The formalization fix? Land titling and land concessions in Cambodia

Issuing land titles to smallholder farmers has long been embraced as a way to promote lending and land markets, but is increasingly being reframed as a way to protect smallholders from irresponsible agricultural investment. This brief examines the case of Cambodia, where over the last decade extensive land titling efforts have occurred alongside a wave of large-scale land concessions. The problem, however, is that titling has failed to live up to the rhetoric of systematic coverage, and has often focused on areas where tenure was already relatively secure. Areas outside the titling zone, in contrast, have become formalized de facto through the process of granting land concessions to investors. This undermines pro-poor development significantly.

Development and characterization of a scaffold-free 3D spheroid model of iPSC-derived human cardiomyocytes

Purpose: Cardiomyocytes are terminally differentiated cells in the adult heart and ischemia and cardiotoxic compounds can lead to cell death and irreversible decline of cardiac function. As testing platforms, isolated organs and primary cells from rodents have been the standard in research and toxicology, but there is a need for better models that more faithfully recapitulate native human biology. Hence, a new in vitro model comprising the advantages of 3D cell culture and the availability of induced pluripotent stem cells (iPSC) from human origin was developed and characterized. Methods: Human cardiomyocytes (CMs) derived from induced pluripotent stem cells (iPSCs) were studied in standard 2D culture and as cardiac microtissues (MTs) formed in hanging drops. 2D cultures were examined using immunofluorescence microscopy and Western blotting while the cardiac MTs were subjected to immunofluorescence, contractility, and pharmacological investigations. Results: iPSC-derived CMs in 2D culture showed well-formed myofibrils, cell-cell contacts positive for connexin-43, and other typical cardiac proteins. The cells reacted to pro-hypertrophic growth factors with a substantial increase in myofibrils and sarcomeric proteins. In hanging drop cultures, iPSC-derived cardiomyocytes formed spheroidal MTs within 4 days showing a homogeneous tissue structure with well-developed myofibrils extending throughout the whole spheroid without a necrotic core. MTs showed spontaneous contractions for more than 4 weeks that were recorded by optical motion tracking, sensitive to temperature, and responsive to electrical pacing. Contractile pharmacology was tested with several agents known to modulate cardiac rate and viability. Calcium-transients underlay the contractile activity and were also responsive to electrical stimulation, caffeine-induced Ca2+-release, extracellular calcium levels. Conclusions: 3D culture using iPSC-derived human cardiomyocytes provides an organoid human-based cellular platform that is free of necrosis and recapitulates vital cardiac functionality, thereby providing new and promising relevant model for the evaluation and development of new therapies and detection of cardiotoxicity.

The yeast ZRT1 gene encodes the zinc transporter protein of a high-affinity uptake system induced by zinc limitation.

The yeast Saccharomyces cerevisiae has two separate systems for zinc uptake. One system has high affinity for substrate and is induced in zinc-deficient cells. The second system has lower affinity and is not highly regulated by zinc status. The ZRT1 gene encodes the transporter for the high-affinity system, called Zrt1p. The predicted amino acid sequence of Zrt1p is similar to that of Irt1p, a probable Fe(II) transporter from Arabidopsis thaliana. Like Irt1p, Zrt1p contains eight potential transmembrane domains and a possible metal-binding domain. Consistent with the proposed role of ZRT1 in zinc uptake, overexpressing this gene increased high-affinity uptake activity, whereas disrupting it eliminated that activity and resulted in poor growth of the mutant in zinc-limited media. Furthermore, ZRT1 mRNA levels and uptake activity were closely correlated, as was zinc-limited induction of a ZRT1-lacZ fusion. These results suggest that ZRT1 is regulated at the transcriptional level by the intracellular concentration of zinc. ZRT1 is an additional member of a growing family of metal transport proteins.

