Trends of child undernutrition in rural Ecuadorian communities with differential access to roads, 2004–2013

Road access can influence protective and risk factors associated with nutrition by affecting various social and biological processes. In northern coastal Ecuador, the construction of new roads created a remoteness gradient among villages, providing a unique opportunity to examine the impact of roads on child nutritional outcomes 10 years after the road was built. Anthropometric and haemoglobin measurements were collected from 2,350 children <5 years in Esmeraldas, Ecuador, from 2004 to 2013 across 28 villages with differing road access. Logistic generalized estimating equation models assessed the longitudinal association between village remoteness and prevalence of stunting, wasting, underweight, overweight, obesity, and anaemia. We examined the influence of socio‐economic characteristics on the pathway between remoteness and nutrition by comparing model results with and without household‐level socio‐economic covariates. Remoteness was associated with stunting (OR = 0.43, 95% CI [0.30, 0.63]) and anaemia (OR = 0.56, 95% CI [0.44, 0.70]). Over time, the prevalence of stunting was generally decreasing but remained higher in villages closer to the road compared to those farther away. Obesity increased (0.5% to 3%) over time; wasting was high (6%) but stable during the study period. Wealth and education partially explained the better nutritional outcomes in remote vs. road villages more than a decade after some communities gained road access. Establishing the extent to which these patterns persist requires additional years of observation.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144663/1/mcn12588.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144663/2/mcn12588_am.pd

A Defective Meiotic Outcome of a Failure in Homologous Pairing and Synapsis Is Masked by Meiotic Quality Control.

Successful gamete production is ensured by meiotic quality control, a process in which germ cells that fail in bivalent chromosome formation are eliminated during meiotic prophase. To date, numerous meiotic mutants have been isolated in a variety of model organisms, using defects associated with a failure in bivalent formation as hallmarks of the mutant. Presumably, the meiotic quality control mechanism in those mutants is overwhelmed. In these mutants, all germ cells fail in bivalent formation, and a subset of cells seem to survive the elimination process and develop into gametes. It is possible that mutants that are partially defective in bivalent formation were missed in past genetic screens, because no evident meiotic defects associated with failure in bivalent formation would have been detectable. Meiotic quality control effectively eliminates most failed germ cells, leaving predominately successful ones. Here, we provide evidence supporting this possibility. The Caenorhabditis elegans mrg-1 loss-of-function mutant does not appear to be defective in bivalent formation in diakinesis oocytes. However, defects in homologous chromosome pairing and synapsis during the preceding meiotic prophase, prerequisites for successful bivalent formation, were observed in most, but not all, germ cells. Failed bivalent formation in the oocytes became evident once meiotic quality control was abrogated in the mrg-1 mutant. Both double-strand break repair and synapsis checkpoints are partly responsible for eliminating failed germ cells in the mrg-1 mutant. Interestingly, removal of both checkpoint activities from the mrg-1 mutant is not sufficient to completely suppress the increased germline apoptosis, suggesting the presence of a novel meiotic checkpoint mechanism

<i>mrg-1</i> (<i>lf</i>) exhibits increased synapsis failure when combined with germline apoptosis mutations.

<p>(A) Full projections of optically sectioned indirect immunofluorescence images of HIM-3 (green) and SYP-1 (red) in pachytene nuclei. Examples of nuclei that were scored as having partial SC are indicated with arrows (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0134871#sec008" target="_blank">Materials and Methods</a> for a description of the scoring method). Bar: 5 μm. (B) Quantification of SC assembly. The histogram shows the percentage of nuclei with partial synapsis in each of the four subzones. (C) Schematic diagram of germline subzones used to score partial synapsis.</p

<i>mrg-1</i> (<i>lf</i>) fails to form bivalents when combined with germline apoptosis mutations.

