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Sample records for bovine mitochondrial factor

  1. Increase of mitochondrial DNA content and transcripts in early bovine embryogenesis associated with upregulation of mtTFA and NRF1 transcription factors

    Directory of Open Access Journals (Sweden)

    Heyman Yvan

    2005-11-01

    Full Text Available Abstract Background Recent work has shown that mitochondrial biogenesis and mitochondrial functions are critical determinants of embryonic development. However, the expression of the factors controlling mitochondrial biogenesis in early embryogenesis has received little attention so far. Methods We used real-time quantitative PCR to quantify mitochondrial DNA (mtDNA in bovine oocytes and in various stages of in vitro produced embryos. To investigate the molecular mechanisms responsible for the replication and the transcriptional activation of mtDNA, we quantified the mRNA corresponding to the mtDNA-encoded cytochrome oxidase 1 (COX1, and two nuclear-encoded factors, i.e. the Nuclear Respiratory Factor 1 (NRF1, and the nuclear-encoded Mitochondrial Transcription Factor A (mtTFA. Results Unlike findings reported in mouse embryos, the mtDNA content was not constant during early bovine embryogenesis. We found a sharp, 60% decrease in mtDNA content between the 2-cell and the 4/8-cell stages. COX1 mRNA was constant until the morula stage after which it increased dramatically. mtTFA mRNA was undetectable in oocytes and remained so until the 8/16-cell stage; it began to appear only at the morula stage, suggesting de novo synthesis. In contrast, NRF1 mRNA was detectable in oocytes and the quantity remained constant until the morula stage. Conclusion Our results revealed a reduction of mtDNA content in early bovine embryos suggesting an active process of mitochondrial DNA degradation. In addition, de novo mtTFA expression associated with mitochondrial biogenesis activation and high levels of NRF1 mRNA from the oocyte stage onwards argue for the essential function of these factors during the first steps of bovine embryogenesis.

  2. Characteristics of bovine oocytes with different meiotic competence in terms of their mitochondrial status and expression of nuclear-encoded factors

    Czech Academy of Sciences Publication Activity Database

    Machatková, M.; Jeseta, M.; Hulínská, P.; Knitlová, D.; Němcová, Lucie; Kaňka, Jiří

    2012-01-01

    Roč. 47, č. 5 (2012), s. 806-814. ISSN 0936-6768 R&D Projects: GA MZe QI91A018 Grant ostatní: GA ČR(CZ) GD523/08/H064 Institutional research plan: CEZ:AV0Z50450515 Keywords : bovine oocytes * mitochondrial status * nuclear - encoded factors Subject RIV: GI - Animal Husbandry ; Breeding Impact factor: 1.392, year: 2012

  3. Association between mitochondrial DNA haplotype compatibility and increased efficiency of bovine intersubspecies cloning

    Institute of Scientific and Technical Information of China (English)

    Hao Yan; Zhonghai Yan; Qingwen Ma; Fei Jiao; Shuzhen Huang; Fanyi Zeng; Yitao Zeng

    2011-01-01

    Reconstructed embryos derived from intersubspecies somatic cell nuclear transfer (SCNT) have poorer developmental potential than those from intrasubspecies SCNT. Based on our previous study that Holstein dairy bovine (HD) mitochondrial DNA (mtDNA) haplotype compatibility between donor karyoplast and recipient cytoplast is crucial for SCNT embryo development, we performed intersubspecies SCNT using HD as donor karyoplast and Luxi yellow heifer (LY) as recipient cytoplast according to mtDNA haplotypes determined by polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP) analysis. The results demonstrated that intersubspecies mtDNA homotype SCNT embryos had higher pre- and post-implantation developmental competence than intrasubspecies mtDNA heterotype embryos as well as improved blastocyst reprogramming status, including normal H3K9 dimethylation pattern and promoter hypomethylation of pluripotent genes such as Oct4 and Sox2, suggesting that intersubspecies SCNT using LY oocytes maintains HD cloning efficiency and may reprogram HD nuclei to develop into a normal cloned animal ultimately. Our results indicated that karyoplast-cytoplast interactions and mtDNA haplotype compatibility may affect bovine intersubspecies SCNT efficiency. This study on bovine intersubspecies SCNT is valuable for understanding the mechanisms of mtDNA haplotype compatibility between karyoplast and cytoplast impacting the bovine SCNT efficiency, and provides an alternative and economic resource for HD cloning.

  4. Arrangement of electron transport chain components in bovine mitochondrial supercomplex I1III2IV1

    OpenAIRE

    Althoff, Thorsten; Mills, Deryck J; Popot, Jean-Luc; Kühlbrandt, Werner

    2011-01-01

    The respiratory chain in the inner mitochondrial membrane contains three large multi-enzyme complexes that together establish the proton gradient for ATP synthesis, and assemble into a supercomplex. A 19-Å 3D map of the 1.7-MDa amphipol-solubilized supercomplex I1III2IV1 from bovine heart obtained by single-particle electron cryo-microscopy reveals an amphipol belt replacing the membrane lipid bilayer. A precise fit of the X-ray structures of complex I, the complex III dimer, and monomeric co...

  5. NP04634 prevents cell damage caused by calcium overload and mitochondrial disruption in bovine chromaffin cells.

    Science.gov (United States)

    Valero, Teresa; del Barrio, Laura; Egea, Javier; Cañas, Noelia; Martínez, Ana; García, Antonio G; Villarroya, Mercedes; López, Manuela G

    2009-04-01

    Marine sponges are becoming a rich source of potential new medicines. NP04634 is a synthetic derivative of 11,19 dideoxyfistularin, a natural product of the Mediterranean sponge Aplysina cavernicola. We report the cytoprotective effects of this new compound in isolated bovine chromaffin cells exposed to cytotoxic stimuli that have been related to neuronal cell death, i.e. Ca(2+) overload and mitochondrial dysfunction. Cell death was achieved by: (i) causing Ca(2+) overload through voltage-dependent calcium channels by exposing the cells to 30 mM K(+), 5 mM Ca(2+) plus 0.3 microM FPL64176 (an L-type Ca(2+)-channel activator); (ii) incubating the cells with veratridine, causing cytosolic Ca(2+) concentration ([Ca(2+)](c)) oscillations and mitochondrial disruption; and (iii) blocking mitochondrial complexes I and V using a combination of 30 microM rotenone and 10 microM oligomycin. At 10 microM, NP04634 caused significant protection against 30K(+)/5Ca(2+)/FPL-induced toxicity. NP04634 caused a concentration-dependent reduction in [Ca(2+)](c) induced by 70 mM K(+) in cells loaded with Fluo-4; maximum blockade was 67% at 30 microM. Veratridine caused continuous [Ca(2+)](c) oscillations that translated into 43.4+/-2% cell death. In this model, NP04634 caused 42% and 67% protection at 3 and 10 microM, respectively. NP04634 reduced [Ca(2+)](c) oscillations and mitochondrial depolarization caused by veratridine. NP04634 at 10 microM also protected against mitochondrial disruption caused by rotenone plus oligomycin. In conclusion, NP04634 is a novel compound of marine origin with cytoprotective properties that might have potential therapeutic implications under pathological circumstances involving Ca(2+) overload and mitochondrial disruption, such as in certain neurodegenerative diseases and/or stroke. PMID:19233161

  6. Mitochondrial transcription termination factor 2 binds to entire mitochondrial DNA and negatively regulates mitochondrial gene expression

    Institute of Scientific and Technical Information of China (English)

    Weiwei Huang; Min Yu; Yang Jiao; Jie Ma; Mingxing Ma; Zehua Wang; Hong Wu; Deyong Tan

    2011-01-01

    Mitochondrial transcription termination factor 2 (mTERF2) is a mitochondriai matrix protein that binds to the mitochondriai DNA.Previous studies have shown that overexpression of mTERF2 can inhibit cell proliferation, but the mechanism has not been well defined so far.This study aimed to present the binding pattern of mTERF2 to the mitochondrial DNA (mtDNA) in vivo, and investigated the biological function of mTERF2 on the replication of mtDNA, mRNA transcription, and protein translation.The mTERF2 binding to entire mtDNA was identified via the chromatin immunoprecipitation analysis.The mtDNA replication efficiency and expression levels of mitochondria genes were significantly inhibited when the mTERF2 was overexpressed in HeLa cells.The inhibition level of mtDNA content was the same with the decreased levels of mRNA and mitochondrial protein expression.Overall, the mTERF2 might be a cell growth inhibitor based on its negative effect on mtDNA replication, which eventually own-regulated all of the oxidative phosphorylation components in the mitochondria that were essential for the cell's energy metabolism.

  7. Exercise-induced mitochondrial biogenesis - with special reference to mitochondrial transcription factors and lipin-1

    OpenAIRE

    Wallman Appel, Susanna E

    2012-01-01

    Mitochondrial biogenesis is one prominent adaptation to endurance training in skeletal muscle tissue. An increased mitochondrial density of the muscle fibres contributes to an enhanced aerobic capacity and thereby to improved fatigueresistance. Multiple signalling pathways and transcriptional networks are involved in controlling mitochondrial biogenesis. The transcriptional co-regulator lipin-1 is one factor proposed to contribute, based on its ability to interact with PGC-1α a...

  8. Human mitochondrial transcription factor A reduction and mitochondrial dysfunction in Hashimoto's hypothyroid myopathy.

    OpenAIRE

    Siciliano, Gabriele; Monzani, Fabio; Manca, Maria Laura; Tessa, Alessandra; Caraccio, Nadia; Tozzi, Giulia; Piemonte, Fiorella; Mancuso, Michelangelo; Santorelli, Filippo Maria; Ferrannini, Eleuterio; Murri, Luigi

    2002-01-01

    BACKGROUND: Mitochondrial changes have been described in muscle tissue in acquired hypothyroidism. Among the molecular mechanisms by which thyroid hormones regulate expression of nuclear genes encoding for regulatory proteins of mitochondrial respiratory function, the mitochondrial transcription factor A (h-mtTFA) has been proposed to be a target of thyroid hormone action. The aim of this study has been to relate h-mtTFA levels in the skeletal muscle of patients affected by Hashimoto's hypoth...

  9. Mitochondrial integrity in a neonatal bovine model of right ventricular dysfunction.

    Science.gov (United States)

    Bruns, Danielle R; Brown, R Dale; Stenmark, Kurt R; Buttrick, Peter M; Walker, Lori A

    2015-01-15

    Right ventricular (RV) function is a key determinant of survival in patients with both RV and left ventricular (LV) failure, yet the mechanisms of RV failure are poorly understood. Recent studies suggest cardiac metabolism is altered in RV failure in pulmonary hypertension (PH). Accordingly, we assessed mitochondrial content, dynamics, and function in hearts from neonatal calves exposed to hypobaric hypoxia (HH). This model develops severe PH with concomitant RV hypertrophy, dilation, and dysfunction. After 2 wk of HH, pieces of RV and LV were obtained along with samples from age-matched controls. Comparison with control assesses the effect of hypoxia, whereas comparison between the LV and RV in HH assesses the additional impact of RV overload. Mitochondrial DNA was unchanged in HH, as was mitochondrial content as assessed by electron microscopy. Immunoblotting for electron transport chain subunits revealed a small increase in mitochondrial content in HH in both ventricles. Mitochondrial dynamics were largely unchanged. Activity of individual respiratory chain complexes was reduced (complex I) or unchanged (complex V) in HH. Key enzymes in the glycolysis pathway were upregulated in both HH ventricles, alongside upregulation of hypoxia-inducible factor-1α protein. Importantly, none of the changes in expression or activity were different between ventricles, suggesting the changes are in response to HH and not RV overload. Upregulation of glycolytic modulators without chamber-specific mitochondrial dysfunction suggests that mitochondrial capacity and activity are maintained at the onset of PH, and the early RV dysfunction in this model results from mechanisms independent of the mitochondria. PMID:25416385

  10. Factors affecting chromatin stability of bovine spermatozoa.

    Science.gov (United States)

    Khalifa, T A A; Rekkas, C A; Lymberopoulos, A G; Sioga, A; Dimitriadis, I; Papanikolaou, Th

    2008-03-01

    The structural stability of transcriptionally inert paternal chromatin is of vital importance for the fertilization process and early embryonic development. Accordingly, a series of eight experiments were conducted during a 7-month period to investigate: (1) effects of bull breed, individuality, successive ejaculations, semen quality characteristics (SQC), semen dilution rates and hypothermic storage of semen in a Tris-egg yolk extender on incidence of sperm nuclear chromatin instability (NCI), and (2) effects of the interaction between variation of NCI within a frozen ejaculate and variation of oocytes quality due to maturation time and/or season on the efficiency of in vitro embryo production (IVEP). Semen samples were collected once a week from six bulls using an AV and only ejaculates (n=220) of >0.30x10(9) sperm/ml and >or=60% motility were used. NCI was measured by: (1) detection of lysine-rich histones in sperm chromatin using aniline blue staining, (2) sperm susceptibility to acid-induced nuclear DNA denaturation in situ using acridine orange test, and (3) sperm susceptibility to nuclear chromatin decondensation (NCD). Bovine oocytes (n=695) were matured in vitro for 18 or 24 h, fertilized after sperm selection through a swim-up procedure and cultured for 72 h. The results showed that the 2nd ejaculates were superior to the 1st ones with respect to chromatin stability. Dilution of semen to 49.67+/-8.56x10(6) sperm/ml (1:19) decreased resistance of sperm to NCD. Cooling of semen had no significant effect on chromatin stability. Cryopreservation of semen augmented sperm vulnerability to DNA denaturation. Improvement of SQC (semen volume, sperm motility, velocity, viability and morphological normalcy) was generally concomitant with increase of sperm resistance to NCI. While Blonde d'Aquitaine bulls had a resistance to NCD higher than Limousine bulls in fresh semen, the former showed a greater susceptibility to DNA denaturation than the latter in cooled semen

  11. Characterization of the reaction of decoupling ubiquinone with bovine mitochondrial respiratory complex I.

    Science.gov (United States)

    Masuya, Takahiro; Okuda, Kenji; Murai, Masatoshi; Miyoshi, Hideto

    2016-08-01

    We previously produced the unique ubiquinone QT ("decoupling" quinone), the catalytic reduction of which in NADH-quinone oxidoreduction with bovine heart mitochondrial NADH-ubiquinone oxidoreductase (complex I) is completely decoupled from proton translocation across the membrane domain. This feature is markedly distinct from those of typical short-chain quinones such as ubiquinone-1. To further characterize the features of the QT reaction with complex I, we herein synthesized three QT analogs, QT2-QT4, and characterized their electron transfer reactions. We found that all aspects of electron transfer (e.g. electron-accepting activity and membrane potential formation) vary significantly among these analogs. The features of QT2 as decoupling quinone were slightly superior to those of original QT. Based on these results, we conclude that the bound positions of QTs within the quinone binding cavity susceptibly change depending on their side-chain structures, and the positions, in turn, govern the behavior of QTs as electron acceptors. PMID:27140857

  12. Mannheimia haemolytica Leukotoxin Induces Apoptosis of Bovine Lymphoblastoid Cells (BL-3) via a Caspase-9-Dependent Mitochondrial Pathway

    OpenAIRE

    Atapattu, Dhammika N.; Czuprynski, Charles J.

    2005-01-01

    Mannheimia haemolytica is a key pathogen in the bovine respiratory disease complex. It produces a leukotoxin (LKT) that is an important virulence factor, causing cell death in bovine leukocytes. The LKT binds to the β2 integrin CD11a/CD18, which usually activates signaling pathways that facilitate cell survival. In this study, we investigated mechanisms by which LKT induces death in bovine lymphoblastoid cells (BL-3). Incubation of BL-3 cells with a low concentration of LKT results in the act...

  13. Analysis of mitochondrial transcription factor A SNPs in alcoholic cirrhosis

    OpenAIRE

    Tang, Chun; LIU, HONGMING; TANG, YONGLIANG; Guo, Yong; LIANG, XIANCHUN; GUO, LIPING; Pi, Ruxian; Yang, Juntao

    2013-01-01

    Genetic susceptibility to alcoholic cirrhosis (AC) exists. We previously demonstrated hepatic mitochondrial DNA (mtDNA) damage in patients with AC compared with chronic alcoholics without cirrhosis. Mitochondrial transcription factor A (mtTFA) is central to mtDNA expression regulation and repair; however, it is unclear whether there are specific mtTFA single nucleotide polymorphisms (SNPs) in patients with AC and whether they affect mtDNA repair. In the present study, we screened mtTFA SNPs i...

  14. Antibody Tracing, Seroepidemiology and Risk Factors of Bovine Respiratory Syncytial Virus and Bovine Adenovirus-3 in Dairy Holstein Farms

    Directory of Open Access Journals (Sweden)

    Mahsa FARZINPOUR

    2016-01-01

    Full Text Available Antibody tracing, risk factors and seroepidemiology of bovine respiratory syncytial virus and bovine adenovirus-3 were investigated in 22 Industrial and Semi-Industrial dairy Holstein farms. Serum samples (n=736 from various ages of unvaccinated cows were collected from May to September 2012. Risk factors including age, past history of respiratory diseases, amount of milk production, husbandry type and herd size were considered. Data were analyzed by Chi-square and logistic regression. Results indicated that the infection with some of individual viruses was related to past history of respiratory disease and herd size. No specific pattern was seen on the effect of level of milk production on seropositivity of animals. The seroprevalence for BRSV and BAV-3 were 89.1% and 88%, respectively. The present study indicates that infections of bovine respiratory viruses frequently occur in cattle of Fars province and the main viral cause of primary occurrence of respiratory diseases may be due to aforementioned viruses.

  15. Drosophila nuclear factor DREF regulates the expression of the mitochondrial DNA helicase and mitochondrial transcription factor B2 but not the mitochondrial translation factor B1

    OpenAIRE

    Fernández-Moreno, Miguel A.; Hernández, Rosana; Adán, Cristina; Roberti, Marina; Bruni, Francesco; Polosa, Paola Loguercio; Cantatore, Palmiro; Matsushima, Yuichi; Kaguni, Laurie S.; Garesse, Rafael

    2013-01-01

    DREF [DRE (DNA replication-related element)-binding factor] controls the transcription of numerous genes in Drosophila, many involved in nuclear DNA (nDNA) replication and cell proliferation, three in mitochondrial DNA (mtDNA) replication and two in mtDNA transcription termination. In this work, we have analysed the involvement of DREF in the expression of the known remaining genes engaged in the minimal mtDNA replication (d-mtDNA helicase) and transcription (the activator d-mtTFB2) machineri...

  16. A Human Mitochondrial Transcription Factor Is Related to RNA Adenine Methyltransferases and Binds S-Adenosylmethionine

    OpenAIRE

    McCulloch, Vicki; Seidel-Rogol, Bonnie L.; Shadel, Gerald S.

    2002-01-01

    A critical step toward understanding mitochondrial genetics and its impact on human disease is to identify and characterize the full complement of nucleus-encoded factors required for mitochondrial gene expression and mitochondrial DNA (mtDNA) replication. Two factors required for transcription initiation from a human mitochondrial promoter are h-mtRNA polymerase and the DNA binding transcription factor, h-mtTFA. However, based on studies in model systems, the existence of a second human mito...

  17. Herd-level Risk Factors Associated with Bovine Brucellosis Seropositivity and Abortion in Bangladesh

    OpenAIRE

    Islam, Md. Atiqul

    2011-01-01

    A cross-sectional study was conducted to determine the seroprevalence and to identify the herd level risk factors associated with bovine brucellosis seropositivity and abortion in the Mymensingh and Sherpur districts of Bangladesh.

  18. Heparin Binds Endothelial Cell Growth Factor, the Principal Endothelial Cell Mitogen in Bovine Brain

    Science.gov (United States)

    Maciag, Thomas; Mehlman, Tevie; Friesel, Robert; Schreiber, Alain B.

    1984-08-01

    Endothelial cell growth factor (ECGF), an anionic polypeptide mitogen, binds to immobilized heparin. The interaction between the acidic polypeptide and the anionic carbohydrate suggests a mechanism that is independent of ion exchange. Monoclonal antibodies to purified bovine ECGF inhibited the biological activity of ECGF in crude preparations of bovine brain. These data indicate that ECGF is the principal mitogen for endothelial cells from bovine brain, that heparin affinity chromatography may be used to purify and concentrate ECGF, and that the affinity of ECGF for heparin may have structural and perhaps biological significance.

  19. Mitochondrial integrity in a neonatal bovine model of right ventricular dysfunction

    OpenAIRE

    Bruns, Danielle R; Brown, R. Dale; Stenmark, Kurt R.; Buttrick, Peter M.; Walker, Lori A.

    2014-01-01

    Right ventricular (RV) function is a key determinant of survival in patients with both RV and left ventricular (LV) failure, yet the mechanisms of RV failure are poorly understood. Recent studies suggest cardiac metabolism is altered in RV failure in pulmonary hypertension (PH). Accordingly, we assessed mitochondrial content, dynamics, and function in hearts from neonatal calves exposed to hypobaric hypoxia (HH). This model develops severe PH with concomitant RV hypertrophy, dilation, and dys...

  20. Factors affecting the infectivity of lymphocytes from cattle with bovine leukosis virus.

    OpenAIRE

    Buxton, B A; Schultz, R D

    1984-01-01

    Peripheral blood mononuclear cells were obtained from 13 bovine leukosis virus infected cattle and inoculated subcutaneously into 29 recipient adult steers to determine (a) the number of mononuclear cells (equivalent amount of blood) necessary to cause infection and (b) factors influencing infectivity of mononuclear cells from bovine leukosis virus-infected animals. A total of 55 inoculations were made. Inoculation of 1 X 10(4), 2 X 10(4) and 5 X 10(4) mononuclear cells caused seroconversion ...

  1. Seroprevalence and risk factors associated with bovine herpesvirus 1 and bovine viral diarrhea virus in North-Eastern Mexico

    Science.gov (United States)

    Segura-Correa, J.C.; Zapata-Campos, C.C.; Jasso-Obregón, J.O.; Martinez-Burnes, J.; López-Zavala, R.

    2016-01-01

    Bovine herpesvirus 1 (BoHV-1) and bovine viral diarrhea virus (BVDV) are well known etiological agents of cattle that produce important economic losses due to reproductive failures and calf mortality, as well as enteric and respiratory disease. Tamaulipas is located northeast of Mexico, an important cattle production and the principal exporter of calf and heifer to the United States. The objectives of this study were to estimate the seroprevalence of BoHV-1 and of BVDV, and to determine the effects of risk factors on these infections. Blood samples of cattle from 57 farms from rural districts of Tamaulipas were collected. The samples were tested for antibodies against BoHV-1 and BVDV using commercial ELISA kits. Data on potential risk factors were obtained using a questionnaire administered to the farmer at the time the blood samples were taken. The seroprevalences for BoHV-1 and BVDV were 64.4% and 47.8%, respectively. In the logistic regression analysis, the significant risk factors were rural district, herd size and cattle introduced to the farm. This study confirms the high seroprevalence of BoHV-1 and BVDV in unvaccinated cattle in Tamaulipas, Mexico. The results of this study could be used for the development of BoHV-1 and BVDV prevention and control program in North-Eastern, Mexico.

  2. GABP Transcription Factor (Nuclear Respiratory Factor 2) Is Required for Mitochondrial Biogenesis

    OpenAIRE

    Yang, Zhong-Fa; Drumea, Karen; Mott, Stephanie; Wang, Junling; Rosmarin, Alan G.

    2014-01-01

    Mitochondria are membrane-bound cytoplasmic organelles that serve as the major source of ATP production in eukaryotic cells. GABP (also known as nuclear respiratory factor 2) is a nuclear E26 transformation-specific transcription factor (ETS) that binds and activates mitochondrial genes that are required for electron transport and oxidative phosphorylation. We conditionally deleted Gabpa, the DNA-binding component of this transcription factor complex, from mouse embryonic fibroblasts (MEFs) t...

  3. Dynamic mitochondrial localization of nuclear transcription factor HMGA1

    International Nuclear Information System (INIS)

    It has been well established that high mobility group A1 (HMGA1) proteins act within the nucleus of mammalian cells as architectural transcription factors that regulate the expression of numerous genes. Here, however, we report on the unexpected cytoplasmic/mitochondrial localization of the HMGA1 proteins within multiple cell types. Indirect immunofluorescence, electron microscopic immunolocalization, and Western blot studies revealed that, in addition to the nucleus, HMGA1 proteins could also be found in both the cytoplasm and mitochondria of randomly dividing populations of wild-type murine NIH3T3 cells and transgenic human MCF-7 breast cancer epithelial cells expressing a hemagglutinin tagged-HMGA1a fusion protein. While the molecular mechanisms underlying these novel subcellular localization patterns have not yet been determined, initial synchronization studies revealed a dynamic, cell cycle-dependent translocation of HMGA1 proteins from the nucleus into the cytoplasm and mitochondria of NIH3T3 cells. Furthermore, preliminary functionality studies utilizing a modified 'chromatin' immunoprecipitation protocol revealed that HMGA1 retains its DNA binding capabilities within the mitochondria and associates with the regulatory D-loop region in vivo. We discuss potential new biological roles for the classically nuclear HMGA1 proteins with regard to the observed nucleocytoplasmic translocation, mitochondrial internalization, and regulatory D-loop DNA binding

  4. Structural basis for S-adenosylmethionine binding and methyltransferase activity by mitochondrial transcription factor B1

    OpenAIRE

    Guja, Kip E.; Venkataraman, Krithika; Yakubovskaya, Elena; Hui SHI; Mejia, Edison; Hambardjieva, Elena; Karzai, A. Wali; Garcia-Diaz, Miguel

    2013-01-01

    Eukaryotic transcription factor B (TFB) proteins are homologous to KsgA/Dim1 ribosomal RNA (rRNA) methyltransferases. The mammalian TFB1, mitochondrial (TFB1M) factor is an essential protein necessary for mitochondrial gene expression. TFB1M mediates an rRNA modification in the small ribosomal subunit and thus plays a role analogous to KsgA/Dim1 proteins. This modification has been linked to mitochondrial dysfunctions leading to maternally inherited deafness, aminoglycoside sensitivity and di...

  5. Insulin-like growth factor 1 (IGF-1) therapy: Mitochondrial dysfunction and diseases.

    Science.gov (United States)

    Sádaba, M C; Martín-Estal, I; Puche, J E; Castilla-Cortázar, I

    2016-07-01

    This review resumes the association between mitochondrial function and diseases, especially neurodegenerative diseases. Additionally, it summarizes the major role of IGF-1 as a mitochondrial protector, as studied in several experimental models (cirrhosis, aging …). The contribution of mitochondrial dysfunction to impairments in insulin metabolic signaling is also suggested by gene array analysis showing that reductions in gene expression, that regulates mitochondrial ATP production, are associated with insulin resistance and type 2 diabetes mellitus. Moreover, reductions in oxidative capacity of mitochondrial electron transport chain are manifested in obese, insulin-resistant and diabetic patients. Genetic and environmental factors, oxidative stress, and alterations in mitochondrial biogenesis can adversely affect mitochondrial function, leading to insulin resistance and several pathological conditions, such as type 2 diabetes. Finally, it remains essential to know the exact mechanisms involved in mitochondrial generation and metabolism, mitophagy, apoptosis, and oxidative stress to establish new targets in order to develop potentially effective therapies. One of the newest targets to recover mitochondrial dysfunction could be the administration of IGF-1 at low doses. In the last years, it has been observed that IGF-1 therapy has several beneficial effects: restores physiological IGF-1 levels; improves insulin resistance and lipid metabolism; exerts mitochondrial protection; and has hepatoprotective, neuroprotective, antioxidant and antifibrogenic effects. In consequence, treatment of mitochondrial dysfunctions with low doses of IGF-1 could be a powerful and useful effective therapy to restore normal mitochondrial functions. PMID:27020404

  6. Significant associations of the mitochondrial transcription factor A promoter polymorphisms with marbling and subcutaneous fat depth in Wagyu x Limousin F2 crosses

    International Nuclear Information System (INIS)

    Mitochondrial transcription factor A (TFAM), a nucleus-encoded protein, regulates the initiation of transcription and replication of mitochondrial DNA (mtDNA). Decreased expression of nuclear-encoded mitochondrial genes has been associated with onset of obesity in mice. Therefore, we hypothesized genetic variants in TFAM gene influence mitochondrial biogenesis consequently affecting body fat deposition and energy metabolism. In the present study, both cDNA (2259 bp) and genomic DNA (16,666 bp) sequences were generated for the bovine TFAM gene using a combination of in silico cloning with targeted region PCR amplification. Alignment of both cDNA and genomic sequences led to the determination of genomic organization and characterization of the promoter region of the bovine TFAM gene. Two closely linked A/C and C/T single nucleotide polymorphisms (SNPs) were found in the bovine TFAM promoter and then genotyped on 237 Wagyu x Limousin F2 animals with recorded phenotypes for marbling and subcutaneous fat depth (SFD). Statistical analysis demonstrated that both SNPs and their haplotypes were associated with marbling (P = 0.0153 for A/C, P = 0.0026 for C/T, and P = 0.0004 for haplotype) and SFD (P = 0.0200 for A/C, P = 0.0039 for C/T, and P = 0.0029 for haplotype), respectively. A search for transcriptional regulatory elements using MatInspector indicated that both SNPs lead to a gain/loss of six putative-binding sites for transcription factors relevant to fat deposition and energy metabolism. Our results suggest for the first time that TFAM gene plays an important role in lipid metabolism and may be a strong candidate gene for obesity in mammals

  7. Insulin-like growth factor induced signals activate mitochondrial respiration

    OpenAIRE

    Hütter, E.; Unterluggauer, H.; Viertler, H.P.; Jansen-Dürr, P

    2008-01-01

    From experiments with lower eukaryotes it is known that the metabolic rate and also the rate of aging are tightly controlled by the IGF / insulin signal transduction pathway. The mitochondrial theory of aging implies that an increased metabolic rate leads to increased mitochondrial activity; increased production of reactive oxygen species due to these alterations would speed up the aging process. To address the question if mitochondrial activity is influenced by insulin / IGF signalling, we h...

  8. Involvement of GATA transcription factors in the regulation of endogenous bovine interferon-tau gene transcription.

    Science.gov (United States)

    Bai, Hanako; Sakurai, Toshihiro; Kim, Min-Su; Muroi, Yoshikage; Ideta, Atsushi; Aoyagi, Yoshito; Nakajima, Hiromi; Takahashi, Masashi; Nagaoka, Kentaro; Imakawa, Kazuhiko

    2009-12-01

    Expression of interferon-tau (IFNT), necessary for pregnancy establishment in ruminant ungulates, is regulated in a temporal and spatial manner. However, molecular mechanisms by which IFNT gene transcription is regulated in this manner have not been firmly established. In this study, DNA microarray/RT-PCR analysis between bovine trophoblast CT-1 and Mardin-Darby bovine kidney (MDBK) cells was initially performed, finding that transcription factors GATA2, GATA3, and GATA6 mRNAs were specific to CT-1 cells. These mRNAs were also found in Days 17, 20, and 22 (Day 0 = day of estrus) bovine conceptuses. In examining other bovine cell lines, ovary cumulus granulosa (oCG) and ear fibroblast (EF) cells, GATA2 and GATA3, but not GATA6, were found specific to the bovine trophoblast cells. In transient transfection analyses using the upstream region (-631 to +59 bp) of bovine IFNT gene (bIFNT, IFN-tau-c1), over-expression of GATA2/GATA3 did not affect the transcription of bIFNT-reporter construct in human choriocarcinoma JEG3 cells. Transfection of GATA2, GATA3, ETS2, and/or CDX2, however, was effective in the up-regulation of the bIFNT construct transfected into bovine oCG and EF cells. One Point mutation studies revealed that among six potential GATA binding sites located on the upstream region of the bIFNT gene, the one next to ETS2 site exhibited reduced luciferase activity. In CT-1 cells, endogenous bIFNT gene transcription was up-regulated by over-expression of GATA2 or GATA3, but down-regulated by siRNA specific to GATA2 mRNA. These data suggest that GATA2/3 is involved in trophoblast-specific regulation of bIFNT gene transcription. PMID:19598245

  9. Effects of Water Soluble Phosphotidylserine on Bovine Factor Xa: Functional and Structural Changes Plus Dimerization

    OpenAIRE

    Majumder, Rinku; Wang, Jianfang; Lentz, Barry R.

    2003-01-01

    Previous work has shown that two molecules of a soluble form of phosphatidylserine, C6PS, bind to human and bovine factor Xa. Activity measurements along with the fluorescence of active-site-labeled human factor Xa showed that two linked sites specifically regulate the active site conformation and proteolytic activity of the human enzyme. These results imply, but cannot demonstrate, a C6PS-induced factor Xa conformational change. The purpose of this paper is to extend these observations to bo...

  10. The reaction of NADPH with bovine mitochondrial NADH:ubiquinone oxidoreductase revisited: I. Proposed consequences for electron transfer in the enzyme

    OpenAIRE

    Albracht, S.P.J.

    2010-01-01

    Bovine NADH:ubiquinone oxidoreductase (Complex I) is the first complex in the mitochondrial respiratory chain. It has long been assumed that it contained only one FMN group. However, as demonstrated in 2003, the intact enzyme contains two FMN groups. The second FMN was proposed to be located in a conserved flavodoxin fold predicted to be present in the PSST subunit. The long-known reaction of Complex I with NADPH differs in many aspects from that with NADH. It was proposed that the second fla...

  11. Growth inhibitory factors in bovine faeces impairs detection of Salmonella Dublin by conventional culture procedure

    DEFF Research Database (Denmark)

    Baggesen, Dorte Lau; Nielsen, L.R.; Sørensen, Gitte;

    2007-01-01

    Aims: To analyse the relative importance of different biological and technical factors on the analytical sensitivity of conventional culture methods for detection of Salmonella Dublin in cattle faeces. Methods and Results: Faeces samples collected from six adult bovines from different salmonella-...

  12. The mitochondrial fusion-promoting factor mitofusin is a substrate of the PINK1/parkin pathway.

    Directory of Open Access Journals (Sweden)

    Angela C Poole

    Full Text Available Loss-of-function mutations in the PINK1 or parkin genes result in recessive heritable forms of parkinsonism. Genetic studies of Drosophila orthologs of PINK1 and parkin indicate that PINK1, a mitochondrially targeted serine/threonine kinase, acts upstream of Parkin, a cytosolic ubiquitin-protein ligase, to promote mitochondrial fragmentation, although the molecular mechanisms by which the PINK1/Parkin pathway promotes mitochondrial fragmentation are unknown. We tested the hypothesis that PINK1 and Parkin promote mitochondrial fragmentation by targeting core components of the mitochondrial morphogenesis machinery for ubiquitination. We report that the steady-state abundance of the mitochondrial fusion-promoting factor Mitofusin (dMfn is inversely correlated with the activity of PINK1 and Parkin in Drosophila. We further report that dMfn is ubiquitinated in a PINK1- and Parkin-dependent fashion and that dMfn co-immunoprecipitates with Parkin. By contrast, perturbations of PINK1 or Parkin did not influence the steady-state abundance of the mitochondrial fission-promoting factor Drp1 or the mitochondrial fusion-promoting factor Opa1, or the subcellular distribution of Drp1. Our findings suggest that dMfn is a direct substrate of the PINK1/Parkin pathway and that the mitochondrial morphological alterations and tissue degeneration phenotypes that derive from mutations in PINK1 and parkin result at least in part from reduced ubiquitin-mediated turnover of dMfn.

  13. Effects of carbon monoxide (CO) delivery by a CO donor or hemoglobin on vascular hypoxia inducible factor 1α and mitochondrial respiration

    OpenAIRE

    Reiter, Chad E. N.; Alayash, Abdu I.

    2012-01-01

    We examined carbon monoxide (CO) delivery by carbon monoxide-releasing molecule 2 (CORM-2) or hemoglobin (Hb) on cellular oxygen sensing and mitochondrial respiration in bovine aortic endothelial cells (BAECs). CORM-2 reduced hypoxia-inducible factor-1α (HIF-1α) and endothelin-1 (ET-1) expression in normoxic and hypoxic cells, but while Hb alone significantly reduced HIF-1α stabilization in hypoxic cells, CO delivered by Hb (Hb-CO) had no effect on HIF-1α stabilization. CO dose-dependently in...

  14. Structural analysis and DNA binding of the HMG domains of the human mitochondrial transcription factor A

    OpenAIRE

    Gangelhoff, Todd A.; Mungalachetty, Purnima S.; Nix, Jay C.; Mair E A Churchill

    2009-01-01

    The mitochondrial transcription factor A (mtTFA) is central to assembly and initiation of the mitochondrial transcription complex. Human mtTFA (h-mtTFA) is a dual high mobility group box (HMGB) protein that binds site-specifically to the mitochondrial genome and demarcates the promoters for recruitment of h-mtTFB1, h-mtTFB2 and the mitochondrial RNA polymerase. The stoichiometry of h-mtTFA was found to be a monomer in the absence of DNA, whereas it formed a dimer in the complex with the light...

  15. Replication factors transiently associate with mtDNA at the mitochondrial inner membrane to facilitate replication

    NARCIS (Netherlands)

    Rajala, N.; Gerhold, J.M.; Martinsson, P.; Klymov, A.; Spelbrink, H.

    2014-01-01

    Mitochondrial DNA (mtDNA) is organized in discrete protein-DNA complexes, nucleoids, that are usually considered to be mitochondrial-inner-membrane associated. Here we addressed the association of replication factors with nucleoids and show that endogenous mtDNA helicase Twinkle and single-stranded

  16. Common mitochondrial polymorphisms as risk factor for endometrial cancer

    OpenAIRE

    2009-01-01

    Endometrial carcinoma is the most commonly diagnosed gynaecological cancer in developed countries. Although the molecular genetics of this disease has been in the focus of many research laboratories for the last 20 years, relevant prognostic and diagnostic markers are still missing. At the same time mitochondrial DNA mutations have been reported in many types of cancer during the last two decades. It is therefore very likely that the mitochondrial genotype is one of the cancer susceptibility ...

  17. Butyric acid stimulates bovine neutrophil functions and potentiates the effect of platelet activating factor.

    Science.gov (United States)

    Carretta, M D; Hidalgo, A I; Burgos, J; Opazo, L; Castro, L; Hidalgo, M A; Figueroa, C D; Taubert, A; Hermosilla, C; Burgos, R A

    2016-08-01

    Increased short-chain fatty acid (SCFA) production is associated with subacute ruminal acidosis (SARA) and activation of inflammatory processes. In humans and rodents, SCFAs modulate inflammatory responses in the gut via free fatty acid receptor 2 (FFA2). In bovines, butyric acid is one of the most potent FFA2 agonists. Its expression in bovine neutrophils has recently been demonstrated, suggesting a role in innate immune response in cattle. This study aimed to evaluate if butyric acid modulates oxidative and non-oxidative functions or if it can potentiate other inflammatory mediators in bovine neutrophils. Our results showed that butyric acid can activate bovine neutrophils, inducing calcium (Ca(2+)) influx and mitogen-activated protein kinase (MAPK) phosphorylation, two second messengers involved in FFA2 activation. Ca(2+) influx induced by butyric acid was dependent on the extracellular and intracellular Ca(2+) source and phospholipase C (PLC) activation. Butyric acid alone had no significant effect on reactive oxygen species (ROS) production and chemotaxis; however, a priming effect on platelet-activating factor (PAF), a potent inflammatory mediator, was observed. Butyric acid increased CD63 expression and induced the release of neutrophil granule markers matrix metalloproteinase-9 (MMP-9) and lactoferrin. Finally, we observed that butyric acid induced neutrophil extracellular trap (NET) formation without affecting cellular viability. These findings suggest that butyric acid, a component of the ruminal fermentative process, can modulate the innate immune response of ruminants. PMID:27288853

  18. Oocyte-secreted factors in oocyte maturation media enhance subsequent development of bovine cloned embryos.

    Science.gov (United States)

    Su, Jianmin; Wang, Yongsheng; Zhang, Lei; Wang, Bo; Liu, Jun; Luo, Yan; Guo, Zekun; Quan, Fusheng; Zhang, Yong

    2014-04-01

    Successful in vitro maturation (IVM) and oocyte quality both affect the subsequent development of cloned embryos derived from somatic-cell nuclear transfer (SCNT). Developmental competence is usually lower in oocytes matured in vitro compared with those that matured in vivo, possibly due to insufficient levels of oocyte-secreted factors (OSFs) and disrupted oocyte-cumulus communication. This study investigated the effects of OSFs secreted by denuded oocytes (DOs) during IVM on the subsequent developmental competence of cloned bovine embryos. Cumulus-oocyte complexes (COCs) from antral follicles of slaughtered-cow ovaries collected from an abattoir were divided into four groups: COCs co-cultured with and without DOs in maturation media used for SCNT, as well as COCs co-cultured with and without DOs in maturation media used for in vitro fertilization (IVF). Based on the developmental competence and embryo quality of bovine embryos generated from these four groups, we found that co-culturing the COCs with DOs enhanced the in vitro development of IVF and cloned bovine embryos, and potentially generated more high-quality cloned blastocysts that possessed locus-specific histone modifications at levels similar to in vitro-fertilized embryos. These results strongly suggest that co-culturing COCs with DOs enhances subsequent developmental competence of cloned bovine embryo. PMID:24420374

  19. The mitochondrial transcription factor A functions in mitochondrial base excision repair

    DEFF Research Database (Denmark)

    Canugovi, Chandrika; Maynard, Scott; Bayne, Anne-Cécile V;

    2010-01-01

    mitochondria, whereas base excision repair (BER) has been comprehensively characterized in these organelles. The BER proteins are associated with the inner membrane in mitochondria and thus with the mitochondrial nucleoid, where TFAM is also situated. However, a function for TFAM in BER has not yet been...

  20. Mitochondrial Transcription Factor B2 Is Essential for Metabolic Function in Drosophila melanogaster Development*

    OpenAIRE

    Adán, Cristina; Matsushima, Yuichi; Hernández-Sierra, Rosana; Marco-Ferreres, Raquel; Fernández-Moreno, Miguel Ángel; González-Vioque, Emiliano; Calleja, Manuel; Aragón, Juan J.; Kaguni, Laurie S.; Garesse, Rafael

    2008-01-01

    Characterization of the basal transcription machinery of mitochondrial DNA (mtDNA) is critical to understand mitochondrial pathophysiology. In mammalian in vitro systems, mtDNA transcription requires mtRNA polymerase, transcription factor A (TFAM), and either transcription factor B1 (TFB1M) or B2 (TFB2M). We have silenced the expression of TFB2M by RNA interference in Drosophila melanogaster. RNA interference knockdown of TF2BM causes lethality by arrest of larval deve...

  1. Isolation of bovine corneal keratan sulfate and its growth factor and morphogen binding.

    Science.gov (United States)

    Weyers, Amanda; Yang, Bo; Solakyildirim, Kemal; Yee, Vienna; Li, Lingyun; Zhang, Fuming; Linhardt, Robert J

    2013-05-01

    Keratan sulfate (KS) is an important glycosaminoglycan that is found in cartilage, reproductive tissues, and neural tissues. Corneal KS glycosaminoglycan is found N-linked to lumican, keratocan and mimecan proteoglycans, and has been widely studied by investigators interested in corneal development and diseases. Recently, the availability of corneal KS has become severely limited, owing to restrictions on the shipment of bovine central nervous system byproducts across international borders in an effort to prevent additional cases of mad cow disease. We report a simple method for the purification of multi-milligram quantities of bovine corneal KS, and characterize its structural properties. We also examined its protein-binding properties, and discovered that corneal KS bound with high affinity to fibroblast growth factor-2 and sonic hedgehog, a growth factor and a morphogen involved in corneal development and healing. PMID:23402351

  2. Investigations of extracellular matrix proteases, apoptotic and anti-apoptotic factors in the bovine corpus luteum

    OpenAIRE

    Kliem, Heike

    2006-01-01

    The study is subdivided into two different parts: the first part deals with the development of a method to gain uterus milk in vivo during the preimplantation periode in cattle for the investigation of regulatory factors. The second part investigates different proteases in bovine follicles 20 hours after GnRH (Gonadotropin releasing hormone) injection (shortly bevor ovulation) for comparable as well as in the corpus luteum (CL) during oestrous cycle and induced luteolysis. In addition apoptot...

  3. Transfer factors feed/meat in bovine and pigs

    International Nuclear Information System (INIS)

    Meat samples of young bulls and pigs have been selected in various parts of the FRG and examined for their content of Cs-137, Sr-90, and Pb-210. The data determined by measurement for each of the location-specific samples revealed a transfer factor for Cs-137 ranging between 3 x 10-2 and 7.5 x 10-2. For Sr-90, agreement between measured data and the theoretical value given in the General Instructions and Standard Values for Calculation is found, whereas for Pb-210, the relevant values differ by two decimal exponents, so that the transfer factor is to be corrected. (DG/HP)

  4. Cardioprotection by modulation of mitochondrial respiration during ischemia–reperfusion: Role of apoptosis-inducing factor

    International Nuclear Information System (INIS)

    Highlights: •Blockade of electron transport prevents the loss of AIF from mitochondria during IR. •Blockade of electron transport decreases caspase-independent cell death during IR. •Mitochondrial AIF content is down-regulated in Harlequin mice. •Blockade of electron transport protects Harlequin mouse hearts during IR. •Amobarbital protection is partially dependent on mitochondrial AIF content. -- Abstract: The transient, reversible blockade of electron transport (BET) during ischemia or at the onset of reperfusion protects mitochondria and decreases cardiac injury. Apoptosis inducing factor (AIF) is located within the mitochondrial intermembrane space. A release of AIF from mitochondria into cytosol and nucleus triggers caspase-independent cell death. We asked if BET prevents the loss of AIF from mitochondria as a mechanism of protection in the buffer perfused heart. BET during ischemia with amobarbital, a rapidly reversible inhibitor of mitochondrial complex I, attenuated a release of AIF from mitochondria into cytosol, in turn decreasing the formation of cleaved and activated PARP-1. These results suggest that BET-mediated protection may occur through prevention of the loss of AIF from mitochondria during ischemia–reperfusion. In order to further clarify the role of mitochondrial AIF in BET-mediated protection, Harlequin (Hq) mice, a genetic model with mitochondrial AIF deficiency, were used to test whether BET could still decrease cell injury in Hq mouse hearts during reperfusion. BET during ischemia protected Hq mouse hearts against ischemia–reperfusion injury and improved mitochondrial function in these hearts during reperfusion. Thus, cardiac injury can still be decreased in the presence of down-regulated mitochondrial AIF content. Taken together, BET during ischemia protects both hearts with normal mitochondrial AIF content and hearts with mitochondrial AIF deficiency. Although preservation of mitochondrial AIF content plays a key role in

  5. Cardioprotection by modulation of mitochondrial respiration during ischemia–reperfusion: Role of apoptosis-inducing factor

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Aijun [Department of Internal Medicine (Division of Cardiology), Virginia Commonwealth University, Richmond, VA 23298 (United States); Department of Anesthesiology, Tongji Hospital, Huazhong University of Science and Technology, Wuhan 430030 (China); Szczepanek, Karol; Hu, Ying [Department of Internal Medicine (Division of Cardiology), Virginia Commonwealth University, Richmond, VA 23298 (United States); Lesnefsky, Edward J. [Department of Internal Medicine (Division of Cardiology), Virginia Commonwealth University, Richmond, VA 23298 (United States); Department of Biochemistry and Molecular Biology, Virginia Commonwealth University, Richmond, VA 23298 (United States); Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, VA 23298 (United States); McGuire Department of Veterans Affairs Medical Center, Richmond, VA 23249 (United States); Chen, Qun, E-mail: qchen8@vcu.edu [Department of Internal Medicine (Division of Cardiology), Virginia Commonwealth University, Richmond, VA 23298 (United States)

    2013-06-14

    Highlights: •Blockade of electron transport prevents the loss of AIF from mitochondria during IR. •Blockade of electron transport decreases caspase-independent cell death during IR. •Mitochondrial AIF content is down-regulated in Harlequin mice. •Blockade of electron transport protects Harlequin mouse hearts during IR. •Amobarbital protection is partially dependent on mitochondrial AIF content. -- Abstract: The transient, reversible blockade of electron transport (BET) during ischemia or at the onset of reperfusion protects mitochondria and decreases cardiac injury. Apoptosis inducing factor (AIF) is located within the mitochondrial intermembrane space. A release of AIF from mitochondria into cytosol and nucleus triggers caspase-independent cell death. We asked if BET prevents the loss of AIF from mitochondria as a mechanism of protection in the buffer perfused heart. BET during ischemia with amobarbital, a rapidly reversible inhibitor of mitochondrial complex I, attenuated a release of AIF from mitochondria into cytosol, in turn decreasing the formation of cleaved and activated PARP-1. These results suggest that BET-mediated protection may occur through prevention of the loss of AIF from mitochondria during ischemia–reperfusion. In order to further clarify the role of mitochondrial AIF in BET-mediated protection, Harlequin (Hq) mice, a genetic model with mitochondrial AIF deficiency, were used to test whether BET could still decrease cell injury in Hq mouse hearts during reperfusion. BET during ischemia protected Hq mouse hearts against ischemia–reperfusion injury and improved mitochondrial function in these hearts during reperfusion. Thus, cardiac injury can still be decreased in the presence of down-regulated mitochondrial AIF content. Taken together, BET during ischemia protects both hearts with normal mitochondrial AIF content and hearts with mitochondrial AIF deficiency. Although preservation of mitochondrial AIF content plays a key role in

  6. Prevalence and risk factors for bruises in Chilean bovine carcasses

    NARCIS (Netherlands)

    Strappini, A.C.; Frankena, K.; Metz, J.H.M.; Kemp, B.

    2010-01-01

    Records of cattle slaughtered at two Chilean slaughterhouses (SLH1 and SLH2) were used to determine prevalence and risk factors for carcasses with bruises. Bruise prevalence amounted to 12.3% but differed between slaughterhouses (20.8% for SLH1 and 8.6% for SLH2 respectively). Bruise severity grade

  7. Mitochondrial transcription factor A regulated ionizing radiation-induced mitochondrial biogenesis in human lung adenocarcinoma A549 cells

    International Nuclear Information System (INIS)

    Mitochondrial transcription factor A (TFAM), the first well-characterized transcription factor from vertebrate mitochondria, is closely related to mitochondrial DNA (mtDNA) maintenance and repair. Recent evidence has shown that the ratio of mtDNA to nuclearDNA (nDNA) is increased in both human cells and murine tissues after ionizing radiation (IR). However, the underlying mechanism has not as yet been clearly identified. In the present study, we demonstrated that in human lung adenocarcinoma A549 cells, expression of TFAM was upregulated, together with the increase of the relative mtDNA copy number and cytochrome c oxidase (COX) activity after α-particle irradiation. Furthermore, short hairpin RNA (shRNA)-mediated TFAM knockdown inhibited the enhancement of the relative mtDNA copy number and COX activity caused by α-particles. Taken together, our data suggested that TFAM plays a crucial role in regulating mtDNA amplification and mitochondrial biogenesis under IR conditions. (author)

  8. DmTTF, a novel mitochondrial transcription termination factor that recognises two sequences of Drosophila melanogaster mitochondrial DNA

    Science.gov (United States)

    Roberti, Marina; Polosa, Paola Loguercio; Bruni, Francesco; Musicco, Clara; Gadaleta, Maria Nicola; Cantatore, Palmiro

    2003-01-01

    Using a combination of bioinformatic and molecular biology approaches a Drosophila melanogaster protein, DmTTF, has been identified, which exhibits sequence and structural similarity with two mitochondrial transcription termination factors, mTERF (human) and mtDBP (sea urchin). Import/processing assays indicate that DmTTF is synthesised as a precursor of 410 amino acids and is imported into mitochondria, giving rise to a mature product of 366 residues. Band-shift and DNase I protection experiments show that DmTTF binds two homologous, short, non-coding sequences of Drosophila mitochondrial DNA, located at the 3′ end of blocks of genes transcribed on opposite strands. The location of the target sequences coincides with that of two of the putative transcription termination sites previously hypothesised. These results indicate that DmTTF is the termination factor of mitochondrial transcription in Drosophila. The existence of two DmTTF binding sites might serve not only to stop transcription but also to control the overlapping of a large number of transcripts generated by the peculiar transcription mechanism operating in this organism. PMID:12626700

  9. Time resolved bovine host reponse to virulence factors mapped in milk by selected reaction monitoring

    DEFF Research Database (Denmark)

    Bislev, Stine Lønnerup; Kusebauch, Ulrike; Codrea, Marius Cosmin;

    major milk proteins. In this study, we present a sensitive selected reaction monitoring (SRM) proteomics approach, targeting proteins suggested to play key roles in the bovine host response to mastitis. 17 biomarker candidates related to inflammatory response and mastitis were selected. The 17 candidate......TIME RESOLVED BOVINE HOST RESPONSE TO VIRULENCE FACTORS, MAPPED IN MILK BY SELECTED REACTION MONITORING S.L. Bislev1, U. Kusebauch2, M.C. Codrea1, R. Moritz2, C.M. Røntved1, E. Bendixen1 1 Department of Animal Science, Faculty of Science and Technology, Aarhus University, Tjele, Denmark; 2...... Institute for Systems Biology, Seattle, Washington, USA Mastitis is beyond doubt the largest health problem in modern milk production. Many different pathogens can cause infections in the mammary gland, and give rise to severe toll on animal welfare, economic gain as well as on excessive use of antibiotics...

  10. Variation in macrophage migration inhibitory factor [MIF] immunoreactivity during bovine gestation

    DEFF Research Database (Denmark)

    Paulesu, L.; Pfarrer, C.; Romagnoli, R.;

    2012-01-01

    Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine involved in several aspects of the immune response. MIF appears to play important roles in materno-fetal immuno-tolerance during placental establishment, modulation and growth as studied in epitheliochorial porcine and...... hemochorial human and mouse placentae. Here we studied the bovine placenta being multiplex, villous and synepitheliochorial with a low degree of invasion, to see if MIF could be involved. Placental tissues sampled from 12 cows at 9 stages of gestation (days 18-250), and endometrial tissues from two non...... reestablishment of vascularisation, the vasculature in the caruncular area showed MIF reactivity. While supporting involvement of MIF in different placental types, the spatio-temporal variation in the bovine placenta suggests a regulatory role for MIF mainly in the interhemal barrier and during vascular...

  11. Early Exercise Affects Mitochondrial Transcription Factors Expression after Cerebral Ischemia in Rats

    Directory of Open Access Journals (Sweden)

    Yongshan Hu

    2012-02-01

    Full Text Available Increasing evidence shows that exercise training is neuroprotective after stroke, but the underlying mechanisms are unknown. To clarify this critical issue, the current study investigated the effects of early treadmill exercise on the expression of mitochondrial biogenesis factors. Adult rats were subjected to ischemia induced by middle cerebral artery occlusion followed by reperfusion. Expression of two genes critical for transcriptional regulation of mitochondrial biogenesis, peroxisome proliferator-activated receptor coactivator-1 (PGC-1 and nuclear respiratory factor-1 (NRF-1, were examined by RT-PCR after five days of exercise starting at 24 h after ischemia. Mitochondrial protein cytochrome C oxidase subunit IV (COX IV was detected by Western blot. Neurological status and cerebral infarct volume were evaluated as indices of brain damage. Treadmill training increased levels of PGC-1 and NRF-1 mRNA, indicating that exercise promotes rehabilitation after ischemia via regulation of mitochondrial biogenesis.

  12. Expression of mitochondrial transcription factor A in endometrial carcinomas: clinicopathologic correlations and prognostic significance

    OpenAIRE

    Toki, Naoyuki; Kagami, Seiji; Kurita, Tomoko; Kawagoe, Toshinori; Matsuura, Yusuke; Hachisuga, Toru; Matsuyama, Atsuji; Hashimoto, Hiroshi; Izumi, Hiroto; Kohno, Kimitoshi

    2010-01-01

    Mitochondrial transcription factor A (mtTFA) is necessary for both transcription and maintenance of mitochondrial DNA. This study was conducted to elucidate the clinicopathologic and prognostic significance of mtTFA in patients with endometrial carcinoma. This study investigated the relationship between the immunohistochemical expression of mtTFA and various clinicopathological variables in 276 endometrial carcinomas, including 245 endometrioid adenocarcinomas and 31 nonendometrioid carcinoma...

  13. Early Exercise Affects Mitochondrial Transcription Factors Expression after Cerebral Ischemia in Rats

    OpenAIRE

    Yongshan Hu; Jianhong Zhu; Pengyue Zhang; Jie Jia; Hongying Sha; Yi Wu; Qi Zhang

    2012-01-01

    Increasing evidence shows that exercise training is neuroprotective after stroke, but the underlying mechanisms are unknown. To clarify this critical issue, the current study investigated the effects of early treadmill exercise on the expression of mitochondrial biogenesis factors. Adult rats were subjected to ischemia induced by middle cerebral artery occlusion followed by reperfusion. Expression of two genes critical for transcriptional regulation of mitochondrial biogenesis, peroxisome pro...

  14. The Adipocyte-Expressed Forkhead Transcription Factor Foxc2 Regulates Metabolism Through Altered Mitochondrial Function

    OpenAIRE

    Lidell, Martin E.; Seifert, Erin L.; Westergren, Rickard; Heglind, Mikael; Gowing, Adrienne; Sukonina, Valentina; Arani, Zahra; Itkonen, Paula; Wallin, Simonetta; Westberg, Fredrik; Fernandez-Rodriguez, Julia; Laakso, Markku; Nilsson, Tommy; Peng, Xiao-Rong; Harper, Mary-Ellen

    2011-01-01

    OBJECTIVE Previous findings demonstrate that enhanced expression of the forkhead transcription factor Foxc2 in adipose tissue leads to a lean and insulin-sensitive phenotype. These findings prompted us to further investigate the role of Foxc2 in the regulation of genes of fundamental importance for metabolism and mitochondrial function. RESEARCH DESIGN AND METHODS The effects of Foxc2 on expression of genes involved in mitochondriogenesis and mitochondrial function were assessed by quantitati...

  15. Muscle-Specific Loss of Apoptosis-Inducing Factor Leads to Mitochondrial Dysfunction, Skeletal Muscle Atrophy, and Dilated Cardiomyopathy

    OpenAIRE

    Joza, Nicholas; Oudit, Gavin Y.; Brown, Doris; Bénit, Paule; Kassiri, Zamaneh; Vahsen, Nicola; Benoit, Loralyn; Patel, Mikin M.; Nowikovsky, Karin; Vassault, Anne; Backx, Peter H; Wada, Teiji; Kroemer, Guido; Rustin, Pierre; Penninger, Josef M.

    2005-01-01

    Cardiac and skeletal muscle critically depend on mitochondrial energy metabolism for their normal function. Recently, we showed that apoptosis-inducing factor (AIF), a mitochondrial protein implicated in programmed cell death, plays a role in mitochondrial respiration. However, the in vivo consequences of AIF-regulated mitochondrial respiration resulting from a loss-of-function mutation in Aif are not known. Here, we report tissue-specific deletion of Aif in the mouse. Mice in which Aif has b...

  16. The role of mitochondrial factors in apoptosis: a Russian roulette with more than one bullet.

    Science.gov (United States)

    van Loo, G; Saelens, X; van Gurp, M; MacFarlane, M; Martin, S J; Vandenabeele, P

    2002-10-01

    Mitochondria are 'life-essential' organelles for the production of metabolic energy in the form of ATP. Paradoxically mitochondria also play a key role in controlling the pathways that lead to cell death. This latter role of mitochondria is more than just a 'loss of function' resulting in an energy deficit but is an active process involving different mitochondrial proteins. Cytochrome c was the first characterised mitochondrial factor shown to be released from the mitochondrial intermembrane space and to be actively implicated in apoptotic cell death. Since then, other mitochondrial proteins, such as AIF, Smac/DIABLO, endonuclease G and Omi/HtrA2, were found to undergo release during apoptosis and have been implicated in various aspects of the cell death process. Members of the Bcl-2 protein family control the integrity and response of mitochondria to apoptotic signals. The molecular mechanism by which mitochondrial intermembrane space proteins are released and the regulation of mitochondrial homeostasis by Bcl-2 proteins is still elusive. This review summarises and evaluates the current knowledge concerning the complex role of released mitochondrial proteins in the apoptotic process. PMID:12232790

  17. Ascorbate blocks endothelium-derived hyperpolarizing factor (EDHF)-mediated vasodilatation in the bovine ciliary vascular bed and rat mesentery

    OpenAIRE

    McNeish, Alister J.; Wilson, William S; Martin, William

    2002-01-01

    The effects of ascorbate were assessed on vasodilatation mediated by endothelium-derived hyperpolarizing factor (EDHF) in the ciliary vascular bed of the bovine isolated perfused eye and in the rat isolated perfused mesenteric arterial bed.In the bovine eye, EDHF-mediated vasodilator responses induced by acetylcholine or bradykinin were powerfully blocked when ascorbate (50 μM) was included in the perfusion medium for at least 120 min; with acetylcholine a normally-masked muscarinic vasoconst...

  18. Risk factors associated with within-herd transmission of bovine leukemia virus on dairy farms in Japan

    OpenAIRE

    Konishi Misako; Kameyama Ken-ichiro; Hayama Yoko; Yamamoto Takehisa; Tsutsui Toshiyuki; Kobayashi Sota; Murakami Kenji

    2010-01-01

    Abstract Background Although several attempts have been made to control enzootic bovine leukosis (EBL) at the local level, a nationwide control program has not been implemented in Japan, except for passive surveillance. Effective control of EBL requires that the transmission routes of bovine leukemia virus (BLV) infection should be identified and intercepted based on scientific evidence. In this cross-sectional study, we examined the risk factors associated with within-herd transmission of BL...

  19. Measurement of bovine somatotropin (bST) and insulin-like growth factor-1 (IGF-1) in bovine milk using an electrochemiluminescent assay.

    Science.gov (United States)

    McGrath, Michael F; Bogosian, Gregg; Fabellar, Anabella C; Staub, Robin L; Vicini, John L; Widger, Leslie A

    2008-08-27

    Bovine somatotropin (bST) and insulin-like growth factor-1 (IGF-1) are peptide hormones that are involved in the regulation of milk production in dairy cows. Because these hormones are present at extremely low concentration in fresh and processed bovine milk, a highly sensitive and specific electrochemiluminescent immunoassay (ECLIA) has been developed to better estimate the concentration of these hormones in milk. The assay employs an imager, a capture antibody bound to a carbon electrode, and a detection antibody coupled to a ruthenium label. In the presence of tripropylamine and an electric pulse, ruthenium generates light proportional to the amount of antigen bound, and the light is captured as signal by a charge-coupled device (CCD) camera. Using bovine milk as the starting matrix, 99.69% of bST and 104.79% of IGF-1 were recoverable. The limit of detection (LOD) was <5 pg/mL for bST and <1 pg/mL for IGF-1. The limit of quantification (LOQ) was <14 pg/mL for bST in milk and <2 pg/mL of IGF-1. The assay is highly specific and shows <0.2% cross-reactivity with other peptide hormones found in bovine milk such as insulin and IGF-2. These data indicate this new, ECLIA is highly sensitive and specific for estimating the concentration of bST or IGF-1 in milk. PMID:18671399

  20. Depletion of mitochondrial fission factor DRP1 causes increased apoptosis in human colon cancer cells

    International Nuclear Information System (INIS)

    Highlights: ► DRP1 is required for mitochondrial fission in colon cancer cells. ► DRP1 participates in inhibition of colon cancer cell apoptosis. ► DRP1 can inhibit apoptosis through the regulation of cytochrome c release. -- Abstract: Mitochondria play a critical role in regulation of apoptosis, a form of programmed cell death, by releasing apoptogenic factors including cytochrome c. Growing evidence suggests that dynamic changes in mitochondrial morphology are involved in cellular apoptotic response. However, whether DRP1-mediated mitochondrial fission is required for induction of apoptosis remains speculative. Here, we show that siRNA-mediated DRP1 knockdown promoted accumulation of elongated mitochondria in HCT116 and SW480 human colon cancer cells. Surprisingly, DRP1 down-regulation led to decreased proliferation and increased apoptosis of these cells. A higher rate of cytochrome c release and reductions in mitochondrial membrane potential were also revealed in DRP1-depleted cells. Taken together, our present findings suggest that mitochondrial fission factor DRP1 inhibits colon cancer cell apoptosis through the regulation of cytochrome c release and mitochondrial membrane integrity.

  1. In organello footprint analysis of human mitochondrial DNA: human mitochondrial transcription factor A interactions at the origin of replication.

    OpenAIRE

    Ghivizzani, S.C.; Madsen, C S; Nelen, M.R.; Ammini, C V; Hauswirth, W W

    1994-01-01

    Using in organello footprint analysis, we demonstrate that within human placental mitochondria there is a high level of protein-DNA binding at regularly phased intervals throughout a 500-bp region encompassing the D-loop DNA origins and two promoter regions. Comparison with in vitro DNase I protection studies indicates that this protein-DNA interaction is due to non-sequence-specific binding by human mitochondrial transcription factor A (h-mtTFA). Since h-mtTFA can bend and wrap DNA, like its...

  2. Organelle RNA recognition motif-containing (ORRM) proteins are plastid and mitochondrial editing factors in Arabidopsis.

    Science.gov (United States)

    Shi, Xiaowen; Bentolila, Stephane; Hanson, Maureen R

    2016-05-01

    Post-transcriptional C-to-U RNA editing occurs at specific sites in plastid and plant mitochondrial transcripts. Members of the Arabidopsis pentatricopeptide repeat (PPR) motif-containing protein family and RNA-editing factor Interacting Protein (RIP, also known as MORF) family have been characterized as essential components of the RNA editing apparatus. Recent studies reveal that several organelle-targeted RNA recognition motif (RRM)-containing proteins are involved in either plastid or mitochondrial RNA editing. ORRM1 (Organelle RRM protein 1) is essential for plastid editing, whereas ORRM2, ORRM3 and ORRM4 are involved in mitochondrial RNA editing. The RRM domain of ORRM1, ORRM3 and ORRM4 is required for editing activity, whereas the auxiliary RIP and Glycine-Rich (GR) domains mediate the ORRM proteins' interactions with other editing factors. The identification of the ORRM proteins as RNA editing factors further expands our knowledge of the composition of the editosome. PMID:27082488

  3. A case-control study of risk factors for bovine brucellosis seropositivity in Peninsular Malaysia.

    Science.gov (United States)

    Anka, Mukhtar Salihu; Hassan, Latiffah; Khairani-Bejo, Siti; Zainal, Mohamed Abidin; Mohamad, Ramlan Bin; Salleh, Annas; Adzhar, Azri

    2014-01-01

    Bovine brucellosis was first reported in Peninsular Malaysia in 1950. A subsequent survey conducted in the country revealed that the disease was widespread. Current knowledge on the potential risk factors for brucellosis occurrence on cattle farms in Malaysia is lacking. Therefore, we conducted a case-control study to identify the potential herd-level risk factors for bovine brucellosis occurrence in four states in the country, namely Kelantan, Pahang, Selangor and Negeri Sembilan. Thirty-five cases and 36 controls of herds were selected where data on farm management, biosecurity, medical history and public health were collected. Multivariable logistic regression identified that Brucella seropositive herds were more likely to; have some interaction with wildlife (OR 8.9, 95% CI = 1.59-50.05); originated from farms where multiple species such as buffalo/others (OR 41.8, 95% CI = 3.94-443.19) and goat/sheep (OR 8.9, 95%Cl = 1.10-71.83) were reared, practice extensive production system (OR 13.6, 95% CI 1.31-140.24) and have had episodes of abortion in the past (OR 51.8, 95% CI = 4.54-590.90) when compared to seronegative herds. Considering the lack of information on the epidemiology of bovine brucellosis in peninsular Malaysia and absence of information on preventing the inception or spread of the disease, this report could contribute to the on-going area-wise national brucellosis eradication program. PMID:25265020

  4. Structure Identification of Euphorbia Factor L3 and Its Induction of Apoptosis through the Mitochondrial Pathway

    Directory of Open Access Journals (Sweden)

    Hui Zhang

    2011-04-01

    Full Text Available In this article, we have focused on the structure identification of Euphorbia factor L3 belonging to the lathyrane diterpenoids isolated from Caper Euphorbia Seed. Its anticancer activity in vitro against lung cancer A549 cells was also investigated and the IC50 values were 34.04 ± 3.99 μM. Furthermore, Euphorbia factor L3 could induce apoptosis in A549 cells via the mitochondrial pathway including loss of mitochondrial potential and release of cytochrome c.

  5. Distinct roles for two purified factors in transcription of Xenopus mitochondrial DNA.

    OpenAIRE

    Antoshechkin, I; Bogenhagen, D F

    1995-01-01

    Transcription of Xenopus laevis mitochondrial DNA (xl-mtDNA) by the mitochondrial RNA polymerase requires a dissociable factor. This factor was purified to near homogeneity and identified as a 40-kDa protein. A second protein implicated in the transcription of mtDNA, the Xenopus homolog of the HMG box protein mtTFA, was also purified to homogeneity and partially sequenced. The sequence of a cDNA clone encoding xl-mtTFA revealed a high degree of sequence similarity to human and Saccharomyces c...

  6. Evidence for the involvement of coupling factor B in the H+ channel of the mitochondrial H+-ATPase.

    OpenAIRE

    Sanadi, D. R.; Pringle, M.; Kantham, L; J. B. Hughes; A Srivastava

    1984-01-01

    Membrane energization by ATP has been measured in vesicles containing purified bovine heart mitochondrial H+-ATPase (ATP synthase) with the voltage-sensitive dye oxonol VI. The dithiol chelator, Cd2+, and the thiol oxidant, copper o-phenanthroline, produced discharge of the membrane potential when added at the steady state and inhibited its establishment when added prior to energization by ATP. These effects, which were reversed by dithiothreitol, were not accompanied by an increase in the no...

  7. Mitochondrial protection by low doses of insulin-like growth factor- Ⅰ in experimental cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Raquel Pérez; María García-Fernández; Matías Díaz-Sánchez; Juan E Puche; Gloria Delgado; Marian Conchillo; Jordi Muntané; Inma Castilla-Cortázar

    2008-01-01

    AIM:To characterize the mitochondrial dysfunction in experimental cirrhosis and to study whether insulin-like growth factor- I (IGF-I) therapy (4 wk) is able to in-duce beneficial effects on damaged mitochondria leading to cellular protection.METHODS:Wistar rats were divided into three groups:Control group,untreated cirrhotic rats and cirrhotic rats treated with IGF-I treatment (2 μg/100 g bw/d).Mitochondrial function was analyzed by flow cytometry in isolated hepatic mitochondria,caspase 3 activation was assessed by Western blot and apoptosis by TUNEL in the three experimental groups.RESULTS:Untreated cirrhotic rats showed a mitochondrial dysfunction characterized by a significant reduction of mitochondrial membrane potential (in status 4 and 3);an increase of intramitochondrial reactive oxigen species (ROS) generation and a significant reduction of ATPase activity.IGF-Ⅰ therapy normalized mitochondrial function by increasing the membrane potential and ATPase activity and reducing the intramitochondrial free radical production.Activity of the electron transport complexes Ⅰ and Ⅲ was increased in both cirrhotic groups.In addition,untreated cirrhotic rats showed an increase of caspase 3 activation and apoptosis.IGF- Ⅰ therapy reduced the expression of the active peptide of caspase 3 and resulted in reduced apoptosis.CONCLUSION:These results show that IGF- Ⅰ exerts a mitochondrial protection in experimental cirrhosis leading to reduced apoptosis and increased ATP production.

