JNK pathway regulates various physiological processes including inflammatory responses, cell differentiation, cell proliferation, cell death, cell survival and expression of proteins. Deregulation of JNK is linked with various diseases including neurodegenerative disease, autoimmune disease, diabetes, cancer, cardiac hypertrophy and asthma. Three distinct genes JNK1, JNK2 and JNK3 have been identified as regulator of JNK pathway. JNK1 and JNK2 have broad tissue distribution and play a potential role in insulin resistance, inflammation and cell signaling. JNK3 is predominantly found in the CNS neurons, making it an attractive target for neurodegenerative disorders. In this review, we summarize the evidence supporting JNK as a potent therapeutic target, and small molecules from various chemical classes as JNK inhibitors.
Single cell messenger RNA sequencing (scRNA-seq) provides a window into transcriptional landscapes in complex tissues. The recent introduction of droplet based transcriptomics platforms has enabled the parallel screening of thousands of cells. Large-scale single cell transcriptomics is advantageous as it promises the discovery of a number of rare cell sub-populations. Existing algorithms to find rare cells scale unbearably slowly or terminate, as the sample size grows to the order of tens of thousands. We propose Finder of Rare Entities (FiRE), an algorithm that, in a matter of seconds, assigns a rareness score to every individual expression profile under study. We demonstrate how FiRE scores can help bioinformaticians focus the downstream analyses only on a fraction of expression profiles within ultra-large scRNA-seq data. When applied to a large scRNA-seq dataset of mouse brain cells, FiRE recovered a novel sub-type of the pars tuberalis lineage.
Enhanced production of steviol glycosides (SGs) was observed in callus and suspension culture of Stevia rebaudiana treated with proline and polyethylene glycol (PEG). To study their effect, yellow-green and compact calli obtained from in vitro raised Stevia leaves were sub-cultured on MS medium supplemented with 2.0 mg l(-1) NAA and different concentrations of proline (2.5-10 mM) and PEG (2.5-10 %) for 2 weeks, and incubated at 24 ± 1 °C and 22.4 μmol m(-2) s(-1) light intensity provided by white fluorescent tubes for 16 h. Callus and suspension culture biomass (i.e. both fresh and dry weight content) was increased with 5 mM proline and 5 % PEG, while at further higher concentrations, they got reduced. Further, quantification of SGs content in callus (collected at 15th day) and suspension culture (collected at 10th and 15th day) treated with and without elicitors was analysed by HPLC. It was observed that chemical stress enhanced the production of SGs significantly. In callus, the content of SGs increased from 0.27 (control) to 1.09 and 1.83 % with 7.5 mM proline and 5 % PEG, respectively, which was about 4.0 and 7.0 times higher than control. However, in the case of suspension culture, the same concentrations of proline and polyethylene glycol enhanced the SG content from 1.36 (control) to 5.03 and 6.38 %, respectively, on 10th day which were 3.7 times and 4.7 times higher than control.
Steviol glycosides are natural non-caloric sweeteners which are extracted from the leaves of Stevia rebaudiana plant. Present study deals the effect of salts (NaCl and Na2CO3) on callus and suspension culture of Stevia plant for steviol glycoside (SGs) production. Yellow-green and compact calli obtained from in vitro raised Stevia leaves sub-cultured on MS medium supplemented with 2.0 mg l(-1) NAA and different concentrations of NaCl (0.05-0.20%) and Na2CO3 (0.0125-0.10%) for 2 weeks, and incubated at 24 ± 1 °C and 22.4 μmol m(-2) s(-1) light intensity provided by white fluorescent tubes for 16 h. Callus and suspension biomass cultured on salts showed less growth as well as browning of medium when compared with control. Quantification of SGs content in callus culture (collected on 15th day) and suspension cultures (collected at 10th and 15th days) treated with and without salts were analyzed by HPLC. It was found that abiotic stress induced by the salts increased the concentration of SGs significantly. In callus, the quantity of SGs got increased from 0.27 (control) to 1.43 and 1.57% with 0.10% NaCl, and 0.025% Na2CO3, respectively. However, in case of suspension culture, the same concentrations of NaCl and Na2CO3 enhanced the SGs content from 1.36 (control) to 2.61 and 5.14%, respectively, on the 10th day.
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