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Background: A food system transformation is needed to address food and nutrition security, minimise impacts on planetary health, reduce climate change emissions, and contribute to equity, diversity, and the Sustainable Development Goals. Scope and approach: This paper summarizes findings of the European Commission's High Level Expert Group on Food Systems Science, which reviewed obstacles that prevent food systems policy from achieving society-wide impacts. These barriers include knowledge and translation gaps in food-related science-policy-interfaces (SPIs), insufficient attention to the priorities of diverse stakeholders, and a failure to adequately consider equity, diversity, political economy, and societal engagements. Key findings & conclusions: Three potential pathways can ensure science and policy support food systems transformation: (1) Adapt the current SPI landscape with extra resources and a wider mandate to ensure coordinated action across the full food system, (2) Enhance the current policy landscape with a range of multisectoral taskforces designed to fulfill specific functions such as creating an enhanced food systems data portal, and (3) Establish a “network of networks” to provide both global coordination as well as organize defined agendas at global through to regional scales. In embarking on these pathways, a revised science-policy-society landscape (SPSIs) should deliver the following core functions: (1) Engage and empower multi-stakeholder dialogue; (2) Build capacity at multiple scales to translate evidence into tangible real-world outcomes; (3) Ensure access to openly accessible data for the entire food system; (4) Use models, forecasts, and scenario building exercises to explore the potential future of food systems; (5) Produce assessment reports and policy publications; and (6) Establish fora for diplomacy that will be empowered to create standards set targets and establish policy.

Background Naturally occurring germline gene deletions (KO) represent a unique setting to interrogate gene functions. Complete deletions and differential expression of the human glycosyltransferase UGT2B17 and UGT2B28 genes are linked to prostate cancer (PCa) risk and progression, leukaemia, autoimmune and other diseases. Methods The systemic metabolic consequences of UGT deficiencies were examined using untargeted and targeted mass spectrometry-based metabolomics profiling of carefully matched, treatment-naive PCa cases. Results Each UGT KO differentially affected over 5% of the 1545 measured metabolites, with divergent metabolic perturbations influencing the same pathways. Several of the perturbed metabolites are known to promote PCa growth, invasion and metastasis, including steroids, ceramides and kynurenine. In UGT2B17 KO, reduced levels of inactive steroid-glucuronides were compensated by sulfated derivatives that constitute circulating steroid reservoirs. UGT2B28 KO presented remarkably lower levels of oxylipins paralleled by reduced inflammatory mediators, but higher ceramides unveiled as substrates of the enzyme in PCa cells. Conclusion The distinctive and broad metabolic rewiring caused by UGT KO reinforces the need to examine their unique and divergent functions in PCa biology.

O consumo de carne, especialmente de carne bovina, é frequentemente questionado por seus efeitos sobre a saúde humana, particularmente devido à crescente prevalência da obesidade. Para ajudar a ver se são coincidências ou co-incidências, o artigo utiliza recursos de mapeamento, mapas foram produzidos pelas bases de dados FAO e WHO FaoStat, usando o software Cartes et Données (Articque) La consommation de viande, en particulier de viande bovine, est souvent mise en cause pour ses effets sur la santé humaine, notamment en raison de la croissante prévalence de l'obésité à laquelle elle est associée par certains. Pour aider à voir s’il s’agit de coincidences ou de co-incidences, l’article utilise les ressources de la cartographie, les cartes ont été produites à partir des base de données FaoStat de la FAO et de l’OMS, en utilisant le logiciel Cartes et Données (Articque) puis un traitement graphique complémentaire sur Adobe Illustrator Consumption of meat, especially beef, is often questioned for its effects on human health, particularly because of the growing prevalence of obesity with which it is associated by some. To help see if these are coincidences or co-incidences, the article uses mapping resources, maps were produced from FAO and WHO FaoStat databases, using the Cartes et Données software (Articque) then an additional graphic processing on Adobe Illustrator

PDF file - 126K, Supplementary Table 1. Genotype frequencies 1 of htSNPs in steroidogenic genes and their association with BCR in Caucasians (n=526). Supplementary Table 2. Association between htSNPs in the steroidogenic pathway and prostate cancer-specific mortality in Asians under ADT (n=601) Supplementary Table 3. Non-significant associations between htSNPs in candidate steroidogenic pathways and prostate cancer-specific mortality in Asians under ADT (n=601) Supplementary Table 4. Non-significant associations between htSNPs in candidate steroidogenic pathways and all cause mortality in Asians under ADT (n=601)

