Sulforaphane, a cancer chemopreventive agent, induces pathways associated with membrane biosynthesis in response to tissue damage by aflatoxin B1

Aflatoxin B[subscript 1] (AFB[subscript 1]) is one of the major risk factors for liver cancer globally. A recent study showed that sulforaphane (SF), a potent inducer of phase II enzymes that occurs naturally in widely consumed vegetables, effectively induces hepatic glutathione S-transferases (GSTs) and reduces levels of hepatic AFB[subscript 1]-DNA adducts in AFB[subscript 1]-exposed Sprague Dawley rats. The present study characterized the effects of SF pre-treatment on global gene expression in the livers of similarly treated male rats. Combined treatment with AFB[subscript 1] and SF caused reprogramming of a network of genes involved in signal transduction and transcription. Changes in gene regulation were observable 4 h after AFB[subscript 1] administration in SF-pretreated animals and may reflect regeneration of cells in the wake of AFB[subscript 1]-induced hepatotoxicity. At 24 h after AFB[subscript 1] administration, significant induction of genes that play roles in cellular lipid metabolism and acetyl-CoA biosynthesis was detected in SF-pretreated AFB[subscript 1]-dosed rats. Induction of this group of genes may indicate a metabolic shift toward glycolysis and fatty acid synthesis to generate and maintain pools of intermediate molecules required for tissue repair, cell growth and compensatory hepatic cell proliferation. Collectively, gene expression data from this study provide insights into molecular mechanisms underlying the protective effects of SF against AFB[subscript 1] hepatotoxicity and hepatocarcinogenicity, in addition to the chemopreventive activity of this compound as a GST inducer.National Institutes of Health (U.S.) (Grants ES016313, P30-ES002109, P01 ES006052, P30 ES003819, and P30 CA006973

Macrophages, Nitric Oxide and microRNAs Are Associated with DNA Damage Response Pathway and Senescence in Inflammatory Bowel Disease

Background: Cellular senescence can be a functional barrier to carcinogenesis. We hypothesized that inflammation modulates carcinogenesis through senescence and DNA damage response (DDR). We examined the association between senescence and DDR with macrophage levels in inflammatory bowel disease (IBD). In vitro experiments tested the ability of macrophages to induce senescence in primary cells. Inflammation modulating microRNAs were identified in senescence colon tissue for further investigation. Methodology/Principal Findings: Quantitative immunohistochemistry identified protein expression by colon cell type. Increased cellular senescence (HP1γ; P = 0.01) or DDR (γH2A.X; P = 0.031, phospho-Chk2, P = 0.014) was associated with high macrophage infiltration in UC. Co-culture with macrophages (ANA-1) induced senescence in >80% of primary cells (fibroblasts MRC5, WI38), illustrating that macrophages induce senescence. Interestingly, macrophage-induced senescence was partly dependent on nitric oxide synthase, and clinically relevant NO• levels alone induced senescence. NO• induced DDR in vitro, as detected by immunofluorescence. In contrast to UC, we noted in Crohn’s disease (CD) that senescence (HP1γ; P<0.001) and DDR (γH2A.X; P<0.05, phospho-Chk2; P<0.001) were higher, and macrophages were not associated with senescence. We hypothesize that nitric oxide may modulate senescence in CD; epithelial cells of CD had higher levels of NOS2 expression than in UC (P = 0.001). Microarrays and quantitative-PCR identified miR-21 expression associated with macrophage infiltration and NOS2 expression. Conclusions: Senescence was observed in IBD with senescence-associated β-galactosidase and HP1γ. Macrophages were associated with senescence and DDR in UC, and in vitro experiments with primary human cells showed that macrophages induce senescence, partly through NO•, and that NO• can induce DDR associated with senescence. Future experiments will investigate the role of NO• and miR-21 in senescence. This is the first study to implicate macrophages and nitrosative stress in a direct effect on senescence and DDR, which is relevant to many diseases of inflammation, cancer, and aging.Cancer Research Institute (New York, N.Y.) (Intramural Research Program)National Cancer Institute (U.S.) (Cancer Research Training Award Fellowship)Danish Cancer SocietyDanish National Research FoundationEuropean Commission (projects: Infla-Care, Biomedreg and DDResponse

Selected 'Starter kit' energy system modelling data for selected countries in Africa, East Asia, and South America (#CCG, 2021)

Energy system modeling can be used to develop internally-consistent quantified scenarios. These provide key insights needed to mobilise finance, understand market development, infrastructure deployment and the associated role of institutions, and generally support improved policymaking. However, access to data is often a barrier to starting energy system modeling, especially in developing countries, thereby causing delays to decision making. Therefore, this article provides data that can be used to create a simple zero-order energy system model for a range of developing countries in Africa, East Asia, and South America, which can act as a starting point for further model development and scenario analysis. The data are collected entirely from publicly available and accessible sources, including the websites and databases of international organisations, journal articles, and existing modeling studies. This means that the datasets can be easily updated based on the latest available information or more detailed and accurate local data. As an example, these data were also used to calibrate a simple energy system model for Kenya using the Open Source Energy Modeling System (OSeMOSYS) and three stylized scenarios (Fossil Future, Least Cost and Net Zero by 2050) for 2020–2050. The assumptions used and the results of these scenarios are presented in the appendix as an illustrative example of what can be done with these data. This simple model can be adapted and further developed by in-country analysts and academics, providing a platform for future work

