An Analysis of the Chemical Composition of the Atmosphere of Venus on an AMS of the Venera-12 Using a Gas Chromatograph

Eight analyses of the atmosphere of Venus were made beginning at an altitude of 42 km right down to the surface of the planet. The following were detected in the atmosphere of Venus: nitrogen in concentrations of 2.5 plus or minus 0.5 volumetric %, argon ir concentrations (4 plus or minus 2) x 10 to the minus 3 power volumetric %, CO--(2.8 plus or minus 1.4) x 10 to the minus 3 power volumetric % and SO2 in concentrations (1.3 plus or minus 0.6) x 10 to the minus 2 power volumetric %. The upper limits were estimated for the content of oxygen and water equal to 2 x 10 to the minus 3 power and 10 to the minus 2 power volumetric %, respectively

Chemical analysis of aerosol in the Venusian cloud layer by reaction gas chromatography on board the Vega landers

The experiment on sulfuric acid aerosol determination in the Venusian cloud layer on board the Vega landers is described. An average content of sulfuric acid of approximately 1 mg/cu m was found for the samples taken from the atmosphere at heights from 63 to 48 km and analyzed with the SIGMA-3 chromatograph. Sulfur dioxide (SO2) was revealed in the gaseous sample at the height of 48 km. From the experimental results and blank run measurements, a suggestion is made that the Venusian cloud layer aerosol consists of more complicated particles than the sulfuric acid water solution does

Rsp5/​Nedd4 is the main ubiquitin ligase that targets cytosolic misfolded proteins following heat stress

The heat-shock response is a complex cellular program that induces major changes in protein translation, folding and degradation to alleviate toxicity caused by protein misfolding. Although heat shock has been widely used to study proteostasis, it remained unclear how misfolded proteins are targeted for proteolysis in these conditions. We found that ​Rsp5 and its mammalian homologue ​Nedd4 are important E3 ligases responsible for the increased ubiquitylation induced by heat stress. We determined that ​Rsp5 ubiquitylates mainly cytosolic misfolded proteins upon heat shock for proteasome degradation. We found that ubiquitylation of heat-induced substrates requires the Hsp40 co-chaperone ​Ydj1 that is further associated with ​Rsp5 upon heat shock. In addition, ubiquitylation is also promoted by PY ​Rsp5-binding motifs found primarily in the structured regions of stress-induced substrates, which can act as heat-induced degrons. Our results support a bipartite recognition mechanism combining direct and chaperone-dependent ubiquitylation of misfolded cytosolic proteins by ​Rsp5

Проблема современных классификаций гепатоцеллюлярного рака. Аналитический

Hepatocellular carcinoma (HCC) in vast majority of cases develops on the background of the chronic liver diseases, more often – viral hepatitis B and C, and is diagnosed at the advanced stages [1, 3]. Despite the advantages of the modern oncology (some patients live till appearance of brain metastases [1]), prognosis in HCC is still poor. In general, prognosis depends on not only biological characteristics of the tumor itself, but also on the background of the liver condition, often – at the stage of the cirrhosis. As distinct from the other malignant tumor of liver – cholangiocellular carcinoma, there are no universal prognostic classifications for HCC [2]. International classification TNM used for majority of solid tumors is not appropriate to be ‘reference’ for HCC [4]. There are several prognostic scales and classifications created recently in West and Asian countries. For the creation of such systems they use more often the regression model on the basis of prognostic variables of the investigated population. Currently, there is no universal prognostic classification or scale for HCC ГЦР. Almost all these classifications included the features; liver function, tumor characteristics, clinical behavior, undercurrent diseases, presence of the cirrhosis [3]. Гепатоцеллюлярный рак (ГЦР) в подавляющем большинстве случаев развивается на фоне хронических заболеваний печени, чаще – вирусных гепатитов В и С, и часто диагностируется на поздних стадиях [1, 3]. Несмотря на некоторые успехи современной онкологии (некоторые пациенты «доживают» даже до метастазов ГЦР в головной мозг [1]), прогноз при ГЦР остается плохим. В целом прогноз зависит не только от биологических характеристик самой опухоли, но и от фонового заболевания печени, часто – на стадии цирроза. В отличие от другой злокачественной опухоли печени – холангиоцеллюлярной карциномы, для ГЦР нет универсальных прогностических классификаций [2]. Так, международная классификация TNM, используемая для большинства солидных опухолей, не может применяться в качестве «референсной» для ГЦР [4]. Для определения прогноза c последующей тактикой ведения в западных и азиатских странах в последние годы разработаны различные шкалы оценки и классификации ГЦР. Для создания таких систем чаще используют регрессионную модель на основании прогностических переменных изучаемой популяции. На сегодняшний день не существует универсальной и признанной всеми прогностической шкалы или классификации ГЦР. Почти все эти классификации включают в себя такие признаки, как: функция печени, характеристики опухоли, клинические проявления, сопутствующие заболевания, наличие цирроза [3].

