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Antibiograms gives an overview of the cumulative susceptibility of formal antibiotics to bacterial isolates, which reflects the portion of each bacterium susceptible to a given antibiotic formulation by using antimicrobial susceptibility testing. The objective of this study is to gather and analyse data from drug utilization evaluation (DUE) studies and antimicrobial susceptibility tests in order to create an antibiogram toolkit that will help clinicians to select appropriate antimicrobial agents for initial empirical antibiotic therapy at point of care settings and avoid irrational use of antibiotics.A prospective interventional study was conducted at tertiary care hospital, biological samples of infectious patients were collected from various wards as per ClinicalLaboratory Standards Institute CLSI M39-A4 guidelines. Antimicrobial susceptibility results were analysed using WHONET software. Antibiotic stewardship committee was formed and involved in monitoring the usage of antibiotics, measuring outcomes, collecting feedback and finding the scope for improving the application of antibiogram toolkit in the hospital. Antibiotic usage tracking method was followed to know the level of adherence to the prescribing guidelines by the health care professionals.A total of 157 samples were obtained from various wards of the hospital. In that, Escherichia coli, Staphylococcus aureus and Klebsiella Pneumoniae were isolated in significant numbers. Antibacterial susceptibility results were collected, an initial antibiogram was developed for 18 antibacterial agents with respect to 3 gram-positive (+) and 1 gram-negative (-) organisms. 90% of prescribers mentioned that the antibiogram was useful, and 76% of them adhered to the guidelines. 26% were not adhered due to the patient-related factors.In our study, we have used qualitative and quantitative evaluation of drug utilization (DUE) reports to understand the existing prescribing pattern of antibiotics and setting target organisms and antibacterials to develop the hospital antibiogram. Combining DUE studies and antibiogram development was helpful in implementing effective antibiotic policies for the hospital. Further, this study pattern will be continued on a yearly basis and focused on developing cumulative antibiograms to understand the changes in resistance pattern of antimicrobials and utilization of antibiotics in the hospital.

To determine experimentally how the multiple folding pathways of a protein differ, in the order in which the structural parts are assembled, has been a long-standing challenge. To resolve whether structure formation during folding can progress in multiple ways, the complex folding landscape of monellin has been characterized, structurally and temporally, using the multisite time-resolved FRET methodology. After an initial heterogeneous polypeptide chain collapse, structure formation proceeds on parallel pathways. Kinetic analysis of the population evolution data across various protein segments provides a clear structural distinction between the parallel pathways. The analysis leads to a phenomenological model that describes how and when discrete segments acquire structure independently of each other in different subensembles of protein molecules. When averaged over all molecules, structure formation is seen to progress as α-helix formation, followed by core consolidation, then β-sheet formation, and last end-to-end distance compaction. Parts of the protein that are closer in the primary sequence acquire structure before parts separated by longer sequence.

The NtrC family of proteins senses external stimuli and accordingly stimulates stress and virulence pathways via activation of associated σ

NtrC family of proteins sense external stimuli and accordingly stimulate stress and virulence pathways via activation of associated σ54-dependent RNA polymerases. Here, we establish that MopR, an NtrC protein, harbors a dynamic bi-directional electrostatic network that connects the phenol pocket to two distal regions, namely the “G-hinge” and the “allo-steric-linker”. While G-hinge influences the entry of phenol, the allosteric-linker passes the signal to the downstream ATPase domain. Phenol binding induces a rewiring of the electrostatic connections by eliciting dynamic allostery, and it was demonstrated that perturbation of the core relay residues results in a complete loss of ATPase stimulation. A mutation of the G-hinge,∼20Å from the phenol pocket, demonstrated altered flexibility by shifting the pattern of conformational states accessed, leading to a protein with 7-fold enhanced phenol binding ability and enhanced transcriptional activation. A global analysis illustrates that dynamic allostery-driven conserved community networks are universal and evolutionarily conserved across species.

α-Synuclein (α-Syn) aggregation and amyloid formation is directly linked with Parkinson's disease pathogenesis. However, the early events involved in this process remain unclear. Here, using the in vitro reconstitution and cellular model, we show that liquid-liquid phase separation of α-Syn precedes its aggregation. In particular, in vitro generated α-Syn liquid-like droplets eventually undergo a liquid-to-solid transition and form an amyloid hydrogel that contains oligomers and fibrillar species. Factors known to aggravate α-Syn aggregation, such as low pH, phosphomimetic substitution and familial Parkinson's disease mutations, also promote α-Syn liquid-liquid phase separation and its subsequent maturation. We further demonstrate α-Syn liquid-droplet formation in cells. These cellular α-Syn droplets eventually transform into perinuclear aggresomes, the process regulated by microtubules. This work provides detailed insights into the phase-separation behaviour of natively unstructured α-Syn and its conversion to a disease-associated aggregated state, which is highly relevant in Parkinson's disease pathogenesis.

