A novel biogenic Allium cepa leaf mediated silver nanoparticles for antimicrobial, antioxidant, and anticancer effects on MCF-7 cell line.

In the present study, Allium cepa leaf extract was utilized to reduce the silver nitrate into the nanoscale range of silver ions (Ag NPs). The biosynthesized Ag NPs were extensively characterized by X-ray diffraction analysis (XRD), Dynamic light scattering analysis (DLS), UV-Visible spectroscopy (UV-vis), Transmission electron microscopy (TEM), Energy dispersive X-ray analysis (EDX) and Fourier transform infrared spectroscopy (FTIR). The antioxidant activity of synthesized Ag NPs was verified by DPPH assay. From the results obtained from XRD and DLS studies, the size of Ag NPs was determined to be around 54.3 nm. The measured zeta potential value of -19.1 mV confirms the excellent stability of biosynthesized Ag NPs. TEM analyses reveal that the biosynthesized Ag NPs have a spherical structure of 13 nm in size. The presence of various functional groups was confirmed through FTIR studies and EDAX verifies the weight percentage of silver content in biosynthesized nanoparticles to be 30.33%. In the present study, anti-cancer activity was carried out by using breast cancer cell line MCF-7. Further, silver nanoparticles exhibited antimicrobial effectiveness against gram-positive Bacillus cereus and gram-negative Escherichia coli. The MTT assay also showed better cytotoxic activity against the MCF- 7 cell line.

Peptidoglycan-treated tumor antigen-pulsed dendritic cells impart complete resistance against tumor rechallenge.

Solid tumors elicit suppressive T cell responses which impair antigen-presenting cell (APC) functions. Such immune suppression results in uncontrolled tumor growth and mortality. Addressing APC dysfunction, dendritic cell (DC)-mediated anti-tumor vaccination was extensively investigated in both mice and humans. These studies never achieved full resistance to tumor relapse. Herein, we describe a repetitive RM-1 murine tumor rechallenge model for recurrence in humans. Using this newly developed model, we show that priming with tumor antigen-pulsed, Toll-like receptor (TLR)2 ligand-activated DCs elicits a host-protective anti-tumor immune response in C57BL/6 mice. Upon stimulation with the TLR2 ligand peptidoglycan (PGN), the tumor antigen-pulsed DCs induce complete resistance to repetitive tumor challenges. Intra-tumoral injection of PGN reduces tumor growth. The tumor resistance is accompanied by increased expression of interleukin (IL)-27, T-box transcription factor TBX21 (T-bet), IL-12, tumor necrosis factor (TNF)-α and interferon (IFN)-γ, along with heightened cytotoxic T lymphocyte (CTL) functions. Mice primed four times with PGN-stimulated tumor antigen-pulsed DCs remain entirely resistant to repeat challenges with RM-1 tumor cells, suggesting complete prevention of relapse and recurrence of tumor. Adoptive transfer of T cells from these mice, which were fully protected from RM-1 rechallenge, confers anti-tumor immunity to syngeneic naive recipient mice upon RM-1 challenge. These observations indicate that PGN-activated DCs induce robust host-protective anti-tumor T cells that completely resist tumor growth and recurrence.

Common and distinct patterns of grey-matter volume alteration in major depression and bipolar disorder: evidence from voxel-based meta-analysis.

