c-Jun N-Terminal Kinase 1 Is Required for Toll-Like Receptor 1 Gene Expression in Macrophages

P. 5027-5034The regulation of innate immune responses to pathogens occurs through the interaction of Toll-like receptors (TLRs) with pathogen-associated molecular patterns and the activation of several signaling pathways whose contribution to the overall innate immune response to pathogens is poorly understood. We demonstrate a mechanism of control of murine macrophage responses mediated by TLR1/2 heterodimers through c-Jun N-terminal kinase 1 (JNK1) activity. JNK controls tumor necrosis factor alpha production and TLR-mediated macrophage responses to Borrelia burgdorferi, the causative agent of Lyme disease, and the TLR1/TLR2-specific agonist PAM3CSK4. JNK1, but not JNK2, activity regulates the expression of the tlr1 gene in the macrophage cell line RAW264.7, as well as in primary CD11b cells. We also show that the proximal promoter region of the human tlr1 gene contains an AP-1 binding site that is subjected to regulation by the kinase and binds two complexes that involve the JNK substrates c-Jun, JunD, and ATF-2. These results demonstrate that JNK1 regulates the response to TLR1/2 ligands and suggest a positive feedback loop that may serve to increase the innate immune response to the spirocheteS

The role of Notch in regulation of G1 -S progression of cell cycle in T cells

Notch signaling is critical for the regulation of differentiation, proliferation and apoptosis in many cell types. Notch receptors and various Notch ligands have been shown to have a regulatory effect on cell cycle progression during the processes of development and differentiation. Cyclins are proteins that regulate cell cycle check-points, thereby controlling cell cycle progression. The D-cyclins, specifically, are required for overcoming the G1/S checkpoint. It has been shown previously (Ronchini et al) that NotchIC regulates the expression of Cyclin D1, one member of the Cyclin-D family. It has also been reported (Sicinska et al.) that Cyclin D3-/- mice display impaired thymocyte development and do not develop Notch1-induced leukemia. Based on these observations, we hypothesized that cyclin D3 may be a downstream target of Notch signaling in T cells. We observed that T cell receptor signaling increases Cyclin D3, cdk4 and cdk6 expression in peripheral T cells and inhibiting Notch activity reduces Cyclin D3, cdk4 and cdk6 expression in activated T cells. Using reporter assays, as well as chromatin immunoprecipitation, we show that the transactivation domain of Notch1 is critical for regulating the Cyclin D3 promoter. We demonstrate that cyclin D3-cdk4 and cdk6 is also responsible for cell cycle progression in Notch-dependent human T-ALL cell lines. We show that Cyclin D3 and cdk4/6 are important targets in constitutively active Notch signaling in leukemic T cells, as they can partially override the G1 arrest observed with GSI treatment. Together, our data indicate that Notch signaling controls peripheral and leukemic T cell proliferation. Furthermore, we have begun to outline a possible mechanism for the regulated expression of Cyclin D3 and cdk4/6 in leukemic T cells, and through our future experiments we hope to reveal the oncogenic potential of Cyclin D3 as a target of dysregulated Notch1 signaling

Effectiveness of Individual Nutritional Counseling in Improving Biochemical Indices and Nutrition Knowledge of Chronic Kidney Disease Patients

Aim: The aim of the present study was to assess the impact of nutritional counseling on biochemical parameters and nutrition knowledge of chronic kidney disease (CKD) patients. Materials and Methods: The study was conducted on 70 CKD patients, stages 3 and 4, between 25 and 80 years of age. The baseline data were collected from Fortis Hospital, Jaipur, Rajasthan, using interview schedule, which included information on demographic profile, anthropometric measurements, biochemical parameters, medical history, and dietary pattern of the patients. The nutritional counseling was conducted in two phases, the first phase included counseling that was imparted to patients on the basis of their biochemical parameters, followed by monitoring for 4 weeks. Thereafter, second phase counseling, based on results obtained from the first phase, was imparted. The data were once again collected and analyzed after a period of 12 weeks. Results and Conclusion: Hypertensive nephropathy was the most common cause of CKD, followed by diabetes mellitus and glomerulonephritis. Anthropometric measurements showed little change in mean body mass index of the patients, post counseling, however, nonsignificant. On the other hand, a significant decrease was observed in serum creatinine, blood urea nitrogen, serum potassium, and serum phosphorus levels. Nutritional counseling exhibited a strong positive impact on nutrition knowledge of CKD patients

Nutrient Dense Ready to Prepare Meetha cheela for Elderly People at Risk of Malnutrition

