights on the utilization of systematic medicinal chemistry approaches to mitigate safety liabilities while improving potency during progression from an initial genotoxic hit, the benzothiazole N-oxides (BTOs) to the lead-like AMES negative, crowded benzothiazoles (cBTs). These findings offer opportunities for development of safe clinical candidates against tuberculosis. The design strategy adopted could find potential application in discovery of safe drugs in other therapy areas too.

In this paper an attempt has been made to correlate the structural modifications and luminescence efficiencies by changing the environment of the glass network by modifying oxides. Sm3+ doped lead borate (SPB) and lead cadmium alumino borate (SCPB) glasses have been fabricated by melt quench technique at high temperature. The glass samples are characterized by XRD, FTIR, optical absorptions, fluorescence and density measurements. The effect of Sm3+ ion and glass host interaction on the emission spectra has been discussed in the view of the ionicity and covalency of hosts. The ratio of the intensities of electric to magnetic dipole emissions are calculated by varying both the concentration of the Sm3+ ion and the composition of the glass matrix. The XRD profile of all the glasses confirms their amorphous nature and FTIR spectrum shows the presence of BO3 and BO4 groups. These glasses have shown strong absorption bands in the visible (VIS and NIR) region and emit strong orange red wavelengths when excited by ultraviolet light. The concentration quenching has been noticed and ascribed to energy transfer through cross-relaxation between Sm3+ ions. Shifting of UV absorption edge towards longer wavelength with addition of Sm2O3 concentration has been observed. Incorporation of Al2O3 and CdO in 2nd glass system is responsible for strong effect on luminescence of the present glass system. Based on these results, an attempt has been made to throw some light on the relationship between the structural modifications and luminescence efficiencies in two different glass hosts as a laser active medium in the visible region. Moreover the optical basicity values were theoretically determined along with covalent behavior of two glass systems.

A total of 14 microbial isolates werecharacterized and out of 14, IS1 and IS14 were observed to be most effective because of their high relative growth and resistance against heavy metals. Further, these two isolates were assessed for their ability to remove Zinc and Lead from medium amended with heavy metals. IS1, Bacillus thuringiensis strain "Simi" (Accession number KF 916618.1) was found to be more effective as compared to IS14, Bacillus subtilis strainPSB (Accession number KF 279045.1) for the remediation of heavy metals. IS1 showed mean of 54% biodegradation efficacy in the first three days and from day 4 onwards the mean percentage of biodegradation efficacy decreased to around 31%. The results of the present study showed that the metal resistant bacteria can be used for heavy metal bioaccumulation.

The key to shortening tuberculosis (TB) drug regimen lies in eliminating the reservoir of non-replicating persistent (NRP) Mycobacterium tuberculosis (Mtb). Pyrazinamide (PZA) is the only known drug used as part of a combination therapy that is believed to kill NRP Mtb and achieve sterilization. PZA is active only under low pH screening conditions. Screening and identification of NRP-active anti-TB compounds are severely limited because compounds are usually inactive under regular assay conditions. In an effort to design novel NRP-active anti-TB compounds, we used pyrazinamide as a core and hybridized it with the fragments derived from marketed drugs. One of these designs, compound 8, was a hybrid with fluoroquinolone. This compound exhibited >10 fold improvement in NRP activity under low pH condition as compared to pyrazinamide and a modest activity (0.8 log10 kill) under nutritionally starved NRP condition. Furthermore, compound 8 was active against fluoroquinolone-resistant strains and did not show any activity in a DNA supercoiling assay (gyrase inhibition), suggesting that its mechanism of action is not that of the parent fluoroquinolone. These results provide a novel avenue in the exploration of new chemotypes that are active against non-replicating Mtb.

A newly isolated strain Pseudomonas fluorescens (Accession number KF 279042.1) have potential in diesel degradation and can be recommended for bioremediation of sites that are contaminated with diesel. This bacterium was characterized on the basis of microbiological, biochemical and molecular analysis. Bacterial growth optimization was studied based on carbon source, nitrogen source, pH and temperature. The strain was selected based on its ability to show growth in medium containing diesel. In addition, optimum temperature and pH for increased growth by the isolate were found to be 37 o C and pH 8.0 indicating the maximum utilization of diesel. At the same time, production of protease and urease enzymes during the utilization of diesel was also assayed following the standard procedures.

