Chemical scaffolds with structural similarities to siderophores of nonribosomal peptide-polyketide origin as novel antimicrobials against Mycobacterium tuberculosis and Yersinia pestis

Mycobacterium tuberculosis (Mtb) and Yersinia pestis (Yp) produce siderophores with scaffolds of nonribosomal peptide-polyketide origin. Compounds with structural similarities to these siderophores were synthesized and evaluated as antimicrobials against Mtb and Yp under iron-limiting conditions mimicking the iron scarcity these pathogens encounter in the host and under standard iron-rich conditions. Several new antimicrobials were identified, including some with increased potency in the iron-limiting condition. Our study illustrates the possibility of screening compound libraries in both iron-rich and iron-limiting conditions to identify antimicrobials that may selectively target iron scarcity-adapted bacteria and highlights the usefulness of building combinatorial libraries of compounds having scaffolds with structural similarities to siderophores to feed into antimicrobial screening programs.     

Assessment of Blood-Brain Barrier Function and the Neuroinflammatory Response in the Rat Brain by Using Cerebral Open Flow Microperfusion (cOFM)

Blood-brain barrier (BBB) impairment in systemic inflammation leads to neuroinflammation. Several factors including cytokines, chemokines and signal transduction molecules are implicated in BBB dysfunction in response to systemic inflammation. Here, we have adopted a novel in vivo technique; namely, cerebral open flow microperfusion (cOFM), to perform time-dependent cytokine analysis (TNF-alpha, IL-6 and IL-10) in the frontal cortex of the rat brain in response to a single peripheral administration of lipopolysaccharide (LPS). In parallel, we monitored BBB function using sodium fluorescein as low molecular weight reporter in the cOFM sample. In response to the systemic LPS administration, we observed a rapid increase of TNF-alpha in the serum and brain, which coincides with the BBB disruption. Brain IL-6 and IL-10 synthesis was delayed by approximately 1 h. Our data demonstrate that cOFM can be used to monitor changes in brain cytokine levels and BBB disruption in a rat sepsis model.     

Bulges in left-handed G-quadruplexes

G-quadruplex (G4) DNA structures with a left-handed backbone progression have unique and conserved structural features. Studies on sequence dependency of the structures revealed the prerequisites and some minimal motifs required for left-handed G4 formation. To extend the boundaries, we explore the adaptability of left-handed G4s towards the existence of bulges. Here we present two X-ray crystal structures and an NMR solution structure of left-handed G4s accommodating one, two and three bulges. Bulges in left-handed G4s show distinct characteristics as compared to those in right-handed G4s. The elucidation of intricate structural details will help in understanding the possible roles and limitations of these unique structures.     

Calcium Chloride Made E. coli Competent for Uptake of Extraneous DNA Through Overproduction of OmpC Protein

In the standard method of transformation of Escherichia coli with extraneous DNA, cells are made competent for DNA uptake by incubating in ice-cold 100?mM CaCl₂. Analysis of the whole protein profile of CaCl₂-treated E. coli cells by the techniques of one- and two-dimensional gel electrophoresis, MALDI-MS and immunoprecipitation revealed overproduction of outer membrane proteins OmpC, OmpA and heat-shock protein GroEL. In parity, transformation efficiency of E. coli ompC mutant by plasmid pUC19 DNA was found to be about 40?% lower than that of the wild type strain. Moreover, in E. coli cells containing groEL-bearing plasmid, induction of GroEL caused simultaneous overproduction of OmpC. On the other hand, less OmpC was synthesized in E. coli groEL mutant compared to its wild type counterpart, by CaCl₂-shock. From these results it can be suggested that in the process of CaCl₂-mediated generation of competence, the heat-shock chaperone GroEL has specific role in DNA entry into the cell, possibly through the overproduced OmpC and OmpA porins.     

Floral biology,breeding system and pollination ecology of Justicia betonica L. (Acanthaceae): An assessment of its low reproductive success in West Bengal,India

Besides its importance as an ornamental plant, Justicia betonica L. is also used as a medicinal plant for the treatment of several human disorders. However, the population size and abundance of the plant species are very low in Indian states, including West Bengal. The breeding system and pollination ecology of J. betonica are still unclear. Therefore, some reproductive aspects were investigated in order to provide important information for the sustainability of the species. The flowering duration spanned from December to May, with its peak in February–March. Flower opening time was much earlier (5.00–8.00 a.m.) on a hot day (in April–May) than on a cold day (10.00 a.m.–12.00 p.m. in December–January). The time of anther dehiscence coincided with the flower opening time; however, the stigma became receptive later. The plant species is self-compatible but dependent on pollinators for fruit and seed sets. Members of different insect groups like ants, bees, butterflies, flies, moths and wasps visit the flowers. Among them, Allorhynchium metallicum and Halictus acrocephalus are the primary pollinators (based on the “relative pollinator service”). The plant species showed a significant pollination deficit (coefficient of pollination deficit [D] = 0.32) in the open condition. Larvae of the florivorous moth Gatesclarkeana erotias significantly reduced reproductive success by eating their floral parts, ovules and immature seeds. In conclusion, combining the pollination deficit and the feeding activity of phytophagous insects (moth larvae) may reduce the reproductive fitness of J. betonica in the study regions.     

An in silico structural insights into Plasmodium LytB protein and its inhibition

In most of the pathogenic organisms including Plasmodium falciparum, isoprenoids are synthesized via MEP (MethylErythritol 4-Phosphate) pathway. LytB is the last enzyme of this pathway which catalyzes the conversion of (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate (HMBPP) into the two isoprenoid precursors: isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Since the MEP pathway is not used by humans, it represents an attractive target for the development of new anti-malarial compounds or inhibitors. Here a systematic in silico study has been conducted to get an insight into the structure of Plasmodium lytB as well as its affinities towards different inhibitors. We used comparative modeling technique to predict the three-dimensional (3D) structure of Plasmodium LytB taking Escherichia coli LytB protein (PDB ID: 3KE8) as template and the model was subsequently refined through molecular dynamics (MD) simulation. A large ligand data-set containing diphospate group was subjected for virtual screening against the target using GOLD 5.2 program. Considering the mode of binding and affinities, 17 leads were selected on basis of binding energies in comparison to its substrate HMBPP (Gold.Chemscore.DG: -20.9734 kcal/mol). Among them, five were discarded because of their inhibitory activity towards other human enzymes. The rest 12 potential leads carry all the properties of any “drug like” molecule and the knowledge of Plasmodium LytB-inhibitory mechanism which can provide valuable support for the anti-malarial-inhibitor design in future.     

Privacy preserving sub-feature selection based on fuzzy probabilities

The feature selection addresses the issue of developing accurate models for classification in data mining. The aggregated data collection from distributed environment for feature selection makes the problem of accessing the relevant inputs of individual data records. Preserving the privacy of individual data is often critical issue in distributed data mining. In this paper, it proposes the privacy preservation of individual data for both feature and sub-feature selection based on data mining techniques and fuzzy probabilities. For privacy purpose, each party maintains their privacy as the instruction of data miner with the help of fuzzy probabilities as alias values. The techniques have developed for own database of data miner in distributed network with fuzzy system and also evaluation of sub-feature value included for the processing of data mining task. The feature selection has been explained by existing data mining techniques i.e., gain ratio using fuzzy optimization. The estimation of gain ratio based on the relevant inputs for the feature selection has been evaluated within the expected upper and lower bound of fuzzy data set. It mainly focuses on sub-feature selection with privacy algorithm using fuzzy random variables among different parties in distributed environment. The sub-feature selection is uniquely identified for better class prediction. The algorithm provides the idea of selecting sub-feature using fuzzy probabilities with fuzzy frequency data from data miner’s database. The experimental result shows performance of our findings based on real world data set.     

Deletion of both methionine sulfoxide reductase A and methionine sulfoxide reductase C genes renders Salmonella Typhimurium highly susceptible to hypochlorite stress and poultry macrophages

Molecular Biology Reports - Salmonella Typhimurium survives and replicates inside the oxidative environment of phagocytic cells. Proteins, because of their composition and location, are the...