Apoptosis signal-regulating kinases (ASK1-3) are apical kinases of the p38 and JNK MAP kinase pathways. They are activated by diverse stress stimuli, including reactive oxygen species, cytokines, and osmotic stress; however, a molecular understanding of how ASK proteins are controlled remains obscure. Here, we report a biochemical analysis of the ASK1 kinase domain in conjunction with its N-terminal thioredoxin-binding domain, along with a central regulatory region that links the two. We show that in solution the central regulatory region mediates a compact arrangement of the kinase and thioredoxin-binding domains and the central regulatory region actively primes MKK6, a key ASK1 substrate, for phosphorylation. The crystal structure of the central regulatory region reveals an unusually compact tetratricopeptide repeat (TPR) region capped by a cryptic pleckstrin homology domain. Biochemical assays show that both a conserved surface on the pleckstrin homology domain and an intact TPR region are required for ASK1 activity. We propose a model in which the central regulatory region promotes ASK1 activity via its pleckstrin homology domain but also facilitates ASK1 autoinhibition by bringing the thioredoxin-binding and kinase domains into close proximity. Such an architecture provides a mechanism for control of ASK-type kinases by diverse activators and inhibitors and demonstrates an unexpected level of autoregulatory scaffolding in mammalian stress-activated MAP kinase signaling.itogen-activated protein (MAP) kinase cascades transmit signals from membrane-associated receptors to intracellular targets to effect changes in cellular behavior. They form a hierarchical system in which activated upstream kinases (MAP3Ks) phosphorylate intermediate MAP kinase kinases (MAP2Ks), which in turn phosphorylate terminal MAP kinases, primarily ERK, p38, and JNK and their isoforms (1). Extensive studies have focused on the activation of RAS-RAF-MEK upstream in the ERK pathway and provided fertile ground for the discovery of new therapeutics (2). In contrast to the ERK pathway, which primarily promotes cellular proliferation, JNK and p38 phosphorylate a range of substrates to promote inflammation and cell death (1, 3). In addition, cross-regulation among the p38, JNK, and ERK pathways is important for the efficacy of various cancer therapies that are in use or in development (4, 5). Molecular details on the more diverse upstream regulation of the p38 and JNK pathways are currently less clear, however.Apoptosis signal-regulating kinases (ASK1-3) are MAP3Ks that trigger cellular responses to redox stress and inflammatory cytokines (6, 7) and play vital roles in innate immunity and viral infection (8-11). When activated, ASK1-3 activate JNK and p38 via phosphorylation of MAP2Ks (MKK3/4/6/7) (12). The key initiator role of ASK1-3 in this pathway means that either too much or too little ASK activity can have pathological effects. For instance, inhibiting ASK1 is beneficial against gastric cancer (13,14), but inactivating mutations in ASK1...
CRISPR-Cas adaptive immune systems provide bacteria and archaea with defense16 against their viruses and other mobile genetic elements 1 . CRISPR-Cas immunity 17 involves the formation of ribonucleoprotein complexes that specifically bind and 18 degrade foreign nucleic acids 2,3 . Despite advances in the biotechnological exploitation 19 of select systems, multiple CRISPR-Cas types remain uncharacterized 4 . Here, we 20 investigated a type I-D system from Synechocystis and revealed the Cascade complex, 21 which is required for interference, forms a hybrid ribonucleoprotein complex that is 22 structurally and genetically related to both type I and III systems 5-8 . Surprisingly, the 23 type I-D complex contained multiple functionally-important small subunit proteins 24 encoded from an internal in-frame translation initiation site within the large subunit 25 gene, cas10d. Structural analysis revealed that these small subunits bound the 26 complex similarly to Cas11 small subunits in other type I and III systems, where they 27 are encoded as a separate gene. We show that internal translation of small subunits 28 from within large subunit genes is conserved across diverse type I-D, I-B and I-C 29 systems, which account for ~23% of all sequenced CRISPR-Cas systems 4 . Indeed, we 30 demonstrate that small subunits are expressed from within the cas8c large subunit 31 gene in the Desulfovibrio vulgaris type I-C system. Our work reveals an unexpected 32 aspect of CRISPR-Cas evolution and expansion of the coding potential from within 1 single cas genes. 2 3
