MAO A VNTR polymorphism and amygdala volume in healthy subjects

The X-linked Monoamine Oxidase A (MAO A) gene presents a well known functional polymorphism consisting of a variable number of tandem repeats (VNTR) (long and short variants) previously associated with altered neural function of the amygdala. Using automatic subcortical segmentation (Freesurfer), we investigated whether amygdala volume could be influenced by this genotype. We studied 109 healthy subjects (age range 18-80 years; 59 male and 50 female), 74 carrying the MAO A High-activity allele and 35 the MAO A Low-activity allele. No significant effect of the MAO A polymorphism or interaction effect between polymorphism × gender was found on amygdalar volume. Thus, our findings suggest that the reported impact of the MAO A polymorphism on amygdala function is not coupled with consistent volumetric changes in healthy subjects. Future studies are needed to investigate whether the association between volume of the amygdala and the MAO A VNTR polymorphism is influenced by social/psychological variables, such as impulsivity, trauma history and cigarette smoking behaviour, not taken into account in this work

Monitoring of cfrp-strengthened reinforced concrete bridge spans in low temperature conditions

The article discusses strengthening bridges using composite materials at extreme low temperatures. Provides the results some experimental studies FRP strengthened concrete samples at low temperatures

Ataxin-1 and ataxin-2 intermediate-length PolyQ expansions in amyotrophic lateral sclerosis.

OBJECTIVE: Recent evidence suggests that intermediate-length polyglutamine (PolyQ) expansions in the ataxin-2 (ATXN-2) gene are a risk factor for amyotrophic lateral sclerosis (ALS). This work was undertaken with the aim to investigate the frequency of ataxin-1 (ATXN-1) and ATXN-2 PolyQ expansions in a cohort of patients with sporadic ALS (sALS) and patients with familial ALS (fALS) from southern Italy. METHODS: We assessed the PolyQ lengths of ATXN-1 and ATXN-2 in 405 patients with sALS, 13 patients with fALS, and 296 unrelated controls without history of neurodegenerative disorders. RESULTS: We found significantly higher intermediate PolyQ expansions ≥ 32 for ATXN-1 alleles and ≥ 28 for ATXN-2 alleles in the sALS cohort (ATXN-1: ALS, 7.07% vs controls, 2.38%; p = 0.0001; ATXN-2: ALS, 2.72% vs controls, 0.5%; p = 0.001). ATXN-1 CAT and ATXN-2 CAA interruptions were detected in patients with ALS only. Age at onset, site of onset, and sex were not significantly related to the ATXN-1 or ATXN-2 PolyQ repeat length expansions. CONCLUSIONS: Both ATXN-1 and ATXN-2 PolyQ intermediate expansions are independently associated with an increased risk for ALS

FUS MUTATIONS IN SPORADIC AMYOTROPHIC LATERAL SCLEROSIS: CLINICAL AND GENETIC ANALYSIS

Fused in sarcoma (FUS) or translocation in liposarcoma (TLS), a DNA/RNA-binding protein, causes a dominant autosomal inherited form of amyotrophic lateral sclerosis (ALS), ALS 6. Its main role in neurodegeneration is highlighted by the presence of cytoplasmic accumulation of its mutant protein form in ALS patients. To further define the frequency and spectrum of FUS gene mutations, we have performed a molecular screening of a cohort of 327 Italian patients from Southern Italy with sporadic ALS (SALS). We identified 4 patients carrying 3 different missense mutations and several polymorphisms. Two different substitutions occurring in the same amino acidic position have been observed in 2 patients: R521G and R521C respectively; P525L mutation has been found in 2 additional cases. Most of the patients with FUS mutations showed early symptom onset and had short disease survival. We also detected 4 different polymorphic variants (3=-untranslated region [UTR] variant, c.*41G.A; c.52313ins[GAGGTG]; c.335-15del[TTTT]; and rs13331793) in 9 patients from within our cohort. This study underlines the importance of population-based mutation screening of newly identified genes. \ua9 2011 Elsevier Inc. All rights reserved