Finding robust brain substrates of mood disorders is an important target for research. The degree to which major depression (MDD) and bipolar disorder (BD) are associated with common and/or distinct patterns of volumetric changes is nevertheless unclear. Furthermore, the extant literature is heterogeneous with respect to the nature of these changes. We report a meta-analysis of voxel-based morphometry (VBM) studies in MDD and BD. We identified studies published up to January 2015 that compared grey matter in MDD (50 data sets including 4101 individuals) and BD (36 data sets including 2407 individuals) using whole-brain VBM. We used statistical maps from the studies included where available and reported peak coordinates otherwise. Group comparisons and conjunction analyses identified regions in which the disorders showed common and distinct patterns of volumetric alteration. Both disorders were associated with lower grey-matter volume relative to healthy individuals in a number of areas. Conjunction analysis showed smaller volumes in both disorders in clusters in the dorsomedial and ventromedial prefrontal cortex, including the anterior cingulate cortex and bilateral insula. Group comparisons indicated that findings of smaller grey-matter volumes relative to controls in the right dorsolateral prefrontal cortex and left hippocampus, along with cerebellar, temporal and parietal regions were more substantial in major depression. These results suggest that MDD and BD are characterised by both common and distinct patterns of grey-matter volume changes. This combination of differences and similarities has the potential to inform the development of diagnostic biomarkers for these conditions.

Pairwise contact energy statistical potentials can help to find probability of point mutations.

To adopt a particular fold, a protein requires several interactions between its amino acid residues. The energetic contribution of these residue-residue interactions can be approximated by extracting statistical potentials from known high resolution structures. Several methods based on statistical potentials extracted from unrelated proteins are found to make a better prediction of probability of point mutations. We postulate that the statistical potentials extracted from known structures of similar folds with varying sequence identity can be a powerful tool to examine probability of point mutation. By keeping this in mind, we have derived pairwise residue and atomic contact energy potentials for the different functional families that adopt the (α/ß)8 TIM-Barrel fold. We carried out computational point mutations at various conserved residue positions in yeast Triose phosphate isomerase enzyme for which experimental results are already reported. We have also performed molecular dynamics simulations on a subset of point mutants to make a comparative study. The difference in pairwise residue and atomic contact energy of wildtype and various point mutations reveals probability of mutations at a particular position. Interestingly, we found that our computational prediction agrees with the experimental studies of Silverman et al. (Proc Natl Acad Sci 2001;98:3092-3097) and perform better prediction than iMutant and Cologne University Protein Stability Analysis Tool. The present work thus suggests deriving pairwise contact energy potentials and molecular dynamics simulations of functionally important folds could help us to predict probability of point mutations which may ultimately reduce the time and cost of mutation experiments. Proteins 2016; 85:54-64. © 2016 Wiley Periodicals, Inc.

High frequency of mitochondrial DNA mutations in HIV-infected treatment-experienced individuals.

OBJECTIVES: We recently observed a decrease in deoxyribonucleotide (dNTP) pools in HIV-infected individuals on antiretroviral therapy (ART). Alterations in dNTPs result in mutations in mitochondrial DNA (mtDNA) in cell culture and animal models. Therefore, we investigated whether ART is associated with mitochondrial genome sequence variation in peripheral blood mononuclear cells (PBMCs) of HIV-infected treatment-experienced individuals. METHODS: In this substudy of a case-control study, 71 participants were included: 22 'cases', who were HIV-infected treatment-experienced patients with mitochondrial toxicity, 25 HIV-infected treatment-experienced patients without mitochondrial toxicity, and 24 HIV-uninfected controls. Total DNA was extracted from PBMCs and purified polymerase chain reaction (PCR) products were subjected to third-generation sequencing using the PacBio Single Molecule Real-Time (SMRT) sequencing technology. The sequences were aligned against the revised Cambridge reference sequence for human mitochondrial DNA (NC_012920.1) for detection of variants. RESULTS: We identified a total of 123 novel variants, 39 of them in the coding region. HIV-infected treatment-experienced patients with and without toxicity had significantly higher average numbers of mitochondrial variants per participant than HIV-uninfected controls. We observed a higher burden of mtDNA large-scale deletions in HIV-infected treatment-experienced patients with toxicity compared with HIV-uninfected controls (P = 0.02). The frequency of mtDNA molecules containing a common deletion (mt.δ4977) was higher in HIV-infected treatment-experienced patients with toxicity compared with HIV-uninfected controls (P = 0.06). There was no statistically significant difference in mtDNA variants between HIV-infected treatment-experienced patients with and without toxicity. CONCLUSIONS: The frequency of mtDNA variants (mutations and large-scale deletions) was higher in HIV-infected treatment-experienced patients with or without ART-induced toxicity than in uninfected controls.

