Three stages of the future physics researchers training at V. N. Karazin KhNU – SCPT laboratory

The work is dedicated to the good practice examples in the process of preparation of the future students for the departments of Physics. It have been supposed the three stages of the secondary school students’ experimental skills development. To teach students how to make simple research the extracurricular courses have been organised at the V. N. Karazin KhNU — SCPT Laboratory which is situated at the Department of Physics and Technology at the premises of V. N. Karazin Kharkiv National University. During such training students gain special profound knowledge of physics and seriously improve their experimental skills by doing self-made experimental projects using recycled materials, simple household objects, ordinary toys by means of real tools.Работа посвящена удачному опыту в привлечении и подготовке школьников к поступлению на физические факультеты ВУЗов Украины. Выделяются три этапа развития и формирования экспериментальных умений школьников. Для дополнительного обучения детей сотрудники физико- технического факультета ХНУ имени В. Н. Каразина и НФТЦ создали специальную лабораторию интерактивных методов обучения. Во время занятий учащиеся школ Харькова и области получают дополнительную подготовку по физике, серьезно повышают свои экспериментальные навыки, знакомясь с научным исследовательским оборудованием. Школьники делают свои первые исследовательские проекты, используя предметы домашнего обихода, обыкновенные игрушки, а также отходы производства и ненужные части недорого оборудования.Робота присвячена вдалого досвіду в залученні і підготовці школярів до вступу на фізичні факультети ВНЗ України. Виділяються три етапи розвитку та формування експериментальних умінь школярів. Для додаткового навчання дітей співробітники фізико-технічного факультету ХНУ імені В. Н. Каразіна та НФТЦ створили спеціальну лабораторію інтерактивних методів навчання. Під час занять учні шкіл Харкова і області отримують додаткову підготовку з фізики, серйозно підвищують свої експериментальні навички, знайомлячись з науковим дослідницьким обладнанням. Школярі роблять свої перші дослідні проекти, використовуючи предмети домашнього вжитку, звичайні іграшки, а також відходи виробництва і непотрібні частини недорого обладнання

Accumulation of Mitochondrial DNA Common Deletion Since The Preataxic Stage of Machado-Joseph Disease

Molecular alterations reflecting pathophysiologic changes thought to occur many years before the clinical onset of Machado-Joseph disease (MJD)/spinocerebellar ataxia type 3 (SCA3), a late-onset polyglutamine disorder, remain unidentified. The absence of molecular biomarkers hampers clinical trials, which lack sensitive measures of disease progression, preventing the identification of events occurring prior to clinical onset. Our aim was to analyse the mtDNA content and the amount of the common deletion (m.8482_13460del4977) in a cohort of 16 preataxic MJD mutation carriers, 85 MJD patients and 101 apparently healthy age-matched controls. Relative expression levels of RPPH1, MT-ND1 and MT-ND4 genes were assessed by quantitative real-time PCR. The mtDNA content was calculated as the difference between the expression levels of a mitochondrial gene (MT-ND1) and a nuclear gene (RPPH1); the amount of mtDNA common deletion was calculated as the difference between expression levels of a deleted (MT-ND4) and an undeleted (MT-ND1) mitochondrial genes. mtDNA content in MJD carriers was similar to that of healthy age-matched controls, whereas the percentage of the common deletion was significantly increased in MJD subjects, and more pronounced in the preclinical stage (p < 0.05). The BCL2/BAX ratio was decreased in preataxic carriers compared to controls, suggesting that the mitochondrial-mediated apoptotic pathway is altered in MJD. Our findings demonstrate for the first time that accumulation of common deletion starts in the preclinical stage. Such early alterations provide support to the current understanding that any therapeutic intervention in MJD should start before the overt clinical phenotype

Promoter Variation and Expression Levels of Inflammatory Genes IL1A, IL1B, IL6 and TNF in Blood of Spinocerebellar Ataxia Type 3 (SCA3) Patients

