TYK2 is a nonreceptor tyrosine kinase involved in adaptive and innate immune responses. A deactivating coding variant has previously been shown to prevent receptor-stimulated activation of this kinase and provides high protection from several common autoimmune diseases but without immunodeficiency. An agent that recapitulates the phenotype of this deactivating coding variant may therefore represent an important advancement in the treatment of autoimmunity. BMS-986165 is a potent oral agent that similarly blocks receptor-stimulated activation of TYK2 allosterically and with high selectivity and potency afforded through optimized binding to a regulatory domain of the protein. Signaling and functional responses in human TH17, TH1, B cells, and myeloid cells integral to autoimmunity were blocked by BMS-986165, both in vitro and in vivo in a phase 1 clinical trial. BMS-986165 demonstrated robust efficacy, consistent with blockade of multiple autoimmune pathways, in murine models of lupus nephritis and inflammatory bowel disease, supporting its therapeutic potential for multiple immune-mediated diseases.

Inositol signaling is believed to play a crucial role in various aspects of plant growth and adaptation. As an important component in biosynthesis and degradation of myo-inositol and its derivatives, inositol phosphatases could hydrolyze the phosphate of the inositol ring, thus affecting inositol signaling. Until now, more than 30 members of inositol phosphatases have been identified in plants, which are classified intofive families, including inositol polyphosphate 5-phosphatases (5PTases), suppressor of actin (SAC) phosphatases, SAL1 phosphatases, inositol monophosphatase (IMP), and phosphatase and tensin homologue deleted on chromosome 10 (PTEN)-related phosphatases. The current knowledge was revised here in relation to their substrates and function in response to abiotic stress. The potential mechanisms were also concluded with the focus on their activities of inositol phosphatases. The general working model might be that inositol phosphatases would degrade the Ins(1,4,5)P3 or phosphoinositides, subsequently resulting in altering Ca2+ release, abscisic acid (ABA) signaling, vesicle trafficking or other cellular processes.

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Core Ideas Dry pea yield, protein, and resistant starch varied greatly across Montana. Yield and protein were mainly determined by environments. Resistant starch is controlled by genetics to a great extent. Effects of drought index, growth period, seed size, and seed weight on yield, protein, and starch were analyzed. Pea (Pisum sativum L.) has long been an important component of the human diet, providing an excellent source of protein. In addition to its protein, pea starch, especially resistant starch (RS), has received an extensive attention in food industries in recent years. We evaluated nine pea cultivars varying in cotyledon color, grain weight, maturity group, and phenology planted at five locations with diverse climatic conditions across Montana in 2013 and 2014 to assess genetic and environmental factors affecting their yield, protein, RS, and total starch (TS). Grain yield varied from 982 to 5951 kg ha−1, RS content ranged from 5 to 53 g kg−1, and protein from 159 to 251 g kg−1. Statistical analysis showed that environment was the most important driving factor in grain yield, protein, and TS determination whereas RS content was mainly determined by cultivar. Drought at all phenological stages reduced pea yield and different cultivars tended to respond differently. Yield was positively correlated with protein, implying a potential to select/breed a cultivar with higher yield and protein. Protein was negatively correlated with TS, thus protein‐ or starch‐type cultivars may be bred for different end users. Compared to other cultivars tested, DS Admiral was the most promising one with above average yield, protein, and RS.

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