Reconstruction and analysis of the gene regulatory network for cell wall function in Arabidopsis thaliana L. leaves in response to water deficit.

The plant cell wall represents the outer compartment of the plant cell, which provides a physical barrier and triggers signaling cascades under the influence of biotic and abiotic stressors. Drought is a factor that negatively affects both plant growth and development. Cell wall proteins (CWP) play an important role in the plant response to water deficit. The adaptation mechanisms of the cell wall to water loss are of interest for identifying important genetic factors determining plant drought resistance and provide valuable information on biomarkers for further selection aimed at increasing the yield of crop plants. Using ANDSystem, a gene network describing the regulation of CWPs under water restriction conditions was reconstructed. The analysis of the gene network and the transcriptome data analysis allowed prioritizing transcription factors (TF) based on their enrichment of differentially expressed genes regulated by them. As a result, scores were calculated, acting as indicators of the association of TFs with water deficit. On the basis of the score values, eight most significant TFs were selected. The highest priority was given to the TF GBF3. CWPs were prioritized according to the criterion of summing up the scores of transcription factors regulating these genes. Among the most prioritized CWPs were the AT5G03350 gene encoding a lectin-like protein, AT4G20860 encoding BBE-like 22 required for the oxidation of cellulose degradation products, and AT4G37800 encoding xyloglucan endotransglucosylase/ hydrolase 7. Overall, the implemented algorithm could be used for prediction of regulatory interactions between transcription factors and target genes encoding cell wall proteins in plants.

[N-aсetyltransferase (NAT2) gene polymorphism and gene network analysis]. / Polimorfizm variantov gena N-atsetiltransferazy 2 (NAT2) i analiz gennoi seti.

To search for new targets of therapy, it is necessary to reconstruct the gene network of the disease, and identify the interaction of genes, proteins, and drug compounds. Using the online bioinformatics tools we have analyzed the current data set related to the metabolism of xenobiotics, mediated by the N-acetyltransferase 2 (NAT2) gene. The study of allelic polymorphism of the NAT2 gene has a prognostic value, allowing to determine the risk of a number of oncological diseases, the degree of increased risk due to smoking and exposure to chemical carcinogens, including drugs. The aim of this study was to determine the frequencies of two important "slow" variants of the NAT2 gene (NAT2*5, rs1801280 and NAT2*7, rs1799931), which significantly affected the rate of xenobiotic acetylation among the indigenous Nenets population of Northern Siberia. The obtained frequencies of polymorphic variants among the Nenets occupy an intermediate value between those for Europeans and Asians, which might indicate specific features of adaptation. We present a model of the distribution of two polymorphic variants of the NAT2 gene involved in the biotransformation of xenobiotics to study the characteristics of their metabolism in the indigenous inhabitants of Yamal.

[Reconstruction of gene network associated with Parkinson disease for gene targets search]. / Rekonstruktsiia gennoi seti bolezni Parkinsona dlia poiska genov-mishenei.

Accumulation of genetic data in the field of Parkinson's disease research culminated in identifying risk factors and confident prediction of the disease occurrence. To find new gene-targets for diagnostics and therapy we have to reconstruct gene network of the disease, to cluster genes in the network, to reveal key (hub) genes with largest number of interactions in the network. Using the on-line bioinformatics tools OMIM, PANTHER, g:Profiler, GeneMANIA, and STRING-DB, we have analyzed the current array of data related to Parkinson's disease, calculated the categories of gene ontologies for a large list of genes, visualized them, and built gene networks containing the identified key objects and their relationships. However, translating the results into biological understanding is still a promising major challenge. The analysis of the genes associated with the disease, the assessment of their place in the gene network (connectivity) allows us to evaluate them as target genes for medicinal effects.

[Differential alternative splicing in brain regions of rats selected for aggressive behavior].

Profiles of alternative mRNA isoforms have been determined in three brain regions of rats from an aggressive and a tame line selected for 74 generations. Among 2319 genes with alternatively spliced exons, approximately 84% were confirmed by analyzing public databases. Based on Gene Ontology-guided clustering of alternatively spliced genes, it has been found that the sample was enriched in synapse-specific genes (FDR < 10^(-17)). Patterns of gene expression in the brains of animals with genetically determined high or low aggression were more frequently found to differ in the use of alternatively spliced exons than in animals environmentally conditioned for increased or lowered propensity to aggression. For the Adcyap1r1 gene, five alternatively spliced mRNA isoforms have been represented differentially in aggressive animals. A detailed analysis of the gene that encodes glutamate ionotropic receptor NMDA type subunit 1 (Grin1) has confirmed significant differences in the levels of its alternatively spliced isoforms in certain brain regions of tame and aggressive rats. These differences may affect the behavior in rats genetically selected for aggression levels.

[Computer methods of analysis of chromosome contacts in the cell nucleus based on sequencing technology data]. / Komp'iuternye metody analiza khromosomnykh kontaktov v iadre kletki po dannym tekhnologii sekvenirovaniia.

The study spatial chromosome structure and chromosome folding in the interphase cell nucleus is an important challenge of world science. Detection of eukaryotic genome regions that physically interact with each other could be done by modern sequencing technologies. A basic method of chromosome folding by total sequencing of contacting DNA fragments is HI-C. Long-range chromosomal interactions play an important role in gene transcription and regulation. The study of chromosome interactions, 3D (three-dimensional) genome structure and its effect on gene transcription allows revealing fundamental biological processes from a viewpoint of structural regulation and are important for cancer research. The technique of chromatin immunoprecipitation and subsequent sequencing (ChIP-seq) make possible to determine binding sites of transcription factors that regulate expression of eukaryotic genes; genome transcription factors binding maps have been. The ChIA-PET technology allows exploring not only target protein binding sites, but also pairs of such sites on proximally located and interacting with each other chromosomes co-located in three-dimensional space of the cell nucleus. Here we discuss the principles of the construction of genomic maps and matrices of chromosome contacts according to ChIA-PET and Hi-C data that capture the chromosome conformation and overview existing software for 3D genome analysis including in house programs of gene location analysis in topological domains.

Transcription factors for the modulation of pluripotency and reprogramming.

Pluripotency and self-renewal are the defining traits of embryonic stem cells (ESCs) and this status quo is maintained by the core transcription factors Oct4, Sox2, and Nanog. Genome-wide mapping of the binding sites of these pivotal factors and other ESC transcriptional regulators has unraveled the transcriptional network governing pluripotency. Strikingly, a sizeable fraction of the binding sites of Oct4 and Nanog are not conserved in mouse and human ESCs. Binding site turnover and the presence of species-specific transposable elements are some of the factors contributing to this disp arity. Hence, comparing human and mouse ESCs will shed new light on the design of transcriptional regulatory networks for pluripotency. Despite the significant differences among pluripotent mammalian stem cells, the same set of transcription factors (Oct4, Sox2, Klf4, and c-Myc) can be used to reprogram human and mouse somatic cells into induced pluripotent stem cells. Recent works also demonstrate that there are multiple ways of imparting pluripotency. For instance, the nuclear receptors Nr5a2 and Esrrb can, respectively, substitute for Oct4 and Klf4 in reprogramming. This chapter summarizes the different roles of transcription factors in the modulation of pluripotent states and in the induction of pluripotent phenotypes.

Search for Lorentz and CPT violation effects in Muon spin precession.

The spin precession frequency of muons stored in the (g-2) storage ring has been analyzed for evidence of Lorentz and CPT violation. Two Lorentz and CPT violation signatures were searched for a nonzero delta omega a(=omega a mu+ - omega a mu-) and a sidereal variation of omega a mu+/-). No significant effect is found, and the following limits on the standard-model extension parameters are obtained: bZ = -(1.0+/-1.1) x 10(-23) GeV; (m mu dZ0 + HXY)=(1.8+/-6.0) x 10(-23) GeV; and the 95% confidence level limits b perpendicular mu+ <1.4 x 10(-24) GeV and b perpendicular mu- <2.6 x 10(-24) GeV.

New method of measuring electric dipole moments in storage rings.

A new highly sensitive method of looking for electric dipole moments of charged particles in storage rings is described. The major systematic errors inherent in the method are addressed and ways to minimize them are suggested. It seems possible to measure the muon EDM to levels that test speculative theories beyond the standard model.

Complexity: an internet resource for analysis of DNA sequence complexity.

The search for DNA regions with low complexity is one of the pivotal tasks of modern structural analysis of complete genomes. The low complexity may be preconditioned by strong inequality in nucleotide content (biased composition), by tandem or dispersed repeats or by palindrome-hairpin structures, as well as by a combination of all these factors. Several numerical measures of textual complexity, including combinatorial and linguistic ones, together with complexity estimation using a modified Lempel-Ziv algorithm, have been implemented in a software tool called 'Complexity' (http://wwwmgs.bionet.nsc.ru/mgs/programs/low_complexity/). The software enables a user to search for low-complexity regions in long sequences, e.g. complete bacterial genomes or eukaryotic chromosomes. In addition, it estimates the complexity of groups of aligned sequences.

Measurement of the negative muon anomalous magnetic moment to 0.7 ppm.

The anomalous magnetic moment of the negative muon has been measured to a precision of 0.7 ppm (ppm) at the Brookhaven Alternating Gradient Synchrotron. This result is based on data collected in 2001, and is over an order of magnitude more precise than the previous measurement for the negative muon. The result a(mu(-))=11 659 214(8)(3) x 10(-10) (0.7 ppm), where the first uncertainty is statistical and the second is systematic, is consistent with previous measurements of the anomaly for the positive and the negative muon. The average of the measurements of the muon anomaly is a(mu)(exp)=11 659 208(6) x 10(-10) (0.5 ppm).

Measurement of the positive muon anomalous magnetic moment to 0.7 ppm.

A higher precision measurement of the anomalous g value, a(mu)=(g-2)/2, for the positive muon has been made at the Brookhaven Alternating Gradient Synchrotron, based on data collected in the year 2000. The result a(mu(+))=11 659 204(7)(5)x10(-10) (0.7 ppm) is in good agreement with previous measurements and has an error about one-half that of the combined previous data. The present world average experimental value is a(mu)(expt)=11 659 203(8)x10(-10) (0.7 ppm).

Precise measurement of the positive muon anomalous magnetic moment.

A precise measurement of the anomalous g value, a(mu) = (g-2)/2, for the positive muon has been made at the Brookhaven Alternating Gradient Synchrotron. The result a(mu+) = 11 659 202(14) (6) x 10(-10) (1.3 ppm) is in good agreement with previous measurements and has an error one third that of the combined previous data. The current theoretical value from the standard model is a(mu)(SM) = 11 659 159.6(6.7) x 10(-10) (0.57 ppm) and a(mu)(exp) - a(mu)(SM) = 43(16) x 10(-10) in which a(mu)(exp) is the world average experimental value.

Freezing of gait in patients with advanced Parkinson's disease.

BACKGROUND: Freezing of Gait (FOG) is one of the most disturbing and least understood symptom in advanced stage of Parkinson's disease (PD). The contribution of the underlying pathological process and the antiparkinsonian treatment to the development of FOG are controversial. OBJECTIVE: To study the relationships between clinical features of PD and therapeutic modalities in patients with advanced PD and FOG. METHODS: Consecutive patients with 5 years or more of PD symptoms (n = 172) (99 men) with mean age at symptoms onset of 58.3 +/- 13.2 years and mean symptoms duration of 11.8 +/- 5.6 years were studied. Clinical data were collected during the last office visit through physical examination, detailed history, review of patients' charts, and other documents. A patient was considered as "freezer" if he/she reported recent experience that the legs got stuck to the ground while trying to walk. The presence of dyskinesia, early morning dystonia or significant postural reflex abnormalities were assessed through history and neurological examination. Duration of treatment with antiparkinsonian drugs was calculated from history charts. Chi square and t test were used to compare the patients with and without FOG. Logistic regression was used for the comparison of association between the presence of FOG (dependent variable) disease duration and disease stage (explanatory variables) and duration of treatment with anti-parkinsonian drugs. RESULTS: The study population consisted of 45 patients at Hoehn and Yahr (H&Y) stage 2.5 (26%), 104 patients at stage 3 (60.5%), and 23 patients at H&Y stages 4-5 (13.5%). Ninety one patients (53%) reported FOG at the time of the study. Severity of the disease expressed by H&Y stage at "off" was a significant contributing factor for FOG with a significant trend (z = 4.38, p < 0.0001), as was longer duration of levodopa treatment, and confirmed by FOG using the multivariate logistic regression (p = 0.01 and p = 0.004, respectively). Using a univariate model, longer duration of treatment with dopamine agonists contribute to the appearance of FOG (p = 0.07) while longer duration of amantadine treatment decreased the appearance of FOG (p = 0.09). There was a significant association between FOG and the presence of dyskinesia (p < 0.002), early morning foot dystonia (p < 0.003) and significant postural instability (p < 0.0005). CONCLUSION: FOG is a common symptom in advanced PD. It is mainly related to disease progression and levodopa treatment.

Anal sphincter EMG does not distinguish between multiple system atrophy and Parkinson's disease.

Clinical distinction of multiple system atrophy (MSA) from Parkinson's disease (PD) is often difficult. Several recent reports indicate that objective classification may be accomplished using electromyographic (EMG) testing of the anal or urethral sphincters, but some authors have found that these tests are not reliable for this purpose. We studied 13 patients with PD and 10 with probable MSA, as diagnosed by consensus of four movement disorders specialists, according to accepted clinical criteria. Anal sphincter EMG was performed blind to the clinical diagnosis. We found no significant differences in the mean duration of motor unit potentials (MUPs), mean MUP amplitude, or prevalence of polyphasic potentials, satellite potentials, very long duration MUPs, or spontaneous activity between the two groups. Thus, anal sphincter EMG does not differentiate between PD and MSA.

Risk factors for dementia, depression and psychosis in long-standing Parkinson's disease.

