Highly frequent PIK3CA amplification is associated with poor prognosis in gastric cancer

<p>Abstract</p> <p>Background</p> <p>The phosphoinositide 3-kinase (PI3K)/Akt pathway plays a fundamental role in cell proliferation and survival in human tumorigenesis, including gastric cancer. <it>PIK3CA </it>mutations and amplification are two major causes of overactivation of this pathway in human cancers. However, until this work, there was no sound investigation on the association of <it>PIK3CA </it>mutations and amplification with clinical outcome in gastric cancer, particularly the latter.</p> <p>Methods</p> <p>Using direct sequencing and real-time quantitative PCR, we examined <it>PIK3CA </it>mutations and amplification, and their association with clinicopathological characteristics and clinical outcome of gastric cancer patients.</p> <p>Results</p> <p><it>PIK3CA </it>mutations and amplification were found in 8/113 (7.1%) and 88/131 (67%) gastric cancer patients, respectively. <it>PIK3CA </it>amplification was closely associated with increased phosphorylated Akt (p-Akt) level. No relationship was found between <it>PIK3CA </it>mutations and clinicopathological characteristics and clinical outcome in gastric cancer. <it>PIK3CA </it>amplification was significantly positively associated with cancer-related death. Importantly, Kaplan-Meier survival curves revealed that the patients with <it>PIK3CA </it>amplification had significantly shorter survival times than the patients without <it>PIK3CA </it>amplification.</p> <p>Conclusions</p> <p>Our data showed that <it>PIK3CA </it>mutations were not common, but its amplification was very common in gastric cancer and may be a major mechanism in activating the PI3K/Akt pathway in gastric cancer. Importantly, Kaplan-Meier survival curves revealed that <it>PIK3CA </it>amplification was significantly positively associated with poor survival of gastric cancer patients. Collectively, the PI3K/Akt signaling pathway may be an effective therapeutic target in gastric cancer.</p

A review of elliptical and disc galaxy structure, and modern scaling laws

A century ago, in 1911 and 1913, Plummer and then Reynolds introduced their models to describe the radial distribution of stars in `nebulae'. This article reviews the progress since then, providing both an historical perspective and a contemporary review of the stellar structure of bulges, discs and elliptical galaxies. The quantification of galaxy nuclei, such as central mass deficits and excess nuclear light, plus the structure of dark matter halos and cD galaxy envelopes, are discussed. Issues pertaining to spiral galaxies including dust, bulge-to-disc ratios, bulgeless galaxies, bars and the identification of pseudobulges are also reviewed. An array of modern scaling relations involving sizes, luminosities, surface brightnesses and stellar concentrations are presented, many of which are shown to be curved. These 'redshift zero' relations not only quantify the behavior and nature of galaxies in the Universe today, but are the modern benchmark for evolutionary studies of galaxies, whether based on observations, N-body-simulations or semi-analytical modelling. For example, it is shown that some of the recently discovered compact elliptical galaxies at 1.5 < z < 2.5 may be the bulges of modern disc galaxies.Comment: Condensed version (due to Contract) of an invited review article to appear in "Planets, Stars and Stellar Systems"(www.springer.com/astronomy/book/978-90-481-8818-5). 500+ references incl. many somewhat forgotten, pioneer papers. Original submission to Springer: 07-June-201

Characterising droughts in Central America with uncertain hydro-meteorological data

Central America is frequently affected by droughts that cause significant socio-economic and environmental problems. Drought characterisation, monitoring and forecasting are potentially useful to support water resource management. Drought indices are designed for these purposes, but their ability to characterise droughts depends on the characteristics of the regional climate and the quality of the available data. Local comprehensive and high-quality observational networks of meteorological and hydrological data are not available, which limits the choice of drought indices and makes it important to assess available datasets. This study evaluated which combinations of drought index and meteorological dataset were most suitable for characterising droughts in the region. We evaluated the standardised precipitation index (SPI), a modified version of the deciles index (DI), the standardised precipitation evapotranspiration index (SPEI) and the effective drought index (EDI). These were calculated using precipitation data from the Climate Hazards Group Infra-Red Precipitation with Station (CHIRPS), the CRN073 dataset, the Climate Research Unit (CRU), ECMWF Reanalysis (ERA-Interim) and a regional station dataset, and temperature from the CRU and ERA-Interim datasets. The gridded meteorological precipitation datasets were compared to assess how well they captured key features of the regional climate. The performance of all the drought indices calculated with all the meteorological datasets was then evaluated against a drought index calculated using river discharge data. Results showed that the selection of database was more important than the selection of drought index and that the best combinations were the EDI and DI calculated with CHIRPS and CRN073. Results also highlighted the importance of including indices like SPEI for drought assessment in Central America.Universidad de Costa Rica/[805-B0-810]/UCR/Costa RicaUniversidad de Costa Rica/[805-A9-532]/UCR/Costa RicaUniversidad de Costa Rica/[805-B3-600]/UCR/Costa RicaUniversidad de Costa Rica/[805-B0-065]/UCR/Costa RicaUniversidad de Costa Rica/[805-B3-413]/UCR/Costa RicaUniversidad de Costa Rica/[805-B4-227]/UCR/Costa RicaUniversidad de Costa Rica/[805-B4-228]/UCR/Costa RicaUniversidad de Costa Rica/[805-B5-295]/UCR/Costa RicaUppsala University/[54100006]//SueciaMarie Curie Intra-European Fellowship/[No.329762]//EuropaUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro de Investigaciones Geofísicas (CIGEFI)UCR::Vicerrectoría de Docencia::Ciencias Básicas::Facultad de Ciencias::Escuela de Físic

Profit enhancing competitive pressure in vertically related industries

Coevolution of viruses and their hosts represents a dynamic molecular battle between the immune system and viral factors that mediate immune evasion. After the abandonment of smallpox vaccination, cowpox virus infections are an emerging zoonotic health threat, especially for immunocompromised patients. Here we delineate the mechanistic basis of how cowpox viral CPXV012 interferes with MHC class I antigen processing. This type II membrane protein inhibits the coreTAP complex at the step after peptide binding and peptide-induced conformational change, in blocking ATP binding and hydrolysis. Distinct from other immune evasion mechanisms, TAP inhibition is mediated by a short ER-lumenal fragment of CPXV012, which results from a frameshift in the cowpox virus genome. Tethered to the ER membrane, this fragment mimics a high ER-lumenal peptide concentration, thus provoking a trans-inhibition of antigen translocation as supply for MHC I loading. These findings illuminate the evolution of viral immune modulators and the basis of a fine-balanced regulation of antigen processing

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS