Mainstreaming access and benefit sharing in agricultural Research and Development: a workshop for researchers, practitioners and policy makers in selected African countries and organizations

The workshop Mainstreaming access and benefit sharing in agricultural Research and Development: a workshop for researchers, practitioners and policy makers in selected African countries and organizations was held at the International Livestock Research Institute (ILRI) in Addis Ababa from the 21st to the 24th of November 2022. The workshop was co-organized by the African Union Commission, ILRI and the CGIAR Genebank Initiative, and funded by the CGIAR Genebank Initiative. It brought together about 35 participants from national and international research organizations, regional and continental intergovernmental organizations, national ministries of environment and agriculture, private sector and farmers’ associations. The list of participants can be found in Annex 1 of this report. The objectives of the workshop were: • Raise awareness about the role of ABS in reaching pan-African objectives of sustainable agricultural development, food security and climate change adaptation. • Facilitate exchange of experiences in implementing ABS systems • Raise the profile of ABS procedures for reaching development objetives • Identify examples of how organizations have mainstreamed compliance with national ABS measures • Identify challenges for parties and brainstorm on potential solutions. • Exchange views on ABS for digital sequence information (DSI), taking into account practitioners’ actual use of DSI and ongoing international level consideration of the issue. • Initiate or strengthen dialogue between practitioners and national policy makers about guiding principles for mainstreaming ABS in agricultural research and development, • Advance the development of AUC template for material transfer agreement. • Advance on the consideration of ABS issues within concrete initiatives, including the Consortium Agreement on genomic reference resource for African cattle and the African Network of Animal Germplasm Biobanks The workshop agenda included the main following topics: - Setting the scene on ABS in Africa - ABS in agricultural research and development projects - Guiding principles for mainstreaming ABS in agricultural research and development - The African Union Commission template of Material Transfer Agreemen

Agrobiodiversity and integrated seed systems to improve smallholder livelihoods

Crop and tree diversity are essential to agriculture sustainability and food and nutrition security. The diversity of species and varieties that are available for farmers and the ways through which this diversity is made accessible to them depend on seed systems. But what must seed systems be like to enhance agrobiodiversity and smallholders’ livelihoods? Our authors take a look at the strengths and weaknesses of existing seed systems and experiences gained from a ten-year project in five countries on three continents

Advances in the registration of farmers’ varieties: Four cases from the global South

Over the last few decades, there has been a growing appreciation of crop varieties developed by local farmers, commonly referred to as farmers’ varieties. These varieties often have attractive characteristics for both producers and consumers, such as adaptability to harsh environmental conditions and high nutritional values. Yet they are usually not sold in formal markets, and tend to be limited to farmers’ seed systems. This is partially due to national seed laws that, in an effort to guarantee good quality seed of uniform and stable varieties, create obstacles for farmers’ varieties to reach the market. This article describes the experiences of four countries—Bolivia, Laos, Nepal and Zimbabwe—that are developing alternative variety registration systems for farmers’ varieties. Most of these cases have never been documented before. The cases present the main drivers behind and approaches to the registration of farmers’ varieties in different legal contexts and at different stages of development. We conclude that farmers’ variety registration systems can generate benefits including faster and cheaper variety releases, improved farmer incomes, and a larger diversity of well-adapted varieties in the market—but some important issues are still to be resolved

Technical assistance to strengthen national agricultural research organizations’ capacity to use digital sequence information. A submission from CGIAR

CGIAR submitted this report in response to an open request from the Plant Treaty Secretary, for submissions regarding, a) contracting parties’ and stakeholders’ capacity building needs for accessing and using digital sequence information (DSI)/genomic sequence data (GSD) and b) ‘technical assistance’ and ‘actions taken’ by stakeholders (including CGIAR) ‘to reduce the existing gap on capacity regarding DSI/GSD’. The primary objective of this paper is to respond to the second part of the request by sharing information about how CGIAR Centers and Initiatives have been assisting organizations outside CGIAR to access, generate, share, analyse, and use DSI for the conservation of plant genetic resources for food and agriculture (PRGFA) and for the use of PGRFA in pre-breeding and breeding. This paper does not provide an exhaustive account of all of the Centers’ relevant activities, but it does provide a general overview of the kinds of activities in which the Centers have been engaged. CGIAR very much appreciates the Governing Body’s initiative, as expressed in Resolution 16/2022, to ask the Plant Treaty Secretariat to gather and synthesize information about both demand for, and supply of, capacity strengthening related to DSI linked to plant genetic resources for food and agriculture, with the overall objective of working to close the capacity gap between developed and developing countries. It is our hope that, based on the outcomes of this exercise, CGIAR will be able to further adapt and improve its own approach to capacity sharing in response to needs prioritized by the Governing Body