<p>(A) Full projections of optically sectioned indirect immunofluorescence images of HIM-3 (green) with DAPI-stained DNA (blue) in oocytes from the -1 to -3 positions. The periphery of each oocyte is indicated by the dotted circle. Both the <i>ced-4</i> (left) and <i>mrg-1</i> (right) single mutants typically display six DAPI-stained bodies with cross-shaped HIM-3 staining per oocyte, demonstrating successful bivalent formation. The <i>ced-4 mrg-1</i> double mutant (middle) often displays diakinesis oocytes with more than six DAPI-stained bodies, some of which lack cross-shaped HIM-3 staining, indicating failed bivalent formation. Bar: 20 μm. (B) Histogram showing the percentage of gonads with oocytes from the -1 to -3 positions displaying more than six DAPI-stained bodies. The <i>ced-3; mrg-1</i>, <i>ced-4 mrg-1</i>, and <i>ced-9; mrg-1</i> double mutants display a substantially greater number of oocytes with more than six DAPI-stained bodies in at least one of three late diakinesis oocytes. This increase is statistically significant compared with the <i>mrg-1</i> single mutant (p = 0.0057, p<0.0001, p = 0.0067, respectively, Fisher’s exact test).</p

Induction of germline apoptosis in <i>mrg-1(lf)</i> is partly dependent on <i>cep-1</i> and <i>pch-2</i>.

<p>Histograms comparing wild-type and <i>mrg-1</i> mutant worms (A); <i>cep-1</i> and <i>mrg-1;cep-1</i> mutants (B); <i>pch-2</i> and <i>mrg-1; pch-2</i> mutants (C); and <i>cep-1; pch-2</i> and <i>cep-1; pch-2; mrg-1</i> mutants (D). Schematic diagram of germline subzones used to score apoptotic cell corpses (E). The <i>cep-1; mrg-1</i> mutant showed fewer total apoptotic cells than did the <i>mrg-1</i> mutant (p<0.0001, Mann-Whitney test). However, this number is still significantly higher than that seen with the wild type or the <i>cep-1</i> single mutant (p<0.0001). Similarly, the <i>pch-2; mrg-1</i> mutant showed fewer apoptotic cells than did the <i>mrg-1</i> mutant (p<0.0001), but more apoptotic cells than either the wild type or the <i>pch-2</i> single mutant (p<0.0001). The <i>cep-1; pch-2; mrg-1</i> triple mutant showed fewer apoptotic cells than the <i>mrg-1</i> single mutant (p<0.0001), <i>cep-1; mrg-1</i> double mutant (p = 0.0214), and <i>pch-2; mrg-1</i> double mutant (p = 0.0001), but significantly more than either the wild type or the cep-1; pch-2 double mutant (p<0.0001). The standard error bars indicate 1 standard deviation.</p

<i>mrg-1</i> (<i>lf</i>) exhibits increased failure to form bivalents when combined with meiotic checkpoint mutations

<p>(A) Full projections of optically sectioned DAPI-stained DNA images in oocytes from positions -1 to -3. The periphery of each oocyte is indicated by the dotted circle. Six DAPI-stained bodies per oocyte were usually observed in the <i>mrg-1</i> single mutant, demonstrating successful bivalent formation. The <i>cep-1; mrg-1</i> or <i>pch-2; mrg-1</i> double mutants frequently displayed diakinesis oocytes with more than six DAPI-stained bodies, indicating failed bivalent formation. The <i>cep-1; pch-2; mrg-1</i> triple mutant showed the most obvious failure in bivalent formation among the four strains tested. All four strains have ced-1::GFP in the background (not shown). The same image data that was analyzed in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0134871#pone.0134871.g003" target="_blank">Fig 3</a> was used for this analysis. Bar: 10 μm. (B) Histogram showing the percentage of gonads with oocytes from the -1 to -3 positions displaying more than six DAPI-stained bodies. The <i>cep-1; mrg-1</i>, <i>pch-2; mrg-1</i>, and <i>cep-1; pch-2; mrg-1</i> mutants display substantially increased populations of oocytes with more than six DAPI-stained bodies in at least one of three late diakinesis oocytes. This increase is statistically significant except for <i>pch-2; mrg-1</i> when compared to the <i>mrg-1</i> single mutant (p = 0.0374, p = 0.0738, p = 0.0015, respectively, Fisher’s exact test).</p