Whole-genome characterization of lung adenocarcinomas lacking the RTK/RAS/RAF pathway

RTK/RAS/RAF pathway alterations (RPAs) are a hallmark of lung adenocarcinoma (LUAD). In this study, we use whole-genome sequencing (WGS) of 85 cases found to be RPA(−) by previous studies from The Cancer Genome Atlas (TCGA) to characterize the minority of LUADs lacking apparent alterations in this pathway. We show that WGS analysis uncovers RPA(+) in 28 (33%) of the 85 samples. Among the remaining 57 cases, we observe focal deletions targeting the promoter or transcription start site of STK11 (n = 7) or KEAP1 (n = 3), and promoter mutations associated with the increased expression of ILF2 (n = 6). We also identify complex structural variations associated with high-level copy number amplifications. Moreover, an enrichment of focal deletions is found in TP53 mutant cases. Our results indicate that RPA(−) cases demonstrate tumor suppressor deletions and genome instability, but lack unique or recurrent genetic lesions compensating for the lack of RPAs. Larger WGS studies of RPA(−) cases are required to understand this important LUAD subset. © 2021 The AuthorsCarrot-Zhang et al. perform whole-genome characterization of lung adenocarcinomas (LUADs) lacking RTK/RAS/RAF pathway alterations (RPAs) and identify mutations or structural variants in both coding and non-coding spaces that define a unique entity of RPA(−) LUADs and potentially explain the underlying biology of this disease

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities 1,2 . This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity 3�6 . Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55 of the global rise in mean BMI from 1985 to 2017�and more than 80 in some low- and middle-income regions�was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing�and in some countries reversal�of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories. © 2019, The Author(s)

The Present Status of Variety Selection in Potato

選種用的馬鈴薯材料依其來源分成二類，歷年篩選結果分別敘述。 第一類為亞洲蔬菜中心所提供的921品系（原育種目標為耐熱性），在農試所田區經數代繁殖及營養系選留，一些較不受毒素病為害之品系，經過品系試驗、區域試驗及示範栽培並配合病理人員之抗病性檢定後，選出一黃皮、黃肉、鮮食品質佳，對PVY病毒耐病性強之品系，於82年3月2日通過審查命名為台農一號。第二類為育種品系均為國際馬鈴薯中心提供之薯球族群：第一族群為對PVY病毒免疫性呈分離的薯球族群，經過一次接種PV-m（嵌紋）系統篩選以及五次田間篩選，在第六次種植前以ELISA偵測所保留種薯上之PVY-m，並淘汰47％的種薯，其餘薯球種植後僅8個品系共約3％的種薯再表現毒素病徵，顯示此類育種品系田間抗病性穩定。第二族群為具多種抗病性的分離薯球族群，除抗毒素病外，並有對晚疫病、早疫病及青枯病的抗病性，已經四次田間繁殖及篩選並曾以ELISA篩檢不帶PVY-m的種薯，淘汰44％的薯球後，其餘種薯再種植還有約15％的發病率。以上二薯球族群都有農藝性狀表現較優的品系，經初步田間重複試驗及調查，將繼續就抗病性，薯球產量及薯球比重等特性選育加工用品種。 This paper reports the variety selection tasks in potato conducted at Taiwan Agricultural Research Institute (TARI) during the past decade. Breeding materials were categorized into two groups according to their original source and results obtained were separately described. The first group included 921 clones from the Asian Vegetable Research and Development Center, originally for trials of heat tolerance. The amount of clones decreased as the number of propagation cycles increased due to virus contarmination. Some clones performed well in terms of good tuber yield and insignificant virus infection. Selected clones underwent a series of variety and regional trials. With the confirmation of its resistance to PVY through serological tests, a clone with oval tubers of yellow skin and yellow flesh was registered as Tainung No. 1 on Mar 2, 1993. This variety is good for table use. The second group, introduced from the International Potato Center, was further divided into two subgroups. The first subgroup included 50 tuber families segregating for PVY resistance. After inoculating PVY-m at the time of first planting and additional five consecutive crops of screening, 53% of the tuber families were selected for PVY resistance by ELISA test. Only 3% of the selected families showed viral symptoms in later field trials. The second subgroup included 52 tuber families with multiple resistances to PVX, PVY, bacterial wilt, late blight, early blight, and potato leaf-roll virus either alone or in combination. Fifty-six percent of the tuber families were selected for their negative reaction to PVY after a series of field screening and ELISA test. However, 15 % of the selected families showed viral symptoms in the field. Clones with good traits and high tuber specific gravity were available in both subgroups. Based on the information secured, variety for both table-use and processing purposes could be selected in the near future with continuous efforts

Arginine restores nitric oxide activity and inhibits monocyte accumulation after vascular injury in hypercholesterolemic rabbits

AbstractObjectives. This study sought to determine whether the alterations in vascular function and structure after balloon injury in hypercholesterolemic rabbits could be inhibited by dietary arginine.Background. Administration of arginine (the nitric oxide [NO] precursor) restores vascular NO activity in hypercholesterolemic animals. We and other investigators have shown that enhancement of vascular NO activity can inhibit myointimal hyperplasia after vascular injury in normocholesterolemic animals.Methods. Twenty-eight New Zealand White rabbits received either normal rabbit chow, 0.5% cholesterol diet or 0.5% cholesterol diet plus l-arginine hydrochloride (2.25% wt/vol) in the drinking water. After 6 weeks of dietary intervention, the left iliac artery of each animal was subjected to a balloon injury. Four weeks later, the iliac arteries were harvested for vascular reactivity studies and immunohistochemical analysis.Results. Vascular injury induced intimal thickening that was largely composed of vascular smooth muscle cells and extracellular matrix. In the setting of hypercholesterolemia, vascular injury induced an exuberant myointimal lesion that was augmented by the accumulation of lipid-laden macrophages. Dietary arginine reduced intimal thickening in the injured vessels of hypercholesterolemic animals and substantially inhibited the accumulation of macrophages in the lesion (from 28% to 5% of the lesion area, p < 0.001).Conclusions. We report that lesions induced by vascular injury in hypercholesterolemic animals are markedly reduced by oral administration of arginine. Moreover, we find that the nature of the lesion is altered, with a striking reduction in the percentage of macrophages comprising the lesion

Up-Regulation of Interleukin-17 Expression by Human Papillomavirus Type 16 E6 in Nonsmall Cell Lung Cancer

BACKGROUND: Human papillomavirus (HPV) 16/18 infection is associated with nonsmoking lung cancer. In this study, the authors investigated a putative correlation between interleukin (IL)-17 expression and HPV infection in clinical nonsmall cell lung cancer (NSCLC) tissues and examined the effects of HPV infection on a human NSCLC cell line. METHODS: IL-17 expression was investigated in 79 NSCLC tumor tissues by immunohistochemistry. Growth rate, IL-17 mRNA, and secreting protein levels were also examined in HPV 16/18 E6-transfected H1299 human NSCLC cells. RESULTS: Immunohistochemical data showed that 48.1% of lung tumors had IL-17 staining, which was significantly associated with patients' sex (P=.03), HPV infection (P=.002), and tumor stage (P=.03). Significant correlations of IL-17 with IL-6 (P<.001) and IL-17 with Mcl-1 (P<.001) expression were also observed. Cell growth rate was increased, and IL-17/Mcl-1 expression levels were elevated in HPV 16 E6-transfected H1299 cells. The transfected E6 oncoproteins can significantly up-regulate expression levels of IL-17 and antiapoptotic protein Mcl-1. CONCLUSIONS: The study suggests that HPV infection-induced IL-17 levels can stimulate Mcl-1 expression through the PI3K pathway and promote lung tumor cell progression through a p53-and IL-6-independent pathway. Cancer 2010; 116: 4800-9. (C) 2010 American Cancer Society