The main objective of this work was to synthesize, characterize and evaluate the anticancer activity of novel pyrimidine derivatives. The present investigation was undertaken to synthesize pyrimidine derivatives containing pyrrole nucleus The compounds 4-[aminomethyl]-N-(4-methyl-3-{[4-(1H-pyrrol-2-yl) pyrimidin-2-yl]amino}phenyl) benzamide (13f) and 4-[(propylamino) methyl]-N-(4-methyl-3-{ [4-(1H- pyrrol-2-yl) pyrimidin-2 -yl] amino} phenyl) benzamide (13h) was prepared by conventional method. All the synthesized compounds were characterized by spectral (IR, NMR and MS) methods. The synthesized compounds were evaluated for their in vitro anticancer activity against non-small cell lung cancer A549 cell line by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. All the synthesized compounds showed characteristic peaks in FTIR, 1H NMR and Mass spectral analysis. In vitro anticancer activity revealed that 13f and 13h showed more potent anticancer activity as compared to the standard drug sunitinib. We designed and synthesized novel pyrimidine derivatives by conventional method. The anticancer activity determined by MTT assay showed compound 13f and 13h can be developed as a potential anticancer agent.

The reaction coordinates of a molecular photo-switch 2-(4′-diethylamino-2′-hydroxyphenyl)-1H-imidazo-[4,5-b]pyridine (DHP) were tuned with nanoparticles and surfactants.

The effect of water, confinement and confined water on the proton transfer of 3,5-bis(2-hydroxyphenyl)-1H-1,2,4-triazole (bis-HPTA) was investigated. Water alters the proton transfer process. At higher pH, an anion is formed in water and it undergoes intermolecular proton transfer and forms a keto tautomer. Confinement of molecule in β-cyclodextrin affects the intramolecular proton transfer. It also prevents the intermolecular proton transfer of the anionic form. In reverse micelle, the molecule resides in the interfacial region and interacts with bound water. The intermolecular hydrogen bond of the surfactants opens the intramolecular hydrogen bond in the weaker β-ring of bis-HPTA. It led to single tautomer emission from bis-HPTA. An increase in water amount enhances the relative amount of trans-enol, but predominantly tautomer emission is observed.

Liquid-liquid phase separation (LLPS) and subsequent liquid-to-solid transition is implicated in membraneless organelles formation as well as disease associated protein aggregation. However, how liquid-to-solid transition is initiated inside a liquid droplet remains unclear. Here, using studies at single droplet resolution, we show that liquid-to-solid transition of α-synuclein (α-Syn) liquid droplets is associated with significant changes in the local microenvironment as well as secondary structure of the protein, which is prominently observed at the center of the liquid droplets. With the ageing of liquid droplets, the “structured” core at the center gradually expands and propagates over entire droplets. Further, during droplet fusion, smaller, homogeneous droplets progressively dissolve and supply proteins to the larger, heterogeneous droplets containing solid-like core at their center. The present study will significantly help to understand the physical mechanism of LLPS and liquid-to-solid transition in biological compartmentalization as well as in protein aggregation associated with human neurodegenerative disorders.Abstract Figure

The effect of solvents and supramolecular hosts on the binding of metal ion with an excited state intramolecular proton transfer (ESIPT) active fluorophore 2-(2'-hydroxyphenyl)benzoxazole (HPBO) are investigated to scrutinize a possible metal ion carry and delivery system. The fluorophore forms strong fluorescent complex with Zn

Fluorescent nucleic acid base mimics serve as excellent site-specific and real-time reporters of the local and global dynamics. In this work, using the fluorescent guanine mimic 6-methylisoxanthopterin (6-MI), we unravel the differential dynamics of replication fork barrier/terminator sequences (RFB1 and RFB3) mediated by fork blocking protein (Fob1). By strategic and site-specific incorporation of this probe, we show that 6-MI is able to capture the changes in global dynamics exhibited by Fob1 and aids in distinguishing between varied architectural forms like double-stranded DNA versus Holliday junctions (HJs). This is important as these barriers are hotspots for recombination. Fluorescence lifetime and anisotropy decay studies further revealed that Fob1 strongly dampens the dynamics in double-stranded RFB1, and the sequence inherently possesses lesser flexibility in comparison to RFB3. We show that 6-MI can probe the differential oligomeric status of Fob1 in response to various architectures, that is, double-stranded versus HJs. This work highlights the unique advantages of 6-MI as a probe when incorporated in nucleic acid frameworks.

To obtain proper insight into how structure develops during a protein folding reaction, it is necessary to understand the nature and mechanism of the polypeptide chain collapse reaction, which marks the initiation of folding. Here, the time-resolved fluorescence resonance energy transfer technique, in which the decay of the fluorescence light intensity with time is used to determine the time evolution of the distribution of intra-molecular distances, has been utilized to study the folding of the small protein, monellin. It is seen that when folding begins, about one-third of the protein molecules collapse into a molten globule state (IMG), from which they relax by continuous further contraction to transit to the native state. The larger fraction gets trapped into a metastable misfolded state. Exit from this metastable state occurs via collapse to the lower free energy IMG state. This exit is slow, on a time scale of seconds, because of activation energy barriers. The trapped misfolded molecules as well as the IMG molecules contract continuously and slowly as structure develops. A phenomenological model of Markovian evolution of the polymer chain undergoing folding, incorporating these features, has been developed, which fits well the experimentally observed time evolution of distance distributions. The observation that the "wrong turn" to the misfolded state has not been eliminated by evolution belies the common belief that the folding of functional protein sequences is very different from that of a random heteropolymer, and the former have been selected by evolution to fold quickly.