Elderly people suffer from a number of physical, psychological, and social changes which makes them vulnerable to malnutrition. These changes present the need to develop nutrient dense products which can be easily prepared by them. The present study was planned with the objective to prepare such a product. The ingredients for the ready to prepare (RTP) sweet cheela mix were subjected to various processing techniques to increase nutrient availability and digestibility. A combination of wheat, green gram whole, and finger millet (ragi) was used in different proportions (15%, 30%, 45%, and 60%) in the first stage of value addition. Value addition was carried out in the most acceptable variation from Stage 1, using processed mango, nuts, and oilseeds in different proportions (10%, 20%, and 30%). The RTP meetha cheela mix of the most acceptable variation was selected through sensory evaluation and then subjected to biochemical analysis and shelf life assessment. The results revealed MCF3 (30%) to be the most acceptable variation after Stage 2 value addition, which contained flours of malted finger millet, wheat, green gram along with dried ripe mango, almonds, raisins, sunflower seeds, and sesame seeds. The prepared mix had statistically significant higher amount of fat, fiber, ash, carbohydrate, energy, Vitamin C, β carotene, Vitamin E, calcium, potassium, and total antioxidant activity. Low moisture levels and vacuum packaging provided the product a good shelf life till 3 months

Effect of Low Temperature on Fatigue Crack Growth Rate of HSLA Steel

The material used in this investigation is an ASTM A633 Grade C, HSLA steel which is a normalized high-strength low-alloy steel. Which is widely used structural steel for welded, riveted or bolted construction requiring superior notch toughness performance at low ambient temperatures. Typical applications for A633 Gr.C include utility pole base plates, off-shore oil and gas platforms, construction equipment frames, electric shovel dipper handles and suspension components. Hence the importance of predicting fatigue life and its performance of at low ambient temperature is very important. In the present investigation an attempt has been made to study the effects of low-temperature on fatigue crack growth behavior of HSLA steel. Tests were carried out using CT specimens, at low temperature under mode-I condition. It is observed that crack growth rate increases with decreasing temperature upto DBTT. Further reduction of temperature registered increase in crack growth rate in most of the cases. The behavior has been explained on the basis of impact energy of the material at different temperature, fractographic observations as well as relative humidity in the cold chamber. Exponential model has been developed to predict fatigue life at low temperature. The predicted results of the models were found to be in good agreement with the experimental data

Electro-capacitive performance of haemoglobin/polypyrrole composites for high power density electrode

Abstract Background Haemoglobin (Hb)-doped polypyrrole (PPy) composites serving as energy storage material have rarely been premeditated. Methods In this perspective, a novel class of haemoglobin/polypyrrole composites (HPyCs) by doping metal derivative Hb into PPy matrix with concentrations (PPy, 1%, 2% and 3% Hb in w/w) has been synthesized by cationic surfactant assisted dilute polymerization method. The obtained samples were exemplified by Fourier transform-infrared spectroscopy (FT-IR) and thermogravimetric-differential thermal analysis-differential thermogravimetry (TG-DTA-DTG). Electrochemical capacitance (Cs, F/g) of electrodes fabricated from PPy and HPyCs over stainless steel in the presence of sulphonated polysulphone as binder has been investigated in KOH solution (1.0 M) with reference to Ag/AgCl at scan rate (V/s) ranging 0.001–0.2. HPyC3% has shown Cs of 445.75F/g along with energy and power densities of 14.37 Wh/kg and 596.54 Wh/kg respectively, which is greater as compared to 200.56F/g for PPy. Conclusion The composites show good charge-discharge with improved electrochemical cyclic stability of the HPyCs over PPy. This behaviour points out that fabricated HPyCs may dole out as prospective electrode materials for development of electrochemical supercapacitors

CircAMOTL1 RNA and AMOTL1 Protein: Complex Functions of <i>AMOTL1</i> Gene Products

The complexity of the cellular proteome facilitates the control of a wide range of cellular processes. Non-coding RNAs, including microRNAs and long non-coding RNAs, greatly contribute to the repertoire of tools used by cells to orchestrate various functions. Circular RNAs (circRNAs) constitute a specific class of non-coding RNAs that have recently emerged as a widely generated class of molecules produced from many eukaryotic genes that play essential roles in regulating cellular processes in health and disease. This review summarizes current knowledge about circRNAs and focuses on the functions of AMOTL1 circRNAs and AMOTL1 protein. Both products from the AMOTL1 gene have well-known functions in physiology, cancer, and other disorders. Using AMOTL1 as an example, we illustrate how focusing on both circRNAs and proteins produced from the same gene contributes to a better understanding of gene functions