An efficient method for C-N bond formation via aza-Michael addition of γ-aminopropylsilatranes to substituted N-phenylmaleimides under mild conditions is described. The five receptors enclosing the maleimide moiety have been synthesized by the aza-Michael addition to strong nucleophile γ-aminopropylsilatrane producing silatranes possessing substituted N-phenylsuccinimide at the axial position without any catalyst. All the compounds have been characterized by elemental analysis, spectroscopic techniques and thermo-gravimetric analysis. The synthesized compounds have been screened for possible antimicrobial properties and results have shown modest activity.

The CeO2–BaO–B2O3 glasses containing different concentrations of CeO2 show that decrease in optical band gap and shift of band edge towards higher wavelength are due the presence of Ce4+ and BO4 groups after gamma irradiation. It is also found that transmittance of the glasses increases after gamma ray exposure. FTIR measurement confirms the conversion of three fold borate BO3 to tetrahedral BO4 groups. The density and covalency of the glasses increases slightly after gamma irradiation. The observed changes were negligible which shows the radiation hardness of these glasses.

Type II topoisomerases are well conserved across the bacterial species, and inhibition of DNA gyrase by fluoroquinolones has provided an attractive option for treatment of tuberculosis (TB). However, the emergence of fluoroquinolone-resistant strains of Mycobacterium tuberculosis (Mtb) poses a threat for its sustainability. A scaffold hopping approach using the binding mode of novel bacterial topoisomerase inhibitors (NBTIs) led to the identification of a novel class of benzimidazoles as DNA gyrase inhibitors with potent anti-TB activity. Docking of benzimidazoles to a NBTI bound crystal structure suggested that this class of compound makes key contacts in the enzyme active site similar to the reported NBTIs. This observation was further confirmed through the measurement of DNA gyrase inhibition, and activity against Mtb strains harboring mutations that confer resistance to aminopiperidines based NBTIs and Mtb strains resistant to moxifloxacin. Structure-activity relationship modification at the C-7 position of the left-hand side ring provided further avenue to improve hERG selectivity for this chemical series that has been the major challenges for NBTIs.

DNA gyrase is a clinically validated target for developing drugs against Mycobacterium tuberculosis (Mtb). Despite the promise of fluoroquinolones (FQs) as anti-tuberculosis drugs, the prevalence of pre-existing resistance to FQs is likely to restrict their clinical value. We describe a novel class of N-linked aminopiperidinyl alkyl quinolones and naphthyridones that kills Mtb by inhibiting the DNA gyrase activity. The mechanism of inhibition of DNA gyrase was distinct from the fluoroquinolones, as shown by their ability to inhibit the growth of fluoroquinolone-resistant Mtb. Biochemical studies demonstrated this class to exert its action via single-strand cleavage rather than double-strand cleavage, as seen with fluoroquinolones. The compounds are highly bactericidal against extracellular as well as intracellular Mtb. Lead optimization resulted in the identification of potent compounds with improved oral bioavailability and reduced cardiac ion channel liability. Compounds from this series are efficacious in various murine models of tuberculosis.

A novel pyrazolopyridone class of inhibitors was identified from whole cell screening against Mycobacterium tuberculosis (Mtb). The series exhibits excellent bactericidality in vitro, resulting in a 4 log reduction in colony forming units following compound exposure. The significant modulation of minimum inhibitory concentration (MIC) against a Mtb strain overexpressing the Rv3790 gene suggested the target of pyrazolopyridones to be decaprenylphosphoryl-β-D-ribose-2'-epimerase (DprE1). Genetic mapping of resistance mutation coupled with potent enzyme inhibition activity confirmed the molecular target. Detailed biochemical characterization revealed the series to be a noncovalent inhibitor of DprE1. Docking studies at the active site suggest that the series can be further diversified to improve the physicochemical properties without compromising the antimycobacterial activity. The pyrazolopyridone class of inhibitors offers an attractive non-nitro lead series targeting the essential and vulnerable DprE1 enzyme for the discovery of novel antimycobacterial agents to treat both drug susceptible and drug resistant strains of Mtb.

We propose a refractive index sensor, based on grating-assisted directional coupler, by comprising two coupled asymmetric strip waveguides with a top-loaded grating structure. We have studied variation of the sensitivity with the waveguide parameters to optimize the design of the sensor. The proposed sensor is an on-chip device with a high refractive index sensitivity of 104nm/RIU with $ \pm $ 140 nm fabrication tolerance, which is more than two times higher than the reported work, and the sensor can also achieve the ultrahigh sensitivity 105nm/RIU with the fabrication tolerance $ \pm $ 13nm. The sensor has large dynamic range from refractive index 1.0 to 1.55. We have also studied the propagation loss due to side wall roughness of the strip waveguide and found that it does not significantly affect sensor performance.