Monitoring regional blockade.

This review attempts to draw on the published literature to address three practical clinical questions. First, what means of testing the degree of regional blockade pre-operatively are available, and can eventual success or failure be determined soon after injection? Second, is it possible to predict if a block inserted after the induction of general anaesthesia will be effective when the patient wakes? Third, what features, and what duration, should cause concern when a block does not resolve as expected after surgery? Although the relevant literature is limited, we recommend testing of multiple sensory modalities before surgery commences; temperature and thermographic changes may offer additional early warning of success or failure. There are a number of existing methods of assessing nociception under general anaesthesia, but none has yet been applied to gauge the onset of a regional block. Finally, criteria for further investigation and neurological referral when block symptoms persist postoperatively are presented.

Toll-like receptors and CD40 modulate each other's expression affecting Leishmania major infection.

Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns and results in innate immune system activation that results in elicitation of the adaptive immune response. One crucial modulator of the adaptive immune response is CD40. However, whether these molecules influence each other's expression and functions is not known. Therefore, we examined the effects of TLRs on CD40 expression on macrophages, the host cell for the protozoan parasite Leishmania major. While polyinosinic-polycytidylic acid [poly (I:C)], a TLR-3 ligand, lipopolysaccharide (LPS), a TLR-4 ligand, imiquimod, a TLR-7/8 ligand and cytosine-phosphate-guanosine (CpG), a TLR-9 ligand, were shown to enhance CD40 expression, CD40 stimulation enhanced only TLR-9 expression. Therefore, we tested the synergism between CD40 and CpG in anti-leishmanial immune response. In Leishmania-infected macrophages, CpG was found to reduce CD40-induced extracellular stress-regulated kinase (ERK)1/2 activation; with the exception of interleukin (IL)-10, these ligands had differential effects on CD40-induced IL-1α, IL-6 and IL-12 production. CpG significantly enhanced the anti-leishmanial function of CD40 with differential effects on IL-4, IL-10 and interferon (IFN)-γ production in susceptible BALB/c mice. Thus, we report the first systematic study on CD40-TLR cross-talk that regulated the experimental L. major infection.

The practical management of refractory schizophrenia--the Maudsley Treatment REview and Assessment Team service approach.

OBJECTIVE: To describe a practical approach to the community management of treatment-resistant schizophrenia (TRS). METHOD: A descriptive review of an approach to the assessment and management of patients with TRS, including the community titration of clozapine treatment, and a report of the management recommendations for the first one hundred patients assessed by the Treatment REview and Assessment Team (TREAT). RESULTS: The standardized model for the community assessment, management and titration of clozapine is described. To date, 137 patients have been referred to this service and 100 patients (72%) attended for assessment. Of these, 33 have been initiated on clozapine while fifteen have had clozapine recommended but have not wished to undertake clozapine treatment. Other management options recommended have included augmentation strategies and long-acting injectable antipsychotics. CONCLUSION: The service had increased the number of patients receiving community assessment and initiation of clozapine by five-fold relative to the rate prior to the establishment of the service. The large number of referrals and high attendance rate indicates that there is clinical demand for the model. Systematic evaluation is required to determine the clinical and cost-effectiveness of this model and its potential application to other clinical settings.

Nanodiamond-structured zinc composite coatings with strong bonding and high load-bearing capacity.

