Differential growth identified in salamander larvae half‐sib cohorts: Survival strategy?

In this study we describe the growth of several different larval cohorts (i.e. half-siblings of the same mother born on the same day) of a rare, xeric-adapted salamander Salamandra s. infraimmaculata Martens, 1885, under constant density and food conditions from birth to metamorphosis. The larvae spend the critical first phase of their lives in water, mostly in temporary ponds. Age and weight at metamorphosis were highly affected by varying food conditions. We have identified six different growth modes that these larvae use, both fast growing and slow growing. Each larval cohort was found to use 2-4 different such growth modes regardless of their initial weight. Fast growing modes (I-III) will enable larvae to survive dry years, and metamorphose bigger. Slow growing modes (IV-VI), used by 8% of the larval population, will enable survival only in rainy years. These last growth modes effect differential temporal dispersal in wet years by delaying the emergence of postmetamorphs onto land. Distribution of growth modes in the larval population is affected by food but not by density conditions. Late-born, fast-growing larvae will have an advantage in dry years being able to metamorphose and disperse, whereas the slow-growing larvae will survive only in wet years.     

Imaging analysis of collagen fiber networks in cusps of porcine aortic valves: effect of their local distribution and alignment on valve functionality

The cusps of native aortic valve (AV) are composed of collagen bundles embedded in soft tissue, creating a heterogenic tissue with asymmetric alignment in each cusp. This study compares native collagen fiber networks (CFNs) with a goal to better understand their influence on stress distribution and valve kinematics. Images of CFNs from five porcine tricuspid AVs are analyzed and fluid-structure interaction models are generated based on them. Although the valves had similar overall kinematics, the CFNs had distinctive influence on local mechanics. The regions with dilute CFN are more prone to damage since they are subjected to higher stress magnitudes.     

The C. elegans ric-3 gene is required for maturation of nicotinic acetylcholine receptors

Mutations in ric-3 (resistant to inhibitors of cholinesterase) suppress the neuronal degenerations caused by a gain of function mutation in the Caenorhabditis elegans DEG-3 acetylcholine receptor. RIC-3 is a novel protein with two transmembrane domains and extensive coiled-coil domains. It is expressed in both muscles and neurons, and the protein is concentrated within the cell bodies. We demonstrate that RIC-3 is required for the function of at least four nicotinic acetylcholine receptors. However, GABA and glutamate receptors expressed in the same cells are unaffected. In ric-3 mutants, the DEG-3 receptor accumulates in the cell body instead of in the cell processes. Moreover, co-expression of ric-3 in Xenopus laevis oocytes enhances the activity of the C.elegans DEG-3/DES-2 and of the rat alpha-7 acetylcholine receptors. Together, these data suggest that RIC-3 is specifically required for the maturation of acetylcholine receptors.     

Mutations in the extracellular domain and in the membrane-spanning domains interfere with nicotinic acetylcholine receptor maturation

The deg-3(u662) mutation is a degeneration-causing mutation in a Caenorhabditis elegans nicotinic acetylcholine receptor. In a large screen for mutations that suppress the deleterious effects of this mutation we identified 32 mutations in the deg-3 gene. Among these, 11 are missense mutations, affecting seven residues within the extracellular domain or the membrane-spanning domains. All of these mutations greatly reduce the degeneration-causing activity of deg-3(u662). All but one of these mutations cause defective localization of the DEG-3 protein, as seen in immunohistochemical analysis. Thus our screen identifies multiple residues within the nicotinic acetylcholine receptor needed for normal folding, assembly, or trafficking of this receptor. Interestingly, these mutations lead to distinct localization defects suggesting differences in their effect on DEG-3's maturation process. Specifically, mutations in the extracellular domain lead to a phenotype more severe than mutations in the membrane-spanning domains. Differences in the effects of the mutations are also predicted by homology-based modeling, showing that some mutations in the extracellular domain are likely to disrupt the native fold of the protein, while others are likely to disrupt trafficking.     

Freshwater salinization syndrome: from emerging global problem to managing risks

Freshwater salinization is an emerging global problem impacting safe drinking water, ecosystem health and biodiversity, infrastructure corrosion, and food production. Freshwater salinization originates from diverse anthropogenic and geologic sources including road salts, human-accelerated weathering, sewage, urban construction, fertilizer, mine drainage, resource extraction, water softeners, saltwater intrusion, and evaporative concentration of ions due to hydrologic alterations and climate change. The complex interrelationships between salt ions and chemical, biological, and geologic parameters and consequences on the natural, social, and built environment are called Freshwater Salinization Syndrome (FSS). Here, we provide a comprehensive overview of salinization issues (past, present, and future), and we investigate drivers and solutions. We analyze the expanding global magnitude and scope of FSS including its discovery in humid regions, connections to human-accelerated weathering and mobilization of ‘chemical cocktails.’ We also present data illustrating: (1) increasing trends in salt ion concentrations in some of the world’s major freshwaters, including critical drinking water supplies; (2) decreasing trends in nutrient concentrations in rivers due to regulations but increasing trends in salinization, which have been due to lack of adequate management and regulations; (3) regional trends in atmospheric deposition of salt ions and storage of salt ions in soils and groundwater, and (4) applications of specific conductance as a proxy for tracking sources and concentrations of groups of elements in freshwaters. We prioritize FSS research needs related to better understanding: (1) effects of saltwater intrusion on ecosystem processes, (2) potential health risks from groundwater contamination of home wells, (3) potential risks to clean and safe drinking water sources, (4) economic and safety impacts of infrastructure corrosion, (5) alteration of biodiversity and ecosystem functions, and (6) application of high-frequency sensors in state-of-the art monitoring and management. We evaluate management solutions using a watershed approach spanning air, land, and water to explore variations in sources, fate and transport of different salt ions (e.g. monitoring of atmospheric deposition of ions, stormwater management, groundwater remediation, and managing road runoff). We also identify tradeoffs in management approaches such as unanticipated retention and release of chemical cocktails from urban stormwater management best management practices (BMPs) and unintended consequences of alternative deicers on water quality. Overall, we show that FSS has direct and indirect effects on mobilization of diverse chemical cocktails of ions, metals, nutrients, organics, and radionuclides in freshwaters with mounting impacts. Our comprehensive review suggests what could happen if FSS were not managed into the future and evaluates strategies for reducing increasing risks to clean and safe drinking water, human health, costly infrastructure, biodiversity, and critical ecosystem services.

     

Halofuginone prevents extracellular matrix deposition in diabetic nephropathy

Transforming growth factor-β (TGF-β) is known to promote the accumulation of extracellular matrix (ECM) and the development of diabetic nephropathy. Halofuginone, an analog of febrifugine, has been shown to block TGF-β₁ signaling and subsequent type I collagen production. Here, the inhibitory effect of halofuginone on diabetic nephropathy was examined. Halofuginone suppressed Smad2 phosphorylation induced by TGF-β₁ in cultured mesangial cells. In addition, the expression of TGF-β type 2 receptor decreased by halofuginone. Halofuginone showed an inhibitory effect on type I collagen and fibronectin expression promoted by TGF-β₁. An in vivo experiment using db/db mice confirmed the ability of halofuginone to suppress mesangial expansion and fibronectin overexpression in the kidneys. Moreover, an analysis of urinary 8-OHdG level and dihydroethidium fluorescence revealed that halofuginone reduced oxidative stress in the glomerulus of db/db mice. These data indicate that halofuginone prevents ECM deposition and decreases oxidative stress, thereby suppressing the progression of diabetic nephropathy.