Comparison of substrate specificity of the ubiquitin ligases Nedd4 and Nedd4-2 using proteome arrays

Target recognition by the ubiquitin system is mediated by E3 ubiquitin ligases. Nedd4 family members are E3 ligases comprised of a C2 domain, 2–4 WW domains that bind PY motifs (L/PPxY) and a ubiquitin ligase HECT domain. The nine Nedd4 family proteins in mammals include two close relatives: Nedd4 (Nedd4-1) and Nedd4L (Nedd4-2), but their global substrate recognition or differences in substrate specificity are unknown. We performed in vitro ubiquitylation and binding assays of human Nedd4-1 and Nedd4-2, and rat-Nedd4-1, using protein microarrays spotted with ∼8200 human proteins. Top hits (substrates) for the ubiquitylation and binding assays mostly contain PY motifs. Although several substrates were recognized by both Nedd4-1 and Nedd4-2, others were specific to only one, with several Tyr kinases preferred by Nedd4-1 and some ion channels by Nedd4-2; this was subsequently validated in vivo. Accordingly, Nedd4-1 knockdown or knockout in cells led to sustained signalling via some of its substrate Tyr kinases (e.g. FGFR), suggesting Nedd4-1 suppresses their signalling. These results demonstrate the feasibility of identifying substrates and deciphering substrate specificity of mammalian E3 ligases

System Approach to the Development of Intelligent Complexes of Oncological Diagnostics

The system approach to the development of intellectual complexes in cancer diagnosis are discussed in the article. Distinctive features of this approach: the participation of pathologist at the stage of description of recognizable images (the description is based on traditional assessments of quality informative features of tumors); the set of the most similar probabilistic diagnoses is forming on the classification stage of recognition; final histological diagnosis is made by pathologist. The proposed approach has been successfully tested in clinical practice. Keywords: image processing, image description, image classification, pattern recognition, qualitative attributes of tumor images, interactive recognition, cancer diagnosis, decision support syste

The Rho GDI Rdi1 regulates Rho GTPases by distinct mechanisms

© 2008 by The American Society for Cell Biology. Under the License and Publishing Agreement, authors grant to the general public, effective two months after publication of (i.e.,. the appearance of) the edited manuscript in an online issue of MBoC, the nonexclusive right to copy, distribute, or display the manuscript subject to the terms of the Creative Commons–Noncommercial–Share Alike 3.0 Unported license (http://creativecommons.org/licenses/by-nc-sa/3.0).The small guanosine triphosphate (GTP)-binding proteins of the Rho family are implicated in various cell functions, including establishment and maintenance of cell polarity. Activity of Rho guanosine triphosphatases (GTPases) is not only regulated by guanine nucleotide exchange factors and GTPase-activating proteins but also by guanine nucleotide dissociation inhibitors (GDIs). These proteins have the ability to extract Rho proteins from membranes and keep them in an inactive cytosolic complex. Here, we show that Rdi1, the sole Rho GDI of the yeast Saccharomyces cerevisiae, contributes to pseudohyphal growth and mitotic exit. Rdi1 interacts only with Cdc42, Rho1, and Rho4, and it regulates these Rho GTPases by distinct mechanisms. Binding between Rdi1 and Cdc42 as well as Rho1 is modulated by the Cdc42 effector and p21-activated kinase Cla4. After membrane extraction mediated by Rdi1, Rho4 is degraded by a novel mechanism, which includes the glycogen synthase kinase 3β homologue Ygk3, vacuolar proteases, and the proteasome. Together, these results indicate that Rdi1 uses distinct modes of regulation for different Rho GTPases.Deutsche Forschungsgemeinschaf

