Phenotypic analysis of a suite of double mutants lacking both SS5 and other proteins implicated in starch granule initiation allows us to propose how SS5 may act in this process.In rice (Oryza sativa) endosperm cells, mRNAs encoding glutelin and prolamine are translated on distinct cortical-endoplasmic reticulum (ER) subdomains (the cisternal-ER and protein body (PB)-ER), a process that facilitates targeting of their proteins to different endomembrane compartments. Although the cis- and trans-factors responsible for mRNA localization have been defined over the years, how these mRNAs are transported to the cortical ER has yet to be resolved. Here, we show that the two interacting glutelin zipcode RNA-binding proteins (RBPs), RBP-P and RBP-L, form a quaternary complex with the membrane fusion factors N-ethylmaleimide-sensitive factor (NSF) and the small GTPase Rab5a, enabling mRNA transport on endosomes. Direct interaction of RBP-L with Rab5a, between NSF and RBP-P, and between NSF and Rab5a were established. Biochemical and microscopic analyses confirmed the co-localization of these RBPs with NSF on Rab5a-positive endosomes that carry glutelin mRNAs. Analysis of a loss-of-function rab5a mutant showed that glutelin mRNA and the quaternary complex were mis-targeted to the extracellular paramural body structure formed by aborted endosomal trafficking, further confirming the involvement of endosomal trafficking in glutelin mRNA transport. Overall, these findings demonstrate that mRNA localization in plants co-opts membrane trafficking via the acquisition of new functional binding properties between RBPs and two essential membrane trafficking factors, thus defining an endosomal anchoring mechanism in mRNA localization.Phosphatidic acid (PA) is a key phospholipid in glycerolipid metabolism and signaling. Diacylglycerol kinase (DGK) produces PA by phosphorylating diacylglycerol, a crucial step in PA metabolism. Although DGK activity is known to be involved in plant development and stress response, how specific DGK isoforms function in development and phospholipid metabolism remains elusive. Here, we showed that Arabidopsis DGK2 and DGK4 are crucial for gametogenesis and biosynthesis of phosphatidylglycerol and phosphatidylinositol in the endoplasmic reticulum (ER).  https://www.selleckchem.com/products/myk-461.html  With comprehensive transcriptomic data of 7 DGKs and genetic crossing, we found that dgk2-1/- dgk4-1/- plants were gametophyte-lethal, although parental single homozygous plants were viable. The dgk2-1/+ dgk4-1/+ double heterozygote showed defective pollen growth and seed development because of non-viable mutant gametes. DGK2 and DGK4 localized to the endoplasmic reticulum (ER) and were involved in PA production for pollen growth. Transgenic knock-down lines of DGK2 and DGK4 confirmed the gametophyte defect and also revealed defective leaf and root growth. Glycerolipid analysis in the knockdown lines showed that phosphatidylglycerol and phosphatidylinositol metabolism was affected differently in floral buds and leaves. These results suggest that DGK2 and DGK4 are essential during gametogenesis and are required for ER-localized phospholipid metabolism in vegetative and reproductive growth.New York City (NYC) has emerged as one of the epicenters of the current SARS-CoV-2 pandemic. To identify the early transmission events underlying the rapid spread of the virus in the NYC metropolitan area, we sequenced the virus causing COVID-19 in patients seeking care at the Mount Sinai Health System. Phylogenetic analysis of 84 distinct SARS-CoV2 genomes indicates multiple, independent but isolated introductions mainly from Europe and other parts of the United States. Moreover, we find evidence for community transmission of SARS-CoV-2 as suggested by clusters of related viruses found in patients living in different neighborhoods of the city.Objectives The window of opportunity (WOO) hypothesis suggests a limited time frame to stop rheumatoid arthritis (RA). We hypothesised that a WOO could either be represented by a hyperbolic ('curved') decline in the chance to achieve the outcome sustained drug-free remission (sDFR) over time, after which achieving sDFR is not possible anymore, or by a more gradual linear decline approaching zero chance to achieve sDFR. Methods Patients with RA (symptom duration less then 2 years) were included from two randomised trials BehandelStrategieën (BeSt), n=508 and Induction therapy with Methotrexate and Prednisone in Rheumatoid Or Very Early arthritic Disease (IMPROVED), n=479. Cox-regression was performed to assess the shape of the association between symptom duration and sDFR (Disease Activity Score less then 1.6, no disease-modifying anti-rheumatic drugs for ≥1 year) for patients starting slow-acting monotherapy (IMPROVED, BeSt) or fast-acting combination therapy (BeSt). Likelihood ratio tests were used to compare the fit of linear and non-linear models in both databases separately. Predictions from the best fitting models were used to assess whether the absolute risk to achieve sDFR approaches zero with increasing symptom duration. Results In BeSt and IMPROVED, 54/226 and 110/421 patients achieved sDFR with fast-acting treatment, and 53/243 (BeSt) with slow-acting treatment. Non-linear models did not fit better than linear models (fast-acting treatment BeSt p=0.743, IMPROVED p=0.337; slow-acting treatment BeSt p=0.609). After slow-acting monotherapy, linear models declined steeper. None of the models approached zero chance to achieve sDFR over time. Conclusions The chance to achieve sDFR decreased gradually over time, and decreased fastest in patients starting slow-acting monotherapy. In both treatment groups, we found no evidence for a WOO within 2 years symptom duration.World War II had a profound, but uneven, impact on the delivery of services designed to support the bodies and minds of English children. This article, which is based on a study of a rural local authority located in North-West England, explores the influence of World War II on children's welfare services. Drawing on detailed case files relating to individual children and reports published by local and national policy makers, the article advances three related arguments which together nuance existing understandings of the conflict and its longer-term consequences. First, the article argues that many of the problems associated with evacuees were already familiar to medical and social work professionals. This awareness has important consequences for how we conceptualise the wartime proposals that attracted policy makers' attention. Second, the article shows that the arrival of evacuees into reception areas initially resulted in an expansion of children's services. A fuller understanding of Britain's welfare state, however, must acknowledge that local authorities continued to wield significant influence over the delivery of specialist services once the conflict ended.