Ubiquitination of HIV-1 and MuLV Gag

AbstractOur previous biochemical studies of HIV-1 and MuLV virions isolated and identified mature Gag products, HIV-1 p6Gag and MuLV p12Gag, that were conjugated to a single ubiquitin. To study the importance of the monoubiquitination of Gag, a series of lysine to arginine mutants were constructed that eliminated ubiquitination at one or both of the lysines in HIV-1NL4-3 p6Gag and both lysines in Moloney MuLV p12Gag. HPLC and immunoblot analysis of the HIV-1 mutants demonstrated that either of the lysines in p6Gag, K27 or K33, could be monoubiquitinated. However, infectivity assays showed that monoubiquitination of HIV-1 p6Gag or MuLV p12Gag is not required for viral replication in vitro. Pulse-chase radiolabeling of HIV-1-producing cells revealed that monoubiquitination of p6Gag does not affect the short-term release of virus from the cell, the maturation of Pr55Gag, or the sensitivity of these processes to proteasome inhibitors. Experiments with protease-deficient HIV-1 showed that Pr55Gag can be monoubiquitinated, suggesting that p6Gag is first modified as a domain within Gag. Examination of the proteins inside an HIV-1 mutant found that free ubiquitin was incorporated into the virions in the absence of the lysines in p6Gag, showing that the ubiquitin inside the virus is not initially brought in as a p6Gag conjugate. Although our results establish that monoubiquitination of p6Gag and p12Gag is not required for viral replication in vitro, this modification may be a by-product of interactions between Gag and cellular proteins during assembly and budding

Влияние дифференцированных функциональных состояний на функции вегетативной нервной системы, сердечнососудистой системы и на восприятие боли. Существуют ли возможности применения в медицине?

Catedra Anesteziologie şi Reanimatologie nr. 1, USMF „Nicolae Testemiţanu”, Fundaţia „Feţele Culturii”, St.-Petersburg, Federaţia RusăThis paper presents the results of a study of the influence of specially generated conditions on the cardiovascular and autonomic nervous system and pain threshold. These conditions were induced by a technique of self-regulation propagated by Igor Kalinauskas, the Differentiated Functional States (DFS) technique. The researcher, a psychologist, an expert in DFS, developed 16 distinct functional states which where then grouped in 4 levels and 4 rhythms. The parameters of the cardiovascular and autonomic nervous system were monitored and registered with the use of Kubichek’s system of Tetrapolar Rheography. The pain threshold was tested by a mechanical algometer. The findings suggest the presence of an autonomic nervous system response pattern for each DFS rhythm. The validity of the results, however, is limited by their having been assessed in only one pilot study. The DFS which included a vibrational component showed a tendency to produce a hyperkinetic haemodynamic pattern. The pain threshold in certain DFS showed an approximately two-fold increase. Conclusion: DFS offers a unexplored capacity for the human body to maintain homeostasis and adapt to its environmenton.В работе представлены результаты объективизации воздействия на вегетативную нервную систему, сердечно-сосудистую систему и болевой порог специальных состояний, сфомированных согласно концепции психической саморегуляции разработанной академиком И. Калинаускасом Методика Дифференцированных Функциональных Состояний (МДФС). Оператор-психолог, специалист в области МДФС, сформировал состояния с 4-мя ритмами и 4-мя уровнями для каждого ритма (итого 16 ДФС). Параметры вегетативной нервной и сердечно-сосудистой систем регистрировались с помощью тетраполярной реографии по Кубичеку. Тестирование болевого порога производилось механическим сенсориметром. Обнаружено, что вегетативные изменения стремятся к образованию паттернов, специфических для каждого исследуемого состояния (утверждение закономерно в рамках наличия одного исследуемого). ДФС, которые включают дополнительный вибрационный компонент, стремятся к образованию гемодинамического паттерна преимущественно гиперкинетического характера. При некоторых ДФС наблюдалось повышение болевого порога примерно в два раза. Таким образом МДФС предлагает привлекательный, но пока мало исследованный, метод, который позволяет повысить способности организма к адаптации

Mapping the complete glycoproteome of virion-derived HIV-1 gp120 provides insights into broadly neutralizing antibody binding

The surface envelope glycoprotein (SU) of Human immunodeficiency virus type 1 (HIV-1), gp120SU plays an essential role in virus binding to target CD4+ T-cells and is a major vaccine target. Gp120 has remarkably high levels of N-linked glycosylation and there is considerable evidence that this “glycan shield” can help protect the virus from antibody-mediated neutralization. In recent years, however, it has become clear that gp120 glycosylation can also be included in the targets of recognition by some of the most potent broadly neutralizing antibodies. Knowing the site-specific glycosylation of gp120 can facilitate the rational design of glycopeptide antigens for HIV vaccine development. While most prior studies have focused on glycan analysis of recombinant forms of gp120, here we report the first systematic glycosylation site analysis of gp120 derived from virions produced by infected T lymphoid cells and show that a single site is exclusively substituted with complex glycans. These results should help guide the design of vaccine immunogens

Performance optimization and load-balancing modeling for superparametrization by 3D LES

In order to eliminate climate uncertainty w.r.t. cloud and convection parametrizations, superpramaterization (SP) [1] has emerged as one of the possible ways forward. We have implemented (regional) superparametrization of the ECMWF weather model OpenIFS [2] by cloud-resolving, three-dimensional large-eddy simulations. This setup, described in [3], contains a two-way coupling between a global meteorological model that resolves large-scale dynamics, with many local instances of the Dutch Atmospheric Large Eddy Simulation (DALES) [4], resolving cloud and boundary layer physics. The model is currently prohibitively expensive to run over climate or even seasonal time scales, and a global SP requires the allocation of millions of cores. In this paper, we study the performance and scaling behavior of the LES models and the coupling code and present our implemented optimizations. We mimic the observed load imbalance with a simple performance model and present strategies to improve hardware utilization in order to assess the feasibility of a world-covering superparametrization. We conclude that (quasi-)dynamical load-balancing can significantly reduce the runtime for such large-scale systems with wide variability in LES time-stepping speeds

High-resolution superparameterization of OpenIFS with DALES

Poster about superparameterization of clouds, convection and turbulence in the global atmospheric model OpenIFS, using DALES, a high-resolution, three-dimensional large-eddy simulation code

Состояние глюкокортикоидной функции и ее регуляция у больных раком гортани в зависимости от стадии заболевания

Glucocorticoid supply of the organism of patients with laryngeal cancer at different stages of malignant process has been studied. Formation and development of laryngeal cancer is accompanied by hormone-metabolic disturbances of hypophysis-adrenalocortical system, their character and degree of development being determined to a large extent by the stage of malignant process.Изучено состояние глюкокортикоидной обеспеченности организма больных раком гортани при различных стадиях опухолевого процесса. Становление и развитие рака гортани сопровождается гормонально-метаболическими нарушениями со стороны гипофизарно-адренокортикальной системы, характер и степень развития которых в значительной степени определяются стадией опухолевого процесса