Экстратестикулярная шваннома мошонки. Клинический случай и обзор литературы

Schwannoma is a benign tumor that grows from the Schwann cells forming the myelin sheath of peripheral nerves. The clinical manifestations are nonspecific and generally due to compression of the adjacent structures of a growing tumor. The location of the tumor in the scrotum is rare; its primary diagnosis is difficult and only immunohistochemical examination allows the final diagnosis to be established. The authors present a clinical case of a patient operated on at the Urology Department, Moscow Clinical Research Center, for intrascrotal schwannoma causing impaired microcirculation in the scrotal skin to form purulent scrotal ulcers. In terms of the benign pattern and extratesticular localization of the tumor, its removal without orchifuniculectomy can yield a good clinical result.Шваннома – доброкачественная опухоль, растущая из шванновских клеток, формирующих миелиновую оболочку периферических нервов. Клинические проявления неспецифичны и, как правило, обусловлены компрессией прилежащих структур растущей опухолью. Локализация опухоли в мошонке редка, первичная диагностика трудна, и лишь имунногистохимическое исследование позволяет установить окончательный диагноз. Мы представляем клиническое наблюдение пациента, оперированного в урологическом отделение МКНЦ по поводу шванномы мошонки, вызвавшей нарушение микроциркуляции кожи мошонки с формированием гнойной язвы мошонки. С учетом доброкачественного характера опухоли и экстратестикулярной локализации удаление опухоли без выполнения орхфуникулэктомии позволяет достичь хорошего клинического результата

The ubiquitin ligase Nedd4-1 participates in denervation-induced skeletal muscle atrophy in mice

Skeletal muscle atrophy is a consequence of muscle inactivity resulting from denervation, unloading and immobility. It accompanies many chronic disease states and also occurs as a pathophysiologic consequence of normal aging. In all these conditions, ubiquitin-dependent proteolysis is a key regulator of the loss of muscle mass, and ubiquitin ligases confer specificity to this process by interacting with, and linking ubiquitin moieties to target substrates through protein:protein interaction domains. Our previous work suggested that the ubiquitin-protein ligase Nedd4-1 is a potential mediator of skeletal muscle atrophy associated with inactivity (denervation, unloading and immobility). Here we generated a novel tool, the Nedd4-1 skeletal muscle-specific knockout mouse (myo(Cre);Nedd4-1(flox/flox)) and subjected it to a well validated model of denervation induced skeletal muscle atrophy. The absence of Nedd4-1 resulted in increased weights and cross-sectional area of type II fast twitch fibres of denervated gastrocnemius muscle compared with wild type littermates controls, at seven and fourteen days following tibial nerve transection. These effects are not mediated by the Nedd4-1 substrates MTMR4, FGFR1 and Notch-1. These results demonstrate that Nedd4-1 plays an important role in mediating denervation-induced skeletal muscle atrophy in vivo

Methods designed for the identification and characterization of in vitro and in vivo chromatin assembly mutants in Saccharomyces cerevisiae

Assembly of DNA into chromatin allows for the formation of a barrier that protects naked DNA from protein and chemical agents geared to degrade or metabolize DNA. Chromatin assembly occurs whenever a length of DNA becomes exposed to the cellular elements, whether during DNA synthesis or repair. This report describes tools to study chromatin assembly in the model system Saccharomyces cerevisiae. Modifications to an in vitro chromatin assembly assay are described that allowed a brute force screen of temperature sensitive (ts) yeast strains in order to identify chromatin assembly defective extracts. This screen yielded mutations in genes encoding two ubiquitin protein ligases (E3s): RSP5, and a subunit of the Anaphase Promoting Complex (APC), APC5. Additional modifications are described that allow for a rapid analysis and an in vivo characterization of yeast chromatin assembly mutants, as well as any other mutant of interest. Our analysis suggests that the in vitro and in vivo chromatin assembly assays are responsive to different cellular signals, including cell cycle cues that involve different molecular networks