Bacteriological examination of drinking water with reference to coliforms in Jeedimetla, Hyderabad, India

Most probable number (MPN) test was done to detect the coliform in water samples collected from mobile vendors, protected well and municipal tap water supplied from Jeedimetla municipality. The study revealed that the number of coliforms was very high ( 1500) in water samples collected frommobile vendors. The bacteria were identified as Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. Bacteriological examination of water samples collected from different sources showed that the water of mobile vendors and ground water of jeedimetla area was not potable while themunicipal tap water was found to be safe for drinking

Lipid peroxidation is essential for α-synuclein-induced cell death.

Parkinson's disease is the second most common neurodegenerative disease and its pathogenesis is closely associated with oxidative stress. Deposition of aggregated α-synuclein (α-Syn) occurs in familial and sporadic forms of Parkinson's disease. Here, we studied the effect of oligomeric α-Syn on one of the major markers of oxidative stress, lipid peroxidation, in primary co-cultures of neurons and astrocytes. We found that oligomeric but not monomeric α-Syn significantly increases the rate of production of reactive oxygen species, subsequently inducing lipid peroxidation in both neurons and astrocytes. Pre-incubation of cells with isotope-reinforced polyunsaturated fatty acids (D-PUFAs) completely prevented the effect of oligomeric α-Syn on lipid peroxidation. Inhibition of lipid peroxidation with D-PUFAs further protected cells from cell death induced by oligomeric α-Syn. Thus, lipid peroxidation induced by misfolding of α-Syn may play an important role in the cellular mechanism of neuronal cell loss in Parkinson's disease. We have found that aggregated α-synuclein-induced production of reactive oxygen species (ROS) that subsequently stimulates lipid peroxidation and cell death in neurons and astrocytes. Specific inhibition of lipid peroxidation by incubation with reinforced polyunsaturated fatty acids (D-PUFAs) completely prevented the effect of α-synuclein on lipid peroxidation and cell death

Effects of organizationally endorsed coaching on performance and validity of situational judgment tests

There is growing interest in organizationally provided or organizationally endorsed coaching. However, little is known about the effects of such coaching on test scores in operational settings. This study reports on an examination of such a program in the context of the use of a situational judgment test (SJT) for medical school admissions. We examine the effects of multiple types of coaching methods on SJT scores and on their construct-related and predictive validities. Results suggest that (1) commercial coaching techniques may not be as effective as previously thought, whereas organizationally provided methods may be more effective, and that (2) the criterion-related validity of the SJT scores is not degraded by the availability of coaching. Generally, this study illustrates that concerns about potential unfairness of coaching can be countered by making effective coaching available to all examinees, in the form of organizationally endorsed coaching

Computational Analysis of Cholangiocarcinoma Phosphoproteomes Identifies Patient-Specific Drug Targets

Cholangiocarcinoma is a form of hepatobiliary cancer with an abysmal prognosis. Despite advances in our understanding of cholangiocarcinoma pathophysiology and its genomic landscape, targeted therapies have not yet made a significant impact on its clinical management. The low response rates of targeted therapies in cholangiocarcinoma suggest that patient heterogeneity contributes to poor clinical outcome. Here we used mass spectrometry–based phosphoproteomics and computational methods to identify patient-specific drug targets in patient tumors and cholangiocarcinoma-derived cell lines. We analyzed 13 primary tumors of patients with cholangiocarcinoma with matched nonmalignant tissue and 7 different cholangiocarcinoma cell lines, leading to the identification and quantification of more than 13,000 phosphorylation sites. The phosphoproteomes of cholangiocarcinoma cell lines and patient tumors were significantly correlated. MEK1, KIT, ERK1/2, and several cyclin-dependent kinases were among the protein kinases most frequently showing increased activity in cholangiocarcinoma relative to nonmalignant tissue. Application of the Drug Ranking Using Machine Learning (DRUML) algorithm selected inhibitors of histone deacetylase (HDAC; belinostat and CAY10603) and PI3K pathway members as high-ranking therapies to use in primary cholangiocarcinoma. The accuracy of the computational drug rankings based on predicted responses was confirmed in cell-line models of cholangiocarcinoma. Together, this study uncovers frequently activated biochemical pathways in cholangiocarcinoma and provides a proof of concept for the application of computational methodology to rank drugs based on efficacy in individual patients. SIGNIFICANCE: Phosphoproteomic and computational analyses identify patient-specific drug targets in cholangiocarcinoma, supporting the potential of a machine learning method to predict personalized therapies