BOLSA FAMÍLIA: IMPORTANTE DETERMINANTE PARA A EDUCAÇÃO E CRESCIMENTO SOCIOECONÔMICO DO BRASIL

Esta dissertação trata de um tema relativamente novo, com literatura escassa, praticamente sem estudos teóricos que o abordem. Referenciais são encontrados em publicações feitas em seminários e palestras bem como em artigos e notas jornalísticas. Esta dissertação se trata de trabalho exploratório, analítico descritivo com base documental. O Programa Bolsa Família, tema central deste trabalho, é uma ferramenta para distribuição de renda que funciona de forma simples e tem sido efetiva para o atendimento de famílias que vivem abaixo da linha de pobreza. Ele é resultado da fusão de vários outros programas dispersos e com efetividade questionável Bolsa Escola, Auxílio Gás e Cartão Alimentação. O Programa Bolsa Família beneficia famílias em situação de pobreza com renda mensal de R$ 70 a R$ 140 per capita e em extrema pobreza com renda mensal abaixo de R$ 70 reais per capita. Também estabelece condicionalidades de educação e saúde. Atualmente, há cerca de 13 milhões de famílias inscritas no Programa Bolsa Família que cumprem as condições do Cadastro Único esta é praticamente a totalidade das famílias pobres segundo critérios do PNAD 2006 (Pesquisa Nacional de Domicílios). Na realidade, houve substancial injeção de recursos em áreas outrora relegadas ao acaso, criando novos consumidores, bem como empreendedores, além de atrair investimentos. Quanto à educação, nota-se que há redução do analfabetismo. Há um crescimento vegetativo do Índice de Desenvolvimento Humano (IDH) no qual o Brasil situa-se em 84⁰ lugar dentre as 187 nações controladas pelo PNUD (Programa das Nações Unidas para o Desenvolvimento) em 2011. As variáveis que compõem o índice crescem timidamente, destaca-se queda no item expectativa de escolaridade esperada das crianças em idade de ingresso na escola (no Brasil, aos seis anos), que caiu no período 2000-2011, esse fato pode indicar falha estrutural no ensino brasileiro. Esse estudo indica que há desenvolvimento socioeconômico em áreas carentes, particularmente na Região Nordeste. Observa-se também a reversão da migração que historicamente era de norte/nordeste a sudeste. Também nota-se redução da taxa de fecundidade das brasileiras, o que é vantajoso. O Brasil também está com a vantagem do Bônus demográfico , quando a população economicamente ativa supera a população dependente, o que é um excelente fator de crescimento por atrair investimentos. Apesar de melhorias observadas na década 2000-2010, elas ainda são insuficientes. Quanto ao desenvolvimento humano , o Brasil está muito distante das nações desenvolvidas, com IDH de 0,718, que cresceu na última década à taxa de 0,769% ao ano. Nesse ritmo, até alcançarmos o IDH norueguês -- primeiro colocado, ou o australiano -- segundo colocado, que é de 0,943 serão necessários 35/36 anos. Isso nos leva a pensar que, a não ser que o acaso nos ajude, o sonho de nos juntarmos aos primeiros é questionável. Com respeito ao Programa Bolsa Família, esse prova ser uma frente social para a eliminação da desigualdade, seus beneficiários eram classificados como pobres e extremamente pobres e foram resgatados.

Metabolism Regulates the Fate and Function of T Lymphocytes

Proper balancing of the activities of metabolic pathways to meet the challenge of providing necessary products for biosynthetic and energy demands of the cell is a key requirement for maintaining cell viability and allowing for cell proliferation. Cell metabolism has been found to play a crucial role in numerous cell settings, including in the cells of the immune system, where a successful immune response requires rapid proliferation and successful clearance of dangerous pathogens followed by resolution of the immune response. Additionally, it is now well known that cell metabolism is markedly altered from normal cells in the setting of cancer, where tumor cells rapidly and persistently proliferate. In both settings, alterations to the metabolic profile of the cells play important roles in promoting cell proliferation and survival.

It has long been known that many types of tumor cells and actively proliferating immune cells adopt a metabolic phenotype of aerobic glycolysis, whereby the cell, even under normoxic conditions, imports large amounts of glucose and fluxes it through the glycolytic pathway and produces lactate. However, the metabolic programs utilized by various immune cell subsets have only recently begun to be explored in detail, and the metabolic features and pathways influencing cell metabolism in tumor cells in vivo have not been studied in detail. The work presented here examines the role of metabolism in regulating the function of an important subset of the immune system, the regulatory T cell (Treg) and the role and regulation of metabolism in the context of malignant T cell acute lymphoblastic leukemia (T-ALL). We show that Treg cells, in order to properly function to suppress auto-inflammatory disease, adopt a metabolic program that is characterized by oxidative metabolism and active suppression of anabolic signaling and metabolic pathways. We found that the transcription factor FoxP3, which is highly expressed in Treg cells, drives this phenotype. Perturbing the metabolic phenotype of Treg cells by enforcing increased glycolysis or driving proliferation and anabolic signaling through inflammatory signaling pathways results in a reduction in suppressive function of Tregs.

