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Drought stress imposes a serious threat to crop productivity and nutritional security. Drought adaptation mechanisms involve complex regulatory network comprising of various sensory and signaling molecules. In this context, melatonin has emerged as a potential signaling molecule playing a crucial role in imparting stress tolerance in plants. Melatonin pretreatment regulates various plant physiological processes such as osmoregulation, germination, photosynthesis, senescence, primary/secondary metabolism, and hormonal cross-talk under water deficit conditions. Melatonin-mediated regulation of ascorbate-glutathione (AsA-GSH) cycle plays a crucial role to scavenge reactive oxygen species generated in the cells during drought. Here, in this review, the current knowledge on the role of melatonin to ameliorate adverse effects of drought by modulating morphological, physiological, and redox regulatory processes is discussed. The role of melatonin to improve water absorption capacity of roots by regulating aquaporin channels and hormonal cross-talk involved in drought stress mitigation are also discussed. Overall, melatonin is a versatile bio-molecule involved in growth promotion and yield enhancement under drought stress that makes it a suitable candidate for eco-friendly crop production to ensure food security.

Cheese is a product of ancient biotechnological practices, which has been revolutionized as a functional food product in many parts of the world. Bioactive compounds, such as peptides, polysaccharides, and fatty acids, have been identified in traditional cheese products, which demonstrate functional properties such as antihypertensive, antioxidant, immunomodulation, antidiabetic, and anticancer activities. Besides, cheese-making probiotic lactic acid bacteria (LAB) exert a positive impact on gut health, aiding in digestion, and improved nutrient absorption. Advancement in biotechnological research revealed the potential of metabolite production with prebiotics and bioactive functions in several strains of LAB, yeast, and filamentous fungi. The application of specific biocatalyst producing microbial strains enhances nutraceutical value, resulting in designer cheese products with multifarious health beneficial effects. This review summarizes the biotechnological approaches applied in designing cheese products with improved functional properties.

Mycobacterium tuberculosis (Mtb) infects millions of people each year. These bacilli can survive inside macrophages. To favor their survival, pathogen alters various signal transduction pathways in host cells. Phospholipase C (PLC) signaling regulates various processes in mammalian cells but has never been investigated for their roles in regulating phagocytosis and killing of mycobacteria by macrophages. Here, we report that infection with Mtb but not Mycobacterium smegmatis (MS) induces phosphorylation of PLC-γ2 at tyrosine 1217 in J774A.1 cells. Small interfering RNA-mediated knockdown of PLC-γ2 expression leads to the enhanced killing of both MS and Mtb by these cells suggesting that Mtb activates PLC-γ2 to promote its intracellular survival within macrophages. Knockdown of PLC-γ2 also lead to increased uptake of Mtb but not MS by J774.A.1 cells. Further, we have observed that PLC-γ2 was required for Mtb-induced inhibition of expression of proinflammatory cytokine tumor necrosis factor-α, inducible nitric oxide synthase, and chemokine (C-C motif) ligand 5 (RANTES). Altogether, our results for the first time demonstrate that Mtb induces activation of macrophages PLC-γ2 to inhibit their mycobactericidal response.

Objective Transforming growth factor β–activated kinase 1 (TAK1) is a key MAPKKK family protein in interleukin-1β (IL-1β), tumor necrosis factor (TNF), and Toll-like receptor signaling. This study was undertaken to examine the posttranslational modification of TAK1 and its therapeutic regulation in rheumatoid arthritis (RA). Methods The effect of TAK1, IL-1 receptor–associated kinase 1 (IRAK-1), and TNF receptor–associated factor 6 (TRAF6) inhibition was evaluated in IL-1β–stimulated human RA synovial fibroblasts (RASFs). Western blotting, immunoprecipitation, and 20S proteasome assay were used to study the ubiquitination process in RASFs. The efficacy of epigallocatechin-3-gallate (EGCG), a potent antiinflammatory molecule, in regulating these processes in RASFs was evaluated. Molecular docking was performed to examine the interaction of EGCG with human TAK1, IRAK-1, and TRAF6. These findings were confirmed using a rat model of adjuvant-induced arthritis (AIA). Results Inhibition of TAK1, but not IRAK-1 or TRAF6, completely abrogated IL-1β–induced IL-6 and IL-8 synthesis in RASFs. EGCG inhibited TAK1 phosphorylation at Thr184/187 and occupied the C174 position, an ATP-binding site, to inhibit its kinase activity. EGCG pretreatment also inhibited K63-linked autoubiquitination of TRAF6, a posttranslational modification essential for TAK1 autophosphorylation, by forming a stable H bond at the K124 position on TRAF6. Furthermore, EGCG enhanced proteasome-associated deubiquitinase expression to rescue proteins from proteasomal degradation. Western blot analyses of joint homogenates from rats with AIA showed a significant increase in K48-linked polyubiquitination, TAK1 phosphorylation, and TRAF6 expression when compared to naive rats. Administration of EGCG (50 mg/kg/day) for 10 days ameliorated AIA in rats by reducing TAK1 phosphorylation and K48-linked polyubiquitination. Conclusion Our findings provide a rationale for targeting TAK1 for the treatment of RA with EGCG.