  8. MCUR1 Is a Scaffold Factor for the MCU Complex Function and Promotes Mitochondrial Bioenergetics

    Directory of Open Access Journals (Sweden)

    Dhanendra Tomar

    2016-05-01

    Full Text Available Mitochondrial Ca2+ Uniporter (MCU-dependent mitochondrial Ca2+ uptake is the primary mechanism for increasing matrix Ca2+ in most cell types. However, a limited understanding of the MCU complex assembly impedes the comprehension of the precise mechanisms underlying MCU activity. Here, we report that mouse cardiomyocytes and endothelial cells lacking MCU regulator 1 (MCUR1 have severely impaired [Ca2+]m uptake and IMCU current. MCUR1 binds to MCU and EMRE and function as a scaffold factor. Our protein binding analyses identified the minimal, highly conserved regions of coiled-coil domain of both MCU and MCUR1 that are necessary for heterooligomeric complex formation. Loss of MCUR1 perturbed MCU heterooligomeric complex and functions as a scaffold factor for the assembly of MCU complex. Vascular endothelial deletion of MCU and MCUR1 impaired mitochondrial bioenergetics, cell proliferation, and migration but elicited autophagy. These studies establish the existence of a MCU complex that assembles at the mitochondrial integral membrane and regulates Ca2+-dependent mitochondrial metabolism.

  9. Genetic variation of the mitochondrial D-loop region containing mitochondrial transcription factor (TFAM) binding sites is not associated with marbling in Wagyu X Limousin F2 crosses

    OpenAIRE

    Michal, Jennifer J.; Kunej, Tanja; Dovč, Peter; Jiang, Zhihua

    2015-01-01

    Mitochondrial transcription factor A (TFAM) is a nucleus-encoded protein that is essential for initiation of transcription and replication of mitochondrial DNA (mtDNA). It has been shown that TFAM binds the entire length of the mtDNA,but with higher affinitz to sequences around both mitochondrial promoters located in 3' domain of the D-loop region. The objectives of this study were to detect genetic polymorphisms in the sequence flanking TFAM binding sites of the mtDNA D-loop region and inves...

  10. Evidence for the Involvement of Coupling Factor B in the H+ Channel of the Mitochondrial H+-ATPase

    Science.gov (United States)

    Rao Sanadi, D.; Pringle, Michael; Kantham, Lakshmi; Hughes, James B.; Srivastava, Archana

    1984-03-01

    Membrane energization by ATP has been measured in vesicles containing purified bovine heart mitochondrial H+-ATPase (ATP synthase) with the voltage-sensitive dye oxonol VI. The dithiol chelator, Cd2+, and the thiol oxidant, copper o-phenanthroline, produced discharge of the membrane potential when added at the steady state and inhibited its establishment when added prior to energization by ATP. These effects, which were reversed by dithiothreitol, were not accompanied by an increase in the nonspecific H+ permeability of the membrane. Passive H+ conduction in proteoliposomes containing F0 (hydrophobic segment of ATP synthase) was assayed by the quenching of 9-aminoacridine fluorescence after establishing a K+ diffusion potential. This conductance was blocked by Cd2+, an inhibitor of coupling factor B (FB). Labeling of F0 with 115Cd2+ at the concentrations that inhibited the F0 conductance followed by gel electrophoresis yielded a single radioactive band with a molecular weight corresponding to FB, the presence of which in the F0 preparation was confirmed by immunoblot staining. The data offer strong evidence that FB is an essential component of the H+ channel of F0, because H+ conduction through the channel is inhibited by chemical modification of FB.

  11. The thumb subdomain of yeast mitochondrial RNA polymerase is involved in processivity, transcript fidelity and mitochondrial transcription factor binding

    Science.gov (United States)

    Velazquez, Gilberto; Sousa, Rui; Brieba, Luis G

    2015-01-01

    Single subunit RNA polymerases have evolved 2 mechanisms to synthesize long transcripts without falling off a DNA template: binding of nascent RNA and interactions with an RNA:DNA hybrid. Mitochondrial RNA polymerases share a common ancestor with T-odd bacteriophage single subunit RNA polymerases. Herein we characterized the role of the thumb subdomain of the yeast mtRNA polymerase gene (RPO41) in complex stability, processivity, and fidelity. We found that deletion and point mutants of the thumb subdomain of yeast mtRNA polymerase increase the synthesis of abortive transcripts and the probability that the polymerase will disengage from the template during the formation of the late initial transcription and elongation complexes. Mutations in the thumb subdomain increase the amount of slippage products from a homopolymeric template and, unexpectedly, thumb subdomain deletions decrease the binding affinity for mitochondrial transcription factor (Mtf1). The latter suggests that the thumb subdomain is part of an extended binding surface area involved in binding Mtf1. PMID:25654332

  12. Mitochondrial translation factors of Trypanosoma brucei: elongation factor-Tu has a unique subdomain that is essential for its function

    Czech Academy of Sciences Publication Activity Database

    Cristodero, M.; Mani, J.; Oeljeklaus, S.; Aeberhard, L.; Hashimi, Hassan; Ramrath, D.J.F.; Lukeš, Julius; Warscheid, B.; Schneider, A.

    2013-01-01

    Roč. 90, č. 4 (2013), s. 744-755. ISSN 0950-382X R&D Projects: GA ČR GAP305/12/2261 Institutional support: RVO:60077344 Keywords : mitochondrial translation * Trypanosoma brucei * EF-Tu Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.026, year: 2013

  13. Control of Mitochondrial Transcription Specificity Factors (TFB1M and TFB2M) by Nuclear Respiratory Factors (NRF-1 and NRF-2) and PGC-1 Family Coactivators

    OpenAIRE

    Gleyzer, Natalie; Vercauteren, Kristel; Scarpulla, Richard C.

    2005-01-01

    In vertebrates, mitochondrial DNA (mtDNA) transcription is initiated bidirectionally from closely spaced promoters, HSP and LSP, within the D-loop regulatory region. Early studies demonstrated that mtDNA transcription requires mitochondrial RNA polymerase and Tfam, a DNA binding stimulatory factor that is required for mtDNA maintenance. Recently, mitochondrial transcription specificity factors (TFB1M and TFB2M), which markedly enhance mtDNA transcription in the presence of Tfam and mitochondr...

  14. Structural basis for S-adenosylmethionine binding and methyltransferase activity by mitochondrial transcription factor B1.

    Science.gov (United States)

    Guja, Kip E; Venkataraman, Krithika; Yakubovskaya, Elena; Shi, Hui; Mejia, Edison; Hambardjieva, Elena; Karzai, A Wali; Garcia-Diaz, Miguel

    2013-09-01

    Eukaryotic transcription factor B (TFB) proteins are homologous to KsgA/Dim1 ribosomal RNA (rRNA) methyltransferases. The mammalian TFB1, mitochondrial (TFB1M) factor is an essential protein necessary for mitochondrial gene expression. TFB1M mediates an rRNA modification in the small ribosomal subunit and thus plays a role analogous to KsgA/Dim1 proteins. This modification has been linked to mitochondrial dysfunctions leading to maternally inherited deafness, aminoglycoside sensitivity and diabetes. Here, we present the first structural characterization of the mammalian TFB1 factor. We have solved two X-ray crystallographic structures of TFB1M with (2.1 Å) and without (2.0 Å) its cofactor S-adenosyl-L-methionine. These structures reveal that TFB1M shares a conserved methyltransferase core with other KsgA/Dim1 methyltransferases and shed light on the structural basis of S-adenosyl-L-methionine binding and methyltransferase activity. Together with mutagenesis studies, these data suggest a model for substrate binding and provide insight into the mechanism of methyl transfer, clarifying the role of this factor in an essential process for mitochondrial function. PMID:23804760

  15. Sero-epidemiological survey and risk factors associated with bovine brucellosis among slaughtered cattle in Nigeria

    Directory of Open Access Journals (Sweden)

    Victor O. Akinseye

    2016-03-01

    Full Text Available Bovine brucellosis is endemic in Nigeria; however, limited data exist on nationwide studies and risk factors associated with the disease. Using a cross-sectional sero-epidemiological survey, we determined the prevalence of and risk factors for brucellosis in slaughtered cattle in three geographical regions of Nigeria. Serum samples from randomly selected unvaccinated cattle slaughtered over a period of 3 years (between December 2010 and September 2013 from northern, southern and south-western Nigeria were tested for antibodies to Brucella abortus using the Rose Bengal test. Data associated with risk factors of brucellosis were analysed by Stata Version 12. In all, 8105 cattle were screened. An overall seroprevalence of 3.9% (315/8105 was recorded by the Rose Bengal test, with 3.8%, 3.4% and 4.0% from the northern, southern and south-western regions, respectively. Bivariate analysis showed that cattle screened in northern Nigeria were less likely to be seropositive for antibodies to Brucella spp. than those from south-western Nigeria (odds ratio = 0.94; 95% confidence interval: 0.73–1.22. However, logistic regression analysis revealed that breed ( p = 0.04 and sex ( p £ 0.0001 of cattle were statistically significant for seropositivity to Brucella spp. The study found that brucellosis was endemic at a low prevalence among slaughtered cattle in Nigeria, with sex and breed of cattle being significant risk factors. Considering the public health implications of brucellosis, we advocate coordinated surveillance for the disease among diverse cattle populations in Nigeria, as is carried out in most developed countries.Keywords: Bovine brucellosis, RBT, Epidemiology, Public Health, Nigeria

  16. Crystal structure of the transcription factor sc-mtTFB offers insights into mitochondrial transcription

    OpenAIRE

    Schubot, Florian D; Chen, Chun-Jung; Rose, John P.; Dailey, Tamara A.; Dailey, Harry A.; Wang, Bi-Cheng

    2001-01-01

    Although it is commonly accepted that binding of mitochondrial transcription factor sc-mtTFB to the mitochondrial RNA polymerase is required for specific transcription initiation in Saccharomyces cerevisiae, its precise role has remained undefined. In the present work, the crystal structure of sc-mtTFB has been determined to 2.6 Å resolution. The protein consists of two domains, an N-terminal α/β-domain and a smaller domain made up of four α-helices. Contrary to previous predictions, sc-mtTFB...

  17. Cyclin D1 repression of nuclear respiratory factor 1 integrates nuclear DNA synthesis and mitochondrial function

    OpenAIRE

    Wang, Chenguang; Li, Zhiping; Lu, Yinan; Du, Runlei; Katiyar, Sanjay; Yang, Jianguo; Fu, Maofu; Leader, Jennifer E.; Quong, Andrew; Novikoff, Phyllis M.; Pestell, Richard G

    2006-01-01

    Cyclin D1 promotes nuclear DNA synthesis through phosphorylation and inactivation of the pRb tumor suppressor. Herein, cyclin D1 deficiency increased mitochondrial size and activity that was rescued by cyclin D1 in a Cdk-dependent manner. Nuclear respiratory factor 1 (NRF-1), which induces nuclear-encoded mitochondrial genes, was repressed in expression and activity by cyclin D1. Cyclin D1-dependent kinase phosphorylates NRF-1 at S47. Cyclin D1 abundance thus coordinates nuclear DNA synthesis...

  18. Elucidation of separate, but collaborative functions of the rRNA methyltransferase-related human mitochondrial transcription factors B1 and B2 in mitochondrial biogenesis reveals new insight into maternally inherited deafness

    OpenAIRE

    Cotney, Justin; McKay, Sharen E.; Shadel, Gerald S.

    2009-01-01

    Mitochondrial biogenesis is controlled by signaling networks that relay information to and from the organelles. However, key mitochondrial factors that mediate such pathways and how they contribute to human disease are not understood fully. Here we demonstrate that the rRNA methyltransferase-related human mitochondrial transcription factors B1 and B2 are key downstream effectors of mitochondrial biogenesis that perform unique, yet cooperative functions. The primary function of h-mtTFB2 is mtD...

  19. Impaired Transport of Mitochondrial Transcription Factor and the Metabolic Memory Phenomenon Associated with the Progression of Diabetic Retinopathy

    OpenAIRE

    Santos, Julia M.; Kowluru, Renu A.

    2013-01-01

    Diabetes damages retinal mitochondrial DNA (mtDNA), and compromises the mtDNA transcription. In the transcription and replication of mtDNA, nuclear-encoded transcription factor A (TFAM) is considered as a key activator, and we have shown that in diabetes while retinal TFAM gene expression is increased, its mitochondrial levels are decreased. This study investigates the role of mitochondrial outer and inner membrane transport systems in the transfer of TFAM into the mitochondria in diabetes, a...

  20. Oocyte Factors Suppress Mitochondrial Polynucleotide Phosphorylase to Remodel the Metabolome and Enhance Reprogramming

    Directory of Open Access Journals (Sweden)

    Swea-Ling Khaw

    2015-08-01

    Full Text Available Oocyte factors not only drive somatic cell nuclear transfer reprogramming but also augment the efficiency and quality of induced pluripotent stem cell (iPSC reprogramming. Here, we show that the oocyte-enriched factors Tcl1 and Tcl1b1 significantly enhance reprogramming efficiency. Clonal analysis of pluripotency biomarkers further show that the Tcl1 oocyte factors improve the quality of reprogramming. Mechanistically, we find that the enhancement effect of Tcl1b1 depends on Akt, one of its putative targets. In contrast, Tcl1 suppresses the mitochondrial polynucleotide phosphorylase (PnPase to promote reprogramming. Knockdown of PnPase rescues the inhibitory effect from Tcl1 knockdown during reprogramming, whereas PnPase overexpression abrogates the enhancement from Tcl1 overexpression. We further demonstrate that Tcl1 suppresses PnPase’s mitochondrial localization to inhibit mitochondrial biogenesis and oxidation phosphorylation, thus remodeling the metabolome. Hence, we identified the Tcl1-PnPase pathway as a critical mitochondrial switch during reprogramming.

  1. Genetic and non-genetic factors responsible for mitochondrial failure and Alzheimer’s disease

    OpenAIRE

    Gao Kuo; Niu Meiying; Zhai Xing; Huang Youliang; Tian Xin; Li Tiangang

    2014-01-01

    The objective of this review article is to explain the factors responsible for damaged mitochondria and its association with Alzheimer’s disease. Alzheimer’s disease (AD) is fairly produced by dysfunctional mitochondria that are alternatively caused by excessive reactive oxygen species and mitochondrial dynamic imbalance. In the pathogenesis of AD, there is important role of many factors including amyloid-beta peptide (A ), tau-proteins, and mutations in pr...

  2. A review of the factors affecting the costs of bovine mastitis : review article

    Directory of Open Access Journals (Sweden)

    K.R. Petrovski

    2006-06-01

    Full Text Available Mastitis is one of the most prevalent production diseases affecting the dairy cattle industry worldwide. Its occurrence is associated with direct and indirect losses and expenditures. When estimating the cost of mastitis to the dairy industry the cost of the control programmes must be added. The direct losses of mastitis are the only costs obvious to the farmer. The difference between the costs of mastitis on one side and the benefits of mastitis control on the other side will give us a picture of the economic efficacy of the mastitis control programme. Continuing education of the farmer is needed for better mastitis control programmes. This article is an attempt to review briefly all relevant factors included in the economics of bovine mastitis and to illustrate the authors' view of some of the costs.

  3. Immunohistochemical localization of basic fibroblast growth factor in bovine ovarian follicles.

    Science.gov (United States)

    van Wezel, I L; Umapathysivam, K; Tilley, W D; Rodgers, R J

    1995-12-29

    Basic fibroblast growth factor (bFGF, FGF2) controls cell proliferation and differentiation in many organs and tissues. In the ovary, cells proliferate and differentiate during folliculogenesis and during formation of the corpus luteum. While previous studies have inferred a role for bFGF in these processes, the precise contribution of bFGF to follicular activation or recruitment has not been established. For this reason, bFGF was immunolocalized in bovine follicles, using anti-bFGF immunoglobulin specific for the 1-24-amino acid terminus of the 18-kDa peptide. Basic FGF was immunolocalized to the cytoplasm of oocytes from bovine primordial and primary follicles. Strong immunostaining was also observed in corpora lutea, the ovarian surface epithelium, and smooth muscle cells surrounding blood vessels, while substantial levels of immunostaining were also present in cells of the theca interna. In most of the healthy antral follicles examined, the three or so layers of granulosa cells which were closest to the basement membrane were also stained, with greatest levels of staining at the most basal region of each cell. Atretic antral follicles had significant and uniform levels of immunostaining throughout the theca interna and the membrana granulosa. Immunostaining as described above was reduced to background levels when the primary specific immunoglobulin was preabsorbed with a 350 molar excess of peptide comprising the NH2-terminal 24 amino acids of bFGF. Based upon our previous observations and those reported here, we propose that basic fibroblast growth factor is synthesized by immature oocytes, especially those from primordial and primary follicles, and that bFGF has a potential role in activating follicle growth via stimulation of granulosa cell proliferation and follicular basement membrane synthesis. PMID:8824888

  4. Modulation of mitochondrial function and morphology by interaction of Omi/HtrA2 with the mitochondrial fusion factor OPA1

    Energy Technology Data Exchange (ETDEWEB)

    Kieper, Nicole; Holmstroem, Kira M.; Ciceri, Dalila; Fiesel, Fabienne C. [Center of Neurology and Hertie Institute for Clinical Brain Research, 72076 Tuebingen (Germany); Wolburg, Hartwig [Institute of Pathology, University of Tuebingen, 72076 Tuebingen (Germany); Ziviani, Elena; Whitworth, Alexander J. [Medical Research Council Centre for Developmental and Biomedical Genetics, University of Sheffield, Sheffield S10 2TN (United Kingdom); Martins, L. Miguel [Cell Death Regulation Laboratory, MRC Toxicology Unit, Leicester LE1 9HN (United Kingdom); Kahle, Philipp J., E-mail: philipp.kahle@uni-tuebingen.de [Center of Neurology and Hertie Institute for Clinical Brain Research, 72076 Tuebingen (Germany); Krueger, Rejko, E-mail: rejko.krueger@uni-tuebingen.de [Center of Neurology and Hertie Institute for Clinical Brain Research, 72076 Tuebingen (Germany)

    2010-04-15

    Loss of Omi/HtrA2 function leads to nerve cell loss in mouse models and has been linked to neurodegeneration in Parkinson's and Huntington's disease. Omi/HtrA2 is a serine protease released as a pro-apoptotic factor from the mitochondrial intermembrane space into the cytosol. Under physiological conditions, Omi/HtrA2 is thought to be involved in protection against cellular stress, but the cytological and molecular mechanisms are not clear. Omi/HtrA2 deficiency caused an accumulation of reactive oxygen species and reduced mitochondrial membrane potential. In Omi/HtrA2 knockout mouse embryonic fibroblasts, as well as in Omi/HtrA2 silenced human HeLa cells and Drosophila S2R+ cells, we found elongated mitochondria by live cell imaging. Electron microscopy confirmed the mitochondrial morphology alterations and showed abnormal cristae structure. Examining the levels of proteins involved in mitochondrial fusion, we found a selective up-regulation of more soluble OPA1 protein. Complementation of knockout cells with wild-type Omi/HtrA2 but not with the protease mutant [S306A]Omi/HtrA2 reversed the mitochondrial elongation phenotype and OPA1 alterations. Finally, co-immunoprecipitation showed direct interaction of Omi/HtrA2 with endogenous OPA1. Thus, we show for the first time a direct effect of loss of Omi/HtrA2 on mitochondrial morphology and demonstrate a novel role of this mitochondrial serine protease in the modulation of OPA1. Our results underscore a critical role of impaired mitochondrial dynamics in neurodegenerative disorders.

  5. Modulation of mitochondrial function and morphology by interaction of Omi/HtrA2 with the mitochondrial fusion factor OPA1

    International Nuclear Information System (INIS)

    Loss of Omi/HtrA2 function leads to nerve cell loss in mouse models and has been linked to neurodegeneration in Parkinson's and Huntington's disease. Omi/HtrA2 is a serine protease released as a pro-apoptotic factor from the mitochondrial intermembrane space into the cytosol. Under physiological conditions, Omi/HtrA2 is thought to be involved in protection against cellular stress, but the cytological and molecular mechanisms are not clear. Omi/HtrA2 deficiency caused an accumulation of reactive oxygen species and reduced mitochondrial membrane potential. In Omi/HtrA2 knockout mouse embryonic fibroblasts, as well as in Omi/HtrA2 silenced human HeLa cells and Drosophila S2R+ cells, we found elongated mitochondria by live cell imaging. Electron microscopy confirmed the mitochondrial morphology alterations and showed abnormal cristae structure. Examining the levels of proteins involved in mitochondrial fusion, we found a selective up-regulation of more soluble OPA1 protein. Complementation of knockout cells with wild-type Omi/HtrA2 but not with the protease mutant [S306A]Omi/HtrA2 reversed the mitochondrial elongation phenotype and OPA1 alterations. Finally, co-immunoprecipitation showed direct interaction of Omi/HtrA2 with endogenous OPA1. Thus, we show for the first time a direct effect of loss of Omi/HtrA2 on mitochondrial morphology and demonstrate a novel role of this mitochondrial serine protease in the modulation of OPA1. Our results underscore a critical role of impaired mitochondrial dynamics in neurodegenerative disorders.

  6. Mitochondrial Inhibitory Factor Protein 1 Functions as an Endogenous Inhibitor for Coupling Factor 6.

    Science.gov (United States)

    Kawai, Misato; Osanai, Tomohiro; Tanaka, Makoto; Magota, Koji; Tomita, Hirofumi; Okumura, Ken

    2016-07-01

    Coupling factor 6 (CF6) forces a counter-clockwise rotation of plasma membrane F1 Fo complex unlike a proton-mediated clockwise rotation in the mitochondria, resulting in ATP hydrolysis, proton import, and apoptosis. Inhibitory peptide 1 (IF1) inhibits a unidirectional counter-clockwise rotation of F1 Fo complex without affecting ATP synthesis by a clockwise rotation. We tested the hypothesis that IF1 may antagonize the biological action of CF6 in human embryonic kidney 293 cells. We generated mature and immature IF1 expression vectors and those labeled with GFP at the C-terminus. In the immature IF1-GFP overexpressing cells, the mitochondrial network of IF1-GFP was newly found at the plasma membrane after peripheral translocation, whereas in mature IF1-GFP transfected cells, a less punctuate rather homogenous pattern was found in the cytoplasm. IF1 protein was detected in the exosome fraction of culture media, and it was enhanced by mature or immature IF1 transfection. Extracellular ATP hydrolysis was enhanced by CF6, whereas immature or mature IF1 transfection suppressed ATP hydrolysis in response to CF6. Intracellular pH was decreased by CF6 but was unchanged after immature IF1 transfection. CF6-induced increase in apoptotic cells was blocked by immature or mature IF1, being accompanied by protein kinase B (PKB) phosphorylation. IF1 antagonizes the pro-apoptotic action of CF6 by relief of intracellular acidification and resultant phosphorylation of PKB. Given the widespread biological actions of CF6, the physiological and pathological functions of IF1 may be expected to be complex. J. Cell. Biochem. 117: 1680-1687, 2016. © 2015 Wiley Periodicals, Inc. PMID:26659871

  7. Herd-level risk factors for infection with bovine leukemia virus in Canadian dairy herds.

    Science.gov (United States)

    Nekouei, Omid; VanLeeuwen, John; Sanchez, Javier; Kelton, David; Tiwari, Ashwani; Keefe, Greg

    2015-05-01

    Enzootic bovine leukosis (EBL) is an economically important infection of dairy cattle worldwide, which is caused by bovine leukemia virus (BLV). The prevalence of infection in Canadian dairy herds is high and continues to increase; however, there has not been a national program to control BLV. This cross-sectional study was conducted to identify potentially important risk factors for BLV infection on Canadian dairy herds, which is a prerequisite to developing an effective control program. During 1998-2003, based on a stratified two-stage random sampling process, 315 dairy farms from seven provinces of Canada were selected. Within each farm, 9-45 cows were bled and tested with a commercial serum ELISA kit for BLV antibodies. A comprehensive questionnaire, targeting potentially important herd-level management indicators, was successfully administered in 272 herds. A zero-inflated negative binomial (ZINB) regression model was fit to the resulting data to assess the potential associations between BLV seropositivity and a variety of herd-level factors. Seventy-eight percent of the herds were identified as BLV-positive (had one or more test positive animals). In the negative-binomial part of the final ZINB model, herds with clinical cases of leukosis during the 12 months prior to sampling, as well as herds which purchased animals with unknown BLV infection status in the last five years, had a significantly larger proportion of BLV positive animals. Based on a significant interaction between two of the risk factors, changing gloves between cows during pregnancy examination was not statistically associated with lower proportion of infected cows compared with not changing gloves, in the western Canadian provinces. In the logistic part of the model, herds from eastern Canadian provinces and those not purchasing cows in the last five years had increased odds of being free from BLV. The high prevalence of infection across Canada should be addressed through the development and

  8. Factors that affect the reproductive efficiency of the recipient within a bovine embryo transfer program

    Directory of Open Access Journals (Sweden)

    Arturo Duica A.

    2007-12-01

    Full Text Available The embryo transfer is a biotechnological technique that allows increasing the descendant of animals with high genetic value. The positive results, represented in pregnancy after the application of this technique, are affected by some factors that are inherent to the donor, the embryo, the technique, and the recipients which receive a strange embryo in the uterus allowing pregnancy. This review describes some factors affecting the reproductive efficiency of the recipients of bovine embryos within a program of embryo transfer. Its important to evaluate the parameters in this kind of recipients, as race, age, physiological status, health status, weight, reproductive tract integrity and management, and also too monitoring the ovarian structures while the estrus synchronization, and within previous and posterior stages in embryo transfer procedure. Therefore an optimum follicular development will be determinant to corpus luteum formation which generates enough serum progesterone concentrations to offer a right uterine environment allowing the optimum embryo development. Controlling the factors that affect the efficiency of the embryo transfer, it will obtain an increasing of positive results represented in pregnancies and births of individuals come from animals with high genetic value.

  9. Mitochondrial structure and dynamics as critical factors in honey bee (Apis mellifera L.) caste development.

    Science.gov (United States)

    Santos, Douglas Elias; Alberici, Luciane Carla; Hartfelder, Klaus

    2016-06-01

    The relationship between nutrition and phenotype is an especially challenging question in cases of facultative polyphenism, like the castes of social insects. In the honey bee, Apis mellifera, unexpected modifications in conserved signaling pathways revealed the hypoxia response as a possible mechanism underlying the regulation of body size and organ growth. Hence, the current study was designed to investigate possible causes of why the three hypoxia core genes are overexpressed in worker larvae. Parting from the hypothesis that this has an endogenous cause and is not due to differences in external oxygen levels we investigated mitochondrial numbers and distribution, as well as mitochondrial oxygen consumption rates in fat body cells of queen and worker larvae during the caste fate-critical larval stages. By immunofluorescence and electron microscopy we found higher densities of mitochondria in queen larval fat body, a finding further confirmed by a citrate synthase assay quantifying mitochondrial functional units. Oxygen consumption measurements by high-resolution respirometry revealed that queen larvae have higher maximum capacities of ATP production at lower physiological demand. Finally, the expression analysis of mitogenesis-related factors showed that the honey bee TFB1 and TFB2 homologs, and a nutritional regulator, ERR, are overexpressed in queen larvae. These results are strong evidence that the differential nutrition of queen and worker larvae by nurse bees affects mitochondrial dynamics and functionality in the fat body of these larvae, hence explaining their differential hypoxia response. PMID:27058771

  10. The role of exercise and exercise-related factors in the control of mitochondrial oxidative function

    OpenAIRE

    Walsh, Brandon

    2002-01-01

    The effects of exercise and exercise-related factors on the control of mitochondrial oxidative function were investigated in human and rat skeletal muscle. Oxidative function was assessed through the measurement of oxygen consumption in chemically permeabilized (skinned) fibers. Mitochondria in skinned muscle fibers remain in their natural structural environment, permitting sophisticated mechanisms of respiratory control to be studied while allowing the surrounding milieu to...

  11. Social factors affecting seasonal variation in bovine trypanosomiasis on the Jos Plateau, Nigeria

    Science.gov (United States)

    2013-01-01

    Background African Animal Trypanosomiasis (AAT) is a widespread disease of livestock in Nigeria and presents a major constraint to rural economic development. The Jos Plateau was considered free from tsetse flies and the trypanosomes they transmit due to its high altitude and this trypanosomiasis free status attracted large numbers of cattle-keeping pastoralists to the area. The Jos Plateau now plays a major role in the national cattle industry in Nigeria, accommodating approximately 7% of the national herd, supporting 300,000 pastoralists and over one million cattle. During the past two decades tsetse flies have invaded the Jos Plateau and animal trypanosomiasis has become a significant problem for livestock keepers. Here we investigate the epidemiology of trypanosomiasis as a re-emerging disease on the Plateau, examining the social factors that influence prevalence and seasonal variation of bovine trypanosomiasis. Methods In 2008 a longitudinal two-stage cluster survey was undertaken on the Jos Plateau. Cattle were sampled in the dry, early wet and late wet seasons. Parasite identification was undertaken using species-specific polymerase chain reactions to determine the prevalence and distribution of bovine trypanosomiasis. Participatory rural appraisal was also conducted to determine knowledge, attitudes and practices concerning animal husbandry and disease control. Results Significant seasonal variation between the dry season and late wet season was recorded across the Jos Plateau, consistent with expected variation in tsetse populations. However, marked seasonal variations were also observed at village level to create 3 distinct groups: Group 1 in which 50% of villages followed the general pattern of low prevalence in the dry season and high prevalence in the wet season; Group 2 in which 16.7% of villages showed no seasonal variation and Group 3 in which 33.3% of villages showed greater disease prevalence in the dry season than in the wet season. Conclusions

  12. Outer mitochondrial membrane localization of apoptosis-inducing factor: mechanistic implications for release

    Directory of Open Access Journals (Sweden)

    Seong‑Woon Yu

    2009-11-01

    Full Text Available Poly(ADP-ribose polymerase-1-dependent cell death (known as parthanatos plays a pivotal role in many clinically important events including ischaemia/reperfusion injury and glutamate excitotoxicity. A recent study by us has shown that uncleaved AIF (apoptosis-inducing factor, but not calpain-hydrolysed truncated-AIF, was rapidly released from the mitochondria during parthanatos, implicating a second pool of AIF that might be present in brain mitochondria contributing to the rapid release. In the present study, a novel AIF pool is revealed in brain mitochondria by multiple biochemical analyses. Approx. 30% of AIF loosely associates with the outer mitochondrial membrane on the cytosolic side, in addition to its main localization in the mitochondrial intermembrane space attached to the inner membrane. Immunogold electron microscopic analysis of mouse brain further supports AIF association with the outer, as well as the inner, mitochondrial membrane in vivo. In line with these observations, approx. 20% of uncleaved AIF rapidly translocates to the nucleus and functionally causes neuronal death upon NMDA (N-methyl-d-aspartate treatment. In the present study we show for the first time a second pool of AIF in brain mitochondria and demonstrate that this pool does not require cleavage and that it contributes to the rapid release of AIF. Moreover, these results suggest that this outer mitochondrial pool of AIF is sufficient to cause cell death during parthanatos. Interfering with the release of this outer mitochondrial pool of AIF during cell injury paradigms that use parthanatos hold particular promise for novel therapies to treat neurological disorders.

  13. Epidermal growth factor receptor is required for estradiol-stimulated bovine satellite cell proliferation.

    Science.gov (United States)

    Reiter, B C; Kamanga-Sollo, E; Pampusch, M S; White, M E; Dayton, W R

    2014-07-01

    The objective of this study was to assess the role of the epidermal growth factor receptor (EGFR) in estradiol-17β (E2)-stimulated proliferation of cultured bovine satellite cells (BSCs). Treatment of BSC cultures with AG1478 (a specific inhibitor of EGFR tyrosine kinase activity) suppresses E2-stimulated BSC proliferation (P LR3-IGF-1 (an IGF1 analogue that binds normally to the insulin-like growth factor receptor (IGFR)-1 but has little or no affinity for IGF binding proteins) in cultured BSCs (P < 0.05). Even though EGFR siRNA treatment has no effect on IGFR-1β mRNA expression in cultured BSCs, IGFR-1β protein level is substantially reduced in BSCs treated with EGFR siRNA. These data suggest that EGFR silencing results in post-transcriptional modifications that result in decreased IGFR-1β protein levels. Although it is clear that functional EGFR is necessary for E2-stimulated proliferation of BSCs, the role of EGFR is not clear. Transactivation of EGFR may directly stimulate proliferation, or EGFR may function to maintain the level of IGFR-1β which is necessary for E2-stimulated proliferation. It also is possible that the role of EGFR in E2-stimulated BSC proliferation may involve both of these mechanisms. PMID:24906928

  14. Expression of DNAJA1 in bovine muscles according to developmental age and management factors.

    Science.gov (United States)

    Cassar-Malek, I; Guillemin, N; Hocquette, J-F; Micol, D; Bauchart, D; Picard, B; Jurie, C

    2011-05-01

    We have recently shown that the expression of the DNAJA1 gene encoding a heat shock protein (Hsp40) is a negative marker of meat tenderness in Charolais bulls. To acquire knowledge on the regulation of DNAJA1 expression, we analysed the abundance of DNAJA1 transcripts and protein during development and according to management factors (e.g. feeding treatments, growth path and stress status) in different bovine muscles during postnatal life. We report here a developmental expression profile for DNAJA1 with decreased levels of transcript and protein during the progression of myogenesis. During postnatal life, we found the highest expression of DNAJA1 in the most oxidative muscles. No effect was detected for dietary treatment (pasture v. maize-based diet), growth path (compensatory growth after a restriction period) or pre-slaughter stress status. Therefore, the genetic background and muscle type could be considered as the main factors regarding the level of DNAJA1. Integration of the knowledge gained from this study should help to predict muscle metabolic properties and the ability of the live animals to give high sensory quality meat. PMID:22440026

  15. Contagious bovine pleuropneumonia: Seroprevalence and risk factors in Western Oromia, Ethiopia.

    Science.gov (United States)

    Daniel, Garuma; Abdurahaman, Mukarim; Tuli, Getachew; Deresa, Benti

    2016-01-01

    Contagious bovine pleuropneumonia (CBPP) is one of the most important threats to cattle health and production in Ethiopia. At the livestock farm of the Bako Agricultural Research Center, an outbreak of respiratory disease of cattle occurred in May 2011, and many animals were affected and died before the disease was diagnosed. Therefore, this study was designed to determine the seroprevalence of CBPP antibodies in selected districts of Western Oromia Region and to assess the potential risk factors for the occurrence of the disease. A crosssectional study was conducted from November 2013 to March 2014 in three selected districts of Western Oromia Region. A total of 386 sera were examined for the presence of specific antibodies against Mycoplasma mycoidesmycoides small colony (MmmSC), using a competitive enzyme-linked immunosorbent assay. The risk factors that were evaluated in this study were geographical location, age, sex, breed and body condition. The overall seroprevalence in this study was 28.5%. The seroprevalence of Mycoplasma mycoidesmycoides small colony antibodies at the district level was 40.3%, 19.0% and 5.7% in Gobbu Sayyo, BakoTibbe and Horro districts, respectively. There was a statistically significant variation ( p 0.05) with the serological status of the animal. This study showed that the overall prevalence of CBPP in Western Oromia Zones was high. This warrants the implementation of appropriate preventive and control measures to minimise the economic losses associated with the disease. PMID:27247066

  16. Sero-epidemiological survey and risk factors associated with bovine brucellosis among slaughtered cattle in Nigeria.

    Science.gov (United States)

    Akinseye, Victor O; Adesokan, Hezekiah K; Ogugua, Akwoba J; Adedoyin, Folashade J; Otu, Patricia I; Kwaghe, Ayi V; Kolawole, Noah O; Okoro, Oyinye J; Agada, Charity A; Tade, Adeniyi O; Faleke, Olufemi O; Okeke, Anyanwu L; Akanbi, Ibikunle M; Ibitoye, Mofoluwake M; Dipeolu, Morenike O; Dale, Emma J; Lorraine, Perrett; Taylor, Andrew V; Awosanya, Emmanuel A; Cadmus, Eniola O; Stack, Judy A; Cadmus, Simeon I

    2016-01-01

    Bovine brucellosis is endemic in Nigeria; however, limited data exist on nationwide studies and risk factors associated with the disease. Using a cross-sectional sero-epidemiological survey, we determined the prevalence of and risk factors for brucellosis in slaughtered cattle in three geographical regions of Nigeria. Serum samples from randomly selected unvaccinated cattle slaughtered over a period of 3 years (between December 2010 and September 2013) from northern, southern and south-western Nigeria were tested for antibodies to Brucella abortus using the Rose Bengal test. Data associated with risk factors of brucellosis were analysed by Stata Version 12. In all, 8105 cattle were screened. An overall seroprevalence of 3.9% (315/8105) was recorded by the Rose Bengal test, with 3.8%, 3.4% and 4.0% from the northern, southern and south-western regions, respectively. Bivariate analysis showed that cattle screened in northern Nigeria were less likely to be seropositive for antibodies to Brucella spp. than those from south-western Nigeria (odds ratio = 0.94; 95% confidence interval: 0.73-1.22). However, logistic regression analysis revealed that breed ( p = 0.04) and sex ( p £ 0.0001) of cattle were statistically significant for seropositivity to Brucella spp. The study found that brucellosis was endemic at a low prevalence among slaughtered cattle in Nigeria, with sex and breed of cattle being significant risk factors. Considering the public health implications of brucellosis, we advocate coordinated surveillance for the disease among diverse cattle populations in Nigeria, as is carried out in most developed countries. PMID:27247065

  17. Negative transcriptional regulation of mitochondrial transcription factor A (TFAM) by nuclear TFAM

    International Nuclear Information System (INIS)

    Highlights: • TFAM localizes in nuclei and mitochondria of neuronal cells. • Nuclear TFAM does not bind the Tfam promoter. • Nuclear TFAM reduced the Tfam promoter activity via suppressing NRF-1 activity. • A novel self-negative feedback regulation of Tfam gene expression is explored. • FAM may play different roles depending on its subcellular localizations. - Abstract: The nuclear DNA-encoded mitochondrial transcription factor A (TFAM) is synthesized in cytoplasm and transported into mitochondria. TFAM enhances both transcription and replication of mitochondrial DNA. It is unclear, however, whether TFAM plays a role in regulating nuclear gene expression. Here, we demonstrated that TFAM was localized to the nucleus and mitochondria by immunostaining, subcellular fractionation, and TFAM-green fluorescent protein hybrid protein studies. In HT22 hippocampal neuronal cells, human TFAM (hTFAM) overexpression suppressed human Tfam promoter-mediated luciferase activity in a dose-dependent manner. The mitochondria targeting sequence-deficient hTFAM also repressed Tfam promoter activity to the same degree as hTFAM. It indicated that nuclear hTFAM suppressed Tfam expression without modulating mitochondrial activity. The repression required for nuclear respiratory factor-1 (NRF-1), but hTFAM did not bind to the NRF-1 binding site of its promoter. TFAM was co-immunoprecipitated with NRF-1. Taken together, we suggest that nuclear TFAM down-regulate its own gene expression as a NRF-1 repressor, showing that TFAM may play different roles depending on its subcellular localizations

  18. Negative transcriptional regulation of mitochondrial transcription factor A (TFAM) by nuclear TFAM

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Jin; Kang, Young Cheol; Park, Wook-Ha; Jeong, Jae Hoon; Pak, Youngmi Kim, E-mail: ykpak@khu.ac.kr

    2014-07-18

    Highlights: • TFAM localizes in nuclei and mitochondria of neuronal cells. • Nuclear TFAM does not bind the Tfam promoter. • Nuclear TFAM reduced the Tfam promoter activity via suppressing NRF-1 activity. • A novel self-negative feedback regulation of Tfam gene expression is explored. • FAM may play different roles depending on its subcellular localizations. - Abstract: The nuclear DNA-encoded mitochondrial transcription factor A (TFAM) is synthesized in cytoplasm and transported into mitochondria. TFAM enhances both transcription and replication of mitochondrial DNA. It is unclear, however, whether TFAM plays a role in regulating nuclear gene expression. Here, we demonstrated that TFAM was localized to the nucleus and mitochondria by immunostaining, subcellular fractionation, and TFAM-green fluorescent protein hybrid protein studies. In HT22 hippocampal neuronal cells, human TFAM (hTFAM) overexpression suppressed human Tfam promoter-mediated luciferase activity in a dose-dependent manner. The mitochondria targeting sequence-deficient hTFAM also repressed Tfam promoter activity to the same degree as hTFAM. It indicated that nuclear hTFAM suppressed Tfam expression without modulating mitochondrial activity. The repression required for nuclear respiratory factor-1 (NRF-1), but hTFAM did not bind to the NRF-1 binding site of its promoter. TFAM was co-immunoprecipitated with NRF-1. Taken together, we suggest that nuclear TFAM down-regulate its own gene expression as a NRF-1 repressor, showing that TFAM may play different roles depending on its subcellular localizations.

  19. Interaction of mammalian mitochondrial elongation factor EF-Tu with guanine nucleotides.

    OpenAIRE

    Cai, Y. C.; Bullard, J. M.; Thompson, N L; Spremulli, L L

    2000-01-01

    Elongation factor Tu (EF-Tu) promotes the binding of aminoacyl-tRNA (aa-tRNA) to the acceptor site of the ribosome. During the elongation cycle, EF-Tu interacts with guanine nucleotides, aa-tRNA and its nucleotide exchange factor (EF-Ts). Quantitative determination of the equilibrium dissociation constants that govern the interactions of mammalian mitochondrial EF-Tu (EF-Tu(mt)) with guanine nucleotides was the focus of the work reported here. Equilibrium dialysis with [3H]GDP was used to mea...

  20. Risk factors for herd-level bovine-tuberculosis seropositivity in transhumant cattle in Uganda.

    Science.gov (United States)

    Oloya, J; Muma, J B; Opuda-Asibo, J; Djønne, B; Kazwala, R; Skjerve, E

    2007-08-16

    We investigated the prevalence and risk factors to positive herd-level tuberculin reactivity between October 2003 to May 2004 to bovine tuberculosis (BTB) in the four transhumant districts of Uganda: three districts (Karamoja region) of nomadic transhumance cattle rearing (30 superherds and 1522 cattle), and one district (Nakasongola) of fixed-transhumance (7 herds and 342 cattle). We used the comparative intradermal skin-test, sampled 50 animals per superherd/herd, and considered herd positive if there was at least one reactor. Of the 30 superherds under nomadic transhumance, 60% (95% CI 41.4, 79) were tuberculin-test positive; of the 7 fixed herds, 14.3% (95% CI -20.7, 49.2) were tuberculin test positive. The true herd prevalence was estimated at 46.6%. Many risk factors were collinear. The final multivariable logistic-regression model included: recent introductions from market (OR=3.4; 95% CI 1.1, 10.3), drinking water form mud holes during dry season (OR=49; 95% CI 9.1, 262), and the presence of monkeys (OR=0.08; 95% CI 0.0, 0.6) or warthogs (OR=0.1; 95% CI 0.0, 0.3). No association was found between herd size or number of herd contacts with reactors; it was probably masked by the effect of high between-herd interactions. Provision of water from mud holes in dry river beds and introductions of new animals are risk factors that might be targeted to control BTB in transhumance areas. PMID:17482694

  1. Expression of lymphangiogenic vascular endothelial growth factor family members in bovine corpus luteum.

    Science.gov (United States)

    Berisha, B; Schilffarth, S; Kenngott, R; Sinowatz, F; Meyer, H H D; Schams, D

    2013-08-01

    The aim of this study was to evaluate mRNA expression, protein concentration and localization of the assumedly important lymphangiogenic factors VEGFC and VEGFD and the receptor FLT4 in bovine corpora lutea (CL) during different physiological stages. In experiment 1, CL were collected in a slaughterhouse and stages (days 1-2, 3-4, 5-7, 8-12, 13-16, >18) of oestrous cycle and month 8 of pregnancy. In experiment 2, prostaglandin F2α (PGF)-induced luteolysis was performed in 30 cows, which were injected with PGF analogue on day 8-12 (mid-luteal phase), and CL were collected before and 0.5, 2, 4, 12, 24, 48 and 64 h after PGF injection. The mRNA expression was characterized by RT-qPCR. All three factors were clearly expressed and showed significant changes during different groups and periods examined in both experiments. Protein concentrations of VEGFD and FLT4 measured by ELISA were not detectable in early cyclic CL but increased to higher plateau levels during pregnancy. After PGF-induced luteolysis FLT4 protein showed an increase within 2-24 h after the injection. FLT4 localization by immunohistochemistry in the cytoplasm of luteal cells was relatively weak in early CL. It increased in late CL and especially in CL during pregnancy. During pregnancy, a positive FLT4 staining in both the nucleus and cytoplasm of lymphatic endothelial cells in peripheral tissue was observed. In conclusion, our results lead to the assumption that lymphangiogenic factors are produced and regulated in CL and may be involved in mechanisms regulating CL function, especially during pregnancy. PMID:23126445

  2. The three-dimensional structure of bovine platelet factor 4 at 3.0-A resolution.

    Science.gov (United States)

    St Charles, R; Walz, D A; Edwards, B F

    1989-02-01

    Platelet factor 4 (PF4), which is released by platelets during coagulation, binds very tightly to negatively charged oligosaccharides such as heparin. To date, six other proteins are known that are homologous in sequence with PF4 but have quite different functions. The structure of a tetramer of bovine PF4 complexed with one Ni(CN)4(2-) molecule has been determined at 3.0 A resolution and refined to an R factor of 0.28. The current model contains residues 24-85, no solvent, and one overall temperature factor. Residues 1-13, which carried an oligosaccharide chain, were removed with elastase to induce crystallization; residues 14-23 and presumably 86-88 are disordered in the electron density map. Because no heavy atom derivative was isomorphous with the native crystals, the complex of PF4 with one Ni(CN)4(2-) molecule was solved using a single, highly isomorphous Pt(CN)4(2-) derivative and the iterative, single isomorphous replacement method. The secondary structure of the PF4 subunit, from amino- to carboxyl-terminal end, consists of an extended loop, three strands of antiparallel beta-sheet arranged in a Greek key, and one alpha-helix. The tetramer contains two extended, six-stranded beta-sheets, each formed by two subunits, which are arranged back-to-back to form a "beta-bilayer" structure with two buried salt bridges sandwiched in the middle. The carboxyl-terminal alpha-helices, which contain lysine residues that are thought to be intimately involved in binding heparin, are arranged as antiparallel pairs on the surface of each extended beta-sheet. PMID:2914894

  3. Occurrence and factors associated with bovine cysticercosis recorded in cattle at meat inspection in Denmark in 2004-2011

    DEFF Research Database (Denmark)

    Calvo Artavia, Francisco Fernando; Nielsen, Liza Rosenbaum; Dahl, J.;

    2013-01-01

    cattle population, (2) estimate the animal level prevalence (3) provide descriptive statistics of potential risk factors for BC, and (4) determine attributable risks and fractions of selected risk factors potentially useful for a future risk-based meat inspection system. In total, 348 cases of BC were......Current EU regulation requires that every bovine carcass is examined for bovine cysticercosis (BC) at meat inspection. This is costly and might be superfluous at low BC prevalence. However, from a consumer view-point it may be important to identify and manage infected carcasses to avoid human...... infection. If relevant data could be effectively used to classify animals with respect to their risk of being infected, then the current meat inspection could be replaced by a more cost-effective system targeting high-risk animals. This study aimed to (1) describe the distribution of BC cases in the Danish...

  4. Tumor necrosis factor alpha inhibits in vitro bovine embryo development through a prostaglandin mediated mechanism

    Directory of Open Access Journals (Sweden)

    Jackson Lauren R

    2012-03-01

    Full Text Available Abstract Mastitis or other infectious diseases have been related to reduced fertility in cattle. Inflammatory cytokines such as tumor necrosis factor α (TNFα are released in response to infection and may have negative effects on embryo development. In the current study the effect of exposure to TNFα on the development of in vitro fertilized bovine embryos was examined. Indomethacin, a prostaglandin synthesis inhibitor, was used to determine if blockade of prostaglandin synthesis would alter the effects of TNFα. Ovaries were obtained from a local abattoir and immature COC were isolated from 2-10 mm follicles, in vitro matured and fertilized. After fertilization, groups of presumptive zygotes were randomly placed into either control development medium, medium containing 25 ng/mL TNFα or medium containing 25 ng/mL TNFα plus 1 μg/mL indomethacin. The proportion of blastocysts formed was assessed at day 7 of culture. Fewer embryos exposed to TNFα alone reached the blastocyst stage (17.5 ± 2.4%, P

  5. Individual factors associated with L- and H-type Bovine Spongiform Encephalopathy in France

    Directory of Open Access Journals (Sweden)

    Sala Carole

    2012-05-01

    Full Text Available Abstract Background Cattle with L-type (L-BSE and H-type (H-BSE atypical Bovine Spongiform encephalopathy (BSE were identified in 2003 in Italy and France respectively before being identified in other countries worldwide. As of December 2011, around 60 atypical BSE cases have currently been reported in 13 countries, with over one third in France. While the epidemiology of classical BSE (C-BSE has been widely described, atypical BSEs are still poorly documented, but appear to differ from C-BSE. We analysed the epidemiological characteristics of the 12 cases of L-BSE and 11 cases of H-BSE detected in France from January 2001 to late 2009 and looked for individual risk factors. As L-BSE cases did not appear to be homogeneously distributed throughout the country, two complementary methods were used: spatial analysis and regression modelling. L-BSE and H-BSE were studied separately as both the biochemical properties of their pathological prion protein and their features differ in animal models. Results The median age at detection for L-BSE and H-BSE cases was 12.4 (range 8.4-18.7 and 12.5 (8.3-18.2 years respectively, with no significant difference between the two distributions. However, this median age differed significantly from that of classical BSE (7.0 (range 3.5-15.4 years. A significant geographical cluster was detected for L-BSE. Among animals over eight years of age, we showed that the risk of being detected as a L-BSE case increased with age at death. This was not the case for H-BSE. Conclusion To the best of our knowledge this is the first study to describe the epidemiology of the two types of atypical BSE. The geographical cluster detected for L-BSE could be partly due to the age structure of the background-tested bovine population. Our regression analyses, which adjusted for the effect of age and birth cohort showed an age effect for L-BSE and the descriptive analysis showed a particular age structure in the area where the cluster was

  6. Shiga Toxin-Producing Escherichia coli Isolated from Bovine Mastitic Milk: Serogroups, Virulence Factors, and Antibiotic Resistance Properties

    OpenAIRE

    Hassan Momtaz; Farhad Safarpoor Dehkordi; Taghi Taktaz; Amir Rezvani; Sajad Yarali

    2012-01-01

    The aim of this study was to detect the virulence factors, serogroups, and antibiotic resistance properties of Shiga toxin-producing Escherichia coli, by using 268 bovine mastitic milk samples which were diagnosed using California Mastitis Test. After E. coli identification, PCR assays were developed for detection of different virulence genes, serogroups, and antibiotic resistance genes of Escherichia coli. The antibiotic resistance pattern was studied using disk diffusion method. Out of 268 ...

  7. Cytokine regulation by virus infection: bovine viral diarrhea virus, a flavivirus, downregulates production of tumor necrosis factor alpha in macrophages in vitro.

    OpenAIRE

    Adler, H; Jungi, T. W.; Pfister, H; Strasser, M; Sileghem, M; Peterhans, E

    1996-01-01

    Bovine bone marrow-derived macrophages were infected in vitro with noncytopathic or cytopathic strains of bovine viral diarrhea virus. Infection with both biotypes resulted in a decreased production of tumor necrosis factor alpha upon stimulation with heat-inactivated Salmonella dublin or lipopolysaccharide. Other macrophage functions were not downregulated, indicating that the observed effect was not due to a loss in macrophage viability. The downregulated production of tumor necrosis factor...

  8. Mitochondrial haplogroups H and J: risk and protective factors for ischemic cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Mariana Fernández-Caggiano

    Full Text Available BACKGROUND: Since mitochondria are the principal source of reactive oxygen species (ROS, these organelles may play an important role in ischemic cardiomyopathy (IC development. The mitochondrial genome may influence this disease. The aim of the present study was to test the relationship between IC development and the impact of single nucleotide polymorphisms (SNPs in mitochondrial DNA (mtDNA defining the mitochondrial haplogroups in a population study. METHODOLOGY AND PRINCIPAL FINDINGS: Ten major European haplogroups were identified by using the single base extension technique and by polymerase chain reaction-restriction fragment length polymorphism. Frequencies and Odds Ratios for the association between IC patients (n = 358 and healthy controls (n = 423 were calculated. No convincing associations between classical risk factors for ischemic cardiomyopathy development and haplogroups were found. However, compared to healthy controls, the prevalence of haplogroup H was significantly higher in IC patients (40.0% vs 50.0%, p-value = 0.039 while the frequency of haplogroup J was significantly lower (11.1% vs 5.6%, p-value = 0.048. The analysis of the SNPs characterizing the European mtDNA haplogroups showed that the m.7028C allele (40.0% vs 50.0%, p-value = 0.005 and m.14766C allele (43.0% vs 54.2%, p-value = 0.002 were overrepresented in IC patients, meanwhile the m.10398G allele (19.8% vs 13.1%, p-value = 0.015 and m.4216C allele (22.2% vs 16.5%, p-value = 0.044 were found as protective factors against IC. CONCLUSIONS AND SIGNIFICANCE: Our results showed that the haplogroups H and J were found as a risk and protective factors for ischemic cardiomyopathy development, respectively.

  9. The HMG-box mitochondrial transcription factor xl-mtTFA binds DNA as a tetramer to activate bidirectional transcription.

    OpenAIRE

    Antoshechkin, I; Bogenhagen, D F; Mastrangelo, I A

    1997-01-01

    The mitochondrial HMG-box transcription factor xl-mtTFA activates bidirectional transcription by binding to a site separating two core promoters in Xenopus laevis mitochondrial DNA (mtDNA). Three independent approaches were used to study the higher order structure of xl-mtTFA binding to this site. First, co-immunoprecipitation of differentially tagged recombinant mtTFA derivatives established that the protein exists as a multimer. Second, in vitro chemical cross-linking experiments provided e...

  10. Posttranslational Modification of Mitochondrial Transcription Factor A in Impaired Mitochondria Biogenesis: Implications in Diabetic Retinopathy and Metabolic Memory Phenomenon

    OpenAIRE

    Santos, Julia M.; Mishra, Manish; Kowluru, Renu A.

    2014-01-01

    Mitochondrial transcription factor A (TFAM) is one of the key regulators of the transcription of mtDNA. In diabetes, despite increase in gene transcripts of TFAM, its protein levels in the mitochondria are decreased and mitochondria copy numbers become subnormal. The aim of this study is to investigate the mechanism(s) responsible for decreased mitochondrial TFAM in diabetes. Using retinal endothelial cells, we have investigated the effect of overexpression of cytosolic chaperone, Hsp70, and ...

  11. Mutant mitochondrial elongation factor G1 and combined oxidative phosphorylation deficiency

    OpenAIRE

    Newbold, RF; Coenen, MJH; Antonicka, H; Ugalde, C; F. Sasarman; Rossi, R.; Heister, A.; Trijbels, FJMF; van den Heuvel, LP; Shoubridge, EA; Smeitink, JAM

    2004-01-01

    Although most components of the mitochondrial translation apparatus are encoded by nuclear genes, all known molecular defects associated with impaired mitochondrial translation are due to mutations in mitochondrial DNA. We investigated two siblings with a severe defect in mitochondrial translation, reduced levels of oxidative phosphorylation complexes containing mitochondrial DNA (mtDNA)–encoded subunits, and progressive hepatoencephalopathy. We mapped the defective gene to a region on chromo...

  12. A Saccharomyces cerevisiae mitochondrial transcription factor, sc-mtTFB, shares features with sigma factors but is functionally distinct.

    OpenAIRE

    Shadel, G S; Clayton, D A

    1995-01-01

    In Saccharomyces cerevisiae mitochondria, sc-mtTFB is a 341-amino-acid transcription factor required for initiation of transcription from mitochondrial DNA promoters. Specific transcription in vitro requires only sc-mtTFB and the bacteriophage-related core sc-mtRNA polymerase. Mutational analysis of sc-mtTFB has defined two regions of the protein that are important for normal function both in vivo and in vitro. These regions overlap portions of the protein that exhibit similarity to conserved...

  13. Polymorphism and expression of the tumor necrosis factor receptor II gene in cows infected with the bovine leukemia virus.

    Science.gov (United States)

    Stachura, A; Brym, P; Bojarojć-Nosowicz, B; Kaczmarczyk, E

    2016-01-01

    A single T>C nucleotide polymorphism (rs42686850) of bovine tumor necrosis factor receptor type II gene (TNF-RII) is located within a sequence with allele-specific affinity to bind E2F transcription factors, considered pivotal in the regulation of cell cycle and cell proliferation. The objective of the study was to determine the effect of this SNP and BLV infection on the TNF-RII gene expression at the mRNA and protein levels in peripheral blood mononuclear cells (PBMC). We noted that analyzed TNF-RII gene polymorphism influenced the expression of the TNF-RII gene at the mRNA level but only in BLV-positive cows. Concurrently, no statistically significant association was found between gene polymorphism and TNF-RII expression at the protein level. However, we found a significant effect of BLV infection status on the amount of TNF-RII mRNA and the percentage of PBMC expressing TNF-RII. These results show an unclear effect of considered T>C polymorphism on TNF-RII gene expression in bovine leukocytes and they suggest the involvement of BLV in modifying the TNF-RII expression in BLV-infected cows potentially implying the EBL (Enzootic Bovine Leukosis) associated pathogenesis. PMID:27096796

  14. Conserved roles of fibroblast growth factor receptor 2 signaling in the regulation of inner cell mass development in bovine blastocysts.

    Science.gov (United States)

    Akizawa, Hiroki; Nagatomo, Hiroaki; Odagiri, Haruka; Kohri, Nanami; Yamauchi, Nobuhiko; Yanagawa, Yojiro; Nagano, Masashi; Takahashi, Masashi; Kawahara, Manabu

    2016-06-01

    A common process during preimplantation mammalian development is blastocyst formation, which utilizes signaling through fibroblast growth factor receptor 2 (FGFR2), yet the mechanisms through which FGFR2 signaling affect preimplantation development in bovine embryos remain incompletely understood. Here, we used RNA-interference to investigate the in vitro development, the frequency of blastomere apoptosis, and the mRNA expression of developmental marker genes in FGF receptor 2-knockdown (FGFR2-KD) bovine embryos. A reduction in FGFR2 mRNA did not affect preimplantation development or the frequency of apoptotic blastomeres, but did enhanced proliferation of the inner cell mass in blastocysts (P cattle. Mol. Reprod. Dev. 83: 516-525, 2016. © 2016 Wiley Periodicals, Inc. PMID:27060901

  15. Effects of Insulin-like Growth Factor-1 on Development of Somatic Cell Cloned Bovine Embryos.

    Science.gov (United States)

    Qu, Pengxiang; Li, Yanyan; Deng, Tengfei; Jia, Dan; Qing, Suzhu; Su, Jianmin; Zhang, Yong; Wang, Yongsheng

    2016-06-01

    The aim of this study was to assess the effect of insulin-like growth factor-1 (IGF-1) on the developmental competence of somatic cell nuclear transfer (SCNT) bovine embryos. First, the expression levels of IGF-1 receptor (IGF-1R) and IGF-1 in the oocytes and embryos of different developmental stages were examined. Then the effects of exogenous IGF-1 on the development of SCNT embryos were evaluated both in vitro and in vivo. The results showed that IGF-1 was not expressed in both IVF and SCNT embryos, whereas IGF-1R could be detected throughout the preimplantation stages in both protein and mRNA levels. Also, exogenous IGF-1 had no obvious impact on the developmental competence of IVF embryos. However, it could improve the developmental competence of SCNT embryos in terms of blastocyst developmental rate (31.3% vs. 43.2%, p < 0.05), total cell number (93.0 ± 9.9 vs. 101.0 ± 9.8, p < 0.05), ratio of inner cell mass (ICM) to trophectoderm (TE) (0.29 ± 0.006 vs. 0.39 ± 0.005, p < 0.05), and apoptosis index in day 7 blastocysts (2.5 ± 0.22 vs. 8.7 ± 0.41, p < 0.05) compared to the control group. Although no statistical difference in pregnancy rate and birth rate was observed after embryo transfer, there was an upward tendency in both examined terms in the IGF-1-supplemented group when compared with the control group. In conclusion, the present study showed that supplementing exogenous IGF-1 to the culture medium has an obvious positive effect on the development competence of SCNT embryos. PMID:27135251

  16. Red meat consumption and cancer: reasons to suspect involvement of bovine infectious factors in colorectal cancer.

    Science.gov (United States)

    zur Hausen, Harald

    2012-06-01

    An increased risk for colorectal cancer has been consistently reported for long-time consumption of cooked and processed red meat. This has frequently been attributed to chemical carcinogens arising during the cooking process of meat. Long-time fish or poultry consumption apparently does not increase the risk, although similar or higher concentrations of chemical carcinogens were recorded in their preparation for consumption. The geographic epidemiology of colorectal cancer seems to correspond to regions with a high rate of beef consumption. Countries with a virtual absence of beef in the diet (India) or where preferably lamb or goat meat is consumed (several Arabic countries) reveal low rates of colorectal cancer. In China, pork consumption has a long tradition, with an intermediate colorectal cancer rate. In Japan and Korea, large scale beef and pork imports started after World War II or after the Korean War. A steep rise in colorectal cancer incidence was noted after 1970 in Japan and 1990 in Korea. The consumption of undercooked beef (e.g., shabu-shabu, Korean yukhoe and Japanese yukke) became very popular in both countries. The available data are compatible with the interpretation that a specific beef factor, suspected to be one or more thermoresistant potentially oncogenic bovine viruses (e.g., polyoma-, papilloma- or possibly single-stranded DNA viruses) may contaminate beef preparations and lead to latent infections in the colorectal tract. Preceding, concomitant or subsequent exposure to chemical carcinogens arising during cooking procedures should result in increased risk for colorectal cancer synergistic with these infections. PMID:22212999

  17. Determination of transforming growth factor-beta 1 (TGF-beta 1) and insulin-like growth factor (IGF-1) in bovine colostrum samples.

    Science.gov (United States)

    Ginjala, V; Pakkanen, R

    1998-01-01

    The major growth factors in bovine colostrum are transforming growth factor-beta s (TGF-beta 1 and TGF-beta 2) and insulin-like growth factors (IGF-1 and IGF-2). Recently, TGF-beta 2 content of bovine colostrum was measured using a TGF-beta 2 specific ELISA (1) and now we have validated ELISAs for for bovine TGF-beta 1 and IGF-1. The concentrations of IGF-1 and TGF-beta 1 in the first milking after calving were 248-1850 ng/ml and 12.4-42.6 ng/ml, respectively, and they declined in correlation with total protein concentration to 27.0-101 ng/ml (IGF-1) and 0.80-3.49 ng/ml(TGF-beta 1) by the fifth milkings. The amount of TGF-beta 1 was on average 5.3 +/- 1.4% of that of TGF-beta 2 and there is a high correlation (r = 0.966) between the concentrations of these growth factors in the same samples. No free TGF-beta 1 form of could be detected. PMID:9682131

  18. Human mitochondrial transcription factor A functions in both nuclei and mitochondria and regulates cancer cell growth

    International Nuclear Information System (INIS)

    Highlights: → Mitochondrial transcription factor A (mtTFA) localizes in nuclei and binds tightly to the nuclear chromatin. → mtTFA contains two putative nuclear localization signals (NLS) in the HMG-boxes. → Overexpression of mtTFA enhances the growth of cancer cells, whereas downregulation of mtTFA inhibits their growth by regulating mtTFA target genes, such as baculoviral IAP repeat-containing 5 (BIRC5; also known as survivin). → Knockdown of mtTFA expression induces p21-dependent G1 cell cycle arrest. -- Abstract: Mitochondrial transcription factor A (mtTFA) is one of the high mobility group protein family and is required for both transcription from and maintenance of mitochondrial genomes. However, the roles of mtTFA have not been extensively studied in cancer cells. Here, we firstly reported the nuclear localization of mtTFA. The proportion of nuclear-localized mtTFA varied among different cancer cells. Some mtTFA binds tightly to the nuclear chromatin. DNA microarray and chromatin immunoprecipitation assays showed that mtTFA can regulate the expression of nuclear genes. Overexpression of mtTFA enhanced the growth of cancer cell lines, whereas downregulation of mtTFA inhibited their growth by regulating mtTFA target genes, such as baculoviral IAP repeat-containing 5 (BIRC5; also known as survivin). Knockdown of mtTFA expression induced p21-dependent G1 cell cycle arrest. These results imply that mtTFA functions in both nuclei and mitochondria to promote cell growth.

  19. A case-control study of risk factors for bovine cysticercosis in Danish cattle herds

    DEFF Research Database (Denmark)

    Calvo Artavia, Francisco Fernando; Nielsen, Liza Rosenbaum; Dahl, J.;

    2013-01-01

    Bovine cysticercosis (BC) is a zoonotic, parasitic infection in cattle. Under the current EU meat inspection regulation, every single carcass from all bovines above 6 weeks of age is examined for BC. This method is costly and makes more sense in countries with higher number of BC-infected animals...... increasing herd size probably because the larger herds generally tend to keep cattle indoors in Denmark. The results are useful to guide future data recording that can be supplied by the farmer as food chain information and then be used for differentiated meat inspection in low- and high-risk groups...

  20. The neurogenic basic helix-loop-helix transcription factor NeuroD6 enhances mitochondrial biogenesis and bioenergetics to confer tolerance of neuronal PC12-NeuroD6 cells to the mitochondrial stressor rotenone

    International Nuclear Information System (INIS)

    The fundamental question of how and which neuronal specific transcription factors tailor mitochondrial biogenesis and bioenergetics to the need of developing neuronal cells has remained largely unexplored. In this study, we report that the neurogenic basic helix-loop-helix transcription factor NeuroD6 possesses mitochondrial biogenic properties by amplifying the mitochondrial DNA content and TFAM expression levels, a key regulator for mitochondrial biogenesis. NeuroD6-mediated increase in mitochondrial biogenesis in the neuronal progenitor-like PC12-NEUROD6 cells is concomitant with enhanced mitochondrial bioenergetic functions, including increased expression levels of specific subunits of respiratory complexes of the electron transport chain, elevated mitochondrial membrane potential and ATP levels produced by oxidative phosphorylation. Thus, NeuroD6 augments the bioenergetic capacity of PC12-NEUROD6 cells to generate an energetic reserve, which confers tolerance to the mitochondrial stressor, rotenone. We found that NeuroD6 induces an adaptive bioenergetic response throughout rotenone treatment involving maintenance of the mitochondrial membrane potential and ATP levels in conjunction with preservation of the actin network. In conclusion, our results support the concept that NeuroD6 plays an integrative role in regulating and coordinating the onset of neuronal differentiation with acquisition of adequate mitochondrial mass and energetic capacity to ensure energy demanding events, such as cytoskeletal remodeling, plasmalemmal expansion, and growth cone formation. -- Highlights: ► NeuroD6 induces mitochondrial biogenesis in neuroprogenitor-like cells. ► NeuroD6 augments the bioenergetic reserve of the neuronal PC12-NeuroD6 cells. ► NeuroD6 increases the mitochondrial membrane potential and ATP levels. ► NeuroD6 confers tolerance to rotenone via an adaptive mitochondrial response.

  1. The neurogenic basic helix-loop-helix transcription factor NeuroD6 enhances mitochondrial biogenesis and bioenergetics to confer tolerance of neuronal PC12-NeuroD6 cells to the mitochondrial stressor rotenone

    Energy Technology Data Exchange (ETDEWEB)

    Baxter, Kristin Kathleen; Uittenbogaard, Martine [Department of Anatomy and Regenerative Biology, George Washington University Medical Center, Washington, DC (United States); Chiaramello, Anne, E-mail: achiaram@gwu.edu [Department of Anatomy and Regenerative Biology, George Washington University Medical Center, Washington, DC (United States)

    2012-10-15

    The fundamental question of how and which neuronal specific transcription factors tailor mitochondrial biogenesis and bioenergetics to the need of developing neuronal cells has remained largely unexplored. In this study, we report that the neurogenic basic helix-loop-helix transcription factor NeuroD6 possesses mitochondrial biogenic properties by amplifying the mitochondrial DNA content and TFAM expression levels, a key regulator for mitochondrial biogenesis. NeuroD6-mediated increase in mitochondrial biogenesis in the neuronal progenitor-like PC12-NEUROD6 cells is concomitant with enhanced mitochondrial bioenergetic functions, including increased expression levels of specific subunits of respiratory complexes of the electron transport chain, elevated mitochondrial membrane potential and ATP levels produced by oxidative phosphorylation. Thus, NeuroD6 augments the bioenergetic capacity of PC12-NEUROD6 cells to generate an energetic reserve, which confers tolerance to the mitochondrial stressor, rotenone. We found that NeuroD6 induces an adaptive bioenergetic response throughout rotenone treatment involving maintenance of the mitochondrial membrane potential and ATP levels in conjunction with preservation of the actin network. In conclusion, our results support the concept that NeuroD6 plays an integrative role in regulating and coordinating the onset of neuronal differentiation with acquisition of adequate mitochondrial mass and energetic capacity to ensure energy demanding events, such as cytoskeletal remodeling, plasmalemmal expansion, and growth cone formation. -- Highlights: Black-Right-Pointing-Pointer NeuroD6 induces mitochondrial biogenesis in neuroprogenitor-like cells. Black-Right-Pointing-Pointer NeuroD6 augments the bioenergetic reserve of the neuronal PC12-NeuroD6 cells. Black-Right-Pointing-Pointer NeuroD6 increases the mitochondrial membrane potential and ATP levels. Black-Right-Pointing-Pointer NeuroD6 confers tolerance to rotenone via an adaptive

  2. Prevalence and risk factor's analysis of bovine brucellosis in peri-urban areas under intensive system of production in Gujarat, India

    OpenAIRE

    Patel, M. D.; Patel, P. R.; M. G. Prajapati; A. N. Kanani; K. K. Tyagi; A. B. Fulsoundar

    2014-01-01

    Aim: A study on surveillance of bovine brucellosis in dairy herds of peri-urban areas under intensive system of production was carried out by milk-ELISA. Various risk factors were identified having significant association with occurrence of bovine brucellosis in dairy herds of peri-urban areas. Materials and Methods: Five randomly selected peri-uban areas of six cities of Gujarat were included in the present study. Five randomly selected dairy herds under intensive system of production fro...

  3. Expression of mitochondrial transcription factor A (TFAM) during porcine gametogenesis and preimplantation embryo development.

    Science.gov (United States)

    Antelman, J; Manandhar, G; Yi, Y-J; Li, R; Whitworth, K M; Sutovsky, M; Agca, C; Prather, R S; Sutovsky, P

    2008-11-01

    Mitochondrial transcription factor A (TFAM) is responsible for stability, maintenance, and transcriptional control of mitochondrial DNA (mtDNA). We have studied the expression and distribution of TFAM in the gametes and preimplantation embryos of the domestic pig (Sus scrofa). We hypothesized that TFAM is not present in the boar sperm mitochondria to reduce the possibility of paternal mtDNA propagation in the progeny. In contrast, we anticipated that Tfam gene is expressed in a developmental stage-dependent manner in porcine oocytes and embryos. The appropriate TFAM band of 25 kDa was detected by Western blotting in ejaculated boar spermatozoa, as well as in porcine oocytes and zygotes. Boar sperm extracts also displayed several bands >25 kDa suggestive of post-translational modification by ubiquitination, confirmed by affinity purification of ubiquitinated proteins. TFAM immunoreactivity was relegated to the sperm tail principal piece and sperm head in fully differentiated spermatozoa. The content of Tfam mRNA increased considerably from the germinal vesicle to blastocyst stage and also between in vitro fertilized and cultured blastocysts compared to in vivo-derived blastocysts. TFAM protein accumulated in the oocytes during maturation and was reduced by proteolysis after fertilization. This pattern was not mirrored in parthenogenetically activated oocytes and zygotes reconstructed by SCNT, suggesting deviant processing of TFAM protein and transcript after oocyte/embryo manipulation. Thus, TFAM may exert a critical role in porcine gametogenesis and preimplantation embryo development. Altogether, our data on the role of TFAM in mitochondrial function and inheritance have broad implications for cell physiology and evolutionary biology. PMID:18636550

  4. Direct linkage of mitochondrial genome variation to risk factors for type 2 diabetes in conplastic strains

    Czech Academy of Sciences Publication Activity Database

    Pravenec, Michal; Hyakukoku, M.; Houštěk, Josef; Zídek, Václav; Landa, Vladimír; Mlejnek, Petr; Mikšík, Ivan; Mothejzíková-Dudová, Kristýna; Pecina, Petr; Vrbacký, Marek; Drahota, Zdeněk; Vojtíšková, Alena; Mráček, Tomáš; Kazdová, L.; Oliyarnyk, O.; Wang, Ji.; Ho, Ch.; Qi, N.; Sugimoto, K.; Kurtz, T.

    2007-01-01

    Roč. 17, č. 9 (2007), s. 1319-1326. ISSN 1088-9051 R&D Projects: GA MŠk(CZ) 1M0520; GA ČR(CZ) GA301/06/0028; GA ČR GA303/07/0781 Grant ostatní: GA UK(CZ) 24/2005; GA UK(CZ) 26/2005; National Institutes of Health(US) HL35018; National Institutes of Health(US) HL56028; National Institutes of Health(US) HL63709; EURATOOLS(XE) LSHG-CT-2005-019015 Institutional research plan: CEZ:AV0Z50110509 Source of funding: R - rámcový projekt EK Keywords : mitochondrial genome * conplastic strains * risk factors for type 2 diabetes Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 11.224, year: 2007

  5. Effect of growth factors on oocyte maturation and allocations of inner cell mass and trophectoderm cells of cloned bovine embryos.

    Science.gov (United States)

    Arat, Sezen; Caputcu, Arzu Tas; Cevik, Mesut; Akkoc, Tolga; Cetinkaya, Gaye; Bagis, Haydar

    2016-08-01

    This study was conducted to determine the additive effects of exogenous growth factors during in vitro oocyte maturation (IVM) and the sequential culture of nuclear transfer (NT) embryos. Oocyte maturation and culture of reconstructed embryos derived from bovine granulosa cells were performed in culture medium supplemented with either epidermal growth factor (EGF) alone or a combination of EGF with insulin-like growth factor-I (IGF-I). The maturation rates of oocytes matured in the presence of EGF or the EGF + IGF-I combination were significantly higher than those of oocytes matured in the presence of only fetal calf serum (FCS) (P 0.05). IGF-I alone or in combination with EGF in sequential embryo culture medium significantly increased the ratio of inner cell mass (ICM) to total blastocyst cells (P media of cloned bovine embryos increased the ICM without changing the total cell number. These unknown and uncontrolled effects of growth factors can alter the allocation of ICM and trophectoderm cells (TE) in NT embryos. A decrease in TE cell numbers could be a reason for developmental abnormalities in embryos in the cloning system. PMID:26444069

  6. Effect of insulin-like growth factor-1 during in vitro oocyte maturation and in vitro culture of bovine embryos

    OpenAIRE

    Quetglas M.D.; Coelho L.A.; Garcia J.M.; Oliveira Filho E.B.; Esper C.R.

    2001-01-01

    The effects of insulin-like growth factor-I (IGF-I) on in vitro maturation (IVM) (experiment I) and on in vitro embryo development (experiment II) of bovine oocytes fertilized in vitro, were evaluated in terms of cleavage (CR), blastocyst (BR) and hatching (HR) rates. For IVM, immature cumulus-oocyte complexes were cultured in TCM-199 medium supplemented with Hepes, sodium bicarbonate, sodium pyruvate, additives, fetal calf serum (B-199 medium) and gonadotropins (14 U/ml PMSG and 7 U/ml hCG)....

  7. Risk factors for bovine tuberculosis in low incidence regions related to the movements of cattle

    OpenAIRE

    Gates, M Carolyn; Volkova, Victoriya V.; Woolhouse, Mark EJ

    2013-01-01

    BackgroundBovine tuberculosis (bTB) remains difficult to eradicate from low incidence regions partly due to the imperfect sensitivity and specificity of routine intradermal tuberculin testing. Herds with unconfirmed reactors that are incorrectly classified as bTB-negative may be at risk of spreading disease, while those that are incorrectly classified as bTB-positive may be subject to costly disease eradication measures. This analysis used data from Scotland in the period leading to Officiall...

  8. Risk factors for bovine tuberculosis in low incidence regions related to the movements of cattle

    OpenAIRE

    Gates, M Carolyn; Volkova, Victoriya V.; Woolhouse, Mark EJ

    2013-01-01

    Background Bovine tuberculosis (bTB) remains difficult to eradicate from low incidence regions partly due to the imperfect sensitivity and specificity of routine intradermal tuberculin testing. Herds with unconfirmed reactors that are incorrectly classified as bTB-negative may be at risk of spreading disease, while those that are incorrectly classified as bTB-positive may be subject to costly disease eradication measures. This analysis used data from Scotland in the period leading to Official...

  9. Isolation of bovine corneal keratan sulfate and its growth factor and morphogen binding

    OpenAIRE

    Weyers, Amanda; Yang, Bo; Solakyildirim, Kemal; Yee, Vienna; Li, Lingyun; Zhang, Fuming; Linhardt, Robert

    2013-01-01

    Keratan sulfate (KS) is an important glycosaminoglycan that is found in cartilage, reproductive, and neural tissues. Corneal KS glycosaminoglycan is found N-linked to lumican, keratocan, and mimecan proteoglycans and has been widely studied by investigators interested in corneal development and diseases. Recently, the availability of corneal KS has become severely limited due to restricted the shipment of bovine central nervous system by-products across international borders in efforts to pre...

  10. Translational regulation by mRNA associated factors during bovine oocyte maturation and early embryonic development

    Czech Academy of Sciences Publication Activity Database

    Siemer, C.; Smiljakovic, T.; Bhojawni, M.; Kubelka, Michal; Tomek, W.

    Malden : Wiley-Blackwell, 2009 - (Rodriguez-Martinez, H.; Iaverne, M.), s. 35-36 ISSN 0936-6768. [42nd Annual Conference of Physiology and Pathology of Reproduction/ 34th Mutual Conference on Veterinary and Human Reproductive Medicine. Leipzig (DE), 26.02.2009-27.02.2009] R&D Projects: GA ČR GA524/07/1087 Institutional research plan: CEZ:AV0Z50450515 Keywords : Oocyte maturation * Bovine embryo Subject RIV: ED - Physiology

  11. Mitochondrial cytopathies.

    Science.gov (United States)

    El-Hattab, Ayman W; Scaglia, Fernando

    2016-09-01

    Mitochondria are found in all nucleated human cells and perform a variety of essential functions, including the generation of cellular energy. Most of mitochondrial proteins are encoded by the nuclear DNA (nDNA) whereas a very small fraction is encoded by the mitochondrial DNA (mtDNA). Mutations in mtDNA or mitochondria-related nDNA genes can result in mitochondrial dysfunction which leads to a wide range of cellular perturbations including aberrant calcium homeostasis, excessive reactive oxygen species production, dysregulated apoptosis, and insufficient energy generation to meet the needs of various organs, particularly those with high energy demand. Impaired mitochondrial function in various tissues and organs results in the multi-organ manifestations of mitochondrial diseases including epilepsy, intellectual disability, skeletal and cardiac myopathies, hepatopathies, endocrinopathies, and nephropathies. Defects in nDNA genes can be inherited in an autosomal or X-linked manners, whereas, mtDNA is maternally inherited. Mitochondrial diseases can result from mutations of nDNA genes encoding subunits of the electron transport chain complexes or their assembly factors, proteins associated with the mitochondrial import or networking, mitochondrial translation factors, or proteins involved in mtDNA maintenance. MtDNA defects can be either point mutations or rearrangements. The diagnosis of mitochondrial disorders can be challenging in many cases and is based on clinical recognition, biochemical screening, histopathological studies, functional studies, and molecular genetic testing. Currently, there are no satisfactory therapies available for mitochondrial disorders that significantly alter the course of the disease. Therapeutic options include symptomatic treatment, cofactor supplementation, and exercise. PMID:26996063

  12. Finding biomarkers in non-model species: literature mining of transcription factors involved in bovine embryo development

    Directory of Open Access Journals (Sweden)

    Turenne Nicolas

    2012-08-01

    Full Text Available Abstract Background Since processes in well-known model organisms have specific features different from those in Bos taurus, the organism under study, a good way to describe gene regulation in ruminant embryos would be a species-specific consideration of closely related species to cattle, sheep and pig. However, as highlighted by a recent report, gene dictionaries in pig are smaller than in cattle, bringing a risk to reduce the gene resources to be mined (and so for sheep dictionaries. Bioinformatics approaches that allow an integration of available information on gene function in model organisms, taking into account their specificity, are thus needed. Besides these closely related and biologically relevant species, there is indeed much more knowledge of (i trophoblast proliferation and differentiation or (ii embryogenesis in human and mouse species, which provides opportunities for reconstructing proliferation and/or differentiation processes in other mammalian embryos, including ruminants. The necessary knowledge can be obtained partly from (i stem cell or cancer research to supply useful information on molecular agents or molecular interactions at work in cell proliferation and (ii mouse embryogenesis to supply useful information on embryo differentiation. However, the total number of publications for all these topics and species is great and their manual processing would be tedious and time consuming. This is why we used text mining for automated text analysis and automated knowledge extraction. To evaluate the quality of this “mining”, we took advantage of studies that reported gene expression profiles during the elongation of bovine embryos and defined a list of transcription factors (or TF, n = 64 that we used as biological “gold standard”. When successful, the “mining” approach would identify them all, as well as novel ones. Methods To gain knowledge on molecular-genetic regulations in a non model organism, we offer an

  13. Detection of methicillin resistance and slime factor production of Staphylococcus aureus in bovine mastitis

    OpenAIRE

    Alper Ciftci; Arzu Findik; Ertan Emek Onuk; Serap Savasan

    2009-01-01

    This study aimed to detect methicillin resistant and slime producing Staphylococcus aureus in cases of bovine mastitis. A triplex PCR was optimized targetting 16S rRNA, nuc and mecA genes for detection of Staphylococcus species, S. aureus and methicillin resistance, respectively. Furthermore, for detection of slime producing strains, a PCR assay targetting icaA and icaD genes was performed. In this study, 59 strains were detected as S. aureus by both conventional tests and PCR, and 13 of them...

  14. Haplogroup T Is an Obesity Risk Factor: Mitochondrial DNA Haplotyping in a Morbid Obese Population from Southern Italy

    Directory of Open Access Journals (Sweden)

    Carmela Nardelli

    2013-01-01

    Full Text Available Mitochondrial DNA (mtDNA haplogroups have been associated with the expression of mitochondrial-related diseases and with metabolic alterations, but their role has not yet been investigated in morbid obese Caucasian subjects. Therefore, we investigated the association between mitochondrial haplogroups and morbid obesity in patients from southern Italy. The mtDNA D-loop of morbid obese patients (n=500; BMI > 40 kg/m2 and controls (n=216; BMI 45 kg/m2 and in fact together account for 8% of the BMI. In conclusion, our finding that haplogroup T increases the risk of obesity by about two-fold, suggests that, besides nuclear genome variations and environmental factors, the T haplogroup plays a role in morbid obesity in our study population from southern Italy.

  15. Sero-positivity and associated risk factors for contagious bovine pleuropneumonia under two cattle production systems in North Central Nigeria.

    Science.gov (United States)

    Alhaji, Nma Bida; Babalobi, Olutayo Olajide

    2016-02-01

    A cross-sectional survey of 765 cattle in 125 nomadic and 375 cattle in 125 sedentary herds was conducted to investigate prevalence and risk factors for contagious bovine pleuropneumonia (CBPP) in the two production systems of Niger State in North Central Nigeria, between January and August 2013. Data on herd characteristics were collected using structured questionnaires administered on herd owners. Serological analysis was conducted using competitive enzyme linked immunosorbent assay (c-ELISA) test. Descriptive, univariate, and multivariate statistical analyses were conducted with OpenEpi version 2.3.1 software. Statistical significance was held at P trekking during migrations (P = 0.0009). This study had shown the burden of CBPP in the two production systems. Sero-diagnosis and risk factor identification should be institutionalized as elements of epidemio-surveillance and control strategies for CBPP, especially in resource-poor pastoralists' settlements in Nigeria. PMID:26563271

  16. Exenatide Reduces Tumor Necrosis Factor-α-induced Apoptosis in Cardiomyocytes by Alleviating Mitochondrial Dysfunction

    Institute of Scientific and Technical Information of China (English)

    Yuan-Yuan Cao; Zhang-Wei Chen; Yan-Hua Gao; Xing-Xu Wang; Jian-Ying Ma; Shu-Fu Chang; Ju-Ying Qian

    2015-01-01

    Background: Tumor necrosis factor-α (TNF-α) plays an important role in progressive contractile dysfunction in several cardiac diseases.The cytotoxic effects of TNF-α are suggested to be partly mediated by reactive oxygen species (ROS)-and mitochondria-dependent apoptosis.Glucagon-like peptide-1 (GLP-1) or its analogue exhibits protective effects on the cardiovascular system.The objective of the study was to assess the effects of exenatide, a GLP-1 analogue, on oxidative stress, and apoptosis in TNF-c-treated cardiomyocytes in vitro.Methods: Isolated neonatal rat cardiomyocytes were divided into three groups: Control group, with cells cultured in normal conditions without intervention;TNF-α group, with cells incubated with TNF-c (40 ng/ml) for 6, 12, or 24 h without pretreatment with exenatide;and exenatide group, with cells pretreated with exenatide (100 nmol/L) 30 mins before TNF-α (40 ng/ml) stimulation.We evaluated apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and flow cytometry, measured ROS production and mitochondrial membrane potential (MMP) by specific the fluorescent probes, and assessed the levels of proteins by Western blotting for all the groups.Results: Exenatide pretreatment significantly reduced cardiomyocyte apoptosis as measured by flow cytometry and TUNEL assay at 12 h and 24 h.Also, exenatide inhibited excessive ROS production and maintained MMP.Furthermore, declined cytochrome-c release and cleaved caspase-3 expression and increased bcl-2 expression with concomitantly decreased Bax activation were observed in exenatide-pretreated cultures.Conclusion: These results suggested that exenatide exerts a protective effect on cardiomyocytes, preventing TNF-α-induced apoptosis;the anti-apoptotic effects may be associated with protection of mitochondrial function.

  17. Neurodegeneration from mitochondrial insufficiency: nutrients, stem cells, growth factors, and prospects for brain rebuilding using integrative management.

    Science.gov (United States)

    Kidd, Parris M

    2005-12-01

    Degenerative brain disorders (neurodegeneration) can be frustrating for both conventional and alternative practitioners. A more comprehensive, integrative approach is urgently needed. One emerging focus for intervention is brain energetics. Specifically, mitochondrial insufficiency contributes to the etiopathology of many such disorders. Electron leakages inherent to mitochondrial energetics generate reactive oxygen free radical species that may place the ultimate limit on lifespan. Exogenous toxins, such as mercury and other environmental contaminants, exacerbate mitochondrial electron leakage, hastening their demise and that of their host cells. Studies of the brain in Alzheimer's and other dementias, Down syndrome, stroke, Parkinson's disease, multiple sclerosis, amyotrophic lateral sclerosis, Huntington's disease, Friedreich's ataxia, aging, and constitutive disorders demonstrate impairments of the mitochondrial citric acid cycle and oxidative phosphorylation (OXPHOS) enzymes. Imaging or metabolic assays frequently reveal energetic insufficiency and depleted energy reserve in brain tissue in situ. Orthomolecular nutrients involved in mitochondrial metabolism provide clinical benefit. Among these are the essential minerals and the B vitamin group; vitamins E and K; and the antioxidant and energetic cofactors alpha-lipoic acid (ALA), ubiquinone (coenzyme Q10; CoQ10), and nicotinamide adenine dinucleotide, reduced (NADH). Recent advances in the area of stem cells and growth factors encourage optimism regarding brain regeneration. The trophic nutrients acetyl L-carnitine (ALCAR), glycerophosphocholine (GPC), and phosphatidylserine (PS) provide mitochondrial support and conserve growth factor receptors; all three improved cognition in double-blind trials. The omega-3 fatty acid docosahexaenoic acid (DHA) is enzymatically combined with GPC and PS to form membrane phospholipids for nerve cell expansion. Practical recommendations are presented for integrating these

  18. The reaction of NADPH with bovine mitochondrial NADH:ubiquinone oxidoreductase revisited: II. Comparison of the proposed working hypothesis with literature data.

    NARCIS (Netherlands)

    S.P.J. Albracht

    2010-01-01

    The first purification of bovine NADH:ubiquinone oxidoreductase (Complex I) was reported nearly half a century ago (Hatefi et al. J Biol Chem 237:1676-1680, 1962). The pathway of electron-transfer through the enzyme is still under debate. A major obstacle is the assignment of EPR signals to the indi

  19. Rol de la mitocondria y el estrés oxidativo en el bloqueo del desarrollo de embriones bovinos producidos in vitro Mitochondrial rol and oxidative stress in the developmental blockade of in vitro produced bovine embryos

    Directory of Open Access Journals (Sweden)

    AM Tarazona

    2010-01-01

    Full Text Available Uno de los mayores obstáculos en la producción de embriones in vitro con fines de investigación básica, comerciales, o de conservación, es el detenimiento temprano del clivaje que ocurre de forma específica en una etapa del desarrollo. Para explicar este fenómeno se han postulado diferentes factores causales como: desórdenes en la cromatina, rearreglos del citoesqueleto, estrés oxidativo y daños mitocondriales. Esta última propuesta ha recibido gran atención, debido a que la mitocondria es fuente de especies reactivas de oxígeno (EROs y el estrés oxidativo es un mediador crítico de procesos fisiológicos y estados patológicos. Durante los últimos años se ha demostrado que el peróxido de hidrógeno (H2O2 es una molécula pivotante capaz de desencadenar muerte celular por diferentes mecanismos que pueden involucrar o no a los factores de transcripción: NFκB - p53, y es ejecutado por caspasas efectoras. Se cree que la mitocondria podría estar jugando un papel importante como productora o como blanco del H2O2, y como mediadora en la muerte por apoptosis de los embriones. El objetivo de esta revisión es mostrar el estado del arte en cuanto a la apoptosis desencadenada por estrés oxidativo y mediada por la mitocondria en los embriones bovinos producidos in vitro, como parte de la explicación del bloqueo del clivaje y la baja eficiencia que aún se tiene en este proceso.One of the biggest obstacles in the in vitro embryo production for basic research, commercial purposes, or conservation, is the blockade of the early cleavage, which occurs on a species-specific manner in a particular stage of development. To explain this phenomenon some causative factors have been postulated such as: disturbances in chromatin, cytoskeleton rearrangement, oxidative stress and mitochondrial damage. The latter has received considerable attention because mitochondrion is a source of reactive oxygen species (ROS, and oxidative stress is a critical

  20. α-transforming growth factor secreted by untransformed bovine anterior pituitary cells in culture. I. Purification from conditioned medium

    International Nuclear Information System (INIS)

    A 6-kDa α-transforming growth factor (TGF) was purified 100,000-fold to homogeneity from the culture fluid conditioned by normal bovine anterior pituitary-derived cells. Initial purification of the acid-soluble TGF from concentrated conditioned medium was achieved by Bio-Gel P-60 gel filtration (apparent molecular mass of 9 kDa). After the Bio-Gel step, three different steps of reverse-phase fast-protein liquid chromatography on the same Pharmacia C18 column, using linear acetonitrile gradients, gave complete purification. The ion-pairing agents used in the three consecutive steps were: 0.1% trifluoroacetic acid, 0.13% heptafluorobutyric acid, and again, 0.1% trifluoroacetic acid at a shallower gradient. Homogeneity was confirmed by reverse-phase high performance liquid chromatography, and by polyacrylamide gel electrophoresis, where TGF visualization was facilitated by autoradiography of 125I-TGF. The 125I-TGF bound to epidermal growth factor (EGF) receptors and after elution ran identically to the starting material. The molecular mass of TGF is 6 kDa by polyacrylamide gel electrophoresis and 6.6 kDa by amino acid analysis. The amino acid composition of bovine TGF is similar to that of rat or human αTGF and distinct from epidermal growth factor. Colony-stimulating activity was lost after purification, but the TGF retained its ability to stimulate thymidine uptake by quiescent cells. This mitogenic activity could be blocked completely by anti-EGF-receptor monoclonal antibodies, indicating that the activity was mediated through the EGF-receptor

  1. Molecular epidemiology of bovine tuberculosis in wild animals in Spain: a first approach to risk factor analysis.

    Science.gov (United States)

    Parra, A; Larrasa, J; García, A; Alonso, J M; de Mendoza, J Hermoso

    2005-10-31

    In human tuberculosis (Mycobacterium tuberculosis), molecular epidemiology has accurately indicated the risk factors involved in active transmission of the disease, by comparing individuals whose isolates belong to a cluster with patients whose strains are considered unique. Nevertheless, this application has not been used in bovine tuberculosis (Mycobacterium bovis). Our study describes the integration of epidemiological data into molecular classification data on M. bovis isolates. These were isolated from wild ungulates in Extremadura (western Spain) with the objective of detecting the risk factors linked to the association of strains in clades, which are indicators of the active spread of the disease. The molecular markers used were spoligotyping + VNTR typing (loci: VNTR 2165, VNTR 2461, VNTR 0577, VNTR 0580, VNTR 3192 VNTR 2163a and VNTR 2163b) on a population of 59 M. bovis strains isolated from deer (Cervus elaphus), 112 from wild boar (Sus scrofa), six from bovines, 28 from pigs and 2 from goats (n=207). Epidemiological variables included the animal species from which the strain was isolated, pathological condition of the host (incipient lesion, early and late generalisation), date of sampling (during or after the reproductive period) and hunting season. Bivariant analysis was used to establish the risk factors connected to the association of strains and later, the variables were evaluated by means of logistic regression. Molecular typing grouped a total of 131 strains (64.21%) in 28 clusters and 76 isolates shows unique profiles. The association of strains was connected to the appearance of macroscopic lesions during the reproductive period (O.R. 4.80; 95% CI 1.09-22.99, PActive spread was not connected to any species in particular, or to any concrete pathological condition. PMID:16143470

  2. Risk factors associated with within-herd transmission of bovine leukemia virus on dairy farms in Japan

    Directory of Open Access Journals (Sweden)

    Konishi Misako

    2010-01-01

    Full Text Available Abstract Background Although several attempts have been made to control enzootic bovine leukosis (EBL at the local level, a nationwide control program has not been implemented in Japan, except for passive surveillance. Effective control of EBL requires that the transmission routes of bovine leukemia virus (BLV infection should be identified and intercepted based on scientific evidence. In this cross-sectional study, we examined the risk factors associated with within-herd transmission of BLV on infected dairy farms in Japan. Blood samples taken from 30 randomly selected adult cows at each of 139 dairy farms were tested by enzyme-linked immunosorbent assay (ELISA. Information on herd management was collected using a structured questionnaire. Results Infected farms were defined as those with more than one ELISA-positive animal and accounted for 110 (79.1% of the 139 farms in the study. Completed questionnaires obtained from 90 of these 110 farms were used for statistical analysis. Seroprevalence, which was defined as the proportions of animals that tested positive out of all animals tested on the farm, was 17.1%, 48.1%, and 68.5% for the 25th, 50th, and 75th percentiles, respectively. A mixed logistic regression analysis implicated a loose housing system, dehorning, and a large number of horseflies in summer as risk factors (coefficient = 0.71, 1.11, and 0.82; p = 0.03, Conclusion Control of EBL in infected dairy farms in Japan will be improved by focusing particularly on these risk and protective factors.

  3. Hypoxia Inducible Factors Modulate Mitochondrial Oxygen Consumption and Transcriptional Regulation of Nuclear-Encoded Electron Transport Chain Genes.

    Science.gov (United States)

    Hwang, Hye Jin; Lynn, Scott G; Vengellur, Ajith; Saini, Yogesh; Grier, Elizabeth A; Ferguson-Miller, Shelagh M; LaPres, John J

    2015-06-23

    Hypoxia inducible factor-1 (HIF1) is a stress-responsive nuclear transcription factor that is activated with a decrease in oxygen availability. HIF1 regulates the expression of genes involved in a cell's adaptation to hypoxic stress, including those with mitochondrial specific function. To gain a more comprehensive understanding of the role of HIF1 in mitochondrial homeostasis, we studied the link between hypoxia, HIF1 transactivation, and electron transport chain (ETC) function. We established immortalized mouse embryonic fibroblasts (MEFs) for HIF1α wild-type (WT) and null cells and tested whether HIF1α regulates mitochondrial respiration by modulating gene expressions of nuclear-encoded ETC components. High-throughput quantitative real-time polymerase chain reaction was performed to screen nuclear-encoded mitochondrial genes related to the ETC to identify those whose regulation was HIF1α-dependent. Our data suggest that HIF1α regulates transcription of cytochrome c oxidase (CcO) heart/muscle isoform 7a1 (Cox7a1) under hypoxia, where it is induced 1.5-2.5-fold, whereas Cox4i2 hypoxic induction was HIF1α-independent. We propose that adaptation to hypoxic stress of CcO as the main cellular oxygen consumer is mediated by induction of hypoxia-sensitive tissue-specific isoforms. We suggest that HIF1 plays a central role in maintaining homeostasis in cellular respiration during hypoxic stress via regulation of CcO activity. PMID:26030260

  4. GSK3 inactivation is involved in mitochondrial complex IV defect in transforming growth factor (TGF) {beta}1-induced senescence

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Hae-Ok; Jung, Hyun-Jung; Seo, Yong-Hak; Lee, Young-Kyoung [Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon 443-721 (Korea, Republic of); Department of Molecular Science and Technology, The Graduate School, Ajou University, Suwon 443-721 (Korea, Republic of); Hwang, Sung-Chul [Department of Pulmonary and Critical Care Medicine, Ajou University School of Medicine, Suwon 443-721 (Korea, Republic of); Seong Hwang, Eun [Department of Life Science, University of Seoul, Seoul 130-743 (Korea, Republic of); Yoon, Gyesoon, E-mail: ypeace@ajou.ac.kr [Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon 443-721 (Korea, Republic of); Department of Molecular Science and Technology, The Graduate School, Ajou University, Suwon 443-721 (Korea, Republic of)

    2012-09-10

    Transforming growth factor {beta}1 (TGF {beta}1) induces Mv1Lu cell senescence by persistently producing mitochondrial reactive oxygen species (ROS) through decreased complex IV activity. Here, we investigated the molecular mechanism underlying the effect of TGF {beta}1 on mitochondrial complex IV activity. TGF {beta}1 progressively phosphorylated the negative regulatory sites of both glycogen synthase kinase 3 (GSK3) {alpha} and {beta}, corresponding well to the intracellular ROS generation profile. Pre-treatment of N-acetyl cysteine, an antioxidant, did not alter this GSK3 phosphorylation (inactivation), whereas pharmacological inhibition of GSK3 by SB415286 significantly increased mitochondrial ROS, implying that GSK3 phosphorylation is an upstream event of the ROS generation. GSK3 inhibition by SB415286 decreased complex IV activity and cellular O{sub 2} consumption rate and eventually induced senescence of Mv1Lu cell. Similar results were obtained with siRNA-mediated knockdown of GSK3. Moreover, we found that GSK3 not only exists in cytosol but also in mitochondria of Mv1Lu cell and the mitochondrial GSK3 binds complex IV subunit 6b which has no electron carrier and is topologically located in the mitochondrial intermembrane space. Involvement of subunit 6b in controlling complex IV activity and overall respiration rate was proved with siRNA-mediated knockdown of subunit 6b. Finally, TGF {beta}1 treatment decreased the binding of the subunit 6b to GSK3 and subunit 6b phosphorylation. Taken together, our results suggest that GSK3 inactivation is importantly involved in TGF {beta}1-induced complex IV defects through decreasing phosphorylation of the subunit 6b, thereby contributing to senescence-associated mitochondrial ROS generation.

  5. GSK3 inactivation is involved in mitochondrial complex IV defect in transforming growth factor (TGF) β1-induced senescence

    International Nuclear Information System (INIS)

    Transforming growth factor β1 (TGF β1) induces Mv1Lu cell senescence by persistently producing mitochondrial reactive oxygen species (ROS) through decreased complex IV activity. Here, we investigated the molecular mechanism underlying the effect of TGF β1 on mitochondrial complex IV activity. TGF β1 progressively phosphorylated the negative regulatory sites of both glycogen synthase kinase 3 (GSK3) α and β, corresponding well to the intracellular ROS generation profile. Pre-treatment of N-acetyl cysteine, an antioxidant, did not alter this GSK3 phosphorylation (inactivation), whereas pharmacological inhibition of GSK3 by SB415286 significantly increased mitochondrial ROS, implying that GSK3 phosphorylation is an upstream event of the ROS generation. GSK3 inhibition by SB415286 decreased complex IV activity and cellular O2 consumption rate and eventually induced senescence of Mv1Lu cell. Similar results were obtained with siRNA-mediated knockdown of GSK3. Moreover, we found that GSK3 not only exists in cytosol but also in mitochondria of Mv1Lu cell and the mitochondrial GSK3 binds complex IV subunit 6b which has no electron carrier and is topologically located in the mitochondrial intermembrane space. Involvement of subunit 6b in controlling complex IV activity and overall respiration rate was proved with siRNA-mediated knockdown of subunit 6b. Finally, TGF β1 treatment decreased the binding of the subunit 6b to GSK3 and subunit 6b phosphorylation. Taken together, our results suggest that GSK3 inactivation is importantly involved in TGF β1-induced complex IV defects through decreasing phosphorylation of the subunit 6b, thereby contributing to senescence-associated mitochondrial ROS generation.

  6. Ciliary neurotrophic factor activates NF-κB to enhance mitochondrial bioenergetics and prevent neuropathy in sensory neurons of streptozotocin-induced diabetic rodents

    OpenAIRE

    Saleh, Ali; Roy Chowdhury, Subir K.; Smith, Darrel R.; Balakrishnan, Savitha; Tessler, Lori; Martens, Corina; Morrow, Dwane; Schartner, Emily; Frizzi, Katie E.; Calcutt, Nigel A.; Fernyhough, Paul

    2012-01-01

    Diabetes causes mitochondrial dysfunction in sensory neurons that may contribute to peripheral neuropathy. Ciliary neurotrophic factor (CNTF) promotes sensory neuron survival and axon regeneration and prevents axonal dwindling, nerve conduction deficits and thermal hypoalgesia in diabetic rats. In this study, we tested the hypothesis that CNTF protects sensory neuron function during diabetes through normalization of impaired mitochondrial bioenergetics. In addition, we investigated whether th...

  7. The neurogenic basic helix–loop–helix transcription factor NeuroD6 concomitantly increases mitochondrial mass and regulates cytoskeletal organization in the early stages of neuronal differentiation

    Directory of Open Access Journals (Sweden)

    Kristin Kathleen Baxter

    2009-09-01

    Full Text Available Mitochondria play a central role during neurogenesis by providing energy in the form of ATP for cytoskeletal remodelling, outgrowth of neuronal processes, growth cone activity and synaptic activity. However, the fundamental question of how differentiating neurons control mitochondrial biogenesis remains vastly unexplored. Since our previous studies have shown that the neurogenic bHLH (basic helix–loop–helix transcription factor NeuroD6 is sufficient to induce differentiation of the neuronal progenitor-like PC12 cells and that it triggers expression of mitochondrial-related genes, we investigated whether NeuroD6 could modulate the mitochondrial biomass using our PC12-ND6 cellular paradigm. Using a combination of flow cytometry, confocal microscopy and mitochondrial fractionation, we demonstrate that NeuroD6 stimulates maximal mitochondrial mass at the lamellipodia stage, thus preceding axonal growth. NeuroD6 triggers remodelling of the actin and microtubule networks in conjunction with increased expression of the motor protein KIF5B, thus promoting mitochondrial movement in developing neurites with accumulation in growth cones. Maintenance of the NeuroD6-induced mitochondrial mass requires an intact cytoskeletal network, as its disruption severely reduces mitochondrial mass. The present study provides the first evidence that NeuroD6 plays an integrative role in co-ordinating increase in mitochondrial mass with cytoskeletal remodelling, suggestive of a role of this transcription factor as a co-regulator of neuronal differentiation and energy metabolism.

  8. Neurochemical sensitization associated with systemic administration of tumor necrosis factor-alpha: adjuvant action in combination with bovine serum albumin.

    Science.gov (United States)

    Anisman, Hymie; Turrin, Nicolas P; Merali, Zul; Hayley, Shawn

    2003-12-01

    Tumor necrosis factor-alpha (TNF-alpha) provokes a time-dependent sensitization of brain monoamine activity, plasma corticosterone activity and sickness behavior, the latter being reminiscent of septic or anaphylactic shock. In this investigation, bovine serum albumin (BSA) elicited similar corticosterone and sickness profiles, whereas the monoamine changes were not observed. The sensitization elicited by mTNF-alpha plus BSA was markedly greater than that elicited by BSA alone. Carrier-free TNF-alpha promoted the sensitization of brain monoamine activity, but not sickness or corticosterone. It is suggested that mTNF-alpha acts as an adjuvant to the anaphylactic actions elicited by BSA, but may provoke a sensitization of monoamine activity which is time-dependent and varies across brain regions. PMID:14644035

  9. Risk factors associated with increased bovine leukemia virus proviral load in infected cattle in Japan from 2012 to 2014.

    Science.gov (United States)

    Ohno, Ayumu; Takeshima, Shin-nosuke; Matsumoto, Yuki; Aida, Yoko

    2015-12-01

    Bovine leukemia virus (BLV) is the causative agent of enzootic bovine leukosis, a malignant B cell lymphoma. BLV has spread worldwide and causes serious problems. After infection, the BLV genome is integrated into the host DNA and can be amplified during periods of latency. We previously designed degenerate primers using the Coordination of Common Motifs (CoCoMo) algorithm to establish a new quantitative real-time PCR method (BLV-CoCoMo-qPCR-2) of measuring the proviral load of both known and novel BLV variants. Here, we aimed to examine the correlation between proviral load and risk factors for BLV infection, such as breeding systems, parousity, and colostrum feeding. Blood and serum samples were collected from 83 BLV-positive farms in 22 prefectures of Japan, and the BLV proviral load and anti-BLV antibody levels were measured. BLV was detected in 73.3% (1039/1,417) of cattle by BLV-CoCoMo-qPCR-2 and the provirus was detected in 93 of 1039 antibody-negative samples. The results showed that the proviral load increased with progression of lymphocytosis. Next, the risk factors associated with increasing BLV infection rate were examined along with any association with proviral load. The proviral load was higher in cattle with lymphocytosis than in healthy cattle, and higher in multiparous cows than in nulliparous cows. Finally, proviral loads were higher in contact breeding systems than in non-contact breeding systems. Taken together, these findings may help to formulate a plan for eliminating BLV from contaminated farms. This is the first nationwide study to estimate BLV proviral load in Japanese cattle. PMID:26321160

  10. Comparison of the prevalence and incidence of infection with bovine virus diarrhoea virus (BVDV) in Denmark and Michigan and association with possible risk factors

    DEFF Research Database (Denmark)

    Houe, H.; Baker, J.C.; Maes, R.K.;

    1995-01-01

    Based on 2 previous surveys on the occurrence of infection with bovine virus diarrhoea virus (BVDV) in Danish and Michigan dairy herds, the prevalence and incidence of the infection were compared. The presence of certain possible risk factors for the occurrence of infection in the 2 areas were su...

  11. Mitochondrial Dynamics and Mitochondrial Dysfunction in Diabetes.

    Science.gov (United States)

    Wada, Jun; Nakatsuka, Atsuko

    2016-06-01

    The mitochondria are involved in active and dynamic processes, such as mitochondrial biogenesis, fission, fusion and mitophagy to maintain mitochondrial and cellular functions. In obesity and type 2 diabetes, impaired oxidation, reduced mitochondrial contents, lowered rates of oxidative phosphorylation and excessive reactive oxygen species (ROS) production have been reported. Mitochondrial biogenesis is regulated by various transcription factors such as peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), peroxisome proliferator-activated receptors (PPARs), estrogen-related receptors (ERRs), and nuclear respiratory factors (NRFs). Mitochondrial fusion is promoted by mitofusin 1 (MFN1), mitofusin 2 (MFN2) and optic atrophy 1 (OPA1), while fission is governed by the recruitment of dynamin-related protein 1 (DRP1) by adaptor proteins such as mitochondrial fission factor (MFF), mitochondrial dynamics proteins of 49 and 51 kDa (MiD49 and MiD51), and fission 1 (FIS1). Phosphatase and tensin homolog (PTEN)-induced putative kinase 1 (PINK1) and PARKIN promote DRP1-dependent mitochondrial fission, and the outer mitochondrial adaptor MiD51 is required in DRP1 recruitment and PARKIN-dependent mitophagy. This review describes the molecular mechanism of mitochondrial dynamics, its abnormality in diabetes and obesity, and pharmaceuticals targeting mitochondrial biogenesis, fission, fusion and mitophagy. PMID:27339203

  12. The human mitochondrial ribosome recycling factor is essential for cell viability.

    NARCIS (Netherlands)

    Rorbach, J.; Richter, R.; Wessels, H.J.; Wydro, M.; Pekalski, M.; Farhoud, M.; Kuhl, I.; Gaisne, M.; Bonnefoy, N.; Smeitink, J.A.M.; Lightowlers, R.N.; Chrzanowska-Lightowlers, Z.M.

    2008-01-01

    The molecular mechanism of human mitochondrial translation has yet to be fully described. We are particularly interested in understanding the process of translational termination and ribosome recycling in the mitochondrion. Several candidates have been implicated, for which subcellular localization

  13. Expression and Methylation of Mitochondrial Transcription Factor A in Chronic Obstructive Pulmonary Disease Patients with Lung Cancer

    OpenAIRE

    Hong Peng; Min Yang; Zhi-yong Chen; Ping Chen; Cha-xiang Guan; Xu-dong Xiang; Shan Cai; Yan Chen; Xiang Fang

    2013-01-01

    BACKGROUND: Apoptosis plays a central role in the pathogenesis of chronic obstructive pulmonary disease (COPD), and this process can be regulated by mitochondrial transcription factor A (mtTFA). Epigenetics is involved in the regulation and modification of the genes involved in lung cancer and COPD. In this study, we determined the expression of mtTFA and its methylation levels in the COPD patients with lung cancer. METHODS: Twenty-one squamous cell lung cancer patients, 11 with COPD and 10 w...

  14. Study of modifiers factors associated to mitochondrial mutations in individuals with hearing impairment

    International Nuclear Information System (INIS)

    Hearing impairment is the most prevalent sensorial deficit in the general population. Congenital deafness occurs in about 1 in 1000 live births, of which approximately 50% has hereditary cause in development countries. Non-syndromic deafness can be caused by mutations in both nuclear and mitochondrial genes. Mutations in mtDNA have been associated with aminoglycoside-induced and non-syndromic deafness in many families worldwide. However, the nuclear background influences the phenotypic expression of these pathogenic mutations. Indeed, it has been proposed that nuclear modifier genes modulate the phenotypic manifestation of the mitochondrial A1555G mutation in the MTRNR1 gene. The both putative nuclear modifiers genes TRMU and MTO1 encoding a highly conserved mitochondrial related to tRNA modification. It has been hypothesizes that human TRMU and also MTO1 nuclear genes may modulate the phenotypic manifestation of deafness-associated mitochondrial mutations. The aim of this work was to elucidate the contribution of mitochondrial mutations, nuclear modifier genes mutations and aminoglycoside exposure in the deafness phenotype. Our findings suggest that the genetic background of individuals may play an important role in the pathogenesis of deafness-associated with mitochondrial mutation and aminoglycoside-induced.

  15. Effects of green tea polyphenols, insulin-like growth factor I and glucose on developmental competence of bovine oocytes

    Directory of Open Access Journals (Sweden)

    Zhengguang Wang

    2012-12-01

    Full Text Available The present study examined the effects of green tea polyphenols (GTP, insulin-like growth factor-I (IGF-I and glucose on oocyte in vitro maturation, subsequent embryo development and blastocyst quality in bovine. Cumulus-oocyte complexes (COC were aspirated from the ovaries and cultured in synthetic oviduct fluid supplemented with MEM amino acids (SOFaa media supplemented with one of the following supplements: GTP (0, 10, 15 and 20 µM, IGF-I (0, 50, 100 and 150 ng/mL or glucose (0, 1.5, 5.6 and 20 mM for 24 h. The results showed that oocytes cultured in media supplemented with 15 µM GTP, 100 ng/mL IGF-I and 5.6 mM glucose, in separate experiments, have higher cleavage and blastocyst rates compared with oocytes cultured in media without or with other concentration of GTP, IGF-I and glucose. Then these three substances with the concentration above were added together into SOFaa media and constituted a modified medium (Modified SOFaa. The COC were cultured in control SOFaa media and modified SOFaa media, respectively. The results showed that modified SOFaa media increased the intracellular glutathione concentration of matured oocytes, blastocyst rates and total cell numbers and cell numbers of inner cell mass per blastocyst compared with the control. Supplementing of GTP, IGF-I and glucose synchronously to maturation media can increase the intracellular GSH concentration of oocytes after in vitro maturation, and improve the embryo development and blastocyst quality in bovine.

  16. Prevalence and risk factor's analysis of bovine brucellosis in peri-urban areas under intensive system of production in Gujarat, India

    Directory of Open Access Journals (Sweden)

    M. D. Patel

    2014-07-01

    Full Text Available Aim: A study on surveillance of bovine brucellosis in dairy herds of peri-urban areas under intensive system of production was carried out by milk-ELISA. Various risk factors were identified having significant association with occurrence of bovine brucellosis in dairy herds of peri-urban areas. Materials and Methods: Five randomly selected peri-uban areas of six cities of Gujarat were included in the present study. Five randomly selected dairy herds under intensive system of production from each selected peri-urban area were included for further investigation. In total, 199 bulk and 582 individual milk samples were screened by milk-ELISA. Forty three different risk factors were identified and grouped into four major categories as general characteristics of farms, introduction of infection to farms, management systems of farms and exposure of disease. Further, their distribution and association with prevalence of bovine brucellosis was studied. Results: The overall herd and animal prevalence in peri-urban areas was 33.70 and 11.90%, respectively. Out of 11 risk factors on general characteristics of dairy farms, only five (herd size, type of animals, type of breed, age of owner and knowledge gained by owners showed significant (p<0.05 association with occurrence of bovine brucellosis. None of risk factors on introduction of infection to farms (n=6 and management systems of farms (n=11 was found significantly associated with occurrence of brucellosis. Among risk factors on exposure of disease (n=15, history of abortion, retention of placenta, still birth and metritis/endometritis showed significant (p<0.05 association with prevalence of bovine brucellosis. Conclusion: It was concluded that prevalence of bovine brucellosis in dairy herds under intensive system of production in peri-urban areas of Gujarat was comparatively higher than reported overall prevalence of brucellosis. Risk factors like larger herd in close confinement without adequate sheds

  17. Analysis of mRNA Associated factors During Bovine Oocyte Maturation and Early Embryonic Development

    Czech Academy of Sciences Publication Activity Database

    Siemer, C.; Smiljakovic, T.; Bhojawni, M.; Leiding, C.; Kanitz, W.; Kubelka, Michal; Tomek, W.

    2009-01-01

    Roč. 76, č. 12 (2009), s. 1208-1219. ISSN 1040-452X R&D Projects: GA ČR GA524/07/1087 Institutional research plan: CEZ:AV0Z50450515 Keywords : In Vitro maturation * Poly(A) binding protein * Initiation-factor 4E Subject RIV: ED - Physiology Impact factor: 2.041, year: 2009

  18. Crystal Structure of the Bovine lactadherin C2 Domain, a Membrane Binding Motif, Shows Similarity of the C2 Domains of Factor V and Factor VIII

    Energy Technology Data Exchange (ETDEWEB)

    Lin,L.; Huai, Q.; Huang, M.; Furie, B.; Furie, B.

    2007-01-01

    Lactadherin, a glycoprotein secreted by a variety of cell types, contains two EGF domains and two C domains with sequence homology to the C domains of blood coagulation proteins factor V and factor VIII. Like these proteins, lactadherin binds to phosphatidylserine (PS)-containing membranes with high affinity. We determined the crystal structure of the bovine lactadherin C2 domain (residues 1 to 158) at 2.4 Angstroms. The lactadherin C2 structure is similar to the C2 domains of factors V and VIII (rmsd of C? atoms of 0.9 Angstroms and 1.2 Angstroms, and sequence identities of 43% and 38%, respectively). The lactadherin C2 domain has a discoidin-like fold containing two ?-sheets of five and three antiparallel ?-strands packed against one another. The N and C termini are linked by a disulfide bridge between Cys1 and Cys158. One ?-turn and two loops containing solvent-exposed hydrophobic residues extend from the C2 domain ?-sandwich core. In analogy with the C2 domains of factors V and VIII, some or all of these solvent-exposed hydrophobic residues, Trp26, Leu28, Phe31, and Phe81, likely participate in membrane binding. The C2 domain of lactadherin may serve as a marker of cell surface phosphatidylserine exposure and may have potential as a unique anti-thrombotic agent.

  19. Crystal Structure of the Bovine lactadherin C2 Domain, a Membrane Binding Motif, Shows Similarity to the C2 Domains of Factor V and Factor VIII

    Energy Technology Data Exchange (ETDEWEB)

    Lin,L.

    2007-01-01

    Lactadherin, a glycoprotein secreted by a variety of cell types, contains two EGF domains and two C domains with sequence homology to the C domains of blood coagulation proteins factor V and factor VIII. Like these proteins, lactadherin binds to phosphatidylserine (PS)-containing membranes with high affinity. We determined the crystal structure of the bovine lactadherin C2 domain (residues 1 to 158) at 2.4 {angstrom}. The lactadherin C2 structure is similar to the C2 domains of factors V and VIII (rmsd of C{sub {alpha}} atoms of 0.9 {angstrom} and 1.2 {angstrom}, and sequence identities of 43% and 38%, respectively). The lactadherin C2 domain has a discoidin-like fold containing two {beta}-sheets of five and three antiparallel {beta}-strands packed against one another. The N and C termini are linked by a disulfide bridge between Cys1 and Cys158. One {beta}-turn and two loops containing solvent-exposed hydrophobic residues extend from the C2 domain {beta}-sandwich core. In analogy with the C2 domains of factors V and VIII, some or all of these solvent-exposed hydrophobic residues, Trp26, Leu28, Phe31, and Phe81, likely participate in membrane binding. The C2 domain of lactadherin may serve as a marker of cell surface phosphatidylserine exposure and may have potential as a unique anti-thrombotic agent.

  20. α-transforming growth factor secreted by untransformed bovine anterior pituitary cells in culture. II. Identification using a sequence-specific monoclonal antibody

    International Nuclear Information System (INIS)

    Untransformed bovine anterior pituitary cells cultured in serum-free defined medium secrete an epidermal growth factor (EGF)-like peptide with an amino acid composition similar to rat or human α-transforming growth factor (αTGF). To further characterize the bovine pituitary αTGF, it was compared to a human αTGF partially purified from the conditioned medium of a human melanoma cell line. An anti-αTGF monoclonal antibody, MF9, was produced from hybridomas derived from mice immunized with a 17-residue synthetic peptide corresponding to the carboxyl-terminal sequence of rat αTGF. The hybridoma supernatants were initially screened for the ability to immunoprecipitate 125I-peptide and then tested for recognition of human αTGF. Only 2 of 36 antipeptide antibodies recognized the native αTGF. The binding of 125I-peptide to MF9 was displaced by human αTGF but not by EGF. Bovine pituitary αTGF also displaced the binding of 125I-peptide to MF9 in a similar manner to human αTGF. Both iodinated human and bovine pituitary αTGF were immunoprecipitated by MF9 whereas 125I-EGF was not. Tryptic digests of both 125I-αTGFs chromatographed to give a single, indistinguishable peak of iodinated material on a reverse-phase C18 high performance liquid chromatography column when eluted with two different solvent systems, suggesting the generation of a single and identical tyrosine-containing tryptic peptide from both αTGFs. The comparisons of the bovine pituitary and human melanoma αTGF using a sequence-specific monoclonal antibody and peptide mapping suggest that these αTGFs are related and that αTGF production is not limited to transformed or fetal sources

  1. Udder quarter risk factors associated with prevalence of bovine clinical mastitis

    OpenAIRE

    Nakov Dimitar; Trajcev Metodija

    2012-01-01

    A cross sectional study was carried out to estimate prevalence of clinical mastitis on udder quarters level and to determinate the quarter risk factors associated with the development of clinical mastitis during lactation.The individual risk factors included assessments of parity, season of year when case of clinical mastitis was occurred, conformation characteristics of udder quarters and teats and distance from front and rear teat end to the floor. Cows with clinical mastitis were detected ...

  2. Cloning and functional analysis of human mTERFL encoding a novel mitochondrial transcription termination factor-like protein

    International Nuclear Information System (INIS)

    Serum plays an important role in the regulation of cell cycle and cell growth. To identify novel serum-inhibitory factors and study their roles in cell cycle regulation, we performed mRNA differential display analysis of U251 cells in the presence or absence of serum and cloned a novel gene encoding the human mitochondrial transcription termination factor-like protein (mTERFL). The full-length mTERFL cDNA has been isolated and the genomic structure determined. The mTERFL gene consists of three exons and encodes 385 amino acids with 52% sequence similarity to the human mitochondrial transcription termination factor (mTERF). However, mTERFL and mTERF have an opposite expression pattern in response to serum. The expression of mTERFL is dramatically inhibited by the addition of serum in serum-starved cells while the mTERF is rather induced. Northern blot analysis detected three mTERFL transcripts of 1.7, 3.2, and 3.5 kb. Besides the 3.2 kb transcript that is unique to skeletal muscle, other two transcripts express predominant in heart, liver, pancreas, and skeletal muscle. Expression of the GFP-mTERFL fusion protein in HeLa cells localized it to the mitochondria. Furthermore, ectopic expression of mTERFL suppresses cell growth and arrests cells in the G1 stage demonstrated by MTT and flow cytometry analysis. Collectively, our data suggest that mTERFL is a novel mTERF family member and a serum-inhibitory factor probably participating in the regulation of cell growth through the modulation of mitochondrial transcription

  3. Targeting and function of the mitochondrial fission factor GDAP1 are dependent on its tail-anchor.

    Directory of Open Access Journals (Sweden)

    Konstanze M Wagner

    Full Text Available Proteins controlling mitochondrial dynamics are often targeted to and anchored into the mitochondrial outer membrane (MOM by their carboxyl-terminal tail-anchor domain (TA. However, it is not known whether the TA modulates protein function. GDAP1 is a mitochondrial fission factor with two neighboring hydrophobic domains each flanked by basic amino acids (aa. Here we define GDAP1 as TA MOM protein. GDAP1 carries a single transmembrane domain (TMD that is, together with the adjacent basic aa, critical for MOM targeting. The flanking N-terminal region containing the other hydrophobic domain is located in the cytoplasm. TMD sequence, length, and high hydrophobicity do not influence GDAP1 fission function if MOM targeting is maintained. The basic aa bordering the TMD in the cytoplasm, however, are required for both targeting of GDAP1 as part of the TA and GDAP1-mediated fission. Thus, this GDAP1 region contains critical overlapping motifs defining intracellular targeting by the TA concomitant with functional aspects.

  4. Insulin-like growth factor binding proteins in follicular fluid from morphologically distinct healthy and atretic bovine antral follicles.

    Science.gov (United States)

    Irving-Rodgers, H F; Catanzariti, K D; Master, M; Grant, P A; Owens, P C; Rodgers, R J

    2003-01-01

    In bovine follicles 2-5 mm in diameter, two morphologically distinct types of healthy follicles and two types of atretic follicles have been described recently. Healthy follicles either have columnar basal granulosa cells with follicular basal lamina composed of many layers or 'loops' or they have rounded basal cells with a conventional single-layered, aligned follicular basal lamina. In atretic follicles, cell death either commences at the basal layer and progresses to the antrum (basal atresia) with macrophage penetration of the membrana granulosa or death progresses from the antrum in a basal direction (antral atresia). Little is known about how these different phenotypes develop. To determine whether insulin-like growth factor binding protein (IGFBP) levels in follicular fluid differ between these different types of follicles, we measured IGFBP levels in fluids from these follicles. A total of 61 follicles were assessed by light microscopy and characterized by morphological analysis as either healthy, with columnar or rounded basal granulosa cells, or as undergoing antral or basal atresia. The IGFBP concentration in the follicular fluid of individual follicles from the four groups (n = 12-20 per group) was identified by Western ligand blots using (125)I-insulin-like growth factor (IGF)-II as a probe. Insulin-like growth factor binding proteins 2, 3 (44 and 40 kDa), 4 (glycosylated and non-glycosylated) and 5 were observed. The levels (per volume of fluid) of IGFBPs 2, 4 and 5 were greater in atretic follicles than in healthy follicles. However, there were no statistical differences in levels of each IGFBP between either the two types of healthy follicle or between the two types of atretic follicles. Thus, IGFBP levels are not related to the different types of healthy or atretic follicles. PMID:12921699

  5. Risk factors for failure to detect bovine tuberculosis in cattle from infected herds across Northern Ireland (2004-2010).

    Science.gov (United States)

    Lahuerta-Marin, Angela; McNair, James; Skuce, Robin; McBride, Stewart; Allen, Michelle; Strain, Sam A J; Menzies, Fraser D; McDowell, Stanley J W; Byrne, Andrew W

    2016-08-01

    Correctly identifying animals that are truly infected with a pathogen using ante-mortem tests is the cornerstone of any disease eradication programme. Failure to identify all infected animals will impede the progress towards controlling and eradicating disease and may also have unforeseen consequences when specific prevention measures are in place to avoid animal-to-animal transmission. In the case of bovine tuberculosis (bTB), the screening ante-mortem test, the Single Comparative Intradermal Tuberculin Test (SCITT), can exhibit moderate sensitivity which can result in a "hidden burden" of infection residing within the population. Using an animal-level dataset relating to the disclosure of infected cattle with Mycobacterium bovis, the causative agent of bTB within infected herds in Northern Ireland, we investigated what factors influenced the probability of an animal being a false-negative when truly infected (using post-mortem (PM) microbiological culture confirmation results to assess infection status). We found that different risk factors affected the probability of a test-negative outcome on infected animals depending on the ante-mortem test or their combination (SICTT and/or interferon gamma (IFN-ɣ) testing). Using multivariable models, SCITT disclosure performance varied significantly by age, location (region), and production type. The IFN-ɣ tests were significantly affected by region or season, but these effects depended on the cut-off used during interpretation of the test which affected the tests characteristics. Parallel use of SCITT and IFN-ɣ tests resulted in the least number of false-negatives, and their disclosure was affected by season and age-class. Understanding the factors that lead to the non-disclosure of infected animals is essential to optimise large-scale bTB disease eradication programmes. PMID:27474001

  6. Some physical and chemical properties of the smooth muscle inhibitory factor in extracts of the bovine retractor penis muscle.

    Science.gov (United States)

    Gillespie, J S; Hunter, J C; Martin, W

    1981-06-01

    1. A method of extracting and partially purifying a smooth muscle inhibitory factor from the bovine retractor penis is described. This consists of extraction in methanol followed by adsorption on an anion exchange resin, elution from the resin with 500 mM-sodium chloride solution and, if necessary, removal of adenine nucleotides by adsorption on alumina. 2. The inhibitory factor exists in a stable pharmacologically inactive form and an unstable pharmacologically active form. Conversion to the active form is by a brief exposure to acid at pH 2.0. 3. The inhibitory factor is insoluble in ether or acetone but soluble in methanol. Anhydrous methanol, however, irreversibly destroys pharmacological activity especially if the inhibitory factor is in the active form. This effect of methanol is prevented by the presence of 20-30-% water. 4. The inhibitory factor binds to an anion exchange resin but not to a cation exchange resin. It can be eluted from the resin by 500 mM-sodium chloride solution. 5. The molecular weight of the inhibitory factor, as judged by the ability to pass ultrafiltration membranes, is about 500. 6. Inhibitory activity is unaffected by the proteases trypsin, subtilisin or pepsin or by leucine aminopeptidase, pyroglutamate aminopeptidase or carboxypeptidase. The inhibitory effect of the extract and the inhibitory response to stimulation of the non-adrenergic, non-cholinergic nerves are also unaffected by the protease inhibitor, aprotinin. The active material, therefore, is unlikely to be a peptide. 7. Inhibitory activity is abolished by exposure of the extracts to periodic acid or sodium periodate. Acetic anhydride in pyridine also abolishes activity but the vehicle pyridine is also effective. 8. Sodium borohydride but not borate abolishes inhibitory activity when added to the acid-activated material at pH 2.0 but has no effect or may even potentiate activity if added to the stable inactive form at pH 9.0. When added to the acid-activated but

  7. Mitochondrial-targeted antioxidant therapy decreases transforming growth factor-β-mediated collagen production in a murine asthma model.

    Science.gov (United States)

    Jaffer, Omar A; Carter, A Brent; Sanders, Philip N; Dibbern, Megan E; Winters, Christopher J; Murthy, Shubha; Ryan, Alan J; Rokita, Adam G; Prasad, Anand M; Zabner, Joseph; Kline, Joel N; Grumbach, Isabella M; Anderson, Mark E

    2015-01-01

    Asthma is a disease of acute and chronic inflammation in which cytokines play a critical role in orchestrating the allergic inflammatory response. IL-13 and transforming growth factor (TGF)-β promote fibrotic airway remodeling, a major contributor to disease severity. Improved understanding is needed, because current therapies are inadequate for suppressing development of airway fibrosis. IL-13 is known to stimulate respiratory epithelial cells to produce TGF-β, but the mechanism through which this occurs is unknown. Here, we tested the hypothesis that reactive oxygen species (ROS) are a critical signaling intermediary between IL-13 or allergen stimulation and TGF-β-dependent airway remodeling. We used cultured human bronchial epithelial cells and an in vivo mouse model of allergic asthma to map a pathway where allergens enhanced mitochondrial ROS, which is an essential upstream signal for TGF-β activation and enhanced collagen production and deposition in airway fibroblasts. We show that mitochondria in airway epithelium are an essential source of ROS that activate TGF-β expression and activity. TGF-β from airway epithelium stimulates collagen expression in fibroblasts, contributing to an early fibrotic response to allergen exposure in cultured human airway cells and in ovalbumin-challenged mice. Treatment with the mitochondrial-targeted antioxidant, (2-(2,2,6,6-Tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl)triphenylphosphonium chloride (mitoTEMPO), significantly attenuated mitochondrial ROS, TGF-β, and collagen deposition in OVA-challenged mice and in cultured human epithelial cells. Our findings suggest that mitochondria are a critical source of ROS for promoting TGF-β activity that contributes to airway remodeling in allergic asthma. Mitochondrial-targeted antioxidants may be a novel approach for future asthma therapies. PMID:24988374

  8. Investigation of risk factors of bovine mastitis in Ethiopia; Isolation of mastitis causing agents and determination of the content of somatic cells in milk

    OpenAIRE

    Frese, Mathias Lutz

    2010-01-01

    In this thesis, the risk factors of bovine mastitis in different milk production systems in Ethiopia were investigated. Furthermore, mastitis causing agents were isolated after California Mastitis Test (CMT) was used as the field test. Somatic cells were counted and compared with the CMT. Low milk production and low quality of milk are apparently related to a lack of proper hygienic measures throughout the farm clusters.

  9. Impact of exercise on mitochondrial transcription factor expression and damage in the striatum of a chronic mouse model of Parkinson’s disease

    OpenAIRE

    Patki, Gaurav; Lau, Yuen-Sum

    2011-01-01

    The etiology of neurodegenerative disorders like Parkinson’s disease remains unknown, although many genetic and environmental factors are suggested as likely causes. Neuronal oxidative stress and mitochondrial dysfunction have been implicated as possible triggers for the onset and progression of Parkinson’s neurodegeneration. We have recently shown that long-term treadmill exercise prevented neurological, mitochondrial and locomotor deficits in a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropy...

  10. Bovine mastitis prevalence and associated risk factors in dairy cows in Nyagatare District, Rwanda

    Directory of Open Access Journals (Sweden)

    Blaise Iraguha

    2015-03-01

    Full Text Available In response to farmer requests after milk from their herds was rejected by processors due to poor quality, a study was carried out from April to October 2011 to determine the prevalence of sub clinical mastitis, associated risk factors and causative micro-organisms. Samples were collected from 195 dairy cows on 23 randomly selected dairy farms delivering milk to Isangano, Kirebe and Nyagatare milk collection centres in Nyagatare District, Rwanda. The Draminski® Mastitis Detector was used to detect sub clinical mastitis in individual cows based on milk electrical conductivity changes. Risk factors for mastitis that were evaluated included teat-end condition, cow dirtiness, breed, parity, age and stage of lactation. Relationships of these factors with mastitis status were determined using Chi-square analysis, and relative importance as causes of mastitis was assessed using logistic regression. Samples from 16 sub clinical mastitis positive dairy cows were analysed to identify causative micro-organisms using Dairy Quality Control Inspection analytical kits. Sub clinical mastitis prevalence was 52% across the farms. It was higher with increases in, amongst other risk factors, teat-end damage severity, cow dirtiness, and level of pure dairy breed genetics. The risk factors considered accounted for 62% of mastitis prevalence; teat-end condition alone accounted for 30%. Most of the mastitis cases (87.5% were caused by coliform bacteria. Considering that farmers are upgrading their local Ankole cows to cross-breed dairy cows that are more susceptible to mastitis, results from this study indicate the need to dip the teats of cows in sanitisers, improve cow hygiene, and introduce mastitis prevention and control programmes.

  11. Bovine mastitis prevalence and associated risk factors in dairy cows in Nyagatare District, Rwanda

    OpenAIRE

    Blaise Iraguha; Humphrey Hamudikuwanda; Borden Mushonga

    2015-01-01

    In response to farmer requests after milk from their herds was rejected by processors due to poor quality, a study was carried out from April to October 2011 to determine the prevalence of sub clinical mastitis, associated risk factors and causative micro-organisms. Samples were collected from 195 dairy cows on 23 randomly selected dairy farms delivering milk to Isangano, Kirebe and Nyagatare milk collection centres in Nyagatare District, Rwanda. The Draminski® Mastitis Detector was used to d...

  12. Heme deficiency may be a factor in the mitochondrial and neuronal decay of aging

    OpenAIRE

    Atamna, Hani; Killilea, David W.; Killilea, Alison Nisbet; Bruce N. Ames

    2002-01-01

    Heme, a major functional form of iron in the cell, is synthesized in the mitochondria by ferrochelatase inserting ferrous iron into protoporphyrin IX. Heme deficiency was induced with N-methylprotoporphyrin IX, a selective inhibitor of ferrochelatase, in two human brain cell lines, SHSY5Y (neuroblastoma) and U373 (astrocytoma), as well as in rat primary hippocampal neurons. Heme deficiency in brain cells decreases mitochondrial complex IV, activates nitric oxide synthase, alters amyloid precu...

  13. Study on Clinical Bovine Dermatophilosis and its Potential Risk Factors in North Western Ethiopia

    Directory of Open Access Journals (Sweden)

    Meseret Admassu and Sefinew Alemu

    2011-02-01

    Full Text Available A cross-sectional study of dermatophilosis was undertaken from October 2008 to March 2009 on 3456 cattle (3181 indigenous zebu and 275 Holestien-zebu cross with the aim of determining prevalence and associated risk factors in urban and periurban areas of Bahir Dar, north western Ethiopia. Culturing of Dermatiphilus congolensis and Giemsa staining were the techniques used. Thirty six of 3456 examined animals (1.04% had clinical dermatophilosis. Prevalence was higher in cross bred (5.5% than in indigenous zebu (0.7% cattle, in male cattle (1.7% than in female (0.8% , in adults (1.2% than in young (0.8% age groups, in wet (1.6% than in dry season (0.5%, and in cattle infested with tick (2.7% than cattle with no tick infestation (0.4%. Statistically significant difference (p# 0.05 was observed in the prevalence between breeds of cattle, between age groups, between wet and dry seasons, and between cattle with and without tick infestation. Amblyoma variegatum was identified. The study indicated dermatophilosis is a potential determinant factor for the dairy development strategy started through cross breeding in the study area. Tick control especially on crossbred cattle is suggested to reduce the risk of dermatophilosis.

  14. Calf-level factors associated with bovine neonatal pancytopenia--a multi-country case-control study.

    Directory of Open Access Journals (Sweden)

    Bryony A Jones

    Full Text Available Bovine neonatal pancytopenia (BNP, a high fatality condition causing haemorrhages in calves aged less than 4 weeks, was first reported in 2007 in Germany and subsequently observed at low incidence in other European countries and New Zealand. A multi-country matched case-control study was conducted in 2011 to identify calf-level risk factors for BNP. 405 BNP cases were recruited from 330 farms in Belgium, France, Germany and the Netherlands by laboratory confirmation of farmer-reported cases. Up to four calves of similar age from the same farm were selected as controls (1154 calves. Risk factor data were collected by questionnaire. Multivariable modelling using conditional logistic regression indicated that PregSure®BVD (PregSure, Pfizer Animal Health vaccination of the dam was strongly associated with BNP cases (adjusted matched Odds Ratio - amOR 17.8 first lactation dams; 95% confidence interval - ci 2.4, 134.4; p = 0.005, and second or more lactation PregSure-vaccinated dams were more likely to have a case than first lactation vaccinated dams (amOR 2.2 second lactation; ci 1.1, 4.3; p = 0.024; amOR 5.3 third or more lactation; ci 2.9, 9.8; p = <0.001. Feeding colostrum from other cows was strongly associated with BNP if the dam was not PregSure-vaccinated (amOR 30.5; ci 2.1, 440.5; p = 0.012, but the effect was less if the dam was PregSure-vaccinated (amOR 2.1; ci 1.1, 4.0; p = 0.024. Feeding exclusively dam's milk was a higher risk than other types of milk (amOR 3.4; ci 1.6, 7.5; p = 0.002. The population attributable fractions were 0.84 (ci 0.68, 0.92 for PregSure vaccination, 0.13 (ci 0.06, 0.19 for feeding other cows' colostrum, and 0.15 (ci 0.08, 0.22 for feeding dam's milk. No other calf-level factors were identified, suggesting that there are other important factors that are outside the scope of this study, such as genetics, which explain why BNP develops in some PregSure-colostrum-exposed calves but not in

  15. Review-Factors involving in fluctuation of trace metals concentrations in bovine milk.

    Science.gov (United States)

    Perween, Rubina

    2015-05-01

    Milk makes a significant contribution to human diet through provision of macronutrients, vitamins and minerals. The exact composition of milk varies with species among domestic animals according to their neonatal needs. It is recognized that imbalance in the quantity of minerals and trace elements is a serious health hazard especially for infants. Many studies reported the fluctuation in the level of metals in milk due to the influence of several factors such as geographical and exposure to environmental pollution caused by anthropogenic activity. Amongst all sources, industries take lion's share to alter the metal content in milk. The importance of different nutritional and toxic metals in milk from different geographical areas is discussed. PMID:26004711

  16. Risk factors associated with the antimicrobial resistance of Staphylococcus aureus isolated from bovine mastitis

    Directory of Open Access Journals (Sweden)

    Daniele C. Beuron

    2014-10-01

    Full Text Available The objective of this study was to evaluate herd management practices and mastitis treatment procedures as risk factors associated with Staphylococcus aureus antimicrobial resistance. For this study, 13 herds were selected to participate in the study to evaluate the association between their management practices and mastitis treatment procedures and in vitro antimicrobial susceptibility. A total of 1069 composite milk samples were collected aseptically from the selected cows in four different periods over two years. The samples were used for microbiological culturing of S. aureus isolates and evaluation of their antimicrobial susceptibility. A total of 756 samples (70.7% were culture-positive, and S. aureus comprised 27.77% (n=210 of the isolates. The S. aureus isolates were tested using the disk-diffusion susceptibility assay with the following antimicrobials: ampicillin 10mg; clindamycin 2μg; penicillin 1mg; ceftiofur 30μg; gentamicin 10mg; sulfa-trimethoprim 25μg; enrofloxacin 5μg; sulfonamide 300μg; tetracycline 30μg; oxacillin 1mg; cephalothin 30μg and erythromycin 5μg. The variables that were significantly associated with S. aureus resistance were as follows: the treatment of clinical mastitis for ampicillin (OR=2.18, dry cow treatment for enrofloxacin (OR=2.11 and not sending milk samples for microbiological culture and susceptibility tests, for ampicillin (OR=2.57 and penicillin (OR=4.69. In conclusion, the identification of risk factors for S. aureus resistance against various mastitis antimicrobials is an important information that may help in practical recommendations for prudent use of antimicrobial in milk production.

  17. Atrial natriuretic factor R1 receptor from bovine adrenal zona glomerulosa: Purification, characterization, and modulation by amiloride

    International Nuclear Information System (INIS)

    The atrial natriuretic factor (ANF) R1 receptor from bovine adrenal zona glomerulosa was solubilized with Triton X-100 and purified 13,000-fold, to apparent homogeneity, by sequential affinity chromatography on ANF-agarose and steric exclusion high-performance liquid chromatography. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and silver staining of the purified receptor preparation in the absence or presence of dithiothreitol revealed a single protein band of Mr 130,000. Affinity cross-linking of 125I-ANF to the purified receptor resulted in the labeling of the Mr 130,000 band. The purified receptor bound ANF with a specific activity of 6.8 nmol/mg of protein, corresponding to a stoichiometry of 0.9 mol of ANF bound/mol of Mr 130,000 polypeptide. Starting with 500 g of adrenal zona glomerulosa tissue, the authors obtained more than 500 pmol of purified receptor with an overall yield of 9%. The purified receptor showed a typical ANF-R1 pharmacological specificity similar to that of the membrane-bound receptor. The homogeneous Mr 130,000 receptor protein displayed high guanylate cyclase activity [1.4 μmol of cyclic GMP formed min-1 (mg of protein)-1] which was not stimulated by ANF. This finding supports the notion that the ANF binding and the guanylate cyclase activities are intrinsic components of the same polypeptide. Finally, the purified ANF-R1 receptor retained its sensitivity to modulation by amiloride, suggesting the presence of an allosteric binding site for amiloride on the receptor protein

  18. Successful tumour necrosis factor (TNF) blocking therapy suppresses oxidative stress and hypoxia-induced mitochondrial mutagenesis in inflammatory arthritis

    LENUS (Irish Health Repository)

    Biniecka, Monika

    2011-07-25

    Abstract Introduction To examine the effects of tumour necrosis factor (TNF) blocking therapy on the levels of early mitochondrial genome alterations and oxidative stress. Methods Eighteen inflammatory arthritis patients underwent synovial tissue oxygen (tpO2) measurements and clinical assessment of disease activity (DAS28-CRP) at baseline (T0) and three months (T3) after starting biologic therapy. Synovial tissue lipid peroxidation (4-HNE), T and B cell specific markers and synovial vascular endothelial growth factor (VEGF) were quantified by immunohistochemistry. Synovial levels of random mitochondrial DNA (mtDNA) mutations were assessed using Random Mutation Capture (RMC) assay. Results 4-HNE levels pre\\/post anti TNF-α therapy were inversely correlated with in vivo tpO2 (P < 0.008; r = -0.60). Biologic therapy responders showed a significantly reduced 4-HNE expression (P < 0.05). High 4-HNE expression correlated with high DAS28-CRP (P = 0.02; r = 0.53), tender joint count for 28 joints (TJC-28) (P = 0.03; r = 0.49), swollen joint count for 28 joints (SJC-28) (P = 0.03; r = 0.50) and visual analogue scale (VAS) (P = 0.04; r = 0.48). Strong positive association was found between the number of 4-HNE positive cells and CD4+ cells (P = 0.04; r = 0.60), CD8+ cells (P = 0.001; r = 0.70), CD20+ cells (P = 0.04; r = 0.68), CD68+ cells (P = 0.04; r = 0.47) and synovial VEGF expression (P = 0.01; r = 063). In patients whose in vivo tpO2 levels improved post treatment, significant reduction in mtDNA mutations and DAS28-CRP was observed (P < 0.05). In contrast in those patients whose tpO2 levels remained the same or reduced at T3, no significant changes for mtDNA mutations and DAS28-CRP were found. Conclusions High levels of synovial oxidative stress and mitochondrial mutation burden are strongly associated with low in vivo oxygen tension and synovial inflammation. Furthermore these significant mitochondrial genome alterations are rescued following successful anti TNF

  19. Both viral E2 protein and the cellular factor PEBP2 regulate transcription via E2 consensus sites within the bovine papillomavirus type 4 long control region.

    OpenAIRE

    Jackson, M E; Campo, M. S.

    1995-01-01

    The bovine papillomavirus type 4 (BPV4) long control region (LCR) contains three consensus binding sites, E2(1), E2(2), and E2(3) (ACCN6GGT), for the viral E2 transcription factor and a fourth degenerate site, dE2 (ATCN6GGT), which lies 3 bp upstream of E2(3). The E2(2) site was found to bind the cellular transcription factor PEBP2, and mutations at this site reduced basal promoter activity by as much as 60%, indicating an important role for PEBP2 in LCR function. Mutation of the E2(3) or dE2...

  20. Decreased levels of proapoptotic factors and increased key regulators of mitochondrial biogenesis constitute new potential beneficial features of long-lived growth hormone receptor gene-disrupted mice.

    Science.gov (United States)

    Gesing, Adam; Masternak, Michal M; Lewinski, Andrzej; Karbownik-Lewinska, Malgorzata; Kopchick, John J; Bartke, Andrzej

    2013-06-01

    Decreased somatotrophic signaling is among the most important mechanisms associated with extended longevity. Mice homozygous for the targeted disruption of the growth hormone (GH) receptor gene (GH receptor knockout; GHRKO) are obese and dwarf, are characterized by a reduced weight and body size, undetectable levels of GH receptor, high concentration of serum GH, and greatly reduced plasma levels of insulin and insulin-like growth factor-I, and are remarkably long lived. Recent results suggest new features of GHRKO mice that may positively affect longevity-decreased levels of proapoptotic factors and increased levels of key regulators of mitochondrial biogenesis. The alterations in levels of the proapoptotic factors and key regulators of mitochondrial biogenesis were not further improved by two other potential life-extending interventions-calorie restriction and visceral fat removal. This may attribute the primary role to GH resistance in the regulation of apoptosis and mitochondrial biogenesis in GHRKO mice in terms of increased life span. PMID:23197187

  1. The Yeast Mitochondrial RNA Polymerase and Transcription Factor Complex Catalyzes Efficient Priming of DNA Synthesis on Single-stranded DNA.

    Science.gov (United States)

    Ramachandran, Aparna; Nandakumar, Divya; Deshpande, Aishwarya P; Lucas, Thomas P; R-Bhojappa, Ramanagouda; Tang, Guo-Qing; Raney, Kevin; Yin, Y Whitney; Patel, Smita S

    2016-08-01

    Primases use single-stranded (ss) DNAs as templates to synthesize short oligoribonucleotide primers that initiate lagging strand DNA synthesis or reprime DNA synthesis after replication fork collapse, but the origin of this activity in the mitochondria remains unclear. Herein, we show that the Saccharomyces cerevisiae mitochondrial RNA polymerase (Rpo41) and its transcription factor (Mtf1) is an efficient primase that initiates DNA synthesis on ssDNA coated with the yeast mitochondrial ssDNA-binding protein, Rim1. Both Rpo41 and Rpo41-Mtf1 can synthesize short and long RNAs on ssDNA template and prime DNA synthesis by the yeast mitochondrial DNA polymerase Mip1. However, the ssDNA-binding protein Rim1 severely inhibits the RNA synthesis activity of Rpo41, but not the Rpo41-Mtf1 complex, which continues to prime DNA synthesis efficiently in the presence of Rim1. We show that RNAs as short as 10-12 nt serve as primers for DNA synthesis. Characterization of the RNA-DNA products shows that Rpo41 and Rpo41-Mtf1 have slightly different priming specificity. However, both prefer to initiate with ATP from short priming sequences such as 3'-TCC, TTC, and TTT, and the consensus sequence is 3'-Pu(Py)2-3 Based on our studies, we propose that Rpo41-Mtf1 is an attractive candidate for serving as the primase to initiate lagging strand DNA synthesis during normal replication and/or to restart stalled replication from downstream ssDNA. PMID:27311715

  2. The Porcine Mitochondrial Transcription Factor a Gene: Molecular Characterization, Radiation Hybrid Mapping and Genetic Diversity among 12 Pig Breeds

    Directory of Open Access Journals (Sweden)

    Tanja Kunej

    2009-01-01

    Full Text Available Problem statement: Mitochondrial transcription factor A (TFAM is a nucleus-encoded protein that is a key activator of mitochondrial transcription as well as a major participant in mitochondrial genome replication. Genomic characterization of the porcine TFAM gene is, therefore, necessary to determine its involvement in regulation of fat depots and meat quality traits in pigs. Approach: Genomic DNA sequence was determined using a comparative in silico annotation approach. RT-PCR was used for analysis of alternative splicing. Genome location was determined using Radiation Hybrid (RH mapping. Genetic marker was identified by sequencing and genotyped by the PCR-RFLP method with SacI. GENEPOP version 3.3 software was used for statistic analysis. Results: We determined both full-length cDNA and genomic DNA sequences of the porcine TFAM gene. Gene expression analysis revealed an alternative 5’ splice site, which excludes exon 4 of the pig gene. We assigned this gene to porcine chromosome 14 (SSC14. A G/A substitution was detected in intron 1 of porcine TFAM gene and genotyped on a total of 252 animals, including 165 from seven Chinese and 87 from five Western pig breeds. The Bayesian analysis via MCMC (Markov chain Monte Carlo revealed that these two groups of pigs were well separated at this locus during the breed history; 95% of the posterior difference of TFAM allelic frequency between these two pig groups was greater than zero. Conclusion/Recommendations: All these data provided basic genomic information needed for further functional characterization of the porcine TFAM gene. Because marked differences in fat and lean tissue deposition exist between Western and Chinese pig breeds, the G557A mutation in the TFAM gene deserves further evaluation to determine its phenotypic effect on fattening and carcass traits in commercial pig populations.

  3. Macrophages infected with cytopathic bovine viral diarrhea virus release a factor(s) capable of priming uninfected macrophages for activation-induced apoptosis.

    OpenAIRE

    Adler, B; Adler, H; Pfister, H; Jungi, T. W.; Peterhans, E

    1997-01-01

    Bovine bone marrow-derived macrophages infected with the cytopathic biotype of bovine viral diarrhea virus released an antiviral activity into the supernatant which was tentatively characterized as type I interferon because of its physicochemical properties. Such supernatants primed both infected and uninfected macrophages for decreased nitric oxide production and apoptosis in response to lipopolysaccharide. This finding strongly suggests a role of this pathway in the pathogenesis of mucosal ...

  4. Fever and acute phase response induced in dwarf goats by endotoxin and bovine and human recombinant tumour necrosis factor alpha.

    Science.gov (United States)

    van Miert, A S; van Duin, C T; Wensing, T

    1992-12-01

    Tumour necrosis factor (TNF), a polypeptide produced by mononuclear phagocytes, has been implicated as an important mediator of inflammatory processes and of clinical manifestations in acute infectious diseases. To study further the potential role of TNF in infectious diseases, recombinant Escherichia coli (E. coli) derived human (r.HuTNF-alpha) and bovine TNF (r.BoTNF-alpha) were intravenously (i.v.) administered in dwarf goats. Rectal temperature, heart rate, rumen motility, plasma zinc and iron concentrations, and certain other blood biochemical and haematological values were studied and compared with the changes seen after E. coli endotoxin (LPS) was administered (dose: 0.1 microgram/kg i.v.). Following a single injection of 4 micrograms/kg of r.BoTNF-alpha, shivering and biphasic febrile response were observed, accompanied by tachycardia, inhibition of rumen contractions, drop in plasma zinc and iron concentrations, lymphopenia, and neutropenia followed by neutrophilia. The i.v. administration of a single injection of 4 micrograms/kg r.HuTNF-alpha induced shivering and biphasic febrile responses, accompanied by anorexia and a similar drop in plasma trace metal concentrations when compared with r.BoTNF-alpha-treated goats. The TNF-alpha-induced symptoms were essentially the same as those that occurred after LPS administration. However, the time of onset of these changes after the injection of TNF-alpha was significantly shorter than after LPS. Moreover, the r.BoTNF-alpha induced a longer lasting neutrophilic leucopenia, less neutrophilia, and a more persistent lymphopenia than after LPS injection. Neither r.BoTNF-alpha nor LPS caused severe haemo-concentration. Furthermore, no cross-tolerance between r.BoTNF-alpha and LPS could be demonstrated. We conclude that both r.BoTNF-alpha and r.HuTNF-alpha induce many of the physiologic, haematologic and metabolic changes that characterize the acute phase response to LPS. The overlapping biological activities of r

  5. Human Mitochondrial Transcription Factor B1 Interacts with the C-Terminal Activation Region of h-mtTFA and Stimulates Transcription Independently of Its RNA Methyltransferase Activity

    OpenAIRE

    McCulloch, Vicki; Shadel, Gerald S.

    2003-01-01

    A significant advancement in understanding mitochondrial gene expression is the recent identification of two new human mitochondrial transcription factors, h-mtTFB1 and h-mtTFB2. Both proteins stimulate transcription in collaboration with the high-mobility group box transcription factor, h-mtTFA, and are homologous to rRNA methyltransferases. In fact, the dual-function nature of h-mtTFB1 was recently demonstrated by its ability to methylate a conserved rRNA substrate. Here, we demonstrate tha...

  6. Insulin-like growth factor-I and insulin-like growth factor binding proteins in the bovine mammary gland: Receptors, endogenous secretion, and appearance in milk

    Energy Technology Data Exchange (ETDEWEB)

    Campbell, P.G.

    1988-01-01

    This is the first study to characterize both insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding proteins (IGFBPs) in bovine milk, to characterize the IGF-I receptor in the dry and lactating mammary gland, and to report de novo synthesis and secretion of IGF-I and IGFBP from normal mammary tissue. Immunoreactive IGF-I was principally associated with 45 kDa IGFBP in milk. Multiparous cows had a higher IGF-I concentration of 307 ng/ml than primiparous cows at 147 ng/ml. IGF-I concentration on day 56 of lactation was 34 ng/ml for combined parity groups. At parturition, IGF-I mass in blood and milk pools was 1.4 and 1.2 mg, respectively. Binding of {sup 125}I-IGF-I was specific for IGF-I with anIC{sub 50} of 2.2 ng which was a 10- and 1273-fold greater affinity than IGF-II and insulin, respectively. Association constants, as determined by Scatchard analysis, were similar for both pregnant and lactating cows at 3.5 and 4.0 L/nM, respectively. In addition, estimated mean receptor concentration was 0.25 and 0.23 pM/mg protein for pregnant and lactating cows, respectively. In a survey of mammary microscomes prepared from 48 cows, {sup 125}I-IGF-I binding declined with progressing lactation and a similar trend was observed during pregnancy.

  7. Effects of Growth Hormone and Growth Factors on the Improvement of Culture Conditions of In vitro Produced Bovine Embryos

    OpenAIRE

    N.R. Mtango; M. D. Varisanga; Tatsuyuki Suzuki

    2002-01-01

    The effect of growth hormone (GH), activin, insulin and epidermal growth factor (EGF) was examined on nucleus maturation, cleavage after fertilization and development of bovine oocytes to blastocysts in vitro. COCs were cultured in the presence of medium alone mSOFaa [Modified oviduct synthetic fluid with amino acids] (control), activin (10ng/ml), EGF (10ng/ml), GH (100ng/ml) and insulin 5µg/ml. There was an increase (P < 0.05 and P < 0.01) in the percentage of oocytes that reached meta...

  8. Competitive binding of viral E2 protein and mammalian core-binding factor to transcriptional control sequences of human papillomavirus type 8 and bovine papillomavirus type 1.

    OpenAIRE

    Schmidt, H. M.; Steger, G; Pfister, H

    1997-01-01

    The promoter P7535 of human papillomavirus type 8 and the promoter P7185 of bovine papillomavirus type 1 are negatively regulated by viral E2 proteins via the promoter proximal binding sites P2 and BS1, respectively. Mutations of these E2 binding sites can reduce basal promoter activity. This suggests binding of a transcription-stimulating factor and may indicate that repression by E2 is due to competitive binding of viral and cellular proteins. A computer search revealed putative binding sit...

  9. An 8-year longitudinal sero-epidemiological study of bovine leukaemia virus (BLV) infection in dairy cattle in Turkey and analysis of risk factors associated with BLV seropositivity.

    Science.gov (United States)

    Şevik, Murat; Avcı, Oğuzhan; İnce, Ömer Barış

    2015-04-01

    Enzootic bovine leukosis (EBL) which is caused by bovine leukaemia virus (BLV) has an important economic impact on dairy herds due to reduced milk production and restrictions on livestock exports. This study was conducted to determine the BLV infection status in Central Anatolia Region of Turkey, an important milk production centre, and to examine the risk factors such as purchasing cattle, increasing cattle age, cattle breed and herd size associated with transmission of BLV infection. To estimate the rate of BLV infection, a survey for specific antibodies in 28,982 serum samples from animals belonging to 1116 different herds situated in Central Anatolia Region of Turkey were tested from January 2006 to December 2013. A generalized mixed linear model was used to evaluate the risk factors that influenced BLV seroprevalence. Antibodies against BLV were detected in 431 (2.28 %) of 18,822 Holstein and 29 (0.28 %) of 10,160 Brown Swiss cows. Among 1116 herds, 132 herds (11.82 %) had one or more positive animals. Also results of our study show that the prevalence of BLV infection increased from 2006 to 2011, and it tends to reduce with BLV control programme. Furthermore, we found positive associations between percentage of seropositive animal and increasing cattle age, herd size, cattle breed and purchased cattle. Age-specific prevalence showed that BLV prevalence increased with age. These factors should be taken into consideration for control of BLV infection. PMID:25708566

  10. Mitochondrial Dynamics in Diabetes

    OpenAIRE

    Yoon, Yisang; Galloway, Chad A.; Jhun, Bong Sook; Yu, Tianzheng

    2011-01-01

    Mitochondria are at the center of cellular energy metabolism and regulate cell life and death. The cell biological aspect of mitochondria, especially mitochondrial dynamics, has drawn much attention through implications in human pathology, including neurological disorders and metabolic diseases. Mitochondrial fission and fusion are the main processes governing the morphological plasticity and are controlled by multiple factors, including mechanochemical enzymes and accessory proteins. Emergin...

  11. The neurogenic basic helix–loop–helix transcription factor NeuroD6 confers tolerance to oxidative stress by triggering an antioxidant response and sustaining the mitochondrial biomass

    Directory of Open Access Journals (Sweden)

    Martine Uittenbogaard

    2010-05-01

    Full Text Available Preserving mitochondrial mass, bioenergetic functions and ROS (reactive oxygen species homoeostasis is key to neuronal differentiation and survival, as mitochondria produce most of the energy in the form of ATP to execute and maintain these cellular processes. In view of our previous studies showing that NeuroD6 promotes neuronal differentiation and survival on trophic factor withdrawal, combined with its ability to stimulate the mitochondrial biomass and to trigger comprehensive antiapoptotic and molecular chaperone responses, we investigated whether NeuroD6 could concomitantly modulate the mitochondrial biomass and ROS homoeostasis on oxidative stress mediated by serum deprivation. In the present study, we report a novel role of NeuroD6 as a regulator of ROS homoeostasis, resulting in enhanced tolerance to oxidative stress. Using a combination of flow cytometry, confocal fluorescence microscopy and mitochondrial fractionation, we found that NeuroD6 sustains mitochondrial mass, intracellular ATP levels and expression of specific subunits of respiratory complexes upon oxidative stress triggered by withdrawal of trophic factors. NeuroD6 also maintains the expression of nuclear-encoded transcription factors, known to regulate mitochondrial biogenesis, such as PGC-1α (peroxisome-proliferator-activated receptor γ co-activator-1α, Tfam (transcription factor A, mitochondrial and NRF-1 (nuclear respiratory factor-1. Finally, NeuroD6 triggers a comprehensive antioxidant response to endow PC12-ND6 cells with intracellular ROS scavenging capacity. The NeuroD6 effect is not limited to the classic induction of the ROS-scavenging enzymes, such as SOD2 (superoxide dismutase 2, GPx1 (glutathione peroxidase 1 and PRDX5 (peroxiredoxin 5, but also to the recently identified powerful ROS suppressors PGC-1α, PINK1 (phosphatase and tensin homologue-induced kinase 1 and SIRT1. Thus our collective results support the concept that the NeuroD6–PGC-1α–SIRT1

  12. Influence of imaging factors on image quality in bovine computed radiography (CR) using portable X-ray equipment

    International Nuclear Information System (INIS)

    The purpose of this study was to investigate the effect of X-ray tube-cassette distance and image scanning time on image quality to establish the benefit of Computed Radiography (CR) in bovine clinical practice. The tube-cassette distance had no effect on the visual evaluation score (graininess and sharpness). The image scanning time correlated with graininess but not sharpness. From these results, it was concluded that accidental variations in the tube-cassette distance and variations in image scanning time of several hours will not be major problems in clinical practice. CR is considered a useful X-ray system in bovine clinical imaging in which the maintenance of reproducible tube-cassette distance is difficult and variations in image scanning time is assumed

  13. Mitochondrial Transcription Factors TFA, TFB1 and TFB2: A Search for DNA Variants/Haplotypes and the Risk of Cardiac Hypertrophy

    OpenAIRE

    Cristina Alonso-Montes; Castro, Mónica G.; Julián R. Reguero; Andreas Perrot; Cemil Özcelik; Christian Geier; Posch, Maximilian G.; César Morís; Victoria Alvarez; Marta Ruiz-Ortega; Eliecer Coto

    2008-01-01

    Mitochondrial transcription factors mtTFA, mtTFB1 and mtTFB2 are required for the replication of mitochondrial DNA (mtDNA), regulating the number of mtDNA copies. Mice with a mtTFA deletion showed a reduced number of mtDNA copies, a reduction in respiratory chain activity, and a characteristic dilated cardiomyopathy. DNA variants in these genes could be involved in the risk for cardiac hypertrophy (HCM). We determined the variation in the TFAM, TFB1M, and TFB2M genes (using SSCA, DHPLC, and d...

  14. Impaired coactivator activity of the Gly482 variant of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) on mitochondrial transcription factor A (Tfam) promoter

    International Nuclear Information System (INIS)

    Mitochondrial dysfunction may cause diabetes or insulin resistance. Peroxisome proliferation-activated receptor-γ (PPAR-γ) coactivator-1 α (PGC-1α) increases mitochondrial transcription factor A (Tfam) resulting in mitochondrial DNA content increase. An association between a single nucleotide polymorphism (SNP), G1444A(Gly482Ser), of PGC-1α coding region and insulin resistance has been reported in some ethnic groups. In this study, we investigated whether a change of glycine to serine at codon 482 of PGC-1α affected the Tfam promoter activity. The cDNA of PGC-1α variant bearing either glycine or serine at 482 codon was transfected into Chang human hepatocyte cells. The PGC-1α protein bearing glycine had impaired coactivator activity on Tfam promoter-mediated luciferase. We analyzed the PGC-1α genotype G1444A and mitochondrial DNA (mtDNA) copy number from 229 Korean leukocyte genomic DNAs. Subjects with Gly/Gly had a 20% lower amount of peripheral blood mtDNA than did subjects with Gly/Ser and Ser/Ser (p < 0.05). No correlation was observed between diabetic parameters and PGC-1α genotypes in Koreans. These results suggest that PGC-1α variants with Gly/Gly at 482nd amino acid may impair the Tfam transcription, a regulatory function of mitochondrial biogenesis, resulting in dysfunctional mtDNA replication

  15. RECENT ADVANCES IN STRUCTURE-FUNCTIONAL STUDIES OF MITOCHONDRIAL FACTOR B

    OpenAIRE

    Belogrudov, Grigory I.

    2009-01-01

    Since the early studies on the resolution and reconstitution of the oxidative phosphorylation system from animal mitochondria, coupling factor B was recognized as an essential component of the machinery responsible for energy-driven ATP synthesis. At the phenomenological level, factor B was agreed to lie at the interface of energy transfer between the respiratory chain and the ATP synthase complex. However, biochemical characterization of the factor B polypeptide has proved difficult. It was ...

  16. Serological survey of bovine brucellosis in Fulani nomadic cattle breeds (Bos indicus) of North-central Nigeria: Potential risk factors and zoonotic implications.

    Science.gov (United States)

    Alhaji, N B; Wungak, Y S; Bertu, W J

    2016-01-01

    A cross sectional study was conducted to investigate seroprevalence and associated risk factors of bovine brucellosis in Fulani nomadic herds in the 3 agro-ecological zones of Niger State, North-central Nigeria between January and August 2013. A total of 672 cattle in 113 herds were screened for Brucella antibodies using Rose Bengal Plate Test (RBPT) and confirmed by Lateral flow Assay (LFA). Data on herd characteristics and zoonotic factors were collected using structured questionnaire administered on Fulani herd owners. Factors associated with Brucella infection were tested using Chi-square test and multivariable logistic model. The overall cattle-level seroprevalence was 1.9% (95% CI: 1.1-3.2) with highest in agro-zone C (3.2%). Herd-level seroprevalence was 9.7% (95% CI: 5.23-16.29) and highest in agro-zone C (13.5%). Sex and agro-ecological zones were significantly (Ppractices were significantly associated with brucellosis occurrence. Inhalation of droplets from milk of infected cows, and drinking raw milk were less likely [OR 0.27; 95% CI: 0.09-0.82 and OR 0.27; 95% CI: 0.08-0.99, respectively] not to predisposed to brucellosis in humans. Eating infected raw meat, and contact with infected placenta were more likely [OR 7.49; 95% CI: 2.06-28.32 and OR 5.74; 95% CI: 1.78-18.47, respectively] to be risks for the disease in humans. These results highlighted the important risk factors for bovine brucellosis in Fulani herds. Thus, brucellosis control programs which take these factors into consideration will be beneficial. PMID:26464048

  17. Mitochondrial biogenesis in brown adipose tissue is associated with differential expression of transcription regulatory factors

    Czech Academy of Sciences Publication Activity Database

    Villena, J. A.; Carmona, M. C.; Rodriguez de la Concepción, M.; Rossmeisl, Martin; Vinas, O.; Mampel, T.; Iglesias, R.; Giralt, M.; Villarroya, F.

    2002-01-01

    Roč. 59, č. 11 (2002), s. 1934-1944. ISSN 1420-682X Grant ostatní: Ministerio de Ciencia y Tecnología(ES) PM98.0188 Institutional research plan: CEZ:AV0Z5011922 Keywords : brown adipose tissue * mitochondria * transcription factors Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 5.259, year: 2002

  18. Bovine papillomavirus type 1 E2 transcriptional regulators directly bind two cellular transcription factors, TFIID and TFIIB.

    OpenAIRE

    Rank, N M; Lambert, P F

    1995-01-01

    The bovine papillomavirus type 1 (BPV-1) E2 translational open reading frame encodes three proteins that regulate viral transcription and DNA replication: the E2 transcriptional activator (E2TA), the E2 transcriptional repressor (E2TR) and the E8/E2 transcriptional repressor (E8/E2TR). E2TA is a strong activator of papillomaviral promoters and is required for viral DNA replication. E2TR and E8/E2TR inhibit the activities of E2TA but also possess weak transactivational properties of their own....

  19. Endogenous and exogenous factors influencing the concentrations of adiponectin in body fluids and tissues in the bovine.

    Science.gov (United States)

    Sauerwein, Helga; Häußler, Susanne

    2016-07-01

    Adiponectin, one of the messenger molecules secreted from adipose tissue that are collectively termed adipokines, has been demonstrated to play a central role in lipid and glucose metabolism in humans and laboratory rodents; it improves insulin sensitivity and exerts antidiabetic and antiinflammatory actions. Adiponectin is synthesized as a 28 kDa monomer but is not secreted as such; instead, it is glycosylated and undergoes multimerization to form different molecular weight multimers before secretion. Adiponectin is one of the most abundant adipokines (μg/mL range) in the circulation. The concentrations are negatively correlated with adipose depot size, in particular with visceral fat mass in humans. Adiponectin exerts its effects by activating a range of different signaling molecules via binding to 2 transmembrane receptors, adiponectin receptor 1 and adiponectin receptor 2. The adiponectin receptor 1 is expressed primarily in the skeletal muscle, whereas adiponectin receptor 2 is predominantly expressed in the liver. Many of the functions of adiponectin are relevant to growth, lactation, and health and are thus of interest in both beef and dairy production systems. Studies on the role of the adiponectin protein in cattle have been impeded by the lack of reliable assays for bovine adiponectin. Although there are species-specific bovine adiponectin assays commercially available, they suffer from a lack of scientific peer-review of validity. Quantitative data about the adiponectin protein in cattle available in the literature emerged only during the last 3 yr and were largely based on Western blotting using either antibodies against human adiponectin or partial peptides from the bovine sequence. Using native bovine high-molecular-weight adiponectin purified from serum, we were able to generate a polyclonal antiserum that can be used for Western blot but also in an ELISA system, which was recently validated. The objective of this review is to provide an overview

  20. Genetic risk factors affecting mitochondrial function are associated with kidney disease in people with Type 1 diabetes

    DEFF Research Database (Denmark)

    Swan, E J; Salem, R M; Sandholm, N;

    2015-01-01

    AIM: To evaluate the association with diabetic kidney disease of single nucleotide polymorphisms (SNPs) that may contribute to mitochondrial dysfunction. METHODS: The mitochondrial genome and 1039 nuclear genes that are integral to mitochondrial function were investigated using a case (n = 823...... phenotypes to those of the discovery collection. Association analyses were performed using the plink genetic analysis toolset, with adjustment for relevant covariates. RESULTS: A total of 25 SNPs were evaluated in the mitochondrial genome, but none were significantly associated with diabetic kidney disease...... or end-stage renal disease. A total of 38 SNPs in nuclear genes influencing mitochondrial function were nominally associated with diabetic kidney disease and 16 SNPS were associated with end-stage renal disease, secondary to diabetic kidney disease, with meta-analyses confirming the same direction of...

  1. Haplogroup T Is an Obesity Risk Factor: Mitochondrial DNA Haplotyping in a Morbid Obese Population from Southern Italy

    OpenAIRE

    Fabrizio Pasanisi; Lucia Sacchetti; Pasqualina Buono; Eduardo Farinaro; Franco Contaldo; Massimo Pezzuti; Giuseppe Castaldo; Valentina Capobianco; Maddalena Ferrigno; Giuseppe Labruna; Rosario Liguori; Cristina Mazzaccara; Carmela Nardelli

    2013-01-01

    Mitochondrial DNA (mtDNA) haplogroups have been associated with the expression of mitochondrial-related diseases and with metabolic alterations, but their role has not yet been investigated in morbid obese Caucasian subjects. Therefore, we investigated the association between mitochondrial haplogroups and morbid obesity in patients from southern Italy. The mtDNA D-loop of morbid obese patients (n = 500; BMI > 40 kg/m2) and controls (n = 216; BMI < 25 kg/m2) was sequenced to determine the mtDN...

  2. Mitochondrial role of Apoptosis-Inducing Factor (AIF): Oxidative Phosphorylation and Reactive Oxygen Species.

    OpenAIRE

    Apostolova, Nadezda

    2008-01-01

    The apoptotic function of Apoptosis-inducing factor (AIF) is well documented in the literature, but its physiological role in the mitochondrion is less certain. Using a small interfering RNA (siRNA) strategy, we studied whether modulation of AIF expression in cultured cells influenced the production of reactive oxygen species (ROS). We found that siAIF-transfected cells had reduced AIF protein levels and this was paralleled by a significant increase in ROS. We tested the genera...

  3. Mitochondrial haplogroups

    DEFF Research Database (Denmark)

    Benn, Marianne; Schwartz, Marianne; Nordestgaard, Børge G;

    2008-01-01

    Rare mutations in the mitochondrial genome may cause disease. Mitochondrial haplogroups defined by common polymorphisms have been associated with risk of disease and longevity. We tested the hypothesis that common haplogroups predict risk of ischemic cardiovascular disease, morbidity from other...

  4. ERas protein is overexpressed and binds to the activated platelet-derived growth factor β receptor in bovine urothelial tumour cells associated with papillomavirus infection.

    Science.gov (United States)

    Russo, Valeria; Roperto, Franco; Esposito, Iolanda; Ceccarelli, Dora Maria; Zizzo, Nicola; Leonardi, Leonardo; Capparelli, Rosanna; Borzacchiello, Giuseppe; Roperto, Sante

    2016-06-01

    Embryonic stem cell-expressed Ras (ERas) encodes a constitutively active form of guanosine triphosphatase (GTPase) that binds to and activates phosphatidylinositol 3 kinase (PI3K), which in turn phosphorylates and activates downstream targets such as Akt. The current study evaluated ERas regulation and expression in papillomavirus-associated urothelial tumours in cattle grazing on lands rich in bracken fern. ERas was found upregulated and overexpressed by PCR, real time PCR and Western blot. Furthermore, protein overexpression was also confirmed by immunohistochemistry. ERas was found to interact physically and colocalise with the activated platelet derived growth factor β receptor (PDGFβR) by coimmunoprecipitation and laser scanning confocal investigations. Phosphorylation of Akt, a downstream effector both of ERas and PDGFβR, appeared to be increased in urothelial tumour cells. Altogether, these data indicate that ERas/PDGFβR complex could play a role in the pathogenesis of bovine papillomavirus-associated bladder neoplasia. PMID:27256024

  5. The Forkhead Transcription Factor Hcm1 Promotes Mitochondrial Biogenesis and Stress Resistance in Yeast

    OpenAIRE

    Rodríguez Colman, Maria José; Reverter Branchat, Gemma; Sorolla Bardají, Maria Alba; Tamarit Sumalla, Jordi; Ros Salvador, Joaquim; Cabiscol Català, Elisa

    2010-01-01

    In Saccharomyces cerevisiae, the forkhead transcription factor Hcm1 is involved in chromosome segregation, spindle pole dynamics, and budding. We found that Hcm1 interacts with the histone deacetylase Sir2 and shifts from cytoplasm to the nucleus in the G1/S phase or in response to oxidative stress stimuli. The nuclear localization of Hcm1 depends on the activity of Sir2 as revealed by activators and inhibitors of the sirtuins and the Δsir2 mutant. Hcm1-overexpressing cells display more mitoc...

  6. In Vitro Infection of Bovine Monocytes with Mycoplasma bovis Delays Apoptosis and Suppresses Production of Gamma Interferon and Tumor Necrosis Factor Alpha but Not Interleukin-10

    OpenAIRE

    Mulongo, Musa; Prysliak, Tracy; Scruten, Erin; Napper, Scott; Perez-Casal, Jose

    2014-01-01

    Mycoplasma bovis is one of the major causative pathogens of bovine respiratory complex disease (BRD), which is characterized by enzootic pneumonia, mastitis, pleuritis, and polyarthritis. M. bovis enters and colonizes bovine respiratory epithelial cells through inhalation of aerosol from contaminated air. The nature of the interaction between M. bovis and the bovine innate immune system is not well understood. We hypothesized that M. bovis invades blood monocytes and regulates cellular functi...

  7. Genetic risk factors affecting mitochondrial function are associated with kidney disease in people with Type 1 diabetes

    Science.gov (United States)

    Swan, E J; Salem, R M; Sandholm, N; Tarnow, L; Rossing, P; Lajer, M; Groop, P H; Maxwell, A P; McKnight, A J

    2015-01-01

    Aim To evaluate the association with diabetic kidney disease of single nucleotide polymorphisms (SNPs) that may contribute to mitochondrial dysfunction. Methods The mitochondrial genome and 1039 nuclear genes that are integral to mitochondrial function were investigated using a case (n = 823 individuals with diabetic kidney disease) vs. control (n = 903 individuals with diabetes and no renal disease) approach. All people included in the analysis were of white European origin and were diagnosed with Type 1 diabetes before the age of 31 years. Replication was conducted in 5093 people with similar phenotypes to those of the discovery collection. Association analyses were performed using the plink genetic analysis toolset, with adjustment for relevant covariates. Results A total of 25 SNPs were evaluated in the mitochondrial genome, but none were significantly associated with diabetic kidney disease or end-stage renal disease. A total of 38 SNPs in nuclear genes influencing mitochondrial function were nominally associated with diabetic kidney disease and 16 SNPS were associated with end-stage renal disease, secondary to diabetic kidney disease, with meta-analyses confirming the same direction of effect. Three independent signals (seven SNPs) were common to the replication data for both phenotypes with Type 1 diabetes and persistent proteinuria or end-stage renal disease. Conclusions Our results suggest that SNPs in nuclear genes that influence mitochondrial function are significantly associated with diabetic kidney disease in a white European population. What’s new? Mitochondrial dysfunction has been identified in diabetic kidney disease, but relatively large-scale genetic and epigenetic studies focused on mitochondria have not yet been described. We report a novel case–control analysis, with independent replication, of genetic variation focused on the mitochondrial genome and 1039 nuclear genes that are important for mitochondrial function. Single nucleotide

  8. Key Role of the Adenylate Moiety and Integrity of the Adenylate-Binding Site for the NAD(+)/H Binding to Mitochondrial Apoptosis-Inducing Factor.

    Science.gov (United States)

    Sorrentino, Luca; Calogero, Alessandra Maria; Pandini, Vittorio; Vanoni, Maria Antonietta; Sevrioukova, Irina F; Aliverti, Alessandro

    2015-12-01

    Apoptosis-inducing factor (AIF) is a mitochondrial flavoprotein with pro-life and pro-death activities, which plays critical roles in mitochondrial energy metabolism and caspase-independent apoptosis. Defects in AIF structure or expression can cause mitochondrial abnormalities leading to mitochondrial defects and neurodegeneration. The mechanism of AIF-induced apoptosis was extensively investigated, whereas the mitochondrial function of AIF is poorly understood. A unique feature of AIF is the ability to form a tight, air-stable charge-transfer (CT) complex upon reaction with NADH and to undergo a conformational switch leading to dimerization, proposed to be important for its vital and lethal functions. Although some aspects of interaction of AIF with NAD(+)/H have been analyzed, its precise mechanism is not fully understood. We investigated how the oxidized and photoreduced wild-type and G307A and -E variants of murine AIF associate with NAD(+)/H and nicotinamide mononucleotide (NMN(+)/H) to determine the role of the adenylate moiety in the binding process. Our results indicate that (i) the adenylate moiety of NAD(+)/H is crucial for the association with AIF and for the subsequent structural reorganization of the complex, but not for protein dimerization, (ii) FAD reduction rather than binding of NAD(+)/H to AIF initiates conformational rearrangement, and (iii) alteration of the adenylate-binding site by the G307E (equivalent to a pathological G308E mutation in human AIF) or G307A replacements decrease the affinity and association rate of NAD(+)/H, which, in turn, perturbs CT complex formation and protein dimerization but has no influence on the conformational switch in the regulatory peptide. PMID:26535916

  9. Clinical applications of bovine colostrum therapy

    DEFF Research Database (Denmark)

    Rathe, Mathias; Müller, Klaus; Sangild, Per Torp;

    2014-01-01

    Bovine colostrum, the first milk that cows produce after parturition, contains high levels of growth factors and immunomodulatory components. Some healthy and diseased individuals may gain health benefits by consuming bovine colostrum as a food supplement. This review provides a systematic...

  10. The Contribution of Infections with Bovine Viral Diarrhea Viruses to Bovine Respiratory Disease

    Science.gov (United States)

    The contribution of bovine viral diarrhea viruses (BVDV) to the development of bovine respiratory disease is the sum of a number of different factors. These factors include the contribution of acute uncomplicated BVDV infections, the high incidence of respiratory disease in animals persistently inf...

  11. Antiviral effects of bovine interferons on bovine respiratory tract viruses.

    OpenAIRE

    Fulton, R W; Downing, M M; Cummins, J M

    1984-01-01

    The antiviral effects of bovine interferons on the replication of bovine respiratory tract viruses were studied. Bovine turbinate monolayer cultures were treated with bovine interferons and challenged with several bovine herpesvirus 1 strains, bovine viral diarrhea virus, parainfluenza type 3 virus, goat respiratory syncytial virus, bovine respiratory syncytial virus, bovine adenovirus type 7, or vesicular stomatitis virus. Treatment with bovine interferons reduced viral yield for each of the...

  12. Functional assay, expression of growth factors and proteins modulating bone-arrangement in human osteoblasts seeded on an anorganic bovine bone biomaterial

    Directory of Open Access Journals (Sweden)

    O Trubiani

    2010-07-01

    Full Text Available The basic aspects of bone tissue engineering include chemical composition and geometry of the scaffold design, because it is very important to improve not only cell attachment and growth but especially osteodifferentiation, bone tissue formation, and vascularization. Geistlich Bio-Oss® (GBO is a xenograft consisting of deproteinized, sterilized bovine bone, chemically and physically identical to the mineral phase of human bone.In this study, we investigated the growth behaviour and the ability to form focal adhesions on the substrate, using vinculin, a cytoskeletal protein, as a marker. Moreover, the expression of bone specific proteins and growth factors such as type I collagen, osteopontin, bone sialoprotein, bone morphogenetic protein-2 (BMP-2, BMP-7 and de novo synthesis of osteocalcin in normal human osteoblasts (NHOst seeded on xenogenic GBO were evaluated. Our observations suggest that after four weeks of culture in differentiation medium, the NHOst showed a high affinity for the three dimensional biomaterial; in fact, cellular proliferation, migration and colonization were clearly evident. The osteogenic differentiation process, as demonstrated by morphological, histochemical, energy dispersive X-ray microanalysis and biochemical analysis was mostly obvious in the NHOst grown on three-dimensional inorganic bovine bone biomaterial. Functional studies displayed a clear and significant response to calcitonin when the cells were differentiated. In addition, the presence of the biomaterial improved the response, suggesting that it could drive the differentiation of these cells towards a more differentiated osteogenic phenotype. These results encourage us to consider GBO an adequate biocompatible three-dimensional biomaterial, indicating its potential use for the development of tissue-engineering techniques.

  13. Effects of retinal growth factor and of the increase of the number of subcultures on sulfated glycosaminoglycans of bovine lens epithelial cells

    International Nuclear Information System (INIS)

    Sulfated glycosaminoglycans of cultured bovine lens epithelial cells grown in the presence and in the absence of a retinal growth factor were investigated comparatively. The newly formed [35S] sulfate-labeled glycosaminoglycans were analysed in the extra-, peri- and intracellular compartments of early (4-5th) and late (17-18h) subcultures. The following results were obtained: (1) Cultured lens epithelial cells grown in the presence or in the absence of the growth factor synthesize chondroitin 4- and 6-sulfates and dermatan sulfate, with heparan sulfate as the main component, the pericellular compartments were particularly rich in heparan sulfate; (2) The distribution pattern of the glycosaminoglycans changes during successive subcultures; the proportion of heparan sulfate increases in the pericellular compartment, the dermatan sulfate to chondroitin sulfate ratio increases in all three compartments; (3) In contrast to the drastic decrease in the fibronectin levels in the presence of growth factor in the early subcultures, only minor differences were found between the glycosaminoglycan patterns for the treated and non-treated cells. ( orig.)

  14. Molecular Regulation of the Mitochondrial F1Fo-ATPsynthase: Physiological and Pathological Significance of the Inhibitory Factor 1 (IF 1

    Directory of Open Access Journals (Sweden)

    Danilo Faccenda

    2012-01-01

    Full Text Available In mammals, the mitochondrial F1Fo-ATPsynthase sets out the energy homeostasis by producing the bulk of cellular ATP. As for every enzyme, the laws of thermodynamics command it; however, it is privileged to have a dedicated molecular regulator that controls its rotation. This is the so-called ATPase Inhibitory Factor 1 (IF1 that blocks its reversal to avoid the consumption of cellular ATP when the enzyme acts as an ATP hydrolase. Recent evidence has also demonstrated that IF1 may control the alignment of the enzyme along the mitochondrial inner membrane, thus increasing the interest for the molecule. We conceived this review to outline the fundamental knowledge of the F1Fo-ATPsynthase and link it to the molecular mechanisms by which IF1 regulates its way of function, with the ultimate goal to highlight this as an important and possibly unique means to control this indispensable enzyme in both physiological and pathological settings.

  15. Mitochondrial vasculopathy

    Science.gov (United States)

    Finsterer, Josef; Zarrouk-Mahjoub, Sinda

    2016-01-01

    Mitochondrial disorders (MIDs) are usually multisystem disorders (mitochondrial multiorgan disorder syndrome) either on from onset or starting at a point during the disease course. Most frequently affected tissues are those with a high oxygen demand such as the central nervous system, the muscle, endocrine glands, or the myocardium. Recently, it has been shown that rarely also the arteries may be affected (mitochondrial arteriopathy). This review focuses on the type, diagnosis, and treatment of mitochondrial vasculopathy in MID patients. A literature search using appropriate search terms was carried out. Mitochondrial vasculopathy manifests as either microangiopathy or macroangiopathy. Clinical manifestations of mitochondrial microangiopathy include leukoencephalopathy, migraine-like headache, stroke-like episodes, or peripheral retinopathy. Mitochondrial macroangiopathy manifests as atherosclerosis, ectasia of arteries, aneurysm formation, dissection, or spontaneous rupture of arteries. The diagnosis relies on the documentation and confirmation of the mitochondrial metabolic defect or the genetic cause after exclusion of non-MID causes. Treatment is not at variance compared to treatment of vasculopathy due to non-MID causes. Mitochondrial vasculopathy exists and manifests as micro- or macroangiopathy. Diagnosing mitochondrial vasculopathy is crucial since appropriate treatment may prevent from severe complications. PMID:27231520

  16. Genetic variation of the mitochondrial D-loop region containing mitochondrial transcription factor (TFAM) binding sites is not associated with marbling in Wagyu X Limousin F2 crosses: Genetska raznolikost mitohondrijske D-loop regije, ki vsebuje vezavno mesto za mitohondrijski transkripcijski faktor A (TFAM), ni povezana z marmoriranostjo pri F2 Wagyu X limousin križancih:

    OpenAIRE

    Dovč, Peter; Jiang, Zhihua; Kunej, Tanja; Michal, Jennifer J.

    2005-01-01

    Mitochondrial transcription factor A (TFAM) is a nucleus-encoded protein that is essential for initiation of transcription and replication of mitochondrial DNA (mtDNA). It has been shown that TFAM binds the entire length of the mtDNA,but with higher affinitz to sequences around both mitochondrial promoters located in 3' domain of the D-loop region. The objectives of this study were to detect genetic polymorphisms in the sequence flanking TFAM binding sites of the mtDNA D-loop region and inves...

  17. Nuclear-encoded factors involved in post-transcriptional processing and modification of mitochondrial tRNAs in human disease

    OpenAIRE

    Powell, Christopher A.; Nicholls, Thomas J.; Minczuk, Michal

    2015-01-01

    The human mitochondrial genome (mtDNA) encodes 22 tRNAs (mt-tRNAs) that are necessary for the intraorganellar translation of the 13 mtDNA-encoded subunits of the mitochondrial respiratory chain complexes. Maturation of mt-tRNAs involves 5′ and 3′ nucleolytic excision from precursor RNAs, as well as extensive post-transcriptional modifications. Recent data suggest that over 7% of all mt-tRNA residues in mammals undergo post-transcriptional modification, with over 30 different modified mt-tRNA ...

  18. Etiology, antimicrobial susceptibility profile of Staphylococcus spp. and risk factors associated with bovine mastitis in the states of Bahia and Pernambuco

    Directory of Open Access Journals (Sweden)

    Carina C. Krewer

    2013-05-01

    Full Text Available The purpose of this paper was to study the etiology of mastitis, determine the antimicrobial susceptibility profile of Staphylococcus spp. and to identify the risk factors associated with infection in dairy cows in the states of Bahia and Pernambuco, Brazil. From the 2,064 milk samples analyzed, 2.6% were associated with cases of clinical mastitis and 28.2% with subclinical mastitis. In the microbiological culture, Staphylococcus spp. (49.1% and Corynebacterium spp. (35.3% were the main agents found, followed by Prototheca spp. (4.6% and Gram negative bacilli (3.6%. In the antimicrobial susceptibility testing, all 218 Staphylococcus spp. were susceptible to rifampicin and the least effective drug was amoxicillin (32.6%. Multidrug resistance to three or more drugs was observed in 65.6% of Staphylococcus spp. The risk factors identified for mastitis were the extensive production system, not providing feed supplements, teat drying process, not disinfecting the teats before and after milking, and inadequate hygiene habits of the milking workers. The presence of multiresistant isolates in bovine milk demonstrates the importance of the choice and appropriate use of antimicrobial agents. Prophylactic and control measures, including teat antisepsis and best practices for achieving hygienic milking should be established in order to prevent new cases of the disease in herds.

  19. Mitochondrial pAL2-1 plasmid homologs are senescence factors in Podospora anserina independent of intrinsic senescence

    NARCIS (Netherlands)

    van Diepeningen, Anne D; Debets, Alfons J M; Slakhorst, S Marijke; Hoekstra, Rolf F

    2008-01-01

    Since the first description of a linear mitochondrial plasmid in Podospora anserina, pAL2-1, and homologous plasmids have gone from being considered beneficial longevity plasmids, via neutral genetic elements, toward mutator plasmids causing senescence. The plasmid has an invertron structure, with t

  20. Differentiation inducing factor 3 mediates its anti-leukemic effect through ROS-dependent DRP1-mediated mitochondrial fission and induction of caspase-independent cell death.

    Science.gov (United States)

    Dubois, Alix; Ginet, Clemence; Furstoss, Nathan; Belaid, Amine; Hamouda, Mohamed Amine; El Manaa, Wedjene; Cluzeau, Thomas; Marchetti, Sandrine; Ricci, Jean Ehrland; Jacquel, Arnaud; Luciano, Frederic; Driowya, Mohsine; Benhida, Rachid; Auberger, Patrick; Robert, Guillaume

    2016-05-01

    Differentiation-inducing factor (DIF) defines a group of chlorinated hexaphenones that orchestrate stalk-cell differentiation in the slime mold Dictyostelium discoideum (DD). DIF-1 and 3 have also been reported to have tumor inhibiting properties; however, the mechanisms that underlie the effects of these compounds remain poorly defined. Herein, we show that DIF-3 rapidly triggers Ca2+ release and a loss of mitochondrial membrane potential (MMP) in the absence of cytochrome c and Smac release and without caspase activation. Consistently with these findings, we also detected no evidence of apoptosis in cells treated with DIF-3 but instead found that this compound induced autophagy. In addition, DIF-3 promoted mitochondrial fission in K562 and HeLa cells, as assessed by electron and confocal microscopy analysis. Importantly, DIF-3 mediated the phosphorylation and redistribution of dynamin-related protein 1 (DRP1) from the cytoplasmic to the microsomal fraction of K562 cells. Pharmacological inhibition or siRNA silencing of DRP1 not only inhibited mitochondrial fission but also protected K562 cells from DIF-3-mediated cell death. Furthermore, DIF-3 potently inhibited the growth of imatinib-sensitive and imatinib-resistant K562 cells. It also inhibited tumor formation in athymic mice engrafted with an imatinib-resistant CML cell line. Finally, DIF-3 exhibited a clear selectivity toward CD34+ leukemic cells from CML patients, compared with CD34- cells. In conclusion, we show that the potent anti-leukemic effect of DIF-3 is mediated through the induction of mitochondrial fission and caspase-independent cell death. Our findings may have important therapeutic implications, especially in the treatment of tumors that exhibit defects in apoptosis regulation. PMID:27027430

  1. Qualitative and quantitative impacts assessment of contagious bovine pleuropneumonia in Fulani pastoral herds of North-central Nigeria: The associated socio-cultural factors.

    Science.gov (United States)

    Alhaji, N B; Babalobi, O O

    2016-06-01

    Contagious bovine pleuropneumonia is one of the most important trans-boundary disease affecting Fulani cattle herds of Nigeria and whose control is urgently needed. A Participatory Epidemiology approach and cross-sectional study were concurrently conducted to investigate qualitative and quantitative impacts of CBPP, respectively and associated socio-cultural factors that influenced exposure of Fulani nomadic pastoral communities to its risk in Niger State, North-central Nigeria between January and December 2013. A total of nine pastoral communities were purposively selected for qualitative impact assessment using Participatory Rural Appraisal tools, while 765 cattle randomly sampled from 125 purposively selected nomadic herds were analyzed using c-ELISA. Data on socio-cultural characteristics were collected using structured questionnaires administered on nomadic herd owners of the 125 selected herds. Kendall's Coefficient of Concordance W statistics and OpenEpi 2.3 were used for statistical analyses. Pastoralists' dependent factors associated with their socio-cultural activities were tested using Chisquare tests and likelihood backward logistic regressions. The mean proportional piles (relative qualitative impact) of CBPP was 12.6%, and nomads agreement on this impact was strong (W=0.6855) and statistically significant (Psource that caused concentration of stocks in one point was fifty three times more likely (OR 53.08; 95% CI: 14.91, 189.00) to be satisfactory practice that influenced occurrence of the disease in herds. This study highlighted the critical gap that exists in terms of significant influence of socio-cultural factors on CBPP occurrence in pastoral herds in Nigeria. Thus, CBPP surveillance, control and prevention programs that take these factors into consideration will be beneficial to the livestock industry in Nigeria, and indeed Africa. PMID:27237398

  2. 6-OHDA-induced apoptosis and mitochondrial dysfunction are mediated by early modulation of intracellular signals and interaction of Nrf2 and NF-κB factors

    International Nuclear Information System (INIS)

    6-Hydroxydopamine (6-OHDA) is a neurotoxin that generates an experimental model of Parkinson's disease in rodents and is commonly employed to induce a lesion in dopaminergic pathways. The characterization of those molecular mechanisms linked to 6-OHDA-induced early toxicity is needed to better understand the cellular events further leading to neurodegeneration. The present work explored how 6-OHDA triggers early downstream signaling pathways that activate neurotoxicity in the rat striatum. Mitochondrial function, caspases-dependent apoptosis, kinases signaling (Akt, ERK 1/2, SAP/JNK and p38) and crosstalk between nuclear factor kappa B (NF-κB) and nuclear factor-erythroid-2-related factor 2 (Nrf2) were evaluated at early times post-lesion. We found that 6-OHDA initiates cell damage via mitochondrial complex I inhibition, cytochrome c and apoptosis-inducing factor (AIF) release, as well as activation of caspases 9 and 3 to induce apoptosis, kinase signaling modulation and NF-κB-mediated inflammatory responses, accompanied by inhibition of antioxidant systems regulated by the Nrf2 pathway. Our results suggest that kinases SAP/JNK and p38 up-regulation may play a role in the early stages of 6-OHDA toxicity to trigger intrinsic pathways for apoptosis and enhanced NF-κB activation. In turn, these cellular events inhibit the activation of cytoprotective mechanisms, thereby leading to a condition of general damage

  3. Specific fixation of bovine brain and retinal acidic and basic fibroblast growth factors to mouse embryonic eye basement membranes

    International Nuclear Information System (INIS)

    The labeling pattern of mouse embryonic eye frozen sections incubated with radioiodinated brain acidic and basic fibroblasts growth factors (aFGF and bFGF) was investigated by autoradiography. Both growth factors bind to basement membranes in a dose-dependent way, with a higher affinity for bFGF. Similar data were obtained with eye-derived growth factors (EDGF), the retinal forms of FGF. There was a heterogeneity in the affinity of the various basement membranes toward these growth factors. The specificity of the growth factor-basement membrane interaction was demonstrated by the following experiments: (i) an excess of unlabeled growth factor displaced the labeling; (ii) unrelated proteins with different isoelectric points did not modify the labeling; and (iii) iodinated EGF or PDGF did not label basement membrane. In order to get a better understanding of the nature of this binding, the authors performed the incubation of the frozen sections with iodinated FGFs preincubated with various compounds. These results demonstrate that FGFs bind specifically to basement membranes, probably on the polysaccharidic part of the proteoheparan sulfate, and suggest that this type of interaction may be a general feature of the mechanism of action of these growth factors

  4. Mitochondrial Myopathy

    Science.gov (United States)

    ... NINDS supports research focused on effective treatments and cures for mitochondrial myopathies and other mitochondrial diseases. Scientists are investigating the possible benefits of exercise programs and nutritional supplements, primarily natural and synthetic versions of CoQ10. While CoQ10 has ...

  5. Inherited mitochondrial neuropathies.

    Science.gov (United States)

    Finsterer, Josef

    2011-05-15

    Mitochondrial disorders (MIDs) occasionally manifest as polyneuropathy either as the dominant feature or as one of many other manifestations (inherited mitochondrial neuropathy). MIDs in which polyneuropathy is the dominant feature, include NARP syndrome due to the transition m.8993T>, CMT2A due to MFN2 mutations, CMT2K and CMT4A due to GDAP1 mutations, and axonal/demyelinating neuropathy with external ophthalmoplegia due to POLG1 mutations. MIDs in which polyneuropathy is an inconstant feature among others is the MELAS syndrome, MERRF syndrome, LHON, Mendelian PEO, KSS, Leigh syndrome, MNGIE, SANDO; MIRAS, MEMSA, AHS, MDS (hepato-cerebral form), IOSCA, and ADOA syndrome. In the majority of the cases polyneuropathy presents in a multiplex neuropathy distribution. Nerve conduction studies may reveal either axonal or demyelinated or mixed types of neuropathies. If a hereditary neuropathy is due to mitochondrial dysfunction, the management of these patients is at variance from non-mitochondrial hereditary neuropathies. Patients with mitochondrial hereditary neuropathy need to be carefully investigated for clinical or subclinical involvement of other organs or systems. Supportive treatment with co-factors, antioxidants, alternative energy sources, or lactate lowering agents can be tried. Involvement of other organs may require specific treatment. Mitochondrial neuropathies should be included in the differential diagnosis of hereditary neuropathies. PMID:21402391

  6. Mycobacterium avium Subspecies paratuberculosis and Bovine Leukemia Virus Seroprevalence and Associated Risk Factors in Commercial Dairy and Beef Cattle in Northern and Northeastern China

    Science.gov (United States)

    Sun, Wu-Wen; Lv, Wen-Fa; Cong, Wei; Meng, Qing-Feng; Wang, Chun-Feng; Shan, Xiao-Feng; Qian, Ai-Dong

    2015-01-01

    Mycobacterium avium subspecies paratuberculosis (MAP) and bovine leukemia virus (BLV) are important pathogens, commonly responsible for economical loss to cattle farms all over the world, yet their epidemiology in commercial dairy and beef cattle in China is still unknown. Thus, from September 2013 to December 2014, a large-scale seroprevalence study was conducted to determine the seroprevalence and identify herd-level risk factors associated with MAP and BLV infection. The source sample was 3674 cattle from 113 herds in northern and northeastern China. Antibodies against MAP and BLV were detected using ELISA tests. At animal-level, the seroprevalence of antibodies against MAP and BLV was 11.79% (433/3674) and 18.29% (672/3674), respectively. At herd-level, the seroprevalence of antibodies against MAP and BLV was 20.35% and 21.24% (24/113), respectively. Herd size was identified to be associated with MAP infection while herd size and presence of cattle introduced from other farms were significantly associated with BLV infection. Further research is needed to confirm these findings and improve the knowledge of the epidemiology of these two pathogens in these regions and elsewhere in China. PMID:26504798

  7. An interferon regulatory factor binding site in the U5 region of the bovine leukemia virus long terminal repeat stimulates Tax-independent gene expression.

    Science.gov (United States)

    Kiermer, V; Van Lint, C; Briclet, D; Vanhulle, C; Kettmann, R; Verdin, E; Burny, A; Droogmans, L

    1998-07-01

    Bovine leukemia virus (BLV) replication is controlled by both cis- and trans-acting elements. The virus-encoded transactivator, Tax, is necessary for efficient transcription from the BLV promoter, although it is not present during the early stages of infection. Therefore, sequences that control Tax-independent transcription must play an important role in the initiation of viral gene expression. This study demonstrates that the R-U5 sequence of BLV stimulates Tax-independent reporter gene expression directed by the BLV promoter. R-U5 was also stimulatory when inserted immediately downstream from the transcription initiation site of a heterologous promoter. Progressive deletion analysis of this region revealed that a 46-bp element corresponding to the 5' half of U5 is principally responsible for the stimulation. This element exhibited enhancer activity when inserted upstream or downstream from the herpes simplex virus thymidine kinase promoter. This enhancer contains a binding site for the interferon regulatory factors IRF-1 and IRF-2. A 3-bp mutation that destroys the IRF recognition site caused a twofold decrease in Tax-independent BLV long terminal repeat-driven gene expression. These observations suggest that the IRF binding site in the U5 region of BLV plays a role in the initiation of virus replication. PMID:9621009

  8. Effect of recombinant bovine somatotropin on plasma concentrations of insulin-like growth factor I, insulin and membrane integrity of bull spermatozoa.

    Science.gov (United States)

    Vieira, M B; Bianchi, I; Madeira, E M; Roll, V F B; Oliveira, C A; Viau, P; Pivato, I; Severo, N C; Del Pino, F A B; Schneider, A; Corrêa, M N

    2010-12-01

    This study aimed to evaluate the effect of the exogenous recombinant bovine somatotropin (rbST) on plasma concentrations of insulin-like growth factor I (IGF-I), insulin and semen quality of bulls. Twenty bulls (Aberdeen Angus and Brangus) were divided by breed into two groups. Placebo group was injected with NaCl 0.9% (s.c.) and treatment group with rbST (s.c., 500 mg) at days 0 and 14 of the experiment. Immediately after semen collection, blood samples were taken on days 0, 14, 28, 42 and 56 of the experiment. Semen was also collected on day 70 of the experiment. Evaluation of sperm motility was performed at pre-freezing and post-thawing stage, whereas assessment of sperm membrane integrity was performed after freezing and thawing. Analysis of data revealed that the effect of treatment and treatment-by-collection day on plasma concentrations of IGF-I and insulin was not significant. However, mean plasma concentrations of IGF-I and insulin were affected (p  0.05) at pre-freezing and post-thawing stage. Intactness of plasmalemma and tail membrane of spermatozoa at post-thawing stage was higher (p < 0.05) in rbST-treated group than in control. In conclusion, rbST did not affect plasma concentrations of IGF-I and insulin, however, it did improve post-thaw sperm membrane integrity. PMID:19663813

  9. Fatores de risco hospitalar para implante de bioprótese valvar de pericárdio bovino Hospital risk factors for bovine pericardial bioprosthesis valve implantation

    Directory of Open Access Journals (Sweden)

    Mateus W. De Bacco

    2007-08-01

    Full Text Available FUNDAMENTO: Identificação de fatores de risco pré-operatórios na cirurgia cardíaca valvar visa melhor resultado cirúrgico pela possível neutralização de condições relacionadas com morbi-mortalidade aumentada. OBJETIVO: Este estudo objetiva identificar fatores de risco hospitalar em pacientes submetidos a implante de bioprótese de pericárdio bovino. MÉTODOS: Estudo retrospectivo incluindo 703 pacientes consecutivos submetidos a implante de pelo menos uma bioprótese de pericárdio bovino St. Jude Medical-Biocor® de setembro de 1991 a dezembro de 2005 no Instituto de Cardiologia do RS, sendo 392 aórticos, 250 mitrais e 61 mitro-aórticos. Analisadas as características sexo, idade, índice de massa corporal, classe funcional (New York Heart Association - NYHA, fração de ejeção, lesão valvar, hipertensão arterial sistêmica, diabete melito, função renal, arritmias cardíacas, cirurgia cardíaca prévia, revascularização miocárdica, plastia tricúspide e caráter eletivo, de urgência ou de emergência da cirurgia. Desfecho primordial foi mortalidade hospitalar. Utilizou-se regressão logística para examinar relação entre fatores de risco e mortalidade hospitalar. RESULTADOS: Ocorreram 101 (14,3% óbitos hospitalares. Características significativamente relacionadas à mortalidade aumentada foram sexo feminino (p 2,4mg/dl (p=0,004, classe funcional IV (pBACKGROUND: Identification of preoperative heart valve surgery risk factors aim to improve surgical outcomes with the possibility to offset conditions related to increased morbidity and mortality. OBJECTIVE: Intent of this study is to identify hospital risk factors in patients undergoing bovine pericardial bioprosthesis implantation. METHODS: Retrospective study including 703 consecutive patients who underwent implantation of at least one St. Jude Medical-Biocor™ bovine pericardial bioprosthesis between September 1991 and December 2005 at the Rio Grande do Sul

  10. Contagious bovine pleuropneumonia (CBPP) in the Maasai ecosystem of south-western Kenya: Evaluation of seroprevalence, risk factors and vaccine safety and efficacy.

    OpenAIRE

    Mtui-Malamsha, Niwael Jesse

    2009-01-01

    Contagious bovine pleuropneumonia (CBPP) is a bovine bacterial disease of major economic importance in sub-Saharan Africa. Vaccination has been recommended to control the disease in endemic areas such as the Maasai ecosystems of Kenya and Tanzania; however, the currently used live attenuated vaccine has been reported to have poor vaccine safety and efficacy. To compare standard (current) and an improved (buffered) version of the live CBPP-vaccine, several epidemiological studie...

  11. 77 FR 29914 - Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products

    Science.gov (United States)

    2012-05-21

    ... RIN 0579-AC68 Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products AGENCY... live bovines and products derived from bovines with regard to bovine spongiform encephalopathy. This.... SUPPLEMENTARY INFORMATION: On March 16, 2012, we published in the Federal Register (77 FR 15848-15913, Docket...

  12. Insulin-like Growth Factor-I (IGF-I) in Reproduction System of Female Bovine

    Institute of Scientific and Technical Information of China (English)

    QI Meiyu; ZviRoth; LIU Di

    2011-01-01

    Insulin-like growth factor-I (IGF-I) plays a key role in female reproduction, because it has the effect of anti-apoptosis improving cell proliferation, transformation and differentiation. This paper reviewed the effects of IGF-I on ovary, follicle growth, acquisition of oocyte competence and preimplantation embryo viability, and then summarized different points about IGF-1 for reproduction system

  13. Staphylococcus aureus induces TGF-β1 and bFGF expression through the activation of AP-1 and NF-κB transcription factors in bovine mammary gland fibroblasts.

    Science.gov (United States)

    Wu, Jianmei; Ding, Yulin; Bi, Yannan; Wang, Yi; Zhi, Yu; Wang, Jinling; Wang, Fenglong

    2016-06-01

    Staphylococcus aureus is a common Gram-positive pathogen that causes bovine mastitis, a persistent infection of the bovine mammary gland. To better understand the importance of bovine mammary fibroblasts (BMFBs) and the roles of the TLR-NF-κB and TLR-AP-1 signaling pathways in the regulation of S. aureus-associated mastitis and mammary fibosis, BMFBs cultured in vitro were stimulated with different concentrations of heat-inactivated S. aureus to analyze the gene and protein expression of toll-like receptor 2 (TLR2), toll-like receptor 4 (TLR4), transforming growth factor beta 1 (TGF-β1), basic fibroblast growth factor (bFGF) as well as the protein expression of nuclear factor-kappa B (NF-κB) and activation protein-1 (AP-1) by means of quantitative polymerase chain reaction (qPCR) and western blotting, respectively. Specific NF-κB and AP-1 inhibitors were also used to investigate their effects on the regulation of TGF-β1 and bFGF expression. The results indicated that, in addition to increasing mRNA and protein expression of TLR2 and TLR4, S. aureus could also upregulate TGF-β1 and bFGF mRNA expression and secretion through the activation of NF-κB and AP-1. The increase in TGF-β1 and bFGF expression was shown to be inhibited by AP-1- and NF-κB-specific inhibitors. Taken together, S. aureus induces TGF-β1 and bFGF expression through the activation of AP-1 and NF-κB in BMFBs. This information offers new potential targets for the treatment of bovine mammary fibrosis. PMID:26948281

  14. Mitochondrial Dysfunction and Psychiatric Disorders

    Directory of Open Access Journals (Sweden)

    Shaw-Hwa Jou

    2009-10-01

    Full Text Available Mitochondria are intracellular organelles crucial in the production of cellular energy.Mitochondrial diseases may result from malfunctions in this biochemical cascade. Severalinvestigators have proposed that mitochondrial dysfunction is related to the pathophysiologyof bipolar disorder (BD, major depressive disorder (MDD and schizophrenia (SZ. Theauthors reviewed recent study findings and tried to delineate the current understanding of thecorrelation between mitochondrial dysfunction and psychiatric disorders. A growing body ofevidence suggests that mitochondrial dysfunction is important in patients with psychiatricdisorders. The evidence include impaired energy metabolism in the brain detected usingresults of magnetic resonance spectroscopy, electron microscopy, co-morbidity with mitochondrialdiseases, the effects of psychotropics on mitochondria, increased mitochondrialDNA (mtDNA deletion in the brain, and association with mtDNA mutations/polymorphismsor nuclear-encoded mitochondrial genes. It is possible that the new information willlead to a focus on psychiatric disorder as a metabolic disease. Treatment with psychotropicsmight ultimately enhance energy metabolism and reduce the damage of oxidative stress. Thenext step in the study of mitochondrial dysfunction in patients with psychiatric disordersshould be clarification of how mitochondrial dysfunction, a nonspecific risk factor, causesspecific symptoms. Further study of mitochondrial dysfunction in patients with psychiatricdisorder is expected to be useful for the development of cellular disease markers and newpsychotropics.

  15. Increased pulmonary secretion of tumor necrosis factor-alpha in calves experimentally infected with bovine respiratory syncytial virus

    DEFF Research Database (Denmark)

    Rontved, C. M.; Tjørnehøj, Kirsten; Viuff, B.;

    2000-01-01

    , of which 23 were experimentally infected with BRSV and five were given a mock inoculum. The presence of the cytokine tumor necrosis factor alpha (TNF-alpha) in the BAL fluids was detected and quantified by a capture ELISA. TNF-alpha was detected in 21 of the infected animals. The amount of TNF...... levels of TNF-alpha appeared on the days where severe lung lesions and clinical signs were obvious and the amounts of BRSV-antigen were at their greatest. Although Pasteurellaceae were isolated from some of the BRSV-infected calves, calves treated with antibiotics before and through the whole period of...

  16. Regulation of MMP2 and MMP9 metalloproteinases by FSH and growth factors in bovine granulosa cells

    OpenAIRE

    Portela, Valerio M.; Angela Veiga; Price, Christopher A.

    2009-01-01

    Matrix metalloproteinases (MMP) are key enzymes involved in tissue remodeling. Within the ovary, they are believed to play a major role in ovulation, and have been linked to follicle atresia. To gain insight into the regulation of MMPs, we measured the effect of hormones and growth factors on MMP2 and MMP9 mRNA levels in non-luteinizing granulosa cells in serum-free culture. FSH and IGF1 both stimulated estradiol secretion and inhibited MMP2 and MMP9 mRNA abundance. In contrast, EGF and FGF2 ...

  17. Differential actions of fibroblast growth factors on intracellular pathways and target gene expression in bovine ovarian granulosa cells.

    Science.gov (United States)

    Jiang, Zhongliang; Price, Christopher A

    2012-11-01

    Several fibroblast growth factors (FGFs), including FGF1, FGF4 and FGF10, alter ovarian granulosa cell function. These ligands exhibit different patterns of receptor activation, and their mechanisms of action on granulosa cells remain unknown. The objective of this study was to identify the major pathways and target genes activated by FGF1, FGF4 and FGF10 in primary oestrogenic granulosa cells cultured under serum-free conditions. FGF1 and FGF4 increased levels of mRNA encoding Sprouty family members, SPRY2 and SPRY4, and the orphan nuclear receptors NR4A1 and NR4A3. Both FGF1 and FGF4 decreased levels of mRNA encoding SPRY3 and the pro-apoptotic factor BAX. FGF1 but not FGF4 stimulated expression of the cell cycle regulator, GADD45B. In contrast, FGF10 altered the expression of none of these genes. Western blot demonstrated that FGF4 activated ERK1/2 and Akt signalling rapidly and transiently, whereas FGF10 elicited a modest and delayed activation of ERK1/2. These data show that FGF1 and FGF4 activate typical FGF signalling pathways in granulosa cells, whereas FGF10 activates atypical pathways. PMID:22956519

  18. Bovine mastitis and its association with selected risk factors in smallholder dairy farms in and around Bahir Dar, Ethiopia.

    Science.gov (United States)

    Almaw, G; Zerihun, A; Asfaw, Y

    2008-08-01

    Three hundred fifty one (195 local zebu and 156 Holstein x local zebu crosses) lactating cows of smallholder farms in Bahir Dar 'milk shed' were examined from September 2003 to March 2004 to determine mastitis prevalence, isolate pathogens and identify the role of some potential risk factors. Clinical prevalence was determined through examination of abnormalities of milk, udder or cow. California mastitis test (CMT) was used for determination of subclinical mastitis prevalence. Clinical prevalence at cow level was 3.9% in crossbreds and none in local zebu breeds. Subclinical mastitis at cow level based on CMT was high (34.4%) in crossbreds compared to indigenous zebu (17.9%) (p CMT was 17.9% and 4.9% in crossbreds and local zebu, respectively. The pathogens isolated from mastitic milk (CMT positive milk) were coagulase negative staphylococci (CNS), S. aureus, Str. agalactiae, Str. dysgalactiae, Str. uberis, Micrococcus species, C. bovis, A. pyogens, B. cereus, and S. intermedius. Among these, the most frequent isolates were CNS (50%), S. aureus (19%), Str. agalactiae (8%) and Str. dysgalactiae (7%). Among potential risk factors considered, stage of lactation, parity and breed were found to affect the occurrence of mastitis significantly (p < 0.05). PMID:18575970

  19. Mitochondrial Diseases

    Science.gov (United States)

    ... in your body tissues. If you have a metabolic disorder, something goes wrong with this process. Mitochondrial diseases are a group of metabolic disorders. Mitochondria are small structures that produce energy in ...

  20. Mitochondrial Dysfunction in Gliomas

    Czech Academy of Sciences Publication Activity Database

    Katsetos, C.D.; Anni, H.; Dráber, Pavel

    2013-01-01

    Roč. 20, č. 3 (2013), s. 216-227. ISSN 1071-9091 R&D Projects: GA MŠk LH12050 Institutional support: RVO:68378050 Keywords : gliomas * mitochondrial dysfunction * microtubule proteins Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.883, year: 2013

  1. Mitochondrial dysfunction in epilepsy

    Czech Academy of Sciences Publication Activity Database

    Folbergrová, Jaroslava; Kunz, W.S.

    2012-01-01

    Roč. 12, č. 1 (2012), s. 35-40. ISSN 1567-7249 R&D Projects: GA ČR(CZ) GA309/05/2015; GA ČR GA309/08/0292 Institutional research plan: CEZ:AV0Z50110509 Keywords : epilepsy * mitochondrial dysfunction * neurodegeneration Subject RIV: FH - Neurology Impact factor: 4.025, year: 2012

  2. Genotypes, Virulence Factors and Antimicrobial Resistance Genes of Staphylococcus aureus Isolated in Bovine Subclinical Mastitis from Eastern China

    Directory of Open Access Journals (Sweden)

    Javed Memon§, Yongchun Yang§, Jam Kashifa, Muhammad Yaqoob, Rehana Buriroa, Jamila Soomroa, Wang Liping and Fan Hongjie*

    2013-11-01

    Full Text Available This study was carried out to determine the genotypes, virulence factors and antimicrobial resistance traits of 34 Staphylococcus aureus isolated from subclinical mastitis in Eastern China. Minimal inhibitory concentration (MIC results showed resistance to erythromycin in all isolates. A high frequency of Methicillin resistant S. aureus (MRSA; 29% was observed and these isolates were also highly resistant to penicillin, oxacillin, oxytetracycline and chloramphenicol than methicillin sensitive S. aureus (MSSA isolates. Thirteen pathogenic factors and seven resistance genes including mecA and blaZ gene were checked through PCR. The spaX gene was found in all isolates, whereas cna, spaIg, nuc, clfA, fnbpB, hlA, hlB and seA were present in 35, 79, 85, 59, 35, 85, 71 and 38% isolates, respectively. Nine isolates carried a group of 8 different virulence genes. Moreover, macrolide resistance genes ermB and ermC were present in all isolates. High resistance rate against methicillin was found but no isolate was positive for mecA gene, whereas blaZ and tetK were detected in 82 and 56% isolates, respectively. Genes; fnbpA, seB, seC, seD, dfrK and tetM were not found in any isolate. The statistical association between phenotypic resistance and virulence genes showed, clfA, fnbpB, hlB and seA, were potentially associated with penicillin G, ciprofloxacin, methicillin, chloramphenicol, trimethoprim and oxytetracycline resistance (P≤0.05. REP-PCR based genotyping showed seven distinct genotypes (A-G prevalent in this region. This study reports the presence of multidrug resistant S. aureus in sub-clinical mastitis which were also highly virulent that could be a major obstacle in the treatment of mastitis in this region of China.

  3. Puerperal influence of bovine uterine health status on the mRNA expression of pro-inflammatory factors.

    Science.gov (United States)

    Peter, S; Michel, G; Hahn, A; Ibrahim, M; Lubke-Becker, A; Jung, M; Einspanier, R; Gabler, C

    2015-06-01

    After parturition, uterine bacterial infections lead to inflammatory processes such as subclinical/clinical endometritis with high prevalence in dairy cows. Endometrial epithelial cells participate in this immune response with the production of pro-inflammatory factors. The objective of the present study was to evaluate the endometrial mRNA expression pattern of pro-inflammatory factors during a selected postpartum (pp) period. Dairy cows with three different uterine health conditions on days 24-30 pp (healthy: n = 11, subclinical endometritis: n = 10, clinical endometritis: n = 10) were sampled using the cytobrush technique. Subsequently, each cow was sampled 3 more times in weekly intervals (days 31-37 pp; days 38-44 pp; days 45-51 pp). Samples were subjected to mRNA analysis performed by RT-qPCR. Additionally, an analysis of cultivable bacteria was performed at the early/late stage of the selected puerperal period. mRNA expression of 16 candidate genes was analyzed by using two different approaches. The first approach referred to the initial grouping on days 24-30 pp to reveal long-term effects of the uterine health on the subsequent puerperal period. The second approach considered the current uterine health status at each sampling to elucidate the impact of different points in time. Long-term effects seem to appear for chemokines, prostacyclin synthase and prostaglandin D2 synthase. If related to the current uterine health, the majority of candidate genes were significantly higher expressed in endometritic cows on days 45-51 pp in contrast to earlier stages of the puerperium. Microbiological analysis revealed the significantly higher prevalence of Trueperella pyogenes findings in cows with clinical endometritis on days 24-30 pp, but no correlations were found on days 45-51 pp. In conclusion, a strong immune response to subclinical/clinical endometritis in the late puerperium may be related to the negative impact of these conditions on reproductive performance

  4. Fatores de risco associados à mastite bovina causada por Prototheca zopfii Risk factors associated with bovine mastitis caused by Prototheca zopfii

    Directory of Open Access Journals (Sweden)

    Aline Artioli Machado Yamamura

    2008-06-01

    Full Text Available Este trabalho teve como objetivo o estudo de fatores de risco associados à mastite bovina causada por Prototheca zopfii. Foram analisadas 13 propriedades leiteiras dos Estados do Paraná e de São Paulo, segundo os seguintes critérios de seleção: confirmação prévia de casos de mastite por Prototheca spp., triagem pela pesquisa de Prototheca spp. em tanques de expansão e latões e rebanhos com contagem de células somáticas acima de 5x105cel mL-1. As amostras coletadas consistiram de: leite, água, solo, fezes e swab de teteiras. Prototheca spp. foi isolada de amostras de leite dos quartos mamários com mastite clínica ou subclínica em uma propriedade e de amostras de leite e do ambiente em quatro propriedades, nas quais foi isolada em amostras de: água de bebedouro, abastecimento, esgoto, empoçada no piso de estábulo e sala de ordenha, solo de piquete e pasto, teteiras, fezes de bezerros e suínos. Do total de 383 vacas examinadas, Prototheca spp. foi isolada em 20 (5,2% vacas, sendo caracterizada como P. zopfii em 18. Os fatores de risco associados à mastite causada por P. zopfii foram: criação das vacas a pasto, alimentação dos animais com pasto e silagem, realização de ordenha mecânica em estábulo, permanência das vacas após ordenha em piquete sem alimento, criação de suínos próxima às instalações dos bovinos, existência de cães, gatos e roedores, falta de higienização dos tetos com água, pré-imersão dos tetos em aplicador com retorno e sem a troca do anti-séptico, alimentação dos bezerros com leite de vacas com mastite clínica e serem as vacas da raça holandesa.This research had as objective the study of risk factors associated with bovine mastitis caused by Prototheca zopfii. Thirteen dairy herds in Paraná and São Paulo states were analyzed and selected according to the following criteria: previous confirmation of Prototheca spp. mastitis cases, screening of Prototheca spp. in bulk tanks and

  5. Cultured bovine brain capillary endothelial cells (BBCEC) - a blood-brain barrier model for studying the binding and internalization of insulin and insulin-like growth factor 1

    Energy Technology Data Exchange (ETDEWEB)

    Keller, B.T.; Borchardt, R.T.

    1987-05-01

    Cultured bovine brain capillary endothelial cells (BBCEC) have previously been reported by their laboratory as a working model for studying nutrient and drug transport and metabolism at the blood-brain barrier. In the present study, they have utilized this culture system to investigate the binding and internalization of (/sup 125/I)-labelled insulin (INS) and insulin-like growth factor 1(IGF-1) by BBCEC. After 2 hrs at 23/sup 0/C, the specific binding of INS and IGF-1 was 1.6% and 13.6%, respectively. At 37/sup 0/C, the maximum specific binding was 0.9% for INS and 5.8% for IGF-1. Using an acid-wash technique to assess peptide internalization, it was observed that, at 37/sup 0/C, approximately 60% of the bound INS rapidly became resistant to acid treatment, a value which was constant over 2 hr. With IGF-1, a similar proportion of the bound material, 62%, became resistant by 30 min, but subsequently decreased to 45% by 2 hr. Scatchard analysis of competitive binding studies indicated the presence of two binding sites for each protein, having K/sub d/'s of 0.82 nM and 19.2 nM for INS and 0.39 nM and 3.66 nM for IGF-1. Little change in the amount of INS binding was observed over a four-day interval as the cultures became a confluent monolayer. The present report of binding and internalization of these proteins suggests that the BBCEC may utilize a receptor-mediated process to internalize and/or transport (transcytosis) INS and IGF-1 from the circulation.

  6. Effect of recombinant bovine granulocyte colony-stimulating factor covalently bound to polyethylene glycol injection on neutrophil number and function in periparturient dairy cows.

    Science.gov (United States)

    Kimura, Kayoko; Goff, Jesse P; Canning, Peter; Wang, Chong; Roth, James A

    2014-01-01

    Dairy cows often experience decreased immune function around the time of calving, typified by impaired polymorphonuclear neutrophil (PMN) function and a transient neutropenia. This is associated with increased disease incidence, including mastitis, retained placenta, and metritis. In an attempt to improve PMN functional capacity during the periparturient period, we injected cows with recombinant bovine granulocyte colony-stimulating factor covalently bound to polyethylene glycol (PEG rbG-CSF) twice subcutaneously, about 6d before calving and within 24h after calving. Twenty-one cows in their second pregnancy were enrolled in this study and divided into 2 groups: PEG rbG-CSF treated (n=11) and saline-treated controls (n=10). The PMN numbers quickly and dramatically increased after PEG rbG-CSF administration and remained elevated through the end of the experiment (13d after calving). Exocytosis of myeloperoxidase by stimulated PMN, which is generally decreased in periparturient cows, was markedly increased by PEG rbG-CSF after injection. Higher myeloperoxidase exocytosis persisted for at least 10d after calving. The PMN superoxide anion release and phagocytosis activity did not differ between groups. Injection of PEG rbG-CSF was safe for cows, with no significant negative effects observed. The greatest single effect of PEG rbG-CSF administration was a dramatic increase in circulating numbers of PMN. The increased numbers of PMN ready to move to a site of infection early in the course of an infection may improve the ability of the cow to ward off clinical disease in the periparturient period. PMID:24881799

  7. Characterization of Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) interaction with the Bovine Aortic Endothelial (BAE) cell surface : Examination of the Role of Heparan Sulfate Proteoglycans (HSPG).

    OpenAIRE

    Parghi, Nirav

    1998-01-01

    Insulin-like growth factor binding proteins (IGFBPs) are known to be important modulators of the insulin-like growth factor (IGF-I). However, their precise role is as yet unclear. Further, recent studies have indicated that IGFBP-3 has a receptor mediated growth inhibitory response of its own. In the present study, we quantified the binding characteristics of IGFBP-3 to bovine aortic endothelial (BAE) cells. Binding studies at 4 oC were conducted and a specific binding curve for IGFB...

  8. Herd-level prevalence and risk factors for bovine viral diarrhea virus infection in cattle in the State of Paraíba, Northeastern Brazil.

    Science.gov (United States)

    Fernandes, Leise Gomes; Nogueira, Adriana Hellmeister de Campos; De Stefano, Eliana; Pituco, Edviges Maristela; Ribeiro, Cláudia Pestana; Alves, Clebert José; Oliveira, Tainara Sombra; Clementino, Inácio José; de Azevedo, Sérgio Santos

    2016-01-01

    Serological surveys based on a planned sampling on bovine viral diarrhea virus (BVDV) infection in Brazilian cattle herds are scarce. A cross-sectional study was carried out to determine herd- and animal-level seroprevalences and to identify risk factors associated with herd-level seroprevalence for BVDV infection in the State of Paraíba, Northeastern Brazil, from September 2012 to January 2013. The state was divided into three sampling strata, and for each stratum, the prevalence of herds infected with BVDV and the prevalence of seropositive animals was estimated by a two-stage sampling survey. In total, 2443 animals were sampled from 478 herds. A virus-neutralization test was used for BVDV antibody detection. A herd was considered positive when at least one seropositive animal was detected. The herd- and animal-level prevalences in the State of Paraíba were 65.5% (95% confidence interval (CI) = 61.1-69.7%) and 39.1% (95% CI = 33.1-45.6%), respectively. The frequency of seropositive animals per herd ranged from 10 to 100% (median of 50%). The risk factors identified were as follows: more than six calves aged ≤12 months (odds ratio (OR) = 3.72; 95% CI = 2.08-6.66), animal purchasing (OR = 1.66; 95% CI = 1.08-2.55), pasture rental (OR = 2.15; 95% CI = 1.35-3.55), and presence of veterinary assistance (OR = 2.04; 95% CI = 1.10-3.79). Our findings suggest that the implementation of control and prevention measures among farmers, with the aim of preventing dissemination of the agent in the herds, is necessary. Special attention should be given to addressing the identified risk factors, such as sanitary control prior to animal purchasing and to discourage the pasture rental, as well as to encourage the vaccination in the herds. PMID:26498460

  9. Multiple proteins with essential mitochondrial functions have glycosylated isoforms

    OpenAIRE

    Burnham-Marusich, Amanda R.; Berninsone, Patricia M.

    2012-01-01

    Nucleocytosolic and secreted proteins are commonly glycosylated. However, reports of glycosylated mitochondrial proteins are rare. Using lectin chromatography on bovine heart, we detected low-abundance glycoforms of nuclear-encoded proteins with well-established mitochondrial function: pyruvate dehydrogenase E1α, NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, ADP/ATP translocase, ATP synthase d and oligomycin sensitivity-conferring protein. Notably, the latter two have been previously...

  10. Characterization of insulin-like growth factor I and insulin receptors on cultured bovine adrenal fasciculata cells. Role of these peptides on adrenal cell function

    International Nuclear Information System (INIS)

    We have characterized insulin-like growth factor I (IGF-I) and insulin receptors in cultured bovine adrenal cells by binding and cross-linking affinity experiments. At equilibrium the dissociation constant and the number of binding sites per cell for IGF-I were 1.4 +/- (SE) 0.3 x 10(-9) M and 19,200 +/- 2,100, respectively. Under reduction conditions, disuccinimidyl suberate cross-linked [125I]iodo-IGF-I to one receptor complex with an Mr of 125,000. Adrenal cells also contain specific insulin receptors with an apparent dissociation constant (Kd) of 10(-9) M. Under reduction conditions [125I]iodo-insulin binds to one band with an approximate Mr of 125,000. IGF-I and insulin at micromolar concentrations, but not at nanomolar concentrations, slightly stimulated DNA synthesis, but markedly potentiated the mitogenic action of fibroblast growth factor. Adrenal cells cultured in a serum-free medium containing transferrin, ascorbic acid, and insulin (5 micrograms/ml) maintained fairly constant angiotensin-II (A-II) receptor concentration per cell and increased cAMP release on response to ACTH and their steroidogenic response to both ACTH and A-II. When the cells were cultured in the same medium without insulin, the number of A-II receptors significantly decreased to 65% and the increased responsiveness was blunted. Treatment of such cells for 3 days with increasing concentrations of IGF-I (1-100 ng/ml) produced a 2- to 3-fold increase in A-II receptors and enhanced the cAMP response (3- to 4-fold) to ACTH and the steroidogenic response (4- to 6-fold) to ACTH and A-II. These effects were time and dose dependent (ED50 approximately equal to 10(-9) M). Insulin at micromolar concentrations produced an effect similar to that of IGF-I, but at nanomolar concentrations the effect was far less

  11. Herd-level risk factors for bovine tuberculosis and adoption of related biosecurity measures in Northern Ireland: A case-control study.

    Science.gov (United States)

    O'Hagan, M J H; Matthews, D I; Laird, C; McDowell, S W J

    2016-07-01

    Bovine tuberculosis (bTB) is a zoonotic disease which is endemic in Northern Ireland. As it has proven difficult to eradicate this disease, partly due to a wildlife reservoir being present in the European badger (Meles meles), a case-control study was conducted in a high incidence area in 2010-2011. The aim was to identify risk factors for bTB breakdown relating to cattle and badgers, and to assess the adoption of bTB related biosecurity measures on farms. Face-to-face questionnaires with farmers and surveys of badger setts and farm boundaries were conducted on 117 farms with a recent bTB breakdown (cases) and 75 farms without a recent breakdown (controls). On logistic regression at univariable and multivariable levels, significant risk factors associated with being a case herd included having an accessible badger sett within the farm boundaries in a field grazed in the last year (odds ratio, OR, 4.14; 95% confidence interval, CI, 1.79, 9.55), observation of live badgers (OR 4.14; 95% CI 1.79, 9.55), purchase of beef cattle (OR 4.60; 95% CI 1.61, 13.13), use of contractors to spread slurry (OR 2.83; 95% CI 1.24, 6.49), feeding meal on top of silage (OR 3.55; 95% CI 1.53, 8.23) and feeding magnesium supplement (OR = 3.77; 95% CI 1.39, 10.17). The majority of setts within the farm boundary were stated to be accessible by cattle (77.1%; 95% CI 71.2, 83.0%) and 66.8% (95% CI 63.8, 69.7%) of farm boundaries provided opportunities for nose-to-nose contact between cattle. Adoption of bTB related biosecurity measures, especially with regards to purchasing cattle and badger-related measures, was lower than measures related to disinfection and washing. PMID:27240911

  12. Prevalence of bovine tuberculosis and risk factor assessment in cattle in rural livestock areas of Govuro District in the Southeast of Mozambique.

    Directory of Open Access Journals (Sweden)

    Ivânia Moiane

    Full Text Available BACKGROUND: Bovine tuberculosis (bTB, caused by Mycobacterium bovis, is an infectious disease of cattle that also affects other domestic animals, free-ranging and farmed wildlife, and also humans. In Mozambique, scattered surveys have reported a wide variation of bTB prevalence rates in cattle from different regions. Due to direct economic repercussions on livestock and indirect consequences for human health and wildlife, knowing the prevalence rates of the disease is essential to define an effective control strategy. METHODOLOGY/PRINCIPAL FINDINGS: A cross-sectional study was conducted in Govuro district to determine bTB prevalence in cattle and identify associated risk factors. A representative sample of the cattle population was defined, stratified by livestock areas (n = 14. A total of 1136 cattle from 289 farmers were tested using the single comparative intradermal tuberculin test. The overall apparent prevalence was estimated at 39.6% (95% CI 36.8-42.5 using a diagnostic threshold cut-off according to the World Organization for Animal Health. bTB reactors were found in 13 livestock areas, with prevalence rates ranging from 8.1 to 65.8%. Age was the main risk factor; animals older than 4 years were more likely to be positive reactors (OR = 3.2, 95% CI: 2.2-4.7. Landim local breed showed a lower prevalence than crossbred animals (Landim × Brahman (OR = 0.6, 95% CI: 0.4-0.8. CONCLUSIONS/SIGNIFICANCE: The findings reveal an urgent need for intervention with effective, area-based, control measures in order to reduce bTB prevalence and prevent its spread to the human population. In addition to the high prevalence, population habits in Govuro, particularly the consumption of raw milk, clearly may potentiate the transmission to humans. Thus, further studies on human tuberculosis and the molecular characterization of the predominant strain lineages that cause bTB in cattle and humans are urgently required to evaluate the impact on human health in

  13. Control of bovine hepatic fatty acid oxidation

    Energy Technology Data Exchange (ETDEWEB)

    Jesse, B.W.; Emery, R.S.; Thomas, J.W.

    1986-09-01

    Fatty acid oxidation by bovine liver slices and mitochondria was examined to determine potential regulatory sites of fatty acid oxidation. Conversion of 1-(/sup 14/C)palmitate to /sup 14/CO/sub 2/ and total (/sup 14/C)acid-soluble metabolites was used to measure fatty acid oxidation. Oxidation of palmitate (1 mM) was linear in both liver slice weight and incubation time. Carnitine stimulated palmitate oxidation; 2 mM dl-carnitine produced maximal stimulation of palmitate oxidation to both CO/sup 2/ and acid-soluble metabolites. Propionate (10 mM) inhibited palmitate oxidation by bovine liver slices. Propionate (.5 to 10 mM) had no effect on palmitate oxidation by mitochondria, but malonyl Coenzyme A, the first committed intermediate of fatty acid synthesis, inhibited mitochondrial palmitate oxidation (inhibition constant = .3 ..mu..M). Liver mitochonndrial carnitine palmitoyltransferase exhibited Michaelis constants for palmitoyl Coenzyme A and l-carnitine of 11.5 ..mu..M and .59 mM, respectively. Long-chain fatty acid oxidation in bovine liver is regulated by mechanisms similar to those in rats but adapted to the unique digestive physiology of the bovine.

  14. Control of bovine hepatic fatty acid oxidation

    International Nuclear Information System (INIS)

    Fatty acid oxidation by bovine liver slices and mitochondria was examined to determine potential regulatory sites of fatty acid oxidation. Conversion of 1-[14C]palmitate to 14CO2 and total [14C]acid-soluble metabolites was used to measure fatty acid oxidation. Oxidation of palmitate (1 mM) was linear in both liver slice weight and incubation time. Carnitine stimulated palmitate oxidation; 2 mM dl-carnitine produced maximal stimulation of palmitate oxidation to both CO2 and acid-soluble metabolites. Propionate (10 mM) inhibited palmitate oxidation by bovine liver slices. Propionate (.5 to 10 mM) had no effect on palmitate oxidation by mitochondria, but malonyl Coenzyme A, the first committed intermediate of fatty acid synthesis, inhibited mitochondrial palmitate oxidation (inhibition constant = .3 μM). Liver mitochonndrial carnitine palmitoyltransferase exhibited Michaelis constants for palmitoyl Coenzyme A and l-carnitine of 11.5 μM and .59 mM, respectively. Long-chain fatty acid oxidation in bovine liver is regulated by mechanisms similar to those in rats but adapted to the unique digestive physiology of the bovine

  15. Tumor necrosis factor-α impairs adiponectin signalling, mitochondrial biogenesis, and myogenesis in primary human myotubes cultures.

    Science.gov (United States)

    Sente, Tahnee; Van Berendoncks, An M; Fransen, Erik; Vrints, Christiaan J; Hoymans, Vicky Y

    2016-05-01

    Skeletal muscle metabolic changes are common in patients with chronic heart failure (HF). Previously, we demonstrated a functional skeletal muscle adiponectin resistance in HF patients with reduced left ventricular ejection fraction (HFrEF). We aimed to examine the impact of adiponectin receptor 1 (AdipoR1) deficiency and TNF-α treatment on adiponectin signaling, proliferative capacity, myogenic differentiation, and mitochondrial biogenesis in primary human skeletal muscle cells. Primary cultures of myoblasts and myotubes were initiated from the musculus vastus lateralis of 10 HFrEF patients (left ventricular ejection fraction; 31.30 ± 2.89%) and 10 age- and gender-matched healthy controls. Healthy control cultures were transfected with siAdipoR1 and/or exposed to TNF-α (10 ng/ml; 72 h). Primary cultures from HFrEF patients preserved the features of adiponectin resistance in vivo. AdipoR1 mRNA was negatively correlated with time to reach maximal cell index (r = -0.7319, P = 0.003). SiRNA-mediated AdipoR1 silencing reduced pAMPK (P mitochondrial (FOXO3, P = 0.018) metabolism, impaired myogenesis (MyoD1, P = 0.053; myogenin, P = 0.048) and polarized cytokine secretion toward a growth-promoting phenotype (IL-10, IL-1β, IFN-γ, P < 0.05 for all; Meso Scale Discovery Technology). Major features of adiponectin resistance are retained in primary cultures from the skeletal muscle of HFrEF patients. In addition, our results suggest that an increased inflammatory constitution contributes to adiponectin resistance and confers alterations in skeletal muscle differentiation, growth, and function. PMID:26921438

  16. ß-catenin, a transcription factor activated by canonical Wnt signaling, is expressed in sensory neurons of calves latently infected with bovine herpesvirus 1

    Science.gov (United States)

    Like many a-herpesvirinae subfamily members, bovine herpes virus 1 (BoHV-1) expresses an abundant transcript in latently infected sensory neurons: the latency-related (LR) RNA. LR-RNA encodes a protein (ORF2) that inhibits apoptosis, interacts with Notch family members, interferes with Notch mediate...

  17. The increasing of fibroblast growth factor 2, osteocalcin, and osteoblast due to the induction of the combination of Aloe vera and 2% xenograft concelous bovine

    Directory of Open Access Journals (Sweden)

    Utari Kresnoadi

    2012-12-01

    Full Text Available Background: To make a successfull denture prominent ridge is needed, preservation on tooth extraction socket is needed in order to prevent alveol bone resorption caused by revocation trauma. An innovative modification of the material empirically suspected to be able reduce inflammation caused by the revocation trauma is a combination of Aloe vera and xenograft concelous bovine (XCB and Aloe vera is a biogenic stimulator and accelerating the growth of alveolar ridge bone after tooth extraction. Purpose: The research was aimed to determine of the increasing alveol bone formation by inducing the combination of Aloe vera and 2% xenograft concelous bovine. Methods: To address the problems, the combination of Aloe vera and xenograft concelous bovine was induced into the tooth extraction sockets of Cavia cabayas which devided on 8 groups. Groups control, filled with XCB, Aloe vera and Aloe vera and XCB combination, at 7 days and 30 days after extraction. Afterwards, immunohistochemical examination was conducted to examine the expressions of FGF-2 and osteocalcin, as the product of the growth of osteoblasts. Results: There were significantly increases expression of FGF-2 and osteocalcyn on group which filled with XCB, Aloe vera and combined Aloe vera and XCB. Conclusion: It may be concluded that the induction of the combination of Aloe vera and xenograft concelous bovine into the tooth sockets can enhance the growth expressions of FGF-2 and osteocalcin as the product of osteoblasts, thus, the growth of alveolar bone was increased.Latar belakang: Untuk keberhasilan pembuatan gigitiruan diperlukan ridge yang prominent, maka diperlukan suatu preservasi soket pencabutan gigi untuk mencegah terjadinya resopsi tulang alveolar akibat trauma pencabutan. Suatu inovasi modifikasi bahan yang diduga secara empiris dapat mengurangi keradangan karena trauma pencabutan adalah berupa kombinasi Aloe vera dan xenograft concelous bovine (XCB. Aloe vera yang merupakan

  18. Identification of Factors Interacting with hMSH2 and hMLH1 in the Fetal Liver and Investigations of how Mitochondrial Dysfunction Creates a Mutator Phenotype

    DEFF Research Database (Denmark)

    Rasmussen, Anne Karin

    mutations. Mutations in MMR genes cause hereditary non-polyposis colon cancer. In an effort to identify unidentified genes involved in MMR and tissue-specific MMRassociated factors, we employed the yeast two-hybrid system, using the human hMSH2 as bait and a human fetal liver cDNA library as prey. We...... demonstrated that hMSH2 interacts with a human 5’ → 3’ exonuclease 1 (hEXO1). Data presented in this thesis also support the conclusion that mitochondrial dysfunction leads to spontaneous nuclear DNA damage. We employed the yeast Saccharomyces cerevisiae as a model system to investigate a potential link...... very limited. We decided to investigate O6-methylguanine- DNA methyltransferase (MGMT) because of the fact that its sub-cellular localization has not been determined. We determined that it was localized to nucleus but not to mitochondria in HeLa and breast epithelial cells....

  19. Transcription factor Nurr1 maintains fiber integrity and nuclear-encoded mitochondrial gene expression in dopamine neurons

    OpenAIRE

    Kadkhodaei, B.; Alvarsson, A; Schintu, N.; Ramskold, D.; Volakakis, N.; Joodmardi, E.; Yoshitake, T.; Kehr, J; Decressac, M.; Bjorklund, A; Sandberg, R; Svenningsson, P; Perlmann, T

    2013-01-01

    Developmental transcription factors important in early neuron specification and differentiation often remain expressed in the adult brain. However, how these transcription factors function to mantain appropriate neuronal identities in adult neurons and how transcription factor dysregulation may contribute to disease remain largely unknown. The transcription factor Nurr1 has been associated with Parkinson's disease and is essential for the development of ventral midbrain dopamine (DA) neurons....

  20. 77 FR 20319 - Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products

    Science.gov (United States)

    2012-04-04

    ...; ] DEPARTMENT OF AGRICULTURE Animal and Plant Health Inspection Service 9 CFR Part 93 RIN 0579-AC68 Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products Correction In proposed rule...

  1. 78 FR 73993 - Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products

    Science.gov (United States)

    2013-12-10

    ... Health Inspection Service 9 CFR Parts 92, 93, 94, 95, 96, and 98 RIN 0579-AC68 Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products Corrections In rule document 2013-28228 appearing...

  2. Tumor Necrosis Factor-α and Apoptosis Signal-Regulating Kinase 1 Control Reactive Oxygen Species Release, Mitochondrial Autophagy and C-Jun N-Terminal Kinase/P38 Phosphorylation During Necrotizing Enterocolitis

    Directory of Open Access Journals (Sweden)

    Naira Baregamian

    2009-01-01

    Full Text Available Background: Oxidative stress and inflammation may contribute to the disruption of the protective gut barrier through various mechanisms; mitochondrial dysfunction resulting from inflammatory and oxidative injury may potentially be a significant source of apoptosis during necrotizing enterocolitis (NEC. Tumor necrosis factor (TNFα is thought to generate reactive oxygen species (ROS and activate the apoptosis signal-regulating kinase 1 (ASK1-c-Jun N-terminal kinase (JNK/p38 pathway. Hence, the focus of our study was to examine the effects of TNFα/ROs on mitochondrial function, ASK1-JNK/p38 cascade activation in intestinal epithelial cells during NEC.

  3. Mitochondrial Dysfunction in Neurodegenerative Diseases

    OpenAIRE

    Johri, Ashu; Beal, M. Flint

    2012-01-01

    Neurodegenerative diseases are a large group of disabling disorders of the nervous system, characterized by the relative selective death of neuronal subtypes. In most cases, there is overwhelming evidence of impaired mitochondrial function as a causative factor in these diseases. More recently, evidence has emerged for impaired mitochondrial dynamics (shape, size, fission-fusion, distribution, movement etc.) in neurodegenerative diseases such as Parkinson's disease, Huntington's disease, amyo...

  4. ATP Depletion Via Mitochondrial F1F0 Complex by Lethal Factor is an Early Event in B. Anthracis-Induced Sudden Cell Death

    Directory of Open Access Journals (Sweden)

    Mitchell W. Woodberry

    2009-08-01

    Full Text Available Bacillus anthracis’ primary virulence factor is a tripartite anthrax toxin consisting of edema factor (EF, lethal factor (LF and protective antigen (PA. In complex with PA, EF and LF are internalized via receptor-mediated endocytosis. EF is a calmodulin- dependent adenylate cyclase that induces tissue edema. LF is a zinc-metalloprotease that cleaves members of mitogen-activated protein kinase kinases. Lethal toxin (LT: PA plus LF-induced death of macrophages is primarily attributed to expression of the sensitive Nalp1b allele, inflammasome formation and activation of caspase-1, but early events that initiate these processes are unknown. Here we provide evidence that an early essential event in pyroptosis of alveolar macrophages is LF-mediated depletion of cellular ATP. The underlying mechanism involves interaction of LF with F1F0-complex gamma and beta subunits leading to increased ATPase activity in mitochondria. In support, mitochondrial DNA-depleted MH-S cells have decreased F1F0 ATPase activity due to the lack of F06 and F08 polypeptides and show increased resistance to LT. We conclude that ATP depletion is an important early event in LT-induced sudden cell death and its prevention increases survival of toxin-sensitive cells.

  5. Functional assay, expression of growth factors and proteins modulating bone-arrangement in human osteoblasts seeded on an anorganic bovine bone biomaterial

    OpenAIRE

    O Trubiani; Fulle, S.; T Traini; M Paludi; La Rovere, R.; M Orciani; S. Caputi; Piattelli, A.

    2010-01-01

    The basic aspects of bone tissue engineering include chemical composition and geometry of the scaffold design, because it is very important to improve not only cell attachment and growth but especially osteodifferentiation, bone tissue formation, and vascularization. Geistlich Bio-Oss® (GBO) is a xenograft consisting of deproteinized, sterilized bovine bone, chemically and physically identical to the mineral phase of human bone.In this study, we investigated the growth behaviour and the abili...

  6. Parkinson's disease and mitochondrial gene variations

    DEFF Research Database (Denmark)

    Andalib, Sasan; Vafaee, Manouchehr Seyedi; Gjedde, Albert

    2014-01-01

    Parkinson's disease (PD) is a common disorder of the central nervous system in the elderly. The pathogenesis of PD is a complex process, with genetics as an important contributing factor. This factor may stem from mitochondrial gene variations and mutations as well as from nuclear gene variations...... and mutations. More recently, a particular role of mitochondrial dysfunction has been suggested, arising from mitochondrial DNA variations or acquired mutations in PD pathogenesis. The present review summarizes and weighs the evidence in support of mitochondrial DNA (mtDNA) variations as important...

  7. Unlocking the bovine genome

    Science.gov (United States)

    The draft genome sequence of cattle (Bos taurus) has now been analyzed by the Bovine Genome Sequencing and Analysis Consortium and the Bovine HapMap Consortium, which together represent an extensive collaboration involving more than 300 scientists from 25 different countries. ...

  8. Fatores de virulência em linhagens de Escherichia coli isoladas de mastite bovina Virulence factors in Escherichia coli strains isolated from bovine mastitis

    Directory of Open Access Journals (Sweden)

    M.G. Ribeiro

    2006-10-01

    Full Text Available Avaliou-se a ocorrência de fatores de virulência e do sorotipo O157:H7 em 120 linhagens de Escherichia coli, isoladas de 80 casos de mastite clínica bovina e 40 de mastite subclínica. Verificou-se alfa-hemolisina em oito (6,7% linhagens, isoladas de cinco casos de mastite clínica e três de mastite subclínica e em nenhuma das estirpes detectou-se enteroemolisina. A presença de sideróforos foi encontrada em 11 (9,2% linhagens, sete de mastite clínica e quatro de subclínica. Em duas (1,7% estirpes isoladas de mastite subclínica, identificou-se enterotoxina STa. Observou-se efeito citopático em células vero compatível com a produção de verotoxina-VT em cinco (4,2% linhagens, duas de mastite clínica e três subclínicas. Em uma (0,8% linhagem isolada de mastite clínica, detectou-se efeito citopático compatível com o fator necrosante citotóxico. Nenhuma estirpe apresentou-se sorbitol-negativa no MacConkey-sorbitol, tampouco aglutinou com o sorotipo O157:H7. Os antimicrobianos mais efetivos foram polimixina B (97,5% e norfloxacina (95,8%. Observou-se multi-resistência a dois ou mais antimicrobianos em 24 (20% estirpes, principalmente com o uso de ampicilina e ceftiofur.The occurrence of different virulence factors and O157:H7 serotype investigation in 120 Escherichia coli strains isolated from clinical (80 cases and subclinical (40 cases bovine mastitis was evaluated. Alpha-haemolysin was detected in 8 (6.7% strains (5 clinical and 3 subclinical cases. None strain showed enterohaemolysin production. E. coli growth under iron restriction conditions (siderophores production was observed in 11 (9.2% strains (7 clinical and 4 subclinical cases. STa enterotoxin was detected in 2 (1.7% strains from subclinical cases. Cytotoxic effect in vero cells compatible with verotoxin-VT production was observed in 5 (4.2% strains (2 clinical and 3 subclinical cases. One strain (0.8% isolated from clinical mastitis showed cytophatic effect in vero

  9. Activation of bovine neutrophils by Brucella spp.

    Science.gov (United States)

    Keleher, Lauren L; Skyberg, Jerod A

    2016-09-01

    Brucellosis is a globally important zoonotic infectious disease caused by gram negative bacteria of the genus Brucella. While many species of Brucella exist, Brucella melitensis, Brucella abortus, and Brucella suis are the most common pathogens of humans and livestock. The virulence of Brucella is largely influenced by its ability to evade host factors, including phagocytic killing mechanisms, which are critical for the host response to infection. The aim of this study was to characterize the bovine neutrophil response to virulent Brucella spp. Here, we found that virulent strains of smooth B. abortus, B. melitensis, B. suis, and virulent, rough, strains of Brucella canis possess similar abilities to resist killing by resting, or IFN-γ-activated, bovine neutrophils. Bovine neutrophils responded to infection with a time-dependent oxidative burst that varied little between Brucella spp. Inhibition of TAK1, or SYK kinase blunted the oxidative burst of neutrophils in response to Brucella infection. Interestingly, Brucella spp. did not induce robust death of bovine neutrophils. These results indicate that bovine neutrophils respond similarly to virulent Brucella spp. In addition, virulent Brucella spp., including naturally rough strains of B. canis, have a conserved ability to resist killing by bovine neutrophils. PMID:27436438

  10. Camel and bovine chymosin

    DEFF Research Database (Denmark)

    Langholm Jensen, Jesper; Mølgaard, Anne; Navarro Poulsen, Jens Christian;

    2013-01-01

    Bovine and camel chymosin are aspartic peptidases that are used industrially in cheese production. They cleave the Phe105-Met106 bond of the milk protein κ-casein, releasing its predominantly negatively charged C-terminus, which leads to the separation of the milk into curds and whey. Despite...... having 85% sequence identity, camel chymosin shows a 70% higher milk-clotting activity than bovine chymosin towards bovine milk. The activities, structures, thermal stabilities and glycosylation patterns of bovine and camel chymosin obtained by fermentation in Aspergillus niger have been examined...... interactions arising from variation in the surface charges and the greater malleability both in domain movements and substrate binding contribute to the better milk-clotting activity of camel chymosin towards bovine milk....

  11. Purification of Active Respiratory Supercomplex from Bovine Heart Mitochondria Enables Functional Studies*

    OpenAIRE

    Shinzawa-Itoh, Kyoko; Shimomura, Harunobu; Yanagisawa, Sachiko; Shimada, Satoru; Takahashi, Ryoko; Oosaki, Marika; Ogura, Takashi; Tsukihara, Tomitake

    2015-01-01

    To understand the roles of mitochondrial respiratory chain supercomplexes, methods for consistently separating and preparing supercomplexes must be established. To this end, we solubilized supercomplexes from bovine heart mitochondria with digitonin and then replaced digitonin with amphipol (A8–35), an amphiphilic polymer. Afterward, supercomplexes were separated from other complexes by sucrose density gradient centrifugation. Twenty-six grams of bovine myocardium yielded 3.2 mg of amphipol-s...

  12. Transcription-independent role for human mitochondrial RNA polymerase in mitochondrial ribosome biogenesis

    OpenAIRE

    Surovtseva, Yulia V; Shadel, Gerald S.

    2013-01-01

    Human mitochondrial RNA polymerase, POLRMT, is required for mitochondrial DNA (mtDNA) transcription and forms initiation complexes with human mitochondrial transcription factor B2 (h-mtTFB2). However, POLRMT also interacts with the paralogue of h-mtTFB2, h-mtTFB1, which is a 12S ribosomal RNA methyltransferase required for small (28S) mitochondrial ribosome subunit assembly. Herein, we show that POLRMT associates with h-mtTFB1 in 28S mitochondrial ribosome complexes that are stable in the abs...

  13. Mitochondrial Evolution

    OpenAIRE

    Gray, Michael W

    2012-01-01

    Viewed through the lens of the genome it contains, the mitochondrion is of unquestioned bacterial ancestry, originating from within the bacterial phylum α-Proteobacteria (Alphaproteobacteria). Accordingly, the endosymbiont hypothesis—the idea that the mitochondrion evolved from a bacterial progenitor via symbiosis within an essentially eukaryotic host cell—has assumed the status of a theory. Yet mitochondrial genome evolution has taken radically different pathways in diverse eukaryotic lineag...

  14. Mitochondrial Epigenetics and Environmental Exposure.

    Science.gov (United States)

    Lambertini, Luca; Byun, Hyang-Min

    2016-09-01

    The rising toll of chronic and debilitating diseases brought about by the exposure to an ever expanding number of environmental pollutants and socio-economic factors is calling for action. The understanding of the molecular mechanisms behind the effects of environmental exposures can lead to the development of biomarkers that can support the public health fields of both early diagnosis and intervention to limit the burden of environmental diseases. The study of mitochondrial epigenetics carries high hopes to provide important biomarkers of exposure and disease. Mitochondria are in fact on the frontline of the cellular response to the environment. Modifications of the epigenetic factors regulating the mitochondrial activity are emerging as informative tools that can effectively report on the effects of the environment on the phenotype. Here, we will discuss the emerging field of mitochondrial epigenetics. This review describes the main epigenetic phenomena that modify the activity of the mitochondrial DNA including DNA methylation, long and short non-coding RNAs. We will discuss the unique pattern of mitochondrial DNA methylation, describe the challenges of correctly measuring it, and report on the existing studies that have analysed the correlation between environmental exposures and mitochondrial DNA methylation. Finally, we provide a brief account of the therapeutic approaches targeting mitochondria currently under consideration. PMID:27344144

  15. Temporal increase of platelet mitochondrial respiration is negatively associated with clinical outcome in patients with sepsis

    DEFF Research Database (Denmark)

    Sjövall, Fredrik; Morota, Saori; Hansson, Magnus J;

    2010-01-01

    Mitochondrial dysfunction has been suggested as a contributing factor to the pathogenesis of sepsis-induced multiple organ failure. Also, restoration of mitochondrial function, known as mitochondrial biogenesis, has been implicated as a key factor for the recovery of organ function in patients wi...... sepsis. Here we investigated temporal changes in platelet mitochondrial respiratory function in patients with sepsis during the first week after disease onset.......Mitochondrial dysfunction has been suggested as a contributing factor to the pathogenesis of sepsis-induced multiple organ failure. Also, restoration of mitochondrial function, known as mitochondrial biogenesis, has been implicated as a key factor for the recovery of organ function in patients with...

  16. What Is Mitochondrial DNA?

    Science.gov (United States)

    ... DNA What is mitochondrial DNA? What is mitochondrial DNA? Although most DNA is packaged in chromosomes within ... proteins. For more information about mitochondria and mitochondrial DNA: Molecular Expressions, a web site from the Florida ...

  17. Bovine Herpesvirus 4 infections and bovine mastitis

    NARCIS (Netherlands)

    Wellenberg, Gerardus Johannus

    2002-01-01

    Mastitis is an often occurring disease in dairy cattle with an enormous economic impact for milk producers worldwide. Despite intensive research, which is historically based on the detection of bacterial udder pathogens, still around 20-35% of clinical cases of bovine mastitis have an unknown aetiol

  18. Steroidogenic potential of lyophilized mitochondria from bovine adrenocortical tissue.

    OpenAIRE

    Prasad, V V; Mathur, C; Welch, M; Lieberman, S.

    1992-01-01

    When incubated with [3H]cholesterol, a bovine adrenocortical mitochondrial pellet obtained by centrifugation at 12,000 x g yielded, as expected, only the C21O2 metabolites progesterone and pregnenolone. However, the steroidogenic potential of the 12,000 x g pellet fraction was augmented significantly by lyophilization. After lyophilization, the 12,000 x g pellet converted the sterol into C19 androgens and corticosteroids, in addition to C21O2 pregnane derivatives. Leaching the lyophilized mit...

  19. Herd-level prevalence and associated risk factors for Toxoplasma gondii, Neospora caninum, Chlamydia abortus and bovine viral diarrhoea virus in commercial dairy and beef cattle in eastern, northern and northeastern China.

    Science.gov (United States)

    Sun, Wu-Wen; Meng, Qing-Feng; Cong, Wei; Shan, Xiao-Feng; Wang, Chun-Feng; Qian, Ai-Dong

    2015-11-01

    Although the seroprevalence of Toxoplasma gondii, Neospora caninum, Chlamydia abortus and bovine viral diarrhea virus infection in cattle have been reported in some areas in China, most of them were conducted with small number of cattle samples and very limited districts and neglected the assessment of herd management factors associated with herd-level prevalence of these pathogen infections. Thus, from September 2013 to December 2014, a large-scale seroprevalence study was conducted to determine the animal-level and herd-level seroprevalence and identify herd-level risk factors associated with these pathogen infections in 4487 cattle from 134 herds in five provinces (Heilongjiang, Jilin, Liaoning, Shandong, Hebei) and Inner Mongolia Autonomous Region of China. At animal level, the true prevalence of antibodies against T. gondii, N. caninum, C. abortus and bovine viral diarrhoea virus (BVDV) was 10.48, 17.14, 11.92 and 50.10%, respectively. At herd level, the true prevalence of antibodies against T. gondii, N. caninum, C. abortus and BVDV was 27.16, 29.10, 37.31 and 40.30%, respectively. Multivariate analysis of these characteristics showed that source of water and presence of felids were significantly associated with T. gondii infection in the studied cattle herds. Source of water was significantly associated with N. caninum infection in the studied cattle herds. While herd size and management system were significantly associated with BVDV infection in the studied cattle herds, this is the first report of herd-level prevalence and associated risk factors of T. gondii, N. caninum, C. abortus and BVDV infection in cattle in China. PMID:26231838

  20. Bovine Herpesvirus 4 infections and bovine mastitis

    OpenAIRE

    Wellenberg, Gerardus Johannus

    2002-01-01

    Mastitis is an often occurring disease in dairy cattle with an enormous economic impact for milk producers worldwide. Despite intensive research, which is historically based on the detection of bacterial udder pathogens, still around 20-35% of clinical cases of bovine mastitis have an unknown aetiology. Due to the high number of unknown causes of clinical mastitis, studies were undertaken to gain more insight into the role of viruses in this important disease. For the first time, we found tha...

  1. Increased intrinsic mitochondrial function in humans with mitochondrial haplogroup H

    DEFF Research Database (Denmark)

    Larsen, Steen; Díez-Sánchez, Carmen; Rabøl, Rasmus;

    2014-01-01

    determined their mitochondrial haplogroup, mitochondrial oxidative phosphorylation capacity (OXPHOS), mitochondrial content (citrate synthase (CS)) and VO2max. Intrinsic mitochondrial function is calculated as mitochondrial OXPHOS capacity divided by mitochondrial content (CS). Haplogroup H showed a 30......% higher intrinsic mitochondrial function compared with the other haplo group U. There was no relationship between haplogroups and VO2max. In skeletal muscle from men with mitochondrial haplogroup H, an increased intrinsic mitochondrial function is present....

  2. Stat3 binds to mitochondrial DNA and regulates mitochondrial gene expression in keratinocytes

    OpenAIRE

    Macias, Everardo; Rao, Dharanija; Carbajal, Steve; Kiguchi, Kaoru; DiGiovanni, John

    2014-01-01

    The nuclear transcription factor Stat3 has recently been reported to have a localized mitochondrial regulatory function. Current data suggest that mitochondrial Stat3 (mitoStat3) is necessary for maximal mitochondrial activity and for Ras-mediated transformation independent of Stat3 nuclear activity. We have previously shown that Stat3 plays a pivotal role in epithelial carcinogenesis. Therefore, the aim of the current study was to determine the role of mitoStat3 in epidermal keratinocytes. H...

  3. Mitochondrial Dysregulation in the Pathogenesis of Diabetes: Potential for Mitochondrial Biogenesis-Mediated Interventions

    OpenAIRE

    Anna-Maria Joseph; Joanisse, Denis R.; Baillot, Richard G.; Hood, David A.

    2012-01-01

    Muscle mitochondrial metabolism is a tightly controlled process that involves the coordination of signaling pathways and factors from both the nuclear and mitochondrial genomes. Perhaps the most important pathway regulating metabolism in muscle is mitochondrial biogenesis. In response to physiological stimuli such as exercise, retrograde signaling pathways are activated that allow crosstalk between the nucleus and mitochondria, upregulating hundreds of genes and leading to higher mitochondria...

  4. Hyperglycemia decreases mitochondrial function: The regulatory role of mitochondrial biogenesis

    International Nuclear Information System (INIS)

    Increased generation of reactive oxygen species (ROS) is implicated in 'glucose toxicity' in diabetes. However, little is known about the action of glucose on the expression of transcription factors in hepatocytes, especially those involved in mitochondrial DNA (mtDNA) replication and transcription. Since mitochondrial functional capacity is dynamically regulated, we hypothesized that stressful conditions of hyperglycemia induce adaptations in the transcriptional control of cellular energy metabolism, including inhibition of mitochondrial biogenesis and oxidative metabolism. Cell viability, mitochondrial respiration, ROS generation and oxidized proteins were determined in HepG2 cells cultured in the presence of either 5.5 mM (control) or 30 mM glucose (high glucose) for 48 h, 96 h and 7 days. Additionally, mtDNA abundance, plasminogen activator inhibitor-1 (PAI-1), mitochondrial transcription factor A (TFAM) and nuclear respiratory factor-1 (NRF-1) transcripts were evaluated by real time PCR. High glucose induced a progressive increase in ROS generation and accumulation of oxidized proteins, with no changes in cell viability. Increased expression of PAI-1 was observed as early as 96 h of exposure to high glucose. After 7 days in hyperglycemia, HepG2 cells exhibited inhibited uncoupled respiration and decreased MitoTracker Red fluorescence associated with a 25% decrease in mtDNA and 16% decrease in TFAM transcripts. These results indicate that glucose may regulate mtDNA copy number by modulating the transcriptional activity of TFAM in response to hyperglycemia-induced ROS production. The decrease of mtDNA content and inhibition of mitochondrial function may be pathogenic hallmarks in the altered metabolic status associated with diabetes

  5. Rol de la mitocondria y el estrés oxidativo en el bloqueo del desarrollo de embriones bovinos producidos in vitro Mitochondrial rol and oxidative stress in the developmental blockade of in vitro produced bovine embryos

    OpenAIRE

    AM Tarazona; M Olivera-Angel; YY Lenis

    2010-01-01

    Uno de los mayores obstáculos en la producción de embriones in vitro con fines de investigación básica, comerciales, o de conservación, es el detenimiento temprano del clivaje que ocurre de forma específica en una etapa del desarrollo. Para explicar este fenómeno se han postulado diferentes factores causales como: desórdenes en la cromatina, rearreglos del citoesqueleto, estrés oxidativo y daños mitocondriales. Esta última propuesta ha recibido gran atención, debido a que la mitocondria es fu...

  6. Glycyrrhizic acid prevents ultraviolet-B-induced photodamage: a role for mitogen-activated protein kinases, nuclear factor kappa B and mitochondrial apoptotic pathway.

    Science.gov (United States)

    Afnan, Quadri; Kaiser, Peerzada J; Rafiq, Rather A; Nazir, Lone A; Bhushan, Shashi; Bhardwaj, Subhash C; Sandhir, Rajat; Tasduq, Sheikh A

    2016-06-01

    Glycyrrhizic acid (GA), a natural triterpene, has received attention as an agent that has protective effects against chronic diseases including ultraviolet UV-B-induced skin photodamage. However, the mechanism of its protective effect remains elusive. Here, we used an immortalized human keratinocyte cell line (HaCaT) and a small animal model (BALB/c mice), to investigate the protective effects of GA against UV-B-induced oxidative damage, and additionally, delineated the molecular mechanisms involved in the UV-B-mediated inflammatory and apoptotic response. In the HaCaT cells, GA inhibited the UV-B-mediated increase in intracellular reactive oxygen species (ROS) and down-regulated the release of pro-inflammatory cytokines interleukin (IL)-1α, -1β and -6, tumor necrosis factor (TNF)-α and prostaglandin E2 (PGE2). GA inhibited UV-B-mediated activation of p38 and JNK MAP kinases, COX-2 expression and nuclear translocation of NF-κB. Furthermore, GA inhibited UV-B-mediated apoptosis by attenuating translocation of Bax from the cytosol to mitochondria, thus preserving mitochondrial integrity. GA-treated HaCaT cells also exhibited elevated antiapoptotic Bcl-2 protein, concomitant with reduced caspase-3 cleavage and decreased PARP-1 protein. In BALB/c mice, topical application of GA on dorsal skin exposed to UV-B irradiation protected against epidermal hyperplasia, lymphocyte infiltration and expression of several inflammatory proteins, p38, JNK, COX-2, NF-κB and ICAM-1. Based on the above findings, we conclude that GA protects against UV-B-mediated photodamage by inhibiting the signalling cascades triggered by oxidative stress, including MAPK/NF-κB activation, as well as apoptosis. Thus, GA has strong potential to be used as a therapeutic/cosmeceutical agent against photodamage. PMID:26836460

  7. Normal skin and hypertrophic scar fibroblasts differentially regulate collagen and fibronectin expression as well as mitochondrial membrane potential in response to basic fibroblast growth factor

    Directory of Open Access Journals (Sweden)

    Rui Song

    2011-05-01

    Full Text Available Basic fibroblast growth factor (bFGF regulates skin wound healing; however, the underlying mechanism remains to be defined. In the present study, we determined the effects of bFGF on the regulation of cell growth as well as collagen and fibronectin expression in fibroblasts from normal human skin and from hypertrophic scars. We then explored the involvement of mitochondria in mediating bFGF-inducedeffects on the fibroblasts. We isolated and cultivated normal and hypertrophic scar fibroblasts from tissue biopsies of patients who underwent plastic surgery for repairing hypertrophic scars. The fibroblasts were then treated with different concentrations of bFGF (ranging from 0.1 to 1000 ng/mL. The growth of hypertrophic scar fibroblasts became slower with selective inhibition of type I collagen production after exposure to bFGF. However, type III collagen expression was affected in both normal and hypertrophic scar fibroblasts. Moreover, fibronectin expression in the normal fibroblasts was up-regulated after bFGF treatment. bFGF (1000 ng/mL also induced mitochondrial depolarization in hypertrophic scar fibroblasts (P < 0.01. The cellular ATP level decreased in hypertrophic scar fibroblasts (P < 0.05, while it increased in the normal fibroblasts following treatment with bFGF (P < 0.01. These data suggest that bFGF has differential effects and mechanisms on fibroblasts of the normal skin and hypertrophic scars, indicating that bFGF may play a role in the early phase of skin wound healing and post-burn scar formation.

  8. Cartilage (Bovine and Shark) (PDQ)

    Science.gov (United States)

    ... Ask about Your Treatment Research Cartilage (Bovine and Shark) (PDQ®)–Patient Version Overview Go to Health Professional ... 8 ). Questions and Answers About Cartilage (Bovine and Shark) What is cartilage? Cartilage is a type of ...

  9. Factors influencing the immune response. II. Effects of the physical state of the antigen and of lymphoreticular cell proliferation on the response to intraperitoneal injection of bovine serum albumin in rabbits

    Science.gov (United States)

    Pinckard, R. N.; Weir, D. M.; McBride, W. H.

    1967-01-01

    The injection of Corynebacterium parvum at the same time as centrifuged bovine albumin has been shown not to have the adjuvant effect found when C. parvum is injected 6 days before. The implication of this is discussed and related to mechanisms of antibody synthesis. Whereas particulate alum-precipitated centrifuged bovine albumin was shown to be more effective than centrifuged bovine albumin in inducing primary antibody stimulation, the reverse was true for secondary stimulation by the intraperitoneal route. PMID:6035197

  10. Dynamic changes in the expression of relaxin-like factor (INSL3), cholesterol side-chain cleavage cytochrome p450, and 3beta-hydroxysteroid dehydrogenase in bovine ovarian follicles during growth and atresia.

    Science.gov (United States)

    Irving-Rodgers, Helen F; Bathgate, Ross A D; Ivell, Richard; Domagalski, Roger; Rodgers, Raymond J

    2002-04-01

    Relaxin-like factor (RLF) is a new member of the insulin-relaxin gene family known to be expressed in the ovarian follicular thecal cells of ruminants. To investigate the pattern of RLF expression in development and atresia of bovine follicles, antisera were raised in rats and rabbits to recombinantly expressed bovine pro-RLF and to chemically synthesized ovine RLF B chain, respectively. On dot blotting analysis, the rat antiserum bound to pro-RLF and less strongly to a synthetic mature ovine RLF lacking the C-domain, whereas the rabbit antiserum bound the mature form of ovine RLF. These antisera were used to immunostain bovine ovarian follicles of differing sizes and stages of health and atresia. 3beta-Hydroxysteroid dehydrogenase was colocalized with pro-RLF (n = 86 follicles), and cholesterol side-chain cleavage cytochrome P450 was localized in another section of many of the same follicles (n = 66). Not all follicles expressed pro-RLF in the theca interna, so the results are presented as the proportion of follicles expressing pro-RLF. Both mature and pro-RLF were immunolocalized to steroidogenic thecal cells of healthy follicles. As follicles enlarged to >5 mm, the proportion expressing pro-RLF declined (19/19 for 6 mm). Atresia was divided into antral (antral granulosa cells dying first) or basal (basal cells dying first) and further divided into early, middle, and late. For antral atresia of small follicles (2-5 mm), no decline in the proportion expressing pro-RLF was observed (early 6/6, middle 2/2) until the late stages (1/4). For basal atresia, which only occurs in small follicles (2-5 mm), the proportion expressing pro-RLF declined in the middle (2/5) and late (0/8) stages. In larger follicles (>6 to membrana granulosa was observed. We conclude that the expression of pro-RLF in the theca interna is switched off as follicles enlarge or enter atresia, whereas the expression of steroidogenic enzymes is maintained in the theca interna. PMID:11906911

  11. Selenium supplementation induces mitochondrial biogenesis in trophoblasts

    Czech Academy of Sciences Publication Activity Database

    Khera, A.; Dong, L. F.; Holland, O.; Vanderlelie, J.; Pasdar, E.A.; Neužil, Jiří; Perkins, A.V.

    2015-01-01

    Roč. 36, č. 8 (2015), s. 363-369. ISSN 0143-4004 Institutional support: RVO:86652036 Keywords : Selenium * Reactive oxygen species * Mitochondrial biogenesis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.710, year: 2014

  12. Biogenesis of the mitochondrial phosphate carrier

    OpenAIRE

    Zara, Vincenzo; Rassow, Joachim; Wachter, Elmar; Tropschug, Maximilian; Palmieri, Ferdinando; Neupert, Walter; Pfanner, Nikolaus

    1991-01-01

    The mitochondrial phosphate carrier (PiC) is a member of the family of inner-membrane carrier proteins which are generally synthesized without a cleavable presequence. Surprisingly, the cDNA sequences of bovine and rat PiC suggested the existence of an amino-terminal extension sequence in the precursor of PiC. By expressing PiC in vitro, we found that PiC is indeed synthesized as a larger precursor. This precursor was imported and proteolytically processed by mitochondria, whereby the correct...

  13. Distribution of mitochondrial nucleoids upon mitochondrial network fragmentation and network reintegration in HEPG2 cells

    Czech Academy of Sciences Publication Activity Database

    Tauber, Jan; Dlasková, Andrea; Šantorová, Jitka; Smolková, Katarína; Alán, Lukáš; Špaček, Tomáš; Plecitá-Hlavatá, Lydie; Ježek, Petr

    2013-01-01

    Roč. 45, č. 3 (2013), s. 593-603. ISSN 1357-2725 R&D Projects: GA ČR(CZ) GAP302/10/0346; GA ČR(CZ) GPP304/10/P204; GA ČR(CZ) GAP305/12/1247 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 Keywords : mitochondrial DNA nucleoids * mitochondrial fission * mitochondrial network fragmentation * mitochondrial network reintegration Subject RIV: ED - Physiology Impact factor: 4.240, year: 2013

  14. Improvement of bovine in vitro embryo production by vitamin K₂ supplementation.

    Science.gov (United States)

    Baldoceda-Baldeon, Luis Manuel; Gagné, Dominic; Vigneault, Christian; Blondin, Patrick; Robert, Claude

    2014-11-01

    Mitochondria play an important role during early development in mammalian embryos. It has been shown that properly controlled follicular preparation increases the likelihood of in-vitro-produced bovine embryos reaching the blastocyst stage and that competent embryos exhibit heightened expression of genes associated with mitochondrial function. We hypothesized that apparently incompetent embryos could be rescued by restoring mitochondrial function. It has been shown that vitamin K2 (a membrane-bound electron carrier similar to ubiquinone) can restore mitochondrial dysfunction in eukaryotic cells. The aim of this study was therefore to investigate the effects of vitamin K2 on bovine embryonic development in vitro. The vitamin was found most effective when added 72 h after fertilization. It produced a significant (Pvitamin K2. PMID:25161289

  15. Mitochondrial disease and epilepsy.

    Science.gov (United States)

    Rahman, Shamima

    2012-05-01

    Mitochondrial respiratory chain disorders are relatively common inborn errors of energy metabolism, with a combined prevalence of one in 5000. These disorders typically affect tissues with high energy requirements, and cerebral involvement occurs frequently in childhood, often manifesting in seizures. Mitochondrial diseases are genetically heterogeneous; to date, mutations have been reported in all 37 mitochondrially encoded genes and more than 80 nuclear genes. The major genetic causes of mitochondrial epilepsy are mitochondrial DNA mutations (including those typically associated with the mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes [MELAS] and myoclonic epilepsy with ragged red fibres [MERRF] syndromes); mutations in POLG (classically associated with Alpers syndrome but also presenting as the mitochondrial recessive ataxia syndrome [MIRAS], spinocerebellar ataxia with epilepsy [SCAE], and myoclonus, epilepsy, myopathy, sensory ataxia [MEMSA] syndromes in older individuals) and other disorders of mitochondrial DNA maintenance; complex I deficiency; disorders of coenzyme Q(10) biosynthesis; and disorders of mitochondrial translation such as RARS2 mutations. It is not clear why some genetic defects, but not others, are particularly associated with seizures. Epilepsy may be the presenting feature of mitochondrial disease but is often part of a multisystem clinical presentation. Mitochondrial epilepsy may be very difficult to manage, and is often a poor prognostic feature. At present there are no curative treatments for mitochondrial disease. Individuals with mitochondrial epilepsy are frequently prescribed multiple anticonvulsants, and the role of vitamins and other nutritional supplements and the ketogenic diet remain unproven. PMID:22283595

  16. Bovine milk exosome proteome

    Science.gov (United States)

    Exosomes are 40-100 nm membrane vesicles of endocytic origin and are found in blood, urine, amniotic fluid, bronchoalveolar lavage (BAL) fluid, as well as human and bovine milk. Exosomes are extracellular organelles important in intracellular communication/signaling, immune function, and biomarkers ...

  17. Bovine Spongiform Encephalopathy

    Science.gov (United States)

    Bovine spongiform encephalopathy (BSE), also referred to as “mad cow disease” is a chronic, non-febrile, neuro-degenerative disease affecting the central nervous system. The transmissible spongiform encephalopathies (TSEs) of domestic animals, of which BSE is a member includes scrapie of sheep...

  18. BOVINE VIRAL DIARRHEA VIRUSES

    Science.gov (United States)

    Bovine viral diarrhea virus (BVDV) is an umbrella term for two species of viruses, BVDV1 and BVDV2, within the Pestivirus genus of the Flavivirus family. BVDV viruses are further subclassified as cytopathic and noncytopathic based on their activity in cultured epithelial cells. Noncytopathic BVDV p...

  19. Genotyping bovine coronaviruses.

    Science.gov (United States)

    Bovine coronaviruses (BoCV) are enveloped, single-stranded, positive-sense RNA viruses of the Coronaviridae family. Infection is associated with enteritis and pneumonia in calves and Winter Dysentery in adult cattle. Strains, isolated more than 50 years ago, are used in vaccines and as laboratory ...

  20. Epidemiology, pathology, immunology and diagnosis of bovine farcy: a review.

    Science.gov (United States)

    Hamid, Mohamed E

    2012-06-01

    Bovine farcy (which is caused by Mycobacterium farcinogenes and Mycobacterium senegalense) is a chronic suppurative granulomatous inflammation of the skin and lymphatics of cattle and is seen mostly in sub-Saharan Africa. It is not yet certain whether Nocardia farcinica causes cutaneous nocardiosis (farcy) in animals that mimics bovine farcy. Epidemiological data have steadily reported finding bovine farcy in adult cattle of the transhumance pastoralist tribes of the Sahel and the Sudanian savannah zones. M. farcinogenes and or M. senegalense do not affect other domestic or non-domestic animals; it is not known whether these bacteria are zoonotic. The disease--once widespread in many regions--has disappeared from some countries historically known to have it. Reports of bovine farcy prevalence seem to be linked to the existence of survey initiatives by governments and diagnostic capabilities in each country. Farcy causes economic loss due to damaged hides and also is a public-health burden (because the lymphadenitis due to farcy resembles the lesions of bovine tuberculosis in carcasses and the meat is considered inappropriate for human consumption). The current literature is deficient in establishing definitely the prevalence, transmission patterns, and risk factors of bovine farcy. Ixodid ticks transmit other skin diseases (such as dermatophilosis) and might play a role in bovine farcy (given the similarity in the bio-physiology and geographic distribution of the disease). In addition, the tick-resistance of cattle breeds such as the N'Dama, Fulani or the Nilotic might explain their resistance to bovine farcy. Apart from the judicious use of conventional smear-and-culture methods, few diagnostic tests have been developed; the molecular and serological tests have not been evaluated for reproducibility and accuracy. This review points out aspects of bovine farcy that need further research and updates available data on the prevalence, distribution, risk factors

  1. Application of Functional Genomics for Bovine Respiratory Disease Diagnostics

    OpenAIRE

    Rai, Aswathy N.; William B. Epperson; Bindu Nanduri

    2015-01-01

    Bovine respiratory disease (BRD) is the most common economically important disease affecting cattle. For developing accurate diagnostics that can predict disease susceptibility/resistance and stratification, it is necessary to identify the molecular mechanisms that underlie BRD. To study the complex interactions among the bovine host and the multitude of viral and bacterial pathogens, as well as the environmental factors associated with BRD etiology, genome-scale high-throughput functional ge...

  2. Epidemiology of Bovine Mastitis in Cows of Dharwad District

    OpenAIRE

    Mahantesh M. Kurjogi; Kaliwal, Basappa B

    2014-01-01

    Bovine mastitis is very common in cows of both developed and developing countries. The prevalence of clinical and subclinical mastitis (SCM) varies from region to region. Hence, the present study was carried out to determine the prevalence of mastitis using three diagnostic tests by considering different risk factors like age, lactation, breed, season, quarters, and herd. The results showed that surf field mastitis test (SFMT) is the most sensitive test for diagnosis of bovine mastitis, the o...

  3. VEGF stimulation of mitochondrial biogenesis: requirement of AKT3 kinase

    OpenAIRE

    Wright, Gary L.; Maroulakou, Ioanna G.; Eldridge, Juanita; Liby, Tiera L.; Sridharan, Vijayalakshmi; Tsichlis, Philip N.; Muise-Helmericks, Robin C.

    2008-01-01

    The growth factor, vascular endothelial growth factor (VEGF), induces angiogenesis and promotes endothelial cell (EC) proliferation. Affymetrix gene array analyses show that VEGF stimulates the expression of a cluster of nuclear-encoded mitochondrial genes, suggesting a role for VEGF in the regulation of mitochondrial biogenesis. We show that the serine threonine kinase Akt3 specifically links VEGF to mitochondrial biogenesis. A direct comparison of Akt1 vs. Akt3 gene silencing was performed ...

  4. Mitochondrial RNA granules: Compartmentalizing mitochondrial gene expression.

    Science.gov (United States)

    Jourdain, Alexis A; Boehm, Erik; Maundrell, Kinsey; Martinou, Jean-Claude

    2016-03-14

    In mitochondria, DNA replication, gene expression, and RNA degradation machineries coexist within a common nondelimited space, raising the question of how functional compartmentalization of gene expression is achieved. Here, we discuss the recently characterized "mitochondrial RNA granules," mitochondrial subdomains with an emerging role in the regulation of gene expression. PMID:26953349

  5. Detection and Characterisation of Lactobacillus spp. in the Bovine Uterus and Their Influence on Bovine Endometrial Epithelial Cells In Vitro

    OpenAIRE

    Gärtner, Martina A.; Bondzio, Angelika; Braun, Nicole; Jung, Markus; Einspanier, Ralf; Gabler, Christoph

    2015-01-01

    Bacterial infections and inflammation of the uterus are common in dairy cattle after parturition. In particular, pathogenic bacteria that cause endometritis have been the focus of research in cattle reproduction in the last ten years. The aim of the present study was to identify commensal lactobacilli in the bovine uterus and to examine their influence on the synthesis of pro-inflammatory factors in bovine endometrial epithelial cells in vitro. Lactobacillus species were isolated from healthy...

  6. Melatonin in Mitochondrial Dysfunction and Related Disorders

    Directory of Open Access Journals (Sweden)

    Venkatramanujam Srinivasan

    2011-01-01

    Full Text Available Mitochondrial dysfunction is considered one of the major causative factors in the aging process, ischemia/reperfusion (I/R, septic shock, and neurodegenerative disorders like Parkinson's disease (PD, Alzheimer's disease (AD, and Huntington's disease (HD. Increased free radical generation, enhanced mitochondrial inducible nitric oxide (NO synthase activity, enhanced NO production, decreased respiratory complex activity, impaired electron transport system, and opening of mitochondrial permeability transition pore all have been suggested as factors responsible for impaired mitochondrial function. Melatonin, the major hormone of the pineal gland, also acts as an antioxidant and as a regulator of mitochondrial bioenergetic function. Both in vitro and in vivo, melatonin was effective for preventing oxidative stress/nitrosative stress-induced mitochondrial dysfunction seen in experimental models of PD, AD, and HD. In addition, melatonin is known to retard aging and to inhibit the lethal effects of septic shock or I/R lesions by maintaining respiratory complex activities, electron transport chain, and ATP production in mitochondria. Melatonin is selectively taken up by mitochondrial membranes, a function not shared by other antioxidants. Melatonin has thus emerged as a major potential therapeutic tool for treating neurodegenerative disorders such as PD or AD, and for preventing the lethal effects of septic shock or I/R.

  7. Recombinant human growth hormone and insulin-like growth factor-1 do not affect mitochondrial derived highly reactive oxygen species production in peripheral blood mononuclear cells under conditions of substrate saturation in-vitro

    OpenAIRE

    Keane, James; Tajouri, Lotti; Gray, Bon

    2016-01-01

    Background The purpose of this study was to investigate the mitochondrial effects exerted by physiological and supra-physiological concentrations of recombinant human growth hormone (rhGH) and recombinant insulin-like growth factor-1 (rIGF-1) under conditions of substrate saturation in peripheral blood mononuclear cells (PBMCs). Methods PBMCs from healthy male subjects were treated with either rhGH, at concentrations of 0.5, 5 and 50 μg/L, or rIGF-1 at concentrations of 100, 300 and 500 μg/L ...

  8. Strokes in mitochondrial diseases

    Directory of Open Access Journals (Sweden)

    N V Pizova

    2012-06-01

    Full Text Available It is suggested that mitochondrial diseases might be identified in 22—33% of cryptogenic stroke cases in young subjects. The incidence of mitochondrial disorders in patients with stroke is unknown; it is 0.8 to 7.2% according to the data of some authors. The paper gives data on the prevalence, pathogenesis, and clinical manifestations of mitochondrial diseases, such as mitochondrial encephalopathy, lactic acidosis, and stroke-like syndrome (MELAS and insulin-like episodes; myoclonic epilepsy and ragged-red fibers (MERRF syndrome, and Kearns-Sayre syndrome (sporadic multisystem mitochondrial pathology.

  9. Identification of sequence polymorphism in the D-Loop region of mitochondrial DNA as a risk factor for hepatocellular carcinoma with distinct etiology

    Directory of Open Access Journals (Sweden)

    Zhang Ruixing

    2010-09-01

    Full Text Available Abstract Background Hepatocellular carcinoma (HCC is frequently preceded by hepatitis virus infection or alcohol abuse. Genetic backgrounds may increase susceptibility to HCC from these exposures. Methods Mitochondrial DNA (mtDNA of peripheral blood, tumor, and/or adjacent non-tumor tissue from 49 hepatitis B virus-related and 11 alcohol-related HCC patients, and from 38 controls without HCC were examined for single nucleotide polymorphisms (SNPs and mutations in the D-Loop region. Results Single nucleotide polymorphisms (SNPs in the D-loop region of mt DNA were examined in HCC patients. Individual SNPs, namely the 16266C/T, 16293A/G, 16299A/G, 16303G/A, 242C/T, 368A/G, and 462C/T minor alleles, were associated with increased risk for alcohol- HCC, and the 523A/del was associated with increased risks of both HCC types. The mitochondrial haplotypes under the M haplogroup with a defining 489C polymorphism were detected in 27 (55.1% of HBV-HCCand 8 (72.7% of alcohol- HCC patients, and in 15 (39.5% of controls. Frequencies of the 489T/152T, 489T/523A, and 489T/525C haplotypes were significantly reduced in HBV-HCC patients compared with controls. In contrast, the haplotypes of 489C with 152T, 249A, 309C, 523Del, or 525Del associated significantly with increase of alcohol-HCC risk. Mutations in the D-Loop region were detected in 5 adjacent non-tumor tissues and increased in cancer stage (21 of 49 HBV-HCC and 4 of 11 alcohol- HCC, p Conclusions In sum, mitochondrial haplotypes may differentially predispose patients to HBV-HCC and alcohol-HCC. Mutations of the mitochondrial D-Loop sequence may relate to HCC development.

  10. Antihelmintic Resistance For Gastrointestinal Bovine Nematodes

    OpenAIRE

    Patricia Torres Vásquez; Germán Alonso Prada Sanmiguel; Dildo Márquez Lara

    2007-01-01

    The gastrointestinal nematodes (GIN), in domestic animals, especially in bovines are a very important factor that affects their productivity, because cattle production systems have intervened in the relationship between gastrointestinal parasites (PGI) and the host, breaking therefore the ecological balance between them. In many opportunities the development of parasitic populations have been favored or a parasitic population have been led to extinction, it has made that these populations exp...

  11. Le complexe respiratoire bovin

    OpenAIRE

    Lekeux, Pierre

    1996-01-01

    Les maladies respiratoires des bovins sont, partout dans le monde, la cause principale de mortalité chez les jeunes bovins. Plusieurs facteurs favorisent l'apparition de ce syndrome : des facteurs propres à l'animal, comme l'âge, l'état général et le statut immunitaire; d'autres relatifs à l'environnement, comme les stress engendrés par les changements de régime alimentaire, de température et d'humidité; d'autres encore, liés à la présence d'agents infectieux, comme des bactéries, des virus e...

  12. Genetics of bovine vaccination

    OpenAIRE

    Leach, Richard Jonathan

    2011-01-01

    Infectious disease is an important issue for animal breeders, farmers and governments. Solutions to control infectious disease are needed and research focused on the genetic loci determining variation in immune-related traits has the potential to deliver solutions. The primary aim of this thesis is to discover regions of the bovine genome which influence the immune response post immunisation. To accomplish this two types of immunising agents, a Foot-and-Mouth Disease Virus (FMD...

  13. Vitrification of Bovine Oocytes

    OpenAIRE

    Anchamparuthy, Vahida Muhammed Ismail

    2007-01-01

    Cryopreservation of oocytes is a challenge. Studies were conducted to vitrify mouse zygotes and cumulus-intact bovine oocytes from follicles of different diameters, small (â ¤ 4 mm) and medium (4 to 10 mm), using nylon mesh. The specific goals were to assess changes in apoptotic gene expression (Fas-FasL, Bax, Bcl-2, and survivin) in conjunction with terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and caspase assays. Mouse zygotes were exposed to increasing concentrations...

  14. Unusual mitochondrial genome structures throughout the Euglenozoa

    Czech Academy of Sciences Publication Activity Database

    Roy, J.; Faktorová, Drahomíra; Lukeš, Julius; Burger, G.

    2007-01-01

    Roč. 158, č. 3 (2007), s. 385-396. ISSN 1434-4610 R&D Projects: GA ČR GA204/06/1558; GA MŠk 2B06129 Grant ostatní: Canadian Institutes of Health Research(CA) MOP-79309 Institutional research plan: CEZ:AV0Z60220518 Keywords : euglenozoan protists * mitochondrial chromosomes * mitochondrial ultrastructure Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.102, year: 2007

  15. Mitochondrial Deficiency Is Associated With Insulin Resistance

    OpenAIRE

    Goodpaster, Bret H.

    2013-01-01

    The specific cellular underpinnings or mechanisms of insulin resistance (IR) are not clear. Here I present evidence to support a causal association between mitochondrial energetics and IR. A large body of literature indicates that mitochondrial capacity for oxidative metabolism is lower in human obesity and type 2 diabetes. Whether or not mitochondria play a causal role in IR is hotly debated. First, IR can be caused by many factors, many of which may or may not involve mitochondria. These in...

  16. Cerebral energy metabolism during induced mitochondrial dysfunction

    DEFF Research Database (Denmark)

    Nielsen, T H; Bindslev, TT; Pedersen, S M;

    2013-01-01

    In patients with traumatic brain injury as well as stroke, impaired cerebral oxidative energy metabolism may be an important factor contributing to the ultimate degree of tissue damage. We hypothesize that mitochondrial dysfunction can be diagnosed bedside by comparing the simultaneous changes in...... brain tissue oxygen tension (PbtO(2)) and cerebral cytoplasmatic redox state. The study describes cerebral energy metabolism during mitochondrial dysfunction induced by sevoflurane in piglets....

  17. MITOCHONDRIAL DYSFUNCTION

    Czech Academy of Sciences Publication Activity Database

    Jandová, Anna; Pokorný, Jiří; Kobilková, J.; Trojan, S.; Nedbalová, M.; Dohnalová, A.; Čoček, A.; Mašata, J.; Holaj, J.; Tvrznická, E.; Zvolský, P.; Dvořáková, M.; Cifra, Michal

    2009-01-01

    Roč. 19, č. 4 (2009), s. 379-391. ISSN 1210-0552 Institutional research plan: CEZ:AV0Z20670512 Keywords : Biophysics * Cancer * Electromagnetic fields Subject RIV: JA - Electronics ; Optoelectronics, Electrical Engineering Impact factor: 0.475, year: 2009

  18. Meta-Analysis of mitochondrial DNA reveals several population bottlenecks during worldwide migrations of cattle

    NARCIS (Netherlands)

    Lenstra, Johannes A.; Ajmone-Marsan, Paolo; Beja-Pereira, Albano; Bollongino, Ruth; Bradley, Daniel G.; Colli, Licia; De Gaetano, Anna; Edwards, Ceiridwen J.; Felius, Marleen; Ferretti, Luca; Ginja, Catarina; Hristov, Peter; Kantanen, Juha; Lirón, Juan Pedro; Magee, David A.; Negrini, Riccardo; Radoslavov, Georgi A.

    2014-01-01

    Several studies have investigated the differentiation of mitochondrial DNA in Eurasian, African and American cattle as well as archaeological bovine material. A global survey of these studies shows that haplogroup distributions are more stable in time than in space. All major migrations of cattle ha

  19. Natural Compounds Modulating Mitochondrial Functions

    Directory of Open Access Journals (Sweden)

    Lara Gibellini

    2015-01-01

    Full Text Available Mitochondria are organelles responsible for several crucial cell functions, including respiration, oxidative phosphorylation, and regulation of apoptosis; they are also the main intracellular source of reactive oxygen species (ROS. In the last years, a particular interest has been devoted to studying the effects on mitochondria of natural compounds of vegetal origin, quercetin (Qu, resveratrol (RSV, and curcumin (Cur being the most studied molecules. All these natural compounds modulate mitochondrial functions by inhibiting organelle enzymes or metabolic pathways (such as oxidative phosphorylation, by altering the production of mitochondrial ROS and by modulating the activity of transcription factors which regulate the expression of mitochondrial proteins. While Qu displays both pro- and antioxidant activities, RSV and Cur are strong antioxidant, as they efficiently scavenge mitochondrial ROS and upregulate antioxidant transcriptional programmes in cells. All the three compounds display a proapoptotic activity, mediated by the capability to directly cause the release of cytochrome c from mitochondria or indirectly by upregulating the expression of proapoptotic proteins of Bcl-2 family and downregulating antiapoptotic proteins. Interestingly, these effects are particularly evident on proliferating cancer cells and can have important therapeutic implications.

  20. Life without mitochondrial DNA : studies of transgenic mice

    OpenAIRE

    Wang, Jianming

    2000-01-01

    Mitochondrial DNA (mtDNA) is a closed circular DNA genome that resides in the mitochondrial network. Mutations of mtDNA cause spontaneous and hereditary disorders known as mitochondrial diseases. Mitochondrial transcription factor A (Tfam) is a key factor for transcription of mtDNA in vitro. We disrupted the mouse Tfam gene by using the cre-loxP recombination system to study the in vivo roles of Tfam. This thesis focuses on the analyses of germline knockout mice and the c...

  1. Unravelling the mechanisms regulating muscle mitochondrial biogenesis.

    Science.gov (United States)

    Hood, David A; Tryon, Liam D; Carter, Heather N; Kim, Yuho; Chen, Chris C W

    2016-08-01

    Skeletal muscle is a tissue with a low mitochondrial content under basal conditions, but it is responsive to acute increases in contractile activity patterns (i.e. exercise) which initiate the signalling of a compensatory response, leading to the biogenesis of mitochondria and improved organelle function. Exercise also promotes the degradation of poorly functioning mitochondria (i.e. mitophagy), thereby accelerating mitochondrial turnover, and preserving a pool of healthy organelles. In contrast, muscle disuse, as well as the aging process, are associated with reduced mitochondrial quality and quantity in muscle. This has strong negative implications for whole-body metabolic health and the preservation of muscle mass. A number of traditional, as well as novel regulatory pathways exist in muscle that control both biogenesis and mitophagy. Interestingly, although the ablation of single regulatory transcription factors within these pathways often leads to a reduction in the basal mitochondrial content of muscle, this can invariably be overcome with exercise, signifying that exercise activates a multitude of pathways which can respond to restore mitochondrial health. This knowledge, along with growing realization that pharmacological agents can also promote mitochondrial health independently of exercise, leads to an optimistic outlook in which the maintenance of mitochondrial and whole-body metabolic health can be achieved by taking advantage of the broad benefits of exercise, along with the potential specificity of drug action. PMID:27470593

  2. Unraveling biochemical pathways affected by mitochondrial dysfunctions using metabolomic approaches.

    Science.gov (United States)

    Demine, Stéphane; Reddy, Nagabushana; Renard, Patricia; Raes, Martine; Arnould, Thierry

    2014-01-01

    Mitochondrial dysfunction(s) (MDs) can be defined as alterations in the mitochondria, including mitochondrial uncoupling, mitochondrial depolarization, inhibition of the mitochondrial respiratory chain, mitochondrial network fragmentation, mitochondrial or nuclear DNA mutations and the mitochondrial accumulation of protein aggregates. All these MDs are known to alter the capacity of ATP production and are observed in several pathological states/diseases, including cancer, obesity, muscle and neurological disorders. The induction of MDs can also alter the secretion of several metabolites, reactive oxygen species production and modify several cell-signalling pathways to resolve the mitochondrial dysfunction or ultimately trigger cell death. Many metabolites, such as fatty acids and derived compounds, could be secreted into the blood stream by cells suffering from mitochondrial alterations. In this review, we summarize how a mitochondrial uncoupling can modify metabolites, the signalling pathways and transcription factors involved in this process. We describe how to identify the causes or consequences of mitochondrial dysfunction using metabolomics (liquid and gas chromatography associated with mass spectrometry analysis, NMR spectroscopy) in the obesity and insulin resistance thematic. PMID:25257998

  3. Unraveling Biochemical Pathways Affected by Mitochondrial Dysfunctions Using Metabolomic Approaches

    Directory of Open Access Journals (Sweden)

    Stéphane Demine

    2014-09-01

    Full Text Available Mitochondrial dysfunction(s (MDs can be defined as alterations in the mitochondria, including mitochondrial uncoupling, mitochondrial depolarization, inhibition of the mitochondrial respiratory chain, mitochondrial network fragmentation, mitochondrial or nuclear DNA mutations and the mitochondrial accumulation of protein aggregates. All these MDs are known to alter the capacity of ATP production and are observed in several pathological states/diseases, including cancer, obesity, muscle and neurological disorders. The induction of MDs can also alter the secretion of several metabolites, reactive oxygen species production and modify several cell-signalling pathways to resolve the mitochondrial dysfunction or ultimately trigger cell death. Many metabolites, such as fatty acids and derived compounds, could be secreted into the blood stream by cells suffering from mitochondrial alterations. In this review, we summarize how a mitochondrial uncoupling can modify metabolites, the signalling pathways and transcription factors involved in this process. We describe how to identify the causes or consequences of mitochondrial dysfunction using metabolomics (liquid and gas chromatography associated with mass spectrometry analysis, NMR spectroscopy in the obesity and insulin resistance thematic.

  4. Bovine reproduction in tropical environment

    International Nuclear Information System (INIS)

    In this document it has met relating data to the reproduction of bovine and their handling for the man that it can serve as norms to judge reproductive efficiency but always view in the aspect of the nutritious, climatic circumstances and of handling under which met. Under the previous description one can say that the fertility is the resultant of the interaction among the inheritance, the means and the handling, they vary in particular for each region and property. The fertility can be good, regulate or bad in the measure in that the factors that intervene. The environmental effect on the reproductive processes of the cow represents 80 percent of the variation factors and they include climate, effect of the light, effect of the temperature, effect of the nutritious contribution, effect of psychological factors: the loss of the tendency to the seasonal reproduction is in fact an answer from the animals to its association with the man. The influence of the environment and the feeding of the animals are more intense in the females than in the males, being evidenced that the reproduction control is under the influence hormonal joint with the nutrition. An appropriate nutrition is prerequisite for the beginning of the sexual maturation with an appropriate weight and corporal condition. It is also described the effect and the relationship of the energy contribution about the fertility, the restart of the ovarian activity, its cause of the continuation of the interval childbirth-conception, silent ovulation, organic ancestry and interval among childbirths

  5. Mitochondrial benzodiazepine receptors regulate steroid biosynthesis

    Energy Technology Data Exchange (ETDEWEB)

    Mukhin, A.G.; Papadopoulos, V.; Costa, E.; Krueger, K.E. (Georgetown Univ. School of Medicine, Washington, DC (USA))

    1989-12-01

    Recent observations on the steroid synthetic capability within the brain open the possibility that benzodiazepines may influence steroid synthesis in nervous tissue through interactions with peripheral-type benzodiazepine recognition sites, which are highly expressed in steroidogenic cells and associated with the outer mitochondrial membrane. To examine this possibility nine molecules that exhibit a greater than 10,000-fold difference in their affinities for peripheral-type benzodiazepine binding sites were tested for their effects on a well-established steroidogenic model system, the Y-1 mouse adrenal tumor cell line. 4{prime}-Chlorodiazepam, PK 11195, and PK 14067 stimulated steroid production by 2-fold in Y-1 cells, whereas diazepam, flunitrazepam, zolpidem, and PK 14068 displayed a lower (1.2- to 1.5-fold) maximal stimulation. In contrast, clonazepam and flumazenil did not stimulate steroid synthesis. The potencies of these compounds to inhibit {sup 3}H-labeled PK 11195 binding to peripheral-type benzodiazepine recognition sites correlated with their potencies to stimulate steroid production. Similar findings were observed in bovine and rat adrenocortical cell preparations. These results suggest that ligands of the peripheral-type benzodiazepine recognition site acting on this mitochondrial receptor can enhance steroid production. This action may contribute specificity to the pharmacological profile of drugs preferentially acting on the benzodiazepine recognition site associated with the outer membrane of certain mitochondrial populations.

  6. Mitochondrial benzodiazepine receptors regulate steroid biosynthesis

    International Nuclear Information System (INIS)

    Recent observations on the steroid synthetic capability within the brain open the possibility that benzodiazepines may influence steroid synthesis in nervous tissue through interactions with peripheral-type benzodiazepine recognition sites, which are highly expressed in steroidogenic cells and associated with the outer mitochondrial membrane. To examine this possibility nine molecules that exhibit a greater than 10,000-fold difference in their affinities for peripheral-type benzodiazepine binding sites were tested for their effects on a well-established steroidogenic model system, the Y-1 mouse adrenal tumor cell line. 4'-Chlorodiazepam, PK 11195, and PK 14067 stimulated steroid production by 2-fold in Y-1 cells, whereas diazepam, flunitrazepam, zolpidem, and PK 14068 displayed a lower (1.2- to 1.5-fold) maximal stimulation. In contrast, clonazepam and flumazenil did not stimulate steroid synthesis. The potencies of these compounds to inhibit 3H-labeled PK 11195 binding to peripheral-type benzodiazepine recognition sites correlated with their potencies to stimulate steroid production. Similar findings were observed in bovine and rat adrenocortical cell preparations. These results suggest that ligands of the peripheral-type benzodiazepine recognition site acting on this mitochondrial receptor can enhance steroid production. This action may contribute specificity to the pharmacological profile of drugs preferentially acting on the benzodiazepine recognition site associated with the outer membrane of certain mitochondrial populations

  7. The mitochondrial RNA polymerase contributes critically to promoter specificity in mammalian cells

    OpenAIRE

    Gaspari, Martina; Falkenberg, Maria; Larsson, Nils-Göran; Gustafsson, Claes M.

    2004-01-01

    Initiation of transcription in mammalian mitochondria depends on three proteins: mitochondrial RNA polymerase (POLRMT), mitochondrial transcription factor A (TFAM) and mitochondrial transcription factor B2 (TFB2M). We show here that the recombinant mouse and human transcription machineries are unable to initiate transcription in vitro from the heterologous light-strand promoter (LSP) of mitochondrial DNA. This species specificity is dependent on the interaction of TFAM and POLRMT with specifi...

  8. Altered Mitochondrial Dynamics and TBI Pathophysiology.

    Science.gov (United States)

    Fischer, Tara D; Hylin, Michael J; Zhao, Jing; Moore, Anthony N; Waxham, M Neal; Dash, Pramod K

    2016-01-01

    Mitochondrial function is intimately linked to cellular survival, growth, and death. Mitochondria not only generate ATP from oxidative phosphorylation, but also mediate intracellular calcium buffering, generation of reactive oxygen species (ROS), and apoptosis. Electron leakage from the electron transport chain, especially from damaged or depolarized mitochondria, can generate excess free radicals that damage cellular proteins, DNA, and lipids. Furthermore, mitochondrial damage releases pro-apoptotic factors to initiate cell death. Previous studies have reported that traumatic brain injury (TBI) reduces mitochondrial respiration, enhances production of ROS, and triggers apoptotic cell death, suggesting a prominent role of mitochondria in TBI pathophysiology. Mitochondria maintain cellular energy homeostasis and health via balanced processes of fusion and fission, continuously dividing and fusing to form an interconnected network throughout the cell. An imbalance of these processes, particularly an excess of fission, can be detrimental to mitochondrial function, causing decreased respiration, ROS production, and apoptosis. Mitochondrial fission is regulated by the cytosolic GTPase, dynamin-related protein 1 (Drp1), which translocates to the mitochondrial outer membrane (MOM) to initiate fission. Aberrant Drp1 activity has been linked to excessive mitochondrial fission and neurodegeneration. Measurement of Drp1 levels in purified hippocampal mitochondria showed an increase in TBI animals as compared to sham controls. Analysis of cryo-electron micrographs of these mitochondria also showed that TBI caused an initial increase in the length of hippocampal mitochondria at 24 h post-injury, followed by a significant decrease in length at 72 h. Post-TBI administration of Mitochondrial division inhibitor-1 (Mdivi-1), a pharmacological inhibitor of Drp1, prevented this decrease in mitochondria length. Mdivi-1 treatment also reduced the loss of newborn neurons in the

  9. Herd prevalence of bovine brucellosis and analysis of risk factors in cattle in urban and peri-urban areas of the Kampala economic zone, Uganda

    Directory of Open Access Journals (Sweden)

    Eisler Mark C

    2011-10-01

    Full Text Available Abstract Background Human brucellosis has been found to be prevalent in the urban areas of Kampala, the capital city of Uganda. A cross-sectional study was designed to generate precise information on the prevalence of brucellosis in cattle and risk factors for the disease in its urban and peri-urban dairy farming systems. Results The adjusted herd prevalence of brucellosis was 6.5% (11/177, 95% CI: 3.6%-10.0% and the adjusted individual animal prevalence was 5.0% (21/423, 95% CI: 2.7% - 9.3% based on diagnosis using commercial kits of the competitive enzyme-linked immunosorbent assay (CELISA for Brucella abortus antibodies. Mean within-herd prevalence was found to be 25.9% (95% CI: 9.7% - 53.1% and brucellosis prevalence in an infected herd ranged from 9.1% to 50%. A risk factor could not be identified at the animal level but two risk factors were identified at the herd level: large herd size and history of abortion. The mean number of milking cows in a free-grazing herd (5.0 was significantly larger than a herd with a movement restricted (1.7, p Conclusions Vaccination should be targeted at commercial large-scale farms with free-grazing farming to control brucellosis in cattle in and around Kampala city.

  10. Bovine Virus Diarrhea (BVD)

    OpenAIRE

    Hoar, Bruce R.

    2004-01-01

    Bovine virus diarrhea (BVD) is a complicated disease to discuss as it can result in a wide variety of disease problems from very mild to very severe. BVD can be one of the most devastating diseases cattle encounter and one of the hardest to get rid of when it attacks a herd. The viruses that cause BVD have been grouped into two genotypes, Type I and Type II. The disease syndrome caused by the two genotypes is basically the same, however disease caused by Type II infection is often more severe...

  11. Proteomic Analysis of Bovine Nucleolus

    Institute of Scientific and Technical Information of China (English)

    Amrutlal K.Patel; Doug Olson; Suresh K. Tikoo

    2010-01-01

    Nucleolus is the most prominent subnuclear structure, which performs a wide variety of functions in the eu-karyotic cellular processes. In order to understand the structural and functional role of the nucleoli in bovine cells,we analyzed the proteomie composition of the bovine nueleoli. The nucleoli were isolated from Madin Darby bo-vine kidney cells and subjected to proteomie analysis by LC-MS/MS after fractionation by SDS-PAGE and strongcation exchange chromatography. Analysis of the data using the Mascot database search and the GPM databasesearch identified 311 proteins in the bovine nucleoli, which contained 22 proteins previously not identified in theproteomic analysis of human nucleoli. Analysis of the identified proteins using the GoMiner software suggestedthat the bovine nueleoli contained proteins involved in ribosomal biogenesis, cell cycle control, transcriptional,translational and post-translational regulation, transport, and structural organization.

  12. Mitochondrial DNA haplogroups modify the risk of osteoarthritis by altering mitochondrial function and intracellular mitochondrial signals.

    Science.gov (United States)

    Fang, Hezhi; Zhang, Fengjiao; Li, Fengjie; Shi, Hao; Ma, Lin; Du, Miaomiao; You, Yanting; Qiu, Ruyi; Nie, Hezhongrong; Shen, Lijun; Bai, Yidong; Lyu, Jianxin

    2016-04-01

    Haplogroup G predisposes one to an increased risk of osteoarthritis (OA) occurrence, while haplogroup B4 is a protective factor against OA onset. However, the underlying mechanism is not known. Here, by using trans-mitochondrial technology, we demonstrate that the activity levels of mitochondrial respiratory chain complex I and III are higher in G cybrids than in haplogroup B4. Increased mitochondrial oxidative phosphorylation (OXPHOS) promotes mitochondrial-related ATP generation in G cybrids, thereby shifting the ATP generation from glycolysis to OXPHOS. Furthermore, we found that lower glycolysis in G cybrids decreased cell viability under hypoxia (1% O2) compared with B4 cybrids. In contrast, G cybrids have a lower NAD(+)/NADH ratio and less generation of reactive oxygen species (ROS) under both hypoxic (1% O2) and normoxic (20% O2) conditions than B4 cybrids, indicating that mitochondrial-mediated signaling pathways (retrograde signaling) differ between these cybrids. Gene expression profiling of G and B4 cybrids using next-generation sequencing technology showed that 404 of 575 differentially expressed genes (DEGs) between G and B4 cybrids are enriched in 17 pathways, of which 11 pathways participate in OA. Quantitative reverse transcription PCR (qRT-PCR) analyses confirmed that G cybrids had lower glycolysis activity than B4 cybrids. In addition, we confirmed that the rheumatoid arthritis pathway was over-activated in G cybrids, although the remaining 9 pathways were not further tested by qRT-PCR. In conclusion, our findings indicate that mtDNA haplogroup G may increase the risk of OA by shifting the metabolic profile from glycolysis to OXPHOS and by over-activating OA-related signaling pathways. PMID:26705675

  13. Selenium preserves mitochondrial function, stimulates mitochondrial biogenesis, and reduces infarct volume after focal cerebral ischemia

    Directory of Open Access Journals (Sweden)

    Mehta Suresh L

    2012-07-01

    Full Text Available Abstract Background Mitochondrial dysfunction is one of the major events responsible for activation of neuronal cell death pathways during cerebral ischemia. Trace element selenium has been shown to protect neurons in various diseases conditions. Present study is conducted to demonstrate that selenium preserves mitochondrial functional performance, activates mitochondrial biogenesis and prevents hypoxic/ischemic cell damage. Results The study conducted on HT22 cells exposed to glutamate or hypoxia and mice subjected to 60-min focal cerebral ischemia revealed that selenium (100 nM pretreatment (24 h significantly attenuated cell death induced by either glutamate toxicity or hypoxia. The protective effects were associated with reduction of glutamate and hypoxia-induced ROS production and alleviation of hypoxia-induced suppression of mitochondrial respiratory complex activities. The animal studies demonstrated that selenite pretreatment (0.2 mg/kg i.p. once a day for 7 days ameliorated cerebral infarct volume and reduced DNA oxidation. Furthermore, selenite increased protein levels of peroxisome proliferator-activated receptor-γ coactivator 1alpha (PGC-1α and nuclear respiratory factor 1 (NRF1, two key nuclear factors that regulate mitochondrial biogenesis. Finally, selenite normalized the ischemia-induced activation of Beclin 1 and microtubule-associated protein 1 light chain 3-II (LC3-II, markers for autophagy. Conclusions These results suggest that selenium protects neurons against hypoxic/ischemic damage by reducing oxidative stress, restoring mitochondrial functional activities and stimulating mitochondrial biogenesis.

  14. Mitochondrial morphology and cardiovascular disease

    OpenAIRE

    Ong, Sang-Bing; Hausenloy, Derek J

    2010-01-01

    Mitochondria are dynamic and are able to interchange their morphology between elongated interconnected mitochondrial networks and a fragmented disconnected arrangement by the processes of mitochondrial fusion and fission, respectively. Changes in mitochondrial morphology are regulated by the mitochondrial fusion proteins (mitofusins 1 and 2, and optic atrophy 1) and the mitochondrial fission proteins (dynamin-related peptide 1 and mitochondrial fission protein 1) and have been implicated in a...

  15. 78 FR 72979 - Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products

    Science.gov (United States)

    2013-12-04

    ... risks of other livestock diseases, such as bovine viral diarrhea, foot-and-mouth disease, infectious... Products Derived from Bovines,'' published in the Federal Register on September 18, 2007 (72 FR 53314-53379..., 2012, we published in the Federal Register (77 FR 15848-15913, Docket No. APHIS-2008-0010) a...

  16. Mitochondrial DNA mutations provoke dominant inhibition of mitochondrial inner membrane fusion.

    Directory of Open Access Journals (Sweden)

    Cécile Sauvanet

    Full Text Available Mitochondria are highly dynamic organelles that continuously move, fuse and divide. Mitochondrial dynamics modulate overall mitochondrial morphology and are essential for the proper function, maintenance and transmission of mitochondria and mitochondrial DNA (mtDNA. We have investigated mitochondrial fusion in yeast cells with severe defects in oxidative phosphorylation (OXPHOS due to removal or various specific mutations of mtDNA. We find that, under fermentative conditions, OXPHOS deficient cells maintain normal levels of cellular ATP and ADP but display a reduced mitochondrial inner membrane potential. We demonstrate that, despite metabolic compensation by glycolysis, OXPHOS defects are associated to a selective inhibition of inner but not outer membrane fusion. Fusion inhibition was dominant and hampered the fusion of mutant mitochondria with wild-type mitochondria. Inhibition of inner membrane fusion was not systematically associated to changes of mitochondrial distribution and morphology, nor to changes in the isoform pattern of Mgm1, the major fusion factor of the inner membrane. However, inhibition of inner membrane fusion correlated with specific alterations of mitochondrial ultrastructure, notably with the presence of aligned and unfused inner membranes that are connected to two mitochondrial boundaries. The fusion inhibition observed upon deletion of OXPHOS related genes or upon removal of the entire mtDNA was similar to that observed upon introduction of point mutations in the mitochondrial ATP6 gene that are associated to neurogenic ataxia and retinitis pigmentosa (NARP or to maternally inherited Leigh Syndrome (MILS in humans. Our findings indicate that the consequences of mtDNA mutations may not be limited to OXPHOS defects but may also include alterations in mitochondrial fusion. Our results further imply that, in healthy cells, the dominant inhibition of fusion could mediate the exclusion of OXPHOS-deficient mitochondria from

  17. Viral infections and bovine mastitis: a review

    NARCIS (Netherlands)

    Wellenberg, G.J.; Poel, van der W.H.M.; Oirschot, van J.T.

    2002-01-01

    This review deals with the role of viruses in the aetiology of bovine mastitis. Bovine herpesvirus 1, bovine herpesvirus 4, foot-and-mouth disease virus, and parainfluenza 3 virus have been isolated from milk from cows with clinical mastitis. Intramammary inoculations of bovine herpesvirus 1 or para

  18. AMP-activated protein kinase mediates mitochondrial fission in response to energy stress

    Science.gov (United States)

    Courchet, Julien; Lewis, Tommy L.; Losón, Oliver C.; Hellberg, Kristina; Young, Nathan P.; Chen, Hsiuchen; Polleux, Franck; Chan, David C.; Shaw, Reuben J.

    2016-01-01

    Mitochondria undergo fragmentation in response to electron transport chain (ETC) poisons and mitochondrial DNA–linked disease mutations, yet how these stimuli mechanistically connect to the mitochondrial fission and fusion machinery is poorly understood. We found that the energy-sensing adenosine monophosphate (AMP)–activated protein kinase (AMPK) is genetically required for cells to undergo rapid mitochondrial fragmentation after treatment with ETC inhibitors. Moreover, direct pharmacological activation of AMPK was sufficient to rapidly promote mitochondrial fragmentation even in the absence of mitochondrial stress. A screen for substrates of AMPK identified mitochondrial fission factor (MFF), a mitochondrial outer-membrane receptor for DRP1, the cytoplasmic guanosine triphosphatase that catalyzes mitochondrial fission. Nonphosphorylatable and phosphomimetic alleles of the AMPK sites in MFF revealed that it is a key effector of AMPK-mediated mitochondrial fission. PMID:26816379

  19. Nonviral Gene Delivery of Growth and Differentiation Factor 5 to Human Mesenchymal Stem Cells Injected into a 3D Bovine Intervertebral Disc Organ Culture System

    Directory of Open Access Journals (Sweden)

    Christian Bucher

    2013-01-01

    Full Text Available Intervertebral disc (IVD cell therapy with unconditioned 2D expanded mesenchymal stem cells (MSC is a promising concept yet challenging to realize. Differentiation of MSCs by nonviral gene delivery of growth and differentiation factor 5 (GDF5 by electroporation mediated gene transfer could be an excellent source for cell transplantation. Human MSCs were harvested from bone marrow aspirate and GDF5 gene transfer was achieved by in vitro electroporation. Transfected cells were cultured as monolayers and as 3D cultures in 1.2% alginate bead culture. MSC expressed GDF5 efficiently for up to 21 days. The combination of GDF5 gene transfer and 3D culture in alginate showed an upregulation of aggrecan and SOX9, two markers for chondrogenesis, and KRT19 as a marker for discogenesis compared to untransfected cells. The cells encapsulated in alginate produced more proteoglycans expressed in GAG/DNA ratio. Furthermore, GDF5 transfected MCS injected into an IVD papain degeneration organ culture model showed a partial recovery of the GAG/DNA ratio after 7 days. In this study we demonstrate the potential of GDF5 transfected MSC as a promising approach for clinical translation for disc regeneration.

  20. Mitochondrial Gene Therapy Augments Mitochondrial Physiology in a Parkinson's Disease Cell Model

    OpenAIRE

    Keeney, Paula M; Quigley, Caitlin K.; Dunham, Lisa D.; Papageorge, Christina M.; Iyer, Shilpa; Thomas, Ravindar R.; Schwarz, Kathleen M.; Trimmer, Patricia A; Khan, Shaharyar M.; Portell, Francisco R.; Bergquist, Kristen E.; Bennett, James P.

    2009-01-01

    Neurodegeneration in Parkinson's disease (PD) affects mainly dopaminergic neurons in the substantia nigra, where age-related, increasing percentages of cells lose detectable respiratory activity associated with depletion of intact mitochondrial DNA (mtDNA). Replenishment of mtDNA might improve neuronal bioenergetic function and prevent further cell death. We developed a technology (“ProtoFection”) that uses recombinant human mitochondrial transcription factor A (TFAM) engineered with an N-ter...

  1. Mitochondrial Oxidative Damage in Aging and Alzheimer's Disease: Implications for Mitochondrially Targeted Antioxidant Therapeutics

    OpenAIRE

    Reddy, P. Hemachandra

    2006-01-01

    The overall aim of this article is to review current therapeutic strategies for treating AD, with a focus on mitochondrially targeted antioxidant treatments. Recent advances in molecular, cellular, and animal model studies of AD have revealed that amyloid precursor protein derivatives, including amyloid beta (Aβ) monomers and oligomers, are likely key factors in tau hyperphosphorylation, mitochondrial oxidative damage, inflammatory changes, and synaptic failure in the brain tissue of AD patie...

  2. Myoclonus in mitochondrial disorders.

    Science.gov (United States)

    Mancuso, Michelangelo; Orsucci, Daniele; Angelini, Corrado; Bertini, Enrico; Catteruccia, Michela; Pegoraro, Elena; Carelli, Valerio; Valentino, Maria L; Comi, Giacomo P; Minetti, Carlo; Bruno, Claudio; Moggio, Maurizio; Ienco, Elena Caldarazzo; Mongini, Tiziana; Vercelli, Liliana; Primiano, Guido; Servidei, Serenella; Tonin, Paola; Scarpelli, Mauro; Toscano, Antonio; Musumeci, Olimpia; Moroni, Isabella; Uziel, Graziella; Santorelli, Filippo M; Nesti, Claudia; Filosto, Massimiliano; Lamperti, Costanza; Zeviani, Massimo; Siciliano, Gabriele

    2014-05-01

    Myoclonus is a possible manifestation of mitochondrial disorders, and its presence is considered, in association with epilepsy and the ragged red fibers, pivotal for the syndromic diagnosis of MERRF (myoclonic epilepsy with ragged red fibers). However, its prevalence in mitochondrial diseases is not known. The aims of this study are the evaluation of the prevalence of myoclonus in a big cohort of mitochondrial patients and the clinical characterization of these subjects. Based on the database of the "Nation-wide Italian Collaborative Network of Mitochondrial Diseases," we reviewed the clinical and molecular data of mitochondrial patients with myoclonus among their clinical features. Myoclonus is a rather uncommon clinical feature of mitochondrial diseases (3.6% of 1,086 patients registered in our database). It is not strictly linked to a specific genotype or phenotype, and only 1 of 3 patients with MERRF harbors the 8344A>G mutation (frequently labeled as "the MERRF mutation"). Finally, myoclonus is not inextricably linked to epilepsy in MERRF patients, but more to cerebellar ataxia. In a myoclonic patient, evidences of mitochondrial dysfunction must be investigated, even though myoclonus is not a common sign of mitochondriopathy. Clinical, histological, and biochemical data may predict the finding of a mitochondrial or nuclear DNA mutation. Finally, this study reinforces the notion that myoclonus is not inextricably linked to epilepsy in MERRF patients, and therefore the term "myoclonic epilepsy" seems inadequate and potentially misleading. PMID:24510442

  3. Mitochondrial DNA mutations and male infertility

    Directory of Open Access Journals (Sweden)

    Kumar D

    2009-01-01

    Full Text Available Infertility can be defined as difficulty in conceiving a child after 1 year of unprotected intercourse. Infertility can arise either because of the male factor or female factor or both. According to the current estimates, 15% of couples attempting their first pregnancy could not succeed. Infertility is either primary or secondary. Mitochondria have profound effect on all biochemical pathways, including the one that drivessperm motility. Sperm motility is heavily dependent on the ATP generated by oxidative phosphorylation in the mitochondrial sheath. In this review, the very positive role of mitochondrial genome′s association with infertility is discussed

  4. Altered Mitochondrial Dynamics and TBI Pathophysiology

    Directory of Open Access Journals (Sweden)

    Tara Diane Fischer

    2016-03-01

    Full Text Available Mitochondrial function is intimately linked to cellular survival, growth, and death. Mitochondria not only generate ATP from oxidative phosphorylation, but also mediate intracellular calcium buffering, generation of reactive oxygen species (ROS, and apoptosis. Electron leakage from the electron transport chain, especially from damaged or depolarized mitochondria, can generate excess free radicals that damage cellular proteins, DNA, and lipids. Furthermore, mitochondrial damage releases pro-apoptotic factors to initiate cell death. Previous studies have reported that traumatic brain injury (TBI reduces mitochondrial respiration, enhances production of ROS, and triggers apoptotic cell death, suggesting a prominent role of mitochondria in TBI pathophysiology. Mitochondria maintain cellular energy homeostasis and health via balanced processes of fusion and fission, continuously dividing and fusing to form an interconnected network throughout the cell. An imbalance of these processes, particularly an excess of fission, can be detrimental to mitochondrial function, causing decreased respiration, ROS production, and apoptosis. Mitochondrial fission is regulated by the cytosolic GTPase, dynamin-related protein 1 (Drp1, which translocates to the mitochondrial outer membrane to initiate fission. Aberrant Drp1 activity has been linked to excessive mitochondrial fission and neurodegeneration. Measurement of Drp1 levels in purified hippocampal mitochondria showed an increase in TBI animals as compared to sham controls. Analysis of cryo-electron micrographs of these mitochondria also showed that TBI caused an initial increase in the length of hippocampal mitochondria at 24 hours post-injury, followed by a significant decrease in length at 72 hours. Post-TBI administration of Mdivi-1, a pharmacological inhibitor of Drp1, prevented this decrease in mitochondria length. Mdivi-1 treatment also reduced the loss of newborn neurons in the hippocampus and improved

  5. Epidemiology of Bovine Mastitis in Cows of Dharwad District

    Science.gov (United States)

    Kurjogi, Mahantesh M.; Kaliwal, Basappa B.

    2014-01-01

    Bovine mastitis is very common in cows of both developed and developing countries. The prevalence of clinical and subclinical mastitis (SCM) varies from region to region. Hence, the present study was carried out to determine the prevalence of mastitis using three diagnostic tests by considering different risk factors like age, lactation, breed, season, quarters, and herd. The results showed that surf field mastitis test (SFMT) is the most sensitive test for diagnosis of bovine mastitis, the older age and cows with later part of lactation period were more prone to bovine mastitis, and exotic breeds like Holstein freshen (HF) were more susceptible to bovine mastitis. The highest incidence of mastitis was recorded in monsoon season. The prevalence of subclinical and clinical mastitis was more in single and two quarters, respectively, and the rate of bovine mastitis was more in unorganized herds. The study concluded that SCM is directly associated with age, lactation period, and environmental factors of the cow and clinical mastitis is more associated with breed of the cow and environmental conditions.

  6. Bovine Rhinitis Viruses Are Common in U.S. Cattle with Bovine Respiratory Disease

    OpenAIRE

    Hause, Ben M.; Collin, Emily A.; Anderson, Joe; Hesse, Richard A.; Anderson, Gary

    2015-01-01

    Bovine rhinitis viruses (BRV) are established etiological agents of bovine respiratory disease complex however little research into their epidemiology and ecology has been published for several decades. In the U.S., only bovine rhinitis A virus 1 (BRAV1) has been identified while bovine rhinitis A virus 2 (BRAV2) and bovine rhinitis B virus (BRBV) were previously only identified in England and Japan, respectively. Metagenomic sequencing of a nasal swab from a bovine respiratory disease (BRD) ...

  7. Modifier factors influencing the phenotypic manifestation of the deafness-associated mitochondrial DNA mutations%修饰因子对线粒体DNA突变致聋的影响

    Institute of Scientific and Technical Information of China (English)

    杨爱芬; 郑静; 吕建新; 管敏鑫

    2011-01-01

    Mutations in the mitochondrial DNA have been found to be one of the most important causes of sensorineural hearing loss. In particular, these mutations often occur in the mitochondrial 12S rRNA and tRNA genes. Of these, the homoplasmic A1555G and C1494T mutations in the 12S rRNA have been associated with both aminoglycoside induced and nonsyndromic hearing impairment in many families worldwide. Children carrying the A1555G or C1494T mutation are susceptible to the exposure of ototoxic drugs, thereby inducing or worsening hearing loss. Individuals harboring A1555G or C1494T mutation can also develop hearing loss even in the absence of aminoglycoside exposure. However, matrilineal relatives of intra-families or inter-families carrying the A1555G or C1494T mutation exhibit a wide range of severity,age-at-onset, and audiometric configuration of hearing impairment. These indicate that the A1555G or C1494T mutation is a primary factor underlying the development of deafness but insufficient to produce the clinical phenotype. Thus, other modifier factors, such as aminoglycoside (s), mitochondrial DNA haplotype(s) or nuclear modifier gene(s), play a role in the phenotypic expression of the deafness-associated mitochondrial 12S rRNA A1555G or C1494T mutation. In this review, we summarize the modifier factors for the phenotypic expression of deafness-associated 12S rRNA A1555G and C1494T mutations and propose the molecular pathogenetic mechanism of maternally inherited deafness.%线粒体DNA突变是引起感音神经性耳聋的重要原因之一,这些突变主要位于线粒体12SrRNA和tRNA基因上.其中12S rRNA基因上的同质性A1555G和C1494T突变与氨基糖甙类抗生素造成的耳聋相关.携带这两个突变的个体对耳毒性药物高度敏感,导致临床上常见的"一针致聋"现象.但携带A1555G或C1494T突变的个体在没用药的情况下也能产生非综合征型耳聋,而且同一家系内和不同家系间的母系成员在听力损失

  8. Bovine colostrum: an emerging nutraceutical.

    Science.gov (United States)

    Bagwe, Siddhi; Tharappel, Leo J P; Kaur, Ginpreet; Buttar, Harpal S

    2015-09-01

    Nutraceutical, a term combining the words "nutrition" and "pharmaceuticals", is a food or food product that provides health benefits as an adjuvant or alternative therapy, including the treatment and prevention of infectious diseases in children and adults. There is emerging evidence that bovine colostrum (BC) may be one of the promising nutraceuticals which can prevent or mitigate various diseases in newborns and adults. Immunity-related disorders are one of the leading causes of mortality in the world. BC is rich in immunity, growth and antimicrobial factors, which promote tissue growth and the maturation of digestive tract and immune function in neonatal animals and humans. The immunoglobulins and lactoferrin present in colostrum are known to build natural immunity in newborns which helps to reduce the mortality rate in this population. Also, the side-effect profile of colostrum proteins and possible lactose intolerance is relatively less in comparison with milk. In general, BC is considered safe and well tolerated. Since colostrum has several important nutritional constituents, well-designed, double-blind, placebo-controlled studies with colostrum products should be conducted to widen its therapeutic use. The objectives of this review are to create awareness about the nutraceutical properties of colostrum and to discuss the various ongoing alternative treatments of colostrum and its active ingredients as well as to address colostrum's future nutraceutical and therapeutic implications in humans. PMID:25781716

  9. The Novel Tail-anchored Membrane Protein Mff Controls Mitochondrial and Peroxisomal Fission in Mammalian Cells

    OpenAIRE

    Gandre-Babbe, Shilpa; van der Bliek, Alexander M.

    2008-01-01

    Few components of the mitochondrial fission machinery are known, even though mitochondrial fission is a complex process of vital importance for cell growth and survival. Here, we describe a novel protein that controls mitochondrial fission. This protein was identified in a small interfering RNA (siRNA) screen using Drosophila cells. The human homologue of this protein was named Mitochondrial fission factor (Mff). Mitochondria of cells transfected with Mff siRNA form a closed network similar t...

  10. Mitochondrial functions on oocytes and preimplantation embryos

    Institute of Scientific and Technical Information of China (English)

    Li-ya WANG; Da-hui WANG; Xiang-yang ZOU; Chen-ming XU

    2009-01-01

    Oocyte quality has long been considered as a main limiting factor for in vitro fertilization (IVF). In the past decade,extensive observations demonstrated that the mitochondrion plays a vital role in the oocyte cytoplasm, for it can provide adenosine triphosphate (ATP) for fertilization and preimplantation embryo development and also act as stores of intracellular calcium and proapoptotic factors. During the oocyte maturation, mitochondria are characterized by distinct changes of their distribution pattern from being homogeneous to heterogeneous, which is correlated with the cumulus apoptosis. Oocyte quality decreases with the increasing maternal age. Recent studies have shown that low quality oocytes have some age-related dysfunctions, which include the decrease in mitochondrial membrane potential, increase of mitochondrial DNA (mtDNA) damages, chromosomal aneuploidies,the incidence of apoptosis, and changes in mitochondrial gene expression. All these dysfunctions may cause a high level of developmental retardation and arrest of preimplantation embryos. It has been suggested that these mitochondrial changes may arise from excessive reactive oxygen species (ROS) that is closely associated with the oxidative energy production or calcium overload,which may trigger permeability transition pore opening and subsequent apoptosis. Therefore, mitochondria can be seen as signs for oocyte quality evaluation, and it is possible that the oocyte quality can be improved by enhancing the physical function of mitochondria. Here we reviewed recent advances in mitochondrial functions on oocytes.

  11. Tissue-specific modulation of mitochondrial DNA segregation by a defect in mitochondrial division.

    Science.gov (United States)

    Jokinen, Riikka; Marttinen, Paula; Stewart, James B; Neil Dear, T; Battersby, Brendan J

    2016-02-15

    Mitochondria are dynamic organelles that divide and fuse by remodeling an outer and inner membrane in response to developmental, physiological and stress stimuli. These events are coordinated by conserved dynamin-related GTPases. The dynamics of mitochondrial morphology require coordination with mitochondrial DNA (mtDNA) to ensure faithful genome transmission, however, this process remains poorly understood. Mitochondrial division is linked to the segregation of mtDNA but how it affects cases of mtDNA heteroplasmy, where two or more mtDNA variants/mutations co-exist in a cell, is unknown. Segregation of heteroplasmic human pathogenic mtDNA mutations is a critical factor in the onset and severity of human mitochondrial diseases. Here, we investigated the coupling of mitochondrial morphology to the transmission and segregation of mtDNA in mammals by taking advantage of two genetically modified mouse models: one with a dominant-negative mutation in the dynamin-related protein 1 (Drp1 or Dnm1l) that impairs mitochondrial fission and the other, heteroplasmic mice segregating two neutral mtDNA haplotypes (BALB and NZB). We show a tissue-specific response to mtDNA segregation from a defect in mitochondrial fission. Only mtDNA segregation in the hematopoietic compartment is modulated from impaired Dnm1l function. In contrast, no effect was observed in other tissues arising from the three germ layers during development and in mtDNA transmission through the female germline. Our data suggest a robust organization of a heteroplasmic mtDNA segregating unit across mammalian cell types that can overcome impaired mitochondrial division to ensure faithful transmission of the mitochondrial genome. PMID:26681804

  12. Primary Mitochondrial Disease and Secondary Mitochondrial Dysfunction: Importance of Distinction for Diagnosis and Treatment.

    Science.gov (United States)

    Niyazov, Dmitriy M; Kahler, Stephan G; Frye, Richard E

    2016-07-01

    Mitochondrial disease refers to a heterogeneous group of disorders resulting in defective cellular energy production due to abnormal oxidative phosphorylation (oxphos). Primary mitochondrial disease (PMD) is diagnosed clinically and ideally, but not always, confirmed by a known or indisputably pathogenic mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) mutation. The PMD genes either encode oxphos proteins directly or they affect oxphos function by impacting production of the complex machinery needed to run the oxphos process. However, many disorders have the 'mitochondrial' phenotype without an identifiable mtDNA or nDNA mutation or they have a variant of unknown clinical significance. Secondary mitochondrial dysfunction (SMD) can be caused by genes encoding neither function nor production of the oxphos proteins and accompanies many hereditary non-mitochondrial diseases. SMD may also be due to nongenetic causes such as environmental factors. In our practice, we see many patients with clinical signs of mitochondrial dysfunction based on phenotype, biomarkers, imaging, muscle biopsy, or negative/equivocal mtDNA or nDNA test results. In these cases, it is often tempting to assign a patient's phenotype to 'mitochondrial disease', but SMD is often challenging to distinguish from PMD. Fortunately, rapid advances in molecular testing, made possible by next generation sequencing, have been effective at least in some cases in establishing accurate diagnoses to distinguish between PMD and SMD. This is important, since their treatments and prognoses can be quite different. However, even in the absence of the ability to distinguish between PMD and SMD, treating SMD with standard treatments for PMD can be effective. We review the latest findings regarding mitochondrial disease/dysfunction and give representative examples in which differentiation between PMD and SMD has been crucial for diagnosis and treatment. PMID:27587988

  13. Theileria parva infection induces autocrine growth of bovine lymphocytes.

    OpenAIRE

    Dobbelaere, D A; Coquerelle, T M; Roditi, I J; Eichhorn, M; Williams, R O

    1988-01-01

    Bovine lymphocytes infected with the parasite Theileria parva continuously secrete a growth factor that is essential for their proliferation in vitro and also constitutively express interleukin 2 receptors on their surface. Dilution of the secreted growth factor, caused by culturing cells at low density, results in retardation of culture growth. Human recombinant interleukin 2, however, effectively substitutes for the diluted growth factor by restoring normal growth rates and also allows Thei...

  14. Mitochondrial diseases and epilepsy.

    Science.gov (United States)

    Bindoff, Laurence A; Engelsen, Bernt A

    2012-09-01

    The mitochondrial respiratory chain is the final common pathway for energy production. Defects affecting this pathway can give rise to disease that presents at any age and affects any tissue. However, irrespective of genetic defect, epilepsy is common and there is a significant risk of status epilepticus. This review summarizes our current understanding of the epilepsy that occurs in mitochondrial disease, focusing on three of the most common disorders: mitochondrial myopathy encephalopathy, lactic acidosis and stroke-like episodes (MELAS), myoclonus epilepsy and ragged-red fibers (MERRF), and polymerase gamma (POLG) related disease. In addition, we review the pathogenesis and possible treatment of these disorders. PMID:22946726

  15. Antihelmintic Resistance For Gastrointestinal Bovine Nematodes

    Directory of Open Access Journals (Sweden)

    Patricia Torres Vásquez

    2007-06-01

    Full Text Available The gastrointestinal nematodes (GIN, in domestic animals, especially in bovines are a very important factor that affects their productivity, because cattle production systems have intervened in the relationship between gastrointestinal parasites (PGI and the host, breaking therefore the ecological balance between them. In many opportunities the development of parasitic populations have been favored or a parasitic population have been led to extinction, it has made that these populations express genes that would not express under normal conditions, favoring thus, resistance to medications that were made to their destruction. NGI are highly important in all cattle exploitations, but their inappropriate handling, mainly in the pharmacological aspect, has created vermifuge resistance by some parasitic populations. This article will determine the importance of the vermifuge resistance in cattle exploitations, as a factor of risk for the control of parasitic populations. The most important antihelmintic groups used in bovine are Benzimidazoles, Levamisol and Ivermectine and with these products resistance has been reported by parasitic populations such as in Haemochus contortus, Trichostrongylus. colubriformis, Ostertagia circumcicta, Ostertagia ostertagi. Different risk factors were classified in extrinsic (which don’t depend on the gastrointestinal parasite and intrinsic (which depend directly on gastrointestinal parasites related with genetics which occupy a great importance in the development of the vermifuge resistance.

  16. Bovine Viral Diarrhea Virus-Associated Disease in Feedlot Cattle.

    Science.gov (United States)

    Larson, Robert L

    2015-11-01

    Bovine viral diarrhea virus (BVDv) is associated with bovine respiratory disease complex and other diseases of feedlot cattle. Although occasionally a primary pathogen, BVDv's impact on cattle health is through the immunosuppressive effects of the virus and its synergism with other pathogens. The simple presence or absence of BVDv does not result in consistent health outcomes because BVDv is only one of many risk factors that contribute to disease syndromes. Current interventions have limitations and the optimum strategy for their uses to limit the health, production, and economic costs associated with BVDv have to be carefully considered for optimum cost-effectiveness. PMID:26210765

  17. Effect of the ATPase inhibitor protein IF1 on H+ translocation in the mitochondrial ATP synthase complex

    International Nuclear Information System (INIS)

    The H+ FoF1-ATP synthase complex of coupling membranes converts the proton-motive force into rotatory mechanical energy to drive ATP synthesis. The F1 moiety of the complex protrudes at the inner side of the membrane, the Fo sector spans the membrane reaching the outer side. The IF1 component of the mitochondrial complex is a basic 10 kDa protein, which inhibits the FoF1-ATP hydrolase activity. The mitochondrial matrix pH is the critical factor for the inhibitory binding of the central segment of IF1 (residue 42-58) to the F1-α/β subunits. We have analyzed the effect of native purified IF1 the IF1-(42-58) synthetic peptide and its mutants on proton conduction, driven by ATP hydrolysis or by [K+] gradients, in bovine heart inside-out submitochondrial particles and in liposome-reconstituted FoF1 complex. The results show that IF1, and in particular its central 42-58 segment, displays different inhibitory affinity for proton conduction from the F1 to the Fo side and in the opposite direction. Cross-linking of IF1 to F1-α/β subunits inhibits the ATP-driven H+ translocation but enhances H+ conduction in the reverse direction. These observation are discussed in terms of the rotary mechanism of the FoF1 complex.

  18. Mitochondrial biogenesis: pharmacological approaches.

    Science.gov (United States)

    Valero, Teresa

    2014-01-01

    Organelle biogenesis is concomitant to organelle inheritance during cell division. It is necessary that organelles double their size and divide to give rise to two identical daughter cells. Mitochondrial biogenesis occurs by growth and division of pre-existing organelles and is temporally coordinated with cell cycle events [1]. However, mitochondrial biogenesis is not only produced in association with cell division. It can be produced in response to an oxidative stimulus, to an increase in the energy requirements of the cells, to exercise training, to electrical stimulation, to hormones, during development, in certain mitochondrial diseases, etc. [2]. Mitochondrial biogenesis is therefore defined as the process via which cells increase their individual mitochondrial mass [3]. Recent discoveries have raised attention to mitochondrial biogenesis as a potential target to treat diseases which up to date do not have an efficient cure. Mitochondria, as the major ROS producer and the major antioxidant producer exert a crucial role within the cell mediating processes such as apoptosis, detoxification, Ca2+ buffering, etc. This pivotal role makes mitochondria a potential target to treat a great variety of diseases. Mitochondrial biogenesis can be pharmacologically manipulated. This issue tries to cover a number of approaches to treat several diseases through triggering mitochondrial biogenesis. It contains recent discoveries in this novel field, focusing on advanced mitochondrial therapies to chronic and degenerative diseases, mitochondrial diseases, lifespan extension, mitohormesis, intracellular signaling, new pharmacological targets and natural therapies. It contributes to the field by covering and gathering the scarcely reported pharmacological approaches in the novel and promising field of mitochondrial biogenesis. There are several diseases that have a mitochondrial origin such as chronic progressive external ophthalmoplegia (CPEO) and the Kearns- Sayre syndrome (KSS

  19. Bovine aortic arch: A novel association with thoracic aortic dilation

    International Nuclear Information System (INIS)

    Aim: To investigate whether there is a link between bovine arch and thoracic aortic aneurysm. Materials and methods: Computed tomography (CT) and magnetic resonance imaging (MRI) images of the thorax of 191 patients with dilated thoracic aortas and 391 consecutive, unselected patients as controls were retrospectively reviewed. Bovine arch was considered present if either a shared origin of the left common carotid and innominate arteries or an origin of the left common carotid from the innominate artery was identified. A chi-square test was used to evaluate the significance of differences between subgroups. Results: A trend towards increased prevalence of bovine arch was seen in patients with dilated aortas (26.2%) compared to controls (20.5%, p = 0.12). The association was statistically significant in patients over 70 years old (31.9%, p = 0.019) and when dilation involved the aortic arch (47.6%, p = 0.003). Conclusions: An association between bovine arch and aortic dilation is seen in older patients, and when dilation involves the aortic arch. Bovine arch should be considered a potential risk factor for thoracic aortic aneurysm.

  20. Okra yield fertilized with bovine manure and biofertilizer

    Directory of Open Access Journals (Sweden)

    Ademar Pereira de Oliveira

    2013-12-01

    Full Text Available The use of bovine manure becomes an useful and economic practice for the small and medium producers of vegetables, and the okra plant normally demands high doses of organic fertilizers. This study was carried out, from January to July 2011, at the Federal University of Paraíba, in Areia city - PB, aiming to evaluate the effect of bovine manure and biofertilizer on the productive behavior of the okra plant. The experimental design used was randomized blocks, with four repetitions in factorial scheme 6 x 2, with the doses factors of bovine manure (0, 10, 20, 30, 40 and 50 t ha-1 with and without biofertilizer. The average mass of commercial fruit of okra, with and without biofertilizer was 18 and 16.5 g, respectively, in the doses of 27.5 and 60 t ha-1 of manure. The number of fruit plant-1 without biofertilizer was 30 fruits plant-1 of okra in the dose of 60 t ha-1 and with biofertilizer, the number of fruits plant-1 was 33 fruits in the dose of 28 t ha-1 of bovine manure. The productivity of commercial fruits of okra without biofertilizer was 20.4 t ha-1 and 22 t ha-1 with biofertilizer, respectively, in the doses of 60 and 31 t ha-1 of bovine manure.

  1. Prevalência e fatores de risco para a leptospirose em bovinos de Mato Grosso do Sul Prevalence and risk factors for bovine leptospirosis in Mato Grosso do Sul, Brazil

    Directory of Open Access Journals (Sweden)

    Aline de O. Figueiredo

    2009-05-01

    Full Text Available Foi investigada a prevalência de anticorpos antileptospira em fêmeas bovinas com idade igual ou superior a 24 meses, provenientes de 178 rebanhos de 22 municípios do estado de Mato Grosso do Sul, bem como identificados fatores de risco associados à infecção. Foram analisadas 2.573 amostras de soro sangüíneo por meio do teste de soroaglutinação microscópica perante 10 sorovares de leptospira. Títulos iguais ou superiores a 100 para um ou mais sorovares foram detectados em 1.801 fêmeas (98,8% de 161 (96,5% rebanhos. O sorovar Hardjo (65,6% foi apontado como o mais provável, seguido do sorovar Wolffi (12,3%. Os resultados demonstram que a leptospirose bovina se encontra presente em todos os municípios estudados, com alta prevalência, tanto em animais como em rebanhos. Os fatores de risco identificados neste estudo e associados à infecção por bactérias do gênero lepstopira foram o tipo de exploração pecuária de corte e a raça Zebu.The prevalence of anti-Leptospira spp. antibodies was estimated for female cattle aged 24 months or older. The sample comprised 178 herds from 22 counties in the state of Mato Grosso do Sul, Brazil. The risk factors associated with the presence of infeccion were investigated. A total of 2,573 blood serum samples were tested against 10 leptospira serovars using the microagglutination test (MAT. Titers of 100 or higher for one or more serovars were detected in 1,801 females (98.8% from 161 herds (96.5%. Serovar Hardjo (65.6% was the most frequent, followed by serovar Wolffi (12.3%. These results suggest that bovine leptospirosis is widespread in all the counties under study, with a high prevalence both at the animal and the herd level. Beef farms and the Zebu breed were associated to the higher risk of herd infection by leptospiras.

  2. Mitochondrially targeted anti-cancer agents

    Czech Academy of Sciences Publication Activity Database

    Biasutto, L.; Dong, L.A.; Zoratti, M.; Neužil, Jiří

    2010-01-01

    Roč. 10, č. 6 (2010), s. 670-681. ISSN 1567-7249 Institutional research plan: CEZ:AV0Z50520701 Keywords : Mitochondrial target ing * pro-oxidant effect * reactive oxygen species Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.238, year: 2010

  3. Effect of insulin-like growth factor-1 during in vitro oocyte maturation and in vitro culture of bovine embryos Efeito do fator de crescimento semelhante à insulina-1 durante a maturação in vitro dos oócitos e cultivo in vitro de embriões bovinos

    OpenAIRE

    M.D. Quetglas; L.A Coelho; Garcia, J M; E.B. Oliveira Filho; C.R. Esper

    2001-01-01

    The effects of insulin-like growth factor-I (IGF-I) on in vitro maturation (IVM) (experiment I) and on in vitro embryo development (experiment II) of bovine oocytes fertilized in vitro, were evaluated in terms of cleavage (CR), blastocyst (BR) and hatching (HR) rates. For IVM, immature cumulus-oocyte complexes were cultured in TCM-199 medium supplemented with Hepes, sodium bicarbonate, sodium pyruvate, additives, fetal calf serum (B-199 medium) and gonadotropins (14 U/ml PMSG and 7 U/ml hCG)....

  4. Mitochondrial dynamics and apoptosis

    OpenAIRE

    Suen, Der-Fen; Norris, Kristi L.; Youle, Richard J.

    2008-01-01

    In healthy cells, mitochondria continually divide and fuse to form a dynamic interconnecting network. The molecular machinery that mediates this organelle fission and fusion is necessary to maintain mitochondrial integrity, perhaps by facilitating DNA or protein quality control. This network disintegrates during apoptosis at the time of cytochrome c release and prior to caspase activation, yielding more numerous and smaller mitochondria. Recent work shows that proteins involved in mitochondri...

  5. The plant mitochondrial proteome

    DEFF Research Database (Denmark)

    Millar, A.H.; Heazlewood, J.L.; Kristensen, B.K.;

    2005-01-01

    The plant mitochondrial proteome might contain as many as 2000-3000 different gene products, each of which might undergo post-translational modification. Recent studies using analytical methods, such as one-, two- and three-dimensional gel electrophoresis and one- and two-dimensional liquid...... context to be defined for them. There are indications that some of these proteins add novel activities to mitochondrial protein complexes in plants....

  6. Mitochondrial metabolism and diabetes

    OpenAIRE

    Kwak, Soo Heon; Park, Kyong Soo; Lee, Ki‐Up; Lee, Hong Kyu

    2010-01-01

    Abstract The oversupply of calories and sedentary lifestyle has resulted in a rapid increase of diabetes prevalence worldwide. During the past two decades, lines of evidence suggest that mitochondrial dysfunction plays a key role in the pathophysiology of diabetes. Mitochondria are vital to most of the eukaryotic cells as they provide energy in the form of adenosine triphosphate by oxidative phosphorylation. In addition, mitochondrial function is an integral part of glucose‐stimulated insulin...

  7. Raw bovine milk improves gut responses to feeding relative to infant formula in preterm piglets

    DEFF Research Database (Denmark)

    Li, Yang; Lykke, Mikkel; Chatterton, D E W;

    2014-01-01

    milk) would have less bioactivity than corresponding bovine colostrum (BC) in a preterm pig model, but have improved bioactivity relative to its homogenized, pasteurized, spray-dried equivalent, whole milk powder (WMP), or a bovine milk protein-based infant formula (IF). For 5 days, newborn preterm......For preterm neonates, the quality of the first milk is crucial for intestinal maturation and resistance to necrotizing enterocolitis (NEC). Among other factors, milk quality is determined by the stage of lactation and processing. We hypothesized that unprocessed mature bovine milk (BM; raw bovine...... effects as BM, except for lactase activity and lactose absorption. In conclusion, the maturational and protective effects on the immature intestine decreased in the order BC>BM>WMP, but all three intact bovine milk diets were markedly better than IF. The stage of lactation (colostrum vs. mature milk...

  8. [Understanding mitochondrial genome fragmentation in parasitic lice (Insecta: Phthiraptera)].

    Science.gov (United States)

    Dong, Wen-Ge; Guo, Xian-Guo; Jin, Dao-Chao; Xue, Shi-Peng; Qin, Feng; Simon, Song; Stephen, C Barker; Renfu, Shao

    2013-07-01

    Lice are obligate ectoparasites of mammals and birds. Extensive fragmentation of mitochondrial genomes has been found in some louse species in the families Pediculidae, Pthiridae, Philopteridae and Trichodectidae. For example, the mt genomes of human body louse (Pediculus humanus), head louse (Pediculus capitis), and public louse (Pthirus pubis) have 20, 20 and 14 mini-chromosomes, respectively. These mini-chromosomes might be the results of deletion and recombination of mt genes. The factors and mechanisms of mitochondrial genome fragmentation are currently unknown. The fragmentation might be the results of evolutionary selection or random genetic drift or it is probably related to the lack of mtSSB (mitochondrial single-strand DNA binding protein). Understanding the fragmentation of mitochondrial genomes is of significance for understanding the origin and evolution of mitochondria. This paper reviews the recent advances in the studies of mito-chondrial genome fragmentation in lice, including the phenomena of mitochondrial genome fragmentation, characteristics of fragmented mitochondrial genomes, and some factors and mechanisms possibly leading to the mitochondrial genome fragmentation of lice. Perspectives for future studies on fragmented mt genomes are also discussed. PMID:23853355

  9. Effects of mitochondrial dysfunction on the immunological properties of microglia

    Directory of Open Access Journals (Sweden)

    Ferger Annette I

    2010-08-01

    Full Text Available Abstract Background Neurodegenerative diseases are characterized by both mitochondrial dysfunction and activation of microglia, the macrophages of the brain. Here, we investigate the effects of mitochondrial dysfunction on the activation profile of microglial cells. Methods We incubated primary mouse microglia with the mitochondrial toxins 3-nitropropionic acid (3-NP or rotenone. These mitochondrial toxins are known to induce neurodegeneration in humans and in experimental animals. We characterized lipopolysaccharide- (LPS- induced microglial activation and the alternative, interleukin-4- (IL-4- induced microglial activation in these mitochondrial toxin-treated microglial cells. Results We found that, while mitochondrial toxins did not affect LPS-induced activation, as measured by release of tumor necrosis factor α (TNF-α, interleukin-6 (IL-6 and interleukin-1β (IL-1β, they did inhibit part of the IL-4-induced alternative activation, as measured by arginase activity and expression, induction of insulin-like growth factor 1 (IGF-1 and the counteraction of the LPS induced cytokine release. Conclusions Mitochondrial dysfunction in microglial cells inhibits part of the IL-4-induced alternative response. Because this alternative activation is considered to be associated with wound healing and an attenuation of inflammation, mitochondrial dysfunction in microglial cells might contribute to the detrimental effects of neuroinflammation seen in neurodegenerative diseases.

  10. Predictive qualitative risk model of bovine rabies occurrence in Brazil.

    Science.gov (United States)

    Braga, Guilherme Basseto; Grisi-Filho, José Henrique Hildebrand; Leite, Bruno Meireles; de Sena, Elaine Fátima; Dias, Ricardo Augusto

    2014-03-01

    Bovine rabies remains endemic in Brazil and despite control efforts, the disease still spreads insidiously. The main vector is the hematophagous bat, Desmodus rotundus. The present work aimed to create a predictive qualitative model of the occurrence of bovine rabies in each municipality in 25 of the 27 Brazilian States. The risk of rabies transmission from bats to bovine was estimated using decision-tree models of receptivity and vulnerability. Questionnaires, which covered a number of questions related to the surveillance of possible risk factors, such as bovine rabies outbreaks in the previous year, the presence of bat roosts, bat rabies positivity and environmental changes, were sent to the local veterinary units of each State. The bovine density and geomorphologic features were obtained from national databases and geographic information systems. Of the 433 municipalities presenting bovine rabies outbreaks in 2010, 178 (41.1%) were classified by the model as high risk, 212 (49.0%) were classified as moderate risk, 25 (5.8%) were classified as low risk, whereas the risk was undetermined in 18 municipalities (4.1%). An ROC curve was built to determine if the risk evaluated by the model could adequately discriminate between municipalities with and without rabies occurrence in future years. The risk estimator for the year 2011 was classified as moderately accurate. In the future, these models could allow the targeting of rabies control efforts, with the adoption of control measures directed to the higher risk locations and the optimization of the field veterinary staff deployment throughout the country. Additionally, efforts must be made to encourage continuous surveillance of risk factors. PMID:24433635

  11. Keshan disease and mitochondrial cardiomyopathy

    Institute of Scientific and Technical Information of China (English)

    YANG Fuyu

    2006-01-01

    Keshan disease (KD) is a potentially fatal form of cardiomyopathy (disease of the heart muscle) endemic in certain areas of China. From 1984 to 1986, a national comprehensive scientific investigation on KD in Chuxiong region of Yunnan Province in the southwest China was conducted. The investigation team was composed of epidemiologists, clinic doctors, pathologists, biochemists, biophysicists and specialists in ecological environment. Results of pathological, biochemical and biophysical as well as clinical studies showed: an obvious increase of enlarged and swollen mitochondria with distended crista membranes in myocardium from patients with KD; significant reductions in the activity of oxidative phosphorylation (succinate dehydrogenase, cytochrome oxidase, succinate oxidase, H+-ATPase) of affected mitochondria; decrease in CoQ, cardiolipin, Se and GSHPx activity, while obvious increase in the Ca2+ content. So, it was suggested that mitochondria are the predominant target of the pathogenic factors of KD. Before Chuxiong KD survey only a few cases of mitochondrial cardiomyopathy were studied. During the multidisciplinary scientific investigation on KD in Chuxiong a large amount of samples from KD cases and the positive controls were examined. On the basis of the results obtained it was suggested that KD might be classified as a "Mitochondrial Cardiomyopathy" endemic in China. This is one of the achievements in the three years' survey in Chuxiong and is valuable not only to the deeper understanding of pathogenic mechanism of KD but also to the study of mitochondrial cardiomyopathy in general.Keshan disease is not a genetic disease, but is closely related to the malnutrition (especially microelement Se deficiency). KD occurs along a low Se belt, and Se supplementation has been effective in prevention of such disease. The incidence of KD has sharply decreased along with the steady raise of living standard and realization of preventive measures. At present, patients of

  12. Bovine Tuberculosis, A Zoonotic Disease

    Directory of Open Access Journals (Sweden)

    Tarmudji

    2008-12-01

    Full Text Available Bovine tuberculosis is caused by the infection of Mycobacterium tuberculosis var. bovis (M. bovis. This species is one of Mycobacterium tuberculosis complex, can infect wide range of hosts: cattle and other domesticated animals, wild mammals and humans (zoonotic. M. bovis bacterium from infected hosts can be transmitted to other susceptible animals and humans through respiratory excretes and secretion materials. Humans can be infected with M. bovis by ingested M. bovis contaminated animal products, unpasteurised milk from tuberculosis cows or through respiratory route of contaminated aerosol. Bovine tuberculosis at the first stage does not show any clinical sign but as the disease progress in the next stage which may take several months or years, clinical signs may arise, suh as: fluctuative body temperature, anorexia, lost body weight, coughing, oedema of lymph nodes, increased respiratory frequencies. Pathological lesion of bovine tuberculosis is characterised by the formation of granulomas (tubercles, in which bacterial cells have been localised, most in lymph nodes and pulmonum, but can occur in other organs. The granulomas usually arise in small nodules or tubercles appear yellowish either caseus, caseo-calcareus or calcified. In Indonesia, bovine tuberculosis occurred in dairy cattle since 1905 through the imported dairy cows from Holland and Australian. It was unfortunate that until recently, there were not many research and surveilances of bovine tuberculosis conducted in this country, so the distribution of bovine tuberculosis is unknown. Early serological diagnosis can be done on live cattle by means of tuberculin tests under field conditions. Confirmation can be done by isolation and identification of excreted and secreted samples from the slaughter house. Antibiotic treatment and vaccination were uneffective, therefore the effective control of bovine tuberculosis is suggested by tuberculin tests and by slaughtering the selected

  13. Tracking of wisent–bison–yak mitochondrial evolution

    OpenAIRE

    Zeyland, Joanna; Wolko, Łukasz; Lipiński, Daniel; Woźniak, Anna; Nowak, Agnieszka; Szalata, Marlena; Bocianowski, Jan; Słomski, Ryszard

    2012-01-01

    One of the most informative sources which allow the drawing of far-reaching conclusions about the origins and phylogenetics of many species, including domestic animals and humans, is mitochondrial DNA (mtDNA). One of the important research targets should include the identification of similarities between wild and domestic species. The analysis involved the nucleotide sequences of mtDNA of wisent, auroch, bison, yak, bovine reference sequence (BRS) T3, T3a, T3b, T1, T1a, T1’2’3, T2, T3, T4, T5...

  14. Deceleration of fusion-fission cycles improves mitochondrial quality control during aging.

    Directory of Open Access Journals (Sweden)

    Marc Thilo Figge

    Full Text Available Mitochondrial dynamics and mitophagy play a key role in ensuring mitochondrial quality control. Impairment thereof was proposed to be causative to neurodegenerative diseases, diabetes, and cancer. Accumulation of mitochondrial dysfunction was further linked to aging. Here we applied a probabilistic modeling approach integrating our current knowledge on mitochondrial biology allowing us to simulate mitochondrial function and quality control during aging in silico. We demonstrate that cycles of fusion and fission and mitophagy indeed are essential for ensuring a high average quality of mitochondria, even under conditions in which random molecular damage is present. Prompted by earlier observations that mitochondrial fission itself can cause a partial drop in mitochondrial membrane potential, we tested the consequences of mitochondrial dynamics being harmful on its own. Next to directly impairing mitochondrial function, pre-existing molecular damage may be propagated and enhanced across the mitochondrial population by content mixing. In this situation, such an infection-like phenomenon impairs mitochondrial quality control progressively. However, when imposing an age-dependent deceleration of cycles of fusion and fission, we observe a delay in the loss of average quality of mitochondria. This provides a rational why fusion and fission rates are reduced during aging and why loss of a mitochondrial fission factor can extend life span in fungi. We propose the 'mitochondrial infectious damage adaptation' (MIDA model according to which a deceleration of fusion-fission cycles reflects a systemic adaptation increasing life span.

  15. Exercise induces mitochondrial biogenesis after brain ischemia in rats.

    Science.gov (United States)

    Zhang, Q; Wu, Y; Zhang, P; Sha, H; Jia, J; Hu, Y; Zhu, J

    2012-03-15

    Stroke is a major cause of death worldwide. Previous studies have suggested both exercise and mitochondrial biogenesis contribute to improved post-ischemic recovery of brain function. However, the exact mechanism underlying this effect is unclear. On the other hand, the benefit of exercise-induced mitochondrial biogenesis in brain has been confirmed. In this study, we attempted to determine whether treadmill exercise induces functional improvement through regulation of mitochondrial biogenesis after brain ischemia. We subjected adult male rats to ischemia, followed by either treadmill exercise or non-exercise and analyzed the effect of exercise on the amount of mitochondrial DNA (mtDNA), expression of mitochondrial biogenesis factors, and mitochondrial protein. In the ischemia-exercise group, only peroxisome proliferator activated receptor coactivator-1 (PGC-1) expression was increased significantly after 3 days of treadmill training. However, after 7 days of training, the levels of mtDNA, nuclear respiratory factor 1, NRF-1, mitochondrial transcription factor A, TFAM, and the mitochondrial protein cytochrome C oxidase subunit IV (COXIV) and heat shock protein-60 (HSP60) also increased above levels observed in non-exercised ischemic animals. These changes followed with significant changes in behavioral scores and cerebral infarct volume. The results indicate that exercise can promote mitochondrial biogenesis after ischemic injury, which may serve as a novel component of exercise-induced repair mechanisms of the brain. Understanding the molecular basis for exercise-induced neuroprotection may be beneficial in the development of therapeutic approaches for brain recovery from the ischemic injury. Based upon our findings, stimulation or enhancement of mitochondrial biogenesis may prove a novel neuroprotective strategy in the future. PMID:22266265

  16. Yeast PPR proteins, watchdogs of mitochondrial gene expression

    OpenAIRE

    Herbert, Christopher J.; Golik, Pawel; Bonnefoy, Nathalie

    2013-01-01

    PPR proteins are a family of ubiquitous RNA-binding factors, found in all the Eukaryotic lineages, and are particularly numerous in higher plants. According to recent bioinformatic analyses, yeast genomes encode from 10 (in S. pombe) to 15 (in S. cerevisiae) PPR proteins. All of these proteins are mitochondrial and very often interact with the mitochondrial membrane. Apart from the general factors, RNA polymerase and RNase P, most yeast PPR proteins are involved in the stability and/or transl...

  17. Control mechanisms in mitochondrial oxidative phosphorylation

    Institute of Scientific and Technical Information of China (English)

    Jana Hroudová; Zdeněk Fi(s)ar

    2013-01-01

    Distribution and activity of mitochondria are key factors in neuronal development, synaptic plasticity and axogenesis. The majority of energy sources, necessary for cellular functions, originate from oxidative phosphorylation located in the inner mitochondrial membrane. The adenosine-5'- triphosphate production is regulated by many control mechanism–firstly by oxygen, substrate level, adenosine-5'-diphosphate level, mitochondrial membrane potential, and rate of coupling and proton leak. Recently, these mechanisms have been implemented by "second control mechanisms," such as reversible phosphorylation of the tricarboxylic acid cycle enzymes and electron transport chain complexes, allosteric inhibition of cytochrome c oxidase, thyroid hormones, effects of fatty acids and uncoupling proteins. Impaired function of mitochondria is implicated in many diseases ranging from mitochondrial myopathies to bipolar disorder and schizophrenia. Mitochondrial dysfunctions are usually related to the ability of mitochondria to generate adenosine-5'-triphosphate in response to energy demands. Large amounts of reactive oxygen species are released by defective mitochondria, similarly, decline of antioxidative enzyme activities (e.g. in the elderly) enhances reactive oxygen species production. We reviewed data concerning neuroplasticity, physiology, and control of mitochondrial oxidative phosphorylation and reactive oxygen species production.

  18. Bovine respiratory disease model based on dual infections with infection with bovine viral diarrhea virus and bovine corona virus

    Science.gov (United States)

    Bovine respiratory disease complex (BRDC) is the leading cause of economic loss in the U.S. cattle industry. BRDC likely results from simultaneous or sequential infections with multiple pathogens including both viruses and bacteria. Bovine viral diarrhea virus (BVDV) and bovine corona virus (BoCV...

  19. A haplotype variation affecting the mitochondrial transportation of hMYH protein could be a risk factor for colorectal cancer in Chinese

    International Nuclear Information System (INIS)

    The human MutY homolog (hMYH), a DNA glycolsylase involved in the excision repair of oxidative DNA damage, is currently studied in colorectal cancer (CRC). We previously demonstrated a haplotype variant c.53C>T/c.74G>A of hMYH (T/A) increasing the risk for gastric cancer in Chinese. However, most investigations on correlation between hMYH and CRC are conducted in Western countries and the underlying mechanism has been poorly understood. To determine whether the haplotype T/A variant of hMYH was related to colorectal carcinogenesis, we performed a case-control study in 138 colorectal cancer (CRC) patients and 343 healthy controls in a Chinese population. Furthermore, the C/G for wild-type, C/A or T/G for single base variant and T/A for haplotype variant hMYH cDNAs with a flag epitope tag were cloned into pcDNA3.1+ vector and transfected into cos-7 cell line. Their subcellular localizations were determined by immunofluorescence assay. It was found that the frequency of haplotype variant allele was statistically higher in CRC patients than that in controls (P = 0.02, odds ratio = 5.06, 95% confidence interval = 1.26 – 20.4). Similarly, significant difference of heterozygote frequency was indicated between the two groups (P = 0.019), while no homozygote was found. In addition, immunofluorescence analysis showed that hMYH protein with haplotype T/A variation presented in both nucleus and mitochondria, in contrast to the wild-type protein only converging in mitochondria. However, neither of the single missense mutations alone changed the protein subcelluar localization. Although preliminarily, these results suggest that: the haplotype variant allele of hMYH leads to a missense protein, which partly affects the protein mitochondrial transportation and results as nuclear localization. This observation might be responsible for the increased susceptibility to cancers, including CRC, in Chinese

  20. Exercise-induced mitochondrial dysfunction: a myth or reality?

    Science.gov (United States)

    Ostojic, Sergej M

    2016-08-01

    Beneficial effects of physical activity on mitochondrial health are well substantiated in the scientific literature, with regular exercise improving mitochondrial quality and quantity in normal healthy population, and in cardiometabolic and neurodegenerative disorders and aging. However, several recent studies questioned this paradigm, suggesting that extremely heavy or exhaustive exercise fosters mitochondrial disturbances that could permanently damage its function in health and disease. Exercise-induced mitochondrial dysfunction (EIMD) might be a key proxy for negative outcomes of exhaustive exercise, being a pathophysiological substrate of heart abnormalities, chronic fatigue syndrome (CFS) or muscle degeneration. Here, we overview possible factors that mediate negative effects of exhaustive exercise on mitochondrial function and structure, and put forward alternative solutions for the management of EIMD. PMID:27389587

  1. The Spectrum of Mitochondrial Ultrastructural Defects in Mitochondrial Myopathy.

    Science.gov (United States)

    Vincent, Amy E; Ng, Yi Shiau; White, Kathryn; Davey, Tracey; Mannella, Carmen; Falkous, Gavin; Feeney, Catherine; Schaefer, Andrew M; McFarland, Robert; Gorman, Grainne S; Taylor, Robert W; Turnbull, Doug M; Picard, Martin

    2016-01-01

    Mitochondrial functions are intrinsically linked to their morphology and membrane ultrastructure. Characterizing abnormal mitochondrial structural features may thus provide insight into the underlying pathogenesis of inherited and acquired mitochondrial diseases. Following a systematic literature review on ultrastructural defects in mitochondrial myopathy, we investigated skeletal muscle biopsies from seven subjects with genetically defined mtDNA mutations. Mitochondrial ultrastructure and morphology were characterized using two complimentary approaches: transmission electron microscopy (TEM) and serial block face scanning EM (SBF-SEM) with 3D reconstruction. Six ultrastructural abnormalities were identified including i) paracrystalline inclusions, ii) linearization of cristae and abnormal angular features, iii) concentric layering of cristae membranes, iv) matrix compartmentalization, v) nanotunelling, and vi) donut-shaped mitochondria. In light of recent molecular advances in mitochondrial biology, these findings reveal novel aspects of mitochondrial ultrastructure and morphology in human tissues with implications for understanding the mechanisms linking mitochondrial dysfunction to disease. PMID:27506553

  2. Activation of Hsp90/NOS and increased NO generation does not impair mitochondrial respiratory chain by competitive binding at cytochrome C Oxidase in low oxygen concentrations

    OpenAIRE

    Presley, Tennille; Vedam, Kaushik; Liu, Xiaoping; Zweier, Jay L.; Ilangovan, Govindasamy

    2009-01-01

    Nitric oxide (NO) is known to regulate mitochondrial respiration, especially during metabolic stress and disease, by nitrosation of the mitochondrial electron transport chain (ETC) complexes (irreversible) and by a competitive binding at O2 binding site of cytochrome c oxidase (CcO) in complex IV (reversible). In this study, by using bovine aortic endothelial cells, we demonstrate that the inhibitory effect of endogenously generated NO by nitric oxide synthase (NOS) activation, by either NOS ...

  3. Association of Bovine Viral Diarrhea Virus with Multiple Viral Infections in Bovine Respiratory Disease Outbreaks

    OpenAIRE

    Richer, Lisette; Marois, Paul; Lamontagne, Lucie

    1988-01-01

    We investigated eleven outbreaks of naturally occurring bovine respiratory diseases in calves and adult animals in the St-Hyacinthe area of Quebec. Specific antibodies to bovine herpesvirus-1, bovine viral diarrhea virus, respiratory syncytial virus, parainfluenza type 3 virus, reovirus type 3, and serotypes 1 to 7 of bovine adenovirus were found in paired sera from diseased animals. Several bovine viruses with respiratory tropism were involved concomitantly in herds during an outbreak of bov...

  4. Detection and characterisation of Lactobacillus spp. in the bovine uterus and their influence on bovine endometrial epithelial cells in vitro.

    Directory of Open Access Journals (Sweden)

    Martina A Gärtner

    Full Text Available Bacterial infections and inflammation of the uterus are common in dairy cattle after parturition. In particular, pathogenic bacteria that cause endometritis have been the focus of research in cattle reproduction in the last ten years. The aim of the present study was to identify commensal lactobacilli in the bovine uterus and to examine their influence on the synthesis of pro-inflammatory factors in bovine endometrial epithelial cells in vitro. Lactobacillus species were isolated from healthy bovine uteri and further characterised. Bovine endometrial epithelial cells in the second passage (n = 5 animals were co-cultured with the autochthonous isolates L. buchneri, L. ruminis and L. amylovorus as well as with a commercially available L. vaginalis in different multiplicities of infection (MOI = 1, 5 and 10, respectively. Endometrial epithelial cells cultured without bacteria served as controls. At distinct points in time (2, 4 and 6 h total RNA was extracted from co-cultured epithelial cells and subjected to reverse transcription quantitative PCR of pro-inflammatory factors. Furthermore, the release of such factors by co-cultured epithelial cells was measured by ELISA or EIA after 24 and 48 h. L. ruminis and L. amylovorus induced increased interleukin (IL IL1A, IL6, IL8 and prostaglandin-endoperoxide synthase 2 mRNA levels and the release of IL8 and prostaglandin F(2α in endometrial epithelial cells compared with control cells. In contrast, L. buchneri did not significantly influence the expression and release of these factors. Toll-like receptors 2 and 6 transcripts were found unchanged in co-cultured and untreated epithelial cells in vitro. However, endometrial epithelial cells of each animal showed individual differences in the response to bacterial load. These results suggest that Lactobacillus species are present in the bovine uterus, revealing immunomodulatory properties.

  5. Detection and characterisation of Lactobacillus spp. in the bovine uterus and their influence on bovine endometrial epithelial cells in vitro.

    Science.gov (United States)

    Gärtner, Martina A; Bondzio, Angelika; Braun, Nicole; Jung, Markus; Einspanier, Ralf; Gabler, Christoph

    2015-01-01

    Bacterial infections and inflammation of the uterus are common in dairy cattle after parturition. In particular, pathogenic bacteria that cause endometritis have been the focus of research in cattle reproduction in the last ten years. The aim of the present study was to identify commensal lactobacilli in the bovine uterus and to examine their influence on the synthesis of pro-inflammatory factors in bovine endometrial epithelial cells in vitro. Lactobacillus species were isolated from healthy bovine uteri and further characterised. Bovine endometrial epithelial cells in the second passage (n = 5 animals) were co-cultured with the autochthonous isolates L. buchneri, L. ruminis and L. amylovorus as well as with a commercially available L. vaginalis in different multiplicities of infection (MOI = 1, 5 and 10, respectively). Endometrial epithelial cells cultured without bacteria served as controls. At distinct points in time (2, 4 and 6 h) total RNA was extracted from co-cultured epithelial cells and subjected to reverse transcription quantitative PCR of pro-inflammatory factors. Furthermore, the release of such factors by co-cultured epithelial cells was measured by ELISA or EIA after 24 and 48 h. L. ruminis and L. amylovorus induced increased interleukin (IL) IL1A, IL6, IL8 and prostaglandin-endoperoxide synthase 2 mRNA levels and the release of IL8 and prostaglandin F(2α) in endometrial epithelial cells compared with control cells. In contrast, L. buchneri did not significantly influence the expression and release of these factors. Toll-like receptors 2 and 6 transcripts were found unchanged in co-cultured and untreated epithelial cells in vitro. However, endometrial epithelial cells of each animal showed individual differences in the response to bacterial load. These results suggest that Lactobacillus species are present in the bovine uterus, revealing immunomodulatory properties. PMID:25803719

  6. Neurological mitochondrial cytopathies.

    Directory of Open Access Journals (Sweden)

    Mehndiratta M

    2002-04-01

    Full Text Available The mitochondrial cytopathies are genetically and phenotypically heterogeneous group of disorders caused by structural and functional abnormalities in mitochondria. To the best of our knowledge, there are very few studies published from India till date. Selected and confirmed fourteen cases of neurological mitochondrial cytopathies with different clinical syndromes admitted between 1997 and 2000 are being reported. There were 8 male and 6 female patients. The mean age was 24.42+/-11.18 years (range 4-40 years. Twelve patients could be categorized into well-defined syndromes, while two belonged to undefined group. In the defined syndrome categories, three patients had MELAS (mitochondrial encephalopathy, lactic acidosis and stroke like episodes, three had MERRF (myoclonic epilepsy and ragged red fibre myopathy, three cases had KSS (Kearns-Sayre Syndrome and three were diagnosed to be suffering from mitochondrial myopathy. In the uncategorized group, one case presented with paroxysmal kinesogenic dystonia and the other manifested with generalized chorea alone. Serum lactic acid level was significantly increased in all the patients (fasting 28.96+/-4.59 mg%, post exercise 41.02+/-4.93 mg%. Muscle biopsy was done in all cases. Succinic dehydrogenase staining of muscle tissue showed subsarcolemmal accumulation of mitochondria in 12 cases. Mitochondrial DNA study could be performed in one case only and it did not reveal any mutation at nucleotides 3243 and 8344. MRI brain showed multiple infarcts in MELAS, hyperintensities in putaminal areas in chorea and bilateral cerebellar atrophy in MERRF.

  7. Impaired Mitochondrial Biogenesis in Adipose Tissue in Acquired Obesity.

    Science.gov (United States)

    Heinonen, Sini; Buzkova, Jana; Muniandy, Maheswary; Kaksonen, Risto; Ollikainen, Miina; Ismail, Khadeeja; Hakkarainen, Antti; Lundbom, Jesse; Lundbom, Nina; Vuolteenaho, Katriina; Moilanen, Eeva; Kaprio, Jaakko; Rissanen, Aila; Suomalainen, Anu; Pietiläinen, Kirsi H

    2015-09-01

    Low mitochondrial number and activity have been suggested as underlying factors in obesity, type 2 diabetes, and metabolic syndrome. However, the stage at which mitochondrial dysfunction manifests in adipose tissue after the onset of obesity remains unknown. Here we examined subcutaneous adipose tissue (SAT) samples from healthy monozygotic twin pairs, 22.8-36.2 years of age, who were discordant (ΔBMI >3 kg/m(2), mean length of discordance 6.3 ± 0.3 years, n = 26) and concordant (ΔBMI <3 kg/m(2), n = 14) for body weight, and assessed their detailed mitochondrial metabolic characteristics: mitochondrial-related transcriptomes with dysregulated pathways, mitochondrial DNA (mtDNA) amount, mtDNA-encoded transcripts, and mitochondrial oxidative phosphorylation (OXPHOS) protein levels. We report global expressional downregulation of mitochondrial oxidative pathways with concomitant downregulation of mtDNA amount, mtDNA-dependent translation system, and protein levels of the OXPHOS machinery in the obese compared with the lean co-twins. Pathway analysis indicated downshifting of fatty acid oxidation, ketone body production and breakdown, and the tricarboxylic acid cycle, which inversely correlated with adiposity, insulin resistance, and inflammatory cytokines. Our results suggest that mitochondrial biogenesis, oxidative metabolic pathways, and OXPHOS proteins in SAT are downregulated in acquired obesity, and are associated with metabolic disturbances already at the preclinical stage. PMID:25972572

  8. Mitochondrial fusion and inheritance of the mitochondrial genome.

    Science.gov (United States)

    Takano, Hiroyoshi; Onoue, Kenta; Kawano, Shigeyuki

    2010-03-01

    Although maternal or uniparental inheritance of mitochondrial genomes is a general rule, biparental inheritance is sometimes observed in protists and fungi,including yeasts. In yeast, recombination occurs between the mitochondrial genomes inherited from both parents.Mitochondrial fusion observed in yeast zygotes is thought to set up a space for DNA recombination. In the last decade,a universal mitochondrial fusion mechanism has been uncovered, using yeast as a model. On the other hand, an alternative mitochondrial fusion mechanism has been identified in the true slime mold Physarum polycephalum.A specific mitochondrial plasmid, mF, has been detected as the genetic material that causes mitochondrial fusion in P. polycephalum. Without mF, fusion of the mitochondria is not observed throughout the life cycle, suggesting that Physarum has no constitutive mitochondrial fusion mechanism.Conversely, mitochondria fuse in zygotes and during sporulation with mF. The complete mF sequence suggests that one gene, ORF640, encodes a fusogen for Physarum mitochondria. Although in general, mitochondria are inherited uniparentally, biparental inheritance occurs with specific sexual crossing in P. polycephalum.An analysis of the transmission of mitochondrial genomes has shown that recombinations between two parental mitochondrial genomes require mitochondrial fusion,mediated by mF. Physarum is a unique organism for studying mitochondrial fusion. PMID:20196232

  9. Somatic alterations in mitochondrial DNA and mitochondrial dysfunction in gastric cancer progression.

    Science.gov (United States)

    Lee, Hsin-Chen; Huang, Kuo-Hung; Yeh, Tien-Shun; Chi, Chin-Wen

    2014-04-14

    Energy metabolism reprogramming was recently identified as one of the cancer hallmarks. One of the underlying mechanisms of energy metabolism reprogramming is mitochondrial dysfunction caused by mutations in nuclear genes or mitochondrial DNA (mtDNA). In the past decades, several types of somatic mtDNA alterations have been identified in gastric cancer. However, the role of these mtDNA alterations in gastric cancer progression remains unclear. In this review, we summarize recently identified somatic mtDNA alterations in gastric cancers as well as the relationship between these alterations and the clinicopathological features of gastric cancer. The causative factors and potential roles of the somatic mtDNA alterations in cancer progression are also discussed. We suggest that point mutations and mtDNA copy number decreases are the two most common mtDNA alterations that result in mitochondrial dysfunction in gastric cancers. The two primary mutation types (transition mutations and mononucleotide or dinucleotide repeat instability) imply potential causative factors. Mitochondrial dysfunction-generated reactive oxygen species may be involved in the malignant changes of gastric cancer. The search for strategies to prevent mtDNA alterations and inhibit the mitochondrial retrograde signaling will benefit the development of novel treatments for gastric cancer and other malignancies. PMID:24744584

  10. Mitochondrial Dysfunction and Psychiatric Disorders

    OpenAIRE

    Shaw-Hwa Jou; Nan-Yin Chiu; Chin-San Liu

    2009-01-01

    Mitochondria are intracellular organelles crucial in the production of cellular energy.Mitochondrial diseases may result from malfunctions in this biochemical cascade. Severalinvestigators have proposed that mitochondrial dysfunction is related to the pathophysiologyof bipolar disorder (BD), major depressive disorder (MDD) and schizophrenia (SZ). Theauthors reviewed recent study findings and tried to delineate the current understanding of thecorrelation between mitochondrial dysfunction and p...

  11. Mitochondrial emitted electromagnetic signals mediate retrograde signaling.

    Science.gov (United States)

    Bagkos, Georgios; Koufopoulos, Kostas; Piperi, Christina

    2015-12-01

    Recent evidence shows that mitochondria regulate nuclear transcriptional activity both in normal and cell stress conditions, known as retrograde signaling. Under normal mitochondrial function, retrograde signaling is associated with mitochondrial biogenesis, normal cell phenotype and metabolic profile. In contrast, mitochondrial dysfunction leads to abnormal (oncogenic) cell phenotype and altered bio-energetic profile (nucleus reprogramming). Despite intense research efforts, a concrete mechanism through which mitochondria determine the group of genes expressed by the nucleus is still missing. The present paper proposes a novel hypothesis regarding retrograde signaling. More specifically, it reveals the mitochondrial membrane potential (MMP) and the accompanied strong electromagnetic field (EF) as key regulatory factors of nuclear activity. Mitochondrial emitted EFs extend in long distance and affect the function of nuclear membrane receptors. Depending on their frequencies, EFs can directly activate or deactivate different groups of nuclear receptors and so determine nuclear gene expression. One of the key features of the above hypothesis is that nuclear membrane receptors, besides their own endogenous or chemical ligands (hormones, lipids, etc.), can also be activated by electromagnetic signals. Moreover, normal MMP values (about -140 mV) are associated with the production of high ATP quantities and small levels of reactive oxygen species (ROS) while the hyperpolarization observed in all cancer cell types leads to a dramatic fall in ATP production and an analogous increase in ROS. The diminished ATP and increased ROS production negatively affect the function of all cellular systems including nucleus. Restoration of mitochondrial function, which is characterized by the fluctuation of MMP and EF values within a certain (normal) range, is proposed as a necessary condition for normal nuclear function and cancer therapy. PMID:26474928

  12. Decreased Levels of Proapoptotic Factors and Increased Key Regulators of Mitochondrial Biogenesis Constitute New Potential Beneficial Features of Long-lived Growth Hormone Receptor Gene–Disrupted Mice

    OpenAIRE

    Gesing, Adam; Masternak, Michal M.; Lewinski, Andrzej; Karbownik-Lewinska, Malgorzata; Kopchick, John J.; Bartke, Andrzej

    2012-01-01

    Decreased somatotrophic signaling is among the most important mechanisms associated with extended longevity. Mice homozygous for the targeted disruption of the growth hormone (GH) receptor gene (GH receptor knockout; GHRKO) are obese and dwarf, are characterized by a reduced weight and body size, undetectable levels of GH receptor, high concentration of serum GH, and greatly reduced plasma levels of insulin and insulin-like growth factor-I, and are remarkably long lived. Recent results sugges...

  13. Normal skin and hypertrophic scar fibroblasts differentially regulate collagen and fibronectin expression as well as mitochondrial membrane potential in response to basic fibroblast growth factor

    OpenAIRE

    Rui Song; Hui-Ning Bian; Wen Lai; Hua-De Chen; Ke-Seng Zhao

    2011-01-01

    Basic fibroblast growth factor (bFGF) regulates skin wound healing; however, the underlying mechanism remains to be defined. In the present study, we determined the effects of bFGF on the regulation of cell growth as well as collagen and fibronectin expression in fibroblasts from normal human skin and from hypertrophic scars. We then explored the involvement of mitochondria in mediating bFGF-inducedeffects on the fibroblasts. We isolated and cultivated normal and hypertrophic scar fibroblasts...

  14. Implications of mitochondrial DNA mutations and mitochondrial dysfunction in tumorigenesis

    Institute of Scientific and Technical Information of China (English)

    Jianxin Lu; Lokendra Kumar Sharma; Yidong Bai

    2009-01-01

    Alterations in oxidative phosphorylation resulting from mitochondrial dysfunction have long been hypothesized to be involved in tumorigenesis. Mitochondria have recently been shown to play an important role in regulating both programmed cell death and cell proliferation. Furthermore, mitochondrial DNA (mtDNA) mutations have been found in various cancer cells. However, the role of these mtDNA mutations in tumorigenesis remains largely unknown. This review focuses on basic mitochondrial genetics, mtDNA mutations and consequential mitochondrial dysfunction associated with cancer. The potential molecular mechanisms, mediating the pathogenesis from mtDNA mutations and mitochondrial dysfunction to tumorigenesis are also discussed.

  15. Enterotoxemia em bovino Bovine enterotoxaemia

    Directory of Open Access Journals (Sweden)

    F.C.F. Lobato

    2006-10-01

    Full Text Available This report describes a case of bovine enterotoxaemia in Morro da Garça, Minas Gerais, Brazil. Clostridium perfringens type D was isolated in pure culture and was characterized by biochemical reactions and PCR. By the mouse neutralization test, the presence of epsilon toxin from intestinal content was detected.

  16. Enterotoxemia em bovino Bovine enterotoxaemia

    OpenAIRE

    F.C.F. Lobato; R.A. Assis; V.L.V. Abreu; M.F. Souza Jr.; C.G.R.D. Lima; F.M. Salvarani

    2006-01-01

    This report describes a case of bovine enterotoxaemia in Morro da Garça, Minas Gerais, Brazil. Clostridium perfringens type D was isolated in pure culture and was characterized by biochemical reactions and PCR. By the mouse neutralization test, the presence of epsilon toxin from intestinal content was detected.

  17. trans activation by the full-length E2 proteins of human papillomavirus type 16 and bovine papillomavirus type 1 in vitro and in vivo: cooperation with activation domains of cellular transcription factors.

    OpenAIRE

    Ushikai, M; Lace, M J; Yamakawa, Y.; Kono, M; Anson, J; Ishiji, T; Parkkinen, S; Wicker, N.; Valentine, M E; Davidson, I

    1994-01-01

    Papillomaviral E2 genes encode proteins that regulate viral transcription. While the full-length bovine papillomavirus type 1 (BPV-1) E2 peptide is a strong trans activator, the homologous full-length E2 product of human papillomavirus type 16 (HPV-16) appeared to vary in function in previous studies. Here we show that when expressed from comparable constructs, the full-length E2 products of HPV-16 and BPV-1 trans activate a simple E2- and Sp1-dependent promoter up to approximately 100-fold i...

  18. Assembly of a chimeric respiratory chain from bovine heart submitochondrial particles and cytochrome bd terminal oxidase of Escherichia coli

    OpenAIRE

    Gavrikova, Eleonora V.; Grivennikova, Vera G.; Borisov, Vitaliy B.; Cecchini, Gary; Vinogradov, Andrei D.

    2009-01-01

    Cytochrome bd is a terminal quinol oxidase in Escherichia coli. Mitochondrial respiration is inhibited at cytochrome bc1 (complex III) by myxothiazol. Mixing purified cytochrome bd oxidase with myxothiazol-inhibited bovine heart submitochondrial particles (SMP) restores up to 50% of the original rotenone-sensitive NADH oxidase and succinate oxidase activities in the absence of exogenous ubiquinone analogues. Complex III bypassed respiration and is saturated at amounts of added cytochrome bd s...

  19. Analysis of Mitochondrial Network Morphology in Cultured Myoblasts from Patients with Mitochondrial Disorders

    Czech Academy of Sciences Publication Activity Database

    Sládková, J.; Spáčilová, J.; Čapek, Martin; Tesařová, M.; Hansíková, H.; Honzík, T.; Martínek, J.; Zámečník, J.; Kostková, O.; Zeman, J.

    2015-01-01

    Roč. 39, č. 5 (2015), s. 340-350. ISSN 0191-3123 R&D Projects: GA ČR(CZ) GB14-36804G; GA MŠk(CZ) LH13028 Institutional support: RVO:67985823 Keywords : cristae * Fiji * image analysis * mitochondrial disorders * myoblasts * ultrastructure Subject RIV: EA - Cell Biology Impact factor: 1.078, year: 2014

  20. Propionate induces the bovine cytosolic phosphoenolpyruvate carboxykinase promoter activity.

    Science.gov (United States)

    Zhang, Qian; Koser, Stephanie L; Donkin, Shawn S

    2016-08-01

    Cytosolic phosphoenolpyruvate carboxykinase (PCK1) is a critical enzyme within the metabolic networks for gluconeogenesis, hepatic energy metabolism, and tricarboxylic acid cycle function, and is controlled by several transcription factors including hepatic nuclear factor 4α (HNF4α). The primary objective of the present study was to determine whether propionate regulates bovine PCK1 transcription. The second objective was to determine the action of cyclic AMP (cAMP), glucocorticoids, and insulin, hormonal cues known to modulate glucose metabolism, on bovine PCK1 transcriptional activity. The proximal promoter of the bovine PCK1 gene was ligated to a Firefly luciferase reporter and transfected into H4IIE hepatoma cells. Cells were exposed to treatments for 23 h and luciferase activity was determined in cell lysates. Activity of the PCK1 promoter was linearly induced by propionate, and maximally increased 7-fold with 2.5 mM propionate, which was not muted by 100 nM insulin. Activity of the PCK1 promoter was increased 1-fold by either 1.0 mM cAMP or 5.0µM dexamethasone, and 2.2-fold by their combination. Induction by cAMP and dexamethasone was repressed 50% by 100 nM insulin. Propionate, cAMP, and dexamethasone acted synergistically to induce the PCK1 promoter activity. Propionate-responsive regions, identified by 5' deletion analysis, were located between -1,238 and -409 bp and between -85 and +221 bp. Deletions of the core sequences of the 2 putative HNF4α sites decreased the responsiveness to propionate by approximately 40%. These data indicate that propionate regulates its own metabolism through transcriptional stimulation of the bovine PCK1 gene. This induction is mediated, in part, by the 2 putative HNF4α binding sites in the bovine PCK1 promoter. PMID:27289145

  1. Kajian Fisiologis Penggunaan Bovine Somatotropin (bST) Pada Sapi Pra Afkir

    OpenAIRE

    Dzarnisa Araby; Cut Aida Fitri

    2009-01-01

    Studies of physiological bovine somatotropin (bST) on post lactating dairy ABSTRACT. To increase of milk production nationally with used in dairy cattle business can assist to increase milk production, eighteen post lactating dairy cows in the highland Cipelang Bogor, were used to study the effect used of bovine somatotropin and lactating time. The experimental cows were assigned into a Randomized Block Design with a 3x2 factorial arrangement. The first factor was using of somatotropin (b...

  2. All in good time : dynamics of the bovine estrous cycle investigated with a mathematical model

    OpenAIRE

    Boer, H.M.T.

    2012-01-01

    Bovine fertility is subject of extensive research in animal sciences, especially since a decline in dairy cow fertility has been observed during the last decades. One factor is reduced expression of estrous behavior. Fertility is a complex process, regulated by interactions between brain and reproductive organs. The objective of this thesis was to improve insight in the regulation of dairy cow fertility by developing and using a mechanistic mathematical model of the bovine estrous cycle. The ...

  3. Dynamic regulation of mitochondrial genome maintenance in germ cells.

    Science.gov (United States)

    Kasashima, Katsumi; Nagao, Yasumitsu; Endo, Hitoshi

    2014-01-01

    Mitochondria play a crucial role in the development and function of germ cells. Mitochondria contain a maternally inherited genome that should be transmitted to offspring without reactive oxygen species-induced damage during germ line development. Germ cells are also involved in the mitochondrial DNA (mtDNA) bottleneck; thus, the appropriate regulation of mtDNA in these cells is very important for this characteristic transmission. In this review, we focused on unique regulation of the mitochondrial genome in animal germ cells; paternal elimination and the mtDNA bottleneck in females. We also summarized the mitochondrial nucleoid factors involved in various mtDNA regulation pathways. Among them, mitochondrial transcription factor A (TFAM), which has pleiotropic and essential roles in mtDNA maintenance, appears to have putative roles in germ cell regulation. PMID:24482608

  4. Mitochondrial Processing Peptidase

    Czech Academy of Sciences Publication Activity Database

    Kutejová, Eva; Kučera, Tomáš; Matušková, Anna; Janata, Jiří

    Vol. 1. Oxford : Oxford: Academic Press, 2013 - (Rawlings, N.; Salvesen, G.), s. 1435-1442 ISBN 978-0-12-382219-2 R&D Projects: GA MŠk 2B08064 Institutional support: RVO:61388971 Keywords : mitochondria * mitochondrial peptidase Subject RIV: CE - Biochemistry

  5. Mitochondrial Dysfunction in Cancer

    Directory of Open Access Journals (Sweden)

    KayFMacleod

    2013-12-01

    Full Text Available A mechanistic understanding of how mitochondrial dysfunction contributes to cell growth and tumorigenesis is emerging beyond Warburg as an area of research that is under-explored in terms of its significance for clinical management of cancer. Work discussed in this review focuses less on the Warburg effect and more on mitochondria and how dysfunctional mitochondria modulate cell cycle, gene expression, metabolism, cell viability and other more conventional aspects of cell growth and stress responses. There is increasing evidence that key oncogenes and tumor suppressors modulate mitochondrial dynamics through important signaling pathways and that mitochondrial mass and function vary between tumors and individuals but the sigificance of these events for cancer are not fully appreciated. We explore the interplay between key molecules involved in mitochondrial fission and fusion and in apoptosis, as well as in mitophagy, biogenesis and spatial dynamics and consider how these distinct mechanisms are coordinated in response to physiological stresses such as hypoxia and nutrient deprivation. Importantly, we examine how deregulation of these processes in cancer has knockon effects for cell proliferation and growth. Scientifically, there is also scope for defining what mitochondria dysfunction is and here we address the extent to which the functional consequences of such dysfunction can be determined and exploited for cancer diagnosis and treatment.

  6. Mitochondrial Ion Channels

    Science.gov (United States)

    O’Rourke, Brian

    2009-01-01

    In work spanning more than a century, mitochondria have been recognized for their multifunctional roles in metabolism, energy transduction, ion transport, inheritance, signaling, and cell death. Foremost among these tasks is the continuous production of ATP through oxidative phosphorylation, which requires a large electrochemical driving force for protons across the mitochondrial inner membrane. This process requires a membrane with relatively low permeability to ions to minimize energy dissipation. However, a wealth of evidence now indicates that both selective and nonselective ion channels are present in the mitochondrial inner membrane, along with several known channels on the outer membrane. Some of these channels are active under physiological conditions, and others may be activated under pathophysiological conditions to act as the major determinants of cell life and death. This review summarizes research on mitochondrial ion channels and efforts to identify their molecular correlates. Except in a few cases, our understanding of the structure of mitochondrial ion channels is limited, indicating the need for focused discovery in this area. PMID:17059356

  7. A role for septin 2 in Drp1-mediated mitochondrial fission.

    Science.gov (United States)

    Pagliuso, Alessandro; Tham, To Nam; Stevens, Julia K; Lagache, Thibault; Persson, Roger; Salles, Audrey; Olivo-Marin, Jean-Christophe; Oddos, Stéphane; Spang, Anne; Cossart, Pascale; Stavru, Fabrizia

    2016-06-01

    Mitochondria are essential eukaryotic organelles often forming intricate networks. The overall network morphology is determined by mitochondrial fusion and fission. Among the multiple mechanisms that appear to regulate mitochondrial fission, the ER and actin have recently been shown to play an important role by mediating mitochondrial constriction and promoting the action of a key fission factor, the dynamin-like protein Drp1. Here, we report that the cytoskeletal component septin 2 is involved in Drp1-dependent mitochondrial fission in mammalian cells. Septin 2 localizes to a subset of mitochondrial constrictions and directly binds Drp1, as shown by immunoprecipitation of the endogenous proteins and by pulldown assays with recombinant proteins. Depletion of septin 2 reduces Drp1 recruitment to mitochondria and results in hyperfused mitochondria and delayed FCCP-induced fission. Strikingly, septin depletion also affects mitochondrial morphology in Caenorhabditis elegans, strongly suggesting that the role of septins in mitochondrial dynamics is evolutionarily conserved. PMID:27215606

  8. 77 FR 15847 - Bovine Spongiform Encephalopathy; Importation of Bovines and Bovine Products

    Science.gov (United States)

    2012-03-16

    ... been fed ruminant protein, other than milk protein, during their lifetime; The bovines from which the... from animals that are not known to have been fed ruminant protein, other than milk protein, during... March 16, 2012 Part II Department of Agriculture Animal and Plant Health Inspection Service 9 CFR...

  9. A new bovine conjunctiva model shows that Listeria monocytogenes invasion is associated with lysozyme resistance.

    Science.gov (United States)

    Warren, Jessica; Owen, A Rhys; Glanvill, Amy; Francis, Asher; Maboni, Grazieli; Nova, Rodrigo J; Wapenaar, Wendela; Rees, Catherine; Tötemeyer, Sabine

    2015-08-31

    Listerial keratoconjunctivitis ('silage eye') is a wide spread problem in ruminants causing economic losses to farmers and impacts negatively on animal welfare. It results from direct entry of Listeria monocytogenes into the eye, often following consumption of contaminated silage. An isolation protocol for bovine conjunctival swabbing was developed and used to sample both infected and healthy eyes bovine eyes (n=46). L. monocytogenes was only isolated from one healthy eye sample, and suggests that this organism can be present without causing disease. To initiate a study of this disease, an infection model was developed using isolated conjunctiva explants obtained from cattle eyes post slaughter. Conjunctiva were cultured and infected for 20 h with a range of L. monocytogenes isolates (n=11), including the healthy bovine eye isolate and also strains isolated from other bovine sources, such as milk or clinical infections. Two L. monocytogenes isolates (one from a healthy eye and one from a cattle abortion) were markedly less able to invade conjunctiva explants, but one of those was able to efficiently infect Caco2 cells indicating that it was fully virulent. These two isolates were also significantly more sensitive to lysozyme compared to most other isolates tested, suggesting that lysozyme resistance is an important factor when infecting bovine conjunctiva. In conclusion, we present the first bovine conjunctiva explant model for infection studies and demonstrate that clinical L. monocytogenes isolates from cases of bovine keratoconjunctivitis are able to infect these tissues. PMID:25778543

  10. Organization of the human mitochondrial transcription initiation complex

    OpenAIRE

    Yakubovskaya, Elena; Guja, Kip E.; Eng, Edward T.; Choi, Woo Suk; Mejia, Edison; Beglov, Dmitri; Lukin, Mark; Kozakov, Dima; Garcia-Diaz, Miguel

    2014-01-01

    Initiation of transcription in human mitochondria involves two factors, TFAM and TFB2M, in addition to the mitochondrial RNA polymerase, POLRMT. We have investigated the organization of the human mitochondrial transcription initiation complex on the light-strand promoter (LSP) through solution X-ray scattering, electron microscopy (EM) and biochemical studies. Our EM results demonstrate a compact organization of the initiation complex, suggesting that protein–protein interactions might help m...

  11. Muscle mitochondrial changes with aging and exercise1234

    OpenAIRE

    Lanza, Ian R.; Nair, K. Sreekumaran

    2008-01-01

    Aging has been reported to be accompanied by reduced mitochondrial function and insulin sensitivity. Whether these deleterious effects result from chronological age or lifestyle-related factors such as adiposity and physical inactivity remains debatable. The beneficial effects of exercise on mitochondrial function and insulin sensitivity are well documented; however, it is unclear whether exercise can effectively prevent, reverse, or delay the onset of these age-related dysfunctions. Other in...

  12. Private Mitochondrial DNA Variants in Danish Patients with Hypertrophic Cardiomyopathy

    OpenAIRE

    Hagen, Christian M; Aidt, Frederik H; Havndrup, Ole; Hedley, Paula L.; Jensen, Morten K.; Kanters, Jørgen K.; Pham, Tam T.; Bundgaard, Henning; Christiansen, Michael

    2015-01-01

    Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease primarily caused by mutations in genes coding for sarcomeric proteins. A molecular-genetic etiology can be established in ~60% of cases. Evolutionarily conserved mitochondrial DNA (mtDNA) haplogroups are susceptibility factors for HCM. Several polymorphic mtDNA variants are associated with a variety of late-onset degenerative diseases and affect mitochondrial function. We examined the role of private, non-haplogroup associated, mi...

  13. Pneumolysin causes neuronal cell death through mitochondrial damage

    OpenAIRE

    Braun, Johann S.; Hoffmann, Olaf; Schickhaus, Miriam; Freyer, Dorette; Dagand, Emilie; Bermpohl, Daniela; Mitchell, Tim J.; Bechmann, Ingo; Weber, Joerg R.

    2007-01-01

    Bacterial toxins such as pneumolysin are key mediators of cytotoxicity in infections. Pneumolysin is a pore-forming toxin released by Streptococcus pneumoniae, the major cause of bacterial meningitis. We found that pneumolysin is the pneumococcal factor that accounts for the cell death pathways induced by live bacteria in primary neurons. The pore-forming activity of pneumolysin is essential for the induction of mitochondrial damage and apoptosis. Pneumolysin colocalized with mitochondrial me...

  14. Mitochondrial Dysfunctions in Neurodegenerative Diseases: Relevance to Alzheimer's Disease

    OpenAIRE

    Jana Hroudová; Namrata Singh; Zdeněk Fišar

    2014-01-01

    Mitochondrial dysfunctions are supposed to be responsible for many neurodegenerative diseases dominating in Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD). A growing body of evidence suggests that defects in mitochondrial metabolism and particularly of electron transport chain may play a role in pathogenesis of AD. Structurally and functionally damaged mitochondria do not produce sufficient ATP and are more prominent in producing proapoptotic factors and rea...

  15. Cutaneous mitochondrial respirometry: non-invasive monitoring of mitochondrial function.

    Science.gov (United States)

    Harms, Floor A; Bodmer, Sander I A; Raat, Nicolaas J H; Mik, Egbert G

    2015-08-01

    The recently developed technique for measuring cutaneous mitochondrial oxygen tension (mitoPO2) by means of the Protoporphyrin IX-Triplet State Lifetime Technique (PpIX-TSLT) provides new opportunities for assessing mitochondrial function in vivo. The aims of this work were to study whether cutaneous mitochondrial measurements reflect mitochondrial status in other parts of the body and to demonstrate the feasibility of the technique for potential clinical use. The first part of this paper demonstrates a correlation between alterations in mitochondrial parameters in skin and other tissues during endotoxemia. Experiments were performed in rats in which mitochondrial dysfunction was induced by a lipopolysaccharide-induced sepsis (n = 5) and a time control group (n = 5). MitoPO2 and mitochondrial oxygen consumption (mitoVO2) were measured using PpIX-TSLT in skin, liver and buccal mucosa of the mouth. Both skin and buccal mucosa show a significant mitoPO2-independent decrease (P paper describes the clinical concept of monitoring cutaneous mitochondrial respiration in man. A first prototype of a clinical PpIX-TSLT monitor is described and its usability is demonstrated on human skin. We expect that clinical implementation of this device will greatly contribute to our understanding of mitochondrial oxygenation and oxygen metabolism in perioperative medicine and in critical illness. Our ultimate goal is to develop a clinical monitor for mitochondrial function and the current results are an important step forward. PMID:25388510

  16. DNA methylation status of nuclear-encoded mitochondrial genes underlies the tissue-dependent mitochondrial functions

    Directory of Open Access Journals (Sweden)

    Takasugi Masaki

    2010-08-01

    Full Text Available Abstract Background Mitochondria are semi-autonomous, semi-self-replicating organelles harboring their own DNA (mitochondrial DNA, mtDNA, and their dysregulation is involved in the development of various diseases. While mtDNA does not generally undergo epigenetic modifications, almost all mitochondrial proteins are encoded by nuclear DNA. However, the epigenetic regulation of nuclear-encoded mitochondrial genes (nuclear mt genes has not been comprehensively analyzed. Results We analyzed the DNA methylation status of 899 nuclear mt genes in the liver, brain, and heart tissues of mouse, and identified 636 nuclear mt genes carrying tissue-dependent and differentially methylated regions (T-DMRs. These nuclar mt genes are involved in various mitochondrial functions and they also include genes related to human diseases. T-DMRs regulate the expression of nuclear mt genes. Nuclear mt genes with tissue-specific hypomethylated T-DMRs were characterized by enrichment of the target genes of specific transcription factors such as FOXA2 in the liver, and CEBPA and STAT1 in the brain. Conclusions A substantial proportion of nuclear mt genes contained T-DMRs, and the DNA methylation status of numerous T-DMRs should underlie tissue-dependent mitochondrial functions.

  17. Diagnosis and Control of Bovine Neosporosis.

    Science.gov (United States)

    McAllister, Milton M

    2016-07-01

    Neosporosis is one of the most common and widespread causes of bovine abortion. The causative parasite is transmitted in at least two ways, horizontally from canids, and by endogenous transmission within maternal lines of infected cattle. The prevalence of neosporosis is higher in the dairy industry than in the beef industry because of risk factors associated with intensive feeding. There are no vaccines, but logical management options are discussed that can lower the risk of abortion outbreaks and gradually reduce the prevalence of infection within herds. Steps should be taken to prevent total mixed rations from becoming contaminated by canine feces. If a herd has a high rate of infection that is associated with abortions in heifers, then the rate of reduction of infection prevalence can be speeded by only selecting seronegative replacement heifers to enter the breeding herd. Elimination of all infected cattle is not a recommended goal. PMID:27161392

  18. Characterization of bovine A20 gene: Expression mediated by NF-κB pathway in MDBK cells infected with bovine viral diarrhea virus-1.

    Science.gov (United States)

    Fredericksen, Fernanda; Villalba, Melina; Olavarría, Víctor H

    2016-05-01

    Cytokine production for immunological process is tightly regulated at the transcriptional and posttranscriptional levels. The NF-κB signaling pathway maintains immune homeostasis in the cell through the participation of molecules such as A20 (TNFAIP3), which is a key regulatory factor in the immune response, hematopoietic differentiation, and immunomodulation. Although A20 has been identified in mammals, and despite recent efforts to identify A20 members in other higher vertebrates, relatively little is known about the composition of this regulator in other classes of vertebrates, particularly for bovines. In this study, the genetic context of bovine A20 was explored and compared against homologous genes in the human, mouse, chicken, dog, and zebrafish chromosomes. Through in silico analysis, several regions of interest were found conserved between even phylogenetically distant species. Additionally, a protein-deduced sequence of bovine A20 evidenced many conserved domains in humans and mice. Furthermore, all potential amino acid residues implicated in the active site of A20 were conserved. Finally, bovine A20 mRNA expression as mediated by the bovine viral diarrhea virus and poly (I:C) was evaluated. These analyses evidenced a strong fold increase in A20 expression following virus exposure, a phenomenon blocked by a pharmacological NF-κB inhibitor (BAY 117085). Interestingly, A20 mRNA had a half-life of only 32min, likely due to adenylate- and uridylate-rich elements in the 3'-untranslated region. Collectively, these data identify bovine A20 as a regulator of immune marker expression. Finally, this is the first report to find the bovine viral diarrhea virus modulating bovine A20 activation through the NF-κB pathway. PMID:26809100

  19. Preventing mitochondrial fission impairs mitochondrial function and leads to loss of mitochondrial DNA.

    Directory of Open Access Journals (Sweden)

    Philippe A Parone

    Full Text Available Mitochondria form a highly dynamic tubular network, the morphology of which is regulated by frequent fission and fusion events. However, the role of mitochondrial fission in homeostasis of the organelle is still unknown. Here we report that preventing mitochondrial fission, by down-regulating expression of Drp1 in mammalian cells leads to a loss of mitochondrial DNA and a decrease of mitochondrial respiration coupled to an increase in the levels of cellular reactive oxygen species (ROS. At the cellular level, mitochondrial dysfunction resulting from the lack of fission leads to a drop in the levels of cellular ATP, an inhibition of cell proliferation and an increase in autophagy. In conclusion, we propose that mitochondrial fission is required for preservation of mitochondrial function and thereby for maintenance of cellular homeostasis.

  20. Pathological studies on bovine viral diarrhea

    International Nuclear Information System (INIS)

    Bovine viral diarrhea virus (BVDV) is classified as an RNA virus in the family flavin viride and is a member of the genus pest virus (Collet et al 1989). BVDV has a worldwide distribution and infections in cattle populations (Kahrs et al 1970). It was recognized since 50 years ago, the initial description of an acute enteric disease of cattle in North America, which was characterized by outbreaks of diarrhea and erosive of digestive tract (Olafsonp et al 1946). The disease and causative agent were named bovine viral diarrhea (B V D ) and (B V DV), respectively. This virus was subsequently associated with a sporadically occurring and highly fatal enteric disease that was termed mucosal disease (M D), (Ramsey and Chivers 1953). The initial isolate of BVDV did not produce cytopathic effect in cell culture, whereas an isolate from MD did produce cytopathic effects (Lee et al 1957). In vitro characteristic of non cytopathic or sytopathic effects of BVDV is referred to as the biotype of the virus. It has now been established that MD occurs only when xattle that are born immuno tolerant to and persistently infected with a noncyropathic BVDV become super infected with a cytopathic BVDV. The knowledge of the molecular biology. Pathogenesis and epidemiology of BVDV has greatly evolved in the past 10-15 years and has provided a better understanding of this complex infectious agent. Infection with BVDV can result in a wide spectrum of diseases ranging from subclinical infection s to a highly fatal from known as mucosal disease (ND). The clinical response to infection depends on multiple interactive factors. Host factors that influence the clinical outcome of BVDV infection include whether the host is immunocompetent or immuno tolerant to BVDV, pregnancy status, gestational age of the fetus, immune status (passively derived or actively derived from previous infection or vaccination) and concurrent level of environmental stress

  1. HUMAN MITOCHONDRIAL tRNA MUTATIONS IN MATERNALLY INHERITED DEAFNESS

    Institute of Scientific and Technical Information of China (English)

    ZHENG Jing; GONG Sha-sha; TANG Xiao-wen; ZHU Yi; GUAN Min-xin

    2013-01-01

    Mutations in mitochondrial tRNA genes have been shown to be associated with maternally inherited syn-dromic and non-syndromic deafness. Among those, mutations such as tRNALeu(UUR) 3243A>G associated with syndromic deafness are often present in heteroplasmy, and the non-syndromic deafness-associated tRNA mu-tations including tRNASer(UCN) 7445A>G are often in homoplasmy or in high levels of heteroplasmy. These tRNA mutations are the primary factors underlying the development of hearing loss. However, other tRNA mutations such as tRNAThr 15927G>A and tRNASer(UCN) 7444G>A are insufficient to produce a deafness phe-notype, but always act in synergy with the primary mitochondrial DNA mutations, and can modulate their phenotypic manifestation. These tRNA mutations may alter the structure and function of the corresponding mitochondrial tRNAs and cause failures in tRNAs metabolism. Thereby, the impairment of mitochondrial protein synthesis and subsequent defects in respiration caused by these tRNA mutations, results in mitochon-drial dysfunctions and eventually leads to the development of hearing loss. Here, we summarized the deaf-ness-associated mitochondrial tRNA mutations and discussed the pathophysiology of these mitochondrial tRNA mutations, and we hope these data will provide a foundation for the early diagnosis, management, and treatment of maternally inherited deafness.

  2. Evidence of Mitochondrial Dysfunction in Autism and Implications for Treatment

    Directory of Open Access Journals (Sweden)

    Daniel A. Rossignol

    2008-01-01

    Full Text Available Classical mitochondrial diseases occur in a subset of individuals with autism and are usually caused by genetic anomalies or mitochondrial respiratory pathway deficits. However, in many cases of autism, there is evidence of mitochondrial dysfunction (MtD without the classic features associated with mitochondrial disease. MtD appears to be more common in autism and presents with less severe signs and symptoms. It is not associated with discernable mitochondrial pathology in muscle biopsy specimens despite objective evidence of lowered mitochondrial functioning. Exposure to environ-mental toxins is the likely etiology for MtD in autism. This dysfunction then contributes to a number of diagnostic symptoms and comorbidities observed in autism including: cognitive impairment, language deficits, abnormal energy metabolism, chronic gastrointestinal problems, abnormalities in fatty acid oxidation, and increased oxidative stress. MtD and oxidative stress may also explain the high male to female ratio found in autism due to increased male vulnerability to these dysfunctions. Biomarkers for mitochondrial dysfunction have been identified, but seem widely under-utilized despite available therapeutic interventions. Nutritional supplementation to decrease oxidative stress along with factors to improve reduced glutathione, as well as hyperbaric oxygen therapy (HBOT represent supported and rationale approaches. The underlying pathophysiology and autistic symptoms of affected individuals would be expected to either improve or cease worsening once effective treatment for MtD is implemented.

  3. Gaining mass: the structure of respiratory complex I-from bacterial towards mitochondrial versions.

    Science.gov (United States)

    Letts, James A; Sazanov, Leonid A

    2015-08-01

    The 1MDa, 45-subunit proton-pumping NADH-ubiquinone oxidoreductase (complex I) is the largest complex of the mitochondrial electron transport chain. The molecular mechanism of complex I is central to the metabolism of cells, but has yet to be fully characterized. The last two years have seen steady progress towards this goal with the first atomic-resolution structure of the entire bacterial complex I, a 5Å cryo-electron microscopy map of bovine mitochondrial complex I and a ∼3.8Å resolution X-ray crystallographic study of mitochondrial complex I from yeast Yarrowia lipotytica. In this review we will discuss what we have learned from these studies and what remains to be elucidated. PMID:26387075

  4. Ingested bovine amniotic fluid enhances morphine antinociception in rats

    OpenAIRE

    Corpening, James W.; Doerr, Jean C.; Kristal, Dr. Mark B.

    2000-01-01

    Ingestion by rats of rat placenta or amniotic fluid enhances opioid-mediated, or partly opioid-mediated, antinociception produced by morphine injection, vaginal or cervical stimulation, late pregnancy, and foot shock. This phenomenon is believed to be produced by a placental opioid-enhancing factor (POEF). Ingestion by rats of human or dolphin placenta has also been shown to enhance opioid antinociception, suggesting that POEF may be common to many mammalian species. We tested bovine amnio...

  5. The link between mitochondrial complex I and brain-derived neurotrophic factor in SH-SY5Y cells--The potential of JNX1001 as a therapeutic agent.

    Science.gov (United States)

    Kim, Helena K; Mendonça, Karina M; Howson, Patrick A; Brotchie, Jonathan M; Andreazza, Ana C

    2015-10-01

    Mitochondrial complex I, which is the first member of the electron transport chain responsible for producing ATP, can produce reactive oxygen species and oxidative stress when it becomes dysfunctional. Complex I dysfunction and oxidative stress are strongly implicated in bipolar disorder (BD), a debilitating psychiatric disease, as is decreased levels of brain derived neurotrophic factor (BDNF) found in patients with BD, which is related to complex I activity. JNX1001, a clinical trial ready brain penetrant sapogenin, increases BDNF levels in animal models. Hence, we aimed to examine if JNX1001 can prevent complex I dysfunction-induced alterations produced by rotenone treatment in human neuroblastoma cells (SH-SY5Y). Complex I dysfunction decreased cell viability and increased protein carbonylation and nitration, confirming previous findings. Complex I dysfunction also decreased intracellular and extracellular BDNF levels. JNX1001 pre-treatment prevented complex I dysfunction-induced protein carbonylation and nitration and improved cell viability at concentrations of 30 nM and 300 nM, but more robustly at 300 nM. JNX1001 was also able to prevent decreased intracellular and extracellular BDNF levels, where it produced a ten-fold increase in intracellular BDNF levels at a concentration of 300 nM. While further studies are required to examine the neuroprotective ability of JNX1001 against alterations produced by complex I defect in more complex systems, such as in animal models, the findings of this study demonstrate the potential of JNX1001 to be used as a therapeutic agent to protect against complex I dysfunction-induced alterations that may be highly relevant to BD. PMID:26164791

  6. Mannheimia haemolytica Leukotoxin Binds to Lipid Rafts in Bovine Lymphoblastoid Cells and Is Internalized in a Dynamin-2- and Clathrin-Dependent Manner▿

    OpenAIRE

    Atapattu, Dhammika N.; Czuprynski, Charles J.

    2007-01-01

    Mannheimia haemolytica is the principal bacterial pathogen of the bovine respiratory disease complex. Its most important virulence factor is a leukotoxin (LKT), which is a member of the RTX family of exotoxins produced by many gram-negative bacteria. Previous studies demonstrated that LKT binds to the β2-integrin LFA-1 (CD11a/CD18) on bovine leukocytes, resulting in cell death. In this study, we demonstrated that depletion of lipid rafts significantly decreases LKT-induced bovine lymphoblasto...

  7. Bovine Tuberculosis, A Zoonotic Disease

    OpenAIRE

    Tarmudji; Supar

    2008-01-01

    Bovine tuberculosis is caused by the infection of Mycobacterium tuberculosis var. bovis (M. bovis). This species is one of Mycobacterium tuberculosis complex, can infect wide range of hosts: cattle and other domesticated animals, wild mammals and humans (zoonotic). M. bovis bacterium from infected hosts can be transmitted to other susceptible animals and humans through respiratory excretes and secretion materials. Humans can be infected with M. bovis by ingested M. bovis contaminated animal p...

  8. p53's mitochondrial translocation and MOMP action is independent of Puma and Bax and severely disrupts mitochondrial membrane integrity

    Institute of Scientific and Technical Information of China (English)

    Sonja Wolff; Susan Erster; Gustavo Palacios; Ute M Moll

    2008-01-01

    p53's apoptotic program consists of transcription-dependent and transcription-independent pathways. In the latter, physical interactions between mitochondrial p53 and anti-and pro-apoptotic members of the Bcl2 family of mitochondrial permeability regulators are central. Using isogenic cell systems with defined deficiencies, we characterize in detail how mitochondrial p53 contributes to mitochondrial permeabilization, to what extent its action depends on other key Bcl2 family members and define its release activity. We show that mitochondrial p53 is highly efficient in inducing the release of soluble and insoluble apoptogenic factors by severely disrupting outer and inner mitochondrial membrane integrity. This action is associated with wild-type p53-induced oligomerization of Bax, Bak and VDAC and the formation of a stress-induced endogenous complex between p53 and cyclophilin D, normally located at the inner membrane. Tumor-derived p53 mutants are deficient in activating the Bax/Bak lipid pore. These actions are independent of Puma and Bax. Importantly, the latter distinguishes the mitochondrial from the cytosolic p53 death pathway.

  9. Mitochondrial cholesterol: mechanisms of import and effects on mitochondrial function.

    Science.gov (United States)

    Martin, Laura A; Kennedy, Barry E; Karten, Barbara

    2016-04-01

    Mitochondria require cholesterol for biogenesis and membrane maintenance, and for the synthesis of steroids, oxysterols and hepatic bile acids. Multiple pathways mediate the transport of cholesterol from different subcellular pools to mitochondria. In steroidogenic cells, the steroidogenic acute regulatory protein (StAR) interacts with a mitochondrial protein complex to mediate cholesterol delivery to the inner mitochondrial membrane for conversion to pregnenolone. In non-steroidogenic cells, several members of a protein family defined by the presence of a StAR-related lipid transfer (START) domain play key roles in the delivery of cholesterol to mitochondrial membranes. Subdomains of the endoplasmic reticulum (ER), termed mitochondria-associated ER membranes (MAM), form membrane contact sites with mitochondria and may contribute to the transport of ER cholesterol to mitochondria, either independently or in conjunction with lipid-transfer proteins. Model systems of mitochondria enriched with cholesterol in vitro and mitochondria isolated from cells with (patho)physiological mitochondrial cholesterol accumulation clearly demonstrate that mitochondrial cholesterol levels affect mitochondrial function. Increased mitochondrial cholesterol levels have been observed in several diseases, including cancer, ischemia, steatohepatitis and neurodegenerative diseases, and influence disease pathology. Hence, a deeper understanding of the mechanisms maintaining mitochondrial cholesterol homeostasis may reveal additional targets for therapeutic intervention. Here we give a brief overview of mitochondrial cholesterol import in steroidogenic cells, and then focus on cholesterol trafficking pathways that deliver cholesterol to mitochondrial membranes in non-steroidogenic cells. We also briefly discuss the consequences of increased mitochondrial cholesterol levels on mitochondrial function and their potential role in disease pathology. PMID:25425472

  10. Potential Anticarcinogenic Peptides from Bovine Milk

    OpenAIRE

    Giacomo Pepe; Gian Carlo Tenore; Raffaella Mastrocinque; Paola Stusio; Pietro Campiglia

    2013-01-01

    Bovine milk possesses a protein system constituted by two major families of proteins: caseins (insoluble) and whey proteins (soluble). Caseins ( α S1, α S2, β , and κ ) are the predominant phosphoproteins in the milk of ruminants, accounting for about 80% of total protein, while the whey proteins, representing approximately 20% of milk protein fraction, include β -lactoglobulin, α -lactalbumin, immunoglobulins, bovine serum albumin, bovine lactoferrin, and lactoperoxidase, together with other...

  11. Detection of a Novel Bovine Lymphotropic Herpesvirus

    OpenAIRE

    Rovnak, Joel; Quackenbush, Sandra L.; Reyes, Richard A.; Baines, Joel D.; Parrish, Colin R.; Casey, James W.

    1998-01-01

    Degenerate PCR primers which amplify a conserved region of the DNA polymerase genes of the herpesvirus family were used to provide sequence evidence for a new bovine herpesvirus in bovine B-lymphoma cells and peripheral blood mononuclear cells (PBMC). The sequence of the resultant amplicon was found to be distinct from those of known herpesvirus isolates. Alignment of amino acid sequences demonstrated 70% identity with ovine herpesvirus 2, 69% with alcelaphine herpesvirus 1, 65% with bovine h...

  12. Cancer: Mitochondrial Origins

    OpenAIRE

    Stefano, George B.; Kream, Richard M.

    2015-01-01

    The primacy of glucose derived from photosynthesis as an existential source of chemical energy across plant and animal phyla is universally accepted as a core principle in the biological sciences. In mammalian cells, initial processing of glucose to triose phosphate intermediates takes place within the cytosolic glycolytic pathway and terminates with temporal transport of reducing equivalents derived from pyruvate metabolism by membrane-associated respiratory complexes in the mitochondrial ma...

  13. Mitochondrial Subversion in Cancer

    OpenAIRE

    Chatterjee, Aditi; Dasgupta, Santanu; Sidransky, David

    2011-01-01

    Mitochondria control essential cellular activities including generation of ATP via oxidative phosphorylation. Mitochondrial DNA (mtDNA) mutations in the regulatory D-loop region and somatic mtDNA mutations are common in primary human cancers. The biological impact of a given mutation may vary, depending on the nature of the mutation and the proportion of mutant mtDNAs carried by the cell. Identification of mtDNA mutations in precancerous lesions supports their early contribution to cell trans...

  14. Mitochondrial Energy-Deficient Endophenotype in Autism

    Directory of Open Access Journals (Sweden)

    J. J. Gargus

    2008-01-01

    Full Text Available While evidence points to a multigenic etiology of most autism, the pathophysiology of the disorder has yet to be defined and the underlying genes and biochemical pathways they subserve remain unknown. Autism is considered to be influenced by a combination of various genetic, environmental and immunological factors; more recently, evidence has suggested that increased vulnerability to oxidative stress may be involved in the etiology of this multifactorial disorder. Furthermore, recent studies have pointed to a subset of autism associated with the biochemical endophenotype of mitochondrial energy deficiency, identified as a subtle impairment in fat and carbohydrate oxidation. This phenotype is similar, but more subtle than those seen in classic mitochondrial defects. In some cases the beginnings of the genetic underpinnings of these mitochondrial defects are emerging, such as mild mitochondrial dysfunction and secondary carnitine deficiency observed in the subset of autistic patients with an inverted duplication of chromosome 15q11-q13. In addition, rare cases of familial autism associated with sudden infant death syndrome (SIDS or associated with abnormalities in cellular calcium homeostasis, such as malignant hyperthermia or cardiac arrhythmia, are beginning to emerge. Such special cases suggest that the pathophysiology of autism may comprise pathways that are directly or indirectly involved in mitochondrial energy production and to further probe this connection three new avenues seem worthy of exploration: 1 metabolomic clinical studies provoking controlled aerobic exercise stress to expand the biochemical phenotype, 2 high-throughput expression arrays to directly survey activity of the genes underlying these biochemical pathways and 3 model systems, either based upon neuronal stem cells or model genetic organisms, to discover novel genetic and environmental inputs into these pathways.

  15. Mycobacterium bovis (Bovine Tuberculosis) in Humans

    Science.gov (United States)

    Mycobacterium bovis (Bovine Tuberculosis) in Humans What is Mycobacterium bovis ? In the United States, the majority of tuberculosis (TB) cases in people are caused by Mycobacterium tuberculosis ( ...

  16. Roles for Nox4 in the contractile response of bovine pulmonary arteries to hypoxia

    OpenAIRE

    Ahmad, Mansoor; Kelly, Melissa R.; Zhao, Xiangmin; Kandhi, Sharath; Wolin, Michael S.

    2010-01-01

    Hypoxia appears to promote contraction [hypoxic pulmonary vasoconstriction (HPV)] of bovine pulmonary arteries (BPA) through removal of a peroxide-mediated relaxation. This study examines the roles of BPA Nox oxidases and mitochondria in the HPV response. Inhibitors of Nox2 (0.1 mM apocynin and 50 μM gp91-dstat) and mitochondrial electron transport (10 μM antimycin and rotenone) decreased superoxide generation in BPA without affecting contraction to 25 mM KCl or the HPV response. Transfection...

  17. Replicating animal mitochondrial DNA

    Directory of Open Access Journals (Sweden)

    Emily A. McKinney

    2013-01-01

    Full Text Available The field of mitochondrial DNA (mtDNA replication has been experiencing incredible progress in recent years, and yet little is certain about the mechanism(s used by animal cells to replicate this plasmid-like genome. The long-standing strand-displacement model of mammalian mtDNA replication (for which single-stranded DNA intermediates are a hallmark has been intensively challenged by a new set of data, which suggests that replication proceeds via coupled leading-and lagging-strand synthesis (resembling bacterial genome replication and/or via long stretches of RNA intermediates laid on the mtDNA lagging-strand (the so called RITOLS. The set of proteins required for mtDNA replication is small and includes the catalytic and accessory subunits of DNA polymerase y, the mtDNA helicase Twinkle, the mitochondrial single-stranded DNA-binding protein, and the mitochondrial RNA polymerase (which most likely functions as the mtDNA primase. Mutations in the genes coding for the first three proteins are associated with human diseases and premature aging, justifying the research interest in the genetic, biochemical and structural properties of the mtDNA replication machinery. Here we summarize these properties and discuss the current models of mtDNA replication in animal cells.

  18. RhTFAM treatment stimulates mitochondrial oxidative metabolism and improves memory in aged mice

    OpenAIRE

    Thomas, Ravindar R.; Khan, Shaharyar M.; Smigrodzki, Rafal M.; Onyango, Isaac G.; Dennis, Jameel; Khan, Omer M.; Portell, Francisco R.; Bennett, James P

    2012-01-01

    Mitochondrial function declines with age in postmitotic tissues such as brain, heart and skeletal muscle. Despite weekly exercise, aged mice showed substantial losses of mtDNA gene copy numbers and reductions in mtDNA gene transcription and mitobiogenesis signaling in brain and heart. We treated these mice with weekly intravenous injections of recombinant human mitochondrial transcription factor A (rhTFAM). RhTFAM treatment for one month increased mitochondrial respiration in brain, heart and...

  19. Age-related activation of mitochondrial caspase-independent apoptotic signaling in rat gastrocnemius muscle

    OpenAIRE

    Marzetti, Emanuele; Wohlgemuth, Stephanie Eva; Lees, Hazel Anne; Chung, Hae-young; Giovannini, Silvia; Leeuwenburgh, Christiaan

    2008-01-01

    Mitochondria-mediated apoptosis represents a central process driving age-related muscle loss. However, the temporal relation between mitochondrial apoptotic signaling and sarcopenia as well as the regulation of release of pro-apoptotic factors from the mitochondria has not been elucidated. In this study, we investigated mitochondrial apoptotic signaling in skeletal muscle of rats across a wide age range. We also investigated whether mitochondrial-driven apoptosis was accompanied by changes in...

  20. Factoring

    OpenAIRE

    Lenstra, Arjen K.

