Increased Expression of Cell-Cell Signaling Genes by Stimulated Mononuclear Leukocytes in Patients with Previous Atherothrombotic Stroke A Whole Genome Expression Profile Study

Background/Aims: Inflammation plays an important role in atherosclerosis and stroke. Acute infections are recognized as trigger factors for ischemic stroke. Methods: In this whole genome expression profile study of 15 patients and 15 control subjects, we tested the hypothesis that patients with a history of atherothrombotic stroke show enhanced transcription of inflammatory genes in circulating leukocytes. RNA from unstimulated or lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMCs) was analyzed with Affymetrix U133A GeneChips using a pooling design. Expression of single genes and functional groups of genes was analyzed by global statistical tests. Results: A total of 10,197 probe sets showed positive calls. After correction for multiple testing no single probe set revealed significant differences either without or with LPS stimulation. However, significant global expression differences were found upon LPS stimulation for the group of genes that are involved in cell-cell signaling. Conclusion: LPS stimulation of PBMCs, a condition mimicking bacterial infection, induces differential expression of a group of cell-cell signaling genes in patients with previous atherothrombotic stroke. This finding can be caused by genetic differences between both groups, but acquired risk factors, medication and technical factors may also have contributed to the result. Copyright (C) 2009 S. Karger AG, Base

Административно-деликтный закон в конституционных перспективах кодификации

The subject of the research is the problems of constitutional law enforcement of administrative offences legislation, taking into account the prospects for its new codification.The purpose of the article is confirmation or confutation of the hypothesis that the effectiveness of the new Code of administrative offences depends on whether the legal positions of the Constitutional Court of the Russian Federation on the principles of administrative responsibility will be taken into account when drafting it.The authors use methods of complex analysis, synthesis, as well as formal-legal method of interpretation of Constitution, legislation on administrative offences and judicial decisions of Russian Constitutional Court.The main results and scope of their application. The administrative torts law in Russia is expected to pass through the total review up to the grounds of its codification in close future. The article presents initial positions of that changes within basic frames produced by Russian Constitutional Court. Its case-law has already invaded into many spheres and details in respective sphere of legal rules and also prescribed a lot for their future. This case-law yet is necessarily made within its inherent range for it is ever constrained procedurally by content of actions and cases to be settled. However Russian administrative torts law is destined for reformation in new code-making in view of constitutional case-law and in order to do better with neighbor spheres of legal responsibility. Disputable matters of administrative liability, the company’s responsibility with psychical fiction on its fault (corporative thinking, wishing, desire, diligence), substantial and procedural equity etc. are described and discussed in the article as to the administrative law of torts on in its constitutional dimension.Conclusions. The Code of administrative offences of the Russian Federation does not fully meet the legal needs of society. Work on real improvement of this code will continue, therefore, legal science should be more strongly and persistently to implement in legislative practice constitutional ideas about improvement of codification and ensuring unity of legal space of the country. In particular, it is necessary to settle the debatable aspects of tort liability, the guilt of legal entities when it is addressed by fiction to the phenomena of the psyche (thinking, goals, will, caution), the constitutional and legal foundations of justice in the field of administrative penalties, procedural enforcement of rights and freedoms, etc.С учетом ожидаемого системного пересмотра законодательства об административных правонарушениях описывается исходная к этому обстановка, главным образом с правовых позиций Конституционного Суда Российской Федерации, которые изложены по предмету как небольшой свод правоположений с их юрисдикционными обоснованиями. Фиксируется, что эти позиции привели к заметным конституционно-правовым вмешательствам в административно-деликтное право и многое опреде-лили в нем на будущее в прескриптивных обращениях к законодательным властям. Исходя из ретроспективы и текущего состояния, предполагаются объем и структура предстоящей административно-деликтной кодификации, затрагиваются дискуссионные стороны деликтоспособности, вины юридических лиц, когда она обращена по фикции к явлениям психики (мышлению, целям, воле, осторожности), конституционно-правовые основы справедливости в области административных наказаний, процессуального обеспечения прав и свобод и другое по заявленной теме

The low-temperature germinating spores of the thermophilic Desulfofundulus contribute to an extremely high sulfate reduction in burning coal seams

Burning coal seams, characterized by massive carbon monoxide (CO) emissions, the presence of secondary sulfates, and high temperatures, represent suitable environments for thermophilic sulfate reduction. The diversity and activity of dissimilatory sulfate reducers in these environments remain unexplored. In this study, using metagenomic approaches, in situ activity measurements with a radioactive tracer, and cultivation we have shown that members of the genus Desulfofundulus are responsible for the extremely high sulfate reduction rate (SRR) in burning lignite seams in the Altai Mountains. The maximum SRR reached 564 ± 21.9 nmol S cm−3 day−1 at 60°C and was of the same order of magnitude for both thermophilic (60°C) and mesophilic (23°C) incubations. The 16S rRNA profiles and the search for dsr gene sequences in the metagenome revealed members of the genus Desulfofundulus as the main sulfate reducers. The thermophilic Desulfofundulus sp. strain Al36 isolated in pure culture, did not grow at temperatures below 50°C, but produced spores that germinated into metabolically active cells at 20 and 15°C. Vegetative cells germinating from spores produced up to 0.738 ± 0.026 mM H2S at 20°C and up to 0.629 ± 0.007 mM H2S at 15°C when CO was used as the sole electron donor. The Al36 strain maintains significant production of H2S from sulfate over a wide temperature range from 15°C to 65°C, which is important in variable temperature biotopes such as lignite burning seams. Burning coal seams producing CO are ubiquitous throughout the world, and biogenic H2S may represent an overlooked significant flux to the atmosphere. The thermophilic spore outgrowth and their metabolic activity at temperatures below the growth minimum may be important for other spore-forming bacteria of environmental, industrial and clinical importance

