Defining the Molecular Basis of Tumor Metabolism: a Continuing Challenge Since Warburg's Discovery

Cancer cells are the product of genetic disorders that alter crucial intracellular signaling pathways associated with the regulation of cell survival, proliferation, differentiation and death mechanisms. the role of oncogene activation and tumor suppressor inhibition in the onset of cancer is well established. Traditional antitumor therapies target specific molecules, the action/expression of which is altered in cancer cells. However, since the physiology of normal cells involves the same signaling pathways that are disturbed in cancer cells, targeted therapies have to deal with side effects and multidrug resistance, the main causes of therapy failure. Since the pioneering work of Otto Warburg, over 80 years ago, the subversion of normal metabolism displayed by cancer cells has been highlighted by many studies. Recently, the study of tumor metabolism has received much attention because metabolic transformation is a crucial cancer hallmark and a direct consequence of disturbances in the activities of oncogenes and tumor suppressors. in this review we discuss tumor metabolism from the molecular perspective of oncogenes, tumor suppressors and protein signaling pathways relevant to metabolic transformation and tumorigenesis. We also identify the principal unanswered questions surrounding this issue and the attempts to relate these to their potential for future cancer treatment. As will be made clear, tumor metabolism is still only partly understood and the metabolic aspects of transformation constitute a major challenge for science. Nevertheless, cancer metabolism can be exploited to devise novel avenues for the rational treatment of this disease. Copyright (C) 2011 S. Karger AG, BaselFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Fed ABC UFABC, CCNH, Santo Andre, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Ciencias Biol, São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Bioquim, São Paulo, BrazilUniv Fed Sao Carlos UFSCar, DFQM, Sorocaba, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Ciencias Biol, São Paulo, BrazilUniversidade Federal de São Paulo UNIFESP, Dept Bioquim, São Paulo, BrazilFAPESP: 10/16050-9FAPESP: 10/11475-1FAPESP: 08/51116-0Web of Scienc

Expert consensus document:Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)

Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies with features of biliary tract differentiation. CCA is the second most common primary liver tumour and the incidence is increasing worldwide. CCA has high mortality owing to its aggressiveness, late diagnosis and refractory nature. In May 2015, the "European Network for the Study of Cholangiocarcinoma" (ENS-CCA: www.enscca.org or www.cholangiocarcinoma.eu) was created to promote and boost international research collaboration on the study of CCA at basic, translational and clinical level. In this Consensus Statement, we aim to provide valuable information on classifications, pathological features, risk factors, cells of origin, genetic and epigenetic modifications and current therapies available for this cancer. Moreover, future directions on basic and clinical investigations and plans for the ENS-CCA are highlighted

Evolution of the planning process for protected areas in Latin America

Protected areas in Latin America have increased significantly in area and number in the last decade. Due in part to lack of personnel trained in the planning and management of these areas, many are threatened or unable to provide their potential goods and services. To remedy this situation, several initiatives are underway to share methodological approaches to planning protected areas in Latin America. We analyze the concepts, methods, and experiences in protected areas planning in Latin America during the last three decades. We conclude that the basic elements and procedures of protected area planning initiated in the 1970s have been maintained, but an important evolution occur-red in the strategy of the planning process. More and varied information is now available to planners and valuable tools have been developed for land use planning. In addition, there has been an important effort to develop a participatory planning process recognizing the potential role of protected areas in the sustainable development of rural, high poverty communities. Participatory planning ensures that protected areas contribute to the ecological, economic, and social environment of adjacent communities

Empirical Evidence for the Potential Climate Benefits of Decarbonizing Light Vehicle Transport in the U.S. With Bioenergy from Purpose-Grown Biomass with and without BECCS

Climate mitigation scenarios limiting global temperature increases to 1.5 °C rely on decarbonizing vehicle transport with bioenergy production plus carbon capture and storage (BECCS), but climate impacts for producing different bioenergy feedstocks have not been directly compared experimentally or for ethanol vs electric light-duty vehicles. A field experiment at two Midwest U.S. sites on contrasting soils revealed that feedstock yields of seven potential bioenergy cropping systems varied substantially within sites but little between. Bioenergy produced per hectare reflected yields: miscanthus > poplar > switchgrass > native grasses ≈ maize stover (residue) > restored prairie ≈ early successional. Greenhouse gas emission intensities for ethanol vehicles ranged from 20 to −179 g CO2e MJ–1: maize stover ≫ miscanthus ≈ switchgrass ≈ native grasses ≈ poplar > early successional ≥ restored prairie; direct climate benefits ranged from ∼80% (stover) to 290% (restored prairie) reductions in CO2e compared to petroleum and were similar for electric vehicles. With carbon capture and storage (CCS), reductions in emission intensities ranged from 204% (stover) to 416% (restored prairie) for ethanol vehicles and from 329 to 558% for electric vehicles, declining 27 and 15%, respectively, once soil carbon equilibrates within several decades of establishment. Extrapolation based on expected U.S. transportation energy use suggests that, once CCS potential is maximized with CO2 pipeline infrastructure, negative emissions from bioenergy with CCS for light-duty electric vehicles could capture >900 Tg CO2e year–1 in the U.S. In the future, as other renewable electricity sources become more important, electricity production from biomass would offset less fossil fuel electricity, and the advantage of electric over ethanol vehicles would decrease proportionately.Full Tex

Evapotranspiration and water use efficiency of continuous maize and maize and soybean in rotation in the upper Midwest U.S.

