Towards Prediction of Metabolic Products of Polyketide Synthases: An In Silico Analysis

Sequence data arising from an increasing number of partial and complete genome projects is revealing the presence of the polyketide synthase (PKS) family of genes not only in microbes and fungi but also in plants and other eukaryotes. PKSs are huge multifunctional megasynthases that use a variety of biosynthetic paradigms to generate enormously diverse arrays of polyketide products that posses several pharmaceutically important properties. The remarkable conservation of these gene clusters across organisms offers abundant scope for obtaining novel insights into PKS biosynthetic code by computational analysis. We have carried out a comprehensive in silico analysis of modular and iterative gene clusters to test whether chemical structures of the secondary metabolites can be predicted from PKS protein sequences. Here, we report the success of our method and demonstrate the feasibility of deciphering the putative metabolic products of uncharacterized PKS clusters found in newly sequenced genomes. Profile Hidden Markov Model analysis has revealed distinct sequence features that can distinguish modular PKS proteins from their iterative counterparts. For iterative PKS proteins, structural models of iterative ketosynthase (KS) domains have revealed novel correlations between the size of the polyketide products and volume of the active site pocket. Furthermore, we have identified key residues in the substrate binding pocket that control the number of chain extensions in iterative PKSs. For modular PKS proteins, we describe for the first time an automated method based on crucial intermolecular contacts that can distinguish the correct biosynthetic order of substrate channeling from a large number of non-cognate combinatorial possibilities. Taken together, our in silico analysis provides valuable clues for formulating rules for predicting polyketide products of iterative as well as modular PKS clusters. These results have promising potential for discovery of novel natural products by genome mining and rational design of novel natural products

A new family of type III polyketide synthases in Mycobacterium tuberculosis

The Mycobacterium tuberculosis genome has revealed a remarkable array of polyketide synthases (PKSs); however, no polyketide product has been isolated thus far. Most of the PKS genes have been implicated in the biosynthesis of complex lipids. We report here the characterization of two novel type III PKSs from M. tuberculosis that are involved in the biosynthesis of long-chain α-pyrones. Measurement of steady-state kinetic parameters demonstrated that the catalytic efficiency of PKS18 protein was severalfold higher for long-chain acyl-coenzyme A substrates as compared with the small-chain precursors. The specificity of PKS18 and PKS11 proteins toward long-chain aliphatic acyl-coenzyme A (C12 to C20) substrates is unprecedented in the chalcone synthase (CHS) family of condensing enzymes. Based on comparative modeling studies, we propose that these proteins might have evolved by fusing the catalytic machinery of CHS and β-ketoacyl synthases, the two evolutionarily related members with conserved thiolase fold. The mechanistic and structural importance of several active site residues, as predicted by our structural model, was investigated by performing site-directed mutagenesis. The functional identification of diverse catalytic activity in mycobacterial type III PKSs provide a fascinating example of metabolite divergence in CHS-like proteins

A High Secured Steganalysis using QVDHC Model

Data compression plays a vital role in data security as it saves memory, transfer speed is high, easy to handle and secure. Mainly the compression techniques are categorized into two types. They are lossless, lossy data compression. The data format will be an audio, image, text or video. The main objective is to save memory of using these techniques is to save memory and to preserve data confidentiality, integrity. In this paper, a hybrid approach was proposed which combines Quotient Value Difference (QVD) with Huffman coding. These two methods are more efficient, simple to implement and provides better security to the data. The secret message is encoded using Huffman coding, while the cover image is compressed using QVD. Then the encoded data is embedded into cover image and transferred over the network to receiver. At the receiver end, the data is decompressed to obtain original message. The proposed method shows high level performance when compared to other existing methods with better quality and minimum error

Feasibility test of agricultural residues through characterization for utilization in plasma gasification

Agricultural residues were characterized to determine their feasibility as feedstock for plasma gasification. Husk, stalk, straw and shell were selected for the study and proximate analysis, elemental composition analysis, thermal value analysis were carried out using standard procedures. Producer gas generated from these bio-residues is well suited for plasma gasification process where the working temperature is between 1200-2000ºC. These substances have moisture content in the range of 5-12%, and volatile matter content of 58-70%, offering good burning characteristics and conversion to electricity. The fixed carbon content of 13 to 20% contributes significantly to its calorific value. The average calorific value of selected agricultural residues (18.27 MJ/kg) was higher than the calorific value of feedstock (12 to 16 MJ/kg) used in plasma gasification, thus reinforcing their suitability further. It was found that selected agricultural residues could be adopted and promising fuel for plasma generation and deserve further development as a sustainable and renewable alternative

Park availability and major depression in individuals with chronic conditions: Is there an association in urban India?

