Opposing Roles of Membrane and Soluble Forms of the Receptor for Advanced Glycation End Products in Primary Respiratory Syncytial Virus Infection

Respiratory syncytial virus (RSV), a common respiratory pathogen in infants and the older population, causes pulmonary inflammation and airway occlusion that leads to impairment of lung function. Here, we have established a role for receptor for advanced glycation end products (RAGE) in RSV infection. RAGE-deficient (ager−/−) mice were protected from RSV-induced weight loss and inflammation. This protection correlated with an early increase in type I interferons, later decreases in proinflammatory cytokines, and a reduction in viral load. To assess the contribution of soluble RAGE (sRAGE) to RSV-induced disease, wild-type and ager−/− mice were given doses of sRAGE following RSV infection. Of interest, sRAGE treatment prevented RSV-induced weight loss and neutrophilic inflammation to a degree similar to that observed in ager−/− mice. Our work further elucidates the roles of RAGE in the pathogenesis of respiratory infections and highlights the opposing roles of membrane and sRAGE in modulating the host response to RSV infection

New Era of Air Quality Monitoring from Space: Geostationary Environment Monitoring Spectrometer (GEMS)

GEMS will monitor air quality over Asia at unprecedented spatial and temporal resolution from GEO for the first time, providing column measurements of aerosol, ozone and their precursors (nitrogen dioxide, sulfur dioxide and formaldehyde). Geostationary Environment Monitoring Spectrometer (GEMS) is scheduled for launch in late 2019 - early 2020 to monitor Air Quality (AQ) at an unprecedented spatial and temporal resolution from a Geostationary Earth Orbit (GEO) for the first time. With the development of UV-visible spectrometers at sub-nm spectral resolution and sophisticated retrieval algorithms, estimates of the column amounts of atmospheric pollutants (O3, NO2, SO2, HCHO, CHOCHO and aerosols) can be obtained. To date, all the UV-visible satellite missions monitoring air quality have been in Low Earth orbit (LEO), allowing one to two observations per day. With UV-visible instruments on GEO platforms, the diurnal variations of these pollutants can now be determined. Details of the GEMS mission are presented, including instrumentation, scientific algorithms, predicted performance, and applications for air quality forecasts through data assimilation. GEMS will be onboard the GEO-KOMPSAT-2 satellite series, which also hosts the Advanced Meteorological Imager (AMI) and Geostationary Ocean Color Imager (GOCI)-2. These three instruments will provide synergistic science products to better understand air quality, meteorology, the long-range transport of air pollutants, emission source distributions, and chemical processes. Faster sampling rates at higher spatial resolution will increase the probability of finding cloud-free pixels, leading to more observations of aerosols and trace gases than is possible from LEO. GEMS will be joined by NASA's TEMPO and ESA's Sentinel-4 to form a GEO AQ satellite constellation in early 2020s, coordinated by the Committee on Earth Observation Satellites (CEOS)

Genetic variants in sex hormone pathways and the risk of type 2 diabetes among African American, Hispanic American, and European American postmenopausal women in the US.

BACKGROUND: Sex hormones are implicated in the development of diabetes. However, whether genetic variations in sex hormone pathways (SHPs) contribute to the risk of type 2 diabetes mellitus (T2DM) remains to be determined. This study investigated associations between genetic variations in all candidate genes in SHPs and T2DM risk among a cohort of women participating in the Womens Health Initiative (WHI). METHODS: Single nucleotide polymorphisms (SNPs) located within 30 kb upstream and downstream of SHP genes were comprehensively examined in 8180 African American, 3498 Hispanic American, and 3147 European American women in the WHI. In addition, whether significant SNPs would be replicated in independent populations was examined. RESULTS: After adjusting for age, region, and ancestry estimates and correcting for multiple testing, seven SNPs were significantly associated with the risk of T2DM among Hispanic American women were identified in the progesterone receptor (PGR) gene, with rs948516 showing the greatest significance (odds ratio 0.67; 95% confidence interval 0.57-0.78; P = 8.8 × 10-7 ; false discovery rate, Q = 7.8 × 10-4 ). These findings were not replicated in other ethnic groups in the WHI or in sex-combined analyses in replication studies. CONCLUSION: Significant signals were identified implicating the PGR gene in T2DM development in Hispanic American women in the WHI, which are consistent with genome-wide association studies findings linking PGR to glucose homeostasis. Nevertheless, the PGR SNPs-T2DM association was not statistically significant in other ethnic populations. Further studies, especially sex-specific analyses, are needed to confirm the findings and clarify the role of SHPs in T2DM

Spatial Mapping of Lipids at Cellular Resolution in Embryos of Cotton

Article on the spatial mapping of lipids at cellular resolution in embryos of cotton

Precision targeting of autoantigen-specific B cells in muscle-specific tyrosine kinase myasthenia gravis with chimeric autoantibody receptor T cells.

