Endoplasmic Reticulum Remodeling Tunes IP3-Dependent Ca2+ Release Sensitivity

The activation of vertebrate development at fertilization relies on IP3-dependent Ca2+ release, a pathway that is sensitized during oocyte maturation. This sensitization has been shown to correlate with the remodeling of the endoplasmic reticulum into large ER patches, however the mechanisms involved are not clear. Here we show that IP3 receptors within ER patches have a higher sensitivity to IP3 than those in the neighboring reticular ER. The lateral diffusion rate of IP3 receptors in both ER domains is similar, and ER patches dynamically fuse with reticular ER, arguing that IP3 receptors exchange freely between the two ER compartments. These results suggest that increasing the density of IP3 receptors through ER remodeling is sufficient to sensitize IP3-dependent Ca2+ release. Mathematical modeling supports this concept of ‘geometric sensitization’ of IP3 receptors as a population, and argues that it depends on enhanced Ca2+-dependent cooperativity at sub-threshold IP3 concentrations. This represents a novel mechanism of tuning the sensitivity of IP3 receptors through ER remodeling during meiosis

Micronutrient fortification of food and its impact on woman and child health: A systematic review

Background: Vitamins and minerals are essential for growth and metabolism. The World Health Organization estimates that more than 2 billion people are deficient in key vitamins and minerals. Groups most vulnerable to these micronutrient deficiencies are pregnant and lactating women and young children, given their increased demands. Food fortification is one of the strategies that has been used safely and effectively to prevent vitamin and mineral deficiencies.Methods: A comprehensive search was done to identify all available evidence for the impact of fortification interventions. Studies were included if food was fortified with a single, dual or multiple micronutrients and impact of fortification was analyzed on the health outcomes and relevant biochemical indicators of women and children. We performed a meta-analysis of outcomes using Review Manager Software version 5.1.Results: Our systematic review identified 201 studies that we reviewed for outcomes of relevance. Fortification for children showed significant impacts on increasing serum micronutrient concentrations. Hematologic markers also improved, including hemoglobin concentrations, which showed a significant rise when food was fortified with vitamin A, iron and multiple micronutrients. Fortification with zinc had no significant adverse impact on hemoglobin levels. Multiple micronutrient fortification showed non-significant impacts on height for age, weight for age and weight for height Z-scores, although they showed positive trends. The results for fortification in women showed that calcium and vitamin D fortification had significant impacts in the post-menopausal age group. Iron fortification led to a significant increase in serum ferritin and hemoglobin levels in women of reproductive age and pregnant women. Folate fortification significantly reduced the incidence of congenital abnormalities like neural tube defects without increasing the incidence of twinning. The number of studies pooled for zinc and multiple micronutrients for women were few, though the evidence suggested benefit. There was a dearth of evidence for the impact of fortification strategies on morbidity and mortality outcomes in women and children.Conclusion: Fortification is potentially an effective strategy but evidence from the developing world is scarce. Programs need to assess the direct impact of fortification on morbidity and mortality

Electrically conductive silicon oxycarbide thin films prepared from preceramic polymers

This work focuses on silicon oxycarbide thin film preparation and characterization. The Taguchi method of experimental design was used to optimize the process of film deposition. The prepared ceramic thin films with a thickness of c. 500 nm were characterized concerning their morphology, composition, and electrical properties. The molecular structure of the preceramic polymers used for the preparation of the ceramic thin films as well as the thermomechanical properties of the resulting SiOC significantly influenced the quality of the ceramic films. Thus, an increase in the content of carbon was found beneficial for the preparation of crack-free thin films. The obtained ceramic films exhibited increased electrical conductivity as compared to monolithic SiOC of similar chemical composition. This was shown to correlate with the unique hierarchical microstructure of the SiOC films, which contain large oxygen-depleted particles, mainly consisting of highly graphitized carbon and SiC, homogeneously dispersed in an oxygen-containing amorphous matrix. The matrix was shown to also contain free carbon and to contribute to charge carrier transport between the highly conductive large particles. The ceramic thin films possess electrical conductivities in the range from 5.4 to 8.8 S/cm and may be suitable for implementation in miniaturized piezoresistive strain gauges