Allosteric activation of the nitric oxide receptor soluble guanylate cyclase mapped by cryo-electron microscopy.

Soluble guanylate cyclase (sGC) is the primary receptor for nitric oxide (NO) in mammalian nitric oxide signaling. We determined structures of full-length Manduca sexta sGC in both inactive and active states using cryo-electron microscopy. NO and the sGC-specific stimulator YC-1 induce a 71° rotation of the heme-binding β H-NOX and PAS domains. Repositioning of the β H-NOX domain leads to a straightening of the coiled-coil domains, which, in turn, use the motion to move the catalytic domains into an active conformation. YC-1 binds directly between the β H-NOX domain and the two CC domains. The structural elongation of the particle observed in cryo-EM was corroborated in solution using small angle X-ray scattering (SAXS). These structures delineate the endpoints of the allosteric transition responsible for the major cyclic GMP-dependent physiological effects of NO

Quality of Life Improvement with Sublingual Immunotherapy: A Prospective Study of Efficacy

Due to its excellent safety profile, ease of administration, and economic considerations, sublingual immunotherapy (SLIT) is becoming a preferred form of allergen specific immunotherapy. The efficacy of SLIT is still debated. The purpose of this act of practice trial is to evaluate quality of life outcomes in patients treated with SLIT. Fifty one patients with allergic rhinoconjunctivitis demonstrated by skin testing completed the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) at initiation, at four months and at 10–12 months of SLIT. Significant improvement (P < 0.05) on six of seven domain categories of the RQLQ questionnaire was noted. Total RQLQ scores also showed significant improvement. This study supports SLIT as a modality effective in controlling allergic symptoms

Urban challenges to food and nutrition security

This review of recent literature explores the urban face of food and nutrition security in a more comprehensive, integrated way than most previous efforts. The review is organized around a conceptual framework that identifies food insecurity, inadequate caring behaviors, and poor health as the primary causes of malnutrition. It discusses current knowledge in eight areas that require the special attention of policymakers, development practitioners, and program administrators who wish to improve urban food and nutrition security: the sources and cost of food; incomes and employment; urban agriculture; urban diets; child caregiving practices; childhood mortality, morbidity, and malnutrition; health and environment; and social assistance programs, or safety nets. The review also reports on the magnitude of rural-urban and intra-urban health differences in mortality, morbidity, and malnutrition. In conclusion, the review indicates which policy issues and knowledge gaps remain for future research to address.Urban health. ,Urban poor Services for. ,Food security. ,Malnutrition. ,Child care. ,

Sustainable Transportation for Maine’s Future

Maine is dependent on its transportation infrastructure for continued economic strength and growth, particularly on the 22,670 miles of public roads. Maine ranks fourteenth in the nation for the largest number of highway miles traveled annually per capita - 14,912 per year. Maine is highly reliant on its road system because large areas of the State lack transportation alternatives. This means that the current and future condition of the roadways is a major concern. How such a crucial infrastructure will continue to be supported and enhanced financially to meet the growing needs of the State must be considered carefully

\u3cem\u3emcrA\u3c/em\u3e Gene Abundance Correlates with Hydrogenotrophic Methane Production Rates in Full-scale Anaerobic Waste Treatment Systems

Anaerobic treatment is a sustainable and economical technology for waste stabilization and production of methane as a renewable energy. However, the process is under-utilized due to operational challenges. Organic overload or toxicants can stress the microbial community that performs waste degradation, resulting in system failure. In addition, not all methanogenic microbial communities are equally capable of consistent, maximum biogas production. Opinion varies as to which parameters should be used to monitor the fitness of digester biomass. No standard molecular tools are currently in use to monitor and compare full-scale operations. It was hypothesized that determining the number of gene copies of mcrA, a methanogen-specific gene, would positively correlate with specific methanogenic activity (SMA) rates from biomass samples from six full-scale anaerobic digester systems. Positive correlations were observed between mcrA gene copy numbers and methane production rates against H2 : CO2 and propionate (R2 = 0·67–0·70, P \u3c 0·05) but not acetate (R2 = 0·49, P \u3e 0·05). Results from this study indicate that mcrA gene targeted qPCR can be used as an alternate tool to monitor and compare certain methanogen communities in anaerobic digesters

Editor\u27s Special Section-Larry Schnoor: A Celebration of His Impact on Intercollegiate Forensics

This panel is honoring Professor Larry Schnoor for his lifelong contribu-tions to Intercollegiate Forensics. National Individual Events Tournaments have continued to flourish under his direction. In addition, his constant mentoring has guaranteed the life of this activity. Panelists will describe Professor Schnoor‘s impact on the AFA-NIET, NFA, IOC and both his mentoring of forensic coaches and programs. Professor Schnoor will help to clarify and add to this oral history

Open access series of imaging studies: Longitudinal MRI data in nondemented and demented older adults

The Open Access Series of Imaging Studies (OASIS) is a series of neuroimaging data sets that is publicly available for study and analysis. The present MRI data set consists of a longitudinal collection of 150 subjects aged 60 to 96 all acquired on the same scanner using identical sequences. Each subject was scanned on two or more visits, separated by at least one year for a total of 373 imaging sessions. Subjects were characterized using the Clinical Dementia Rating (CDR) as either nondemented or with very mild to mild Alzheimer‘s disease (AD). 72 of the subjects were characterized as nondemented throughout the study. 64 of the included subjects were characterized as demented at the time of their initial visits and remained so for subsequent scans, including 51 individuals with CDR 0.5 similar level of impairment to individuals elsewhere considered to have ‘mild cognitive impairment’. Another 14 subjects were characterized as nondemented at the time of their initial visit (CDR 0) and were subsequently characterized as demented at a later visit (CDR > 0). The subjects were all right-handed and include both men (n=62) and women (n=88). For each scanning session, 3 or 4 individual T1-weighted MRI scans were obtained. Multiple within-session acquisitions provide extremely high contrast-to-noise making the data amenable to a wide range of analytic approaches including automated computational analysis. Automated calculation of whole brain volume is presented to demonstrate use of the data for measuring differences associated with normal aging and AD

Crystal Structure of the MHC Class I Homolog MIC-A, a γδ T Cell Ligand

AbstractThe major histocompatibility complex (MHC) class I homolog MIC-A functions as a stress-inducible antigen that is recognized by a subset of γδ T cells independent of β2-microglobulin and bound peptides. Its crystal structure reveals a dramatically altered MHC class I fold, both in detail and overall domain organization. The only remnant of a peptide-binding groove is a small cavity formed as the result of disordering a large section of one of the groove-defining helices. Loss of β2-microglobulin binding is due to a restructuring of the interaction interfaces. Structural mapping of sequence variation suggests potential receptor binding sites on the underside of the platform on the side opposite of the surface recognized by αβ T cell receptors on MHC class I–peptide complexes