Muscle-specific tyrosine kinase myasthenia gravis (MuSK MG) is an autoimmune disease that causes life-threatening muscle weakness due to anti-MuSK autoantibodies that disrupt neuromuscular junction signaling. To avoid chronic immunosuppression from current therapies, we engineered T cells to express a MuSK chimeric autoantibody receptor with CD137-CD3ζ signaling domains (MuSK-CAART) for precision targeting of B cells expressing anti-MuSK autoantibodies. MuSK-CAART demonstrated similar efficacy as anti-CD19 chimeric antigen receptor T cells for depletion of anti-MuSK B cells and retained cytolytic activity in the presence of soluble anti-MuSK antibodies. In an experimental autoimmune MG mouse model, MuSK-CAART reduced anti-MuSK IgG without decreasing B cells or total IgG levels, reflecting MuSK-specific B cell depletion. Specific off-target interactions of MuSK-CAART were not identified in vivo, in primary human cell screens or by high-throughput human membrane proteome array. These data contributed to an investigational new drug application and phase 1 clinical study design for MuSK-CAART for the treatment of MuSK autoantibody-positive MG

Development and preliminary usability testing of an electronic conversation guide incorporating patient values and prognostic information in preparation for older people's decision-making near the end of life

Initiating end-of-life conversations can be daunting for clinicians and overwhelming for patients and families. This leads to delays in communicating prognosis and preparing for the inevitable in old age, often generating potentially harmful overtreatment and poor-quality deaths. We aimed to develop an electronic resource, called Communicating Health Alternatives Tool (CHAT) that was compatible with hospital medical records software to facilitate preparation for shared decision-making across health settings with older adults deemed to be in the last year of life.The project used mixed methods including: literature review, user-directed specifications, web-based interface development with authentication and authorization; clinician and consumer co-design, iterative consultation for user testing; and ongoing developer integration of user feedback. An internet-based conversation guide to facilitate clinician-led advance care planning was co-developed covering screening for short-term risk of death, patient values and preferences, and treatment choices for chronic kidney disease and dementia. Printed summary of such discussion could be used to begin the process in hospital or community health services. Clinicians, patients, and caregivers agreed with its ease of use and were generally accepting of its contents and format. CHAT is available to health services for implementation in effectiveness trials to determine whether the interaction and documentation leads to formal decision-making, goal-concordant care, and subsequent reduction of unwanted treatments at the end of life

Development and preliminary usability testing of an electronic conversation guide incorporating patient values and prognostic information in preparation for older people's decision-making near the end of life

Initiating end-of-life conversations can be daunting for clinicians and overwhelming for patients and families. This leads to delays in communicating prognosis and preparing for the inevitable in old age, often generating potentially harmful overtreatment and poor-quality deaths. We aimed to develop an electronic resource, called Communicating Health Alternatives Tool (CHAT) that was compatible with hospital medical records software to facilitate preparation for shared decision-making across health settings with older adults deemed to be in the last year of life.The project used mixed methods including: literature review, user-directed specifications, web-based interface development with authentication and authorization; clinician and consumer co-design, iterative consultation for user testing; and ongoing developer integration of user feedback. An internet-based conversation guide to facilitate clinician-led advance care planning was co-developed covering screening for short-term risk of death, patient values and preferences, and treatment choices for chronic kidney disease and dementia. Printed summary of such discussion could be used to begin the process in hospital or community health services. Clinicians, patients, and caregivers agreed with its ease of use and were generally accepting of its contents and format. CHAT is available to health services for implementation in effectiveness trials to determine whether the interaction and documentation leads to formal decision-making, goal-concordant care, and subsequent reduction of unwanted treatments at the end of life