SALL3 mediates the loss of neuroectodermal differentiation potential in human embryonic stem cells with chromosome 18q loss.

Human pluripotent stem cell (hPSC) cultures are prone to genetic drift, because cells that have acquired specific genetic abnormalities experience a selective advantage in vitro. These abnormalities are highly recurrent in hPSC lines worldwide, but their functional consequences in differentiating cells are scarcely described. In this work, we show that the loss of chromosome 18q impairs neuroectoderm commitment and that downregulation of SALL3, a gene located in the common 18q loss region, is responsible for this failed neuroectodermal differentiation. Knockdown of SALL3 in control lines impaired differentiation in a manner similar to the loss of 18q, and transgenic overexpression of SALL3 in hESCs with 18q loss rescued the differentiation capacity of the cells. Finally, we show that loss of 18q and downregulation of SALL3 leads to changes in the expression of genes involved in pathways regulating pluripotency and differentiation, suggesting that these cells are in an altered state of pluripotency.

Rice availability and stability in Africa under future socio-economic development and climatic change.

As Africa is facing multiple challenges related to food security, frameworks integrating production and availability are urgent for policymaking. Attention should be given not only to gradual socio-economic and climatic changes but also to their temporal variability. Here we present an integrated framework that allows one to assess the impacts of socio-economic development, gradual climate change and climate anomalies. We apply this framework to rice production and consumption in Africa whereby we explicitly account for the continent's dependency on imported rice. We show that socio-economic development dictates rice availability, whereas climate change has only minor effects in the long term and is predicted not to amplify supply shocks. Still, rainfed-dominated or self-producing regions are sensitive to local climatic anomalies, while trade dominates stability in import-dependent regions. Our study suggests that facilitating agricultural development and limiting trade barriers are key in relieving future challenges to rice availability and stability.

A systematic review and evidence assessment of monogenic gene-disease relationships in human female infertility and differences in sex development.

BACKGROUND: As in other domains of medicine, high-throughput sequencing methods have led to the identification of an ever-increasing number of gene variants in the fields of both male and female infertility. The increasing number of recently identified genes allows an accurate diagnosis for previously idiopathic cases of female infertility and more appropriate patient care. However, robust evidence of the gene-disease relationships (GDR) allowing the proper translation to clinical application is still missing in many cases. OBJECTIVE AND RATIONALE: An evidence-based curation of currently identified genes involved in female infertility and differences in sex development (DSD) would significantly improve both diagnostic performance and genetic research. We therefore performed a systematic review to summarize current knowledge and assess the available GDR. SEARCH METHODS: PRISMA guidelines were applied to curate all available information from PubMed and Web of Science on genetics of human female infertility and DSD leading to infertility, from 1 January 1988 to 1 November 2021. The reviewed pathologies include non-syndromic as well as syndromic female infertility, and endocrine and reproductive system disorders. The evidence that an identified phenotype is caused by pathogenic variants in a specific gene was assessed according to a standardized scoring system. A final score (no evidence, limited, moderate, strong, or definitive) was assigned to every GDR. OUTCOMES: A total of 45 271 publications were identified and screened for inclusion of which 1078 were selected for gene and variant extraction. We have identified 395 genes and validated 466 GDRs covering all reported monogenic causes of female infertility and DSD. Furthermore, we present a genetic diagnostic flowchart including 105 genes with at least moderate evidence for female infertility and suggest recommendations for future research. The study did not take into account associated genetic risk factor(s) or oligogenic/polygenic causes of female infertility. WIDER IMPLICATIONS: We have comprehensively reviewed the existing research on the genetics of female infertility and DSD, which will enable the development of diagnostic panels using validated genes. Whole genome analysis is shifting from predominantly research to clinical application, increasing its diagnostic potential. These new diagnostic possibilities will not only decrease the number of idiopathic cases but will also render genetic counselling more effective for infertile patients and their families.

A sustainable future for Africa through continental free trade and agricultural development.

Developing and integrating agricultural markets may be key to addressing Africa's sustainability challenges. By modelling trade costs from farm gate to potential import markets across eight African regions, we investigate the impact of individual components of continental free trade and the complementary role of domestic agricultural development through increased market access for farmers and agricultural intensification. We find that free trade would increase intra-African agricultural trade sixfold by 2030 but-since it does not address local supply constraints-outside food imports and undernourishment would reduce only marginally. Agricultural development could almost eliminate undernourishment in Africa by 2050 at only a small cost of increased global greenhouse gas emissions. While continental free trade will be enabled in Africa through the African Continental Free Trade Area, aligning this with local agricultural development policies is crucial to increase intra-African trade gains, promote food security and achieve climate objectives.

Global hunger and climate change adaptation through international trade.

International trade enables us to exploit regional differences in climate change impacts and is increasingly regarded as a potential adaptation mechanism. Here, we focus on hunger reduction through international trade under alternative trade scenarios for a wide range of climate futures. Under the current level of trade integration, climate change would lead to up to 55 million people who are undernourished in 2050. Without adaptation through trade, the impacts of global climate change would increase to 73 million people who are undernourished (+33%). Reduction in tariffs as well as institutional and infrastructural barriers would decrease the negative impact to 20 million (-64%) people. We assess the adaptation effect of trade and climate-induced specialization patterns. The adaptation effect is strongest for hunger-affected import-dependent regions. However, in hunger-affected export-oriented regions, partial trade integration can lead to increased exports at the expense of domestic food availability. Although trade integration is a key component of adaptation, it needs sensitive implementation to benefit all regions.