Publications by authors named "Manthey G"

Migratory birds possess remarkable accuracy in orientation and navigation, which involves various compass systems including the magnetic compass. Identifying the primary magnetosensor remains a fundamental open question. Cryptochromes (Cry) have been shown to be magnetically sensitive, and Cry4a from a migratory songbird seems to show enhanced magnetic sensitivity compared to Cry4a from resident species.

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Recombination is responsible for breaking up haplotypes, influencing genetic variability, and the efficacy of selection. Bird genomes lack the protein PR domain-containing protein 9, a key determinant of recombination dynamics in most metazoans. Historical recombination maps in birds show an apparent stasis in positioning recombination events.

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The ability of migratory birds to sense magnetic fields has been known for decades, although the understanding of the underlying mechanism is still elusive. Currently, the strongest magnetoreceptor candidate in birds is a protein called cryptochrome 4a. The cryptochrome 4a protein has changed through evolution, apparently endowing some birds with a more pronounced magnetic sensitivity than others.

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A recent study by Xu et al. (, , 594, 535-540) provided strong evidence that cryptochrome 4 (Cry4) is a key protein to endow migratory birds with the magnetic compass sense. The investigation compared the magnetic field response of Cry4 from migratory and nonmigratory bird species and suggested that a difference in magnetic sensitivity could exist.

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11β-Hydroxysteroid dehydrogenase 1 (11β-HSD1) plays an important role in pre-receptor glucocorticoid metabolism. This enzyme is expressed in bone, increases with age, and catalyzes the conversion of the inactive glucocorticoid cortisone into the active glucocorticoid cortisol and vice versa. Here we hypothesized that the physiological activity of 11β-HSD1 to produce cortisol in human mesenchymal progenitor cells (hMSC) is principally sufficient to shift the differentiation potential in the direction of adipogenic.

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RAD52 is a structurally and functionally conserved component of the DNA double-strand break (DSB) repair apparatus from budding yeast to humans. We recently showed that expressing the human gene, in mutant budding yeast cells can suppress both their ionizing radiation (IR) sensitivity and homologous recombination repair (HRR) defects. Intriguingly, we observed that supports DSB repair by a mechanism of HRR that conserves genome structure and is independent of the canonical HR machinery.

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Objective: The aims of this exploratory study were (1) to develop a standardized objective electrophysiological technique with laser-evoked potentials to assess dorsal root damage quantitatively and (2) to correlate these LEP measures with clinical parameters and sensory abnormalities (QST) in the affected dermatome.

Methods: Thirty-eight patients with painful radiculopathy and 20 healthy subjects were investigated with LEP recorded from the affected dermatome and control areas as well as with quantitative sensory testing. Questionnaires evaluating severity and functionality were applied.

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Background: Repetitive painful laser stimuli lead to physiological laser-evoked potential (LEP) habituation, measurable by a decrement of the N2/P2 amplitude. The time course of LEP-habituation is reduced in the capsaicin model for peripheral and central sensitization and in patients with migraine and fibromyalgia. In the present investigation, we aimed to assess the time course of LEP-habituation in a neuropathic pain syndrome, i.

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RAD52 is a homologous recombination (HR) protein that is conserved from bacteriophage to humans. Simultaneously attenuating expression of both the RAD52 gene, and the HR and tumor suppressor gene, BRCA2, in human cells synergistically reduces HR - indicating that RAD52 and BRCA2 control independent mechanisms of HR. We have expressed the human RAD52 gene (HsRAD52) in budding yeast strains lacking the endogenous RAD52 gene and found that HsRAD52 supports repair of DNA double-strand breaks (DSB) by a mechanism of HR that conserves genome structure.

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Background: Recent studies applied laser-evoked potentials (LEP) for the analysis of small nerve fibre function and focused on the detection of stable C-fibre-mediated potentials (C-LEPs); high technical requirements were needed. The diagnostic significance is still controversially discussed. So far, only few studies focused on the susceptibility of C-LEPs to distraction and other influences.

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Background: In Saccharomyces cerevisiae, Rad59 is required for multiple homologous recombination mechanisms and viability in DNA replication-defective rad27 mutant cells. Recently, four rad59 missense alleles were found to have distinct effects on homologous recombination that are consistent with separation-of-function mutations. The rad59-K166A allele alters an amino acid in a conserved α-helical domain, and, like the rad59 null allele diminishes association of Rad52 with double-strand breaks.

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Article Synopsis
  • Homologous recombination is a key DNA repair process in eukaryotes after radiation exposure, especially involving repetitive DNA sequences.
  • The study uses Saccharomyces cerevisiae to model the formation of chromosomal translocations via a method called single-strand annealing and highlights the role of the Rad59 protein.
  • Rad59 has both Rad52-dependent and independent functions, aiding in Rad52's localization at DNA break sites and affecting genome structure after DNA damage.
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Genetic variation is frequently mediated by genomic rearrangements that arise through interaction between dispersed repetitive elements present in every eukaryotic genome. This process is an important mechanism for generating diversity between and within organisms(1-3). The human genome consists of approximately 40% repetitive sequence of retrotransposon origin, including a variety of LINEs and SINEs(4).