In our studies focused on the metabolism of T-ALL, we observed that while T-ALL cells use and require aerobic glycolysis, the glycolytic metabolism of T-ALL is restrained compared to that of an antigen activated T cell. The metabolism of T-ALL is instead balanced, with mitochondrial metabolism also being increased. We observed that the pro-anabolic growth mTORC1 signaling pathway was limited in primary T-ALL cells as a result of AMPK pathway activity. AMPK pathway signaling was elevated as a result of oncogene induced metabolic stress. AMPK played a key role in the regulation of T-ALL cell metabolism, as genetic deletion of AMPK in an in vivo murine model of T-ALL resulted in increased glycolysis and anabolic metabolism, yet paradoxically increased cell death and increased mouse survival time. AMPK acts to promote mitochondrial oxidative metabolism in T-ALL through the regulation of Complex I activity, and loss of AMPK reduced mitochondrial oxidative metabolism and resulted in increased metabolic stress. Confirming a role for mitochondrial metabolism in T-ALL, we observed that the direct pharmacological inhibition of Complex I also resulted in a rapid loss of T-ALL cell viability in vitro and in vivo. Taken together, this work establishes an important role for AMPK to both balance the metabolic pathways utilized by T-ALL to allow for cell proliferation and to also promote tumor cell viability by controlling metabolic stress.

Overall, this work demonstrates the importance of the proper coupling of metabolic pathway activity with the function needs of particular types of immune cells. We show that Treg cells, which mainly act to keep immune responses well regulated, adopt a metabolic program where glycolytic metabolism is actively repressed, while oxidative metabolism is promoted. In the setting of malignant T-ALL cells, metabolic activity is surprisingly balanced, with both glycolysis and mitochondrial oxidative metabolism being utilized. In both cases, altering the metabolic balance towards glycolytic metabolism results in negative outcomes for the cell, with decreased Treg functionality and increased metabolic stress in T-ALL. In both cases, this work has generated a new understanding of how metabolism couples to immune cell function, and may allow for selective targeting of immune cell subsets by the specific targeting of metabolic pathways.

Rwanda's Miracle: From Genocide and Poverty to Peace and Economic Prosperity

The purpose of this thesis was to examine how liberalization and the introduction of pro-poor policies can be successful in post-conflict countries using the Rwanda coffee market as a case study. My research supports the notion that economic development, political stability and peace can be a result of liberalization when policies that are pro-poor and focus on the largest sector of the population are created. The study examines why and how Rwanda chose to liberalize their economy in the way they did by focusing on the intentions of the actors and the effects their actions have had on the coffee market and country as a whole. The findings suggest that Rwanda’s coffee market liberalization has been successful and has contributed to stability and economic development in Rwanda. The conclusion indicates that pro-poor liberalization policies with the assistance from a variety of actors and institutions can lead developing countries on the path to development in ways the international community has not seen before.

Manganese toxicity in Portuguese Cambisols derived from granite: causes, limitations of soil analyses and possible solutions

Cambisols are the major soil type in Portugal. The yield of annual crops in these soils is generally poor, and the situation is aggravated in wet winters. In the south of Portugal, manganese toxicity has been identified as the major cause of poor growth and leaching as the main reason for the negative effect of rainfall observed in Cambisols derived from granite Manganese toxicity also appears to be present in the Cambisols in other regions of Portugal. Manganese toxicity is cross-related to the magnesium concentration, either in the soil solution or in plant shoots. Therefore soil amendment using dolomitic limestone is needed to overcome the problem. Current soil test methods are unable to predict the level of Mn toxicity. However, new approach using the extraction of soil solution is proposed, although further work is needed to fully implement the method.