Inadequate control of thyroid hormones sensitizes to hepatocarcinogenesis and unhealthy aging

An inverse correlation between thyroid hormone levels and longevity has been reported in several species and reduced thyroid hormone levels have been proposed as a biomarker for healthy aging and metabolic fitness. However, hypothyroidism is a medical condition associated with compromised health and reduced life expectancy. Herein, we show, using wild-type and the Pax8 ablated model of hypothyroidism in mice, that hyperthyroidism and severe hypothyroidism are associated with an overall unhealthy status and shorter lifespan. Mild hypothyroid Pax8 +/- mice were heavier and displayed insulin resistance, hepatic steatosis and increased prevalence of liver cancer yet had normal lifespan. These pathophysiological conditions were precipitated by hepatic mitochondrial dysfunction and oxidative damage accumulation. These findings indicate that individuals carrying mutations on PAX8 may be susceptible to develop liver cancer and/or diabetes and raise concerns regarding the development of interventions aiming to modulate thyroid hormones to promote healthy aging or lifespan in mammals

A new class of glycomimetic drugs to prevent free fatty acid-induced endothelial dysfunction

Background: Carbohydrates play a major role in cell signaling in many biological processes. We have developed a set of glycomimetic drugs that mimic the structure of carbohydrates and represent a novel source of therapeutics for endothelial dysfunction, a key initiating factor in cardiovascular complications. Purpose: Our objective was to determine the protective effects of small molecule glycomimetics against free fatty acid­induced endothelial dysfunction, focusing on nitric oxide (NO) and oxidative stress pathways. Methods: Four glycomimetics were synthesized by the stepwise transformation of 2,5­dihydroxybenzoic acid to a range of 2,5­substituted benzoic acid derivatives, incorporating the key sulfate groups to mimic the interactions of heparan sulfate. Endothelial function was assessed using acetylcholine­induced, endotheliumdependent relaxation in mouse thoracic aortic rings using wire myography. Human umbilical vein endothelial cell (HUVEC) behavior was evaluated in the presence or absence of the free fatty acid, palmitate, with or without glycomimetics (1µM). DAF­2 and H2DCF­DA assays were used to determine nitric oxide (NO) and reactive oxygen species (ROS) production, respectively. Lipid peroxidation colorimetric and antioxidant enzyme activity assays were also carried out. RT­PCR and western blotting were utilized to measure Akt, eNOS, Nrf­2, NQO­1 and HO­1 expression. Results: Ex vivo endothelium­dependent relaxation was significantly improved by the glycomimetics under palmitate­induced oxidative stress. In vitro studies showed that the glycomimetics protected HUVECs against the palmitate­induced oxidative stress and enhanced NO production. We demonstrate that the protective effects of pre­incubation with glycomimetics occurred via upregulation of Akt/eNOS signaling, activation of the Nrf2/ARE pathway, and suppression of ROS­induced lipid peroxidation. Conclusion: We have developed a novel set of small molecule glycomimetics that protect against free fatty acidinduced endothelial dysfunction and thus, represent a new category of therapeutic drugs to target endothelial damage, the first line of defense against cardiovascular disease

Levothyroxine enhances glucose clearance and blunts the onset of experimental type 1 diabetes mellitus in mice

BACKGROUND AND PURPOSEThyroid hormones induce several changes in whole body metabolism that are known to improve metabolic homeostasis. However, adverse side effects have prevented its use in the clinic. In view of the promising effects of thyroid hormones, we investigated the effects of levothyroxine supplementation on glucose homeostasis.EXPERIMENTAL APPROACHC57BL/6 mice were treated with levothyroxine from birth to 24 weeks of age, when mice were killed. The effects of levothyroxine supplementation on metabolic health were determined. C57BL/6 mice treated with levothyroxine for 2 weeks and then challenged with streptozotocin to monitor survival. Mechanistic experiments were conducted in the pancreas, liver and skeletal muscle. RIP-B7.1 mice were treated with levothyroxine for 2 weeks and were subsequently immunized to trigger experimental autoimmune diabetes (EAD). Metabolic tests were performed. Mice were killed and metabolic tissues were extracted for immunohistological analyses.KEY RESULTSLong-term levothyroxine supplementation enhanced glucose clearance and reduced circulating glucose in C57BL/6 mice. Levothyroxine increased simultaneously the proliferation and apoptosis of pancreatic beta cells, promoting the maintenance of a highly insulin-expressing beta cell population. Levothyroxine increased circulating insulin levels, inducing sustained activation of IRS1-AKT signalling in insulin-target tissues. Levothyroxine-treated C57BL/6 mice challenged with streptozotocin exhibited extended survival. Levothyroxine blunted the onset of EAD in RIP-B7.1 mice by inducing beta cell proliferation and preservation of insulin-expressing cells.CONCLUSIONS AND IMPLICATIONSInterventions based on the use of thyroid hormones or thyromimetics could be explored to provide therapeutic benefit in patients with type 1 diabetes mellitus

