The crystal structure of a complex involving the D10 T cell receptor (TCR), 16-residue foreign peptide antigen, and the I-Ak self major histocompatibility complex (MHC) class II molecule is reported at 3.2 angstrom resolution. The D10 TCR is oriented in an orthogonal mode relative to its peptide-MHC (pMHC) ligand, necessitated by the amino-terminal extension of peptide residues projecting from the MHC class II antigen-binding groove as part of a mini beta sheet. Consequently, the disposition of D10 complementarity-determining region loops is altered relative to that of most pMHCI-specific TCRs; the latter TCRs assume a diagonal orientation, although with substantial variability. Peptide recognition, which involves P-1 to P8 residues, is dominated by the Valpha domain, which also binds to the class II MHC beta1 helix. That docking is limited to one segment of MHC-bound peptide offers an explanation for epitope recognition and altered peptide ligand effects, suggests a structural basis for alloreactivity, and illustrates how bacterial superantigens can span the TCR-pMHCII surface.

Changes in atmospheric CO 2 concentration have played a central role in algal and plant adaptation and evolution. The commercially important red algal genus, Pyropia (Bangiales) appears to have responded to inorganic carbon (C i ) availability by evolving alternating heteromorphic generations that occupy distinct habitats. The leafy gametophyte inhabits the intertidal zone that undergoes frequent emersion, whereas the sporophyte conchocelis bores into mollusk shells. Here, we analyze a high-quality genome assembly of Pyropia yezoensis to elucidate the interplay between C i availability and life cycle evolution. We find horizontal gene transfers from bacteria and expansion of gene families (e.g. carbonic anhydrase, anti-oxidative related genes), many of which show gametophyte-specific expression or significant up-regulation in gametophyte in response to dehydration. In conchocelis, the release of HCO 3 - from shell promoted by carbonic anhydrase provides a source of C i . This hypothesis is supported by the incorporation of 13 C isotope by conchocelis when co-cultured with 13 C-labeled CaCO 3 .

Purpose Overuse and misuse of antibiotics are the primary risk factors for antibiotics resistance. Inadequate professional competence of primary care physicians might exacerbate these problems in China. This retrospective study aims to document the clinical pattern of antibiotics use and its overuse and misuse rates in rural primary care institutions and to evaluate the association between antibiotics use and characteristics of physicians and their patients. Methods Medical records from 16 primary care hospitals in rural areas of Guizhou province, China were obtained from the Health Information System in 2018. Classification of unnecessary use, incorrect spectrum of antibiotic, escalated use of extended spectrum and combined antibiotics use was based on the Guiding Principle of Clinical Use of Antibiotics (2015, China) and guidelines from the US Centers for Disease Control and Prevention. Generalized Estimating Equations were employed to determine predictive factors for inappropriate antibiotics use. Results A total of 74,648 antibiotics prescriptions were retrieved. Uncomplicated respiratory infection was the most common disease accounting for 58.6% of all prescriptions. The main antibiotic group used was penicillins (51.5%) followed by cephalosporins and macrolides (14% each). Of 57,009 patient visits, only 8.7% of the antibiotic prescriptions were appropriate. Combined use, escalated use of extended spectrum antibiotics, incorrect spectrum and unnecessary antibiotics use was found in 7.8%, 1.9%, 4.3% and 77.3% of patient visits, respectively, of which 28.7% were given intravenously. Antibiotics misuse was significantly more likely among newly employed physicians with lower levels of professional education. Adult patients and those who had public insurance had a higher risk of being prescribed unnecessary antibiotics. Conclusion Overuse of antibiotics for uncomplicated respiratory infection and use of cephalosporins, macrolides and injection antibiotics in primary care are the major problems of clinical practice in rural areas of Guizhou.