Understanding the properties of the unfolded state under folding conditions is of fundamental importance for gaining mechanistic insight into folding as well as misfolding reactions. Toward achieving this objective, the folding reaction of a small protein, monellin, has been resolved structurally and temporally, with the use of the multisite time-resolved FRET methodology. The present study establishes that the initial polypeptide chain collapse is not only heterogeneous but also structurally asymmetric and nonuniform. The population-averaged size for the segments spanning parts of the β-sheet decreases much more than that for the α-helix. Multisite measurements enabled specific and nonspecific components of the initial chain collapse to be discerned. The expanded and compact intermediate subensembles have the properties of a nonspecifically collapsed (hence, random-coil-like) and specifically collapsed (hence, globular) polymer, respectively. During subsequent folding, both the subensembles underwent contraction to varying extents at the four monitored segments, which was close to gradual in nature. The expanded intermediate subensemble exhibited an additional very slow contraction, suggestive of the presence of non-native interactions that result in a higher effective viscosity slowing down intrachain motions under folding conditions.

Flexibility and dynamics in polypeptides and proteins give rise to conformational and structural heterogeneity. Quantification of the level of heterogeneity is essential for providing deeper understanding of molecular mechanisms in protein folding. Fluorescence lifetime distribution generated by the maximum entropy method (MEM) provides an unbiased estimate of intramolecular distance distribution. This article discusses several examples where MEM-generated lifetime distribution brings out site-specific conformational and structural heterogeneity in proteins. Use of the information on intamolecular distance distribution in revealing molecular mechanisms of protein folding is also discussed.

Protein folding/unfolding transitions between the native (N) and unfolded (U) states are usually describable as two-state, only because of the dominant presence of the N and/or U states, because of which high energy intermediates remain undetected. Delineation of the cooperativity underlying these transitions, and characterization of high energy intermediates that are populated sparsely, have been difficult challenges, especially under equilibrium conditions, and require the use of a sensitive probe that reports on both the structures and population distributions of the partially unfolded intermediates. In this study, the use of multisite time-resolved FRET to monitor structural change in five specific segments of the small protein monellin, has brought out local deviations from two-state behavior during unfolding. It is shown that in some segments of the protein structure, denaturant-induced unfolding proceeds first by gradual expansion of the N state, then by an all-or-none transition from the N state ensemble to the U state ensemble, followed finally by expansion of the U state. Segments encompassing the sole helix appear, however, to unfold completely through a gradual transition from the N to U states. Finally, it is shown that equilibrium unfolding of monellin is not only heterogeneous, but that the degree of non-cooperativity differs between the sole α-helix and different parts of the β-sheet.

A low molecular weight organogelator containing 3,5-substituted-1,3,4-oxadiazole and tetrazole units was synthesized and characterized. This compound is only soluble in DMSO and forms a stable gel. The solution and gel exhibit a blue light emission. The gel was characterized by atomic force microscopy, field-emission scanning electron microscopy, 1H NMR and fluorescence measurements. The gel to solution interconversion was reversible for many cycles of heating and cooling. The compound in solution exhibited a high selectivity for the detection of picric acid, a common explosive and water pollutant. Fluorimetric titration studies with nitro explosive compounds revealed that the emission of the compound was red shifted in response to the addition of picric acid, and exhibited a shifting of fluorescence from blue to green. Theoretical and experimental studies revealed that the sensing is due to the complexation of the picrate anion with the protonated fluorophore. The shifting of emission in response to picric acid in the visible region is ideal for the naked eye detection of explosives and therefore it is promising in comparison to the detection methods based on fluorescence quenching.

Chitosan was fabricated via gelation method using CaBr2.xH2O/methanol solution and was studied as a potential adsorbent (MCh) in adsorbing anionic synthetic dyes like Bromophenol blue (BB), Direct blue 6 (DB) and Congo red (CR) from single (one dye species at a time) and multi (having two dyes; binary and all three dyes; tertiary) adsorptive systems. Physico-chemical modifications of MCh surface prior and post modification and dye adsorption were evaluated using scanning electron microscopy, Energy-dispersive X-ray spectroscopy, powder X-ray diffraction analysis, surface area analysis and Fourier-transformed infrared spectroscopy. Influential parameters influencing the adsorption process viz. initial pH of dye solution, MCh dosage, adsorption temperature and initial concentration of dye species were optimised. Adsorptive studies involving single adsorptive setups verified formation of sorbate's (dye species) monolayer over the sorbent's (MCh) surface via chemisorption; as established by Langmuir isotherm and pseudo-second order kinetics model analysis. Theoretical maximum adsorption capacities of MCh for BB, DB and CR was found to be 81.301 mg/g, 163.934 mg/g and 75.758 mg/g, respectively. Meanwhile, for all multi-adsorptive systems, competitive Langmuir isotherm model verified antagonistic behaviour of an individual dye over other dye adsorption over MCh surface in their respective adsorptive systems. Thermodynamics of the sorbate-sorbent interaction was exothermic, spontaneous, with elevated degree of disorderedness; concluding the interaction as thermodynamically favourable. Co-existing metal cations and anionic salts had minimal effect on MCh's adsorption efficiency. Phytotoxicity assay via germination of Vigna mungo seeds verified the efficacy of the adsorbent in eliminating the dye species from single and multi-adsorptive systems.

