RhoA GEF Mcf2lb regulates rosette integrity during collective cell migration.

Multicellular rosettes are transient epithelial structures that serve as important cellular intermediates in the formation of diverse organs. Using the zebrafish posterior lateral line primordium (pLLP) as a model system, we investigated the role of the RhoA GEF Mcf2lb in rosette morphogenesis. The pLLP is a group of ∼150 cells that migrates along the zebrafish trunk and is organized into epithelial rosettes; these are deposited along the trunk and will differentiate into sensory organs called neuromasts (NMs). Using single-cell RNA-sequencing and whole-mount in situ hybridization, we showed that mcf2lb is expressed in the pLLP during migration. Live imaging and subsequent 3D analysis of mcf2lb mutant pLLP cells showed disrupted apical constriction and subsequent rosette organization. This resulted in an excess number of deposited NMs along the trunk of the zebrafish. Cell polarity markers ZO-1 and Par-3 were apically localized, indicating that pLLP cells are properly polarized. In contrast, RhoA activity, as well as signaling components downstream of RhoA, Rock2a and non-muscle Myosin II, were diminished apically. Thus, Mcf2lb-dependent RhoA activation maintains the integrity of epithelial rosettes.

The relationship between altitude and BMI varies across low- and middle-income countries.

OBJECTIVES: Studies suggest that living at high altitude decreases obesity risk, but this research is limited to single-country analyses. We examine the relationship between altitude and body mass index (BMI) among women living in a diverse sample of low- and middle-income countries. MATERIALS AND METHODS: Using Demographic and Health Survey data from 1 583 456 reproductive age women (20-49 years) in 54 countries, we fit regression models predicting BMI and obesity by altitude controlling for a range of demographic factors-age, parity, breastfeeding status, wealth, and education. RESULTS: A mixed-effects model with country-level random intercepts and slopes predicts an overall -0.162 kg/m2 (95% CI -0.220, -0.104) reduction in BMI and lower odds of obesity (OR 0.90, 95% CI 0.87, 0.95) for every 200 m increase in altitude. However, countries vary dramatically in whether they exhibit a negative or positive association between altitude and BMI (34 countries negative, 20 positive). Mixed findings also arise when examining odds of obesity. DISCUSSION: We show that past findings of declining obesity risk with altitude are not universal. Increasing altitude predicts slightly lower BMIs at the global level, but the relationship within individual countries varies in both strength and direction.

Healthfulness, Modernity, and Availability of Food and Beverages: Adolescents' Perceptions in Southern India.

This study uses freelists to document perceptions of healthfulness, modernity, and availability of foods and beverages among adolescents ages 13-18 years (n = 26) in urbanizing India. Among the 10 foods and beverages adolescents perceived as "new," half were also seen as modern and unhealthy, 4 as traditional and unhealthy, and 3 as modern and healthy. Of those 10 "new" foods, 4 were reported as available only in supermarkets, 4 only in kiraana (local) stores, and 6 in both. Adolescents ascribed healthfulness and modernity to food and beverage items and were aware of their availability across stores.

Globalization and Food Prestige among Indian Adolescents.

This study provides a foundation for understanding how globalization and changing food environments are linked to cultural models of food prestige in adolescents. We used methods from cognitive anthropology, including free lists, pile sorts, and consensus modeling, to explore the meanings that Indian adolescents attribute to foods. Adolescents (n = 29) were asked to free list foods eaten outside and inside the home. Different adolescents (n = 65) were asked to pile sort and rank 30 foods identified during the free lists according to which foods are the most prestigious, traditional, routine, and advertised on television. We found that adolescents overwhelmingly believed nontraditional foods to be the most prestigious. Nonlocal foods, both from foreign countries and other regions of India, as well as foods eaten outside the home, were also considered prestigious.

RhoA GEF Mcf2lb regulates rosette integrity during collective cell migration.