The aerospace and automotive industries find that relying solely on the intrinsic resistance of alloys is inadequate to safeguard aircraft and automotive structural components from harsh environmental conditions. While it is difficult to attribute accidents exclusively to coating failure due to the involvement of multiple factors, there are instances where defects in the coating initiate a wear or degradation process, leading to premature and unplanned structural failures. Metallic coatings have been introduced to protect the aircraft mainly from wear due to the extreme temperatures and moisture exposure during their service life. Bare metallic coatings have a limited lifespan and need to be replaced frequently. Herein, the strength and wear resistance of zinc (Zn) coating is enhanced using varying concentrations of diamond particles as an additive in the Zn matrix (Zn-D). The dispersion strengthening mechanism is attributed to the high hardness (70 HRC), and reduced friction-of-coefficient (0.21) and dissipation energy (4.6 × 10-4 J) of electrodeposited Zn-D7.5 (7.5 g l-1 of diamond concentration) composite coating. Moreover, enhanced wear resistance with minimum wear volume (1.12 × 10-3 mm3) and wear rate (1.25 × 10-3 mm3 N-1 m-1) of the Zn-D7.5 composite coating resulted in perfect blending of diamond with Zn. The improved hardness and wear resistance for Zn-D7.5 (optimum 7.5 g l-1 diamond concentration) is due to the steadiness between well-dispersed diamonds in Zn and enrichment in load-bearing ability due to the incorporation of diamond particles. Electronic structure calculations on the zinc-diamond composite models (two configurations adopted) have been performed using the density functional theory (DFT) approach, and the in silico studies appeared to facilitate meaningful and evocative outcomes. Zn-doped diamond (C10@Zn) without hydrogen (H) atoms (binding energy: 418 kcal mol-1, i.e. showing an endothermic reaction and thermodynamically not favourable) was detected to be more stable than the Zn-doped diamond (C10H16@Zn) consisting of hydrogen (H) atoms (binding energy: -33.3 kcal mol-1, i.e. showing an exothermic reaction and thermodynamically preferable). Thus, a composite coating of zinc and diamond can be a suitable candidate for the aerospace and automotive industries.

Role of pretransplant echocardiographic evaluation in predicting outcomes following liver transplantation.

Maintenance of cardiac function is critical to the survival of patients with end-stage liver disease after liver transplantation (LT). We sought to determine whether pre-LT echocardiographic indices of right heart structure and function were independently predictive of morbidity and mortality post-LT. We retrospectively studied 216 consecutive patients who underwent pre-LT 2-dimensional/Doppler echocardiography with subsequent LT from 2007 to 2010. A blinded reader analyzed multiple echocardiographic parameters, including right ventricular structure and function, pulmonary artery systolic pressure (PASP) and the presence and severity of tricuspid regurgitation (TR). On univariate analysis, Model of End-Stage Liver Disease (MELD) score, PASP, presence of ≥mild TR, post-operative renal replacement therapy (RRT) and spontaneous bacterial peritonitis were found to be significant predictors of adverse outcomes. On multivariate analysis, only ≥mild TR was found to predict both patient mortality (p = 0.0024, HR = 3.91, 95% CI: 1.62-9.44) and graft failure (p = 0.0010, HR = 3.70, 95% CI: 1.70-8.06). PASP and MELD correlated with post-LT intensive care unit length of stay (LOS) and, along with hemodialysis, were associated with hospital LOS and time on ventilator. In conclusion, pre-LT echocardiographic assessments of the right heart may be useful in predicting post-LT morbidity and mortality and guiding the selection of appropriate LT candidates.

Measuring endogenous changes in serotonergic neurotransmission in humans: a [11C]CUMI-101 PET challenge study.

