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

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

INFLUENCE OF APOE GENOTYPES ON BIOCHEMICAL INDICES OF IRON AND LIPID METABOLISM IN PATIENTS WITH THE ENDOMETRIUM NEOPLASTIC DISEASES AND HEAL THY WOMEN

Objective. APOE genotype association with the level of iron in plasma and the risk of endometrial neoplastic diseases has not been studied. The aim of the work was to analyze the genotypic associations of the apolipoprotein E (APOE) with iron and lipid levels in endometrial hyperplasia (EH)/endometrial cancer (EC) patients and healthy women.Materials and methods. The biochemical blood levels of iron and cholesterol metabolism detected in women d with diagnosed endometrial hyperplasia (53), endometrial cancer (87) and healthy women (70) are determined on an automated analyzer «OLYMPUS AU – 400”. The genotyping was performed with a PCR-RFLP (polymerase chain reaction with restriction fragment length polymorphism) technique.Results. A statistically significant decrease in the levels of serum iron, transferrin saturation, high-density lipoprotein on the one hand, and a statistically significant increase in body mass index, triglycerides, very low density lipoproteins, atherogenic index in patients with endometrial adenocarcinoma was observed. Statistically significant differences in the distribution of E3, E4, E2 allele frequencies between patients and healthy women (P = 0.048) was revealed. E3 allele frequency was reduced, and the E2 allelewas increased in patients with EC. It was shown that the serum iron level was significantly increased in EC patients and healthy carriers of the genotype E3/E2 (P= 0,0014 and 0,0363 respectively). There was significantly elevated triglyceride level in carriers of the minor genotypes E2/E4, E4/E4 among patients with EH (0,0389).Conclusions. Genotype E3/E2 compared with other APOE genotypes under study is associated with elevated levels of iron and the risk of endometrial cancer. The association APOE 2/2, 2/4, 4/4 as well as 3/2 with endometrial neoplastic diseases requires further investigation. The data obtained can be the basis for the creation of a marker system for determining a high level susceptibility to malignant disease of the female reproductive system