This study examined evapotranspiration (ET) from no-till, rainfed maize and soybean during three growing seasons (May-Sep) of normal rainfall years (2009, 2010, 2011) and a drought year (2012) in Michigan, USA, based on daily soil water uptake measured by time-domain reflectometry at multiple depths through the root zone. During normal rainfall years, growing-season ET was similar between continuous maize (mean ± standard deviation: 471 ± 47 mm) and maize in rotation (469 ± 51 mm). During the drought year, ET decreased by only 3% for continuous maize but by 20% for maize in rotation. During the normal rainfall years, ET for soybean (453 ± 34 mm) was statistically indistinguishable from ET for maize, and was lower during the drought year (333 mm). Water use efficiency (WUE), calculated from harvest yield (grain + corn stover) and ET, was 25.3 ± 4.2 kg ha−1 mm-1 for continuous maize and 27.3 ± 3.1 kg ha−1 mm−1 for maize in rotation during the normal rainfall years, whereas WUEs for both continuous maize and maize in rotation were much lower in the 2012 drought year (14.0 and 15.5 kg ha−1 mm−1, respectively), coincident with lower production. Soybean had a much lower WUE than maize during the three normal years (6.95 ± 0.96 kg ha−1 mm−1) and the drought year (4.57 kg ha−1 mm−1), also explained by lower yield. Both maize and soybean tended to use all available water in the soil profile; there was no consistent difference in ET between these crops, while yield varied markedly from year to year.Full Tex

Empirical evidence for the climate benefits of decarbonizing US automotive transport with liquid vs electric bioenergy and carbon capture and storage

No Full Tex

Positive and negative regulation by SLP-76/ADAP and Pyk2 of chemokine-stimulated T-lymphocyte adhesion mediated by integrin α4β1

Stimulation by chemokines of integrin α4β1-dependent T-lymphocyte adhesion is a crucial step for lymphocyte trafficking. The adaptor Vav1 is required for chemokine-activated T-cell adhesion mediated by α4β1. Conceivably, proteins associating with Vav1 could potentially modulate this adhesion. Correlating with activation by the chemokine CXCL12 of T-lymphocyte attachment to α4β1 ligands, a transient stimulation in the association of Vav1 with SLP-76, Pyk2, and ADAP was observed. Using T-cells depleted for SLP-76, ADAP, or Pyk2, or expressing Pyk2 kinase-inactive forms, we show that SLP-76 and ADAP stimulate chemokine-activated, α4β1-mediated adhesion, whereas Pyk2 opposes T-cell attachment. While CXCL12-promoted generation of high-affinity α4β1 is independent of SLP-76, ADAP, and Pyk2, the strength of α4β1-VCAM-1 interaction and cell spreading on VCAM-1 are targets of regulation by these three proteins. GTPase assays, expression of activated or dominant-negative Rac1, or combined ADAP and Pyk2 silencing indicated that Rac1 activation by CXCL12 is a common mediator response in SLP-76-, ADAP-, and Pyk2-regulated cell adhesion involving α4β1. Our data strongly suggest that chemokine-stimulated associations between Vav1, SLP-76, and ADAP facilitate Rac1 activation and α4β1-mediated adhesion, whereas Pyk2 opposes this adhesion by limiting Rac1 activation.This work was supported by grants SAF2011-24022 from Ministerio de Economía y Competitividad, RD12/0036/0061, and S2010/BMD-2314 from Comunidad de Madrid to J.T.Peer Reviewe

The potential for expanding sustainable biogas production and some possible impacts in specific countries

Current food production practices tend to damage and deplete soil, diminish biodiversity, and degrade water supplies. For agriculture to become environmentally sustainable and simultaneously increase food output for a growing world population, fundamental changes in agricultural production systems are required. Renewable energy can reduce greenhouse gases (GHGs) but we also need simple, low‐cost approaches to remove atmospheric carbon and sequester it in stable forms. Recycling of digestate from the anaerobic digestion of agricultural and waste materials to soils can sequester atmospheric carbon and provide many other economic, social and environmental benefits. Biogasdoneright™ (BDR) is a set of practices that link biogas production with sustainable agriculture. The BDR approach to sustainable agriculture is being implemented on a large scale in Italy. In this paper, we examine the potential impact of implementing BDR in selected other countries. The biomethane potential in these countries, estimated conservatively, varies from about 10–30% of their current annual natural gas consumption. Biomethane from sequential (double) crops provides by far the greatest fraction of the biomethane potential. Double cropping also drives many of the environmental and economic benefits of BDR systems. Depending on where and how widely it is implemented, the production of biogas in BDR systems could have very significant national‐level impacts. For example, sufficient biomethane could be produced in Argentina to completely eliminate imports of natural gas, equivalent to about 28% of Argentina's 2017 trade deficit. In the USA, renewable biogas could generate electricity equal to nearly all of the electricity currently produced by domestic solar and wind resources. © 2020 Society of Chemical Industry and John Wiley & Sons, Lt