Applicability of the cobb angle measurement in idiopathic scoliosis using scanned imaging

OBJECTIVES: To compare the measurement of the Cobb angle on printed radiographs and on scanned radiographs viewed through the software "PixViewer". METHODS: Preoperative radiographs of 23 patients were evaluated on printed films and through the software "PixViewer". The same evaluator, a spine surgeon, chose the proximal and distal limiting vertebrae of the main curve on printed radiographs, without identification of patients, and measured the Cobb angle based on these parameters. The same parameters and measurements were applied to scanned radiographs. The measurements were compared, as well as the choice of limiting vertebrae. RESULTS: The average variation of the Cobb angle between methods was 1.48 ± 1.73°. The intraclass correlation coefficient (ICC) was 0.99, demonstrating excellent reproducibility. CONCLUSION: The Cobb method can be used to evaluate scoliosis through the "PixViewer" tool with the same reliability as the classic method on printed radiographs

Unnatural amino acid analogues of membrane-active helical peptides with anti-mycobacterial activity and improved stability

Objectives The emergence of MDR-TB, coupled with shrinking antibiotic pipelines, has increased demands for new antimicrobials with novel mechanisms of action. Antimicrobial peptides have increasingly been explored as promising alternatives to antibiotics, but their inherent poor in vivo stability remains an impediment to their clinical utility. We therefore systematically evaluated unnatural amino acid-modified peptides to design analogues with enhanced anti-mycobacterial activities. Methods Anti-mycobacterial activities were evaluated in vitro and intracellularly against drug-susceptible and MDR isolates of Mycobacterium tuberculosis using MIC, killing efficacy and intracellular growth inhibition studies. Toxicity profiles were assessed against mammalian cells to verify cell selectivity. Anti-mycobacterial mechanisms were investigated using microfluidic live-cell imaging with time-lapse fluorescence microscopy and confocal laser-scanning microscopy. Results Unnatural amino acid incorporation was well tolerated without an appreciable effect on toxicity profiles and secondary conformations of the synthetic peptides. The modified peptides also withstood proteolytic digestion by trypsin. The all D-amino acid peptide, i(llkk)2i (II-D), displayed superior activity against all six mycobacterial strains tested, with a 4-fold increase in selectivity index as compared with the unmodified L-amino acid peptide in broth. II-D effectively reduced the intracellular bacterial burden of both drug-susceptible and MDR clinical isolates of M. tuberculosis after 4 days of treatment. Live-cell imaging studies demonstrated that II-D permeabilizes the mycobacterial membrane, while confocal microscopy revealed that II-D not only permeates the cell membrane, but also accumulates within the cytoplasm. Conclusions Unnatural amino acid modifications not only decreased the susceptibility of peptides to proteases, but also enhanced mycobacterial selectivity

The Effective Lagrangian for Bulk Fermions in Models with Extra Dimensions

We compute the dimension 6 effective Lagrangian arising from the tree level integration of an arbitrary number of bulk fermions in models with warped extra dimensions. The coefficients of the effective operators are written in terms of simple integrals of the metric and are valid for arbitrary warp factors, with or without an infrared brane, and for a general Higgs profile. All relevant tree level fermion effects in electroweak and flavor observables can be computed using this effective Lagrangian.Comment: 22 pages. V2: typos corrected, matches published versio

Ultraprecise single-molecule localization microscopy enables in situ distance measurements in intact cells

Single-molecule localization microscopy (SMLM) has the potential to quantify the diversity in spatial arrangements of molecules in intact cells. However, this requires that the single-molecule emitters are localized with ultrahigh precision irrespective of the sample format and the length of the data acquisition. We advance SMLM to enable direct distance measurements between molecules in intact cells on the scale between 1 and 20 nm. Our actively stabilized microscope combines three-dimensional real-time drift corrections and achieves a stabilization of <1 nm and localization precision of ∼1 nm. To demonstrate the biological applicability of the new microscope, we show a 4- to 7-nm difference in spatial separations between signaling T cell receptors and phosphatases (CD45) in active and resting T cells. In summary, by overcoming the major bottlenecks in SMLM imaging, it is possible to generate molecular images with nanometer accuracy and conduct distance measurements on the biological relevant length scales