OrgConv: detection of gene conversion using consensus sequences and its application in plant mitochondrial and chloroplast homologs

<p>Abstract</p> <p>Background</p> <p>The ancestry of mitochondria and chloroplasts traces back to separate endosymbioses of once free-living bacteria. The highly reduced genomes of these two organelles therefore contain very distant homologs that only recently have been shown to recombine inside the mitochondrial genome. Detection of gene conversion between mitochondrial and chloroplast homologs was previously impossible due to the lack of suitable computer programs. Recently, I developed a novel method and have, for the first time, discovered recurrent gene conversion between chloroplast mitochondrial genes. The method will further our understanding of plant organellar genome evolution and help identify and remove gene regions with incongruent phylogenetic signals for several genes widely used in plant systematics. Here, I implement such a method that is available in a user friendly web interface.</p> <p>Results</p> <p><monospace>OrgConv</monospace> (<b>Org</b>anellar <b>Conv</b>ersion) is a computer package developed for detection of gene conversion between mitochondrial and chloroplast homologous genes. <monospace>OrgConv</monospace> is available in two forms; source code can be installed and run on a Linux platform and a web interface is available on multiple operating systems. The input files of the feature program are two multiple sequence alignments from different organellar compartments in FASTA format. The program compares every examined sequence against the consensus sequence of each sequence alignment rather than exhaustively examining every possible combination. Making use of consensus sequences significantly reduces the number of comparisons and therefore reduces overall computational time, which allows for analysis of very large datasets. Most importantly, with the significantly reduced number of comparisons, the statistical power remains high in the face of correction for multiple tests.</p> <p>Conclusions</p> <p>Both the source code and the web interface of <monospace>OrgConv</monospace> are available for free from the <monospace>OrgConv</monospace> website <url>http://www.indiana.edu/~orgconv</url>. Although <monospace>OrgConv</monospace> has been developed with main focus on detection of gene conversion between mitochondrial and chloroplast genes, it may also be used for detection of gene conversion between any two distinct groups of homologous sequences.</p

The interest of gait markers in the identification of subgroups among fibromyalgia patients

<p>Abstract</p> <p>Background</p> <p>Fibromyalgia (FM) is a heterogeneous syndrome and its classification into subgroups calls for broad-based discussion. FM subgrouping, which aims to adapt treatment according to different subgroups, relies in part, on psychological and cognitive dysfunctions. Since motor control of gait is closely related to cognitive function, we hypothesized that gait markers could be of interest in the identification of FM patients' subgroups. This controlled study aimed at characterizing gait disorders in FM, and subgrouping FM patients according to gait markers such as stride frequency (SF), stride regularity (SR), and cranio-caudal power (CCP) which measures kinesia.</p> <p>Methods</p> <p>A multicentre, observational open trial enrolled patients with primary FM (44.1 ± 8.1 y), and matched controls (44.1 ± 7.3 y). Outcome measurements and gait analyses were available for 52 pairs. A 3-step statistical analysis was carried out. A preliminary single blind analysis using k-means cluster was performed as an initial validation of gait markers. Then in order to quantify FM patients according to psychometric and gait variables an open descriptive analysis comparing patients and controls were made, and correlations between gait variables and main outcomes were calculated. Finally using cluster analysis, we described subgroups for each gait variable and looked for significant differences in self-reported assessments.</p> <p>Results</p> <p>SF was the most discriminating gait variable (73% of patients and controls). SF, SR, and CCP were different between patients and controls. There was a non-significant association between SF, FIQ and physical components from Short-Form 36 (p = 0.06). SR was correlated to FIQ (p = 0.01) and catastrophizing (p = 0.05) while CCP was correlated to pain (p = 0.01). The SF cluster identified 3 subgroups with a particular one characterized by normal SF, low pain, high activity and hyperkinesia. The SR cluster identified 2 distinct subgroups: the one with a reduced SR was distinguished by high FIQ, poor coping and altered affective status.</p> <p>Conclusion</p> <p>Gait analysis may provide additional information in the identification of subgroups among fibromyalgia patients. Gait analysis provided relevant information about physical and cognitive status, and pain behavior. Further studies are needed to better understand gait analysis implications in FM.</p

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

The serotoninergic receptors of human dendritic cells: identification and coupling to cytokine release.