In aqueous solution, 2-(4-fluorophenylamino)-5-(2,4-dihydroxybenzeno)-1,3,4-thiadiazole (FABT) was found to emit dual emission and the longer wavelength emission was assigned to the combination of aggregation and conformational change. In a number of molecules that possess an intramolecular hydrogen bond between the proton donor and the acceptor, the longer wavelength emission is often observed due to the emission from the tautomer formed by excited state intramolecular proton transfer (ESIPT). Therefore, an analogue of FABT, 2-phenylamino-5-(2-hydroxybenzono)-1,3,4-thiadiazole (PHBT), was synthesized to determine the origin of the longer wavelength emission. The luminescence of PHBT and its methoxy derivatives was studied and compared with that of FABT. Theoretical calculations were also performed on both FABT and PHBT. Based on the experimental and theoretical investigations, the nonexistence of the keto tautomer in the ground state and the origin of the longer wavelength emission are divulged.

A simple, accurate, specific and precise UV Spectrophotometric method has been developed for estimation of Valsartan in bulk and pharmaceutical formulation. The λ max of Valsartan in ethanol was found to be 249 nm. The drug exhibited the linearity in the concentration range of 10-60μg/mL with correlation coefficient of 0.999. the % recovery of the drug for the proposed was found to be between 99.82 to 100.48%. The % RSD values found to be less than 2. No interference was observed in the presence of common pharmaceutical excipients. The method was validated as per ICH guidelines. The developed method was successfully employed for the estimation of Valsartan in pharmaceutical dosage form. The developed method was cost effective with less consumption of solvents and can be used for routine analysis.

A highly stable, spontaneous, and reversible α-helical-structure formation in recombinant and chemically modified α-synuclein protein is demonstrated for the first time in a water-less (1.5 % w/w H2 O) polymer surfactant environment. Using a combination of circular dichroism and ATR-FTIR spectroscopy, we show that whilst native α-synuclein in aqueous solution shows a predominant unordered conformation (≈64 %), mixing with polyethylene glycol based anionic polymer surfactant (PS) and removing water reveals a 25 % unordered, 25 % α-helical, and 27 % β-sheet structure. Interestingly, bioconjugation of native α-synuclein with a diamine molecule, to increase the positive charge on the protein chain, and subsequent electrostatic coupling with the PS forms a conjugate with a retained unordered structure. Removal of water from this system provides a highly stable α-helical (≈74 %) water-less liquid system. Surprisingly, the α-helical-to-unordered state transition is completely reversible and is achieved at ≈25-30 w/w% of water in the system. Moreover, the α-helix shows an extraordinary temporal stability (>6 months) in a waterless environment.

α-Synuclein (α-Syn) aggregation and amyloid formation is directly linked with Parkinson's disease pathogenesis. However, the early events involved in this process remain unclear. Here, using the in vitro reconstitution and cellular model, we show that liquid-liquid phase separation of α-Syn precedes its aggregation. In particular, in vitro generated α-Syn liquid-like droplets eventually undergo a liquid-to-solid transition and form an amyloid hydrogel that contains oligomers and fibrillar species. Factors known to aggravate α-Syn aggregation, such as low pH, phosphomimetic substitution and familial Parkinson's disease mutations, also promote α-Syn liquid-liquid phase separation and its subsequent maturation. We further demonstrate α-Syn liquid-droplet formation in cells. These cellular α-Syn droplets eventually transform into perinuclear aggresomes, the process regulated by microtubules. This work provides detailed insights into the phase-separation behaviour of natively unstructured α-Syn and its conversion to a disease-associated aggregated state, which is highly relevant in Parkinson's disease pathogenesis.

SUMMARYα-Synuclein (α-Syn) aggregation and amyloid formation is directly linked with Parkinson’s disease (PD) pathogenesis. However, the early events involved in this process remain unclear. Here, using in vitro reconstitution and cellular model, we show that liquid-liquid phase separation (LLPS) of α-Syn precedes its aggregation. In particular, in vitro generated α-Syn liquid-like droplets eventually undergo a liquid-to-solid transition and form amyloid-hydrogel containing oligomers and fibrillar species. Factors known to aggravate α-Syn aggregation such as low pH, phosphomimic substitution, and familial PD mutation also promote α-Syn LLPS and its subsequent maturation. We further demonstrate α-Syn liquid droplet formation in cells, under oxidative stress. These cellular α-Syn droplets eventually transform into perinuclear aggresomes, the process regulated by microtubules. The present work provides detailed insights into the phase separation behavior of natively unstructured α-Syn and its conversion to a disease-associated aggregated state, which is highly relevant in PD pathogenesis.

Access control has made a long way from 1960s. With the advent changes of technologies pertaining to location transparency in storage of data, there arises different access control scenarios. Cloud storage, the predominant storage that is being in use currently, also paves way to various access control problems. Though there are various access control mechanisms such as RBAC, ABAC, they are designed on the user’s perspective such as the role held by the user or other attributes assigned to the user. A new access control mechanism called object relationship based access control (RoBAC) has been developed based on the relations held among the users. The policy decision of access control is based on the relationship among the classes followed in the Java programming. Results have shown that this model best suits various scenarios in the cloud environment, and it also shows that the time for making decision either to allow or to deny is reduced compared to the existing system.

