Late Ediacaran Redox Stability and Metazoan Evolution

The Neoproterozoic arrival of animals fundamentally changed Earth's biological and geochemical trajectory. Since the early description of Ediacaran and Cambrian animal fossils, a vigorous debate has emerged about the drivers underpinning their seemingly rapid radiation. Some argue for predation and ecology as central to diversification, whereas others point to a changing chemical environment as the trigger. In both cases, questions of timing and feedbacks remain unresolved. Through these debates, the last fifty years of work has largely converged on the concept that a change in atmospheric oxygen levels, perhaps manifested indirectly as an oxygenation of the deep ocean, was causally linked to the initial diversification of large animals. What has largely been absent, but is provided in this study, is a multi-proxy stratigraphic test of this hypothesis. Here, we describe a coupled geochemical and paleontological investigation of Neoproterozoic sedimentary rocks from northern Russia. In detail, we provide iron speciation data, carbon and sulfur isotope compositions, and major element abundances from a predominantly siliciclastic succession (spanning>1000 m) sampled by the Kel'tminskaya-1 drillcore. Our interpretation of these data is consistent with the hypothesis that the $pO_2$ threshold required for diversification of animals with high metabolic oxygen demands was crossed prior to or during the Ediacaran Period. Redox stabilization of shallow marine environments was, however, also critical and only occurred about 560 million years ago (Ma), when large motile bilaterians first enter the regional stratigraphic record. In contrast, neither fossils nor geochemistry lend support to the hypothesis that ecological interactions altered the course of evolution in the absence of environmental change. Together, the geochemical and paleontological records suggest a coordinated transition from low oxygen oceans sometime before the Marinoan (~635 Ma) ice age, through better oxygenated but still redox-unstable shelves of the early Ediacaran Period, to the fully and persistently oxygenated marine environments characteristic of later Ediacaran successions that preserve the first bilaterian macrofossils and trace fossils.Earth and Planetary SciencesOrganismic and Evolutionary Biolog

Assessment of Stability of Chemical Cholera Vaccine in a New Primary Packaging

The bivalent chemical cholera vaccine is the only drug for the prevention of cholera registered in the Russian Federation. The vaccine has been produced in glass bottles containing 210 tablets. At the same time, modern trends dictate the need to produce the drug in varying dispensing and more practical packaging for the convenience of the consumer.The aim of the work was to study the stability of the properties of the immunobiological medicinal product “Bivalent chemical cholera vaccine” with modified filling and in new primary packaging.Materials and methods. When studying the quality of bivalent chemical cholera vaccine batches, physicochemical parameters, formaldehyde content, specific activity and safety, abnormal toxicity, immunogenicity, and microbiological purity were assessed. Stability in terms of “specific activity” was evaluated using dot immunoassay.Results and discussion. As a result of this work, the use of several dispensing options and new primary packaging of cholera vaccine has been experimentally substantiated. The stability of the finished vaccine preparation has been established in the “accelerated aging” test and during long-term storage. The possibility of using dot immunoassay with a conjugate based on staphylococcal protein A, labeled with colloidal gold, to monitor the stability of cholera vaccine has been experimentally demonstrated

Complex Monitoring of Biochemical and Radionuclide Parameters in Patients with Metastatic Renal Cell Carcinoma during Immunotherapy

Study Objective. To study the effectiveness of complex monitoring of the kidney function, based on biochemical and radionuclide methods in patients with metastatic renal cell carcinoma (mRCC). Materials and Methods. 41 mRCC patients after nephrectomy received nivolumab (n = 23) and interferon-α (n = 18) from 2015 to 2017. At baseline and 2 months after, all patients underwent blood chemistry, urinalysis, Rehberg test, and ELISA to determine serum levels of IL-17A, TGF-β, and erythropoietin. The monitoring of the renal function and urodynamics by complex renal scintigraphy (CRS) was used for all patients using a dual-detector gamma camera and simultaneous data recording in 2 projections. The interpretation of CRS data used the original SENS CRS technology. Study Results. Statistically significant correlations were established between IL-17A, TGF-β, and D (excretion rate of 99mTc-technephore from the parenchyma) and Rnfsc (a stable sign of nephrosclerosis), respectively. A significant correlation was established between the parameters of the complex functional monitoring with the prognosis for the risk of renal failure (RF) and efficacy of immunotherapy in mRCC. Conclusions. All mRCC patients after nephrectomy were recommended to undergo biochemical monitoring with inclusion of TGF-β and IL-17A, as well as radionuclide monitoring (CRS) to determine the RF risk at an early stage