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31.
Singh UP Pathak M Dubey V Bhat HR Gahtori P Singh RK 《Chemical biology & drug design》2012,80(4):572-583
Some novel hybrid 1,3-thiazine-1,3,5-triazine derivatives were synthesized and tested for antibacterial activity. Compounds 8c and 8f were found active against Gram positive and Gram negative microorganisms. Molecular docking studies have been performed on eubacterial ribosomal decoding A site (Escherichia coli 16S rRNA A site) to rationalize the probable mode of action, binding affinity, and orientation of the molecules at the active site of receptor. The structures of all these newly synthesized compounds were confirmed by their elemental analyses and spectral data techniques viz. IR, (1) H NMR, (13) C NMR, and mass. 相似文献
32.
Some hybrid 1,3,4-thiadiazole-1,3,5-triazine derivatives tethered via -S- bridge were synthesized and characterized with the aid of spectroscopic and elemental analysis. These hybrid conjugates were then investigated for their antibacterial activity against selected Gram-positive and Gram-negative bacteria. Excellent to moderate antibacterial activity was presented by the target compounds. 相似文献
33.
Burkholder KM Perry JW Wobus CE Donato NJ Showalter HD Kapuria V O'Riordan MX 《Infection and immunity》2011,79(12):4850-4857
Macrophages are key mediators of antimicrobial defense and innate immunity. Innate intracellular defense mechanisms can be rapidly regulated at the posttranslational level by the coordinated addition and removal of ubiquitin by ubiquitin ligases and deubiquitinases (DUBs). While ubiquitin ligases have been extensively studied, the contribution of DUBs to macrophage innate immune function is incompletely defined. We therefore employed a small molecule DUB inhibitor, WP1130, to probe the role of DUBs in the macrophage response to bacterial infection. Treatment of activated bone marrow-derived macrophages (BMM) with WP1130 significantly augmented killing of the intracellular bacterial pathogen Listeria monocytogenes. WP1130 also induced killing of phagosome-restricted bacteria, implicating a bactericidal mechanism associated with the phagosome, such as the inducible nitric oxide synthase (iNOS). WP1130 had a minimal antimicrobial effect in macrophages lacking iNOS, indicating that iNOS is an effector mechanism for WP1130-mediated bacterial killing. Although overall iNOS levels were not notably different, we found that WP1130 significantly increased colocalization of iNOS with the Listeria-containing phagosome during infection. Taken together, our data indicate that the deubiquitinase inhibitor WP1130 increases bacterial killing in macrophages by enhancing iNOS localization to the phagosome and suggest a potential role for ubiquitin regulation in iNOS trafficking. 相似文献
34.
Anthropometric variations in humans make it difficult to replace a temporomandibular joint (TMJ), successfully using a standard “one-size-fits-all” prosthesis. The case report presents a unique concept of total TMJ replacement with customized and modified TMJ prosthesis, which is cost-effective and provides the best fit for the patient. The process involved in designing and modifications over the existing prosthesis are also described. A 12-year- old female who presented for treatment of left unilateral TMJ ankylosis underwent the surgery for total TMJ replacement. A three-dimensional computed tomography (CT) scan suggested features of bony ankylosis of left TMJ. CT images were converted to a sterolithographic model using CAD software and a rapid prototyping machine. A process of rapid manufacturing was then used to manufacture the customized prosthesis. Postoperative recovery was uneventful, with an improvement in mouth opening of 3.5 cm and painless jaw movements. Three years postsurgery, the patient is pain-free, has a mouth opening of about 4.0 cm and enjoys a normal diet. The postoperative radiographs concur with the excellent clinical results. The use of CAD/CAM technique to design the custom-made prosthesis, using orthopaedically proven structural materials, significantly improves the predictability and success rates of TMJ replacement surgery. 相似文献
35.
36.
Vaibhav Pawar Liu Jingjing Nila Patel Nimrat Kaur Paul W. Doetsch Gerald S. Shadel Hong Zhang Wolfram Siede 《Mechanisms of ageing and development》2009,130(8):501-508
Stationary-phase Saccharomyces cerevisiae can serve as a model for post-mitotic cells of higher eukaryotes. Phosphorylation and activation of the checkpoint kinase Rad53 was observed after more than 2 days of culture if two major pathways of oxidative DNA damage repair, base excision repair (BER) and nucleotide excision repair (NER), are inactive. The wild type showed a low degree of Rad53 phosphorylation when the incubation period was drastically increased. In the ber ner strain, Rad53 phosphorylation can be abolished by inclusion of antioxidants or exclusion of oxygen. Furthermore, this modification and enhanced mutagenesis in extended stationary phase were absent in rho° strains, lacking detectable mitochondrial DNA. This checkpoint response is therefore thought to be dependent on reactive oxygen species originating from mitochondrial respiration. There was no evidence for progressive overall telomere shortening during stationary-phase incubation. Since Rad50 (of the MRN complex) and Mec1 (the homolog of ATR) were absolutely required for the observed checkpoint response, we assume that resected random double-strand breaks are the critical lesion. Single-strand resection may be accelerated by unrepaired oxidative base damage in the vicinity of a double-strand break. 相似文献
37.
