The challenge of achieving basal energy, iron and zinc provision for home consumption through family farming in the Andes: a comparison of coverage through contemporary production systems and selected agricultural interventions

Background Child undernutrition is persistently high in the central Andes of Peru, and numerous smallholder households fail to meet their basic needs of energy, iron and zinc. Food-based approaches assume household-level nutrition can be improved following agricultural interventions. This study assesses for the first time whether current Andean production systems provide sufficient energy, iron and zinc output to meet household-level requirements and explores the likely effect of commonly promoted food-based approaches. Across four communities, we determined the crop and livestock production output for each household (n = 165) during one growing season. The household-level nutritional demand or input was calculated as a function of household composition and daily requirements of energy, iron and zinc as established by FAO/WHO. We examined five scenarios, current practice or status quo and four food-based interventions: (1) increased potato yield, (2) introduced biofortified potatoes, (3) promotion of guinea pigs and (4) a mixed strategy combining all of the above. Results Under status quo, 86, 62 and 76 % of households obtained sufficient production output to meet energy, iron and zinc requirements, respectively. Considering the three parameters simultaneously, 59 % of households were able to meet their energy, iron and zinc requirements. The total crop production among households provided more than the necessary energy, iron and zinc output to meet the demand of all 165 households. Yet, significant differences between households account for individual deficits or surpluses in household-level output–input balances. Potato (Solanum spp.), barley (Hordeum vulgare) and faba (Vicia faba) production was particularly significant in determining the energy, iron and zinc output. Livestock did not make a substantial contribution. The main difference between households with negative versus positive coverage, in terms of household-level production output from agriculture meeting demand (=input), was available cropping area given household size. None of the explored food-based interventions closed the energy, iron and zinc deficit from production among households with negative coverage. Conclusions The smallholder production systems analyzed are only partially capable of providing sufficient production output to cover household-level energy, iron and zinc demands. Of the four interventions examined, a mixed strategy holds most potential for reducing nutrition gaps. Particularly potato yield increases had a positive effect. The carrying capacity of high-altitude Andean farming systems is strained for households with limited land. Food-based approaches to nutrition under scenarios similar to those reported in this study are advised to balance agricultural interventions with options to enhance off-farm access to food

A let-7 microRNA-RALB axis links the immune properties of iPSC-derived megakaryocytes with platelet producibility

iPS細胞由来血小板造血における免疫巨核球の制御機構の発見 血小板の大量製造に向けた巨核球マスターセルの品質管理に応用可能. 京都大学プレスリリース. 2024-03-26.Discovering a new microRNA-regulated pathway to boost iPS cell-derived platelet production. 京都大学プレスリリース. 2024-03-26.We recently achieved the first-in-human transfusion of induced pluripotent stem cell-derived platelets (iPSC-PLTs) as an alternative to standard transfusions, which are dependent on donors and therefore variable in supply. However, heterogeneity characterized by thrombopoiesis-biased or immune-biased megakaryocytes (MKs) continues to pose a bottleneck against the standardization of iPSC-PLT manufacturing. To address this problem, here we employ microRNA (miRNA) switch biotechnology to distinguish subpopulations of imMKCLs, the MK cell lines producing iPSC-PLTs. Upon miRNA switch-based screening, we find imMKCLs with lower let-7 activity exhibit an immune-skewed transcriptional signature. Notably, the low activity of let-7a-5p results in the upregulation of RAS like proto-oncogene B (RALB) expression, which is crucial for the lineage determination of immune-biased imMKCL subpopulations and leads to the activation of interferon-dependent signaling. The dysregulation of immune properties/subpopulations, along with the secretion of inflammatory cytokines, contributes to a decline in the quality of the whole imMKCL population

Silencing of p53 and CDKN1A establishes sustainable immortalized megakaryocyte progenitor cells from human iPSCs

iPS細胞を用いた人工血小板の作製の効率化に成功 血小板のテイラーメイド医療に向けた一歩. 京都大学プレスリリース. 2021-12-03.Platelet transfusions are critical for severe thrombocytopenia but depend on blood donors. The shortage of donors and the potential of universal HLA-null platelet products have stimulated research on the ex vivo differentiation of human pluripotent stem cells (hPSCs) to platelets. We recently established expandable immortalized megakaryocyte cell lines (imMKCLs) from hPSCs by transducing MYC, BMI1, and BCL-XL (MBX). imMKCLs can act as cryopreservable master cells to supply platelet concentrates. However, the proliferation rates of the imMKCLs vary with the starting hPSC clone. In this study, we reveal from the gene expression profiles of several MKCL clones that the proliferation arrest is correlated with the expression levels of specific cyclin-dependent kinase inhibitors. Silencing CDKN1A and p53 with the overexpression of MBX was effective at stably inducing imMKCLs that generate functional platelets irrespective of the hPSC clone. Collectively, this improvement in generating imMKCLs should contribute to platelet industrialization and platelet biology