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The development and usage of safe cell systems for testing agents which possess anti-HIV activity is a very important factor in the design of new drugs. We have described in detail a system we designed that is based on lentiviral vectors (Prokofjeva et. al.,Antiviral Therapy,in print) for swift and completely safe screening of potential HIV-1 replication inhibitors. The system enables one to test the efficiency of the inhibitory activity of compounds whose action is directed towards either wild-type HIV-1 reverse transcriptase or integrase, or mutant enzymes corresponding to the drug-resistant virus form. Testing results of a number of already known drugs, which correlate well with published data as well as data on newly synthesized compounds, were obtained. Application of this system substantially broadens the possibilities of preclinical anti-HIV drugs testing.

Objective: The proteolipid plasmolipin (PLLP) is a tetraspan membrane protein expressed primarily in brain and kidney epithelial cells. In the brain, PLLP is associated with the myelin sheath and is thought to play a role in the regulation of myelin maintenance. Recently PLLP has been identified as [for full text, please go to the a.m. URL], 66. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)

Разработка безопасных клеточных систем, позволяющих тестировать соединения, обладающие антиВИЧ -активностью, весьма важна для создания новых противовирусных препаратов. Нами детально охарактеризована разработанная ранее на основе лентивирусных векторов система (Prokofjeva et. al., Antiviral Therapy, в печати) для быстрого и полностью безопасного скрининга потенциальных ингибиторов репликации ВИЧ-1. Система позволяет проводить испытания ингибиторной активности соединений, действие которых направлено как на обратную транскриптазу и интегразу ВИЧ-1 дикого типа, так и на мутантные ферменты, соответствующие лекарственно-устойчивым формам вируса. Получены результаты тестирования ряда известных препаратов, которые хорошо согласуются с опубликованными данными, а также вновь синтезированных соединений. Применение этой системы существенно расширяет возможности доклинических испытаний анти-ВИЧ-препаратов.

In the present study we have applied the siRNA approach for substantial reduction of AML1-ETO and RUNX1 (K83N) expression, which are frequently found in the leukemic cells. We have designed small hairpin RNAs (shRNA) for targeting AML1-ETO oncogene and a region close to the 5'-untranslated region of mRNA for the mutant RUNX1 (K83N) oncogene and expressed the shRNAs in lentiviral vectors. We report a stable reduction in expression of the oncogenes following the introduction of shRNAs into cells.

Up to 10% of the mouse genome is comprised of endogenous retrovirus (ERV) sequences, and most represent the remains of ancient germ line infections. Our knowledge of the three distinct classes of ERVs is inversely correlated with their copy number, and their characterization has benefited from the availability of divergent wild mouse species and subspecies, and from ongoing analysis of the Mus genome sequence. In contrast to human ERVs, which are nearly all extinct, active mouse ERVs can still be found in all three ERV classes. The distribution and diversity of ERVs has been shaped by host-virus interactions over the course of evolution, but ERVs have also been pivotal in shaping the mouse genome by altering host genes through insertional mutagenesis, by adding novel regulatory and coding sequences, and by their co-option by host cells as retroviral resistance genes. We review mechanisms by which an adaptive coexistence has evolved. (Part of a multi-author review).

Fms-like tyrosine kinase 3 (FLT3) is a class III receptor tyrosine kinase, which plays a role in proliferation and differentiation of B-cell progenitors, myelomonocytic and dendritic cells, as well as in the maintenance of pluripotent hematopoietic stem cells (reviewed in Stirewalt and Radich,1and Schmidt-Arras et al.2). Recently, FLT3 has received much attention as an important oncoprotein. Mutations in FLT3 that lead to constitutive activation are among the most common molecular lesions found in acute myeloid leukemia.3 The most prevalent type of mutations result in internal tandem duplications (ITD) of amino-acid stretches in the juxtamembrane domain of FLT3. FLT3-ITD is constitutively and highly active, can transform myeloid cell lines in vitro4 and can induce a myeloproliferative syndrome. Wild-type FLT3 and FLT3-ITD exhibit qualitative differences in signal transduction. Notably, while FLT3-ITD strongly and directly activates STAT5, ligand-activated wild-type FLT3 is a comparatively weak STAT5 activator (reviewed in Choudhary et al.5). The mechanisms of differential signal transduction are incompletely understood.