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Turf Management Club by John Traynor (page 1) Who Is Superintendent Here by H.E. Frenette (1) Good Turf Can Result from good Sodding (3) Golf Course Superintendent by Edwart Wiacek (4) Picture - Outstanding Senior Prof. Troll Picture - recognition for Blazers St. Andrew\u27s, Scotland by William Hynd (5) Analogy of a Turf Manager by James B. Cole (6) Fish Trouble by Peter A. Langelier and Dennis P. Leger (8) Square Rings by Robert P. McGuire (9) A Different Type of Course by Robert Hall (10) Literature by Pierre Coste (11) Weeds in Golf Course Turf and Their Control by John F. Cornman (A-1) The USe of Liquid Fertilizer by Anthony B. Longo (A-3) Fertilizing a Golf Course Through an Irrigation System by Herbert E. Berg (A-6) The Extent of Winter Injury on Golf Courses by James L. Holmes (A-11) The Problem of Winter Injury by James B. Beard (A-13) Establishing, Maintaining, and Selling Sod for Turf Areas in New England by George F. Stewart (A-20) Problems of Maintaining Turf Around Industrial Grounds by George Moore (A-22) Landscaping Industrial sites by A.W. Boicourt (A-25) Introduction to the panel Discussion on Grasses for Tees and Their Management by Alexander M. Radko (A-28) Building a Golf Tee by Phil Cassidy (A-29) Grasses for Tees and Their Management by Wm. Dest (A-31) Golf Course Tee maintenance by Jim Fulwider (A-32) Tees by F. Thompson (A-33) How to Draw up a Contract by Lawrence D. Rhoades (A-34) My Contract by Lucien E. Duval (A-37) The Golf Car Problem by Geoffrey S. Cornish (A-41) Golf Cars and Turfgrass by Lee Record (A-42) Course Design and Golf Cars by William F. Mitchell (A-42) Golf Cars and the Established Course by Sherwood Moore (A-45) Course Design and Golf Cars by Phil Wogan (a-52) Introduction of Cars to the New Course by M. Ovian (A-56

Differential Impact of Tumor Suppressor Pathways on DNA Damage Response and Therapy-Induced Transformation in a Mouse Primary Cell Model

The RB and p53 tumor suppressors are mediators of DNA damage response, and compound inactivation of RB and p53 is a common occurrence in human cancers. Surprisingly, their cooperation in DNA damage signaling in relation to tumorigenesis and therapeutic response remains enigmatic. In the context of individuals with heritable retinoblastoma, there is a predilection for secondary tumor development, which has been associated with the use of radiation-therapy to treat the primary tumor. Furthermore, while germline mutations of the p53 gene are critical drivers for cancer predisposition syndromes, it is postulated that extrinsic stresses play a major role in promoting varying tumor spectrums and disease severities. In light of these studies, we examined the tumor suppressor functions of these proteins when challenged by exposure to therapeutic stress. To examine the cooperation of RB and p53 in tumorigenesis, and in response to therapy-induced DNA damage, a combination of genetic deletion and dominant negative strategies was employed. Results indicate that loss/inactivation of RB and p53 is not sufficient for cellular transformation. However, these proteins played distinct roles in response to therapy-induced DNA damage and subsequent tumorigenesis. Specifically, RB status was critical for cellular response to damage and senescence, irrespective of p53 function. Loss of RB resulted in a dramatic evolution of gene expression as a result of alterations in epigenetic programming. Critically, the observed changes in gene expression have been specifically associated with tumorigenesis, and RB-deficient, recurred cells displayed oncogenic characteristics, as well as increased resistance to subsequent challenge with discrete therapeutic agents. Taken together, these findings indicate that tumor suppressor functions of RB and p53 are particularly manifest when challenged by cellular stress. In the face of such challenge, RB is a critical suppressor of tumorigenesis beyond p53, and RB-deficiency could promote significant cellular evolution, ultimately contributing to a more aggressive disease

Megadroughts in the Common Era and the Anthropocene

Exceptional drought events, known as megadroughts, have occurred on every continent outside Antarctica over the past ~2,000 years, causing major ecological and societal disturbances. In this Review, we discuss shared causes and features of Common Era (Year 1–present) and future megadroughts. Decadal variations in sea surface temperatures are the primary driver of megadroughts, with secondary contributions from radiative forcing and land–atmosphere interactions. Anthropogenic climate change has intensified ongoing megadroughts in south-western North America and across Chile and Argentina. Future megadroughts will be substantially warmer than past events, with this warming driving projected increases in megadrought risk and severity across many regions, including western North America, Central America, Europe and the Mediterranean, extratropical South America, and Australia. However, several knowledge gaps currently undermine confidence in understanding past and future megadroughts. These gaps include a paucity of high-resolution palaeoclimate information over Africa, tropical South America and other regions; incomplete representations of internal variability and land surface processes in climate models; and the undetermined capacity of water-resource management systems to mitigate megadrought impacts. Addressing these deficiencies will be crucial for increasing confidence in projections of future megadrought risk and for resiliency planning