Herbicide atrazine is a broad spectrum herbicide, used worldwide to protect the crops from weeds, but overuse of atrazine have caused the huge environmental problems from few decades. So it is very essential to study and develop the lab based analytical methods, which are important for the detection of atrazine in environment as well as in biological media. In this study we have collected the soils samples from farm fields and extracted the atrazine by Soxhlet method. Also we have extracted the atrazine from formulated grade considered as standard/pure sample in our study. Both extracted/standard and atrazine samples were characterized by UV and FTIR analysis. Further thin layer chromatography was run to check the purity of soil extracted sample.

CeO2 doped lead borate (CE) and lead alumino borate (CEA) glasses are prepared by melt quench method at high temperature. The main luminescence band of 5d–4f transition of Ce3+ ions with maxima at around 489 nm of Ce3+ ions in these glasses has been observed, along with red shift and larger stokes shift, which shows that the covalency of the rare earth to oxygen bond increases with the increase in CeO2 content at the expense of Al2O3. Shifting of UV absorption edge towards longer wavelength and a decrease in band gap with increase in CeO2 concentration in both the glass systems has been observed. Moreover densification and stabilization of glass network has been observed which is due to conversion of BO3 units to more compact and stable BO4 units. This covalency effect and the formation of BO4 groups with addition of CeO2 and incorporation of Al2O3 content are responsible for clear effect on luminescence of the present glass system. Moreover the optical basicity values were theoretically determined along with density and molar volume.

Samarium doped lithium aluminium borate glasses have been prepared by conventional melt quench technique and their detailed spectroscopic analysis has been done. The structural analysis has been done by using FTIR studies and density is measured by Archimedes method. The UV–vis–NIR absorption spectra show an increase in intensity of different transitions from the ground level 6 H 5/2 to various 2S+1 L J levels with an increase in samarium concentration at the expense of aluminium. The fluorescence spectra show several transitions from 4 G 5/2 to various 6 H J levels along with 4 F 3/2 to 6 H J and 4 G 7/2 to 6 H 5/2 .

Organophosphate pesticides are the ester forms of phosphoric acid usually considered as secure for agriculture uses due to their relatively fast degradation rates. Organophosphorus pesticides have been extensively used in the area of agriculture to manage insect or pests of a number of economically important crops. Organophosphate pesticides are well-known as the inhibitor of acetylcholinesterase activity, not in insects only, but can also affect the nervous system of other organisms as well as humans. Organophosphorus pesticides are not restricted to anticholinesterase action, but comprise genotoxicity and teratogenicity including other environmental and ecological adverse impact. Such severe health and ecological consequences signify a requirement for a better understanding of the fate of organophosphates in the environment. By kept all these things in mind we have written a review on organophosphorus pesticides. In this review we have previewed the different methods of spectroscopic methods of detection including UV-visible, X-ray, Mass analysis, NMR, electrochemical analysis (sensor based) and FTIR. Among all these mass and electrochemical studies were flourished till date and considered as advanced techniques for the analysis of other pesticides also.

The paper undertakes the preparation of Aluminium oxide doped Lithium borate glasses and characterizes to investigate the physical and optical studies of these glasses using density and UV-Visible spectroscopy. Results had been obtained with the help of FTIR Spectra in our previous work which indicate that Al2O3 acts as a network modifier by converting three coordinated boron atoms [ BO3 ] to four coordinated boron atoms [ BO4 ]. The effect of aluminium content on the optical properties of the present glass system has been studied from the optical absorption spectra. It shows the shifting of the band edge towards the higher wavelength and that there is corresponding decrease in the band gap, which is due to the conversion of BO3 to BO4 units. The evaluation of the compact structure of prepared glass samples with the presence of [ BO4 ] groups has been made in terms of the physical properties such as density and molar volume. It is also confirmed by average boron-boron separation results. The research findings confirm that the addition of Aluminium oxide increases the covalent value and corresponding decrease in ionicity behaviour.

