Does education improve health in low- and middle income countries? Results from a systematic review

Despite enormous progress in expanding school enrollment globally, improvements in health have not always followed, raising important questions: Does education, in fact, enable women, men and their families to be healthier? And if so, how? To fill this gap in knowledge, the GIRL Center conducted a systematic review of the evidence for the effects of education on health in low- and middle-income countries

A mammalian Wnt5a-Ror2-Vangl2 axis controls the cytoskeleton and confers cellular properties required for alveologenesis.

Alveolar formation increases the surface area for gas-exchange and is key to the physiological function of the lung. Alveolar epithelial cells, myofibroblasts and endothelial cells undergo coordinated morphogenesis to generate epithelial folds (secondary septa) to form alveoli. A mechanistic understanding of alveologenesis remains incomplete. We found that the planar cell polarity (PCP) pathway is required in alveolar epithelial cells and myofibroblasts for alveologenesis in mammals. Our studies uncovered a Wnt5a-Ror2-Vangl2 cascade that endows cellular properties and novel mechanisms of alveologenesis. This includes PDGF secretion from alveolar type I and type II cells, cell shape changes of type I cells and migration of myofibroblasts. All these cellular properties are conferred by changes in the cytoskeleton and represent a new facet of PCP function. These results extend our current model of PCP signaling from polarizing a field of epithelial cells to conferring new properties at subcellular levels to regulate collective cell behavior

Hedgehog signaling: From basic research to clinical applications

Studies of the major signaling pathways have revealed a connection between development, regeneration, and cancer, highlighting common signaling networks in these processes. The Hedgehog (Hh) pathway plays a central role in the development of most tissues and organs in mammals. Hh signaling is also required for tissue homeostasis and regeneration in adults, while perturbed Hh signaling is associated with human cancers. A fundamental understanding of Hh signaling will not only enhance our knowledge of how the embryos are patterned but also provide tools to treat diseases related to aberrant Hh signaling. Studies have yielded a basic framework of Hh signaling, which establishes the foundation for addressing unresolved issues of Hh signaling. A detailed characterization of the biochemical interactions between Hh components will help explain the production of graded Hh responses required for tissue patterning. Additional cell biological and genetic studies will offer new insight into the role of Hh signaling in homeostasis and regeneration. Finally, drugs that are capable of manipulating the Hh pathway can be used to treat human diseases caused by disrupted Hh signaling. These investigations will serve as a paradigm for studying signal transduction/integration in homeostasis and disease, and for translating discovery from bench to bedside

Dataset: The economic returns to investing in girls

Datasets, code, and other materials associated with the infographic The Economic Returns to Investing in Girls. Included are a brief working paper regarding methodology, statistics and references used for calculated results, as well as data from ILO and the World Bank (downloaded in February-March 2017) utilized to calculate economic returns based on the changes in the gender labor gap

mTORC1 signaling facilitates differential stem cell differentiation to shape the developing murine lung and is associated with mitochondrial capacity

Formation of branched organs requires sequential differentiation of stem cells. In this work, we find that the conducting airways derived from SOX2+ progenitors in the murine lungs fail to form without mTOR complex 1 (mTORC1) signaling and are replaced by lung cysts. Proximal-distal patterning through transitioning of distal SOX9+ progenitors to proximal SOX2+ cells is disrupted. Mitochondria number and ATP production are reduced. Compromised mitochondrial capacity results in a similar defect as that in mTORC1-deficient lungs. This suggests that mTORC1 promotes differentiation of SOX9+ progenitors to form the conducting airways by modulating mitochondrial capacity. Surprisingly, in all mutants, saccules are produced from lung cysts at the proper developmental time despite defective branching. SOX9+ progenitors also differentiate into alveolar epithelial type I and type II cells within saccules. These findings highlight selective utilization of energy and regulatory programs during stem cell differentiation to produce distinct structures of the mammalian lungs

A conserved MST1/2–YAP axis mediates Hippo signaling during lung growth

Hippo signaling is a critical player in controlling the growth of several tissues and organs in diverse species. The current model of Hippo signaling postulates a cascade of kinase activity initiated by the MST1/2 kinases in response to external stimuli. This leads to inactivation of the transcriptional coactivators, YAP/TAZ, due to their cytoplasmic retention and degradation that is correlated with YAP/TAZ phosphorylation. In most tissues examined, YAP plays a more dominant role than TAZ. Whether a conserved Hippo pathway is utilized during lung growth and development is unclear. In particular, the regulatory relationship between MST1/2 and YAP/TAZ in the lung remains controversial. By employing the Shh-Cre mouse line to efficiently inactivate genes in the lung epithelium, we show that loss of MST1/2 kinases in the epithelium can lead to neonatal lethality caused by lung defects. This is manifested by perturbation of lung epithelial cell proliferation and differentiation. These phenotypes are more severe than those produced by Nkx2.1-Cre, highlighting the effects of differential Cre activity on phenotypic outcomes. Importantly, expression of YAP targets is upregulated and the ratio of phospho-YAP to total YAP protein levels is reduced in Mst1/2-deficient lungs, all of which are consistent with a negative role of MST1/2 in controlling YAP function. This model gains further support from both in vivo and in vitro studies. Genetic removal of one allele of Yap or one copy of both Yap and Taz rescues neonatal lethality and lung phenotypes due to loss of Mst1/2. Moreover, knockdown of Yap in lung epithelial cell lines restores diminished alveolar marker expression caused by Mst1/2 inactivation. These results demonstrate that MST1/2 inhibit YAP/TAZ activity and establish a conserved MST1/2-YAP axis in coordinating lung growth during development

Cities and their environments

If it is properly managed with attention not only to human well-being but also to the well-being of the other species that share our common spaces, urbanization can be a powerful force for good. This analytic survey of cities and their environments begins with a review of commonly misunderstood features of the demography of urban population growth and the geography of urban spatial expansion. The principal theme that runs through the remainder of the chapter is the need for unified governance approaches to highly heterogenous spaces, which span core urban areas, the urban fringe, and an outer envelope of rural land, water basins, and a variety of ecological habitats. Some of these critical spaces are large geographic units that extend far beyond the boundaries of municipal jurisdictions as such. The need for some integrating governance mechanism has been apparent for decades in low- and high-income countries alike. The all-too-obvious absence of such joined-up authorities, especially in poor countries, testifies to the legal, administrative, budgetary, technical, and scientific challenges entailed in creating such sustainable governance systems

Dataset: Evidence for causal links between education and maternal and child health, sexual and reproductive health, and malaria: A systematic review (materials)

Though there is a large body of literature that look at the associative relationship between education and health, there has not been a systematic assessment of the causal links between the two with evidence from experimental and quasi-experimental evidence, particularly with a focus on low- and middle-income countries. This study seeks to determine whether a causal link exists between education and health, how that relationship differs between various education exposures and health outcomes, and identify what causal mechanisms may exist. Included in this dataset are the relevant materials that accompany the review