Serotonin (5-HT) neurotransmission is implicated in cognitive and emotional processes and a number of neuropsychiatric disorders. The use of positron emission tomography (PET) to measure ligand displacement has allowed estimation of endogenous dopamine release in the human brain; however, applying this methodology to assess central 5-HT release has proved more challenging. The aim of this study was to assess the sensitivity of a highly selective 5-HT(1A) partial agonist radioligand [(11)C]CUMI-101 to changes in endogenous 5-HT levels induced by an intravenous challenge with the selective 5-HT re-uptake inhibitor (SSRI), citalopram, in healthy human participants. We studied 15 healthy participants who underwent PET scanning in conjunction with [(11)C]CUMI-101 after receiving an intravenous infusion of citalopram 10 mg or placebo in a double-blind, crossover, randomized design. Regional estimates of binding potential (BP(ND)) were obtained by calculating total volumes of distribution (V(T)) for presynaptic dorsal raphe nucleus (DRN) and postsynaptic cortical regions. Relative to placebo, citalopram infusion significantly increased [(11)C]CUMI-101 BP(ND) at postsynaptic 5-HT(1A) receptors in several cortical regions, but there was no change in binding at 5-HT(1A) autoreceptors in the DRN. Across the postsynaptic brain regions, citalopram treatment induced a mean 7% in [(11)C]CUMI-101 BP(ND) (placebo 1.3 (0.2); citalopram 1.4 (0.2); paired t-test P=0.003). The observed increase in postsynaptic [(11)C]CUMI-101 availability identified following acute citalopram administration could be attributable to a decrease in endogenous 5-HT availability in cortical terminal regions, consistent with preclinical animal studies, in which acute administration of SSRIs decreases DRN cell firing through activation of 5-HT(1A) autoreceptors to reduce 5-HT levels in postsynaptic regions. We conclude that [(11)C]CUMI-101 may be sensitive to changes in endogenous 5-HT release in humans.

Spectroscopic, Biological, and Topological Insights on Lemonol as a Potential Anticancer Agent.

A monoterpene alcohol known as lemonol was investigated experimentally as well as theoretically in order to gain insights into its geometrical structure, vibrational frequencies, solvent effects on electronic properties, molecular electrostatic potential, Mulliken atomic charge distribution, natural bond orbital, and Nonlinear Optical properties. The frontier molecular orbital energy gap values of 5.9084 eV (gas), 5.9261 eV (ethanol), 5.9185 eV (chloroform), 5.9253 eV (acetone), and 5.9176 eV (diethyl ether) were predicted, and it shows the kinetic stability and chemical reactivity of lemonol. Topological studies were conducted using Multiwfn software to understand the binding sites and weak interactions in lemonol. The antiproliferative effect of lemonol against the breast cancer cell line Michigan Cancer Foundation (MCF-7) was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, while nuclear damage, condensation, and reactive oxygen species generation were identified using acridine orange/ethidium bromide, propidium iodide, and dichlorodihydrofluorescein diacetate staining. The theoretical and experimental findings are highly correlated, confirming the structure, and the results of in vitro studies suggest that lemonol acts as a potent inhibitor against the human breast cancer cell line MCF-7, highlighting its strong antiproliferative activity.

Health care and equity in India.

In India, despite improvements in access to health care, inequalities are related to socioeconomic status, geography, and gender, and are compounded by high out-of-pocket expenditures, with more than three-quarters of the increasing financial burden of health care being met by households. Health-care expenditures exacerbate poverty, with about 39 million additional people falling into poverty every year as a result of such expenditures. We identify key challenges for the achievement of equity in service provision, and equity in financing and financial risk protection in India. These challenges include an imbalance in resource allocation, inadequate physical access to high-quality health services and human resources for health, high out-of-pocket health expenditures, inflation in health spending, and behavioural factors that affect the demand for appropriate health care. Use of equity metrics in monitoring, assessment, and strategic planning; investment in development of a rigorous knowledge base of health-systems research; development of a refined equity-focused process of deliberative decision making in health reform; and redefinition of the specific responsibilities and accountabilities of key actors are needed to try to achieve equity in health care in India. The implementation of these principles with strengthened public health and primary-care services will help to ensure a more equitable health care for India's population.

Short-term SSRI treatment normalises amygdala hyperactivity in depressed patients.