DETERMINANTS OF THE ADOPTION OF INTEGRATED SOIL FERTILITY MANAGEMENT TECHNOLOGIES IN MBALE DIVISION, KENYA

The agro-climatic conditions in western Kenya present the region as a food surplus area yet people are still reliant on food imports, with the region registering high poverty levels. Depletion of soil fertility and the resulting decline in agricultural productivity in Mbale division has led to many attempts to develop and popularize Integrated Soil Fertility Management (ISFM) technologies that could restore soil fertility. These technologies bridge the gap between high external inputs and extreme forms of traditional low external input agriculture. Some of the ISFM components used by farmers are organic and inorganic inputs and improved seeds. However, the adoption of these technologies is low. The study aimed to examine the factors that influence the adoption of ISFM technologies by smallholder farmers in Mbale division, Kenya. The study was conducted in 9 sub-locations in Mbale division. Purposive sampling was used in selecting the 80 farmers to get the data based on a farm-household survey. Self-administered questionnaires were used to collect data on the determinants of the adoption of ISFM technologies from the sampled farmers in the study area. The study sought to answer the research question: What factors influence the uptake of ISFM technologies by farmers in Mbale division? The hypothesis tested was that the adoption of ISFM technologies is not influenced by age, education, extension services, labour, off-farm income and farm size. Data was analyzed using descriptive statistics. Cross tabulation was used for examining the relationship between categorical (nominal or ordinal) variables, and the bivariate correlations procedure was used to compute the pair wise associations between scale or ordinal variables. Probit regression was used to predict the socio-economic factors influencing the adoption of ISFM technologies among smallholder farmers. Results of the study indicated that education of household head, membership in social groups, age of the household head, off-farm income and farm size were the variables that significantly influenced the adoption of ISFM technologies. The findings show that there is need for a more pro-poor focused approach to achieve sustainable soil fertility management among smallholder farmers. The findings will help farmers, extension officers, researchers and donors in identifying region-specific entry points that can help in developing innovative ISFM technologies.

Association of TNF-α Gene Variants With Clinical Manifestation of Cystic Fibrosis Patients of Iranian Azeri Turkish Ethnicity

Background: Cystic fibrosis (CF), a life-limiting autosomal recessive disorder, is considered a monogenic disease that is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. According to several studies, mutation analysis of the cystic fibrosis transmembrane conductance regulator (CFTR) gene alone is insufficient to predict the phenotypic manifestations observed in cystic fibrosis (CF) patients. In addition, some patients with a milder CF phenotype do not carry any pathogenic mutation. Tumor Necrosis Factor-alpha (TNF-α) contributes to the pathophysiology of CF by causing cachexia. There is a reverse association between TNF-α concentration in patient's sputum and their pulmonary function. Objectives: To assess the effect of non-CFTR genes on the clinical phenotype of CF, two polymorphic sites (-1031T/C and -308G/A) of the TNF-α gene, as a modifier, were studied. Patients and Methods: Focusing on the lung and gastrointestinal involvement as well as the poor growth, we first investigated the role of TNF-α gene in the clinical manifestation of CF. Furthermore, based on the hypothesis that the cumulative effect of specific alleles of multiple CF modifier genes, such as TNF-α, may create the final phenotype, we also investigated the potential role of TNF-α in non-classic CF patients without a known pathogenic mutation. In all, 80 CF patients and 157 healthy control subjects of Azeri Turkish ethnicity were studied by the PCR–RFLP method. The chi-square test with Yates' correction and Fisher's exact test were used for statistical analysis. Results: The allele and genotype distribution of the investigated polymorphisms, and their associated haplotypes were similar in all groups. Conclusions: There was no evidence that supported the association of TNF-α gene polymorphisms with non-classic CF disease or the clinical presentation of classic CF.

Mobilizing Greater Crop and Land Potentials Sustainably

The supply side of the food security engine is the way we farm. The current engine of conventional tillage farming is faltering and needs to be replaced. This presentation will address supply side issues of agriculture to meet future agricultural demands for food and industry using the alternate no-till Conservation Agriculture (CA) paradigm (involving no-till farming with mulch soil cover and diversified cropping) that is able to raise productivity sustainably and efficiently, reduce inputs, regenerate degraded land, minimise soil erosion, and harness the flow of ecosystem services. CA is an ecosystems approach to farming capable of enhancing not only the economic and environmental performance of crop production and land management, but also promotes a mindset change for producing ‘more from less’, the key attitude towards sustainable production intensification. CA is now spreading globally in all continents at an annual rate of 10 Mha and covers some 157 Mha of cropland. Today global agriculture produces enough food to feed three times the current population of 7.21 billion. In 1976, when the world population was 4.15 billion, world food production far exceeded the amount necessary to feed that population. However, our urban and industrialised lifestyle leads to wastage of food of some 30%-40%, as well as waste of enormous amount of energy and protein while transforming crop-based food into animal-derived food; we have a higher proportion of people than ever before who are obese; we continue to degrade our ecosystems including much of our agricultural land of which some 400 Mha is reported to be abandoned due to severe soil and land degradation; and yields of staple cereals appear to have stagnated. These are signs of unsustainability at the structural level in the society, and it is at the structural level, for both supply side and demand side, that we need transformed mind sets about production, consumption and distribution. CA not only provides the possibility of increased crop yields for the low input smallholder farmer, it also provides a pro-poor rural and agricultural development model to support agricultural intensification in an affordable manner. For the high output farmer, it offers greater efficiency (productivity) and profit, resilience and stewardship. For farming anywhere, it addresses the root causes of agricultural land degradation, sub-optimal ecological crop and land potentials or yield ceilings, and poor crop phenotypic expressions or yield gaps. As national economies expand and diversify, more people become integrated into the economy and are able to access food. However, for those whose livelihoods continue to depend on agriculture to feed themselves and the rest of the world population, the challenge is for agriculture to produce the needed food and raw material for industry with minimum harm to the environment and the society, and to produce it with maximum efficiency and resilience against abiotic and biotic stresses, including those arising from climate change. There is growing empirical and scientific evidence worldwide that the future global supplies of food and agricultural raw materials can be assured sustainably at much lower environmental and economic cost by shifting away from conventional tillage-based food and agriculture systems to no-till CA-based food and agriculture systems. To achieve this goal will require effective national and global policy and institutional support (including research and education).