Purpose: Polymorphisms in the genes SRD5A1 and SRD5A2 encoding androgen biosynthetic 5α-reductase enzymes have been associated with an altered risk of biochemical recurrence after radical prostatectomy in localized prostate cancer.Experimental Design: To gain potential insights into SRD5A biologic effects, we examined the relationship between SRD5A prognostic markers and endogenous sex-steroid levels measured by mass spectrometry in plasma samples and corresponding prostatic tissues of patients with prostate cancer.Results: We report that five of the seven SRD5A markers differentially affect sex-steroid profiles of dihydrotestosterone and its metabolites in both the circulation and prostatic tissues of patients with prostate cancer. Remarkably, a 32% increase in intraprostatic testosterone levels was observed in the presence of the high-risk SRD5A rs2208532 polymorphism. Moreover, SRD5A2 markers were associated predominantly with circulating levels of inactive glucuronides. Indeed, the rs12470143 SRD5A2 protective allele was associated with high circulating androstane-3α, 17β-diol-17-glucuronide (3α-diol-17G) levels as opposed to lower levels of both 3α-diol-17G and androsterone-glucuronide observed with the rs2208532 SRD5A2 risk allele. Moreover, SRD5A2 rs676033 and rs523349 (V89L) risk variants, in strong linkage disequilibrium, were associated with higher circulating levels of 3α-diol-3G. The SRD5A2 rs676033 variant further correlated with enhanced intraprostatic exposure to 5α-reduced steroids (dihydrotestosterone and its metabolite 3β-diol). Similarly, the SRD5A1 rs166050C risk variant was associated with greater prostatic exposure to androsterone, whereas no association was noted with circulating steroids.Conclusions: Our data support the association of 5α-reductase germline polymorphisms with the hormonal milieu in patients with prostate cancer. Further studies are needed to evaluate if these variants influence 5α-reductase inhibitor efficacy. Clin Cancer Res; 20(3); 576–84. ©2013 AACR.

PDF file - 146KB, Supplementary Table 1. Genotype Frequencies of Polymorphisms in SULT2B1 and their Association with Biochemical Recurrence in 526 Cases with Localized Prostate Cancer. Supplementary Table 2. Genotype Frequencies of Polymorphisms in COMT and their Association with Biochemical Recurrence in 526 Cases with Localized Prostate Cancer. Supplementary Table 3. Genotype Frequencies of Polymorphisms in CYP1B1 and their Association with Biochemical Recurrence in 526 Cases with Localized Prostate Cancer. Supplementary Table 4. Genotype Frequencies of Polymorphisms in NQO1 and their Association with Biochemical Recurrence in 526 Cases with Localized Prostate Cancer. Supplementary Table 5. Genotype Frequencies of Polymorphisms in NQO2 and their Association with Biochemical Recurrence in 526 Cases with Localized Prostate Cancer. Supplementary Table 6. Association of SNPs with Prostate Cancer Progression for 213 Patients with Locally Advanced Prostate Cancer. Supplementary Table 7. Association of SNPs with the Overall Survival of 213 Patients with Locally Advanced Prostate Cancer.

Purpose: Phenotypic biomarkers are a high priority for patients receiving androgen deprivation therapy (ADT) for prostate cancer given the increasing number of treatment options. This study evaluates serum sex steroids as prognostic biomarkers in men receiving ADT for recurrent prostate cancer.Experimental Design: Retrospective cohort study of Canadian patients in the PR.7 trial (accrual 1999–2005) who received continuous ADT for biochemical recurrence postradiotherapy. Patients were excluded with follow-up Results: Post-ADT initiation, we measured samples in 219 patients as well as two subsequent annual samples in a subset of 101 patients. Testosterone levels correlated with androstenedione (AD) and DHT, while DHT, AD, androsterone (AST), dehydroepiandrosterone (DHEA), and androstenediol (A5diol) were highly correlated to each other and negatively associated with age. Higher tertiles of estrone (E1) and estradiol (E2) were significantly associated with sooner time to CRPC. In patients with longitudinal samples, increases in serum DHEA and AST were significantly associated with sooner time to CRPC. Limitations include the number of events for some groups.Conclusions: Our data suggest the patient hormonal milieu has long-term prognostic value in men receiving ADT for recurrent prostate cancer, including increased levels of E1 and E2 and rising DHEA and AST levels, which predict a shorter time to CRPC. Clin Cancer Res; 24(21); 5305–12. ©2018 AACR.

Purpose: Reliable biomarkers that predict prostate cancer outcomes are urgently needed to improve and personalize treatment approaches. With this goal in mind, we individually and collectively appraised common genetic polymorphisms related to estradiol metabolic pathways to find prostate cancer prognostic markers.Methods: The genetic profiles of 526 men with organ-confined prostate cancer were examined to find common genetic polymorphisms related to estradiol metabolic pathways and these findings were replicated in a cohort of 213 men with more advanced disease (follow-up time for both cohorts, >7.4 years). Specifically, we examined 71 single-nucleotide polymorphisms (SNP) in SULT2A1, SULT2B1, CYP1B1, COMT, CYP3A4, CYP3A5, CYP3A43, NQO1, and NQO2 and assessed the impact of the SNPs alone and in combination on prostate cancer progression and on circulating hormone levels.Results: According to a multivariate analysis, CYP1B1 (rs1800440), COMT (rs16982844), and SULT2B1 (rs12460535, rs2665582, rs10426628) were significantly associated with prostate cancer progression and hormone levels. Remarkably, by combining the SNP information with previously identified HSD17B2 markers, the patients could be stratified into four distinct prognostic subgroups. The most prominent association was observed for the eight-marker combination [CYP1B1 (rs1800440), SULT2B1 (rs12460535, rs2665582, and rs10426628), and HSD17B2 (rs4243229, rs1364287, rs2955162, and rs1119933)].Conclusion: This study identified specific germline variations in estradiol metabolism–related pathways, namely CYP1B1, SULT2B1, and HSD17B2, as novel prognostic markers that are cumulatively associated with increased risk of prostate cancer progression. This panel of markers warrants additional investigation and validation to help stratify patients according to their risk of progression. Clin Cancer Res; 20(11); 2971–83. ©2014 AACR.

PDF file 138K, Relationshio between sex-steroid hormone levels and molecular markers in SRD5A genes

Supplementary Figure 1. Consort diagram of patients included in study; Supplementary Figure 2. Schematic of sex steroids measured using mass spectrometry; Supplementary Figure 3. Prostate cancer survival and overall survival; Supplementary Table 1. Summary results of mass spectrometry based steroid analysis of first samples from PR.7 study; Supplementary Table 2. Pearson intrapatient correlation of measured sex steroids at first measurement during ADT; Supplementary Table 3. Intrapatient correlation of measured steroids in longitudinal samples; Supplementary Table 4. Pearson intrapatient correlation of changes in sex steroids between annual measurements; Supplementary Table 5. Summary of changes over time in measured sex steroids.

Purpose: Prostate cancer is a heterogeneous genetic disease, and molecular methods for predicting prognosis in patients with aggressive form of the disease are urgently needed to better personalize treatment approaches. The objective was to identify host genetic variations in candidate steroidogenic genes affecting hormone levels and prostate cancer progression.Experimental Design: The study examined two independent cohorts composed of 526 Caucasian men with organ-confined prostate cancer and 601 Taiwanese men on androgen–deprivation therapy. Caucasians were genotyped for 109 haplotype-tagging single-nucleotide polymorphisms (SNP) in CYP17A1, ESR1, CYP19A1, and HSD3B1, and their prognostic significance on disease progression was assessed using Kaplan–Meier survival curves and Cox regression models. Positive findings, including previously identified SRD5A1, SRD5A2, HSD17B2, HSD17B3, and HSD17B12 polymorphisms, were then explored in Taiwanese men (n = 32 SNPs). The influence of positive markers on the circulating hormonal levels was then appraised in Caucasians using specific and sensitive mass spectrometry–based methods.Results: After adjusting for known risk factors, variants of CYP17A1 (rs6162), HSD17B2 (rs4243229 and rs7201637), and ESR1 (rs1062577) were associated with progressive disease in both cohorts. Indeed, the presence of these variations was significantly associated with progression in Caucasians (HR, 2.29–4.10; P = 0.0014–2 × 10−7) and survival in Taiwanese patients [HR = 3.74; 95% confidence interval (CI): 1.71–8.19, P = 0.009]. Remarkably, the CYP17A1 rs6162 polymorphism was linked to plasma dehydroepiandrosterone-sulfate (DHEA-S) levels (P = 0.03), HSD17B2 rs7201637 with levels of dihydrotestosterone (P = 0.03), and ESR1 rs1062577 with levels of estrone-S and androsterone-glucuronide (P ≤ 0.05).Conclusion: This study identifies, in different ethnic groups and at different disease stages, CYP17A1, HSD17B2, and ESR1 as attractive prognostic molecular markers of prostate cancer progression. Clin Cancer Res; 19(3); 699–709. ©2012 AACR.

PDF file - 10741K, Supplementary material 2: Representative examples of immunoexpression obtained after incubation of prostate tissue microarrays with the anti-UGT2B15, anti-UGT2B17 or anti-vimentin antibodies.

PDF file - 23K, Supplementary material 9: Doxycycline activation of AR shRNA modulates the mRNA levels of the receptor (A) and its negative (ABCG1, B) and positive (PSA, C) target genes.

PDF file - 6791K, Supplementary material 6: Representative examples of immunoexpression obtained after incubation of prostate tissue microarrays with the anti-UGT2B15, anti-UGT2B17 or anti-vimentin antibodies: Comparison Untreated vs ADTh for 9.0 months.

PDF file - 7458K, Supplementary material 3: Representative examples of immunoexpression obtained after incubation of prostate tissue microarrays with the anti-UGT2B15, anti-UGT2B17 or anti-vimentin antibodies: Comparison BPH vs Untreated.

PDF file - 7565K, Supplementary material 7: Representative examples of immunoexpression obtained after incubation of prostate tissue microarrays with the anti-UGT2B15, anti-UGT2B17 or anti-vimentin antibodies: Comparison Untreated vs castrate resistant tumors.

PDF file - 8925K, Supplementary material 4: Representative examples of immunoexpression obtained after incubation of prostate tissue microarrays with the anti-UGT2B15, anti-UGT2B17 or anti-vimentin antibodies: Comparison Untreated vs ADTh for 1.5 and 2.0 months.