Age at onset in spinocerebellar ataxia type 3 (SCA3/MJD) is incompletely explained by the size of the CAG tract at the ATXN3 gene, implying the existence of genetic modifiers. A role of inflammation in SCA3 has been postulated, involving altered cytokines levels; promoter variants leading to alterations in cytokines expression could influence onset. Using blood from 86 SCA3 patients and 106 controls, this work aimed to analyse promoter variation of four cytokines (IL1A, IL1B, IL6 and TNF) and to investigate the association between variants detected and their transcript levels, evaluated by quantitative PCR. Moreover, the effect of APOE isoforms, known to modulate cytokines, was investigated. Correlations between cytokine variants and onset were tested; the cumulative modifier effects of cytokines and APOE were analysed. Patients carrying the IL6*C allele had a significant earlier onset (4 years in average) than patients carrying the G allele, in agreement with lower mRNA levels produced by IL6*C carriers. The presence of APOE*ɛ2 allele seems to anticipate onset in average 10 years in patients carrying the IL6*C allele; a larger number of patients will be needed to confirm this result. These results highlight the pertinence of conducting further research on the role of cytokines as SCA3 modulators, pointing to the presence of shared mechanisms involving IL6 and APOE

Familial hypercholesterolemia: Molecular characterization of possible cases from the Azores Islands (Portugal)

Familial hypercholesterolemia (FH) is an autosomal dominant disorder of the cholesterol metabolism, which constitutes a risk factor for coronary arterial disease (CAD). In the Azores Islands (Portugal), where mortality from CAD doubles its rate comparatively to the rest of the country and where a high frequency of dyslipidemia has been reported, the prevalence and distribution of FH remain unknown. The molecular characterization of a group of 33 possible cases of FH of Azorean background was undertaken in this study. A DNA array was initially used to search mutations in the LDLR, APOB and PCSK9 loci in 10 unrelated possible cases of FH. No mutations were detected in the array; after sequencing the full LDLR gene, 18 variants were identified, corresponding to two missense (c.806G > A; c.1171G > A) and sixteen synonymous alterations. Six of the synonymous variants which are consistently described in the literature as associated with altered cholesterol levels were used to build haplotypes. The most frequent haplotype corresponded to TTCGCC (45%), a "risk" haplotype, formed exclusively by alleles that were reported to increase cholesterol levels. Some of the variants detected in the full sequencing of the LDLR gene fell within the ligand-binding domain of this gene, defined by exons 2 to 6. To add information as to the role of such variants, these exons were sequenced in the remaining 23 possible FH cases. Two missense alterations (c.185C > T; c.806G > A) were found in this subset of possible FH cases. The missense alteration c.185C > T, identified in one individual, is novel for the Portuguese population. In silico analysis was not conclusive for this alteration, whose role will have to be further investigated. This study represents the first approach to the establishment of the mutational profile of FH in the Azores Islands.This work was supported by the project entitled “High prevalence pathologies in the Azores: genetic and biochemical markers” with reference (M2.1.2/I/026/2008) funded by SRCTE. M. R. receives a PhD fellowship (M3.1.2/F/006/2011) from Fundo Regional para a Ciência. T.C. receives a post-doctoral fellowships from Fundação para a Ciência e a Tecnologia (SFRH/BPD/38659/ 2007) and N. K. (M3.1.7/F/002/2008) and A. R. (M3.1.7/F/031/2011) both receives post-doctoral fellowships from Fundo Regional para a Ciência

Differential mtDNA damage patterns in a transgenic mouse model of Machado-Joseph disease (MJD/SCA3)

Mitochondrial dysfunction has been associated with late onset neurodegenerative disorders, among which is Machado-Joseph disease (MJD/SCA3). In a previous study, using a transgenic mouse model of MJD, we reported a decrease in mitochondrial DNA (mtDNA) copy number and an accumulation of the 3876-bp deletion with age and with phenotype development. We extended this study by analyzing the pattern of mtDNA depletion and the accumulation of the 3876-bp deletion in 12 older transgenic (TG) and 4 wild-type (wt) animals, and by investigating the accumulation of somatic mutations in the D-loop region in 76 mice (42 TG and 34 wt). mtDNA damage was studied in TG and wt mice at different ages and tissues (blood, pontine nuclei, and hippocampus). Results for older mice demonstrate an accumulation of the mtDNA 3867-bp deletion with age, which was more pronounced in TG animals. Furthermore, the tendency for mtDNA copy number decrease with age, in all analyzed tissues of TG and wt animals, was also confirmed. No point mutations were detected in the D-loop, neither in TG nor wt animals, in any of the tissues analyzed. Due to the absence of mtDNA somatic mutations, we can suggest that mtDNA point mutation accumulation cannot be used to monitor the development and progression of the phenotype in this mouse model and likely in any MJD mice model. The present results further confirm not only the association between mtDNA alterations (copy number and deletions) and age, but also between such alterations and the expression of the mutant ataxin-3 in TG mice.NK and AR are a Fundo Regional para a Ciencia postdoctoral fellow (M3.1.7/F/002/2008 and M3.1.7/F/031/2011). This work was partially supported by Generalitat de Catalunya (SGR 2009-566)