Background The diagnosis of temporomandibular disorders (TMDs), specifically TMD myalgia, can be challenging. Although the anatomy of the jaw muscles has been extensively characterized, a structural difference in TMD-myalgia individuals has never been demonstrated. Tendons are a highly specialized tissue with a predominately mechanical function. Collagen fibrils, the main contributor to tendon mechanical properties, begin macroscopic failure at 8% to 10% strain. The characterization of tendon/muscle abnormalities in individuals with chronic, painful TMD myalgia will lay the groundwork for utilizing noninvasive magnetic resonance imaging (MRI) for screening and objective monitoring of patients with TMD myalgia. A structural marker unique to TMD myalgia will aid in its diagnosis and treatment. Objective(s) This study aimed to determine differences in the tendon/muscle volume ratio of the temporalis muscle in patients with TMD myalgia compared with age-/gender-matched controls without facial pain. Study Design This was a retrospective, observational study of the temporalis muscle and tendon on MRI images. The comparison between groups was based on a voxel-based morphometry of anatomic T1-weighted MRI images and analyzed for differences in the tendon/muscle volume ratio. The study included at least 14 patients per group to detect a 5% difference in tendon/muscle volume ratio. An intraclass correlation coefficient was used to evaluate the intrarater test–retest reliability. General linear models were used to test whether the outcome measures (muscle/tendon volume, muscle/tendon T1 signal intensity, tendon/muscle ratio) are different between groups. Results Our pilot data demonstrated similar muscle volumes but significantly smaller tendon volumes and signal intensity when comparing patients with TMD myalgia with healthy controls (P Discussion/Conclusions Preliminary data suggest that chronic TMD myalgia may be associated with structural abnormalities of the temporalis tendon. Should the temporalis tendon/muscle volume ratio prove to be a reliable marker, this metric may be used to evaluate different treatment modalities in a noninvasive manner.

A series of 1-(3-benzyl-4-oxo-3 H- quinazolin-2-yl)-4-(substituted) thiosemicarbazides ( AS1–AS10 ) were obtained by the reaction of 2-hydrazino-3-benzyl quinazolin-4(3 H) -one ( 6 ) with different dithiocarbamic acid methyl ester derivatives. The key intermediate, 3-benzyl-2-thioxo-2,3-dihydro-1 H -quinazolin-4-one ( 4 ), was obtained by the reaction of benzyl amine ( 1 ) with carbon disulphide and sodium hydroxide in dimethyl sulphoxide to give sodium dithiocarbamate, which was methylated with dimethyl sulphate to yield the dithiocarbamic acid methyl ester ( 2 ) and condensation with methyl anthranilate ( 3 ) in ethanol yielded the desired compound ( 4 ) via the thiourea intermediate. The SH group of compound ( 4 ) was methylated in the favourable nucleophilic displacement reaction with hydrazine hydrate, which afforded 2-hydrazino-3-benzyl-3 H- quinazolin-4-one ( 6 ). The IR, and 1H- and 13C-NMR spectra of these compounds showed the presence of peaks due to thiosemicarbazides, carbonyl (C=O), NH and aryl groups. The molecular ion peaks of the quinazolin-4-one moiety ( m / z 144) were observed in all the mass spectra of the compounds AS1–AS10 . Elemental (C, H, N) analysis satisfactorily confirmed purity and elemental composition of the synthesized compounds. All the synthesized compounds were screened for their antimicrobial activity against selective gram positive and gram negative bacteria by agar dilution method. In the present study, compounds AS8 and AS9 emerged as the most active compounds of the series.

In the present study, a greener approach to tanning process based on Gallic acid (GA: Trihydroxy- benzoic acid) assisted chrome tanning has been attempted. The exhaustion, the thermal stability, mechanical strength and organoleptic properties of tanned leather as well as the evaluation of eco-friendly characteristics were investi- gated. The microshrinkage, differential scanning calori- metric and thermo mechanical analyses show the shrinkage temperature, denaturation temperature and % elongation, respectively, of GA-chrome-tanned leather are more than that of chrome alone. Chrome exhaustion greater than 93 % has been achieved. This high exhaust aid offers fullness and softness to leather compared to chrome alone. The environmental impact assessment reveals that the developed high exhaust chrome tanning process is benefi- cial as significant reduction in total solids content (TSC) such as dissolved solids and suspended solids in the effluent is achieved when compared to tanning with chrome alone. The GA could bring about the enhancement of chromium(III) uptake, significant reduction in TSC resulting in improved environmental, economic and social positive impact.

Autoregulation of blood flow is essential for the preservation of organ function to ensure continuous supply of oxygen and essential nutrients and removal of metabolic waste. This is achieved by controlling the diameter of muscular arteries and arterioles that exhibit a myogenic response to changes in arterial blood pressure, nerve activity and tissue metabolism. Large-conductance voltage and Ca(2+)-dependent K(+) channels (BK channels), expressed exclusively in smooth muscle cells (SMCs) in the vascular wall of healthy arteries, play a critical role in regulating the myogenic response. Activation of BK channels by intracellular, local, and transient ryanodine receptor-mediated "Ca(2+) sparks," provides a hyperpolarizing influence on the SMC membrane potential thereby decreasing the activity of voltage-dependent Ca(2+) channels and limiting Ca(2+) influx to promote SMC relaxation and vasodilation. The BK channel α subunit, a large tetrameric protein with each monomer consisting of seven-transmembrane domains, a long intracellular C-terminal tail and an extracellular N-terminus, associates with the β1 and γ subunits in vascular SMCs. The BK channel is regulated by factors originating within the SMC or from the endothelium, perivascular nerves and circulating blood, that significantly alter channel gating properties, Ca(2+) sensitivity and expression of the α and/or β1 subunit. The BK channel thus serves as a central receiving dock that relays the effects of the changes in several such concomitant autocrine and paracrine factors and influences cardiovascular health. This chapter describes the primary mechanism of regulation of myogenic response by BK channels and the alterations to this mechanism wrought by different vasoactive mediators.