BACKGROUND: Antidepressant drugs such as selective serotonin re-uptake inhibitors (SSRIs) remediate negative biases in emotional processing in depressed patients in both behavioural and neural outcome measures. However, it is not clear if these effects occur before, or as a consequence of, changes in clinical state. METHOD: In the present study, we investigated the effects of short-term SSRI treatment in depressed patients on the neural response to fearful faces prior to clinical improvement in mood. Altogether, 42 unmedicated depressed patients received SSRI treatment (10 mg escitalopram daily) or placebo in a randomised, parallel-group design. The neural response to fearful and happy faces was measured on day 7 of treatment using functional magnetic resonance imaging. A group of healthy controls was imaged in the same way. RESULTS: Amygdala responses to fearful facial expressions were significantly greater in depressed patients compared to healthy controls. However, this response was normalised in patients receiving 7 days treatment with escitalopram. There was no significant difference in clinical depression ratings at 7 days between the escitalopram and placebo-treated patients. CONCLUSIONS: Our results suggest that short-term SSRI treatment in depressed patients remediates amygdala hyperactivity in response to negative emotional stimuli prior to clinical improvement in depressed mood. This supports the hypothesis that the clinical effects of antidepressant treatment may be mediated in part through early changes in emotional processing. Further studies will be needed to show if these early effects of antidepressant medication predict eventual clinical outcome.

Search for identical octapeptides in unrelated proteins: Structural plasticity revisited.

Since proteins are dynamic in nature, they can alter their local structure in response to changes in their environment factors such as temperature, pH, phosphorylation, and binding of other small molecules. These conformational changes are extremely important for the correct folding and functioning of proteins. There are also a number of diseases associated with protein conformational change such as amyloid diseases. To stimulate research into the above factors which specify one conformation over another, different theoretical models have been proposed and tested against sequence similar distant structure protein fragments. In order to simplify the computational complexity of identifying conformational changes in proteins, various local sequence search algorithms were employed and the structural plasticity in unrelated proteins was examined by various research groups. In the present work, we revisit the mechanism of structural plasticity in unrelated proteins with increased number of structures in Protein Data Bank by comparing identical octapeptides in unrelated proteins with dictionary of protein secondary structure extracted from existing experimental data. Our goal is to bring out the influence of hydrophobic residues, hydrophilic residues, flanking residues, difference in secondary structural propensities of surrounding residues, difference in phi-psi angles and local and nonlocal interactions in identical octapeptides adopting different conformations. Also we have used surrounding hydrophobicity, environment dependent interaction energy, atomic mean force potential, structural unit contacts and difference profiles models to explore the factors which cause structural plasticity. The results discussed here may provide insights into protein folding, design and function.

Impact of protein binding cavity volume (PCV) and ligand volume (LV) in rigid and flexible docking of protein-ligand complexes.

The importance of protein binding cavity volume (PCV) and ligand volume (LV) in rigid and flexible docking has been studied in 48 protein-ligand complexes belonging to eight protein families. In continuation of our earlier study on protein flexibility in relationship to PCV and LV, this study analyzes the importance of PCV and LV in the scoring and ranking of ligands in docking experiments. Crystal structures of protein-ligand complexes with varied PCV were chosen for docking ligands of varied volume in each protein family. Docking and scoring accuracy have been evaluated by self and cross docking of ligands to the given protein conformation. Effect of PCV and LV in rigid and flexible docking has been studied both in apo and holo proteins. Rigid docking has performed well when appropriate protein conformation is used. Selecting the proteins with appropriate PCV based on the LV information is suggested for better results in ensemble docking.

Al3+ induced planarization, conformational arrest and metallochromic shift in a pyrimidine dione dye: insight from integrated hybrid quantum-classical calculations.

