Altered translation of GATA1 in Diamond-Blackfan anemia

Ribosomal protein haploinsufficiency occurs in diverse human diseases including Diamond-Blackfan anemia (DBA),1,2 congenital asplenia,3 and T-cell leukemia.4 Yet how mutations in such ubiquitously expressed proteins result in cell-type and tissue specific defects remains a mystery.5 Here, we show that GATA1 mutations that reduce full-length protein levels of this critical hematopoietic transcription factor can cause DBA in rare instances. We show that ribosomal protein haploinsufficiency, the more common cause of DBA, can similarly reduce translation of GATA1 mRNA - a phenomenon that appears to result from this mRNA having a higher threshold for initiation of translation. In primary hematopoietic cells from patients with RPS19 mutations, a transcriptional signature of GATA1 target genes is globally and specifically reduced, confirming that the activity, but not the mRNA level, of GATA1 is reduced in DBA patients with ribosomal protein mutations. The defective hematopoiesis observed in DBA patients with ribosomal protein haploinsufficiency can be at least partially overcome by increasing GATA1 protein levels. Our results provide a paradigm by which selective defects in translation due to mutations in ubiquitous ribosomal proteins can result in human disease

A rapid evidence assessment of UK citizen and industry understandings of sustainability - Why our understanding of sustainable food is important when making food choices

The Food Standards Agency (FSA) commissioned the Centre for Food Policy at City, University of London and collaborative partners to carry out a Rapid Evidence Assessment (REA) on UK citizen perceptions of food sustainability. This Executive Summary presents the findings of this REA, along with academic definitions of food sustainability (and how citizen definitions compare to these), and a rapid review of industry and NGO approaches to sustainability amongst a small random selection of 21 organisations across the food system. Please refer to the full report and appendices for detailed findings and methodology. The main research question addressed is: What does sustainability mean to UK citizens when it comes to food and diet? The report addresses the following secondary questions: How does the UK academic literature define sustainability, ‘sustainable food’ and ‘sustainable diet’?, how do citizens’ perceptions compare to this, and ‘What does sustainability mean to industry when it comes to food and diet?’. 'A number of sub-questions and themes were explored to answer the main research question, such as understanding and importance of sustainability and its impact on food choices, trade-offs, drivers and barriers to sustainable food choices and differences across demographic groups. To note: In this Executive Summary we refer to communities and individuals in the UK as “UK citizens”, rather than UK consumers. The use of the term citizen is not meant to be a reference to citizenship either directly via birth in the UK or through the process of naturalization

Altered translation of GATA1 in Diamond-Blackfan anemia

Ribosomal protein haploinsufficiency occurs in diverse human diseases including Diamond-Blackfan anemia (DBA)[superscript 1, 2], congenital asplenia[superscript 3] and T cell leukemia[superscript 4]. Yet, how mutations in genes encoding ubiquitously expressed proteins such as these result in cell-type– and tissue-specific defects remains unknown[superscript 5]. Here, we identify mutations in GATA1, encoding the critical hematopoietic transcription factor GATA-binding protein-1, that reduce levels of full-length GATA1 protein and cause DBA in rare instances. We show that ribosomal protein haploinsufficiency, the more common cause of DBA, can lead to decreased GATA1 mRNA translation, possibly resulting from a higher threshold for initiation of translation of this mRNA in comparison with other mRNAs. In primary hematopoietic cells from patients with mutations in RPS19, encoding ribosomal protein S19, the amplitude of a transcriptional signature of GATA1 target genes was globally and specifically reduced, indicating that the activity, but not the mRNA level, of GATA1 is decreased in patients with DBA associated with mutations affecting ribosomal proteins. Moreover, the defective hematopoiesis observed in patients with DBA associated with ribosomal protein haploinsufficiency could be partially overcome by increasing GATA1 protein levels. Our results provide a paradigm by which selective defects in translation due to mutations affecting ubiquitous ribosomal proteins can result in human disease.National Institutes of Health (U.S.) (Grant P01 HL32262)National Institutes of Health (U.S.) (Grant U54 HG003067-09

Misunderstandings Concerning Genetics Among Patients Confronting Genetic Disease

Critical questions arise about misunderstandings of genetics. We interviewed for 2 h each, 64 individuals who had or were at risk for Huntington's disease (HD), breast cancer or Alpha‐1 antitrypsin deficiency. These individuals revealed various misunderstandings that can affect coping, and testing, treatment and reproductive decisions. A therapeutic misconception about testing appeared: that testing would be helpful in and of itself. Many believed they could control genetic disorders (even HD), yet these beliefs were often incorrect, and could impede coping, testing, and treatment. Misunderstandings about statistics and genetics often fueled each other, and reflected denial, and desires for hope and control. Emotional needs can thus outweigh understandings of genetics and statistics, and providers’ input. Individuals often maintained non‐scientific beliefs, though embarrassed by these. These data have implications for care, and public and professional education. Misunderstandings’ persistence, despite realization of their inaccuracy, suggests that providers need to address not just cognitive facts, but underlying emotional issues

Wealth, household heterogeneity and livelihood diversification of Fulani pastoralists in the Kachia Grazing Reserve, northern Nigeria, during a period of social transition

A mixed methods study was undertaken in the Kachia Grazing Reserve of northern Nigeria. Surveys in March, June and October 2011 included focus group discussions, key informant and in-depth household interviews, concerning livelihood practices, animal health, ownership, and productivity. In May 2011, 249 Fulani families fleeing post-election violence entered the reserve with their livestock, increasing the number of households by one third.Despite being settled within a grazing reserve, over half of households sent all their cattle away on seasonal transhumance and another third sent some away. Cattle accounted for 96% of total tropical livestock units (TLU), of which 26% were cattle kept permanently outside the reserve. While all households cited livestock as their main source of income, 90% grew crops and 55% derived income from off-farm activities. A multiple correspondence analysis showed that for each extra member of a household its TLU value increased by 2.0 [95% CI, 1.4-2.7], while for each additional marriage its TLU increased by 15.7 [95% CI, 7.1-24.3]. A strong association was also observed between small herds, small households with only one wife, alongside marked geographical wealth differences within the reserve. New immigrant families had larger household sizes (33) and livestock holdings (122 TLU) than old settlers (22 people and 67 TLU). Prior to the mass immigration, the distribution of TLU per person was unimodal: 41% of households were classified as 'poor' and 27% as 'medium', whereas post-immigration it was bi-modal, with 26% classified as 'very poor' and 28% as 'medium'.While cattle remain the principal source of Fulani income and wealth, the inhabitants of Kachia Grazing Reserve have diversified their livelihood strategies to respond to changing circumstances and stress, especially the limited availability of grazing within the reserve and political insecurity outside, resulting in continued transhumance, the maintenance of smaller livestock holdings and pushing households into poverty