208 research outputs found

    Mitochondrial TERT enhances mitochondria functions in vivo by protecting mitochondrial DNA integrity from oxidative damage : meeting abstract

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    Mitochondria are essential for respiration and oxidative phosphorylation. Mitochondrial dysfunction due to aging processes is involved in pathologies and pathogenesis of a series of cardiovascular disorders. New results accumulate showing that the enzyme telomerase with its catalytic subunit telomerase reverse transcriptase (TERT) has a beneficial effect on heart functions. The benefit of short-term running of mice for heart function is dependent on TERT expression. TERT can translocate into the mitochondria and mitochondrial TERT (mtTERT) is protective against stress induced stimuli and binds to mitochondrial DNA (mtDNA). Because mtDNA is highly susceptible to damage produced by reactive oxygen species (ROS) which are generated in close proximity to the respiratory chain, the aim of this study was to determine the functions of mtTERT in vivo and in vitro. Therefore, mitochondria from hearts of adult, 2nd generation TERT-deficient mice (TERT -/-) and wt littermates were isolated and state 3 respiration was measured. Strikingly mitochondria from TERT -/- revealed a significantly lower state 3 respiration (TERTwt: 987 +/- 72 pmol/s*mg vs. TERT-/-: 774 +/- 38 pmol/s*mg, p < 0.05, n = 5). These results demonstrated that TERT -/- mice have a so far undiscovered heart phenotype. In contrast mitochondria isolated from liver tissues did not show any differences. To get further insights in the molecular mechanisms, we reduced endogenous TERT levels by shRNA and measured mitochondrial reactive oxygen species (mtROS). mtROS were increased after ablation of TERT (scrambled: 4.98 +/- 1.1% gated vs. shTERT: 2.03 +/- 0.7% gated, p < 0.05, n = 4). We next determined mtDNA deletions, which are caused by mtROS. Semiquantitative realtime PCR of mtDNA deletions revealed that mtTERT protects mtDNA from oxidative damage. To analyze whether mitochondrial integrity is required to protect from apoptosis, vectors with mitochondrially targeted TERT (mitoTERT) and wildtype TERT (wtTERT) were transfected and apoptosis was measured. mitoTERT showed the most prominent protective effect on H2O2 induced apoptosis. In conclusion, mtTERT has a protective role in mitochondria by importantly contributing to mtDNA integrity and thereby enhancing respiration capacity of the heart

    Pistil transcriptome analysis to disclose genes and gene products related to aposporous apomixis in Hypericum perforatum L.

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    Unlike sexual reproduction, apomixis encompasses a number of reproductive strategies,which permit maternal genome inheritance without genetic recombination and syngamy. The key biological features of apomixis are the circumvention of meiosis (i.e., apomeiosis),the differentiation of unreduced embryo sacs and egg cells, and their autonomous development in functional embryos through parthenogenesis, and the formation of viable endosperm either via fertilization-independent means or following fertilization with a sperm cell. Despite the importance of apomixis for breeding of crop plants and although much research has been conducted to study this process, the genetic control of apomixis is still not well understood. Hypericum perforatum is becoming an attractive model system for the study of aposporous apomixis. Here we report results from a global gene expression analysis of H. perforatum pistils collected from sexual and aposporous plant accessions for the purpose of identifying genes, biological processes and molecular functions associated with the aposporous apomixis pathway. Across two developmental stages corresponding to the expression of aposporous apomeiosis and parthenogenesis in ovules, a total of 224 and 973 unigenes were found to be significantly up- and down-regulated with a fold change >= 2 in at least one comparison, respectively.Differentially expressed genes were enriched for multiple gene ontology (GO) terms,including cell cycle, DNA metabolic process, and single-organism cellular process. For molecular functions, the highest scores were recorded for GO terms associated withDNA binding, DNA (cytosine-5-)-methyltransferase activity and heterocyclic compound binding. As deregulation of single components of the sexual developmental pathway is believed to be a trigger of the apomictic reproductive program, all genes involved in sporogenesis, gametogenesis and response to hormonal stimuli were analyzed in great detail. Overall, our data suggest that phenotypic expression of apospory is concomitant with the modulation of key genes involved in the sexual reproductive pathway. Furthermore, based on gene annotation and co-expression, we underline a putative role of hormones and key actors playing in the RNA-directed DNA methylation pathway in regulating the developmental changes occurring during aposporous apomixis in H. perforatum

    Implementation of Warehouse Management System in a Manufacturing Company

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    Bakalářská práce se zabývá implementací systému SAP ve skladovém hospodářství distribučního skladu výrobní společnosti. Práce je rozdělena na čtyři části, první část se zabývá současnými trendy v oblasti logistiky a skladového hospodářství. Druhá část práce pojednává o vývoji podnikových informačních systémů a o logistických procesech v podniku. Třetí část je věnována systému SAP a jeho historickém vývoji, vlastnostech systému a struktuře. Čtvrtá, praktická část práce, je věnována implementaci systému do skladového hospodářství v expedičním skladu výrobní společnosti, popisu stavu před implementací systému a po jejím provedení.This bachelor thesis deals with the implementation of SAP in the management of distribution warehouse of a manufacturing company. The work is divided into four parts, the first part deals with current trends in logistics and warehouse management. The second part deals with the development of business information systems and the logistics processes in the company. The third part is devoted to the SAP system and its historical development, structure and properties of the system used by company. Fourth, the practical part of the work, is devoted to the implementation of warehouse management in the distribution warehouse of manufacturing company, describing the situation before the implementation of the system and after its implementation

    Telomerase as a Therapeutic Target in Cardiovascular Disease.

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    Shortened telomeres have been linked to numerous chronic diseases, most importantly coronary artery disease, but the underlying mechanisms remain ill defined. Loss-of-function mutations and deletions in telomerase both accelerate telomere shortening but do not necessarily lead to a clinical phenotype associated with atherosclerosis, questioning the causal role of telomere length in cardiac pathology. The differential extranuclear functions of the 2 main components of telomerase, telomerase reverse transcriptase and telomerase RNA component, offer important clues about the complex relationship between telomere length and cardiovascular pathology. In this review, we critically discuss relevant preclinical models, genetic disorders, and clinical studies to elucidate the impact of telomerase in cardiovascular disease and its potential role as a therapeutic target. We suggest that the antioxidative function of mitochondrial telomerase reverse transcriptase might be atheroprotective, making it a potential target for clinical trials. Graphic Abstract: A graphic abstract is available for this article.Work in the VA laboratory is supported by the Spanish Ministerio de Ciencia e Innovación (MCIN) (PID2019-108489RB-I00) and the Instituto de Salud Carlos III (ISCIII) (AC17/00067) with co-funding from the European Regional Development Fund (ERDF, “Una manera de hacer Europa”), and the Progeria Research Foundation (Award PRF 2019–77). The CNIC is supported by the ISCIII, the MCIN, and the Pro CNIC Foundation. I. Spyridopoulos is funded by the British Heart Foundation (PG/18/25/33587) and National Institute for Health Research (NIHR) Newcastle Biomedical Research Centre based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University. The work of J. Haendeler and J. Altschmied is in part supported by the Deutsche Forschungsgemeinschaft (DFG) SFB1116, A04 (J. Haendeler and J. Altschmied), HA2868/14-1 (J. Haendeler) and AL288/5-1 (J. Altschmied). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health’. I. Spyridopoulos also receives a grant from TA-Science for the TACTIC trial (Telomerase Activator to Reverse Immunosenescence in Acute Coronary Syndrome).S

    Nuclear-mitochondrial crosstalk – role in aging processes

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    Signal transduction, receptors, mediators and genes: younger than ever - the 13th meeting of the Signal Transduction Society focused on aging and immunology

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    The 13th meeting of the Signal Transduction Society was held in Weimar, from October 28 to 30, 2009. Special focus of the 2009 conference was "Aging and Senescence", which was co-organized by the SFB 728 "Environmentally-Induced Aging Processes" of the University of DĂĽsseldorf and the study group 'Signal Transduction' of the German Society for Cell Biology (DGZ). In addition, several other areas of signal transduction research were covered and supported by different consortia associated with the Signal Transduction Society including the long-term associated study groups of the German Society for Immunology and the Society for Biochemistry and Molecular Biology, and for instance the SFB/Transregio 52 "Transcriptional Programming of Individual T Cell Subsets" located in WĂĽrzburg, Mainz and Berlin. The different research areas that were introduced by outstanding keynote speakers attracted more than 250 scientists, showing the timeliness and relevance of the interdisciplinary concept and exchange of knowledge during the three days of the scientific program. This report gives an overview of the presentations of the conference

    Sequencing of 15 622 Gene-bearing BACs Clarifies the Gene-dense Regions of the Barley Genome

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    Barley (Hordeum vulgare L.) possesses a large and highly repetitive genome of 5.1 Gb that has hindered the development of a complete sequence. In 2012, the International Barley Sequencing Consortium released a resource integrating whole-genome shotgun sequences with a physical and genetic framework. However, because only 6278 bacterial artificial chromosome (BACs) in the physical map were sequenced, fine structure was limited. To gain access to the gene-containing portion of the barley genome at high resolution, we identified and sequenced 15 622 BACs representing the minimal tiling path of 72 052 physical-mapped gene-bearing BACs. This generated ~1.7 Gb of genomic sequence containing an estimated 2/3 of all Morex barley genes. Exploration of these sequenced BACs revealed that although distal ends of chromosomes contain most of the gene-enriched BACs and are characterized by high recombination rates, there are also gene-dense regions with suppressed recombination. We made use of published map-anchored sequence data from Aegilops tauschii to develop a synteny viewer between barley and the ancestor of the wheat D-genome. Except for some notable inversions, there is a high level of collinearity between the two species. The software HarvEST:Barley provides facile access to BAC sequences and their annotations, along with the barley–Ae. tauschii synteny viewer. These BAC sequences constitute a resource to improve the efficiency of marker development, map-based cloning, and comparative genomics in barley and related crops. Additional knowledge about regions of the barley genome that are gene-dense but low recombination is particularly relevant
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