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991.
Sarwat Chowdhury Yen Ting Chen Xingang Fang Wayne Grant Jennifer Pocas Michael D. Cameron Claudia Ruiz Li Lin HaJeung Park Thomas Schröter Thomas D. Bannister Philip V. LoGrasso Yangbo Feng 《Bioorganic & medicinal chemistry letters》2013,23(6):1592-1599
SAR and lead optimization studies for Rock inhibitors based on amino acid-derived quinazolines are described. Studies demonstrated that these amino acid derived quinazolinones were mainly pan-Rock (I & II) inhibitors. While selectivity against other kinases could be achieved, selectivity for most of these compounds against PKA was not achieved. This is distinct from Rock inhibitors based on non-amino acid derived quinazolinones, where high selectivity against PKA could be obtained.22 The inhibitors presented here in some cases possessed sub-nanomolar inhibition of Rock, nanomolar potency in ppMLC cell based assays, low to fair cytochrome P-450 inhibition, and good human microsomal stability. 相似文献
992.
Dissemination of cancer cells to distant organ sites is the leading cause of death due to treatment failure in different types of cancer. Mehlen and Puisieux have reviewed the importance of the development of inappropriate cell survival signaling for various steps in the metastatic process and have noted the particular importance of aberrant cell survival to successful colonization at the metastatic site. Therefore, the understanding of mechanisms that govern cell survival fate of these metastatic cells could lead to the understanding of a new paradigm for the control of metastatic potential and could provide the basis for developing novel strategies for the treatment of metastases. Numerous studies have documented the widespread role of Akt in cell survival and metastasis in colorectal cancer, as well as many other types of cancer. Akt acts as a key signaling node that bridges the link between oncogenic receptors to many essential pro-survival cellular functions, and is perhaps the most commonly activated signaling pathway in human cancer. In recent years, Akt2 and Akt3 have emerged as significant contributors to malignancy alongside the well-characterized Akt1 isoform, with distinct non-overlapping functions. This review is aimed at gaining a better understanding of the Akt-driven cell survival mechanisms that contribute to cancer progression and metastasis and the pharmacological inhibitors in clinical trials designed to counter the Akt-driven cell survival responses in cancer. 相似文献
993.
Suman Kanti Chowdhury Ashish D. Nimbarte Majid Jaridi Robert C. Creese 《Journal of electromyography and kinesiology》2013,23(5):995-1003
Assessment of neuromuscular fatigue is essential for early detection and prevention of risks associated with work-related musculoskeletal disorders. In recent years, discrete wavelet transform (DWT) of surface electromyography (SEMG) has been used to evaluate muscle fatigue, especially during dynamic contractions when the SEMG signal is non-stationary. However, its application to the assessment of work-related neck and shoulder muscle fatigue is not well established. Therefore, the purpose of this study was to establish DWT analysis as a suitable method to conduct quantitative assessment of neck and shoulder muscle fatigue under dynamic repetitive conditions. Ten human participants performed 40 min of fatiguing repetitive arm and neck exertions while SEMG data from the upper trapezius and sternocleidomastoid muscles were recorded. The ten of the most commonly used wavelet functions were used to conduct the DWT analysis. Spectral changes estimated using power of wavelet coefficients in the 12–23 Hz frequency band showed the highest sensitivity to fatigue induced by the dynamic repetitive exertions. Although most of the wavelet functions tested in this study reasonably demonstrated the expected power trend with fatigue development and recovery, the overall performance of the “Rbio3.1” wavelet in terms of power estimation and statistical significance was better than the remaining nine wavelets. 相似文献
994.
In the topmost leaves of low-irradiance (LI) tolerant CO 43 and LI susceptible IR 20 rice cultivars, the contents of chlorophyll
(chl)a andb and carotenoids and the Hill reaction activity increased under LI. The increase was greater in cv. CO 43 than that in cv.
IR 20, and in Chlb than in Chla. The contents of soluble proteins and reducing sugars and nitrate reductase activity of the leaves decreased while the content
of non-reducing sugars increased due to shading. The decrease in reducing sugars was greater in cv. CO 43 than in cv. IR 20.
On the other hand, the decrease in soluble proteins and nitrate reductase was much less in cv. CO 43 as compared with cv.
IR 20.
Communicated by Z. ŠESTáK 相似文献
995.
Shashi Madan H. S. Nainawatee Sunita Jain R. K. Jain M. S. Malik J. B. Chowdhury 《Plant and Soil》1994,163(2):151-156
The magnitude of the effect of salt stress on proline content, pyrroline-5-carboxylate (P5C) reductase activity and water relations was found to be leaf position dependent in an advance generation (R4) of twoBrassica juncea L. somaclones (SR-2 and SR-3) selected in vitro for NaCl-tolerance and the parent cv. Prakash. Free proline content and P5C reductase activity increased with increase in salt stress in all the lines but at different rates; the maximum increase being in the SR-3 derived somaclonal line. At 100 mM NaCl, SR-3 showed a nearly 19 fold increase in proline content compared to a 4–5 fold increase in the other two genotypes. The proline level and P5C reductase activity of the first (youngest) leaf was higher than in the other leaves and decreased linearly with increase in age of the leaf in all the lines. The relationship between relative water content and osmotic potential of the leaves at different positions also varied. The results indicate that a significant effect of salt may appear non-significant if the position of the leaves is not taken into account while sampling. 相似文献
996.