Honey is considered as natural and healthy product that has a highly concentrated solution of a complex mixture of carbohydrates. The quality of a honey depends on its geographical and botanical origin. Therefore, classification of honey according to geographical origin is of great interest. In this study, it is aimed to develop classification models of honey harvested in India based on geographical and botanical origin via GIS analysis. Seventy-seven honey samples were taken from different regions of North India (Punjab, Uttar Pradesh and Rajasthan States) and characterization was carried out on the basis of their quality parameters (moisture content, color, hydroxymethylfurfural (HMF), total reducing sugars, sucrose and fructose/glucose ratio) and these parameters were mapped and interpolated with GIS technologies.

x V 2 O 5 – x CeO 2 –(30− x )PbO–(70− x ) B 2 O 3 glasses are synthesized by using the melt quench technique. The number of studies such as XRD, density, molar volume, optical band gap, refractive index and FTIR spectroscopy are employed to characterize the glasses. The band gap decreases from 2.20 to 1.78 eV and density increases from 3.49 to 4.25 g/cm 3 . FTIR spectroscopy reveals that incorporation of V 2 O 5 in glass network helps to convert the structural units of [BO 3 ] into [BO 4 ]. At higher concentration of vanadium, VO vibration of [VO 5 ] structural units and V–O–V vibration are present. The bond ionicity of glasses increases with incorporation of V 2 O 5 contents.

A concentrated review on the toxicology of inorganic mercury together with an extensive review on the neurotoxicology of methylmercury is presented. The challenges of using inorganic mercury in dental amalgam are reviewed both regarding the occupational exposure and the possible health problems for the dental patients. The two remaining "mysteries" of methylmercury neurotoxicology are also being reviewed; the cellular selectivity and the delayed onset of symptoms. The relevant literature on these aspects has been discussed and some suggestions towards explaining these observations have been presented.

The structural and optical analysis of glasses is carried out by XRD, FTIR, density and UV visible spectroscopic measurement techniques. XRD results have confirmed the glassy nature of the samples. The FTIR spectral analysis reveals that with the combined presence of ZnO and CeO 2 contents in Al 2 O 3 –PbO–B 2 O 3 glasses, more BO 3 groups are transformed into BO 4 . The optical analysis reveals that optical band gap energy decreases more for CeO 2 –ZnO–Al 2 O 3 –PbO–B 2 O 3 glasses (from 2.28 to 1.84 eV). The presence of CeO 2 and ZnO in the glass samples causes more compaction of the borate network due to the formation of more BO 4 groups and the presence of ZnO 4 groups, which results an increase in density, refractive index and decrease of molar volume.

Glass samples of compositions 20PbO–80B 2 O 3 and x WO 3 —(20− x ) ZnO–20PbO–60B 2 O 3 with x varying from 0% to 10% mole fraction are prepared by the melt quench technique. Decrease in the band gap from 2.86 to 2.16 eV for ZnO–PbO–B 2 O 3 glasses with an increase in the WO 3 content has been observed and discussed. The FTIR spectral studies have pointed out the conversion of structural units of BO 3 to BO 4 and WO 4 to WO 6 with the presence of W–O–W vibration of tungsten and incorporation of ZnO 4 structural units of zinc in these glasses. The increase in density from 2.75 to 4.03 gcm −3 for ZnO–PbO–B 2 O 3 glasses is observed with an increase in WO 3 content. Due to the formation of WO 6 , WO 4 and BO 4 units, changes in the atomic structure with WO 3 composition are observed and discussed.

Methylmercury (MeHg), an environmental toxicant primarily found in fish and seafood, poses a dilemma to both consumers and regulatory authorities, given the nutritional benefits of fish consumption versus the possible adverse neurological damage. Several studies have shown that MeHg toxicity is influenced by a number of biochemical factors, such as glutathione (GSH), fatty acids, vitamins, and essential elements, but the cellular mechanisms underlying these complex interactions have not yet been fully elucidated. The objective of this paper is to outline the cellular response to dietary nutrients, as well as to describe the neurotoxic exposures to MeHg. In order to determine the cellular mechanism(s) of toxicity, the effect of pretreatment with biochemical factors (e.g., N-acetyl cysteine, (NAC); diethyl maleate, (DEM); docosahexaenoic acid, (DHA); selenomethionine, SeM; Trolox) and MeHg treatment on intercellular antioxidant status, MeHg content, and other endpoints was evaluated. This paper emphasizes that the protection against oxidative stress offered by these biochemical factors is among one of the major mechanisms responsible for conferring neuroprotection. It is therefore critical to ascertain the cellular mechanisms associated with various dietary nutrients as well as to determine the potential effects of neurotoxic exposures for accurately assessing the risks and benefits associated with fish consumption.