Coexpression of epidermal growth factor receptor with related factors is associated with a poor prognosis in non-small-cell lung cancer

The epidermal growth factor receptor (EGFR) is commonly expressed in non-small-cell lung cancer (NSCLC) and promotes a host of mechanisms involved in tumorigenesis. However, EGFR expression does not reliably predict prognosis or response to EGFR-targeted therapies. The data from two previous studies of a series of 181 consecutive surgically resected stage I-IIIA NSCLC patients who had survived in excess of 60 days were explored. Of these patients, tissue was available for evaluation of EGFR in 179 patients, carbonic anhydrase (CA) IX in 177 patients and matrix metalloproteinase-9 (MMP-9) in 169 patients. We have previously reported an association between EGFR expression and MMP-9 expression. We have also reported that MMP-9 (P=0.001) and perinuclear (p)CA IX (P=0.03) but not EGFR expression were associated with a poor prognosis. Perinuclear CA IX expression was also associated with EGFR expression (P<0.001). Multivariate analysis demonstrated that coexpression of MMP-9 with EGFR conferred a worse prognosis than the expression of MMP-9 alone (P<0.001) and coexpression of EGFR and pCA IX conferred a worse prognosis than pCA IX alone (P=0.05). A model was then developed where the study population was divided into three groups: group 1 had expression of EGFR without coexpression of MMP-9 or pCA IX (number=21); group 2 had no expression of EGFR (number=75); and group 3 had coexpression of EGFR with pCA IX or MMP-9 or both (number=70). Group 3 had a worse prognosis than either groups 1 or 2 (P=0.0003 and 0.027, respectively) and group 1 had a better prognosis than group 2 (P=0.036). These data identify two cohorts of EGFR-positive patients with diametrically opposite prognoses. The group expressing either EGFR and or both MMP-9 and pCA IX may identify a group of patients with activated EGFR, which is of clinical relevance with the advent of EGFR-targeted therapies. © 2004 Cancer Research UK.

Pro-matrix metalloproteinase-2 transfection increases orthotopic primary growth and experimental metastasis of MDA-MB-231 human breast cancer cells in nude mice

The ability to activate pro-matrix metalloproteinase (pro-MMP)-2 via membrane type-MMP is a hallmark of human breast cancer cell lines that show increased invasiveness, suggesting that MMP-2 contributes to human breast cancer progression. To investigate this, we have stably transfected pro-MMP-2 into the human breast cancer cell line MDA-MB-231, which lacks MMP-2 expression but does express its cell surface activator, membrane type 1-MMP. Multiple clones were derived and shown to produce pro-MMP-2 and to activate it in response to concanavalin A. In vitro analysis showed that the pro-MMP-2-transfected clones exhibited an increased invasive potential in Boyden chamber and Matrigel outgrowth assays, compared with the parental cells or those transfected with vector only. When inoculated into the mammary fat pad of nude mice, each of the MMP-2-tranfected clones grew faster than each of the vector controls tested. After intracardiac inoculation into nude mice, pro-MMP-2-transfected clones showed a significant increase in the incidence of metastasis to brain, liver, bone, and kidney compared with the vector control clones but not lung. Increased tumor burden was seen in the primary site and in lung metastases, and a trend toward increased burden was seen in bone, however, no change was seen in brain, liver, or kidney. This data supports a role for MMP-2 in breast cancer progression, both in the growth of primary tumors and in their spread to distant organs. MMP-2 may be a useful target for breast cancer therapy when refinement of MMP inhibitors provides for MMP-specific agents.