The experiment on ten genotypes of gladiolus (Gladiolus grandiflorus L.) was conducted to work out the genetic variability, heritability, genetic advance and genetic divergence effects of their various attributes on spike yield. The analysis of variance revealed that mean squares due to treatments were highly significant for all characters. The magnitude of phenotypic coefficient of variation was higher than corresponding genotypic coefficient of variation for all the characters. Expected genetic advance expressed as per cent of mean ranged from 4.83% to 102.96%. The highest of genetic advance as percentage of mean was recorded for number of cormels per plant (102.96%) and lowest for number of spikes per plant and number of spikes per hectare (4.83%). High genetic advance in percent of mean coupled with high heritability was recorded for the characters of number of cormels per plant, weight of cormels per plant, spike yield per hectare, vase life, average weight of spike, duration of flowering, length of spike, days taken for initiation of spike, number of leaves per plant, days taken for complete sprouting, height of plant, percentage of sprouting, number of cormels per plant provide greater scope for further improvement of these traits in advance generations. Genetic advance ranged from 0.066 to 8278.50. The genetic advance is highest for number of spikes per hectare (q) (8278.50) and lowest number of spikes per plant (0.066). The PCV were higher than GCV for all the characters taken in to consideration. Phenotypic and genotypic coefficient variations were highest for number of cormels per plant (50.04 and 50.11 respectively) and lowest for number of spike per plant (3.44 and 5.04 respectively). Heritability and genetic advance indicate that the additive nature of gene action and reliability of those characters for selection and emerged as ideal traits for improvement through selection. Heritability and genetic advance indicate that the additive nature of gene action and reliability of those characters for selection and emerged as ideal traits for improvement through selection.
Background: Paspalum scorbiculatum is an annual crop and has superior nutritional properties including high micronutrients, dietary fiber content and gluten free. It has low glycemic index (GI) carbohydrate diets help in prevention of Obesity, Diabeties and Cardiovascular diseases, etc. The current study was aimed to find out the suitable pre- sowing seed treatments for Kodo millet. Methods: During the Kharif season 2019- 2020 total of 12 pre- sowing seed treatments were subjected with Botanicals, Magnetic and Electric fields, Thermal (Hot water) treatments and to fix the best treatment based on Seed Quality and Morphological traits of treated seeds. Morphological traits play an major role in crop growth and development where as, the present investigation was carried out with farmer’s variety in field (RBD) design in 3 replications and laboratory (CRD) design in 4 replications in order to “Standardization of different pre- sowing seed treatments on growth, yield and yield attributing traits of Kodo millet (Paspalum scorbiculatum). Seeds were subjected to various pre- sowing seed treatments viz. (T0) control, exposure to Magnetic field at 100 mT, 200 mT, 400 mT for 15,30 and 45 min; exposure to Electric field at 50 mA, 100 mA, 150 mA for 5,10, 15 min. Treatment with botanicals cow dung (5 gm) and Datura leaf extract (2.5 ml) for 12 hrs; Thermal hot water treatment at 46°C and 50°C for 10 min. Result: Among all the treatments, T4-Magnetic field (200 mT) gave the best results in field and lab conditions of field emergence (98.610) and germination% (98.5), Magnetic field (400 mT) shown the good results and significantly higher values of all other yield (45.867, 78.833, 660.480, 165.120) and morphological traits as well as seed quality parameters like shoot length (86.925), root length (44.55), seedling length (13.131), vigour index- I and II (1267.138 and 5.058), fresh (0.343) and dry (0.0524) weight of seedlings and comparatively control (T0) was observed lowest to other treatments. As such, Magnetic treatment is quite effective for seedling establishment to overcome low germination and yield which helps in Qualitative and Quantiative seed production of Millets in sustainable agriculture.
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