A pilot to promote early child development within health systems in Mozambique: a qualitative evaluation.

Health systems offer unique opportunities for integrating services to promote early child development (ECD). However, there is limited knowledge about the implementation experiences of using health services to target nurturing care and ECD, especially in sub-Saharan Africa. We conducted a qualitative implementation evaluation to assess the delivery, acceptability, perceived changes, and barriers and facilitators associated with a pilot strategy that integrated developmental monitoring, nutritional screening, and early learning and nutrition counseling into the existing health facility, and community-based services for young children in rural Mozambique. We completed individual interviews with caregivers (N = 36), providers (N = 27), and district stakeholders (N = 10), and nine facility observational visits at three primary health facilities in October-November 2020. We analyzed data using thematic content analysis. Results supported fidelity to the intended pilot model and acceptability of nurturing care services. Respondents expressed various program benefits, including strengthened health system capacity and improved knowledge, attitudes, and practices regarding nurturing care and ECD. Government leadership and supportive supervision were key facilitators, whereas health system resource constraints were key barriers. We conclude that health systems are promising platforms for supporting ECD and discuss several programmatic recommendations for enhancing service delivery and maximizing potential impacts on nurturing care and ECD outcomes.

Impacts of fire on non-native plant recruitment in black spruce forests of interior Alaska.

Climate change is expected to increase the extent and severity of wildfires throughout the boreal forest. Historically, black spruce (Picea mariana (Mill.) B.S.P.) forests in interior Alaska have been relatively free of non-native species, but the compounding effects of climate change and an altered fire regime could facilitate the expansion of non-native plants. We tested the effects of wildfire on non-native plant colonization by conducting a seeding experiment of non-native plants on different substrate types in a burned black spruce forest, and surveying for non-native plants in recently burned and mature black spruce forests. We found few non-native plants in burned or mature forests, despite their high roadside presence, although invasion of some burned sites by dandelion (Taraxacum officinale) indicated the potential for non-native plants to move into burned forest. Experimental germination rates were significantly higher on mineral soil compared to organic soil, indicating that severe fires that combust much of the organic layer could increase the potential for non-native plant colonization. We conclude that fire disturbances that remove the organic layer could facilitate the invasion of non-native plants providing there is a viable seed source and dispersal vector.

Does environmental enrichment reduce stress? An integrated measure of corticosterone from feathers provides a novel perspective.

Enrichment is widely used as tool for managing fearfulness, undesirable behaviors, and stress in captive animals, and for studying exploration and personality. Inconsistencies in previous studies of physiological and behavioral responses to enrichment led us to hypothesize that enrichment and its removal are stressful environmental changes to which the hormone corticosterone and fearfulness, activity, and exploration behaviors ought to be sensitive. We conducted two experiments with a captive population of wild-caught Clark's nutcrackers (Nucifraga columbiana) to assess responses to short- (10-d) and long-term (3-mo) enrichment, their removal, and the influence of novelty, within the same animal. Variation in an integrated measure of corticosterone from feathers, combined with video recordings of behaviors, suggests that how individuals perceive enrichment and its removal depends on the duration of exposure. Short- and long-term enrichment elicited different physiological responses, with the former acting as a stressor and birds exhibiting acclimation to the latter. Non-novel enrichment evoked the strongest corticosterone responses of all the treatments, suggesting that the second exposure to the same objects acted as a physiological cue, and that acclimation was overridden by negative past experience. Birds showed weak behavioral responses that were not related to corticosterone. By demonstrating that an integrated measure of glucocorticoid physiology varies significantly with changes to enrichment in the absence of agonistic interactions, our study sheds light on potential mechanisms driving physiological and behavioral responses to environmental change.

Copolymerization of divinylsilyl-11-silicotungstic acid with butyl acrylate and hexanediol diacrylate: synthesis of a highly proton-conductive membrane for fuel-cell applications.