Patterns of mitochondrial DNA damage in blood and brain tissues of a transgenic mouse model of Machado-Joseph disease

BACKGROUND: Machado-Joseph disease (MJD) is an autosomal dominant spinocerebellar ataxia caused by a CAG tract expansions in the ATXN3 gene. Patterns of mitochondrial damage associated with pathological findings of brain tissues could provide molecular biomarkers of this disorder. OBJECTIVE: The potential of mitochondrial DNA (mtDNA) damage as a biomarker of MJD progression was investigated using a transgenic mouse model. METHODS: DNA was obtained from affected (pontine nuclei) and nonaffected tissues (hippocampus and blood) of transgenic animals of three distinct age groups: 8 weeks, before onset of the phenotype; 16 weeks, at onset, and 24 weeks, at well-established phenotype. Wild-type littermate mice, serving as controls, were analyzed for the same tissues and age groups. mtDNA damage was studied by fluorescence-based quantitative PCR in 84 transgenic and 93 wild-type samples. RESULTS: A clear pattern of decrease in mtDNA copy number with age and accumulation of 3,867-bp deletions at the initial stages (both being more pronounced in transgenic mice) was observed. Pontine nuclei, the affected tissue in transgenic mice, displayed 1.5 times less copies of mtDNA than nonaffected brain tissue hippocampus (odds ratio = 1.21). Pontine nuclei displayed the highest percentage of mtDNA deletions (6.05% more in transgenic mice). CONCLUSION: These results suggest that mtDNA damage is related to the initiation of the phenotype in transgenic mice; mtDNA 3,867-bp deletions may be a biomarker of the initial stages of the disease.This study was supported by the following grants: DRCT Postdoctoral fellowship to N.K. (M3.1.7/F/002/2008), FCT Postdoctoral fellowship to T.C. (SFRH/BPD/38659/2007) and C.B. (SFRH/BPD/63121/2009), FCT research grants to S.S. (PTDC/SAU-GMG/64076/2006) and A.S.F. (PIC/IC/83013/2007)

Organizational and medical technologies for the optimization of preconception preparation in women with heart defects

The current protocol of preconception preparation in patients with congenital heart disease does not take into account the stratification of patients according to the modified WHO classification and the medical and social characteristics of these women, leading to the formation of complications of gestation. We propose an algorithm for pre-conceptual preparation in patients with CHD, which includes general measures and personified preconception preparation in patients of different risks, depending on their clinical and anamnestic features. Based on the results of an evaluation of the effectiveness of the proposed algorithm, it is shown that it reliably reduces the number of serious pregnancy complications such as pregnancy anemia and placental disorders, which in turn leads to an improvement in perinatal outcomes.Существующий сегодня протокол прегравидарной подготовки у пациенток с врожденными пороками сердца не учитывает стратификацию пациенток по группам материнского риска в соответствии с модифицированной классификацией ВОЗ и медико-социальные особенности этих женщин, приводящие к формированию осложнений гестации. Нами предложен алгоритм преконцепционной подготовки у пациенток с ВПС, предусматривающий мероприятия общего характера и персонифицированной прегравидарной подготовки у пациенток различного риска в зависимости от их клинико-анамнестических особенностей. По результатам проведенной оценки эффективности предложенного алгоритма показано, что он достоверно снижает количество таких серьезных осложнений беременности, как анемия беременной и плацентарные нарушения, что, в свою очередь, приводит к улучшение перинатальных исходов

Specifics of text derivatives propositions in speech ontogeny

The proposed work analyzes the ratio of the primary written text and his oral derivative texts presented as oral paraphrases schoolchildren of the 5th grade of educational texts in social science. The novelty of the work is to study the specifics of the generation of oral secondary texts in ontogen