The neurotransmitter 5-hydroxytryptamine (5-HT), commonly known as serotonin, is stored at peripheral sites in mast cells and released from this peripheral source upon IgE cross-linking. In this study, we investigated the expression of serotoninergic receptors (5-HTR), the signaling pathway, and biological activity of 5-HT on human dendritic cells (DC), showing that immature and mature DC expressed mRNA for different serotoninergic receptors. Thereby, the mRNA of 5-HTR(1B), 5-HTR(1E), 5-HTR(2A), 5-HTR(2B), one splicing variant of the 5-HTR(3), 5-HTR(4), and 5-HTR(7) receptors were detected. Immature DC preferentially expressed mRNA for the heptahelical 5-HTR(1B), 5-HTR(1E), and 5-HTR(2B) receptors, while mature DC mostly expressed 5-HTR(4) and 5-HTR(7). The mRNA expression level of the ligand-gated cation channel 5-HTR(3) and the heptahelical 5-HTR(2A) did not significantly change during maturation. Isotype-selective receptor agonists allowed us to show that 5-HT stimulated 5-HTR(3)-dependent Ca(2+) influx in immature and mature DC. Moreover, we revealed that 5-HTR(1) and 5-HTR(2) receptor stimulation induced intracellular Ca(2+) mobilization via G(i/o) proteins in immature, but not mature, DC. Activation of 5-HTR(4) and 5-HTR(7) induced cAMP elevation in mature DC. Functional studies indicated that activation of 5-HTR(4) and 5-HTR(7) enhanced the release of the cytokines IL-1beta and IL-8, while reducing the secretion of IL-12 and TNF-alpha in mature DC. In summary, our study shows that 5-HT stimulated, in a maturation-dependent manner, different signaling pathways in DC. These data point to a role for 5-HT in regulating the immune response at peripheral sites

Heart Rhythm

BACKGROUND: Experimental data suggest that use of cryoablation in pulmonary vein isolation (PVI) is associated with less cell damage and less thrombus formation compared to radiofrequency (RF) energy. OBJECTIVE: The purpose of this study was to test the hypothesis that cryoablation significantly reduces markers of cell damage, platelet activation, and inflammation in patients undergoing PVI for treatment of atrial fibrillation (AF). METHODS: Sixty patients with symptomatic drug-resistant AF (age 56 +/- 9 years, 48 males, 38 with paroxysmal AF) were randomly assigned to undergo PVI using either an open irrigated-tip RF catheter or a cryoballoon. Markers of cell damage (high-sensitive troponin T [hs-TnT], microparticles), platelet activation (platelet reactivity by aggregometry, expression of platelet surface proteins P-selectin and activated glycoprotein [GP] IIb/IIIa), and inflammatory response (high-sensitive C-reactive protein [hs-CRP]) were determined before and up to 48 hours after the procedure. RESULTS: PVI resulted in a significant rise in hs-TnT, microparticles, markers of platelet activation, and hs-CRP over time, with distinct temporal patterns for each parameter. However, after Bonferroni correction for repeated measurements, no significant differences were noted in these parameters between patients treated with cryoablation or RF energy. Procedural time was significantly shorter in patients treated with cryoballoon (177 +/- 30 minutes vs 200 +/- 46 minutes, P = .03), with no differences in fluoroscopic time, periprocedural complications, or success rate. CONCLUSION: Cryoablation and RF energy result in a comparable rise of markers of cell damage, platelet activation and inflammatory response. The data do not support the concept of an improved safety profile for cryoablation in PVI

076 Кваліфікаційна робота бакалавра "Обґрунтування економічних рішень у сфері управління персоналом підприємства"

Об’єкт дослідження – процеси управління персоналом на підставі стимулювання мотивації праці працівників підприємства малого бізнесу. Предмет дослідження – економічна складова системи стимулювання праці персоналу підприємства малого бізнесу «Видавництво «Грані»». Мета роботи – обґрунтування та розробка рекомендацій щодо вдосконалення економічного управління персоналом на підставі стимулювання мотивації праці працівників підприємства малого бізнесу «Видавництво« Грані»». Методи дослідження – метод наукового узагальнення і систематизації, статистичний, аналітичний, графічний методи. Отримані результати. У першому розділі здійснена характеристика і оцінка методів стимулювання мотивації до праці персоналу малого підприємства, виконана аналіз факторів, що впливають на ефективність стимулювання праці персоналу бізнес-підприємства. У другому розділі здійснено аналіз організаційно-економічного стану малого підприємства «Видавництво« Грані»», виконана оцінка традиційної системи стимулювання і мотивації праці на малому підприємстві. У третьому розділі наведено напрями підвищення ефективності економічного управління персоналом на підставі стимулювання мотивації працівників «Видавництво« Грані»». Сфера практичного застосування результатів роботи – підприємства малого бізнесу в сфері поліграфічного виробництва