Разработка и формализация корпоративной стратегии предприятия

Выпускная квалификационная работа содержит 110 стр., 19 таблиц, 15 рисунков, 30 использованных источников, 2 приложения. Ключевые слова: корпоративная стратегия, SWOT-анализ, матрица Маккински, матрица Томпсона и Стрикленда, модель Артур де Литтл, модель «5 сил Портера», ключевые показатели эффективности, система управления по показателям, корпоративная социальная ответственность. Объектом исследования является корпоративная стратегия ОАО «ТЭМЗ». Целью дипломной работы является рассмотрение проблем разработки и формализации корпоративной стратегии предприятия. В процессе исследования использованы законодательные и методические материалы, учебные пособия, публикации в специальных журналах, связанные с вопросами корпоративного управления. В результате исследования была осуществлена разработка и формализация корпоративной стратегии ОАО «ТЭМЗ». Основные конструктивные, технологические и технико-эксплуатационные характеристики: введение раскрывает актуальность, цель исследования, теоретическую и практическую значимость работы, обосновывается выбор объекта и предмета исследования. В первой главе раскрыты теоретические основы разработки корпоративной стратегии. Во второй главе дана краткая характеристика предприятия, проведен анализ системы корпоративного управления на предприятии ОАО «ТЭМЗ». В третьей главе рассмотрен процесс разработки и формализации стратегии управления для ОАО «ТЭМЗ». Заключение содержит анализ результатов теоретических и экспериментальных исследований работы. Степень внедрения: одна из предложенных в результате разработки и формализации корпоративных стратегий уже принята на ОАО «ТЭМЗ» и включена в соответствующие разделы инвестиционного бизнес-плана. Область применения: полученные результаты разработки и формализации корпоративной стратегии, эффективности социальной ответственности управления могут быть использованы в управленческой работе ОАО «ТЭМЗ»». Экономическая эффективность/значимость работы. Разработанные и формализованные корпоративные стратегии позволят ОАО «ТЭМЗ» повысить производительность труда, уменьшить текучесть кадрового потенциала и производственный травматизм.Final qualifying work contains 110 pages, 19 tables, 15 figures, 30 of the used sources, 2 appendices. Key words: corporate strategy, SWOT analysis, matrix o Machinski, matrix Thompson and Strickland model Arthur de little, model "5 forces of porter", key performance indicators, control system indicators, corporate social responsibility. The object of study is the corporate strategy of JSC "TEMZ". The aim of the thesis is to examine the problems of the development and formalization of corporate strategy. In the process of the study used legislative and methodical materials, textbooks, publications in professional journals related to issues of corporate governance. The study was carried out to develop and formalization of the corporate strategy of JSC "TEMZ". The basic constructive, technological and technical-operational characteristics: the introduction reveals the relevance, research objective, theoretical and practical significance of the research, justify the choice of object and subject of research. The first Chapter describes theoretical basis of development of corporate strategy. The second Chapter gives a brief description of the enterprise, the analysis of the system of corporate management of JSC "TEMZ". The third Chapter describes the development process and the formalization of the strategy management for JSC "TEMZ". The conclusion contains an analysis of the results of theoretical and experimental research work. Degree of implementation: one of the proposed in the development and formalization of corporate strategies already adopted at JSC "TEMZ" and included in relevant sections of the investment business plan. Application field: the results of the development and formalization of corporate strategy, efficiency, social responsibility management can be used in managerial work of JSC "TEMZ". Economic efficiency and significance of the work. Developed and formalized corporate strategy will allow JSC "TEMZ" to increase productivity, to decrease the fluidity of human resources and industrial injuries

Transcriptional and Post-Transcriptional Regulation of SPAST, the Gene Most Frequently Mutated in Hereditary Spastic Paraplegia

Hereditary spastic paraplegias (HSPs) comprise a group of neurodegenerative disorders that are characterized by progressive spasticity of the lower extremities, due to axonal degeneration in the corticospinal motor tracts. HSPs are genetically heterogeneous and show autosomal dominant inheritance in ∼70–80% of cases, with additional cases being recessive or X-linked. The most common type of HSP is SPG4 with mutations in the SPAST gene, encoding spastin, which occurs in 40% of dominantly inherited cases and in ∼10% of sporadic cases. Both loss-of-function and dominant-negative mutation mechanisms have been described for SPG4, suggesting that precise or stoichiometric levels of spastin are necessary for biological function. Therefore, we hypothesized that regulatory mechanisms controlling expression of SPAST are important determinants of spastin biology, and if altered, could contribute to the development and progression of the disease. To examine the transcriptional and post-transcriptional regulation of SPAST, we used molecular phylogenetic methods to identify conserved sequences for putative transcription factor binding sites and miRNA targeting motifs in the SPAST promoter and 3′-UTR, respectively. By a variety of molecular methods, we demonstrate that SPAST transcription is positively regulated by NRF1 and SOX11. Furthermore, we show that miR-96 and miR-182 negatively regulate SPAST by effects on mRNA stability and protein level. These transcriptional and miRNA regulatory mechanisms provide new functional targets for mutation screening and therapeutic targeting in HSP

Morphological correlates of MAO A VNTR polymorphism: new evidence from cortical thickness measurement

A functional variant in the mono-amine oxidase A (MAO A) gene has been shown to impact neural function related to cognitive and affective processing and increase risk for conduct disorders. However, whether MAO A could be a candidate gene for structural variation in the human brain remains to be clarified. This study is the first to investigate the effect of this genotype on brain morphology by measuring cortical thickness. We genotyped 59 healthy male subjects (36 carrying the MAO A High-activity allele and 23 the MAO A Low-activity allele) who underwent structural MRI at 3T. Models of the grey-white and pial surfaces were generated for each individual's cortices, and the distance between these two surfaces was used to compute cortical thickness within a priori regions of interest of the orbitofrontal and cingulate cortices. Surface-based analysis of the cortical mantle showed that the MAO A genotype was associated with structural differences in the orbitofrontal cortex bilaterally, where the MAO A High-activity group showed the highest cortical thickness value and the MAO A Low-activity group the lowest. Otherwise, no significant difference was detected within the cingulate cortex. Thus, we confirm the hypothesis that the MAO A genotype has a specific impact on human brain morphology. In particular, thickness measurement of the orbitofrontal cortex provides new evidence about the biological impact of the MAO A genotype on neural systems relevant to the pathophysiology of behavioural disorders