Yu-Chieh David Chen Vaibhav Menon Ryan Matthew Joseph Anupama Arun Dahanukar 《The Journal of neuroscience》2021,41(27):5791
Insect gustatory systems comprise multiple taste organs for detecting chemicals that signal palatable or noxious quality. Although much is known about how taste neurons sense various chemicals, many questions remain about how individual taste neurons in each taste organ control feeding. Here, we use the Drosophila pharynx as a model to investigate how taste information is encoded at the cellular level to regulate consumption of sugars and amino acids. We first generate taste-blind animals and establish a critical role for pharyngeal input in food selection. We then investigate feeding behavior of both male and female flies in which only selected classes of pharyngeal neurons are restored via binary choice feeding preference assays as well as Fly Liquid-Food Interaction Counter assays. We find instances of integration as well as redundancy in how pharyngeal neurons control behavioral responses to sugars and amino acids. Additionally, we find that pharyngeal neurons drive sugar feeding preference based on sweet taste but not on nutritional value. Finally, we demonstrate functional specialization of pharyngeal and external neurons using optogenetic activation. Overall, our genetic taste neuron protection system in a taste-blind background provides a powerful approach to elucidate principles of pharyngeal taste coding and demonstrates functional overlap and subdivision among taste neurons.SIGNIFICANCE STATEMENT Dietary intake of nutritious chemicals such as sugars and amino acids is essential for the survival of an animal. In insects, distinct classes of taste neurons control acceptance or rejection of food sources. Here, we develop a genetic system to investigate how individual taste neurons in the Drosophila pharynx encode specific tastants, focusing on sugars and amino acids. By examining flies in which only a single class of taste neurons is active, we find evidence for functional overlap as well as redundancy in responses to sugars and amino acids. We also uncover a functional subdivision between pharyngeal and external neurons in driving feeding responses. Overall, we find that different pharyngeal neurons act together to control intake of the two categories of appetitive tastants. 相似文献
38.
39.
Vandana Shashi Thomas R. Kwapil Jessica Kaczorowski Margaret N. Berry Cesar S. Santos Timothy D. Howard Dhruman Goradia Konasale Prasad Diwadkar Vaibhav Rajaprabhakaran Rajarethinam Edward Spence Matcheri S. Keshavan 《Psychiatry Research: Neuroimaging》2010,181(1):1-8
Chromosome 22q11.2 deletion syndrome (22q11DS) is associated with cognitive deficits and morphometric brain abnormalities in childhood and a markedly elevated risk of schizophrenia in adolescence/early adulthood. Determining the relationship between neurocognition and neuroimaging findings would yield crucial information about childhood neurodevelopment and provide a basis for the study of the trajectory that occurs on the pathway to psychosis. We compared morphometric brain findings between non-psychotic children with 22q11DS (n = 22) and healthy controls (n = 16), and examined the association between neurocognitive functioning and morphometric brain findings. Volumetric regional gray matter differences between the 22q11DS and control subjects were measured, and correlations of the regional gray matter volumes and neurocognition were performed. Children with 22q11DS demonstrated reductions in gray matter in several brain regions, chiefly the frontal cortices, the cingulate gyrus and the cerebellum. The volumetric reductions in these salient areas were associated with poor performance in sustained attention, executive function and verbal memory; however, the relation of brain volume with cognitive performance did not differ between the patient and control groups. Thus, children with 22q11DS demonstrate gray matter reductions in multiple brain regions that are thought to be relevant to schizophrenia. The correlation of these volumetric reductions with poor neurocognition indicates that these brain regions may mediate higher neurocognitive functions implicated in schizophrenia. 相似文献
40.
S. Basavaraj Vaibhav Sihorkar T.R. Shantha Kumar Prakash Sundaramurthi Nuggehally R. Srinivas P. Venkatesh 《Pharmaceutical development and technology》2013,18(4):443-451
The purpose of the present study was to investigate the influence of a polyhydroxy base, N-acetyl glucamine (also know as Meglumine), as a ternary component on the complexation of DRF-4367, a poorly water-soluble and weakly acidic anti-inflammatory molecule, with 2-hydroxypropyl-β-cyclodextrin (HPβCD). The molecular inclusion of DRF-4367 with HPβCD alone and in combination with ternary component was aimed at improvement in solubility and, subsequently, dissolution rate-limited oral bioavailability. The solid complexes of DRF-4367 and HPβCD with or without meglumine (binary and ternary systems, respectively) were prepared as coevaporated product in different stoichiometric ratios and compared against physical mixture. The formation of inclusion complexes was confirmed by using classical instrumental techniques. Phase solubility studies suggested that meglumine was responsible for solubility improvement via multiple factors rather than just providing a favorable pH. Mechanisms and factors governing solubility enhancement were investigated by using phase solubility and thermodynamic parameters. The complexation of DRF-4367 with HPβCD is thermodynamically favored because the Gibbs free energies of transfer of the drug to the cyclodextrin cavity are negative. The solubilization efficiency and stability were further improved while retaining the favorable Gibbs free energies of transfer with the addition of meglumine. Inclusion ternary complex of DRF-4367 with HPβCD and meglumine showed significant improvement in dissolution compared with uncomplexed drug and binary system. Moreover, the phenomena of reprecipitation observed with binary system during dissolution could be avoided with meglumine as an enabling ternary component. This improved physicochemical behavior of ternary complex with the novel inclusion of a polyhydroxy base translated into an enhanced oral bioavailability of DRF-4367 compared with either uncomplexed drug or nanosuspension. 相似文献