Mutations in the calreticulin gene (CALR) were recently identified in approximately 70-80% of patients with JAK2-V617F-negative essential thrombocytosis and primary myelofibrosis. All frameshift mutations generate a recurring novel C-terminus. Here we provide evidence that mutant calreticulin does not accumulate efficiently in cells and is abnormally enriched in the nucleus and extracellular space compared to wildtype calreticulin. The main determinant of these findings is the loss of the calcium-binding and KDEL domains. Expression of type I mutant CALR in Ba/F3 cells confers minimal IL-3-independent growth. Interestingly, expression of type I and type II mutant CALR in a nonhematopoietic cell line does not directly activate JAK/STAT signaling compared to wildtype CALR and JAK2-V617F expression. These results led us to investigate paracrine mechanisms of JAK/STAT activation. Here we show that conditioned media from cells expressing type I mutant CALR exaggerate cytokine production from normal monocytes with or without treatment with a toll-like receptor agonist. These effects are not dependent on the novel C-terminus. These studies offer novel insights into the mechanism of JAK/STAT activation in patients with JAK2-V617F-negative essential thrombocytosis and primary myelofibrosis.

Cu(I) dicoordination with thiolate ligands is not common. Yet, different from its homologue proteins, human copper chaperone is known to bind Cu(I) using this low coordination number while binding Cu(I) only via the two conserved Cysteine residues, Cys12 and Cys15. Based on structural analysis, this work determines that the protein possesses two distinct conformations referred to as “in” and “out” due to the relative positioning of Cys12 (one of Cu(I) binding residues). The “out” conformation, with Cys12 pointing out, imposes a buried Cu(I) position, whereas the “in” conformation with Cys12 pointing inwards results in a more exposed Cu(I) thus, available for transfer. Using QM/MM methods along with thermodynamic cycles these two conformations are shown to exhibit different coordination preference, suggesting that the protein has evolved to have a unique Cu(I) protection mechanism. It is proposed that the “out” conformation with a preference to dicoordination prevents Cu(I) interaction with external ligands and/or Cu(I) release to the solvent, whereas the “in” conformation with preference to tricoordinated Cu(I), facilitates Cu(I) transfer to target proteins, where additional ligands are involved. Proteins 2013; 81:1411–1419. © 2013 Wiley Periodicals, Inc.

Summary Polythiophene (PT) is an important conjugated polymer that finds applications in electronic and molecular electronic devices. Considering its application area, its electrical conductivity is of major concern. In the present work electrical conductivity (σ) measurements of chemically synthesized and FeCl3 doped PT samples were carried out using a two probe method by applying voltages from 0 V to 100 V in the temperature range from 313 K to 373 K. There was an increase in electrical conductivity by two orders of magnitude after doping. I–V characteristic curves of undoped and doped samples show negative resistance behavior. From log σ versus 1/T graphs it was found that all doped samples showed a metallic nature, where as undoped polythiophene showed a semiconducting nature. Magnetic susceptibility measurements of all samples were carried out using Guoy's method in the temperature range from 300 K to 500 K to characterize the predominant charge carriers. They revealed that the undoped sample was completely diamagnetic in nature where as for the doped samples a number of transitions from diamagnetic to paramagnetic and vice versa were observed with increase in temperature.

Polythiophene has been chemically synthesized using 2,5– dibromothiophene by debromination with magnesium, catalyzed by nickel chloride. The synthesized polymer was undoped using liquid ammonia and then doped again using 5% (wt/volume) aqueous FeCl3 for 2.5, 5 and 10 hour duration. Characterization of undoped as well as doped samples using elemental analysis and FTIR has been carried out. Elemental analysis shows that concentration of Fe+ atoms increases as the duration of doping increases. The FTIR spectrum reveals the complex formation between FeCl3 and polythiophene. All samples were pressed into pellets of about 1cm in diameter. The pellets were coated with gold (Au) on one side and with aluminum (Al) on other side using vacuum deposition technique. I–V measurements of undoped and FeCl3 doped samples, after coating have been carried out using two probe method. I–V measurements, at room temperature, were carried out by applying d. c. voltage with +ve potential to the side of the pellet coated with Au and –ve potential to Al from 0 V to 1 V in step of 0.01 V and then from 1V to 15 V in step of 0.5 V. The measurements were again carried out after interchanging the polarity of the applied voltage. These characteristics are just similar to the characteristics of conventional tunnel diode in forward bias condition and like Schottky diode in reverse bias condition. Various parameters of tunnel diode such as figure of merit, voltage spread, noise figure etc are calculated using the measurements carried out. Noise figure value of undoped polythiophene is very close to ideal value. The performance of all FeCl3 doped sample reduces, however value of the current ratio Ip/Iv (figure of merit) value for 5 hr. FeCl3 doped polythiophene sample matches with that of silicon (Si) tunnel diode.