New Alzheimer Amyloid β Responsive Genes Identified in Human Neuroblastoma Cells by Hierarchical Clustering

Alzheimer's disease (AD) is characterized by neuronal degeneration and cell loss. Aβ42, in contrast to Aβ40, is thought to be the pathogenic form triggering the pathological cascade in AD. In order to unravel overall gene regulation we monitored the transcriptomic responses to increased or decreased Aβ40 and Aβ42 levels, generated and derived from its precursor C99 (C-terminal fragment of APP comprising 99 amino acids) in human neuroblastoma cells. We identified fourteen differentially expressed transcripts by hierarchical clustering and discussed their involvement in AD. These fourteen transcripts were grouped into two main clusters each showing distinct differential expression patterns depending on Aβ40 and Aβ42 levels. Among these transcripts we discovered an unexpected inverse and strong differential expression of neurogenin 2 (NEUROG2) and KIAA0125 in all examined cell clones. C99-overexpression had a similar effect on NEUROG2 and KIAA0125 expression as a decreased Aβ42/Aβ40 ratio. Importantly however, an increased Aβ42/Aβ40 ratio, which is typical of AD, had an inverse expression pattern of NEUROG2 and KIAA0125: An increased Aβ42/Aβ40 ratio up-regulated NEUROG2, but down-regulated KIAA0125, whereas the opposite regulation pattern was observed for a decreased Aβ42/Aβ40 ratio. We discuss the possibilities that the so far uncharacterized KIAA0125 might be a counter player of NEUROG2 and that KIAA0125 could be involved in neurogenesis, due to the involvement of NEUROG2 in developmental neural processes

Upregulation of CRABP1 in human neuroblastoma cells overproducing the Alzheimer-typical Aβ42 reduces their differentiation potential

<p>Abstract</p> <p>Background</p> <p>Alzheimer's disease (AD) is characterized by neurodegeneration and changes in cellular processes, including neurogenesis. Proteolytic processing of the amyloid precursor protein (APP) plays a central role in AD. Owing to varying APP processing, several β-amyloid peptides (Aβ) are generated. In contrast to the form with 40 amino acids (Aβ₄₀), the variant with 42 amino acids (Aβ₄₂) is thought to be the pathogenic form triggering the pathological cascade in AD. While total-Aβ effects have been studied extensively, little is known about specific genome-wide effects triggered by Aβ₄₂or Aβ₄₀derived from their direct precursor C99.</p> <p>Methods</p> <p>A combined transcriptomics/proteomics analysis was performed to measure the effects of intracellularly generated Aβ peptides in human neuroblastoma cells. Data was validated by real-time polymerase chain reaction (real-time PCR) and a functional validation was carried out using RNA interference.</p> <p>Results</p> <p>Here we studied the transcriptomic and proteomic responses to increased or decreased Aβ₄₂and Aβ₄₀levels generated in human neuroblastoma cells. Genome-wide expression profiles (Affymetrix) and proteomic approaches were combined to analyze the cellular response to the changed Aβ₄₂- and Aβ₄₀-levels. The cells responded to this challenge with significant changes in their expression pattern. We identified several dysregulated genes and proteins, but only the cellular retinoic acid binding protein 1 (CRABP1) was up-regulated exclusively in cells expressing an increased Aβ₄₂/Aβ₄₀ratio. This consequently reduced all-trans retinoic acid (RA)-induced differentiation, validated by CRABP1 knock down, which led to recovery of the cellular response to RA treatment and cellular sprouting under physiological RA concentrations. Importantly, this effect was specific to the AD typical increase in the Aβ₄₂/Aβ₄₀ratio, whereas a decreased ratio did not result in up-regulation of CRABP1.</p> <p>Conclusion</p> <p>We conclude that increasing the Aβ₄₂/Aβ₄₀ratio up-regulates CRABP1, which in turn reduces the differentiation potential of the human neuroblastoma cell line SH-SY5Y, but increases cell proliferation. This work might contribute to the better understanding of AD neurogenesis, currently a controversial topic.</p

ISOMERIZATION OF MOLECULES ON MULTI-PHOTON VIBRATIONAL AND SUBSEQUENT ELECTRON-EXCITATION BY LASER-RADIATION

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ELECTROCHEMICAL HIGH-PRESSURE HF LASER

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FREOUENCY TUNING OF AN e-BEAM PREIONIZED HIGH-PRESSURE CO 2 LASER

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ISOTOPE-SELECTIVE PHOTO-DISSOCIATION OF CF3I MOLECULES BY MULTI-PHOTON VIBRATIONAL AND SUBSEQUENT ELECTRON-EXCITATION BY LASER-RADIATION

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