PDF file - 20K, Supplementary material 1: Age, clinical stage of the disease (cT), tumor grade (Gleason score) and serum PSA from PCa sample donors.

PDF file - 8878K, Supplementary material 5: Representative examples of immunoexpression obtained after incubation of prostate tissue microarrays with the anti-UGT2B15, anti-UGT2B17 or anti-vimentin antibodies: Comparison Untreated vs ADTh for 3.0 and 6.0 months.

TMG Research gGmbH aims to help develop a more systematic understanding of how agri-food systems can be transformed as part of a project on the Assessment and Communication of Climate Impacts of Food (CLIF), funded through the International Climate Initiative (IKI) of the German Federal Ministry for the Environment, Nature Conservation, Nuclear Safety and Consumer Protection (BMUV) and jointly implemented with corsus and WWF Germany. This project promotes sustainable consumption patterns and helps companies, policymakers, and consumers choose more sustainable options in relation to food. The main contribution of TMG to this project is in developing a more systematic understanding of how to transform agri-food systems by publishing a series of strategic reports on the current status of agri-food systems and the likely drivers and agents of their transformation. This report is part of the FORESEE (4C) series on The Transformation of Agri-Food Systems in Times of Multiple Crises, which explores the status quo of the current agri-food system in the light of challenges linked to the multiple crises. This part of the series reviews the blind spots and gaps in the debate around agri-food systems transformation and how these hinder the transformation. Furthermore, this report offers recommendations on how to address these gaps to facilitate an agri-food system transformation aligned to the leading themes of people, planet, and prosperity. The report was drafted by TMG with contributions from an extended group of experts.

It is with complete humility that I admit that I cannot answer the main question posed by this book's coordinators: Do the coexistence and confrontation of agricultural and food models open the way to a new paradigm of territorial development?

Ensuring sustainable food systems requires vastly reducing their environmental and health costs while making healthy and sustainable food affordable to all. One of the central problems of current food systems is that many of the costs of harmful foods are externalized, i.e., are not reflected in market prices. At the same time, the benefits of healthful foods are not appreciated. Due to externalities, sustainable and healthy food is often less affordable to consumers and less profitable for businesses than unsustainable and unhealthy food. Externalities and other market failures lead to unintended consequences for present and future generations, destroying nature and perpetuating social injustices such as underpay for workers, food insecurity, illness, premature death and other harms. We urgently need to address the fundamental causes of these problems. This chapter sets out the results of an analysis to determine the current cost of externalities in food systems and the potential impact of a shift in diets to more healthy and sustainable production and consumption patterns. The current externalities were estimated to be almost double (19.8 trillion USD) the current total global food consumption (9 trillion USD). These externalities accrue from 7 trillion USD (range 4–11) in environmental costs, 11 trillion USD (range 3–39) in costs to human life and 1 trillion USD (range 0.2–1.7) in economic costs. This means that food is roughly a third cheaper than it would be if these externalities were included. More studies are needed to quantify the costs and benefits of food systems that would support a global shift to more sustainable and healthy diets. However, the evidence presented in this chapter points to the urgent need for a system reset to account for these ‘hidden costs’ in food systems and calls for bold actions to redefine the incentives for producing and consuming healthier and more sustainable diets. The first step to correct for these ‘hidden costs’ is to redefine the value of food through true-cost accounting (TCA) so as to address externalities and other market failures. TCA reveals the true value of food by making the benefits of affordable and healthy food visible and revealing the costs of damage to the environment and human health 3.

Food system transformation provides the opportunity to shift current trends in all forms of malnutrition, prioritizing the availability and affordability of nutritious food for all – from shifting priorities in agricultural production, to improved food systems that favor nutrition and sustainability. The task of Action Track 4 is to explore approaches to doing so that will advance equitable livelihoods for producers, businesses, workers across the food system and consumers, with a particular emphasis on addressing inequalities and power imbalances. As the Science Group for AT 4, we explore the nature of these issues, using the drivers of food systems as articulated by the High Level Panel of Experts of the UN Committee on World Food Security (HLPE 2020) as framing. Small and medium-sized producers and people who rely on food systems in rural and urban areas for livelihoods are disproportionately affected by all biophysical and environmental drivers, including soil and water resources and climate change. Unequal opportunity in access to all types of resources reduces overall production, resilience and rural transformation. Advances in innovation, technology and infrastructure have had important impacts on food production and sustainability, transportation and processing along food value chains, marketing, and, ultimately, diets, including the consumption of both nutritious and unhealthy foods. However, achievement of equitable livelihoods in food systems will require that issues of access to contextually suitable innovation and technology, inclusive of indigenous knowledge, be substantially enhanced. Many economic and political factors can be essential causes of inequality and power imbalances at the household, community, national and global levels, which may constrain the ability of food system transformation to deliver poverty reduction and sustainable, equitable livelihoods. Finally, vast evidence illustrates that several socio-cultural and demographic drivers underpin inequalities among and within societies and constrain the potential for some to benefit from actions to improve their livelihoods, particularly women, youths, the disabled, the elderly and indigenous peoples. These issues have been exacerbated by the COVID-19 pandemic. The pandemic is having a significant impact on global commodity markets and trading systems, economic growth, incomes, and poverty levels, with a likely disproportionate burden falling on vulnerable communities in both urban and rural areas. This is likely to worsen inequalities and set back progress against poverty and hunger goals. To address these issues, we must transform not only food systems, but the structures and systems that continue to enable and exacerbate inequities. Drivers of food system inequities are highly interconnected, and progress in addressing one will likely require change across several. For example, globalization and trade interact with other powerful drivers, especially technology resource mobilization and demographic trends, which shape food production, distribution, and consumption. Hence, in the final section, we reflect on several factors that should be part of effective solutions for combating inequalities in food systems, including rights-based approaches. We then share a series of recommendations aimed at enhancing inclusive decision-making, protecting the livelihoods of those living in situations of vulnerability while creating opportunities, adapting institutions and policies to favor equitable food system livelihoods, and increasing investment so as to realize the potential of improved institutional and policy actions. We invite governments, businesses, and organizations to hold themselves and others to account in advancing equitable livelihoods, and open avenues towards realizing the potential of science, innovation, technology, and evidence to favor equitable livelihoods.