Sahara Rai Alimul Chowdhury Renate L. E. P. Reniers Stephen J. Wood Samuel J. E. Lucas 《Free radical research》2018,52(1):57-69
The brain is highly susceptible to oxidative stress due to its high metabolic demand. Increased oxidative stress and depletion of glutathione (GSH) are observed with aging and many neurological diseases. Exercise training has the potential to reduce oxidative stress in the brain. In this study, nine healthy sedentary males (aged 25?±?4 years) undertook a bout of continuous moderate intensity exercise and a high-intensity interval (HII) exercise bout on separate days. GSH concentration in the anterior cingulate was assessed by magnetic resonance spectroscopy (MRS) in four participants, before and after exercise. This was a pilot study to evaluate the ability of the MRS method to detect exercise-induced changes in brain GSH in humans for the first time. MRS is a non-invasive method based on nuclear magnetic resonance, which enables the quantification of metabolites, such as GSH, in the human brain in vivo. To add context to brain GSH data, other markers of oxidative stress were also assessed in the periphery (in blood) at three time points [pre-, immediately post-, and post (~1?hour)-exercise]. Moderate exercise caused a significant decrease in brain GSH from 2.12?±?0.64?mM/kg to 1.26?±?0.36?mM/kg (p?=?.04). Blood GSH levels increased immediately post-HII exercise, 580?±?101?µM to 692?±?102 µM (n?=?9, p?=?.006). The findings from this study show that brain GSH is altered in response to acute moderate exercise, suggesting that exercise may stimulate an adaptive response in the brain. Due to the challenges in MRS methodology, this pilot study should be followed up with a larger exercise intervention trial. 相似文献
997.
Shabina Parveen Atish Roy Chowdhury Junaid Jibran Jawed Suchandra Bhattacharyya Majumdar Bhaskar Saha Subrata Majumdar 《Microbes and infection / Institut Pasteur》2018,20(2):111-121
DUSP4, an inducible protein has a substrate specificity toward ERK1/2, a component of MAP kinase which is enhanced during Leishmania infection. The DUSP4?/? mice show increased susceptibility towards the infection caused by Toxoplasma gondii and Leishmania mexicana. These observations emphatically established the fact that unlike DUSP1, DUSP4 has host protective role. In our study, it has been Leishmania donovani, the causative agent of visceral leishmaniasis (VL) significantly reduced the expression of DUSP4 during infection. In order to find out the host protective role of DUSP4 in macrophages during VL, we silenced DUSP4 prior to infection and the parasite number within macrophage was counted. Under DUSP4 knock-down condition, phosphorylation of p38 MAPK and generation of pro-inflammatory response like IL-12, TNF-α, and iNOS was decreased significantly. Silencing DUSP4 promoted the phosphorylation of ERK1/2 and the generation of anti-inflammatory response like- IL-10, TGF-β with increased Arginase-1 and Cox-2 activity. Glycyrrhizic Acid (GA), an immunomodulator, already known to suppress L. donovani infection, found to up-regulate DUSP4 expression during L. donovani infection. On the other hand, GA failed to increase Th1 cytokine production and decrease Th2 response during DUSP4 knock-down condition suggesting the key role of DUSP4 while providing protection during L. donovani infection. 相似文献
998.
999.
Chowdhury SF Di Lucrezia R Guerrero RH Brun R Goodman J Ruiz-Perez LM Pacanowska DG Gilbert IH 《Bioorganic & medicinal chemistry letters》2001,11(8):977-980
The program DOCK3.5 was used to search the Cambridge Structural Database for novel inhibitors of Leishmanial dihydrofolate reductase. A number of compounds were obtained and screened against the enzyme and against the intact parasite Leishmania donovani and the related organisms Trypanosoma brucei and Trypanosoma cruzi. The compounds screened showed weak activity in both the enzyme assays and the in vitro assays. 相似文献
1000.
In Young Park Pratim Chowdhury Durga Nand Tripathi Reid T. Powell Ruhee Dere Esteban A. Terzo 《MABS-AUSTIN》2016,8(8):1590-1597
Posttranslational modifications (PTMs) on microtubules differentiate these cytoskeletal elements for a variety of cellular functions. We recently identified SETD2 as a dual-function histone and microtubule methyltransferase, and methylation as a new microtubule PTM that occurs on lysine 40 of α-tubulin, which is trimethylated (α-TubK40me3) by SETD2. In the course of these studies, we generated polyclonal (α-TubK40me3 pAb) and monoclonal (α-TubK40me3 mAb) antibodies to a methylated α-tubulin peptide (GQMPSD-Kme3-TIGGGDC). Here, we characterize these antibodies, and the specific mono-, di- or tri-methylated lysine residues they recognize. While both the pAb and mAb antibodies recognized lysines methylated by SETD2 on microtubules and histones, the clone 18 mAb was more specific for methylated microtubules, with little cross-reactivity for methylated histones. The clone 18 mAb recognized specific subsets of microtubules during mitosis and cytokinesis, and lacked the chromatin staining seen by immunocytochemistry with the pAb. Western blot analysis using these antibodies revealed that methylated α-tubulin migrated faster than unmethylated α-tubulin, suggesting methylation may be a signal for additional processing of α-tubulin and/or microtubules. As the first reagents that specifically recognize methylated α-tubulin, these antibodies are a valuable tool for studying this new modification of the cytoskeleton, and the function of methylated microtubules. 相似文献