Autoregulation of blood flow is essential for the preservation of organ function to ensure continuous supply of oxygen and essential nutrients and removal of metabolic waste. This is achieved by controlling the diameter of muscular arteries and arterioles that exhibit a myogenic response to changes in arterial blood pressure, nerve activity and tissue metabolism. Large-conductance voltage and Ca(2+)-dependent K(+) channels (BK channels), expressed exclusively in smooth muscle cells (SMCs) in the vascular wall of healthy arteries, play a critical role in regulating the myogenic response. Activation of BK channels by intracellular, local, and transient ryanodine receptor-mediated "Ca(2+) sparks," provides a hyperpolarizing influence on the SMC membrane potential thereby decreasing the activity of voltage-dependent Ca(2+) channels and limiting Ca(2+) influx to promote SMC relaxation and vasodilation. The BK channel α subunit, a large tetrameric protein with each monomer consisting of seven-transmembrane domains, a long intracellular C-terminal tail and an extracellular N-terminus, associates with the β1 and γ subunits in vascular SMCs. The BK channel is regulated by factors originating within the SMC or from the endothelium, perivascular nerves and circulating blood, that significantly alter channel gating properties, Ca(2+) sensitivity and expression of the α and/or β1 subunit. The BK channel thus serves as a central receiving dock that relays the effects of the changes in several such concomitant autocrine and paracrine factors and influences cardiovascular health. This chapter describes the primary mechanism of regulation of myogenic response by BK channels and the alterations to this mechanism wrought by different vasoactive mediators.

Polychlorinated biphenyls (PCBs) comprise a ubiquitous class of toxic substances associated with carcinogenic and tumor-promoting effects as well as neurotoxic properties. Reactive oxygen species, which is produced from PCBs, alters blood–brain barrier (BBB) integrity, which is paralleled by cytoskeletal rearrangements and redistribution and disappearance of tight junction proteins (TJPs) like claudin-5 and occludin. Quercetin, a potent antioxidant present in onion and other vegetables, appears to protect brain cells against oxidative stress, a tissue-damaging process associated with Alzheimer’s and other neurodegenerative disorders. The aim of this study is to analyze the role of quercetin on oxidative stress markers and transcription of transmembrane and cytoplasmic accessory TJPs on cerebrum, cerebellum and hippocampus of female rats exposed to PCBs. Rats were divided into the following four groups. Group I: received only vehicle (corn oil) intraperitoneally (i.p.); group II: received Aroclor 1254 at a dose of 2 mg/kg body weight (bwt)/day (i.p); group III: received Aroclor 1254 (i.p.) and simultaneously quercetin 50 mg/kg bwt/day through gavage and group IV: received quercetin alone gavage. From the experiment, the levels of hydrogen peroxide, lipid peroxidation and thiobarbituric acid reactive substances were observed to increase significantly in cerebrum, cerebellum and hippocampus as 50%, 25% and 20%, respectively, after exposure to PCB, and the messenger RNA expression of TJP in rats exposed to PCBs is decreased and is retrieved to the normal level simultaneously in quercetin-treated rats. Hence, quercetin can be used as a preventive medicine to PCBs exposure and prevents neurodegenerative disorders.

The aim is to study the effect of Tartrazine (E102) - synthetic food colour - on the antioxidant status of testis of Wistar rats. Twelve male Wistar rats were grouped into 2 groups of six each - Control and Tartrazine-treated groups. Control group was orally administered with water alone while the experimental group was orally administered with tartrazine dissolved in water. The treatment was carried out for 60 days and the activities of antioxidant enzymes - superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) and the levels of their cofactors were subsequently determined in the testis, along with histological studies. Activities of the 4 enzymes showed a common decrease with corresponding alterations in their cofactor levels. The colour orally administered to the experimental animals probably would have generated reactive oxygen species (ROS) and H2O2, thereby disrupting the enzymatic antioxidant defense of their testes. Tartrazine is capable of producing free radicals, which in turn cause damage to the cellular compartment system of rat testis.

Large-scale polynomial product computations often used in aerospace applications such as satellite image processing and sensor networks data processing always pose considerable challenge when processed on networked computing systems. With non-zero communication and computation time delays of the links and processors on a networked infrastructure, the computation becomes all the more challenging. In this research, we attempt to investigate the use of a divisible load paradigm to design efficient strategies to minimize the overall processing time for performing large-scale polynomial product computations in compute cloud environments. We consider a compute cloud system with the resource allocator distributing the entire load to a set of virtual CPU instances (VCI) and the VCIs propagating back the processed results to resource allocator for postprocessing. We consider heterogeneous networks in our analysis and we derive fundamental recursive equations and a closed-form solution for the load fractions to be assigned to each VCI. Our analysis also attempts to eliminate any redundant VCI-link pairs by carefully considering the overheads associated with load distribution and processing. Finally, we quantify the performance of the strategies via rigorous simulation studies.