In order to explore the possibilities of simulating metallochromism by modern molecular modeling, we apply a sequential hybrid quantum-classical approach to a prototype metallochromic system-the Al(3+) ion and pyrimidinedione (PY) dye complex. The complex shows several structural features with relevance for the metallochromism: the PY dye exhibits conformers with dynamical transitions between twisted structures, which are inhibited by the addition of the metal ion leading to planarization and a conformational arrest: the Al(3+) ion behaves like a structure-modifier for both intra and intermolecular degrees of freedom and with respect to the intermolecular solvation shell structure. The sequential approach that we have employed uses DFT/MM molecular dynamics for structure modeling and TDDFT/PCM for property modeling. The computed metallochromic shift between PY and the Al(PY)(3+) complex in DMSO solvent is obtained in excellent agreement with experiment. The results infer optimism for future use of such modeling techniques to design metallochromic indicators.

Application of long-range order to predict unfolding rates of two-state proteins.

Predicting the experimental unfolding rates of two-state proteins and models describing the unfolding rates of these proteins is quite limited because of the complexity present in the unfolding mechanism and the lack of experimental unfolding data compared with folding data. In this work, 25 two-state proteins characterized by Maxwell et al. (Protein Sci 2005;14:602­616) using a consensus set of experimental conditions were taken, and the parameter long-range order (LRO) derived from their three-dimensional structures were related with their experimental unfolding rates ln(k(u)). From the total data set of 30 proteins used by Maxwell et al. (Protein Sci 2005;14:602­616), five slow-unfolding proteins with very low unfolding rates were considered to be outliers and were not included in our data set. Except all beta structural class, LRO of both the all-alpha and mixed-class proteins showed a strong inverse correlation of r = -0.99 and -0.88, respectively, with experimental ln(k(u)). LRO shows a correlation of -0.62 with experimental ln(k(u)) for all-beta proteins. For predicting the unfolding rates, a simple statistical method has been used and linear regression equations were developed for individual structural classes of proteins using LRO, and the results obtained showed a better agreement with experimental results.

Sequence and structural features of binding site residues in protein-protein complexes: comparison with protein-nucleic acid complexes.

BACKGROUND: Protein-protein interactions are important for several cellular processes. Understanding the mechanism of protein-protein recognition and predicting the binding sites in protein-protein complexes are long standing goals in molecular and computational biology. METHODS: We have developed an energy based approach for identifying the binding site residues in protein-protein complexes. The binding site residues have been analyzed with sequence and structure based parameters such as binding propensity, neighboring residues in the vicinity of binding sites, conservation score and conformational switching. RESULTS: We observed that the binding propensities of amino acid residues are specific for protein-protein complexes. Further, typical dipeptides and tripeptides showed high preference for binding, which is unique to protein-protein complexes. Most of the binding site residues are highly conserved among homologous sequences. Our analysis showed that 7% of residues changed their conformations upon protein-protein complex formation and it is 9.2% and 6.6% in the binding and non-binding sites, respectively. Specifically, the residues Glu, Lys, Leu and Ser changed their conformation from coil to helix/strand and from helix to coil/strand. Leu, Ser, Thr and Val prefer to change their conformation from strand to coil/helix. CONCLUSIONS: The results obtained in this study will be helpful for understanding and predicting the binding sites in protein-protein complexes.

Antidiabetic properties of Hibiscus rosa sinensis L. leaf extract fractions on nonobese diabetic (NOD) mouse.

On fractionation the ethanolic extract of H. rosa sinensis leaves, 5 fractions were obtained. Of these, fraction-3 (F3) and fraction-5 (F5) were chosen for detailed investigation on non obese diabetic (NOD) mouse to study anti-diabetic properties because they were more active than others. Serum glucose, glycosylated hemoglobin, triglyceride, cholesterol, blood urea, insulin, LDL, VLDL, and HDL were estimated. Both fractions F3 and F5 on oral feeding (100 and 200 mg/kg body weight) demonstrated insulinotropic nature and protective effect in NOD mice. These fractions may contain potential oral hypoglycemic agent.