Sox6 Is Necessary for Efficient Erythropoiesis in Adult Mice under Physiological and Anemia-Induced Stress Conditions

BACKGROUND: Definitive erythropoiesis is a vital process throughout life. Both its basal activity under physiological conditions and its increased activity under anemia-induced stress conditions are highly stimulated by the hormone erythropoietin. The transcription factor Sox6 was previously shown to enhance fetal erythropoiesis together and beyond erythropoietin signaling, but its importance in adulthood and mechanisms of action remain unknown. We used here Sox6 conditional null mice and molecular assays to address these questions. METHODOLOGY/PRINCIPAL FINDINGS: Sox6fl/flErGFPCre adult mice, which lacked Sox6 in erythroid cells, exhibited compensated anemia, erythroid cell developmental defects, and anisocytotic, short-lived red cells under physiological conditions, proving that Sox6 promotes basal erythropoiesis. Tamoxifen treatment of Sox6fl/flCaggCreER mice induced widespread inactivation of Sox6 in a timely controlled manner and resulted in erythroblast defects before reticulocytosis, demonstrating that impaired erythropoiesis is a primary cause rather than consequence of anemia in the absence of Sox6. Twenty five percent of Sox6fl/flErGFPCre mice died 4 or 5 days after induction of acute anemia with phenylhydrazine. The others recovered slowly. They promptly increased their erythropoietin level and amplified their erythroid progenitor pool, but then exhibited severe erythroblast and reticulocyte defects. Sox6 is thus essential in the maturation phase of stress erythropoiesis that follows the erythropoietin-dependent amplification phase. Sox6 inactivation resulted in upregulation of embryonic globin genes, but embryonic globin chains remained scarce and apparently inconsequential. Sox6 inactivation also resulted in downregulation of erythroid terminal markers, including the Bcl2l1 gene for the anti-apoptotic factor Bcl-xL, and in vitro assays indicated that Sox6 directly upregulates Bcl2l1 downstream of and beyond erythropoietin signaling. CONCLUSIONS/SIGNIFICANCE: This study demonstrates that Sox6 is necessary for efficient erythropoiesis in adult mice under both basal and stress conditions. It is primarily involved in enhancing the survival rate and maturation process of erythroid cells and acts at least in part by upregulating Bcl2l1

Pro-Survival Role for Parkinson's Associated Gene DJ-1 Revealed in Trophically Impaired Dopaminergic Neurons

A mouse genetic study reveals a novel cell-survival role for the Parkinson's disease-associated gene DJ-1 in dopaminergic neurons that have reduced support from endogenous survival factors

Food and Nutrition Security Indicators: A Review

In this paper, we review existing food and nutrition security indicators, discuss some of their advantages and disadvantages, and finally classify them and describe their relationships and overlaps. In order to achieve this, the paper makes reference to the existing definitions of food and nutrition security (FNS), in particular as they have been agreed upon and implemented in the FoodSecure project (www.foodsecure.eu). The main existing conceptual frameworks of FNS predating the present paper are also used as guidelines and briefly discussed. Finally, we make recommendations in terms of the most appropriate FNS indicators to quantify the impacts of various shocks and interventions on food and nutrition security outcomes

Between Hope and Hype: Traditional Knowledge(s) Held by Marginal Communities

Traditional Knowledge (TK) systems have always been integral to the survival and adaptation of human societies. Yet, they enjoy a fairly recent recognition and popularization by scientists, the media, politicians, corporates and the wider public. In this paper we present a typology of key driving forces behind the popularization of TK held by marginal communities: an equality preference motive, a value motive, a compliance motive, a scarcity motive and a strategic motive. Secondly, through the use of a simple model, we discuss the hype's impact on marginal communities. Moreover, we critically assess the outcome of a number of policy instruments that intend, in part, to protect traditional knowledge bases of such communities. Our analysis primarily draws upon secondary literature; policy documents and case studies within economics, the social sciences, conservation biology and legal studies. We argue that whilst the public and institutional hype around TK may have resulted in its prioritization within international conventions and frameworks, its institutionalization may have adversely impacted marginalized communities, and in particular contexts, unintentionally led to the creation of 'new' marginals. We purport that the traditional innovation incentive motive does not hold for protecting TK within a private property regime. Instead we identify a conservation incentive motive and a distribution motive that justify deriving policy instruments that focus on TK to protect marginal communities

Household, community, sub-national and country-level predictors of primary cooking fuel switching in nine countries from the PURE study

Introduction. Switchingfrom polluting (e.g. wood, crop waste, coal)to clean (e.g. gas, electricity) cooking fuels can reduce household air pollution exposures and climate-forcing emissions.While studies have evaluated specific interventions and assessed fuel-switching in repeated cross-sectional surveys, the role of different multilevel factors in household fuel switching, outside of interventions and across diverse community settings, is not well understood. Methods.We examined longitudinal survey data from 24 172 households in 177 rural communities across nine countries within the Prospective Urban and Rural Epidemiology study.We assessed household-level primary cooking fuel switching during a median of 10 years offollow up (∼2005–2015).We used hierarchical logistic regression models to examine the relative importance of household, community, sub-national and national-level factors contributing to primary fuel switching. Results. One-half of study households(12 369)reported changing their primary cookingfuels between baseline andfollow up surveys. Of these, 61% (7582) switchedfrom polluting (wood, dung, agricultural waste, charcoal, coal, kerosene)to clean (gas, electricity)fuels, 26% (3109)switched between different polluting fuels, 10% (1164)switched from clean to polluting fuels and 3% (522)switched between different clean fuels