The protective role of lycopene against various toxicants on various organs and its association with decreased oxidative stress seems to be well established. Sertoli cell function in the adult testis determines daily sperm production. Increasing evidence suggests that environmental pollutants including polychlorinated biphenyls (PCBs) are male infertility, which is associated with oxidative stress. Hence, the present study was designed to find out whether PCBs disrupt Sertoli cell function by inducing oxidative stress or endocrine disruption? Whether lycopene attenuates PCBs-induced disruption in Sertoli cells or not? Adult male rats were divided into four (vehicle control, lycopene, PCBs and PCBs + lycopene treated) groups. After the experimental period (30 days), the animals were decapitated for the blood collection and testes were removed for the isolation of Sertoli cells. In PCBs exposure, serum hormones (FSH, testosterone and estradiol), Sertoli cellular receptors (FSHR and AR) were significantly decreased whereas oxidative stress markers (H 2 O 2 and LPO) and ER-s expression in Sertoli cells were significantly increased. Sertoli cell functional proteins such as connexin 43, transferrin and androgen-binding protein expressions and the level of lactate were significantly decreased. However, simultaneous supplementation of lycopene to PCBs-exposed rats significantly decreased the endocrine disruption and oxidative stress in Sertoli cells. The findings point out that lycopene protects the Sertoli cell function by preventing PCBs-induced oxidative stress and endocrine disruption.

The modern libraries are equipped with latest technological developments ranging from digital Archives, repositories, delivery of the net contents and providing seamless global access to the digital information resources. This paper focuses on the importance of library user studies and stresses the required methodological procedures. Keywords: Digital library, ICT, users.

Health science digital library describes the distribution of the digital resources and digital library initiative of the Tamil Nadu Dr. M.G.R. Medical University. It discusses the brief information about the e-resources available in this University. It explains the method of digitization of previous examination question papers of Under Graduate and Post Graduate courses of Medicine. The total number of question papers digitized for all the courses is 17,489 numbers. A total number of 4652 question papers were digitized under the U.G. course (Medical), 3801 for U.G. course (Para Medical), 4678 for the Post Graduate (Medical) course, 1693 for the Post Graduate (Non-Medical), 1377 for Higher Specialties and 1288 Question papers for Diploma courses. Totally around19614 users accessed this e-resource through the University's website from January to December 2007.

This paper attempts to assess the R&D activity and its output in Health Sciences in India for about three decades, 1970 to 2000. Statistical analysis has been carried out using SPSS and other relevant measures. The subjects like General Medicine, Pharmacology, and Biochemistry were identified to be the top ranked 3 sub-disciplines. Objectives have been examined by using the Activity Index (AI). AI for cross comparison has been computed as suggested by Frame, as it characterizes the relative research effort a country devotes to a specific subject field. India’s R&D emphasis is found to be on Biochemistry among the top three sub-disciplines as its AI is found to be 136 compared to General Medicine and Pharmacology with 109 and 87 as AI respectively. However, India’s published literature is quantitatively larger in General Medicine (6016) than in Biochemistry (1091). With the AI found to be more than 100 in General Medicine and Biochemistry, these two subfields seem to reflect higher activities than the worl...

Prostate cancer is a leading cause of death among the aging men. Surgical or radiotherapy is effective when the cancer is confined to the prostate gland but once the cancer spreads beyond the pelvis even chemotherapy and hormonal ablation therapy fails in curing this disease. Our previous studies have shown that diallyl disulfide (DADS) induces cell cycle arrest and also induces apoptosis in PC-3 cells. And now the present study is focused to see whether there is an activation of caspase cascade pathway. Hence, in the present study the apoptotic effect of DADS is studied by Western blot analysis of caspase-3, -9, -10 and Bcl-2, Bad, and Bax protein. The Apoptotic cells were assessed by Hoechst 33342 staining with 25 and 40 microM concentrations of DADS for 24 h. The results have shown that DADS at 25 and 40 microM concentrations has induced the activation of caspases. There is a significant increase in the expression of caspases (3, 9, and 10). The proapoptotic protein Bax has significantly increased at 40 microM of DADS treatment and there is significant increase of Bad protein at both the concentration. Bcl-2 protein has significantly decreased in DADS treated cells. Therefore, the present investigation serves as evidence that DADS may be a therapeutic drug in the treatment of prostate cancer.

The central role of collagen as the major structural fibrous protein in the mammalian extracellular matrix has motivated a significant effort toward the determi- nation of its mechanical properties at all levels, ranging from single monomers and long-chain polymers to a structural element within a biological tissue. However, the stabiliza- tion of collagen against collagenolytic degradation finds sig- nificance in biomedical and industrial applications. Tannins are plant-derived polyphenols that have the ability to inhibit the collagenase activity at minimum concentration. The in- hibitory effect of wattle (Acacia mollissima) and myrobalan (Terminalia chebula) on the action of collagenase against colla- gen was probed in this study. The kinetics of the inhibition of collagenase by wattle and myrobalan was deduced from the extent of hydrolysis of 2-furanacryloyl-L-leucyl-glycyl- L-prolyl-L-alanine. Both wattle and myrobalan tannin exhib- ited competitive modes of inhibition against collagenase. Circular dichroism studies of collagenase on treatment with wattle and myrobalan revealed changes in the secondary structure of collagenase. These results suggest that the tan- nins of A. mollissima and T. chebula extracts facilitated colla- gen stabilization through collagenase inhibition. 2007

Inhibitory effect of green tea polyphenols viz., catechin and epigallocatechin gallate (EGCG) on the action of collagenase against collagen has been probed in this study. Catechin and EGCG treated collagen exhibited 56 and 95% resistance, respectively, against collagenolytic hydrolysis by collagenase. Whereas direct interaction of catechin and EGCG with collagenase exhibited 70 and 88% inhibition, respectively, to collagenolytic activity of collagenase against collagen and the inhibition was found to be concentration dependent. The kinetics of inhibition of collagenase by catechin and EGCG has been deduced from the extent of hydrolysis of (2-furanacryloyl-L-leucyl-glycyl-L-prolyl-L-alanine), FALGPA. Both catechin and EGCG exhibited competitive mode of inhibition against collagenase. The change in the secondary structure of collagenase on treatment with catechin and EGCG has been monitored using circular dichroism spectropolarimeter. CD spectral studies showed significant changes in the secondary structure of collagenase on treatment with higher concentration of catechin and EGCG. Higher inhibition of EGCG compared to catechin has been attributed to the ability of EGCG to exhibit better hydrogen bonding and hydrophobic interaction with collagenase.