OBJECTIVES: To study the relationships between clinical features of Parkinson's disease (PD) and the development of dementia, depression or psychosis in patients with long-standing disease. BACKGROUND: The natural history of dementia and depression in PD, and its relation to psychosis in long standing PD, are unclear. METHOD: 172 consecutive patients (99 men and 73 women, mean age at symptoms onset 58.3 +/- 13.2 years) with 5 years or more of PD (mean symptom duration of 11.8 +/- 5.6 years) were studied. Clinical data were collected during the last office visit through physical examination, detailed history, review of patient charts and outside documents. Dementia and depression were diagnosed according to DSM-IV criteria, while psychosis was diagnosed if hallucinations or delusions were present. Chi-square and t tests were used to compare the patient characteristics among those with vs. those without mental complications of the disease at different disease stages. Logistic regression was used for the comparison of associations between the presence of dementia or depression (dependent variable) and age at onset of PD, duration of PD and disease staging (explanatory variables). RESULTS: The study population consisted of 45 patients at Hoehn & Yahr (H&Y) stage < or = 2.5 (26%), 104 patients at stage 3 (60.5%) and 23 patients at H&Y stage 4-5 (13.5%). Sixty one patients (36%) had dementia, 55 patients had depression (33%) and 50 patients (27%) had psychosis. Dementia and depression were significantly associated with disease severity as reflected in the H&Y scale (P = 0.0003, Z = 3.59; P = 0.006, Z = 3.22, respectively). These associations were significant also for the older age of PD onset (> or = 59 years n = 89) subgroup (p = 0.001, Z = 3.2 for dementia and p = 0.02, Z = 2.9 for depression), but not for younger onset cases (< 59 years n = 83). Dementia was significantly associated with older age of PD onset (beta = 0.04, p = 0.009) while depression was inversely associated with age of PD onset (beta = -0.04, p = 0.02). The presence of dementia was also significantly associated with depression (beta = 1.49, p = 0.0006). Dementia and depression were found to be independent explanatory variables for the development of psychosis (logistic regression, odds ratio (OR) = 26.0, p < 0.0001; OR = 10.2, p < 0.0001, respectively). In patients with younger age of PD onset, depression more than dementia was strongly correlated with the appearance of psychosis. CONCLUSION: Dementia in PD was related to older age of symptoms onset and old age. Depression was associated with dementia or early age of PD onset. Depression seemed to contribute to the appearance of psychosis even more than dementia, especially in patients with younger age of symptoms onset.

Near doubling of heart rate after intravenous verapamil for treatment of atrial fibrillation without preexcitation.

Initial treatment of atrial fibrillation often involves pharmacological therapy to control ventricular response. While verapamil is usually safe and effective when used for this purpose, we report a proarrhythmic response. In this report a 30-year-old female presented with palpitations associated with atrial fibrillation and a ventricular response of 145 beats/min. Soon after she was given 5 mg of intravenous verapamil her ECG documented a regular wide QRS tachycardia at 290 beats/min. After 7 seconds the rhythm returned to an irregularly irregular narrow QRS tachycardia at 125-150 beats/min. At a later electrophysiology study there was neither evidence of preexcitation nor inducible supraventricular or ventricular tachycardia. These data suggest that verapamil may have been associated with acceleration of the heart rate. The mechanism of proarrhythmia may be related to an alteration in the atrial rhythm from atrial fibrillation to atrial flutter, with additional factors as well.

Clinical assessment of adrenergic tone and responsiveness to beta-blocker therapy in patients with symptomatic ventricular tachycardia and no apparent structural heart disease.

To further define the relation between changing adrenergic tone, beta-blocker therapy, and clinical ventricular tachycardia (VT), we evaluated these factors in 35 patients with VT unrelated to coronary artery disease or ventricular dysfunction. Testing included Holter monitoring (91% had VT), exercise test (69% had VT), Adrenergic responsiveness of VT was graded according to diurnal variation, response to exercise, isoproterenol infusion, and response to beta-blockers. beta-Blockers were effective and well tolerated in this population. There was also a predictable relation between changing adrenergic tone and the arrhythmia response to beta-blocker therapy.

Is the time domain signal-averaged electrocardiogram helpful in patients with ventricular tachycardia without apparent structural heart disease?

The signal-average electrocardiogram (SAECG) has been a screening method for identifying patients at risk for ventricular tachycardia (VT) in the setting of coronary artery disease (CAD). Its significance in patients with VT unrelated to CAD or left ventricular dysfunction is undetermined. In order to define the value of SAECG in this patient population further, we compared the time domain SAECG at 25, 40, and 80 Hz filters in 35 patients with clinically symptomatic VT in the absence of structural heart disease was compared with 10 normal controls and 10 patients with CAD and inducible VT. SAECG data in patients without structural heart disease were intermediate between normal controls and patients with CAD. No single or combined SAECG criterion helped to differentiate between patients with inducible and noninducible VT. There was no concordance to other arrhythmia testing. It was concluded that signal-averaged electrocardiography may have little screening value in VT unrelated to CAD or left ventricular dysfunction.