Green space exposure has been positively correlated with better mental-health indicators in several high income countries, but has not been examined in low- and middle-income countries undergoing rapid urbanization. Building on a study of mental health in adults with a pre-existing chronic condition, we examined the association between park availability and major depression among 1208 adults surveyed in Delhi, India. Major depression was measured using the Mini International Neuropsychiatric Interview. The ArcGIS platform was used to quantify park availability indexed as (i) park distance from households, (ii) area of the nearest park; and within one km buffer area around households - the (iii) number and (iv) total area of all parks. Mixed-effects logistic regression models adjusted for socio-demographic characteristics indicated that relative to residents exposed to the largest nearest park areas (tertile 3), the odds [95% confidence interval] of major depression was 3.1 [1.4-7.0] times higher among residents exposed to the smallest nearest park areas (tertile 1) and 2.1 [0.9-4.8] times higher in residents with mid-level exposure (tertile 2). There was no statistically significant association between other park variables tested and major depression. We hypothesized that physical activity in the form of walking, perceived stress levels and satisfaction with the neighborhood environment may have mediating effects on the association between nearest park area and major depression. We found no significant mediation effects for any of our hypothesized variables. In conclusion, our results provide preliminary and novel evidence from India that availability of large parks in the immediate neighborhood positively impacts mental well-being of individuals with pre-existing chronic conditions, at the opportune time when India is embarking on the development of sustainable cities that aim to promote health through smart urban design - one of the key elements of which is the inclusion of urban green spaces

Priority Medicines for Maternal and Child Health: A Global Survey of National Essential Medicines Lists

BACKGROUND: In April 2011, the World Health Organization (WHO) published a list of "priority medicines" for maternal and child health based on 1) the global burden of disease and 2) evidence of efficacy and safety. The objective of this study was to examine the occurrence of these priority medicines on national essential medicines lists. METHODS AND FINDINGS: All essential medicines lists published since 1999 were selected from the WHO website collection. The most-up-to date list for each country was then selected, resulting in 89 unique country lists. Each list was evaluated for inclusion of medicines (chemical entity, concentration, and dosage form) on the Priority Medicines List. There was global variation in the listing of the Priority Medicines. The most frequently listed medicine was paracetamol, on 94% (84/89) of lists. Sodium chloride, gentamicin and oral rehydration solution were on 93% (83/89) of lists. The least frequently listed medicine was the children's antimalarial rectal artesunate, on 8% of lists (7/89); artesunate injection was on 16% (14/89) of lists. Pediatric artemisinin combination therapy, as dispersible tablets or flexible oral solid dosage form, appeared on 36% (32/89) of lists. Procaine benzylpenicillin, for treatment of pediatric pneumonia and neonatal sepsis, was on 50% (45/89) of the lists. Zinc, for treatment of diarrhoea in children, was included on only 15% (13/89) of lists. For prevention and treatment of postpartum hemorrhage in women, oxytocin was more prevalent on the lists than misoprostol; they were included on 55 (62%) and 31 (35%) of lists, respectively. Cefixime, for treatment of uncomplicated anogenital gonococcal infection in woman was on 26% (23/89) of lists. Magnesium sulfate injection for treatment of severe pre-eclampsia and eclampsia was on 50% (45/89) of the lists. CONCLUSIONS: The findings suggest that countries need to urgently amend their lists to provide all priority medicines as part of the efforts to improve maternal and child health

Diagnosis of depression among adolescents – a clinical validation study of key questions and questionnaire

<p>Abstract</p> <p>Background</p> <p>The objective of the study is to improve general practitioners' diagnoses of adolescent depression. Major depression is ranked fourth in the worldwide disability impact.</p> <p>Method/Design</p> <p>Validation of 1) three key questions, 2) SCL-dep6, 3) SCL-10, 4) 9 other SCL questions and 5) WHO-5 in a clinical study among adolescents. The Composite International Diagnostic Interview (CIDI) is to be used as the gold standard interview. The project is a GP multicenter study to be conducted in both Norway and Denmark. Inclusion criteria are age (14–16) and fluency in the Norwegian and Danish language. A number of GPs will be recruited from both countries and at least 162 adolescents will be enrolled in the study from the patient lists of the GPs in each country, giving a total of at least 323 adolescent participants.</p> <p>Discussion</p> <p>The proportion of adolescents suffering from depressive disorders also seems to be increasing worldwide. Early interventions are known to reduce this illness. The earlier depression can be identified in adolescents, the greater the advantage. Therefore, we hope to find a suitable questionnaire that could be recommended for GPs.</p