    1994-01-01

    Factoring, finding a non-trivial factorization of a composite positive integer, is believed to be a hard problem. How hard we think it is, however, changes almost on a daily basis. Predicting how hard factoring will be in the future, an important issue for cryptographic applications of composite numbers, is therefore a challenging task. The author presents a brief survey of general purpose integer factoring algorithms and their implementations

  1. Nanotechnology inspired tools for mitochondrial dysfunction related diseases.

    Science.gov (United States)

    Wen, Ru; Banik, Bhabatosh; Pathak, Rakesh K; Kumar, Anil; Kolishetti, Nagesh; Dhar, Shanta

    2016-04-01

    Mitochondrial dysfunctions are recognized as major factors for various diseases including cancer, cardiovascular diseases, diabetes, neurological disorders, and a group of diseases so called "mitochondrial dysfunction related diseases". One of the major hurdles to gain therapeutic efficiency in diseases where the targets are located in the mitochondria is the accessibility of the targets in this compartmentalized organelle that imposes barriers toward internalization of ions and molecules. Over the time, different tools and techniques were developed to improve therapeutic index for mitochondria acting drugs. Nanotechnology has unfolded as one of the logical and encouraging tools for delivery of therapeutics in controlled and targeted manner simultaneously reducing side effects from drug overdose. Tailor-made nanomedicine based therapeutics can be an excellent tool in the toolbox for diseases associated with mitochondrial dysfunctions. In this review, we present an extensive coverage of possible therapeutic targets in different compartments of mitochondria for cancer, cardiovascular, and mitochondrial dysfunction related diseases. PMID:26776231

  2. Polymorphisms of mitochondrially encoded proteins.

    OpenAIRE

    Spinner, N B; King, M. C.

    1986-01-01

    Polymorphisms of mitochondrially encoded proteins can be detected in human lymphocytes by sodium dodecyl-sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Using an SDS-polyacrylamide 8 M urea system, 17 mitochondrially encoded proteins are distinguishable. Three of these (ME-6, ME-8, and ME-17) were polymorphic among 92 individuals screened, and these polymorphisms are reported here for the first time. With SDS-polyacrylamide electrophoresis without urea, 18 mitochondrial proteins are de...

  3. The effect of ethidium bromide and chloramphenicol on mitochondrial biogenesis in primary human fibroblasts

    International Nuclear Information System (INIS)

    The expression of mitochondrial components is controlled by an intricate interplay between nuclear transcription factors and retrograde signaling from mitochondria. The role of mitochondrial DNA (mtDNA) and mtDNA-encoded proteins in mitochondrial biogenesis is, however, poorly understood and thus far has mainly been studied in transformed cell lines. We treated primary human fibroblasts with ethidium bromide (EtBr) or chloramphenicol for six weeks to inhibit mtDNA replication or mitochondrial protein synthesis, respectively, and investigated how the cells recovered from these insults two weeks after removal of the drugs. Although cellular growth and mitochondrial gene expression were severely impaired after both inhibitor treatments we observed marked differences in mitochondrial structure, membrane potential, glycolysis, gene expression, and redox status between fibroblasts treated with EtBr and chloramphenicol. Following removal of the drugs we further detected clear differences in expression of both mtDNA-encoded genes and nuclear transcription factors that control mitochondrial biogenesis, suggesting that the cells possess different compensatory mechanisms to recover from drug-induced mitochondrial dysfunction. Our data reveal new aspects of the interplay between mitochondrial retrograde signaling and the expression of nuclear regulators of mitochondrial biogenesis, a process with direct relevance to mitochondrial diseases and chloramphenicol toxicity in humans. -- Highlights: ► Cells respond to certain environmental toxins by increasing mitochondrial biogenesis. ► We investigated the effect of Chloramphenicol and EtBr in primary human fibroblasts. ► Inhibiting mitochondrial protein synthesis or DNA replication elicit different effects. ► We provide novel insights into the cellular responses toxins and antibiotics.

  4. The effect of ethidium bromide and chloramphenicol on mitochondrial biogenesis in primary human fibroblasts

    Energy Technology Data Exchange (ETDEWEB)

    Kao, Li-Pin; Ovchinnikov, Dmitry; Wolvetang, Ernst, E-mail: e.wolvetang@uq.edu.au

    2012-05-15

    The expression of mitochondrial components is controlled by an intricate interplay between nuclear transcription factors and retrograde signaling from mitochondria. The role of mitochondrial DNA (mtDNA) and mtDNA-encoded proteins in mitochondrial biogenesis is, however, poorly understood and thus far has mainly been studied in transformed cell lines. We treated primary human fibroblasts with ethidium bromide (EtBr) or chloramphenicol for six weeks to inhibit mtDNA replication or mitochondrial protein synthesis, respectively, and investigated how the cells recovered from these insults two weeks after removal of the drugs. Although cellular growth and mitochondrial gene expression were severely impaired after both inhibitor treatments we observed marked differences in mitochondrial structure, membrane potential, glycolysis, gene expression, and redox status between fibroblasts treated with EtBr and chloramphenicol. Following removal of the drugs we further detected clear differences in expression of both mtDNA-encoded genes and nuclear transcription factors that control mitochondrial biogenesis, suggesting that the cells possess different compensatory mechanisms to recover from drug-induced mitochondrial dysfunction. Our data reveal new aspects of the interplay between mitochondrial retrograde signaling and the expression of nuclear regulators of mitochondrial biogenesis, a process with direct relevance to mitochondrial diseases and chloramphenicol toxicity in humans. -- Highlights: ► Cells respond to certain environmental toxins by increasing mitochondrial biogenesis. ► We investigated the effect of Chloramphenicol and EtBr in primary human fibroblasts. ► Inhibiting mitochondrial protein synthesis or DNA replication elicit different effects. ► We provide novel insights into the cellular responses toxins and antibiotics.

  5. Muscle regeneration in mitochondrial myopathies

    DEFF Research Database (Denmark)

    Krag, T O; Hauerslev, S; Jeppesen, T D;

    2013-01-01

    Mitochondrial myopathies cover a diverse group of disorders in which ragged red and COX-negative fibers are common findings on muscle morphology. In contrast, muscle degeneration and regeneration, typically found in muscular dystrophies, are not considered characteristic features of mitochondrial...... myopathies. We investigated regeneration in muscle biopsies from 61 genetically well-defined patients affected by mitochondrial myopathy. Our results show that the perturbed energy metabolism in mitochondrial myopathies causes ongoing muscle regeneration in a majority of patients, and some were even affected...

  6. Chronic Arsenic Exposure-Induced Oxidative Stress is Mediated by Decreased Mitochondrial Biogenesis in Rat Liver.

    Science.gov (United States)

    Prakash, Chandra; Kumar, Vijay

    2016-09-01

    The present study was executed to study the effect of chronic arsenic exposure on generation of mitochondrial oxidative stress and biogenesis in rat liver. Chronic sodium arsenite treatment (25 ppm for 12 weeks) decreased mitochondrial complexes activity in rat liver. There was a decrease in mitochondrial superoxide dismutase (MnSOD) activity in arsenic-treated rats that might be responsible for increased protein and lipid oxidation as observed in our study. The messenger RNA (mRNA) expression of mitochondrial and nuclear-encoded subunits of complexes I (ND1 and ND2) and IV (COX I and COX IV) was downregulated in arsenic-treated rats only. The protein and mRNA expression of MnSOD was reduced suggesting increased mitochondrial oxidative damage after arsenic treatment. There was activation of Bax and caspase-3 followed by release of cytochrome c from mitochondria suggesting induction of apoptotic pathway under oxidative stress. The entire phenomenon was associated with decrease in mitochondrial biogenesis as evident by decreased protein and mRNA expression of nuclear respiratory factor 1 (NRF-1), nuclear respiratory factor 2 (NRF-2), peroxisome proliferator activator receptor gamma-coactivator 1α (PGC-1α), and mitochondrial transcription factor A (Tfam) in arsenic-treated rat liver. The results of the present study indicate that arsenic-induced mitochondrial oxidative stress is associated with decreased mitochondrial biogenesis in rat liver that may present one of the mechanisms for arsenic-induced hepatotoxicity. PMID:26767369

  7. Mitochondrial dysfunction in metabolic syndrome and asthma.

    Science.gov (United States)

    Mabalirajan, Ulaganathan; Ghosh, Balaram

    2013-01-01

    Though severe or refractory asthma merely affects less than 10% of asthma population, it consumes significant health resources and contributes significant morbidity and mortality. Severe asthma does not fell in the routine definition of asthma and requires alternative treatment strategies. It has been observed that asthma severity increases with higher body mass index. The obese-asthmatics, in general, have the features of metabolic syndrome and are progressively causing a significant burden for both developed and developing countries thanks to the westernization of the world. As most of the features of metabolic syndrome seem to be originated from central obesity, the underlying mechanisms for metabolic syndrome could help us to understand the pathobiology of obese-asthma condition. While mitochondrial dysfunction is the common factor for most of the risk factors of metabolic syndrome, such as central obesity, dyslipidemia, hypertension, insulin resistance, and type 2 diabetes, the involvement of mitochondria in obese-asthma pathogenesis seems to be important as mitochondrial dysfunction has recently been shown to be involved in airway epithelial injury and asthma pathogenesis. This review discusses current understanding of the overlapping features between metabolic syndrome and asthma in relation to mitochondrial structural and functional alterations with an aim to uncover mechanisms for obese-asthma. PMID:23840225

  8. Application of Functional Genomics for Bovine Respiratory Disease Diagnostics.

    Science.gov (United States)

    Rai, Aswathy N; Epperson, William B; Nanduri, Bindu

    2015-01-01

    Bovine respiratory disease (BRD) is the most common economically important disease affecting cattle. For developing accurate diagnostics that can predict disease susceptibility/resistance and stratification, it is necessary to identify the molecular mechanisms that underlie BRD. To study the complex interactions among the bovine host and the multitude of viral and bacterial pathogens, as well as the environmental factors associated with BRD etiology, genome-scale high-throughput functional genomics methods such as microarrays, RNA-seq, and proteomics are helpful. In this review, we summarize the progress made in our understanding of BRD using functional genomics approaches. We also discuss some of the available bioinformatics resources for analyzing high-throughput data, in the context of biological pathways and molecular interactions. Although resources for studying host response to infection are avail-able, the corresponding information is lacking for majority of BRD pathogens, impeding progress in identifying diagnostic signatures for BRD using functional genomics approaches. PMID:26526746

  9. 运动诱导骨骼肌线粒体生成中沉默信息调节因子1的作用**☆%Silent information regulator factor-1 regulates exercise-induced mitochondrial biogenesis in the skeletal muscle

    Institute of Scientific and Technical Information of China (English)

    张国华

    2013-01-01

    BACKGROUND:Silent information regulator factor-1 is an energy metabolism regulator newly received attention in sports science, which playing roles in skeletal exercise-induced muscle mitochondrial biogenesis with other regulatory factors. OBJECTIVE: To review the effect and mechanism of silent information regulator factor-1 on skeletal muscle mitochondrial biogenesis in exercise. METHODS:The PubMed database and Highwire database were retrieved with computer for the articles on exercise, silent information regulator factor-1 and skeletal muscle mitochondrial biogenesis from January 2000 to January 2013 with the key words of“SIRT1, AMPK, PGC-1α, mitochondrial biogenesis, skeletal muscle, exercise”in English. After primary search, the articles about the association between silent information regulator factor-1 and skeletal muscle mitochondrial biogenesis in exercise were selected. Articles on repeated experiment were excluded. RESULTS AND CONCLUSION:Total y 165 relevant articles were selected, and articles on repetitive research were excluded, so finaly 62 articles were included. As a NAD+-depended deacetylase, silent information regulator factor-1 induced skeletal muscle mitochondrial biogenesis by up-regulated peroxisome proliferator-activated receptor coactivator after activated during exercise. The molecular mechanism involved adenosine monophosphate-activated protein kinase and hypoxia-inducible factor 2α. In recent years, the effect of silent information regulator factor-1 on skeletal muscle mitochondrial biogenesis was doubt, the researchers though that silent information regulator factor-1 was not required for exercise-induced muscle mitochondrial biogenesis. Silent information regulator factor-1 plays an important role in exercise-induced muscle mitochondrial biogenesis. But protein and activity detection methods are different in experimental results.%  背景:沉默信息调节因子1是新近受到体育科学领域关注的能量代谢调节

  10. Fourier analysis of mitochondrial distribution in oocytes

    Science.gov (United States)

    Hollmann, Joseph L.; Brooks, Dana H.; Newmark, Judith A.; Warner, Carol M.; DiMarzio, Charles A.

    2011-03-01

    This paper describes a novel approach to quantifying mitochondrial patterns which are typically described using the qualitative terms "diffuse" "aggregated" and are potentially key indicators for an oocyte's health and survival potential post-implantation. An oocyte was isolated in a confocal image and a coarse grid was superimposed upon it. The spatial spectrum was calculated and an aggregation factor was generated. A classifier for healthy cells was developed and verified. The aggregation factor showed a clear distinction between the healthy and unhealthy oocytes. The ultimate goal is to screen oocytes for viability preimplantation, thus improving the outcome of in vitro fertilization (IVF) treatments.

  11. Inheritance of the yeast mitochondrial genome

    DEFF Research Database (Denmark)

    Piskur, Jure

    1994-01-01

    Mitochondrion, extrachromosomal genetics, intergenic sequences, genome size, mitochondrial DNA, petite mutation, yeast......Mitochondrion, extrachromosomal genetics, intergenic sequences, genome size, mitochondrial DNA, petite mutation, yeast...

  12. NDE1 and GSK3β Associate with TRAK1 and Regulate Axonal Mitochondrial Motility: Identification of Cyclic AMP as a Novel Modulator of Axonal Mitochondrial Trafficking.

    Science.gov (United States)

    Ogawa, Fumiaki; Murphy, Laura C; Malavasi, Elise L V; O'Sullivan, Shane T; Torrance, Helen S; Porteous, David J; Millar, J Kirsty

    2016-05-18

    Mitochondria are essential for neuronal function, providing the energy required to power neurotransmission, and fulfilling many important additional roles. In neurons, mitochondria must be efficiently transported to sites, including synapses, where their functions are required. Neurons, with their highly elongated morphology, are consequently extremely sensitive to defective mitochondrial trafficking which can lead to neuronal ill-health/death. We recently demonstrated that DISC1 associates with mitochondrial trafficking complexes where it associates with the core kinesin and dynein adaptor molecule TRAK1. We now show that the DISC1 interactors NDE1 and GSK3β also associate robustly with TRAK1 and demonstrate that NDE1 promotes retrograde axonal mitochondrial movement. GSK3β is known to modulate axonal mitochondrial motility, although reports of its actual effect are conflicting. We show that, in our system, GSK3β promotes anterograde mitochondrial transport. Finally, we investigated the influence of cAMP elevation upon mitochondrial motility, and found a striking increase in mitochondrial motility and retrograde movement. DISC1, NDE1, and GSK3β are implicated as risk factors for major mental illness. Our demonstration that they function together within mitochondrial trafficking complexes suggests that defective mitochondrial transport may be a contributory disease mechanism in some cases of psychiatric disorder. PMID:26815013

  13. Identification of bovine material in porcine spray-dried blood derivatives using the Polymerase Chain Reaction technique

    Directory of Open Access Journals (Sweden)

    Sánchez A.

    2004-01-01

    Full Text Available Due to the widely supported theory of bovine spongiform encephalopathy (BSE spread in cattle by contaminated animal feeds, screening of feed products has become essential. For many years, manufacturers have used blood and plasma proteins as high quality ingredients of foods for both pets and farm animals. However, in Europe, the Commission Regulation 1234/2003/EC temporally bans the use of processed animal proteins, including blood-derivative products, in feedstuffs for all farm animals which are fattened or bred for the production of food. This regulation has some exceptions, such as the use of non ruminant blood products into the feed of farm fish. Authorization of the re-introduction of these proteins into animal feed formulations, especially non ruminant proteins into the feed for non ruminant farm animals, is expected when adequate control methods to discriminate ruminant proteins exist. Currently, the number of validated methods to differentiate the species of origin for most of the animal by-products is limited. Here we report the development of a rapid and sensitive polymerase chain reaction (PCR-based assay, which allows detection of bovine or porcine specific mitochondrial DNAfrom spray-dried blood derivate products (plasma, whole blood and red cells, as a marker for bovine contamination in porcine products. Sample extracts, suitable for PCR, were easily and quickly obtained with the commercial PrepManTM Ultra reagent (Applied Biosystems. To confirm the porcine origin of the samples, primers targeting a specific region of 134 bp of the porcine cytochrome b coding sequence were designed (cytbporc1-F and cytbporc2-R. Previously published PCR primers (L8129 and H8357, specific for a 271 bp fragment of the bovine mitochondrial ATPase 8-ATPase 6 genes, were chosen to accomplish amplification of bovine DNA. The limit of detection (LOD of the bovine PCR assay was at least of 0.05% (v/v of bovine inclusion in spray-dried porcine plasma or red

  14. Reduced calcium-dependent mitochondrial damage underlies the reduced vulnerability of excitotoxicity-tolerant hippocampal neurons.

    Science.gov (United States)

    Pivovarova, Natalia B; Stanika, Ruslan I; Watts, Charlotte A; Brantner, Christine A; Smith, Carolyn L; Andrews, S Brian

    2008-03-01

    In central neurons, over-stimulation of NMDA receptors leads to excessive mitochondrial calcium accumulation and damage, which is a critical step in excitotoxic death. This raises the possibility that low susceptibility to calcium overload-induced mitochondrial damage might characterize excitotoxicity-resistant neurons. In this study, we have exploited two complementary models of preconditioning-induced excitotoxicity resistance to demonstrate reduced calcium-dependent mitochondrial damage in NMDA-tolerant hippocampal neurons. We have further identified adaptations in mitochondrial calcium handling that account for enhanced mitochondrial integrity. In both models, enhanced tolerance was associated with improved preservation of mitochondrial membrane potential and structure. In the first model, which exhibited modest neuroprotection, mitochondria-dependent calcium deregulation was delayed, even though cytosolic and mitochondrial calcium loads were quantitatively unchanged, indicating that enhanced mitochondrial calcium capacity accounts for reduced injury. In contrast, the second model, which exhibited strong neuroprotection, displayed further delayed calcium deregulation and reduced mitochondrial damage because downregulation of NMDA receptor surface expression depressed calcium loading. Reducing calcium entry also modified the chemical composition of the calcium-buffering precipitates that form in calcium-loaded mitochondria. It thus appears that reduced mitochondrial calcium loading is a major factor underlying the robust neuroprotection seen in highly tolerant cells. PMID:18036152

  15. Scientific Opinion on bovine lactoferrin

    OpenAIRE

    EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA)

    2012-01-01

    Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to carry out the additional assessment for ‘lactoferrin’ as a food ingredient in the context of Regulation (EC) No 258/97 taking into account the comments and objections of a scientific nature raised by Member States. Bovine lactoferrin (bLF) is a protein that occurs naturally in cow’s milk. The applicant intends to market bLF that is isolated from cheese whe...

  16. Microsatellite and Mitochondrial DNA Study of Native Eastern European Cattle Populations: The Case of the Romanian Grey

    OpenAIRE

    Ilie, Daniela Elena; Cean, Ada; Cziszter, Ludovic Toma; Gavojdian, Dinu; Ivan, Alexandra; Kusza, Szilvia

    2015-01-01

    The Eastern European Grey cattle are regarded as the direct descendants of the aurochs (Bos taurus primigenius). Nowadays in Romania, less than 100 Grey animals are being reared and included in the national gene reserve. We examined the genetic diversity among Romanian Grey, Brown, Spotted and Black and White cattle breeds, with a particular focus on Romanian Grey through the use of (i) 11 bovine specific microsatellite markers on 83 animals and (ii) 638 bp length of mitochondrial DNA (mtDNA)...

  17. Tumor necrosis factor-alpha (TNFα) gene polymorphism and expression of membrane-bound TNFα protein on CD11b+ and IgM+ cells in cows naturally infected with bovine leukemia virus.

    Science.gov (United States)

    Bojarojć-Nosowicz, B; Kaczmarczyk, E; Stachura, A; Kubińska, M

    2015-01-01

    The aim of this study was to determine whether SNP at position -824 (promoter region) of the TNFα gene significantly differentiates the size of IgM+, CD5+ and CD11b+ cell subpopulations and affects the expression of membrane-bound TNFα protein (mTNFα) on these cells and their susceptibility to BLV infections. In this study, significant differences were determined for the first time between TNFα genotypes and the percentage of cells with the CD11b+TNFα+p24+ immunophenotype. Furthermore, greater expansion of lymphocytes with the IgM+TNFα+p24+ immunophenotype was reported in cows with the G/G genotype than in A/A homozygotes. Cells with the above immunophenotype were more frequently observed in cows with persistent leukocytosis than in aleukemic cattle. Our results suggest that polymorphism of the TNFα-824 A>G gene and mTNFα protein expression play an important role in the pathogenesis of enzootic bovine leukosis. PMID:26618585

  18. Upstream Pathways Controlling Mitochondrial Function in Major Psychosis: A Focus on Bipolar Disorder.

    Science.gov (United States)

    Machado, Alencar Kolinski; Pan, Alexander Yongshuai; da Silva, Tatiane Morgana; Duong, Angela; Andreazza, Ana Cristina

    2016-08-01

    Mitochondrial dysfunction is commonly observed in bipolar disorder (BD) and schizophrenia (SCZ) and may be a central feature of psychosis. These illnesses are complex and heterogeneous, which is reflected by the complexity of the processes regulating mitochondrial function. Mitochondria are typically associated with energy production; however, dysfunction of mitochondria affects not only energy production but also vital cellular processes, including the formation of reactive oxygen species, cell cycle and survival, intracellular Ca(2+) homeostasis, and neurotransmission. In this review, we characterize the upstream components controlling mitochondrial function, including 1) mutations in nuclear and mitochondrial DNA, 2) mitochondrial dynamics, and 3) intracellular Ca(2+) homeostasis. Characterizing and understanding the upstream factors that regulate mitochondrial function is essential to understand progression of these illnesses and develop biomarkers and therapeutics. PMID:27310240

  19. Molecular Genetics of Mitochondrial Disorders

    Science.gov (United States)

    Wong, Lee-Jun C.

    2010-01-01

    Mitochondrial respiratory chain (RC) disorders (RCDs) are a group of genetically and clinically heterogeneous diseases because of the fact that protein components of the RC are encoded by both mitochondrial and nuclear genomes and are essential in all cells. In addition, the biogenesis, structure, and function of mitochondria, including DNA…

  20. The potato tuber mitochondrial proteome

    DEFF Research Database (Denmark)

    Møller, Ian Max; Salvato, Fernanda; Havelund, Jesper;

    ) and in silico-predicted mitochondrial proteins (2000-3000). Thus, before starting to look for oxidized peptides, we wanted to expand the current compendium of plant mitochondrial proteins while obtaining what could be termed the "baseline proteome" from our model organelle, the potato tuber...

  1. Biochemical diagnosis of mitochondrial disorders

    NARCIS (Netherlands)

    Rodenburg, R.J.T.

    2011-01-01

    Establishing a diagnosis in patients with a suspected mitochondrial disorder is often a challenge. Both knowledge of the clinical spectrum of mitochondrial disorders and the number of identified disease-causing molecular genetic defects are continuously expanding. The diagnostic examination of patie

  2. Mitochondrial glycolate oxidation contributes to photorespiration in higher plants.

    Science.gov (United States)

    Niessen, Markus; Thiruveedhi, Krishnaveni; Rosenkranz, Ruben; Kebeish, Rashad; Hirsch, Heinz-Josef; Kreuzaler, Fritz; Peterhänsel, Christoph

    2007-01-01

    The oxidation of glycolate to glyoxylate is an important reaction step in photorespiration. Land plants and charophycean green algae oxidize glycolate in the peroxisome using oxygen as a co-factor, whereas chlorophycean green algae use a mitochondrial glycolate dehydrogenase (GDH) with organic co-factors. Previous analyses revealed the existence of a GDH in the mitochondria of Arabidopsis thaliana (AtGDH). In this study, the contribution of AtGDH to photorespiration was characterized. Both RNA abundance and mitochondrial GDH activity were up-regulated under photorespiratory growth conditions. Labelling experiments indicated that glycolate oxidation in mitochondrial extracts is coupled to CO(2) release. This effect could be enhanced by adding co-factors for aminotransferases, but is inhibited by the addition of glycine. T-DNA insertion lines for AtGDH show a drastic reduction in mitochondrial GDH activity and CO(2) release from glycolate. Furthermore, photorespiration is reduced in these mutant lines compared with the wild type, as revealed by determination of the post-illumination CO(2) burst and the glycine/serine ratio under photorespiratory growth conditions. The data show that mitochondrial glycolate oxidation contributes to photorespiration in higher plants. This indicates the conservation of chlorophycean photorespiration in streptophytes despite the evolution of leaf-type peroxisomes. PMID:17595195

  3. Production of new amilorides as potent inhibitors of mitochondrial respiratory complex I.

    Science.gov (United States)

    Murai, Masatoshi; Habu, Sayako; Murakami, Sonomi; Ito, Takeshi; Miyoshi, Hideto

    2015-01-01

    Amilorides, well-known inhibitors of Na(+)/H(+) antiporters, have also shown to inhibit bacterial and mitochondrial NADH-quinone oxidoreductase (complex I). Since the membrane subunits ND2, ND4, and ND5 of bovine mitochondrial complex I are homologous to Na(+)/H(+) antiporters, amilorides have been thought to bind to any or all of the antiporter-like subunits; however, there is no direct experimental evidence in support of this notion. Photoaffinity labeling is a powerful technique to identify the binding site of amilorides in bovine complex I. Commercially available amilorides such as 5-(N-ethyl-N-isopropyl)amiloride are not suitable as design templates to synthesize photoreactive amilorides because of their low binding affinities to bovine complex I. Thereby, we attempted to modify the structures of commercially available amilorides in order to obtain more potent derivatives. We successfully produced two photoreactive amilorides (PRA1 and PRA2) with a photolabile azido group at opposite ends of the molecule. PMID:25731956

  4. Mitochondrial gene mutations and type 2 diabetes in Chinese families

    Institute of Scientific and Technical Information of China (English)

    LI Ming-zhen; YU De-min; YU Pei; LIU De-min; WANG Kun; TANG Xin-zhi

    2008-01-01

    Background Numerous mitochondrial DNA mutations are significantly correlated with development of diabetes. This study investigated mitochondrial gene, point mutations in patients with type 2 diabetes and their families. Methods Unrelated patients with type 2 diabetes(n=826)were randomly recruited; unrelated and nondiabetic subjects (n=637)served as controls. The clinical and biochemical data of the participants were collected. Total genome was extracted from peripheral leucocytes. Polymerase chain reaction, restriction fragment length polymorphism (PCR-RFLP)and clonig techniques were used to screen mitochondrial genes including np3316,np3394 and np3426 in the ND1 region and np3243 in the tRNALeu (UUR). Results In 39 diabetics with one or more mitochondrial gene point mutations, the prevalence(4.7%,39/826)of mtDNA mutations was higher than that(0.7%,5/637)in the controls. The identical mutation was found in 23 of 43 tested members from three pedigrees. Affected family members presented with variable clinical features ranging from normal glucose tolerance to impaired glucose tolerance (IGT)(n=2),impaired fasting glucose(IFG)(n=1)to type 2 diabetes (n=13)with 3 family members suffering from hearing loss. Conclusions Type 2 diabetes in China is associated with several mitochondrial gene mutations. Aged patients with diabetic family history had a higher prevalence of mutation and various clinical pictures. Mitochondrial gene mutation might be one of the genetic factors contributing to diabetic familial clustering.

  5. Autophagy plays a role in skeletal muscle mitochondrial biogenesis in an endurance exercise-trained condition.

    Science.gov (United States)

    Ju, Jeong-Sun; Jeon, Sei-Il; Park, Je-Young; Lee, Jong-Young; Lee, Seong-Cheol; Cho, Ki-Jung; Jeong, Jong-Moon

    2016-09-01

    Mitochondrial homeostasis is tightly regulated by two major processes: mitochondrial biogenesis and mitochondrial degradation by autophagy (mitophagy). Research in mitochondrial biogenesis in skeletal muscle in response to endurance exercise training has been well established, while the mechanisms regulating mitophagy and the interplay between mitochondrial biogenesis and degradation following endurance exercise training are not yet well defined. The purpose of this study was to examine the effects of a short-term inhibition of autophagy in response to acute endurance exercise on skeletal muscle mitochondrial biogenesis and dynamics in an exercise-trained condition. Male wild-type C57BL/6 mice performed five daily bouts of 1-h swimming per week for 8 weeks. In order to measure autophagy flux in mouse skeletal muscle, mice were treated with or without 2 days of 0.4 mg/kg/day intraperitoneal colchicine (blocking the degradation of autophagosomes) following swimming exercise training. The autophagic flux assay demonstrated that swimming training resulted in an increase in the autophagic flux (~100 % increase in LC3-II) in mouse skeletal muscle. Mitochondrial fusion proteins, Opa1 and MFN2, were significantly elevated, and mitochondrial fission protein, Drp1, was also increased in trained mouse skeletal muscle, suggesting that endurance exercise training promotes both mitochondrial fusion and fission processes. A mitochondrial receptor, Bnip3, was further increased in exercised muscle when treated with colchicine while Pink/Parkin protein levels were unchanged. The endurance exercise training induced increases in mitochondrial biogenesis marker proteins, SDH, COX IV, and a mitochondrial biogenesis promoting factor, PGC-1α but this effect was abolished in colchicine-treated mouse skeletal muscle. This suggests that autophagy plays an important role in mitochondrial biogenesis and this coordination between these opposing processes is involved in the cellular

  6. Mitochondrial dynamics and cell death in heart failure.

    Science.gov (United States)

    Marín-García, José; Akhmedov, Alexander T

    2016-03-01

    The highly regulated processes of mitochondrial fusion (joining), fission (division) and trafficking, collectively called mitochondrial dynamics, determine cell-type specific morphology, intracellular distribution and activity of these critical organelles. Mitochondria are critical for cardiac function, while their structural and functional abnormalities contribute to several common cardiovascular diseases, including heart failure (HF). The tightly balanced mitochondrial fusion and fission determine number, morphology and activity of these multifunctional organelles. Although the intracellular architecture of mature cardiomyocytes greatly restricts mitochondrial dynamics, this process occurs in the adult human heart. Fusion and fission modulate multiple mitochondrial functions, ranging from energy and reactive oxygen species production to Ca(2+) homeostasis and cell death, allowing the heart to respond properly to body demands. Tightly controlled balance between fusion and fission is of utmost importance in the high energy-demanding cardiomyocytes. A shift toward fission leads to mitochondrial fragmentation, while a shift toward fusion results in the formation of enlarged mitochondria and in the fusion of damaged mitochondria with healthy organelles. Mfn1, Mfn2 and OPA1 constitute the core machinery promoting mitochondrial fusion, whereas Drp1, Fis1, Mff and MiD49/51 are the core components of fission machinery. Growing evidence suggests that fusion/fission factors in adult cardiomyocytes play essential noncanonical roles in cardiac development, Ca(2+) signaling, mitochondrial quality control and cell death. Impairment of this complex circuit causes cardiomyocyte dysfunction and death contributing to heart injury culminating in HF. Pharmacological targeting of components of this intricate network may be a novel therapeutic modality for HF treatment. PMID:26872674

  7. Cleavage of bovine immunoglobulin G1 in whey by an extracellular material from Brucella abortus.

    OpenAIRE

    Nielsen, K.

    1985-01-01

    Culture extracts of in vitro grown Brucella abortus were demonstrated to cleave a part of the Fc portion of bovine immunoglobulin G1 in whey but not in serum or as a purified protein from serum. Supernates from Strains 19 and 2308 of B. abortus were both capable of this hydrolysis whereas living cells were not. The cleavage process was independent of antibody activity to B. abortus, appeared to require factor(s) found only in some whey samples and was ineffective with the other bovine immunog...

  8. Mitochondrial dysfunction induced by ultra-small silver nanoclusters with a distinct toxic mechanism.

    Science.gov (United States)

    Dong, Ping; Li, Jia-Han; Xu, Shi-Ping; Wu, Xiao-Juan; Xiang, Xun; Yang, Qi-Qi; Jin, Jian-Cheng; Liu, Yi; Jiang, Feng-Lei

    2016-05-01

    As noble metal nanoclusters (NCs) are widely employed in nanotechnology, their potential threats to human and environment are relatively less understood. Herein, the biological effects of ultra-small silver NCs coated by bovine serum albumin (BSA) (Ag-BSA NCs) on isolated rat liver mitochondria were investigated by testing mitochondrial swelling, membrane permeability, ROS generation, lipid peroxidation and respiration. It was found that Ag-BSA NCs induced mitochondrial dysfunction via synergistic effects of two different ways: (1) inducing mitochondrial membrane permeability transition (MPT) by interacting with the phospholipid bilayer of the mitochondrial membrane (not with specific MPT pore proteins); (2) damaging mitochondrial respiration by the generation of reactive oxygen species (ROS). As far as we know, this is the first report on the biological effects of ultra-small size nanoparticles (∼2nm) at the sub-cellular level, which provides significant insights into the potential risks brought by the applications of NCs. It would inspire us to evaluate the potential threats of nanomaterials more comprehensively, even though they showed no obvious toxicity to cells or in vivo animal models. Noteworthy, a distinct toxic mechanism to mitochondria caused by Ag-BSA NCs was proposed and elucidated. PMID:26808252

  9. Mechanical stress and ATP synthesis are coupled by mitochondrial oxidants in articular cartilage.

    Science.gov (United States)

    Wolff, Katherine J; Ramakrishnan, Prem S; Brouillette, Marc J; Journot, Brice J; McKinley, Todd O; Buckwalter, Joseph A; Martin, James A

    2013-02-01

    Metabolic adaptation of articular cartilage under joint loading is evident and matrix synthesis seems to be critically tied to ATP. Chondrocytes utilize the glycolytic pathway for energy requirements but seem to require mitochondrial reactive oxygen species (ROS) to sustain ATP synthesis. The role of ROS in regulating ATP reserves under a mechanically active environment is not clear. It is believed that physiological strains cause deformation of the mitochondria, potentially releasing ROS for energy production. We hypothesized that mechanical loading stimulates ATP synthesis via mitochondrial release of ROS. Bovine osteochondral explants were dynamically loaded at 0.5 Hz with amplitude of 0.25 MPa for 1 h. Cartilage response to mechanical loading was assessed by imaging with dihydroethidium (ROS indicator) and a Luciferase-based ATP assay. Electron transport inhibitor rotenone and mitochondrial ROS scavenger MitoQ significantly suppressed mechanically induced ROS production and ATP synthesis. Our findings indicate that mitochondrial ROS are produced as a result of physiological mechanical strains. Taken together with our previous findings of ROS involvement in blunt impact injuries, mitochondrial ROS are important contributors to cartilage metabolic adaptation and their precise role in the pathogenesis of osteoarthritis warrants further investigation. PMID:22930474

  10. Updating of the bovine neosporosis

    Directory of Open Access Journals (Sweden)

    Alexander Martínez Contreras

    2012-06-01

    Full Text Available In the fields of Medicine and bovine production, there is a wide variety of diseases affecting reproduction, in relation to the number of live births, the interval between births and open days, among others. Some of these diseases produce abortions and embryonic death, which explain the alteration of reproductive parameters. Many of these diseases have an infectious origin, such as parasites, bacteria, viruses and fungi, which are transmitted among animals. Besides, some of them have zoonotic features that generate problems to human health. Among these agents, the Neospora caninum, protozoan stands out. Its life cycle is fulfilled in several species of animals like the dog and the coyote. These two act as its definitive hosts and the cattle as its intermediary host. The Neospora caninum causes in the infected animals, reproductive disorders, clinical manifestations and decreased production which affects productivity of small, medium and large producers. Because of this, diagnostic techniques that allow understanding the epidemiological behavior of this disease have been developed. However in spite of being a major agent in the bovine reproductive health, few studies have been undertaken to determine the prevalence of this agent around the world. Therefore, the objective of this review was to collect updated information on the behavior of this parasite, targeting its epidemiology, its symptoms, its impact on production and the methods of its control and prevention.

  11. Adipogenesis of bovine perimuscular preadipocytes

    International Nuclear Information System (INIS)

    In this study, non-transformed progeny adipofibroblasts, derived from mature adipocyte dedifferentiation, was used as a novel in vitro model to study adipogenic gene expression in cattle. Adipofibroblasts from dedifferentiated mature perimuscular fat (PMF) tissue were cultured with differentiation stimulants until the cells exhibited morphological differentiation. Treated cells were harvested from day 2 to 16 for RNA extraction, whereas control cells were cultured without addition of stimulants. Results from time course gene expression assays by quantitative real-time PCR revealed that peroxisome proliferator-activated receptor gamma (PPAR-γ), sterol regulatory element binding protein 1 (SREBP-1) and their six down-stream genes were co-expressed at day 2 post-differentiation induction. When compared to other adipogenesis culture systems, the adipogenic gene expression of bovine PMF adipofibroblasts culture was different, especially to the rodent model. Collectively, these results demonstrated PPAR-γ and SREBP-1 cooperatively play a key role to regulate the re-differentiation of bovine adipofibroblasts, during early conversion stages in vitro

  12. A complete mitochondrial genome sequence from a mesolithic wild aurochs (Bos primigenius).

    LENUS (Irish Health Repository)

    Edwards, Ceiridwen J

    2010-01-01

    BACKGROUND: The derivation of domestic cattle from the extinct wild aurochs (Bos primigenius) has been well-documented by archaeological and genetic studies. Genetic studies point towards the Neolithic Near East as the centre of origin for Bos taurus, with some lines of evidence suggesting possible, albeit rare, genetic contributions from locally domesticated wild aurochsen across Eurasia. Inferences from these investigations have been based largely on the analysis of partial mitochondrial DNA sequences generated from modern animals, with limited sequence data from ancient aurochsen samples. Recent developments in DNA sequencing technologies, however, are affording new opportunities for the examination of genetic material retrieved from extinct species, providing new insight into their evolutionary history. Here we present DNA sequence analysis of the first complete mitochondrial genome (16,338 base pairs) from an archaeologically-verified and exceptionally-well preserved aurochs bone sample. METHODOLOGY: DNA extracts were generated from an aurochs humerus bone sample recovered from a cave site located in Derbyshire, England and radiocarbon-dated to 6,738+\\/-68 calibrated years before present. These extracts were prepared for both Sanger and next generation DNA sequencing technologies (Illumina Genome Analyzer). In total, 289.9 megabases (22.48%) of the post-filtered DNA sequences generated using the Illumina Genome Analyzer from this sample mapped with confidence to the bovine genome. A consensus B. primigenius mitochondrial genome sequence was constructed and was analysed alongside all available complete bovine mitochondrial genome sequences. CONCLUSIONS: For all nucleotide positions where both Sanger and Illumina Genome Analyzer sequencing methods gave high-confidence calls, no discrepancies were observed. Sequence analysis reveals evidence of heteroplasmy in this sample and places this mitochondrial genome sequence securely within a previously identified

  13. 9 CFR 113.310 - Bovine Rhinotracheitis Vaccine.

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Bovine Rhinotracheitis Vaccine. 113... REQUIREMENTS Live Virus Vaccines § 113.310 Bovine Rhinotracheitis Vaccine. Bovine Rhinotracheitis Vaccine shall...-five infectious bovine rhinotracheitis susceptible calves shall be used as test animals (20...

  14. 21 CFR 184.1034 - Catalase (bovine liver).

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Catalase (bovine liver). 184.1034 Section 184.1034... Listing of Specific Substances Affirmed as GRAS § 184.1034 Catalase (bovine liver). (a) Catalase (bovine liver) (CAS Reg. No. 81457-95-6) is an enzyme preparation obtained from extracts of bovine liver. It...

  15. Expression of a mitochondrial progesterone receptor in human spermatozoa correlates with a progestin-dependent increase in mitochondrial membrane potential.

    Science.gov (United States)

    Tantibhedhyangkul, J; Hawkins, K C; Dai, Q; Mu, K; Dunn, C N; Miller, S E; Price, T M

    2014-11-01

    The hyperactivation of human spermatozoa necessary for fertilization requires a substantial increase in cellular energy production. The factors responsible for increasing cellular energy remain poorly defined. This article proposes a role for a novel mitochondrial progesterone receptor (PR-M) in modulation of mitochondrial activity. Basic science studies demonstrate a 38 kDa protein with western blot analysis, consistent with PR-M; whereas imaging studies with confocal and immunoelectron microscopy demonstrate a PR on the mitochondria. Treatment with a PR-specific progestin shows increased mitochondrial membrane potential, not related to induction of an acrosome reaction. The increase in mitochondrial membrane potential was inhibited by a specific PR antagonist, but not affected by an inhibitor to the progesterone-dependent Catsper voltage-activated channel. In conclusion, these studies suggest expression of a novel mitochondrial PR in human spermatozoa with a progestin-dependent increase in mitochondrial activity. This mechanism may serve to enhance cellular energy production as the spermatozoa traverse the female genital tract being exposed to increasing concentrations of progesterone. PMID:25187426

  16. The mitochondrial outer membrane protein hFis1 regulates mitochondrial morphology and fission through self-interaction

    International Nuclear Information System (INIS)

    Mitochondrial fission in mammals is mediated by at least two proteins, DLP1/Drp1 and hFis1. DLP1 mediates the scission of mitochondrial membranes through GTP hydrolysis, and hFis1 is a putative DLP1 receptor anchored at the mitochondrial outer membrane by a C-terminal single transmembrane domain. The cytosolic domain of hFis1 contains six α-helices (α1-α6) out of which α2-α5 form two tetratricopeptide repeat (TPR) folds. In this study, by using chimeric constructs, we demonstrated that the cytosolic domain contains the necessary information for hFis1 function during mitochondrial fission. By using transient expression of different mutant forms of the hFis1 protein, we found that hFis1 self-interaction plays an important role in mitochondrial fission. Our results show that deletion of the α1 helix greatly increased the formation of dimeric and oligomeric forms of hFis1, indicating that α1 helix functions as a negative regulator of the hFis1 self-interaction. Further mutational approaches revealed that a tyrosine residue in the α5 helix and the linker between α3 and α4 helices participate in hFis1 oligomerization. Mutations causing oligomerization defect greatly reduced the ability to induce not only mitochondrial fragmentation by full-length hFis1 but also the formation of swollen ball-shaped mitochondria caused by α1-deleted hFis1. Our data suggest that oligomerization of hFis1 in the mitochondrial outer membrane plays a role in mitochondrial fission, potentially through participating in fission factor recruitment

  17. Mitochondrial uncoupling proteins and energy metabolism

    Directory of Open Access Journals (Sweden)

    Rosa Anna Busiello

    2015-02-01

    Full Text Available Understanding the metabolic factors that contribute to energy metabolism (EM is critical for the development of new treatments for obesity and related diseases. Mitochondrial oxidative phosphorylation is not perfectly coupled to ATP synthesis, and the process of proton-leak plays a crucial role. Proton-leak accounts for a significant part of the resting metabolic rate and therefore enhancement of this process represents a potential target for obesity treatment. Since their discovery, uncoupling proteins have stimulated great interest due to their involvement in mitochondrial-inducible proton-leak. Despite the widely accepted uncoupling/thermogenic effect of uncoupling protein one (UCP1, which was the first in this family to be discovered, the reactions catalyzed by its homologue UCP3 and the physiological role remain under debate.This review provides an overview of the role played by UCP1 and UCP3 in mitochondrial uncoupling/functionality as well as EM and suggests that they are a potential therapeutic target for treating obesity and its related diseases such as type II diabetes mellitus.

  18. Neonatal mitochondrial hepatoencephalopathy caused by novel GFM1 mutations

    Directory of Open Access Journals (Sweden)

    Kirstine Ravn

    2015-06-01

    Full Text Available Disorders caused by defects in the mitochondrial translation system are clinically and genetically heterogeneous. The elongation phase of mitochondrial protein synthesis requires, among many other components, three nuclear-encoded elongation factors: EFTu (TUFM; 602389, EFTs (TSFM; 604723, and EFG1 (GFM1; 606639. Mutations have been identified in the genes encoding all three elongation factors, and they result in combined respiratory chain deficiencies and severe phenotypes with an early fatal outcome. So far, only eleven patients have been reported with mutations in GFM1. Here we describe an additional three patients with novel GFM1 mutations. Our results confirm the tissue-specific effect of GFM1 mutations, since we found only slightly decreased respiratory chain enzyme activities in muscle and fibroblasts, but a severe deficiency in the liver. Hence, a thorough biochemical evaluation is important to guide genetic investigation in patients suspected for a mitochondrial disorder.

  19. Neonatal mitochondrial hepatoencephalopathy caused by novel GFM1 mutations.

    Science.gov (United States)

    Ravn, Kirstine; Schönewolf-Greulich, Bitten; Hansen, Rikke M; Bohr, Anna-Helene; Duno, Morten; Wibrand, Flemming; Ostergaard, Elsebet

    2015-06-01

    Disorders caused by defects in the mitochondrial translation system are clinically and genetically heterogeneous. The elongation phase of mitochondrial protein synthesis requires, among many other components, three nuclear-encoded elongation factors: EFTu (TUFM; 602389), EFTs (TSFM; 604723), and EFG1 (GFM1; 606639). Mutations have been identified in the genes encoding all three elongation factors, and they result in combined respiratory chain deficiencies and severe phenotypes with an early fatal outcome. So far, only eleven patients have been reported with mutations in GFM1. Here we describe an additional three patients with novel GFM1 mutations. Our results confirm the tissue-specific effect of GFM1 mutations, since we found only slightly decreased respiratory chain enzyme activities in muscle and fibroblasts, but a severe deficiency in the liver. Hence, a thorough biochemical evaluation is important to guide genetic investigation in patients suspected for a mitochondrial disorder. PMID:26937387

  20. Scientific Opinion on monitoring procedures at slaughterhouses for bovines

    Directory of Open Access Journals (Sweden)

    EFSA Panel on Animal Health and Welfare (AHAW

    2013-12-01

    Full Text Available This scientific opinion proposes toolboxes of welfare indicators for developing monitoring procedures at slaughterhouses for bovines stunned with penetrative captive bolt or slaughtered without stunning. In particular, the opinion proposes welfare indicators together with their corresponding outcomes of consciousness, unconsciousness or death. In the case of slaughter with captive bolt stunning, the opinion proposes a toolbox of indicators and the outcomes to be used to assess consciousness in bovine animals at three key stages of monitoring: (a after stunning and during shackling and hoisting; (b during neck cutting or sticking; and (c during bleeding. For slaughter of bovines without stunning, a set of indicators and outcomes are proposed in another toolbox to be used for (a assessing unconsciousness, before releasing bovines from restraint; and (b confirming death before carcass dressing begins. Various activities—including a systematic literature review, an online survey and stakeholders’ and hearing experts’ meetings—were conducted to gather information about the specificity, sensitivity and feasibility of the indicators that can be included in the toolboxes. The frequency of checking differs according to the role of each person responsible for ensuring animal welfare. Personnel performing stunning, shackling, hoisting and/or bleeding will have to check all the animals and confirm that they are not conscious following stunning or before release from the restraint. For the animal welfare officer, who has the overall responsibility for animal welfare, a mathematical model for the sampling protocols is proposed, giving some allowance to set the sample size of animals that he/she needs to check at a given throughput rate (total number of animals slaughtered in the slaughterhouse and tolerance level (number of potential failures. Finally, different risk factors and scenarios are proposed to define a ‘normal’ or a

  1. Mitochondrial Cyclophilin D in Vascular Oxidative Stress and Hypertension.

    Science.gov (United States)

    Itani, Hana A; Dikalova, Anna E; McMaster, William G; Nazarewicz, Rafal R; Bikineyeva, Alfiya T; Harrison, David G; Dikalov, Sergey I

    2016-06-01

    Vascular superoxide (O˙2 (-)) and inflammation contribute to hypertension. The mitochondria are an important source of O˙2 (-); however, the regulation of mitochondrial O˙2 (-) and the antihypertensive potential of targeting the mitochondria remain poorly defined. Angiotensin II and inflammatory cytokines, such as interleukin 17A and tumor necrosis factor-α (TNFα) significantly contribute to hypertension. We hypothesized that angiotensin II and cytokines co-operatively induce cyclophilin D (CypD)-dependent mitochondrial O˙2 (-) production in hypertension. We tested whether CypD inhibition attenuates endothelial oxidative stress and reduces hypertension. CypD depletion in CypD(-/-) mice prevents overproduction of mitochondrial O˙2 (-) in angiotensin II-infused mice, attenuates hypertension by 20 mm Hg, and improves vascular relaxation compared with wild-type C57Bl/6J mice. Treatment of hypertensive mice with the specific CypD inhibitor Sanglifehrin A reduces blood pressure by 28 mm Hg, inhibits production of mitochondrial O˙2 (-) by 40%, and improves vascular relaxation. Angiotensin II-induced hypertension was associated with CypD redox activation by S-glutathionylation, and expression of the mitochondria-targeted H2O2 scavenger, catalase, abolished CypD S-glutathionylation, prevented stimulation mitochondrial O˙2 (-), and attenuated hypertension. The functional role of cytokine-angiotensin II interplay was confirmed by co-operative stimulation of mitochondrial O˙2 (-) by 3-fold in cultured endothelial cells and impairment of aortic relaxation incubated with combination of angiotensin II, interleukin 17A, and tumor necrosis factor-α which was prevented by CypD depletion or expression of mitochondria-targeted SOD2 and catalase. These data support a novel role of CypD in hypertension and demonstrate that targeting CypD decreases mitochondrial O˙2 (-), improves vascular relaxation, and reduces hypertension. PMID:27067720

  2. The mitochondrial genome in embryo technologies.

    Science.gov (United States)

    Hiendleder, S; Wolf, E

    2003-08-01

    The mammalian mitochondrial genome encodes for 37 genes which are involved in a broad range of cellular functions. The mitochondrial DNA (mtDNA) molecule is commonly assumed to be inherited through oocyte cytoplasm in a clonal manner, and apparently species-specific mechanisms have evolved to eliminate the contribution of sperm mitochondria after natural fertilization. However, recent evidence for paternal mtDNA inheritance in embryos and offspring questions the general validity of this model, particularly in the context of assisted reproduction and embryo biotechnology. In addition to normal mt DNA haplotype variation, oocytes and spermatozoa show remarkable differences in mtDNA content and may be affected by inherited or acquired mtDNA aberrations. All these parameters have been correlated with gamete quality and reproductive success rates. Nuclear transfer (NT) technology provides experimental models for studying interactions between nuclear and mitochondrial genomes. Recent studies demonstrated (i) a significant effect of mtDNA haplotype or other maternal cytoplasmic factors on the efficiency of NT; (ii) phenotypic differences between transmitochondrial clones pointing to functionally relevant nuclear-cytoplasmic interactions; and (iii) neutral or non-neutral selection of mtDNA haplotypes in heteroplasmic conditions. Mitochondria form a dynamic reticulum, enabling complementation of mitochondrial components and possibly mixing of different mtDNA populations in heteroplasmic individuals. Future directions of research on mtDNA in the context of reproductive biotechnology range from the elimination of adverse effects of artificial heteroplasmy, e.g. created by ooplasm transfer, to engineering of optimized constellations of nuclear and cytoplasmic genes for the production of superior livestock. PMID:12887568

  3. Mitochondrial Dysfunction in Stem Cell Aging

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2015-04-01

    Full Text Available BACKGROUND: Regardless of the precise underlying molecular mechanisms, the fundamental defining manifestation of aging is an overall decline in the functional capacity of various organs to maintain baseline tissue homeostasis and to respond adequately to physiological needs under stress. There is an increasingly urgent need for a more complete understanding of the molecular pathways and biological processes underlying aging and age-related disorders. CONTENT: Mitochondria constitute the most prominent source of adenosine triphosphate (ATP and are implicated in multiple anabolic and catabolic circuitries. In addition, mitochondria coordinate cell-wide stress responses and control non-apoptotic cell death routines. The involvement of mitochondria in both vital and lethal processes is crucial for both embryonic and postembryonic development, as well as for the maintenance of adult tissue homeostasis. Age-associated telomere damage, diminution of telomere ‘capping’ function and associated p53 activation have emerged as prime instigators of a functional decline of tissue stem cells and of mitochondrial dysfunction that adversely affect renewal and bioenergetic support in diverse tissues. Constructing a model of how telomeres, stem cells and mitochondria interact with key molecules governing genome integrity, ‘stemness’ and metabolism provides a framework for how diverse factors contribute to aging and age-related disorders. SUMMARY: Cellular senescence defined as an irreversible proliferation arrest promotes age-related decline in mammalian tissue homeostasis. The aging of tissue-specific stem cell and progenitor cell compartments is believed to be central to the decline of tissue and organ integrity and function in the elderly. Taken into consideration that the overwhelming majority of intracellular reactive oxygen species (ROS are of mitochondrial origin, it is reasonable to posit that the elevated ROS production might be caused by

  4. Melatonin enhances mitophagy and mitochondrial biogenesis in rats with carbon tetrachloride-induced liver fibrosis.

    Science.gov (United States)

    Kang, Jung-Woo; Hong, Jeong-Min; Lee, Sun-Mee

    2016-05-01

    Liver fibrosis leads to liver cirrhosis and failure, and no effective treatment is currently available. Growing evidence supports a link between mitochondrial dysfunction and liver fibrogenesis and mitochondrial quality control-based therapy has emerged as a new therapeutic target. We investigated the protective mechanisms of melatonin against mitochondrial dysfunction-involved liver fibrosis, focusing on mitophagy and mitochondrial biogenesis. Rats were treated with carbon tetrachloride (CCl4 ) dissolved in olive oil (0.5 mL/kg, twice a week, i.p.) for 8 wk. Melatonin was administered orally at 2.5, 5, and 10 mg/kg once a day. Chronic CCl4 exposure induced collagen deposition, hepatocellular damage, and oxidative stress, and melatonin attenuated these increases. Increases in mRNA and protein expression levels of transforming growth factor β1 and α-smooth muscle actin in response to CCl4 were attenuated by melatonin. Melatonin attenuated hallmarks of mitochondrial dysfunction, such as mitochondrial swelling and glutamate dehydrogenase release. Chronic CCl4 exposure impaired mitophagy and mitochondrial biogenesis, and melatonin attenuated this impairment, as indicated by increases in mitochondrial DNA and in protein levels of PTEN-induced putative kinase 1 (PINK1); Parkin; peroxisome proliferator-activated receptor-gamma coactivator 1α (PGC-1α); nuclear respiratory factor 1 (NRF1); and transcription factor A, mitochondrial (TFAM). CCl4 -mediated decreases in mitochondrial fission- and fusion-related proteins, such as dynamin-related protein 1 (DRP1) and mitofusin 2, were also attenuated by melatonin. Moreover, melatonin induced AMP-activated protein kinase (AMPK) phosphorylation. These results suggest that melatonin protects against liver fibrosis via upregulation of mitophagy and mitochondrial biogenesis, and may be useful as an anti-fibrotic treatment. PMID:26882442

  5. All-Atom Molecular Dynamics Simulations Reveal Significant Differences in Interaction between Antimycin and Conserved Amino Acid Residues in Bovine and Bacterial bc1 Complexes

    OpenAIRE

    Kokhan, Oleksandr; Shinkarev, Vladimir P.

    2011-01-01

    Antimycin A is the most frequently used specific and powerful inhibitor of the mitochondrial respiratory chain. We used all-atom molecular dynamics (MD) simulations to study the dynamic aspects of the interaction of antimycin A with the Qi site of the bacterial and bovine bc1 complexes embedded in a membrane. The MD simulations revealed considerable conformational flexibility of antimycin and significant mobility of antimycin, as a whole, inside the Qi pocket. We conclude that many of the dif...

  6. Modulation of the kinetics of cholesterol side-chain cleavage by an activator and by an inhibitor isolated from the cytosol of the cortex of bovine adrenals.

    OpenAIRE

    Warne, P A; Greenfield, N J; Lieberman, S.

    1983-01-01

    Two modulators of sterol side-chain cleavage activity have been detected in the cytosol from the cortex of bovine adrenals. One is an inhibitor of side-chain cleavage which increases the Km of a purified and reconstituted mitochondrial side-chain cleavage system for both cholesterol and cholesterol sulfate. It also lowers the Vmax of cleavage when cholesterol sulfate is the substrate. The other modulator is a low molecular weight protein which in the reconstituted system increases the Vmax of...

  7. Lipid metabolism in mitochondrial membranes.

    Science.gov (United States)

    Mayr, Johannes A

    2015-01-01

    Mitochondrial membranes have a unique lipid composition necessary for proper shape and function of the organelle. Mitochondrial lipid metabolism involves biosynthesis of the phospholipids phosphatidylethanolamine, cardiolipin and phosphatidylglycerol, the latter is a precursor of the late endosomal lipid bis(monoacylglycero)phosphate. It also includes mitochondrial fatty acid synthesis necessary for the formation of the lipid cofactor lipoic acid. Furthermore the synthesis of coenzyme Q takes place in mitochondria as well as essential parts of the steroid and vitamin D metabolism. Lipid transport and remodelling, which are necessary for tailoring and maintaining specific membrane properties, are just partially unravelled. Mitochondrial lipids are involved in organelle maintenance, fission and fusion, mitophagy and cytochrome c-mediated apoptosis. Mutations in TAZ, SERAC1 and AGK affect mitochondrial phospholipid metabolism and cause Barth syndrome, MEGDEL and Sengers syndrome, respectively. In these disorders an abnormal mitochondrial energy metabolism was found, which seems to be due to disturbed protein-lipid interactions, affecting especially enzymes of the oxidative phosphorylation. Since a growing number of enzymes and transport processes are recognised as parts of the mitochondrial lipid metabolism, a further increase of lipid-related disorders can be expected. PMID:25082432

  8. Integrating mitochondrial translation into the cellular context.

    Science.gov (United States)

    Richter-Dennerlein, Ricarda; Dennerlein, Sven; Rehling, Peter

    2015-10-01

    Mitochondrial-encoded subunits of the oxidative phosphorylation system assemble with nuclear-encoded subunits into enzymatic complexes. Recent findings showed that mitochondrial translation is linked to other mitochondrial functions, as well as to cellular processes. The supply of mitochondrial-encoded proteins is coordinated by the coupling of mitochondrial protein synthesis with assembly of respiratory chain complexes. MicroRNAs imported from the cytoplasm into mitochondria were, surprisingly, found to act as regulators of mitochondrial translation. In turn, translation in mitochondria controls cellular proliferation, and mitochondrial ribosomal subunits contribute to the cytoplasmic stress response. Thus, translation in mitochondria is apparently integrated into cellular processes. PMID:26535422

  9. Maintenance and propagation of a deleterious mitochondrial genome by the mitochondrial unfolded protein response.

    Science.gov (United States)

    Lin, Yi-Fan; Schulz, Anna M; Pellegrino, Mark W; Lu, Yun; Shaham, Shai; Haynes, Cole M

    2016-05-19

    Mitochondrial genomes (mitochondrial DNA, mtDNA) encode essential oxidative phosphorylation (OXPHOS) components. Because hundreds of mtDNAs exist per cell, a deletion in a single mtDNA has little impact. However, if the deletion genome is enriched, OXPHOS declines, resulting in cellular dysfunction. For example, Kearns-Sayre syndrome is caused by a single heteroplasmic mtDNA deletion. More broadly, mtDNA deletion accumulation has been observed in individual muscle cells and dopaminergic neurons during ageing. It is unclear how mtDNA deletions are tolerated or how they are propagated in somatic cells. One mechanism by which cells respond to OXPHOS dysfunction is by activating the mitochondrial unfolded protein response (UPR(mt)), a transcriptional response mediated by the transcription factor ATFS-1 that promotes the recovery and regeneration of defective mitochondria. Here we investigate the role of ATFS-1 in the maintenance and propagation of a deleterious mtDNA in a heteroplasmic Caenorhabditis elegans strain that stably expresses wild-type mtDNA and mtDNA with a 3.1-kilobase deletion (∆mtDNA) lacking four essential genes. The heteroplasmic strain, which has 60% ∆mtDNA, displays modest mitochondrial dysfunction and constitutive UPR(mt) activation. ATFS-1 impairment reduced the ∆mtDNA nearly tenfold, decreasing the total percentage to 7%. We propose that in the context of mtDNA heteroplasmy, UPR(mt) activation caused by OXPHOS defects propagates or maintains the deleterious mtDNA in an attempt to recover OXPHOS activity by promoting mitochondrial biogenesis and dynamics. PMID:27135930

  10. Nitrate-containing beetroot enhances myocyte metabolism and mitochondrial content.

    Science.gov (United States)

    Vaughan, Roger A; Gannon, Nicholas P; Carriker, Colin R

    2016-01-01

    Beetroot ( tián cài) juice consumption is of current interest for improving aerobic performance by acting as a vasodilator and possibly through alterations in skeletal muscle metabolism and physiology. This work explored the effects of a commercially available beetroot supplement on metabolism, gene expression, and mitochondrial content in cultured myocytes. C2C12 myocytes were treated with various concentrations of the beetroot supplement for various durations. Glycolytic metabolism and oxidative metabolism were quantified via measurement of extracellular acidification and oxygen consumption, respectively. Metabolic gene expression was measured using quantitative reverse transcription-polymerase chain reaction, and mitochondrial content was assessed with flow cytometry and confocal microscopy. Cells treated with beetroot exhibited significantly increased oxidative metabolism, concurrently with elevated metabolic gene expression including peroxisome proliferator-activated receptor gamma coactivator-1 alpha, nuclear respiratory factor 1, mitochondrial transcription factor A, and glucose transporter 4, leading to increased mitochondrial biogenesis. Our data show that treatment with a beetroot supplement increases basal oxidative metabolism. Our observations are also among the first to demonstrate that beetroot extract is an inducer of metabolic gene expression and mitochondrial biogenesis. These observations support the need for further investigation into the therapeutic and pharmacological effects of nitrate-containing supplements for health and athletic benefits. PMID:26870674

  11. Bayesian Space-Time Patterns and Climatic Determinants of Bovine Anaplasmosis

    Science.gov (United States)

    Hanzlicek, Gregg A.; Raghavan, Ram K.; Ganta, Roman R.; Anderson, Gary A.

    2016-01-01

    The space-time pattern and environmental drivers (land cover, climate) of bovine anaplasmosis in the Midwestern state of Kansas was retrospectively evaluated using Bayesian hierarchical spatio-temporal models and publicly available, remotely-sensed environmental covariate information. Cases of bovine anaplasmosis positively diagnosed at Kansas State Veterinary Diagnostic Laboratory (n = 478) between years 2005–2013 were used to construct the models, which included random effects for space, time and space-time interaction effects with defined priors, and fixed-effect covariates selected a priori using an univariate screening procedure. The Bayesian posterior median and 95% credible intervals for the space-time interaction term in the best-fitting covariate model indicated a steady progression of bovine anaplasmosis over time and geographic area in the state. Posterior median estimates and 95% credible intervals derived for covariates in the final covariate model indicated land surface temperature (minimum), relative humidity and diurnal temperature range to be important risk factors for bovine anaplasmosis in the study. The model performance measured using the Area Under the Curve (AUC) value indicated a good performance for the covariate model (> 0.7). The relevance of climatological factors for bovine anaplasmosis is discussed. PMID:27003596

  12. Bayesian Space-Time Patterns and Climatic Determinants of Bovine Anaplasmosis.

    Science.gov (United States)

    Hanzlicek, Gregg A; Raghavan, Ram K; Ganta, Roman R; Anderson, Gary A

    2016-01-01

    The space-time pattern and environmental drivers (land cover, climate) of bovine anaplasmosis in the Midwestern state of Kansas was retrospectively evaluated using Bayesian hierarchical spatio-temporal models and publicly available, remotely-sensed environmental covariate information. Cases of bovine anaplasmosis positively diagnosed at Kansas State Veterinary Diagnostic Laboratory (n = 478) between years 2005-2013 were used to construct the models, which included random effects for space, time and space-time interaction effects with defined priors, and fixed-effect covariates selected a priori using an univariate screening procedure. The Bayesian posterior median and 95% credible intervals for the space-time interaction term in the best-fitting covariate model indicated a steady progression of bovine anaplasmosis over time and geographic area in the state. Posterior median estimates and 95% credible intervals derived for covariates in the final covariate model indicated land surface temperature (minimum), relative humidity and diurnal temperature range to be important risk factors for bovine anaplasmosis in the study. The model performance measured using the Area Under the Curve (AUC) value indicated a good performance for the covariate model (> 0.7). The relevance of climatological factors for bovine anaplasmosis is discussed. PMID:27003596

  13. Characterization of recombinant human and bovine thyroid-stimulating hormone preparations by mass spectrometry and determination of their endotoxin content

    OpenAIRE

    Schaefer, S.; Hassa, P O; Sieber-Ruckstuhl, N S; Piechotta, M.; Reusch, C E; Roschitzki, B; Boretti, F S

    2013-01-01

    BACKGROUND: The TSH stimulation test to confirm canine hypothyroidism is commonly performed using a recombinant human TSH (rhTSH), as up to date, canine TSH is not yet commercially available. Limiting factors for the use of rhTSH are its high costs and occasional difficulties in product availability. Less expensive bovine TSH preparations (bTSH) purified from bovine pituitary glands are readily commercially available. The aim of this study was to evaluate two different bTSH products as altern...

  14. Orally administered bovine lactoferrin inhibits bacterial translocation in mice fed bovine milk.

    OpenAIRE

    Teraguchi, S.; Shin, K.; Ogata, T; Kingaku, M; Kaino, A; Miyauchi, H; Fukuwatari, Y; Shimamura, S

    1995-01-01

    Feeding of bovine milk to mice induced a high incidence of bacterial translocation from the intestines to the mesenteric lymph nodes, and the bacteria involved were mainly members of the family Enterobacteriaceae. Supplementation of the milk diet with bovine lactoferrin or a pepsin-generated hydrolysate of bovine lactoferrin resulted in significant suppression of bacterial translocation. Our findings suggest that this ability of lactoferrin to inhibit bacterial translocation may be due to its...

  15. Organization of Mitochondrial Gene Expression in Two Distinct Ribosome-Containing Assemblies

    Directory of Open Access Journals (Sweden)

    Kirsten Kehrein

    2015-02-01

    Full Text Available Mitochondria contain their own genetic system that provides subunits of the complexes driving oxidative phosphorylation. A quarter of the mitochondrial proteome participates in gene expression, but how all these factors are orchestrated and spatially organized is currently unknown. Here, we established a method to purify and analyze native and intact complexes of mitochondrial ribosomes. Quantitative mass spectrometry revealed extensive interactions of ribosomes with factors involved in all the steps of posttranscriptional gene expression. These interactions result in large expressosome-like assemblies that we termed mitochondrial organization of gene expression (MIOREX complexes. Superresolution microscopy revealed that most MIOREX complexes are evenly distributed throughout the mitochondrial network, whereas a subset is present as nucleoid-MIOREX complexes that unite the whole spectrum of organellar gene expression. Our work therefore provides a conceptual framework for the spatial organization of mitochondrial protein synthesis that likely developed to facilitate gene expression in the organelle.

  16. Mitochondrial Defects in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Josefa Salgado

    2008-01-01

    Full Text Available Mitochondria play important roles in cellular energy metabolism, free radical generation, and apoptosis. Mitochondrial DNA has been proposed to be involved in carcinogenesis because of its high susceptibility to mutations and limited repair mechanisms in comparison to nuclear DNA. Breast cancer is the most frequent cancer type among women in the world and, although exhaustive research has been done on nuclear DNA changes, several studies describe a variety of mitochondrial DNA alterations present in breast cancer. In this review article, we to provide a summary of the mitochondrial genomic alterations reported in breast cancer and their functional consequences.

  17. Lophotrochozoan mitochondrial genomes

    Energy Technology Data Exchange (ETDEWEB)

    Valles, Yvonne; Boore, Jeffrey L.

    2005-10-01

    Progress in both molecular techniques and phylogeneticmethods has challenged many of the interpretations of traditionaltaxonomy. One example is in the recognition of the animal superphylumLophotrochozoa (annelids, mollusks, echiurans, platyhelminthes,brachiopods, and other phyla), although the relationships within thisgroup and the inclusion of some phyla remain uncertain. While much ofthis progress in phylogenetic reconstruction has been based on comparingsingle gene sequences, we are beginning to see the potential of comparinglarge-scale features of genomes, such as the relative order of genes.Even though tremendous progress is being made on the sequencedetermination of whole nuclear genomes, the dataset of choice forgenome-level characters for many animals across a broad taxonomic rangeremains mitochondrial genomes. We review here what is known aboutmitochondrial genomes of the lophotrochozoans and discuss the promisethat this dataset will enable insight into theirrelationships.

  18. Factores de riesgo del síndrome respiratorio bovino en terneros lactantes de Argentina

    OpenAIRE

    García-Bocanegra, Ignacio; Arenas-Montes, Antonio José; Perea-Remujo, J.A.; Arenas-Casas, Antonio; Torralbo, A.; Borge-Rodríguez, Carmen; Carbonero-Martínez, Alfonso; Maldonado García, Alfonso

    2011-01-01

    An observacional cross-sectional study was performed to determine the risk factors associated to the main viral agents of the bovine respiratory disease: bovine herpesvirus type 1 (HVB1), bovine viral diarrhoea virus (VDVB), bovine respiratory syncytial virus (VRSB) and parainfluenza 3 virus (VPI3). Blood samples from dairy calves in the provinces of Cordova and Santa Fe (Argentina) were obtained, and an epidemiological ques-tionnaire was filled. Antibodies against studied viruses were detect...

  19. Role of mitochondrial damage during cardiac apoptosis in septic rats

    Institute of Scientific and Technical Information of China (English)

    LI Li; HU Bang-chuan; CHEN Chang-qin; GONG Shi-jin; YU Yi-hua; DAI Hai-wen; YAN Jing

    2013-01-01

    Background Myocardial apoptosis is involved in the pathogenesis of sepsis-related myocardial depression.However,the underlying mechanism remains unknown.This study investigated the role of mitochondrial damage and mitochondria-induced oxidative stress during cardiac apoptosis in septic rats.Methods Seventy-two Sprague-Dawley rats were randomly divided into a control group and septic group receiving lipopolysaccharide injection.Heart tissue was removed and changes in cardiac morphology were observed by light microscopy and scanning electron microscopy.In situ apoptosis was examined using terminal transferase-mediated dUTP nick end-labeling assay and nuclear factor-kappa B activation in myocardium by Western blotting to estimate myocardial apoptosis.Appearance of mitochondrial cristae and activation of cytochrome C oxidase were used to evaluate mitochondrial damage.Oxidative stress was assessed by mitochondrial lipid and protein oxidation,and antioxidant defense was assessed by mitochondrial superoxide dismutase and glutathione peroxidase activity.Results Sepsis-induced inflammatory cell infiltration,myocardium degeneration and dropsy were time-dependent.Expanded capillaries were observed in the hearts of infected rats 24 hours post-challenge.Compared with sham-treated rats,the percentage of cell apoptosis increased in a time-dependent manner in hearts from septic rats at 6 hours,12 hours and 24 hours post-injection (P < 0.05).The expression of nuclear factor-kappa B p65 decreased gradually in the cytosol and increased in the nucleus during sepsis,indicating that septic challenge provoked the progressive activation of nuclear factor-kappa B.Mitochondrial cristae and activation of cytochrome C oxidase increased in a time-dependent manner.Both superoxide dismutase and glutathione peroxidase activities decreased,while mitochondrial lipid and protein oxidation increased between 6 and 24 hours after lipopolysaccharide challenge.Conclusions Septic challenge induced

  20. Integrating mitochondrial translation into the cellular context.

    OpenAIRE

    Richter-Dennerlein, R.; Dennerlein Sven, S.; Rehling, P

    2015-01-01

    Mitochondrial-encoded subunits of the oxidative phosphorylation system assemble with nuclear-encoded subunits into enzymatic complexes. Recent findings showed that mitochondrial translation is linked to other mitochondrial functions, as well as to cellular processes. The supply of mitochondrial- encoded proteins is coordinated by the coupling of mitochondrial protein synthesis with assembly of respiratory chain complexes. MicroRNAs imported from the cytoplasm into mitochondria were, surprisin...