Adrenal 11-oxygenated androgens may support cancer progression in men with prostate cancer owing to their abundance and androgenic potential. We hypothesized that preoperative circulating levels of 11-oxygenated androgens influence clinical outcomes in men with newly diagnosed localized prostate cancer.We studied 1,793 treatment-naïve patients and 155 patients who received preoperative treatment with 5α-reductase inhibitors in the prospective PROCURE cohort, for which preoperative plasma samples were obtained prior to radical prostatectomy. Adrenal 11-oxygenated precursors, potent 11-oxygenated androgens and their metabolites (n=7), were quantified using liquid chromatography-tandem mass spectrometry. Circulating levels were evaluated in relation to prognostic factors, disease-free survival, and metastasis-free survival using multivariable Cox proportional hazards models.At a median follow-up of 93.8 months after surgery, 583 patients experienced biochemical recurrence, 104 developed metastatic disease, and 168 diseased. Higher levels of 11-hydroxytestosterone and 11-ketotestosterone were observed in men with PSA20 ng/mL and positive nodal status (Preoperative circulating 11-oxygenated androgen levels are associated with metastasis-free survival in men with localized prostate cancer undergoing radical prostatectomy and are affected by 5α-reductase inhibitor treatment.

Dihydrotestosterone and testosterone are thought to be major contributors of prostate cancer progression and resistance. We studied the modulation of 15 circulating steroids by castration and their association with dihydrotestosterone and testosterone levels.A total of 116 serum samples were collected from 99 prostate cancer patients and categorized as eugonadal, castration-sensitive prostate cancer, castration-resistant prostate cancer, or castration-resistant prostate cancer under abiraterone acetate. Serum levels of 15 steroids were measured using mass spectrometry and compared between groups using analysis of variance. Intrapatient association of steroid levels and the androgens testosterone and dihydrotestosterone were assessed using Pearson correlation and linear regression.Testosterone, dihydrotestosterone, androstenedione, dehydroepiandrosterone, dehydroepiandrosterone-sulfate, androsterone, androstenediol, estrone, estrone-sulfate, estradiol, and androsterone/3α-diol-3/3α-diol-17-glucuronide levels were significantly decreased in castration-sensitive prostate cancer (castrated) compared to eugonadal patients. Testosterone levels were strongly associated with multiple steroids under eugonadal conditions, whereas they were weakly affected by precursor steroids in castrated patients. By contrast, dihydrotestosterone levels under androgen deprivation therapy were associated with testosterone and the backdoor pathway metabolite androsterone. In castration-resistant prostate cancer patients, levels of androstenedione were significantly associated with testosterone level, while testosterone was the only steroid associated with dihydrotestosterone levels.Androgen deprivation therapy significantly reduces the levels of 13 circulating steroids. Upon androgen deprivation therapy initiation, the backdoor pathway metabolite androsterone are strongly associated with dihydrotestosterone levels. Under castration-resistant prostate cancer conditions, androstenedione was significantly associated with testosterone levels, suggesting the presence of tumor-related circulating androgens in these patients. These results provide further rationale to intensify treatments with androgen receptor axis signaling pathway inhibitors in patients with prostate cancer.

International audience; After decades of political, economic, and scientific efforts, humanity has not gotten any closer to global sustainability. With less than a decade to reach the UN Sustainable Development Goals (SDGs) deadline of the 2030 Agenda, we show that global development agendas may be getting lost in translation, from their initial formulation to their final implementation. Sustainability science does not “speak” most of the 2000 languages from Africa, where the lack of indigenous terminology hinders global efforts such as the COVID-19 pandemic fight. Sociolinguistics, social psychology, cognitive ergonomics, geography, environmental sciences, and artificial intelligence (AI) are all relevant disciplinary fields to uncover the “foreign language effect” that hinders the implementation of the SDGs in Africa. We make the case for detecting and addressing language barriers towards multilingual sustainability in Africa by (1) exploring the ”foreign language effect” among African decision-makers and recognising their alternative social representations about sustainability; and (2) detecting Western language stereotypes about sustainability. We propose rethinking SDG-related scientific notions through participatory natural language processing (NLP) and the study of African social representations of sustainability, thus enabling a more inclusive and efficient approach to “sustainability(ies)”.