Methylmercury (MeHg), an environmental toxicant primarily found in fish and seafood poses a dilemma to both consumers and regulatory authorities given the nutritional benefits of fish consumption vs. possible adverse neurological damage caused by MeHg. The present study addresses whether supplementation with 6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid (Trolox), alters the neuro-oxidative effects of MeHg in C6-glioma and B35-neuronal cell lines. As indicators of cytotoxicity, reduced glutathione (GSH), reactive oxygen species (ROS) and mitochondrial activity (MTT) were measured. The cellular mercury (Hg) content was measured with high resolution-inductively coupled plasma mass spectrometry (HR-ICPMS). The amount of MeHg-induced ROS was significantly reduced (p0.05) after treatment with 50muM Trolox in C6 glial cell line. However, treatment with Trolox did not induce any significant increase in GSH levels or MTT activity in either of the cell lines. In addition, treatment with Trolox did not induce any significant changes in intracellular MeHg levels. The MeHg and Trolox treated C6 glial cell line differed significantly (p0.05) from the B35 cell line for MTT, ROS and GSH activity. These findings provide experimental evidence that preincubation with Trolox prevents MeHg-induced ROS generation in C6 glial cell line by quenching of free radicals and not by changes in intracellular GSH or MeHg content.

Among several yeasts isolated from dried flowers of Woodfordia fruticosa, Pichia anomala produced a high titre of cell-bound phytase. The optimization of fermentation variables led to formulation of media and selection of cultural variables that supported enhanced phytase production. The enzyme productivity was very high in fed batch fermentation in air-lift fermentor as compared to that in stirred tank fermentor. Amelioration in the cell-bound phytase activity was observed when yeast cells were permeabilized with Triton-X-100. The enzyme is thermostable and acid stable with broad substrate specificity, the characteristics that are desirable for enzymes to be used in the animal feed industry. The phytase-encoding gene was cloned and sequenced. The 3D structure of the enzyme was proposed by comparative modeling using phytase of Debaryomyces occidentalis (50% sequence identity) as template. When broiler chicks, and fresh water and marine fishes were fed with the feed supplemented with yeast biomass containing phytase, improvement in growth and phosphorus retention, and decrease in the excretion of phosphorus in the faeces were recorded. The cell-bound phytase of P. anomala could effectively dephytinize wheat flour and soymilk.

The effect of methylmercury (MeHg) on reactive oxygen species (ROS) induction in neural cell lines was measured by the fluorescent probe, chloro methyl derivative of di-chloro di-hydro fluoresceindiacetate (CMH2DCFDA). Three different MeHg concentrations (5, 10 and 25 microM) and time periods (30, 50 and 90 min) were studied in C6-glial and B35-neuronal cell lines. In addition, the relationship between MeHg-induced ROS and cell density (day 3 vs. day 4) was also explored. The 14C-labelled MeHg measurements were done to determine the cell associated-MeHg content. At 30 and 50 min exposure, a significant increase (p

Trace element analysis of human hair has the potential to reveal retrospective information about an individual's nutritional status and exposure. As trace elements are incorporated into the hair during the growth process, longitudinal segments of the hair may reflect the body burden during the growth period. We have evaluated the potential of human hair to indicate exposure or nutritional status over time by analysing trace element profiles in single strands of human hair. The hair strands from five healthy and occupationally unexposed subjects were cut into 1-cm long segments starting from the scalp. By using high-resolution inductively coupled plasma mass spectrometry (HR-ICP-MS), we achieved profiles of 12 elements in single strands of human hair, namely, Ag, As, Au, Cd, Cu, Hg, Fe, Pb, Se, Sr, U and Zn. We have shown that trace element analysis along single strands of human hair can yield information about essential and toxic elements, and for some elements, can be correlated with seasonal changes in diet and exposure. The information obtained from the trace element profiles of human hair in this study substantiates the potential of hair as a biomarker.

The extracellular acid phosphatase-encoding Arxula adeninivorans APHO1 gene was isolated using degenerated specific oligonucleotide primers in a PCR screening approach. The gene harbours an ORF of 1449 bp encoding a protein of 483 amino acids with a calculated molecular mass of 52.4 kDa. The sequence includes an N-terminal secretion sequence of 17 amino acids. The deduced amino acid sequence exhibits 54% identity to phytases from Aspergillus awamori, Asp. niger and Asp. ficuum and a more distant relationship to phytases of the yeasts Candida albicans and Debaryomyces hansenii (36-39% identity). The sequence contains the phosphohistidine signature and the conserved active site sequence of acid phosphatases. APHO1 expression is induced under conditions of phosphate limitation. Enzyme isolates from wild and recombinant strains with the APHO1 gene expressed under control of the strong A. adeninivorans-derived TEF1 promoter were characterized. For both proteins, a molecular mass of approx. 350 kDa, corresponding to a hexameric structure, a pH optimum of pH 4.8 and a temperature optimum of 60 degrees C were determined. The preferred substrates include p-nitrophenyl-phosphate, pyridoxal-5-phosphate, 3-indoxyl-phosphate, 1-naphthylphosphate, ADP, glucose-6-phosphate, sodium-pyrophosphate, and phytic acid. Thus the enzyme is a secretory acid phosphatase with phytase activity and not a phytase as suggested by strong homology to such enzymes.