Various epidemiological survey suggests that the central nervous system is the target for many environmental contaminants. One among them is Aroclor 1254, a mixture of polychlorinated biphenyls (PCBs) which explore a spectrum of biochemical and neurotoxic responses in humans and laboratory animals. Learning and motor coordination deficits are the profound effects of PCBs which may be related to cerebral dysfunction. The aim of the study is to elicit the protective effect of melatonin (Mel), a potent, blood brain permeable antioxidant against the effect of Aroclor 1254 on the signaling of glutamate-principal excitatory neurotransmitter and brain derived neurotrophic factor (BDNF) in the cerebral cortex of adult rats which plays a key role in brain functions. Adult male Wistar rats were grouped into four and treated intraperitonealy (i.p) Group I with corn oil (Control), Group II with PCBs (2 mg/kg/bwt), Group III with PCBs + Mel (2 mg/kg/bwt + 5 mg/kg/bwt) and Group IV with Mel (5 mg/kg/bwt). The protein expression of glutamate signaling molecules and mRNA expressions of GLAST, BDNF signaling molecules were analyzed. The results suggest that simultaneous melatonin treatment significantly attenuated the NMDA receptor mediated glutamate excitotoxicity and protects the inhibition of BDNF signaling caused by PCBs exposure in cerebral cortex of adult male rats. Schematic pathway illustrating the proposed mechanism by which melatonin protects against A1254 mediated glutamate induced neurodegeneration in the cerebral cortex of adult male rats. PCBs induced neurodegeneration is caused by the overactivation of NMDAR, followed by the activation of voltage dependent calcium channels leading to the increase in intracellular Ca(2+) that stimulates calpain. Calpain inturn inhibits the PKA α and neurtrophin BDNF, its receptor and downstream signaling MAPK pathway leading to neurodegeneration. Melatonin had scavenged the ROS produced by PCBS and decreased the NMDAR expression which inturn protected the cells from neurodegeneration.

The spectral characteristics of trans-2-[4'-(N,N-dimethylamino)styryl]imidazo[4,5-b]pyridine (t-DMASIP-b) have been investigated using absorption and fluorescence techniques, and compared with 2-(4'-N,N-dimethylamino)imidazo[4,5-b]pyridine (DMAPIP-b). The study reveals that introduction of a C[double bond, length as m-dash]C double bond strongly perturbs the photophysics of the system. Unlike DMAPIP-b, t-DMASIP-b emits a single emission in aprotic and protic solvents. The emission occurs from the locally excited state in nonpolar solvents and from a planar intramolecular charge transfer (PICT) state in polar solvents. Multiple linear regression analysis suggests that among the different solvent parameters, the dipolar interaction contributes more to the stabilization of the system in both the ground and excited states. Theoretical calculations suggest that, unlike in DMAPIP-b, proton coupled twisted intramolecular charge transfer (TICT) emission does not occur in t-DMASIP-b. The higher quantum yield obtained in the viscous solvent glycerol is attributed to the restriction of the twisting of the olefinic bond. The photoirradiation of t-DMASIP-b shows that isomerization takes place in all solvents, including viscous glycerol. The theoretically simulated potential energy surface shows that isomerization occurs via a phantom state, which is a nonradiative process. The rise in temperature favors the photoisomerization, thus, the fluorescence quantum yield decreases. The prototropic study indicates that, unlike in DMAPIP-b, the protonation takes place at different places to form the monocations.

The interaction of a few azole derivatives, 2-(4'-N,N-dimethylaminophenyl)benzimidazole, 2-(4'-N,N-dimethylaminophenyl)benzoxazole, 2-(4'-N,N-dimethylaminophenyl)oxazolo[4,5-b]pyridine with bovine serum albumin (BSA) were examined by absorption and fluorescence spectroscopy. The results were compared with the previously studied imidazopyridine derivative 2-(4'-N,N-dimethylaminophenyl)imidazo[4,5-b]pyridine. Displacement studies were carried out with site selective probes to locate the binding site of these ligands. The spectral shifts and the binding constant vary depending on the nature of the ligand. The fluorescence intensity of both oxazole derivatives 2-(4'-N,N-dimethylaminophenyl)benzoxazole and 2-(4'-N,N-dimethylaminophenyl) oxazolo[4,5-b]pyridine increases substantially in the presence of BSA, whereas the intensity of 2-(4'-N,N-dimethylaminophenyl)benzimidazole decreases. However, hypsochromic shift is observed in presence of BSA. The results obtained from the docking studies are also in good agreement with the experimental results. The location and orientation of binding depend upon the nature of the ligand. The studies revealed that apart from hydrophobic interaction, hydrogen bonding also plays a vital role in the molecular binding. Oxazoles have higher binding affinity than imidazoles and substitution of extra nitrogen further increases the binding affinity.