Las áreas protegidas, las tierras Indígenas y los territorios de las comunidades locales cubren una gran proporción de la cuenca Amazónica. Estas tierras juegan un papel crucial para frenar la deforestación, mantener la estabilidad climática regional, mitigar el cambio climático global y, sobre todo, proteger los derechos sobre la tierra. Sin embargo, los derechos sobre la tierra en la Amazonía corren un riesgo crítico debido a los intereses políticos que impulsan la especulación de la tierra, la expansión de los agronegocios y la tala y minería ilegales, con el consiguiente aumento de las tasas de deforestación, además de las amenazas de cambiar la legislación sobre derechos territoriales.

Este capítulo examina las oportunidades y los enfoques sitio específicos para restaurar los sistemas terrestres y acuáticos, centrándose en las acciones locales y sus beneficios inmediatos. Las considera-ciones sobre el paisaje, la cuenca y el bioma se abordan en el Capítulo 29. Los enfoques de conserva-ción se abordan en el Capítulo 27.

Este capítulo describe algunos de los enfoques necesarios para abordar las principales amenazas a la biodiversidad y los ecosistemas de la Amazonía, es decir, la deforestación, la construcción de represas en los ríos, la minería, la caza, el comercio ilegal, la producción y el tráfico de drogas, la tala ilegal, la sobrepesca y la expansión de la infraestructura.

The paper is a revised version of a research brief produced for the World Food Summit as Moustier, P., Holdsworth, M., Dao The Anh, Pape Abdoulaye Seck, Renting, H., Caron, P., Bricas,N. 2021. Priorities for urban food systems transformations in the global South. United Nations Food Systems Summit 2021 Scientific Group. This brief will be published as a forthcoming book chapter of Joachim von Braun, Kaosar Afsana, Louise Fresco and Mohamed Hag Ali Hassan (eds), Science and Innovations for Food Systems Transformation. Springer.; International audience; Highlights• Research on urban food issues in the global South lacks a systemic approach.• Urban food consumption reflects income disparities.• Urban consumers rely on diverse food retailing and catering formats.• Diverse urban food chains are used in combination to supply cities.• Public policies should better support SMEs in urban food chains.

Science does not progress without controversy as well the societies. In this article, this approach is privileged, aiming to analyze whether they can hinder or speed up the agricultural and food, environmental and sanitary transitions necessary to achieve the Sustainable Development Goals (SDGs). It begins with an alert to the past development model and the limits of the planet, highlighting some themes and forms of action chosen by international institutions and / or scientist’s networks. Then, we selected some controversies and their arguments, related to environmental issues and the evolution of food systems. In the subsequent item, its actors and five sub controversies sought to highlight the difficulties for the transition to circular systems, considered as a vector of sustainability. It is concluded that controversies can block advances for transitions, being essential the design of methods, criteria and indicators for a better understanding of oppositions, as well as the need to include both themes and new approaches in research agendas.

Nucleotide sugars and more specifically UDP-sugars, represent a major source of energy, key components of extracellular matrix, glycosylation and glucuronidation reactions, and emerge as important signaling molecules through P2Y14 purinergic receptor. Despite their pivotal role in a variety of physiological and pathological processes and their potential as biomarkers, UDP-sugar composition of biological fluids remains poorly studied. We developed a liquid chromatography electrospray ionization tandem mass spectrometry in multiple reaction monitoring mode for the simultaneous quantification of UDP-glucose, UDP-galactose, UDP-glucuronic acid, UDP-N-acetylgalactosamine and UDP-N-acetylglucosamine in human blood and urine. Relative to existing methods, UDP-sugar recovery was enhanced with perchloric acid and ammonium formate during sample preparation that also significantly improved chromatographic stability. Performance of the assay was validated and allowed the absolute quantification of UDP-sugars with a wide dynamic range (0.1 to 200 ng/mL) using stable deuterated isotopes as internal standards. We report a fast (13 min run) and sensitive method (limit of detection: 10-30 pg/mL; lower limit of quantification ≤ 0.2 ng/ml) to simultaneously quantify five UDP-sugars in a low volume (100 µL) of plasma and urine. Findings identified sex-specific profiles in both plasma and urine of healthy subjects. Applicability was also successfully demonstrated in specimens collected from individuals displaying a variety of medical conditions. This validated method was optimized for a high-throughput assessment of UDP-sugars in specimens of clinical importance and enabled an accurate and reliable absolute quantification of important UDP-sugars in diverse clinical contexts.