During development, multicellular rosettes serve as important cellular intermediates in the formation of diverse organ systems. Multicellular rosettes are transient epithelial structures that are defined by the apical constriction of cells towards the rosette center. Due to the important role these structures play during development, understanding the molecular mechanisms by which rosettes are formed and maintained is of high interest. Utilizing the zebrafish posterior lateral line primordium (pLLP) as a model system, we identify the RhoA GEF Mcf2lb as a regulator of rosette integrity. The pLLP is a group of ~150 cells that migrates along the zebrafish trunk and is organized into epithelial rosettes; these are deposited along the trunk and will differentiate into sensory organs called neuromasts (NMs). Using single-cell RNA sequencing and whole-mount in situ hybridization, we showed that mcf2lb is expressed in the pLLP during migration. Given the known role of RhoA in rosette formation, we asked whether Mcf2lb plays a role in regulating apical constriction of cells within rosettes. Live imaging and subsequent 3D analysis of mcf2lb mutant pLLP cells showed disrupted apical constriction and subsequent rosette organization. This in turn resulted in a unique posterior Lateral Line phenotype: an excess number of deposited NMs along the trunk of the zebrafish. Cell polarity markers ZO-1 and Par-3 were apically localized, indicating that pLLP cells are normally polarized. In contrast, signaling components that mediate apical constriction downstream of RhoA, Rock-2a and non-muscle Myosin II were diminished apically. Altogether our results suggest a model whereby Mcf2lb activates RhoA, which in turn activates downstream signaling machinery to induce and maintain apical constriction in cells incorporated into rosettes.

Testing the theoretical similarities between food and water insecurity: Buffering hypothesis and effects on mental wellbeing.

Theoretical analyses by anthropologists suggest that food and water insecurity exhibit multiple conceptual parallels, hold similar consequences for wellbeing, and lead to analogous coping strategies aimed at mitigating those consequences. However, these deductions largely originate from studies conducted separately on either food or water insecurity. Thus, these similarities may not bear out when examined in populations facing high rates of both. In particular, some researchers argue that food and water insecurity exert independent but nonetheless iterative effects on mental wellbeing. Others hypothesize that food insecurity mediates the relationship between water insecurity and mental health, especially in agricultural communities. However, relevant studies are limited, and none test this hypothesis in urban areas. Moreover, no data exist on water insecurity and mental wellbeing in adolescents, which hampers comparative analyses of youth resource insecurity. In addition, resource buffering-a long-discussed coping strategy-remains contested with respect to food insecurity and effectively untested with respect to water insecurity. The buffering hypothesis suggests that adults cushion younger household members against resource inadequacies via tradeoffs that yield gender- and age-based disparities in intrahousehold resource distributions. For example, adults may forgo food quality, quantity, or variety in favor of children. It stands to reason that adults similarly buffer children against water scarcity, but, again, this has not been examined. Conducted December 2016-April 2017, this cross-sectional survey included 650 mothers, fathers, boys, and girls living in the slums of Jaipur, India. When controlling for food insecurity, the relationship between water insecurity and psychosocial stress (Perceived Stress Scale-10) was eliminated; water insecurity's effect on anxiety and depression (Hopkins Symptom Checklist-10) remained significant for fathers only. These findings are consistent with the mediation hypothesis. Moreover, pursuant to the buffering hypothesis, parents generally reported more severe resource scarcity than their children; however, girls reported slightly worse water insecurity than fathers.

An ABCG Transporter Functions in Rab Localization and Lysosome-Related Organelle Biogenesis in Caenorhabditis elegans.

ABC transporters couple ATP hydrolysis to the transport of substrates across cellular membranes. This protein superfamily has diverse activities resulting from differences in their cargo and subcellular localization. Our work investigates the role of the ABCG family member WHT-2 in the biogenesis of gut granules, a Caenorhabditis elegans lysosome-related organelle. In addition to being required for the accumulation of birefringent material within gut granules, WHT-2 is necessary for the localization of gut granule proteins when trafficking pathways to this organelle are partially disrupted. The role of WHT-2 in gut granule protein targeting is likely linked to its function in Rab GTPase localization. We show that WHT-2 promotes the gut granule association of the Rab32 family member GLO-1 and the endolysosomal RAB-7, identifying a novel function for an ABC transporter. WHT-2 localizes to gut granules where it could play a direct role in controlling Rab localization. Loss of CCZ-1 and GLO-3, which likely function as a guanine nucleotide exchange factor (GEF) for GLO-1, lead to similar disruption of GLO-1 localization. We show that CCZ-1, like GLO-3, is localized to gut granules. WHT-2 does not direct the gut granule association of the GLO-1 GEF and our results point to WHT-2 functioning differently than GLO-3 and CCZ-1 Point mutations in WHT-2 that inhibit its transport activity, but not its subcellular localization, lead to the loss of GLO-1 from gut granules, while other WHT-2 activities are not completely disrupted, suggesting that WHT-2 functions in organelle biogenesis through transport-dependent and transport-independent activities.