The Structural Basis of Cholesterol Accessibility in Membranes

Although the majority of free cellular cholesterol is present in the plasma membrane, cholesterol homeostasis is principally regulated through sterol-sensing proteins that reside in the cholesterol-poor endoplasmic reticulum (ER). In response to acute cholesterol loading or depletion, there is rapid equilibration between the ER and plasma membrane cholesterol pools, suggesting a biophysical model in which the availability of plasma membrane cholesterol for trafficking to internal membranes modulates ER membrane behavior. Previous studies have predominantly examined cholesterol availability in terms of binding to extramembrane acceptors, but have provided limited insight into the structural changes underlying cholesterol activation. In this study, we use both molecular dynamics simulations and experimental membrane systems to examine the behavior of cholesterol in membrane bilayers. We find that cholesterol depth within the bilayer provides a reasonable structural metric for cholesterol availability and that this is correlated with cholesterol-acceptor binding. Further, the distribution of cholesterol availability in our simulations is continuous rather than divided into distinct available and unavailable pools. This data provide support for a revised cholesterol activation model in which activation is driven not by saturation of membrane-cholesterol interactions but rather by bulk membrane remodeling that reduces membrane-cholesterol affinity.     

Genes invoked in the ovarian transition to menopause

Menopause and the associated declines in ovarian function are major health issues for women. Despite the widespread health impact of this process, the molecular mechanisms underlying the aging-specific decline in ovarian function are almost completely unknown. To provide the first gene–protein analysis of the ovarian transition to menopause, we have established and contrasted RNA gene expression profiles and protein localization and content patterns in healthy young and perimenopausal mouse ovaries. We report a clear distinction in specific mRNA and protein levels that are noted prior to molecular evidence of steroidogenic failure. In this model, ovarian reproductive aging displays similarities with chronic inflammation and increased sensitivity to environmental cues. Overall, our results indicate the presence of mouse climacteric genes that are likely to be major players in aging-dependent changes in ovarian function.     

Habitat area affects arthropod communities directly and indirectly through top predators

Both habitat area and predators are known to affect the diversity and composition of species that live in a locality. In addition, habitat area can influence the presence of predators, indirectly affecting the diversity of prey. Thus, habitat area may influence species diversity directly and indirectly through the presence of top predators. Here we examine the effects of habitat area and predators on the species richness and composition of a foliage living arthropod community in a fragmented complex of glades (small grassland patches within a forested matrix) in the Ozark Plateau, Missouri. We find that a top predator, the eastern collared lizard Crotaphytus collaris collaris , occurs primarily on larger glades. Glade area was positively correlated with arthropod diversity, but only after removing the effect of collared lizard presence. Moreover, collared lizards reduced overall arthropod richness, and shifted the dominance from predatory arthropods (e.g. spiders) and Orthopteran grasshoppers to Homopterans (planthoppers). This study shows the importance of accounting for variation in the presence of a top predator when studying the effect of landscape-level processes on species richness and composition.     

A Drosophila Model Identifies a Critical Role for Zinc in Mineralization for Kidney Stone Disease

Ectopic calcification is a driving force for a variety of diseases, including kidney stones and atherosclerosis, but initiating factors remain largely unknown. Given its importance in seemingly divergent disease processes, identifying fundamental principal actors for ectopic calcification may have broad translational significance. Here we establish a Drosophila melanogaster model for ectopic calcification by inhibiting xanthine dehydrogenase whose deficiency leads to kidney stones in humans and dogs. Micro X-ray absorption near edge spectroscopy (μXANES) synchrotron analyses revealed high enrichment of zinc in the Drosophila equivalent of kidney stones, which was also observed in human kidney stones and Randall’s plaques (early calcifications seen in human kidneys thought to be the precursor for renal stones). To further test the role of zinc in driving mineralization, we inhibited zinc transporter genes in the ZnT family and observed suppression of Drosophila stone formation. Taken together, genetic, dietary, and pharmacologic interventions to lower zinc confirm a critical role for zinc in driving the process of heterogeneous nucleation that eventually leads to stone formation. Our findings open a novel perspective on the etiology of urinary stones and related diseases, which may lead to the identification of new preventive and therapeutic approaches.     

Children’s book series and associated curricula support elementary education and outreach in water resources

Background: Water resources are of fundamental importance to society, and are better managed by stakeholders who understand resource issues. Gaining such knowledge is a lifelong process best begun at an early age and best supported by educational approaches integrating across science, technology, engineering and mathematics (STEM). Research scientists can bring resource education to young audiences through children’s books and curricula that emphasise and integrate across STEM principals.

Aims: To encourage empathy for the environment in younger students, researchers at the Niwot Ridge Long Term Ecological Research site have developed a children’s book series and methods for training teachers in water science education.

Methods: Children’s books in the My Water series are paired with curricula, hands-on learning kits, teacher development training and dissemination of materials through school districts to further water science education.

Results: Thousands of children and educators have received training through the My Water book series, and a more broadly focused, federally funded Schoolyard Children’s Book Series has grown out of these efforts towards water resource education.

Conclusions: Children’s books and curricula that integrate STEM principals can play a key role in the development of environmental empathy and lifelong learning to support resource management.