24S-hydroxycholesterol (i.e., cerebrosterol, 24S-OH-Chol) is the main form of cholesterol elimination from the brain. Liquid chromatography-tandem mass spectrometry methods were developed for the quantification of the total and unesterified/unbound fractions of 24S-OH-Chol, its monosulfate, monoglucuronide, and diconjugate derivatives (24S-OH-Chol-3sulfate [3S], 24S-OH-Chol-24glucuronide [24G] and 24S-OH-Chol-3S, 24G, respectively) in human plasma. Linearity, precision, accuracy, and extraction recovery were validated within the typical physiological and pathological ranges of concentrations for each compound. The lower limit of quantifications was 2.00, 0.33, 0.26, and 0.74 ng/ml for 24S-OH-Chol, 24S-OH-Chol-24G, 24S-OH-Chol-3S, and 24-OH-Chol-3S, 24G, respectively. Extraction recovery values in total and unbound plasma fractions were also analyzed in murine and monkey plasma and varied from 73% in mouse to 113% in cynomolgus monkey. The methods could rapidly (less than 7 min) quantify individual compounds with high sensitivity, accuracy (bias ≤15%), and reproducibility (coefficient of variation [CV] ≤ 17%). Their clinical applications were validated by measuring levels of the 4 compounds in samples from 20 noncholestatic donors, 5 cholestatic patients suffering from primary biliary cirrhosis, and 10 patients suffering from biliary stenosis. Results highlight the abundance of 24S-OH-Chol in the total fraction and the abundance of 24S-OH-Chol-3S and 24G in the unbound ones. While the latter strongly accumulate in plasma fractions of cholestatic patients, levels of 24S-OH-Chol remained similar to those of healthy donors. Our results indicate that this approach is suitable for monitoring cerebrosterol and its conjugates in large-scale clinical studies.

Background High UGT2B17 is associated with poor prognosis in untreated chronic lymphocytic leukaemia (CLL) patients and its expression is induced in non-responders to fludarabine-containing regimens. We examined whether UGT2B17, the predominant lymphoid glucuronosyltransferase, affects leukaemic drug response and is involved in the metabolic inactivation of anti-leukaemic agents. Methods Functional enzymatic assays and patients’ plasma samples were analysed by mass-spectrometry to evaluate drug inactivation by UGT2B17. Cytotoxicity assays and RNA sequencing were used to assess drug response and transcriptome changes associated with high UGT2B17 levels. Results High UGT2B17 in B-cell models led to reduced sensitivity to fludarabine, ibrutinib and idelalisib. UGT2B17 expression in leukaemic cells involved a non-canonical promoter and was induced by short-term treatment with these anti-leukaemics. Glucuronides of both fludarabine and ibrutinib were detected in CLL patients on respective treatment, however UGT2B17 conjugated fludarabine but not ibrutinib. AMP-activated protein kinase emerges as a pathway associated with high UGT2B17 in fludarabine-treated patients and drug-treated cell models. The expression changes linked to UGT2B17 exposed nuclear factor kappa B as a key regulatory hub. Conclusions Data imply that UGT2B17 represents a mechanism altering drug response in CLL through direct inactivation but would also involve additional mechanisms for drugs not inactivated by UGT2B17.

A agricultura familiar representa um dos principais grupos sociais e econômicos no norte do Mato Grosso. Entender a interação entre as políticas públicas e as dinâmicas locais e regionais que afetam esse setor econômico é de fundamental importância para identificar as lacunas e os problemas de ordem política e operacional que dificultam o desenvolvimento da região. Este estudo visa analisar o impacto local e a apropriação das políticas públicas relacionadas ao desenvolvimento rural pela produção familiar e por atores sociais do território denominado Portal da Amazônia, que abrange 16 municípios situados no norte de Mato Grosso. Para tal foram comparados os instrumentos clássicos de política pública para a produção familiar (políticas de crédito, assistência técnica e extensão rural e apoio à valorização econômica ou à qualificação dos produtos), com novos instrumentos participativos de políticas públicas (programas do governo federal que valorizam a gestão ambiental e a produção sustentável). Esses dois grupos de políticas públicas se diferenciam principalmente pela escala de atuação: o primeiro tem cunho mais individual, associado ao dono do lote, e o segundo tem abrangência territorial, aplicado a um grupo de municípios. Os resultados demonstram uma aplicação problemática e deficiente dos instrumentos clássicos, em particular o crédito e a assistência técnica, o que dificulta a gestão ambiental e incentiva práticas produtivas pouco sustentáveis, embora com um potencial de diversificação da assistência técnica e extensão rural (ATER). Os novos instrumentos de políticas públicas com base no território, como o Vida Rural Sustentável têm proporcionado espaços importantes de inovação e organização dos agricultores, assim como uma maior interação com a sociedade civil local. Esses novos instrumentos têm fortalecido o reconhecimento e a importância da produção familiar para a economia da região, incentivando a mesma a buscar a melhoria de sua produção. Uma produção familiar fortalecida, organizada e atuando de forma coletiva é fundamental para a promoção de um desenvolvimento rural que seja baseado na produção sustentável, que respeite o meio ambiente e propicie uma distribuição de renda mais igualitária.

