263 research outputs found
How do changes in the mtDNA and mitochondrial dysfunction influence cancer and cancer therapy? Challenges, opportunities and models
Several mutations in nuclear genes encoding for mitochondrial components have been associated with an increased cancer risk or are even causative, e.g. succinate dehydrogenase (SDHB, SDHC and SDHD genes) and iso-citrate dehydrogenase (IDH1 and IDH2 genes). Recently, studies have suggested an eminent role for mitochondrial DNA (mtDNA) mutations in the development of a wide variety of cancers. Various studies associated mtDNA abnormalities, including mutations, deletions, inversions and copy number alterations, with mitochondrial dysfunction. This might, explain the hampered cellular bioenergetics in many cancer cell types. Germline (e.g. m.10398A>G; m.6253T>C) and somatic mtDNA mutations as well as differences in mtDNA copy number seem to be associated with cancer risk. It seems that mtDNA can contribute as driver or as complementary gene mutation according to the multiple-hit model. This can enhance the mutagenic/clonogenic potential of the cell as observed for m.8993T>G or influences the metastatic potential in later stages of cancer progression. Alternatively, other mtDNA variations will be innocent passenger mutations in a tumor and therefore do not contribute to the tumorigenic or metastatic potential. In this review, we discuss how reported mtDNA variations interfere with cancer treatment and what implications this has on current successful pharmaceutical interventions. Mutations in MT-ND4 and mtDNA depletion have been reported to be involved in cisplatin resistance. Pharmaceutical impairment of OXPHOS by metformin can increase the efficiency of radiotherapy. To study mitochondrial dysfunction in cancer, different cellular models (like ρ0 cells or cybrids), in vivo murine models (xenografts and specific mtDNA mouse models in combination with a spontaneous cancer mouse model) and small animal models (e.g. Danio rerio) could be potentially interesting to use. For future research, we foresee that unraveling mtDNA variations can contribute to personalized therapy for specific cancer types and improve the outcome of the disease
助成研究報告
textabstractIncreasing amounts of data support a role for guanine quadruplex (G4) DNA and RNA structures in various cellular processes. We stained different organisms with monoclonal antibody 1H6 specific for G4 DNA. Strikingly, immuno-electron microscopy showed exquisite specificity for heterochromatin. Polytene chromosomes from Drosophila salivary glands showed bands that co-localized with heterochromatin proteins HP1 and the SNF2 domain-containing protein SUUR. Staining was retained in SUUR knock-out mutants but lost upon overexpression of SUUR. Somatic cells in Macrostomum lignano were strongly labeled, but pluripotent stem cells labeled weakly. Similarly, germline stem cells in Drosophila ovaries were weakly labeled compared to most other cells. The unexpected presence of G4 structures in heterochromatin and the difference in G4 staining between somatic cells and stem cells with germline DNA in ciliates, flatworms, flies and mammals point to a conserved role for G4 structures in nuclear organization and cellular differentiation
Longitudinal double-spin asymmetry and cross section for inclusive neutral pion production at midrapidity in polarized proton collisions at sqrt(s) = 200 GeV
We report a measurement of the longitudinal double-spin asymmetry A_LL and
the differential cross section for inclusive Pi0 production at midrapidity in
polarized proton collisions at sqrt(s) = 200 GeV. The cross section was
measured over a transverse momentum range of 1 < p_T < 17 GeV/c and found to be
in good agreement with a next-to-leading order perturbative QCD calculation.
The longitudinal double-spin asymmetry was measured in the range of 3.7 < p_T <
11 GeV/c and excludes a maximal positive gluon polarization in the proton. The
mean transverse momentum fraction of Pi0's in their parent jets was found to be
around 0.7 for electromagnetically triggered events.Comment: 6 pages, 3 figures, submitted to Phys. Rev. D (RC
Longitudinal scaling property of the charge balance function in Au + Au collisions at 200 GeV
We present measurements of the charge balance function, from the charged
particles, for diverse pseudorapidity and transverse momentum ranges in Au + Au
collisions at 200 GeV using the STAR detector at RHIC. We observe that the
balance function is boost-invariant within the pseudorapidity coverage [-1.3,
1.3]. The balance function properly scaled by the width of the observed
pseudorapidity window does not depend on the position or size of the
pseudorapidity window. This scaling property also holds for particles in
different transverse momentum ranges. In addition, we find that the width of
the balance function decreases monotonically with increasing transverse
momentum for all centrality classes.Comment: 6 pages, 3 figure
Energy and system size dependence of \phi meson production in Cu+Cu and Au+Au collisions
We study the beam-energy and system-size dependence of \phi meson production
(using the hadronic decay mode \phi -- K+K-) by comparing the new results from
Cu+Cu collisions and previously reported Au+Au collisions at \sqrt{s_NN} = 62.4
and 200 GeV measured in the STAR experiment at RHIC. Data presented are from
mid-rapidity (|y|<0.5) for 0.4 < pT < 5 GeV/c. At a given beam energy, the
transverse momentum distributions for \phi mesons are observed to be similar in
yield and shape for Cu+Cu and Au+Au colliding systems with similar average
numbers of participating nucleons. The \phi meson yields in nucleus-nucleus
collisions, normalised by the average number of participating nucleons, are
found to be enhanced relative to those from p+p collisions with a different
trend compared to strange baryons. The enhancement for \phi mesons is observed
to be higher at \sqrt{s_NN} = 200 GeV compared to 62.4 GeV. These observations
for the produced \phi(s\bar{s}) mesons clearly suggest that, at these collision
energies, the source of enhancement of strange hadrons is related to the
formation of a dense partonic medium in high energy nucleus-nucleus collisions
and cannot be alone due to canonical suppression of their production in smaller
systems.Comment: 20 pages and 5 figure
Measurement of the Bottom contribution to non-photonic electron production in collisions at =200 GeV
The contribution of meson decays to non-photonic electrons, which are
mainly produced by the semi-leptonic decays of heavy flavor mesons, in
collisions at 200 GeV has been measured using azimuthal
correlations between non-photonic electrons and hadrons. The extracted
decay contribution is approximately 50% at a transverse momentum of GeV/. These measurements constrain the nuclear modification factor for
electrons from and meson decays. The result indicates that meson
production in heavy ion collisions is also suppressed at high .Comment: 6 pages, 4 figures, accepted by PR
Carbon dioxide-enriched atmosphere enhances biomass accumulation and meristem production in the pioneer shrub Baccharis dracunculifolia (Asteraceae)
Influence of fire history and soil properties on plant species richness and functional diversity in a neotropical savanna
Níveis iônicos e enzimáticos de cutias (Dasyprocta sp.) hígidas, criadas em cativeiro, influência do sexo e da idade
- …