Statistical experimental designs were applied for the optimization of cell-bound phytase production by Pichia anomala in a cost-effective cane molasses medium. Using Plackett–Burman design, cane molasses, urea and inoculum density were identified as significant factors and these factors were subsequently optimized using a central composite design. The optimum variables that supported maximum enzyme titre were 8% cane molasses, 0.4% urea and 2% inoculum density. The validity of the optimized variables was verified in shake-flasks as well as in a laboratory fermenter. An overall 5- and 1.6-fold enhancement in phytase titres (324–1689 U/g DYB) and biomass production (6.4–10 g/l) were attained due to optimization, respectively.

The present investigation was aimed at producing a thermostable and neutral glucoamylase (amyloglucosidase, EC 3.2.1.3) by a thermophilic mould, Thermomucor indicae-seudaticae in submerged cultivation and testing its applicability in starch saccharification. Parametric optimization resulted in the secretion of 30,000 U/l of glucoamylase in a synthetic medium (5% soluble starch, 0.1% yeast extract, 0.05% K2HPO4 and 0.01% MgSO4· 7H2O) using 5 × 106 spores/50 ml of a 3-day-old inoculum at 40 °C and 250 rev/min in shake flasks in 48 h. The enzyme secretion was not affected to any significant extent by the tested additives and detergents. A 1.7-fold increase in glucoamylase secretion was attained when T. indicae-seudaticae was grown in a laboratory fermenter. The enzyme alone catalysed the hydrolysis of soluble starch to an extent of 65%. A prior treatment of starch with thermostable α-amylase and amylopullulanase, followed by glucoamylase, resulted in a greater extent of hydrolysis, 79 and 91%, respectively.

Isolation of biologically active fractions and compounds from the roots of Withania somnifera, a plant used extensively as a constituent of rasayana, in Ayurveda and to test their adaptogenic activity on stress indices using the cold-hypoxia-restraint (C-H-R) model.Bioactivity-guided fractionation of an aqueous extract of the roots of Withania somnifera led to the isolation of a new species of withanolide 1-oxo-5beta, 6beta-epoxy-witha-2-ene-27-ethoxy-olide. Structure elucidation, was carried out using proton nuclear magnetic resonance, infrared (IR), ultraviolet (UV), and mass spectroscopic analysis. Stress-related indices were evaluated, namely serum creatine phosphokinase (CPK) activity, serum lactate dehydrogenase (LDH) activity, serum corticosterone levels, and serum lipid peroxidation (LPO) levels.There was a significant decrease in a serum CPK, LDH, and LPO levels in animals pretreated with (1) fraction-I (20 mg/kg body weight), (2) 1-oxo-5beta, 6beta-epoxy-witha-2-ene-27-ethoxy-olide (2.5 mg/kg body weight) in comparison to control when subjected to C-H-R stress.The results show that the a new species of withanolide, 1-oxo-5beta, 6beta-epoxy-witha-2-ene-27-ethoxy-olide (compound-1) could prove to be an effective agent to counteract C-H-R stress.

The effect of various doses of sodium tellurite (0.4, 0.8, and 2.0 mg/kg body weight, orally) on the activity of antioxidant enzymes (glutathione peroxidase, glutathione reductase, glutathione-S-transferase, and catalase) and content of glutathione and thiobarbituric acid reactive substances (TBARSs) in the cerebrum, cerebellum, and brainstem of male albino mice was studied after 15 d of treatment. All of the doses of tellurium (0.4, 0.8, and 2.0 mg/kg body weight, orally) have depleted the activity of antioxidant enzymes and the content of glutathione dose dependently in the cerebrum, cerebellum, and brainstem and it was significant with the dose of 2.0 mg/kg. On the other hand, the 2.0-mg/kg dose of tellurium has significantly elevated the content of TBARSs in the cerebrum and cerebellum. The 0.8-mg/kg dose of tellurium has significantly depleted the activities of glutathione peroxidase in the cerebrum and brainstem, glutathione-S-transferase in the cerebrum and cerebellum, catalase in the brainstem, and the content of glutathione in the cerebrum and cerebellum. In contrast, this dose has significantly elevated the content of TBARSs in the cerebrum and cerebellum. However, the depletion in the activity of glutathione reductase with various doses of sodium tellurite was not significant in any brain part of mice. The result suggests that sodium tellurite differentially affects the antioxidant status within various parts of the mice brain.