Restoration can be applied in many different Amazonian contexts, but will be most effective at leveraging environmental and social benefits when it is prioritized across the Amazon basin, landscapes, and catchments. Here we outline the considerations that are most relevant for planning and scaling restoration across the Amazon.

This chapter examines site-specific opportunities and approaches to restore terrestrial and aquatic systems, focusing on the local actions and benefits. Landscape and biome-wide considerations are addressed in Chapter 29.

Human activities destroy biodiversity and disrupt the functioning of aquatic and terrestrial ecosystems at different levels. This chapter provides sustainable approaches to address some of the biggest threats to the Amazon’s biodiversity and ecosystems, i.e., deforestation, damming of rivers, mining, hunting, illegal trade, drug, production and trafficking, illegal logging, overfishing, and infrastructure expansion. The role of restoration is addressed in chapters 28 and 29.

Protected areas, Indigenous lands, and local communities’ territories play a critical role in holding back deforestation, maintaining regional and global climate stability, and – above all – protecting land rights. Nevertheless, these lands are currently threatened by political and economic interests that drive land speculation, agribusiness expansion, and illegal logging and mining, resulting in increasing deforestation rates. Governments are also reassessing and walking back territorial rights legislation.

The 4th Global Food Security conference highlighted four major developments: the shift from food security to food systems; a focus on diets and consumption patterns; the importance of unknown futures and inherent uncertainties and risks; and the central role of multi-level connections between local- and global-oriented research. These shifts highlight the importance for research to contribute to dialogue and collective intelligence through evidence-based brokerage, and to move beyond polarization of debates. These shifts also call for the involvement of scientists in multi-stakeholder arrangements to strengthen innovation and learning at different levels, and for their participation in foresight studies to help navigate plausible futures. Delegates discussed five scientific challenges to be addressed through both research investments and by improving science-policy interfaces.

Food Security and Nutrition (FSN) is influenced by diverse and complex factors, and therefore requires a holistic approach to agriculture and food systems plus integration of knowledge from diverse sources in science and society. Using the results of a colloquium held at the University of Hohenheim (Germany) in September 2016 leading up to the recent High Level Panel of Experts (HLPE) Note on Critical and Emerging Issues for Food Security and Nutrition, this article underlines the role of research and innovation as a social and political process and draws attention to neglected types of knowledge. It illustrates the potential of knowledge co-production and co-innovation to transform food systems in order to achieve the Sustainable Development Goals.

Accurate quantification of the metabolic enzyme uridine diphospho-glucuronosyltransferase (UGT) UGT2B17 has been hampered by the high sequence identity with other UGT2B enzymes (as high as 94%) and by the lack of a specific antibody. Knowing the significance of the UGT2B17 pathway in drug and hormone metabolism and cancer, we developed a specific monoclonal antibody (EL-2B17mAb), initially validated by the lack of detection in liver microsomes of an individual carrying no UGT2B17 gene copy and in supersomes expressing UGT2B enzymes. Immunohistochemical detection in livers revealed strong labeling of bile ducts and variable labeling of hepatocytes. Expression levels assessed by immunoblotting were highly correlated to mass spectrometry-based quantification (r = 0.93), and three major expression patterns (absent, low, or high) were evidenced. Livers with very low expression were carriers of the functional rs59678213 G variant, located in the binding site for the transcription factor forkhead box A1 (FOXA1) of the UGT2B17 promoter. The highest level of expression was observed for individuals carrying at least one rs59678213 A allele. Multiple regression analysis indicated that the number of gene copies explained only 8% of UGT2B17 protein expression, 49% when adding rs59678213, reaching 54% when including sex. The novel EL-2B17mAb antibody allowed specific UGT2B17 quantification and exposed different patterns of hepatic expression. It further suggests that FOXA1 is a key driver of UGT2B17 expression in the liver. The availability of this molecular tool will help characterize the UGT2B17 level in various disease states and establish more precisely the contribution of the UGT2B17 enzyme to drug and hormone metabolism.

Ce texte présente une analyse comparée de trois initiatives municipales engageant les organisations d'agriculteurs. L'étude comparative considère surtout les conditions de l'implication des exploitations familiales dans les actions de planification municipale et les stratégies respectives des principales catégories d'acteurs producteurs, responsables politiques, institutions techniques. Les trois expériences analysées présentent des origines, des contextes et des cheminements sensiblement différents. Le premier cas, celui de l'Unité de Planification Agricole de la Municipalité de Juazeiro, dans le nord-est de l'Etat de Bahia représente une expérience d'innovation institutionnelle. Le deuxième exemple, celui de la Commission Eau du Municipe de Pintadas (Sertao sud, Etat de Bahia) correspond à une initiative des associations de producteurs. Enfin, le projet de Taua (Sertao central, Etat du Ceara) associe divers partenaires non gouvernementaux et les services publics à l'action des organisations d'agriculteurs