Использование сравнительного анализа распространения и происхождения кальдер с базальт-андезитовым составом магм для изучения генезиса миоценовых игнимбритов Восточного вулканического пояса Камчатки

Based on the statistical data of the Global Volcanism Program of the Smithsonian Institution and published materials, we present a comparative analysis of caldera-forming eruptions on global scale. The geodynamic settings and genesis of the caldera-forming eruptions with basaltic-andesitic magma compositions are described. The origin of the majority of mafic ignimbrites was related with external water. Such ignimbrites were generated in a submarine environment or with a contact with water. The newly obtained data, paleogeodynamic reconstruction and geological mapping of Miocene mafic ignimbrites of the Eastern volcanic belt (EVB) of Kamchatka confirm their genesis in costal-marine environment. These new data show significance of paleoreconstructions in studies of paleo-volcanoes and relief-forming pyroclastic rocks.На основе статистической обработки базы данных Глобальной программы вулканизма (ГПВ) Смитсоновского института и опубликованных материалов представлен сравнительный анализ кальдерообразующих извержений вулканов Земли. Показаны геодинамические позиции и условия формирования кальдер с базальт-андезитовым составом магм. В основном искомые кальдеры – это щитовые вулканы. Большинство из них имеют массивные лавовые потоки, только в нескольких случаях были описаны игнимбриты с базальт-андезитовым составом магм. Объединяющими признаками происхождения базальт-андезитовых игнимбритов являются контакты горячего пирокластического потока с «внешней» водой. Палеогеодинамические реконструкции Камчатки миоценового времени и анализ материалов геологического картирования базальт-андезитовых игнимбритов Восточного вулканического пояса Камчатки подтверждают их образование в прибрежно-морской обстановке, что согласуется с приведенными результатами изучения происхождения базальт-андезитовых игнимбритов вулканов в других регионах Земли. Полученные данные показывают значимость реконструкций палеогеодинамических обстановок в изучении типов палеовулканов и рельефообразующих пирокластических пород

MicroRNA signature characterizes primary tumors that metastasize in an esophageal adenocarcinoma rat model

Objective: To establish a miRNA signature for metastasis in an animal model of esophageal adenocarcinoma (EAC). Background: The incidence of esophageal adenocarcinoma (EAC) has dramatically increased and esophageal cancer is now the sixth leading cause of cancer deaths worldwide. Mortality rates remain high among patients with advanced stage disease and esophagectomy is associated with high complication rates. Hence, early identification of potentially metastatic disease would better guide treatment strategies. Methods: The modified Levrat's surgery was performed to induce EAC in Sprague-Dawley rats. Primary EAC and distant metastatic sites were confirmed via histology and immunofluorescence. miRNA profiling was performed on primary tumors with or without metastasis. A unique subset of miRNAs expressed in primary tumors and metastases was identified with Ingenuity Pathway Analysis (IPA) along with upstream and downstream targets. miRNAlinked gene expression analysis was performed on a secondary cohort of metastasis positive (n=5) and metastasis negative (n=28) primary tumors. Results: The epithelial origin of distant metastasis was established by IF using villin (VIL1) and mucin 5AC (MUC5AC) antibodies. miRNome analysis identified four down-regulated miRNAs in metastasis positive primary tumors compared to metastasis negative tumors: miR-PLOS 92a-3p (p=0.0001), miR-141-3p (p=0.0022), miR-451-1a (p=0.0181) and miR133a-3p (p=0.0304). Six target genes identified in the top scoring networks by IPA were validated as significantly, differentially expressed in metastasis positive primary tumors: Ago2, Akt1, Kras, Bcl2L11, CDKN1B and Zeb2. Conclusion: In vivo metastasis was confirmed in the modified Levrat's model. Analysis of the primary tumor identified a distinctive miRNA signature for primary tumors that metastasized

Lateral opening in the intact β-barrel assembly machinery captured by cryo-EM

The β-barrel assembly machinery (BAM) is a ~203 kDa complex of five proteins (BamA-E) which is essential for viability in E. coli. BAM promotes the folding and insertion of β-barrel proteins into the outer membrane via a poorly understood mechanism. Several current models suggest that BAM functions through a ‘lateral gating’ motion of the β-barrel of BamA. Here we present a cryo-EM structure of the BamABCDE complex, at 4.9 Å resolution. The structure is in a laterally open conformation showing that gating is independent of BamB binding. We describe conformational changes throughout the complex, and interactions between BamA, B, D, and E and the detergent micelle that suggest communication between BAM and the lipid bilayer. Finally, using an enhanced reconstitution protocol and functional assays, we show that for the outer membrane protein OmpT, efficient folding in vitro requires lateral gating in BAM

Structural and in vitro study of the β-Barrel Assembly Machine in Gram negative bacteria

The β-Barrel assembly machine (BAM) catalyzes the folding and insertion of outer membrane proteins (OMP) in gram-negative bacteria. The protein complex is essential for cell survival due to its critical role in folding the vast number of outer membrane proteins. However, the mechanism by which BAM recognizes, folds, and inserts OMPs is still poorly understood. Of the five subunits in the BAM complex, only BamA and BamD are essential for cell viability. Here, a crystal structure of a BamA-BamD fusion protein from Rhodothermus Marinus is presented and shown to capture the native interaction. I also demonstrate a proof of concept in vitro OMP folding model based on an in vitro transcription translation system which could be used to probe the BAM folding mechanism. The in vitro assay could be further developed to more accurately replicate in vivo folding conditions compared to existing in vitro models

The Mexican Drug War: The Case for a Non-International Armed Conflict Classification

Part I examines the current applicable legal standards and definitions for classifying a NIAC. In addition, Part I provides the historical legal background of the laws of war and how they developed over time in order to accommodate the changing landscape of hostilities and how they were waged in light of newly emerging foes. Part II describes the history of the current conflict between the Mexican government and the drug cartels. In addition, Part II addresses the domestic and global implications of the current nonlegal status of the Mexican drug war. Specifically, Part II analyzes the inadequacy of the current system and discusses the alternative arguments and approaches for ameliorating the escalating violence. Part III argues in favor of classifying the Mexican drug war as a NIAC within current applicable legal standards. Part III principally focuses on cohesively interpreting the Geneva Conventions and Additional Protocols, judicial decisions, the Rome Statute, and other authoritative sources to propose the application of a NIAC classification to the Mexican drug war