Innate immunodeficiency following genetic ablation of Mcl1 in natural killer cells

The cytokine IL-15 is required for natural killer (NK) cell homeostasis; however, the intrinsic mechanism governing this requirement remains unexplored. Here we identify the absolute requirement for myeloid cell leukaemia sequence-1 (Mcl1) in the sustained survival of NK cells in vivo. Mcl1 is highly expressed in NK cells and regulated by IL-15 in a dose-dependent manner via STAT5 phosphorylation and subsequent binding to the 3'-UTR of Mcl1. Specific deletion of Mcl1 in NK cells results in the absolute loss of NK cells from all tissues owing to a failure to antagonize pro-apoptotic proteins in the outer mitochondrial membrane. This NK lymphopenia results in mice succumbing to multiorgan melanoma metastases, being permissive to allogeneic transplantation and being resistant to toxic shock following polymicrobial sepsis challenge. These results clearly demonstrate a non-redundant pathway linking IL-15 to Mcl1 in the maintenance of NK cells and innate immune responses in vivo

Type 2 Innate Lymphoid Cells Protect against Colorectal Cancer Progression and Predict Improved Patient Survival.

Chronic inflammation of the gastrointestinal (GI) tract contributes to colorectal cancer (CRC) progression. While the role of adaptive T cells in CRC is now well established, the role of innate immune cells, specifically innate lymphoid cells (ILCs), is not well understood. To define the role of ILCs in CRC we employed complementary heterotopic and chemically-induced CRC mouse models. We discovered that ILCs were abundant in CRC tumours and contributed to anti-tumour immunity. We focused on ILC2 and showed that ILC2-deficient mice developed a higher tumour burden compared with littermate wild-type controls. We generated an ILC2 gene signature and using machine learning models revealed that CRC patients with a high intratumor ILC2 gene signature had a favourable clinical prognosis. Collectively, our results highlight a critical role for ILC2 in CRC, suggesting a potential new avenue to improve clinical outcomes through ILC2-agonist based therapeutic approaches

An Optimization Model for Technology Adoption of Marginalized Smallholders: Theoretical Support for Matching Technological and Institutional Innovations

The rural poor are often marginalized and restricted from access to markets, public services and information, mainly due to poor connections to transport and communication infrastructure. Despite these unfavorable conditions, agricultural technology investments are believed to unleash unused human and natural capital potentials and alleviate poverty by productivity growth in agriculture. Based on the concept of marginality we develop a theoretical model which shows that these expectations for productivity growth are conditional on human and natural capital stocks and transaction costs. Our model categorizes the rural farm households below the poverty line into four segments according to labor and land endowments. Policy recommendations for segment and location specific investments are provided. Theoretical findings indicate that adjusting rural infrastructure and institutions to reduce transaction costs is a more preferable investment strategy than adjusting agricultural technologies to marginalized production conditions

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

Methodological Review and Revision of the Global Hunger Index

The Global Hunger Index (GHI) is a multidimensional measure of hunger that considers three dimensions: (1) inadequate dietary energy supply, (2) child undernutrition, and (3) child mortality. The initial version of the index included the following three, equally weighted, non-standardized (i.e. unscaled) indicators that are expressed in percent: the proportion of the population that is calorie deficient (FAO's prevalence of undernourishment); the prevalence of underweight in children under five; and the under-five mortality rate. Several decisions regarding the original formulation of the GHI are reconsidered in light of recent discussions in the nutrition community and suggestions by other researchers, namely the choice of the prevalence of child underweight for the child undernutrition dimension, the use of the under-five mortality rate from all causes for the child mortality dimension, and the decision not to standardize the component indicators prior to aggregation. Based on an exploration of the literature, data availability and comparability across countries, and correlation analyses with indicators of micronutrient deficiencies, the index is revised as follows: (1) The child underweight indicator is replaced with child stunting and child wasting; (2) The weight of one third for the child undernutrition dimension is shared equally between the two new indicators; and (3) The component indicators of the index are standardized prior to aggregation, using fixed thresholds set above the maximum values observed in the data set. The under-five mortality rate from all causes is retained, because estimating under-five mortality attributable to nutritional deficiencies would be very costly and make the production of the GHI dependent on statistics about cause-specific mortality rates by country and year that are published irregularly, while the expected benefits are limited

Social Safety Nets for Food and Nutritional Security in India

This paper brings together existing literature on the Mahatma Gandhi National Rural Employment Guarantee Act (MGNRGEA) and the Public Distribution System (PDS) in India, offering a narrative review of the evidence on impacts on food security, health and nutrition of beneficiaries. Both programs operate on a large scale and have the capacity to impact the factors leading to undernutrition. It is evident that despite the deficiencies in implementation, both the MGNREGA and the PDS are inclusive and reach the poor and the marginalized who are likely to also experience greater undernutrition and poor health. Data challenges have however prevented researchers from conducting studies that assess the ultimate impact of these two large-scale programs on health and nutrition. The evidence that exists suggests largely positive impacts indicating a clear potential to make these programs more nutrition sensitive not just by incorporating elements that would explicitly address nutritional concerns but also by directing specific attention to innovations that strengthen critical complementarities and synergies that exist between the two programs

Institutional Environments for Enabling Agricultural Technology Innovations: The Role of Land Rights in Ethiopia, Ghana, India and Bangladesh

Land rights are essential assets for improving the livelihoods of the rural poor. This literature based paper shed light to some land rights issues that are crucial for the effectiveness and sustainability of implementing technological innovations in marginalized rural areas of Ethiopia, Ghana, India and Bangladesh. By analysing country specific land right regimes, this paper aims to understand what institutional conditions might constitute barriers to the effective implementation of technological innovations and how they might be overcome. Land rights issues considered in this paper include public and private ownership of land in Ethiopia, customary and statutory law in Ghana, and gender equality and land rights in India and Bangladesh. A better understanding of institutional barriers for the effective implementation of technological innovations is a precondition for complementing technological with enabling institutional innovations and for improving priority setting, targeting and sequencing in the implementation of productivity increasing development measures