The bacterial peptidoglycan biosynthesis pathway provides multiple targets for antibacterials, as proven by the clinical success of β-lactam and glycopeptide classes of antibiotics. The Mur ligases play an essential role in the biosynthesis of the peptidoglycan building block, N-acetyl-muramic acid-pentapeptide. MurC, the first of four Mur ligases, ligates l-alanine to UDP-N-acetylmuramic acid, initiating the synthesis of pentapeptide precursor. Therefore, inhibiting the MurC enzyme should result in bacterial cell death. Herein, we report a novel class of pyrazolopyrimidines with subnanomolar potency against both Escherichia coli and Pseudomonas aeruginosa MurC enzymes, which demonstrates a concomitant bactericidal activity against efflux-deficient strains. Radio-labeled precursor incorporation showed these compounds selectively inhibited peptidoglycan biosynthesis, and genetic studies confirmed the target of pyrazolopyrimidines to be MurC. In the presence of permeability enhancers such as colistin, pyrazolopyrimidines exhibited low micromolar MIC against the wild-type bacteria, thereby, indicating permeability and efflux as major challenges for this chemical series. Our studies provide biochemical and genetic evidence to support the essentiality of MurC and serve to validate the attractiveness of target for antibacterial discovery.

Diarylthiazole (DAT), a hit from diversity screening, was found to have potent antimycobacterial activity against Mycobacterium tuberculosis (Mtb). In a systematic medicinal chemistry exploration, we demonstrated chemical opportunities to optimize the potency and physicochemical properties. The effort led to more than 10 compounds with submicromolar MICs and desirable physicochemical properties. The potent antimycobacterial activity, in conjunction with low molecular weight, made the series an attractive lead (antibacterial ligand efficiency (ALE)>0.4). The series exhibited excellent bactericidal activity and was active against drug-sensitive and resistant Mtb. Mutational analysis showed that mutations in prrB impart resistance to DAT compounds but not to reference drugs tested. The sensor kinase PrrB belongs to the PrrBA two component system and is potentially the target for DAT. PrrBA is a conserved, essential regulatory mechanism in Mtb and has been shown to have a role in virulence and metabolic adaptation to stress. Hence, DATs provide an opportunity to understand a completely new target system for antimycobacterial drug discovery.

Pantothenate kinase (PanK) catalyzes the phosphorylation of pantothenate, the first committed and rate-limiting step toward coenzyme A (CoA) biosynthesis. In our earlier reports, we had established that the type I isoform encoded by the coaA gene is an essential pantothenate kinase in Mycobacterium tuberculosis , and this vital information was then exploited to screen large libraries for identification of mechanistically different classes of PanK inhibitors. The present report summarizes the synthesis and expansion efforts to understand the structure-activity relationships leading to the optimization of enzyme inhibition along with antimycobacterial activity. Additionally, we report the progression of two distinct classes of inhibitors, the triazoles, which are ATP competitors, and the biaryl acetic acids, with a mixed mode of inhibition. Cocrystallization studies provided evidence of these inhibitors binding to the enzyme. This was further substantiated with the biaryl acids having MIC against the wild-type M. tuberculosis strain and the subsequent establishment of a target link with an upshift in MIC in a strain overexpressing PanK. On the other hand, the ATP competitors had cellular activity only in a M. tuberculosis knockdown strain with reduced PanK expression levels. Additionally, in vitro and in vivo survival kinetic studies performed with a M. tuberculosis PanK ( Mt PanK) knockdown strain indicated that the target levels have to be significantly reduced to bring in growth inhibition. The dual approaches employed here thus established the poor vulnerability of PanK in M. tuberculosis .