Highly conducive to high conductivity: Polyoxometalates were incorporated in the backbone of a hydrocarbon polymer to produce proton-conducting films. These first-generation materials contain large, dispersed clusters of polyoxometalates. Although the morphology of these films is not yet optimal, they already demonstrate practical proton conductivities and proton diffusion within the clusters appears to be very high.

Roles of IP3R and RyR Ca2+ channels in endoplasmic reticulum stress and beta-cell death.

OBJECTIVE: Endoplasmic reticulum (ER) stress has been implicated in the pathogenesis of diabetes, but the roles of specific ER Ca(2+) release channels in the ER stress-associated apoptosis pathway remain unknown. Here, we examined the effects of stimulating or inhibiting the ER-resident inositol trisphosphate receptors (IP(3)Rs) and the ryanodine receptors (RyRs) on the induction of beta-cell ER stress and apoptosis. RESEARCH DESIGN AND METHODS: Kinetics of beta-cell death were tracked by imaging propidium iodide incorporation and caspase-3 activity in real time. ER stress and apoptosis were assessed by Western blot. Mitochondrial membrane potential was monitored by flow cytometry. Cytosolic Ca(2+) was imaged using fura-2, and genetically encoded fluorescence resonance energy transfer (FRET)-based probes were used to measure Ca(2+) in ER and mitochondria. RESULTS: Neither RyR nor IP(3)R inhibition, alone or in combination, caused robust death within 24 h. In contrast, blocking sarco/endoplasmic reticulum ATPase (SERCA) pumps depleted ER Ca(2+) and induced marked phosphorylation of PKR-like ER kinase (PERK) and eukaryotic initiation factor-2alpha (eIF2alpha), C/EBP homologous protein (CHOP)-associated ER stress, caspase-3 activation, and death. Notably, ER stress following SERCA inhibition was attenuated by blocking IP(3)Rs and RyRs. Conversely, stimulation of ER Ca(2+) release channels accelerated thapsigargin-induced ER depletion and apoptosis. SERCA block also activated caspase-9 and induced perturbations of the mitochondrial membrane potential, resulting eventually in the loss of mitochondrial polarization. CONCLUSIONS: This study demonstrates that the activity of ER Ca(2+) channels regulates the susceptibility of beta-cells to ER stress resulting from impaired SERCA function. Our results also suggest the involvement of mitochondria in beta-cell apoptosis associated with dysfunctional beta-cell ER Ca(2+) homeostasis and ER stress.

Glucose and endoplasmic reticulum calcium channels regulate HIF-1beta via presenilin in pancreatic beta-cells.

Pancreatic beta-cell death is a critical event in type 1 diabetes, type 2 diabetes, and clinical islet transplantation. We have previously shown that prolonged block of ryanodine receptor (RyR)-gated release from intracellular Ca(2+) stores activates calpain-10-dependent apoptosis in beta-cells. In the present study, we further characterized intracellular Ca(2+) channel expression and function in human islets and the MIN6 beta-cell line. All three RyR isoforms were identified in human islets and MIN6 cells, and these endoplasmic reticulum channels were observed in close proximity to mitochondria. Blocking RyR channels, but not sarco/endoplasmic reticulum ATPase (SERCA) pumps, reduced the ATP/ADP ratio. Blocking Ca(2+) flux through RyR or inositol trisphosphate receptor channels, but not SERCA pumps, increased the expression of hypoxia-inducible factor (HIF-1beta). Moreover, inhibition of RyR or inositol trisphosphate receptor channels, but not SERCA pumps, increased the expression of presenilin-1. Both HIF-1beta and presenilin-1 expression were also induced by low glucose. Overexpression of presenilin-1 increased HIF-1beta, suggesting that HIF is downstream of presenilin. Our results provide the first evidence of a presenilin-HIF signaling network in beta-cells. We demonstrate that this pathway is controlled by Ca(2+) flux through intracellular channels, likely via changes in mitochondrial metabolism and ATP. These findings provide a mechanistic understanding of the signaling pathways activated when intracellular Ca(2+) homeostasis and metabolic activity are suppressed in diabetes and islet transplantation.