Exploratory analysis of seven Alzheimer's disease genes: disease progression

The relationships between GWAS-identified and replicated genetic variants associated to Alzheimer’s disease (AD) risk and disease progression or therapeutic responses in AD patients are almost unexplored. 701 AD patients with at least three different cognitive evaluations and genotypic information for APOE and six GWAS-significant SNPs were selected for this study. Mean differences in GDS and MMSE were evaluated using non-parametric tests, GLM and mixed models for repeated measurements. Each chart was also reviewed for evidence of treatment with any cholinesterase inhibitor (AChEI), memantine or both. Relationships between therapeutic protocols, genetic markers and progression were explored using stratified analysis looking for specific effects on progression in each therapeutic category separately. Neither calculation rendered a Bonferroni-corrected statistically significant difference in any genetic marker. Mixed model results suggested differences in the average point in MMSE test for patients carrying PICALM GA or AA genotype compared to GG carriers at the end of the follow up (MMSE mean difference= −0.57 C.I.95%[−1.145−0.009], p=0.047). This observations remained unaltered after covariate adjustments although did not achieve predefined multiple testing significance threshold. PICALM SNP also displayed a significant effect protecting against rapid progression during pharmacogenetics assays although it observed effect displayed heterogeneity among AD therapeutic protocols (p=0.039). None of studied genetic markers was convincingly linked to AD progression or drug response. However, by using different statistical approaches, PICALM rs3851179 marker displayed consistent but weak effects on disease progression phenotypes

Post-transplant cyclophosphamide after HLA identical compared to Haploidentical donor transplant in Acute Myeloid Leukemia: a study on behalf of GETH-TC

Post-transplantation cyclophosphamide (PTCY) effectively prevents graft-versus-host disease (GVHD) after unmanipulated HLA-haploidentical hematopoietic stem cell transplantation (HSCT) and achieves low rates of GVHD in HLA-identical transplantation. To compare the outcomes of haploidentical versus HLA identical HSCT in patients undergoing HSCT for acute myeloid leukemia (AML) using PTCY. We conducted a retrospective study of 229 patients undergoing first HSCT for AML using PTCY with additional immunosuppression, 99 from matched sibling or unrelated donor (MSD/MUD) performed in 3 hospitals and 130 from haploidentical donors (haplo group) performed in 20 hospitals within the Spanish Group of Hematopoietic Stem Cell Transplantation and Cellular Therapy. Peripheral blood stem cells were used as graft in 89% of patients; myeloablative conditioning was used in 56%. There were significantly more patients with active disease (5% versus 20%, P = .001), high/very high disease risk index (DRI) (32% versus 67%, P = .000) and prior auto-HSCT (2% versus 11%, P = .010) in the haplo group. Median follow-up was 27 and 62.5 months for MSD/MUD and haplo, respectively. At 2 years, no significant differences were observed in overall survival (OS) (72% versus 62%, P = .07), event-free survival (EFS) (70% versus 54%, P = .055), cumulative incidence of relapse (19% versus 25%, P = .13), non-relapse mortality (14% versus 19%, P = .145), and the composite endpoint of GVHD and relapse-free survival (49% versus 42%, P = .249). Multivariate analysis identified only age and active disease as significant risk factors for OS and EFS; reduced-intensity conditioning, high/very high DRI, and haplo donor were nearly statistically significant for these outcomes. Grade II-IV acute GVHD was lower in MSD/MUD (14% versus 47%, P = .000). Cumulative incidences of grade III-IV acute GVHD (4% versus 9%, P = .14) and moderate-severe chronic GVHD (22% versus 19%, P = .28) were similar. Limitations of our study include limited sample size, differences between haplo and MSD/MUD groups and heterogeneous additional immunosuppression and PTCY timing in MSD/MUD. The use of an HLA-identical donor with PTCY in patients with AML showed lower incidence of clinically significant grade II-IV acute GVHD compared to haplo donors. Further studies with larger sample sizes should be performed to establish a possible benefit of HLA-identical donor on survival. (C) 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc