Structure of the twin-arginine signal-binding protein DmsD from Escherichia coli

The translocation of folded proteins via the twin-arginine translocation (Tat) pathway is regulated to prevent the futile export of inactive substrate. DmsD is part of a class of cytoplasmic chaperones that play a role in preventing certain redox proteins from premature transport. DmsD from Escherichia coli has been crystallized in space group P4_12_12, with unit-cell parameters a = b = 97.45, c = 210.04 Å, in the presence of a small peptide. The structure has been solved by molecular replacement to a resolution of 2.4 Å and refined to an R factor of 19.4%. There are four molecules in the asymmetric unit that may mimic a higher order structure in vivo. There appears to be density for the peptide in a predicted binding pocket, which lends support to its role as the signal-recognition surface for this class of proteins

Do Alternative Therapies Have a Role in Autism?

Interventions considered to be branches of Complementary & Alternative Medicine (CAM) for autism are on the rise. Many new treatments have emerged & traditional beliefs of Ayurveda, Yoga, Behavioral therapy, Speech therapy and Homoeopathy have gained popularity and advocacy among parents. It is imperative that data supporting new treatments should be scrutinized for scientific study design, clinical safety, and scientific validity, before embarking on them as modes of therapy. Practitioners take care in explaining the rationale behind the various approaches that they practice, it is important to indicate possible limitations too during the initial clinical examination and interactive session. Clinicians must remember that parents may have different beliefs regarding the effectiveness of treatment since their information is derived more from the ‘hear-say’ route when they compare benefits/effects of CAM therapies on other children and often underestimate differential tolerance for treatment risks. It is thus significant that practitioners do not assume a "don't ask, don't tell" posture. The scientific validation and support for many interventions is incomplete and very different from the recommendations of the American Academy of Pediatrics Policy Statement. In this article, we discuss the various modes of CAM and their utilities and limitations in relation to autism

Computational binding mechanism of Mycobacterium tuberculosis UDP-NAG enolpyruvyl transferase (MurA) with inhibitors fosfomycin, cyclic disulfide analog RWJ-3981, pyrazolopyrimidine analog RWJ-110192, purine analog RWJ-140998, 5-sulfonoxy-anthranilic aci

Worldwide, tuberculosis (TB) remains the most frequent and important infectious disease causing morbidity and death. One-third of the world's population is infected with Mycobacterium tuberculosis (Mtb), the etiologic agent of TB. In this context, TB is in the top three, with malaria and HIV being the leading causes of death from a single infectious agent, and about two million deaths are attributable to TB annually. The bacterial enzyme MurA catalyzes the transfer of enolpyruvate from phosphoenolpyruvate (PEP) to uridine diphospho-N-acetylglucosamine (UNAG), which is the first committed step of bacterial cell wall biosynthesis. In this work, 3D structural model of Mtb-MurA enzyme has been developed, for the first time, by homology modeling and molecular dynamics simulation techniques. The model provided clear insight in its structure features, i.e. substrate binding pocket, and common docking site. Multiple sequence alignment and 3D structure model provided the putative substrate binding pocket of Mtb-MurA with respect to E.coli MurA. This analysis was helpful in identifying the binding sites and molecular function of the MurA homologue. Molecular docking study was performed on this 3D structural model, using different classes of inhibitors like fosfomycin, cyclic disulfide analog RWJ-3981, pyrazolopyrimidine analog RWJ-110192, purine analog RWJ-140998, 5-sulfonoxy-anthranilic acid derivatives T6361, T6362 and the results showed that the 5-sulfonoxyanthranilic acid derivatives is showed best interaction compared with other inhibitor, taking in to this we also design a new efficient analogs of T6361 and T6362 which are showed even better interaction with Mtb-MurA than the parental5-sulfonoxy-anthranilic acid derivatives. Further the comparative molecular electrostatic potential and cavity depth analysis of Mtb-MurA suggested several important differences in its substrate and inhibitor binding pocket. Such differences could be exploited in the future for designing of a more specific inhibitor for Mtb-MurA enzym

Assessment of Metabolic Parameters For Autism Spectrum Disorders

Autism is a brain development disorder that first appears during infancy or childhood, and generally follows a steady course without remission. Impairments result from maturation-related changes in various systems of the brain. Autism is one of the five pervasive developmental disorders (PDD), which are characterized by widespread abnormalities of social interactions and communication, and severely restricted interests and highly repetitive behavior. The reported incidence of autism spectrum disorders (ASDs) has increased markedly over the past decade. The Centre for Disease Control and Prevention has recently estimated the prevalence of ASDs in the United States at approximately 5.6 per 1000 (1 of 155 to 1 of 160) children. Several metabolic defects, such as phenylketonuria, are associated with autistic symptoms. In deciding upon the appropriate evaluation scheme a clinician must consider a host of different factors. The guidelines in this article have been developed to assist the clinician in the consideration of these factors

Routing in Networks Using Genetic Algorithm

With the increase in traffic, internet service providers are trying their best to provide maximum utilization of resources available. The current traffic load has to be taken into account for computation of paths in routing protocols. Network applications; require the shortest paths to be used for communication purposes. Addressing the selection of path, from a known source to destination is the basic aim of this paper. This paper proposes a method of calculating the shortest path for a network using a combination of Open shortest path first and Genetic Algorithm (OSGA). Genetic Algorithm is used in this paper for optimization of routing. It helps in enhancing the performance of the routers

Fatigue Analysis of High Performance Cement Concrete for Pavements Using the Probabilistic Approach

Cement concrete pavements are designed for flexural fatigue loading due to traffic. Due to its numerous advantages high performance cement concrete is finding it’s way in pavement construction. This paper investigates the fatigue strength of High Performance Cement Concretes subjected to flexural loading. Fatigue studies are conducted on these concretes to obtain the fatigue lives at various stress levels. Static flexural strength tests are conducted to determine the static failure loads on prism specimen. From the experimental studies carried out, the number of load repetitions to failure on the concretes under study is determined for three stress ratios. From the data obtained S-N curves are developed using linear regression models considering log normal distribution as is being presently adopted. Recent literature shows that weibull distribution is found to have more convincing physical features than the lognormal distribution to describe the fatigue behavior o concrete. To incorporate the probability of failure, weibull distribution is considered and Pf-S-N diagram are developed. It is observed that addition of fly ash and silica fume improves the fatigue performance of concrete by48% and 83% at a stress level of 0.75

On the possible use of satellite fixed positions for Argo profiles in case of GPS failures

INCOIS had deployed iridium based PROVOR Bio-Argo floats obtained from NKE, France. These floats are fitted with GPS for obtaining accurate position of the Argo profiles. However there are cases where in the GPS fitted with the Argo floats tend to give wrong positions owing to unknown reasons. In this present work we discuss the possibilities of using the Iridium satellite fixed position in case of GPS failures. For this, analysis was done by comparing the GPS and satellite fixed profiles positions of good floats. These statistics can be used for using the satellite fixed position in case of GPS failures. For each comparison the satellite fixed position with least circular error probability (CEP) radius was chosen. The study suggested that on a average the satellite fixed positions tend to differ from the GPS fixed positions by 0.03 degrees. CEP radii are found to be consistent with the difference between satellite fixed position and GPS position. Based on this we suggest a quality flag of 2 for positions with CEP radius <=4 and flag 4 for any other positions