4-Aminoquinolone piperidine amides (AQs) were identified as a novel scaffold starting from a whole cell screen, with potent cidality on Mycobacterium tuberculosis (Mtb). Evaluation of the minimum inhibitory concentrations, followed by whole genome sequencing of mutants raised against AQs, identified decaprenylphosphoryl-beta-D-ribose 2'-epimerase (DprE1) as the primary target responsible for the antitubercular activity. Mass spectrometry and enzyme kinetic studies indicated that AQs are noncovalent, reversible inhibitors of DprE1 with slow on rates and long residence times of similar to 100 min on the enzyme. In general, AQs have excellent leadlike properties and good in vitro secondary pharmacology profile. Although the scaffold started off as a single active compound with moderate potency from the whole cell screen, structure-activity relationship optimization of the scaffold led to compounds with potent DprE1 inhibition (IC50 < 10 nM) along with potent cellular activity (MIC = 60 nM) against Mtb.

A cellular activity-based screen on Mycobacterium tuberculosis (Mtb) H37Rv using a focused library from the AstraZeneca corporate collection led to the identification of 2-phenylindoles and arylsulphonamides, novel antimycobacterial scaffolds. Both the series were bactericidal in vitro and in an intracellular macrophage infection model, active against drug sensitive and drug resistant Mtb clinical isolates, and specific to mycobacteria. The scaffolds showed promising structure-activity relationships; compounds with submicromolar cellular potency were identified during the hit to lead exploration. Furthermore, compounds from both scaffolds were tested for inhibition of known target enzymes or pathways of antimycobacterial drugs including InhA, RNA polymerase, DprE1, topoisomerases, protein synthesis, and oxidative-phosphorylation. Compounds did not inhibit any of the targets suggesting the potential of a possible novel mode of action(s). Hence, both scaffolds provide the opportunity to be developed further as leads and tool compounds to uncover novel mechanisms for tuberculosis drug discovery.

Treatment of tuberculosis (TB) is impaired by the long duration and complexity of therapy and the rising incidence of drug resistance. There is an urgent need for new agents with improved efficacy, safety, and compatibility with combination chemotherapies. Oxazolidinones offer a potential new class of TB drugs, and linezolid—the only currently approved oxazolidinone—has proven highly effective against extensively drug-resistant (XDR) TB in experimental trials. However, widespread use of linezolid is prohibited by its significant toxicities. AZD5847, a novel oxazolidinone, demonstrates improved in vitro bactericidal activity against both extracellular and intracellular M. tuberculosis compared to that of linezolid. Killing kinetics in broth media and in macrophages indicate that the rate and extent of kill obtained with AZD5847 are superior to those obtained with linezolid. Moreover, the efficacy of AZD5847 was additive when tested along with a variety of conventional TB agents, indicating that AZD5847 may function well in combination therapies. AZD5847 appears to function similarly to linezolid through impairment of the mycobacterial 50S ribosomal subunit. Future studies should be undertaken to further characterize the pharmacodynamics and pharmacokinetics of AZD5847 in both in vitro and animal models as well is in human clinical trials.

Methylmercury (MeHg) is a ubiquitous environmental contaminant which produces well-defined neuropathologic alterations in the central nervous system. The cerebellum and visual cortex are the two primary targets of MeHg-induced neurotoxicity in both humans and mammals, and these targets are also reflected in the clinical symptoms. In the cerebellum, granule cells are extremely sensitive to MeHg-induced neurotoxicity, whereas neighboring Purkinje cells are spared, although they accumulate as much or more MeHg as compared to the cerebellar granule cells. The current review discusses several innate characteristics of each of these two cell types which may contribute to the differential selectivity of MeHg.

Mercury accumulates in all neural cells, yet methylmercury (MeHg) seems to preferentially accumulate in glial cells, such as astrocytes and microglia. Both the cell types are known targets of MeHg poisonings. Recent studies suggest that these cell types exhibit cell-specific responses to this organometal on a highly variable and distinct temporal axis. In general, in vitro cell culture studies have shown that induction of reactive oxygen species (ROS) generation and attenuation of intracellular glutathione (GSH) levels occur most rapidly in microglia, and within minutes of exposure. In contrast, the astrocytes respond on a more protracted time course (hours, not minutes). Our recent studies also suggest that a key regulatory transcription factor NF-E2-related factor 2 (Nrf2) is upregulated and translocated into the microglial nucleus within minutes of exposure to MeHg, while in astrocytes the response occurs at a later time point (hours post exposure). Combined with evidence microglia accumulate significantly higher MeHg levels and possess a lower reductive capacity (e.g., GSH levels) vs. astrocytes, we posit that the unique sensitivities of the two cell types to MeHg reflects cell-specific biochemical and physiological characteristics.