Exploration of the 2016 Yellowstone River fish kill and proliferative kidney disease in wild fish populations

Proliferative kidney disease (PKD) is an emerging disease that recently resulted in a large mortality event of salmonids in the Yellowstone River (Montana, USA). Total PKD fish mortalities in the Yellowstone River were estimated in the tens of thousands, which resulted in a multi-week river closure and an estimated economic loss of US$500,000. This event shocked scientists, managers, and the public, as this was the first occurrence of the disease in the Yellowstone River, the only reported occurrence of the disease in Montana in the past 25 yr, and arguably the largest wild PKD fish kill in the world. To understand why the Yellowstone River fish kill occurred, we used molecular and historical data to evaluate evidence for several hypotheses: Was the causative parasite Tetracapsuloides bryosalmonae a novel invader, was the fish kill associated with a unique parasite strain, and/or was the outbreak caused by unprecedented environmental conditions? We found that T. bryosalmonae is widely distributed in Montana and have documented occurrence of this parasite in archived fish collected in the Yellowstone River prior to the fish kill. T. bryosalmonae had minimal phylogeographic population structure, as the DNA of parasites sampled from the Yellowstone River and distant water bodies were very similar. These results suggest that T. bryosalmonae could be endemic in Montana. Due to data limitations, we could not reject the hypothesis that the fish kill was caused by a novel and more virulent genetic strain of the parasite. Finally, we found that single-year environmental conditions are insufficient to explain the cause of the 2016 Yellowstone River PKD outbreak. Other regional rivers where we documented T. bryosalmonae had similar or even more extreme conditions than the Yellowstone River and similar or more extreme conditions have occurred in the Yellowstone River in the recent past, yet mass PKD mortalities have not been documented in either instance. We conclude by placing these results and unresolved hypotheses into the broader context of international research on T. bryosalmonae and PKD, which strongly suggests that a better understanding of bryozoans, the primary host of T. bryosalmonae, is required for better ecosystem understanding

p53 Plays a Role in Mesenchymal Differentiation Programs, in a Cell Fate Dependent Manner

Background: The tumor suppressor p53 is an important regulator that controls various cellular networks, including cell differentiation. Interestingly, some studies suggest that p53 facilitates cell differentiation, whereas others claim that it suppresses differentiation. Therefore, it is critical to evaluate whether this inconsistency represents an authentic differential p53 activity manifested in the various differentiation programs. Methodology/Principal Findings: To clarify this important issue, we conducted a comparative study of several mesenchymal differentiation programs. The effects of p53 knockdown or enhanced activity were analyzed in mouse and human mesenchymal cells, representing various stages of several differentiation programs. We found that p53 downregulated the expression of master differentiation-inducing transcription factors, thereby inhibiting osteogenic, adipogenic and smooth muscle differentiation of multiple mesenchymal cell types. In contrast, p53 is essential for skeletal muscle differentiation and osteogenic re-programming of skeletal muscle committed cells. Conclusions: These comparative studies suggest that, depending on the specific cell type and the specific differentiatio

Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria

Quinine remains an important anti-malarial drug almost 400 years after its effectiveness was first documented. However, its continued use is challenged by its poor tolerability, poor compliance with complex dosing regimens, and the availability of more efficacious anti-malarial drugs. This article reviews the historical role of quinine, considers its current usage and provides insight into its appropriate future use in the treatment of malaria. In light of recent research findings intravenous artesunate should be the first-line drug for severe malaria, with quinine as an alternative. The role of rectal quinine as pre-referral treatment for severe malaria has not been fully explored, but it remains a promising intervention. In pregnancy, quinine continues to play a critical role in the management of malaria, especially in the first trimester, and it will remain a mainstay of treatment until safer alternatives become available. For uncomplicated malaria, artemisinin-based combination therapy (ACT) offers a better option than quinine though the difficulty of maintaining a steady supply of ACT in resource-limited settings renders the rapid withdrawal of quinine for uncomplicated malaria cases risky. The best approach would be to identify solutions to ACT stock-outs, maintain quinine in case of ACT stock-outs, and evaluate strategies for improving quinine treatment outcomes by combining it with antibiotics. In HIV and TB infected populations, concerns about potential interactions between quinine and antiretroviral and anti-tuberculosis drugs exist, and these will need further research and pharmacovigilance

textureformationofpyrolyticcarboninchemicalvapordepositionandinfiltration

Carbon textures, as a function of methane pressure, obtained at 1100 degrees C by chemical vapor infiltration of a carbon fiber felt with a fiber volume fraction of 7% and a capillary diameter of 1.1 mm, at different surface area/volume ratios of the substrate were characterized using the optical extinction and orientation angle. Significant texture changes with increasing methane pressure were attributed to the nucleation-growth mechanism of carbon formation with growth dominating at lower pressures, and the increasing influence of the nucleation mechanism of carbon formation at higher pressures. Carbon textures resulting from the growth mechanism perfectly agree with the particle filler model. It is postulated that high textured carbon is formed from a gas phase with an optimum ratio of aromatic hydrocarbons (molecular particles) to small linear hydrocarbons (molecular filler), whereas medium and low textured carbon are deposited with an excess of either aromatic or small linear hydrocarbons. Most significant differences in texture formation between chemical vapor infiltration and deposition result from the much lower hydrogen partial pressures in infiltration because hydrogen diffuses to the surface of the porous substrate

Scanning electron microscopy of macerated tissue to visualize the extracellular matrix.

Fibrosis is a component of all forms of heart disease regardless of etiology, and while much progress has been made in the field of cardiac matrix biology, there are still major gaps related to how the matrix is formed, how physiological and pathological remodeling differ, and most importantly how matrix dynamics might be manipulated to promote healing and inhibit fibrosis. There is currently no treatment option for controlling, preventing, or reversing cardiac fibrosis. Part of the reason is likely the sheer complexity of cardiac scar formation, such as occurs after myocardial infarction to immediately replace dead or dying cardiomyocytes. The extracellular matrix itself participates in remodeling by activating resident cells and also by helping to guide infiltrating cells to the defunct lesion. The matrix is also a storage locker of sorts for matricellular proteins that are crucial to normal matrix turnover, as well as fibrotic signaling. The matrix has additionally been demonstrated to play an electromechanical role in cardiac tissue. Most techniques for assessing fibrosis are not qualitative in nature, but rather provide quantitative results that are useful for comparing two groups but that do not provide information related to the underlying matrix structure. Highlighted here is a technique for visualizing cardiac matrix ultrastructure. Scanning electron microscopy of decellularized heart tissue reveals striking differences in structure that might otherwise be missed using traditional quantitative research methods