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Chromosomal translocations are a primary biological response to ionizing radiation (IR) exposure, and are likely to result from the inappropriate repair of the DNA double-strand breaks (DSBs) that are created. An abundance of repetitive sequences in eukaryotic genomes provides ample opportunity for such breaks to be repaired by homologous recombination (HR) between non-allelic repeats. Interestingly, in the budding yeast, Saccharomyces cerevisiae the central strand exchange protein, Rad51 that is required for DSB repair by gene conversion between unlinked repeats that conserves genomic structure also suppresses translocation formation by several HR mechanisms.

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Studies in the budding yeast, Saccharomyces cerevisiae, have demonstrated that a substantial fraction of double-strand break repair following acute radiation exposure involves homologous recombination between repetitive genomic elements. We have previously described an assay in S. cerevisiae that allows us to model how repair of multiple breaks leads to the formation of chromosomal translocations by single-strand annealing (SSA) and found that Rad59, a paralog of the single-stranded DNA annealing protein Rad52, is critically important in this process.

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Article Synopsis
  • Chromosomal translocations often occur in response to DNA double-strand breaks (DSBs) induced by factors like ionizing radiation and chemotherapy, linked to tumors in mammals.
  • Research on budding yeast (*Saccharomyces cerevisiae*) reveals high translocation rates following DSBs near repetitive DNA on non-homologous chromosomes, suggesting that this process utilizes single-strand annealing (SSA).
  • The study identifies the central mismatch repair factor Msh2 as crucial in translocation formation, indicating it stabilizes annealed DNA strands and helps remove non-homologous sequences, while also blocking alternative removal pathways.
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Defective DNA replication can result in substantial increases in the level of genome instability. In the yeast Saccharomyces cerevisiae, the pol3-t allele confers a defect in the catalytic subunit of replicative DNA polymerase delta that results in increased rates of mutagenesis, recombination, and chromosome loss, perhaps by increasing the rate of replicative polymerase failure. The translesion polymerases Pol eta, Pol zeta, and Rev1 are part of a suite of factors in yeast that can act at sites of replicative polymerase failure.

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Exposure to ionizing radiation results in a variety of genome rearrangements that have been linked to tumor formation. Many of these rearrangements are thought to arise from the repair of double-strand breaks (DSBs) by several mechanisms, including homologous recombination (HR) between repetitive sequences dispersed throughout the genome. Doses of radiation sufficient to create DSBs in or near multiple repetitive elements simultaneously could initiate single-strand annealing (SSA), a highly efficient, though mutagenic, mode of DSB repair.

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A pilot study was conducted to determine the concentrations of soluble serum E-cadherin in 36 patients with colorectal cancer or a high-grade dysplasia by the use of an ELISA technique. The results were compared with staging characteristics and concentrations of routine serum carcinoembryonic antigen (CEA). Sixteen patients with benign diseases and nine healthy volunteers served as internal or negative controls.

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The ability to make specific genomic alterations is an invaluable tool to researchers who use genetics and biochemistry to study problems in biology. We have investigated some of the parameters governing DNA fragment transplacement in two commonly used strains of Saccharomyces cerevisiae, S288C and W303-1A. These strains exhibited a marked difference in their capacity to take up plasmid DNA and utilize linear DNA fragments as substrates for transplacement.

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In the budding yeast Saccharomyces cerevisiae, null alleles of several DNA repair and recombination genes confer defects in recombination that grow more severe with decreasing sequence length, indicating that they are required for short-sequence recombination (SSR). RAD1 and RAD10, which encode the subunits of the structure-specific endonuclease Rad1/10, are critical for SSR. MRE11, RAD50, and XRS2, which encode the subunits of M/R/X, another complex with nuclease activity, are also crucially important.

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Background: Mitogen activated protein kinases (MAPKs) play a central role in the regulation of both cell growth and differentiation. They are involved in signal transduction of oncogenes and growth factors. The role of MAPK in colonic carcinoma is unknown.

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Maintaining genome stability requires that recombination between repetitive sequences be avoided. Because short, repetitive sequences are the most abundant, recombination between sequences that are below a certain length are selectively restricted. Novel alleles of the RAD3 and SSL1 genes, which code for components of a basal transcription and UV-damage-repair complex in Saccharomyces cerevisiae, have been found to stimulate recombination between short, repeated sequences.

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The nuclear PET309 gene of Saccharomyces cerevisiae is necessary for expression of the mitochondrial COX1 gene, which encodes subunit I of cytochrome c oxidase. In a pet309 null mutant, there is a defect both in accumulation of COX1 pre-RNA, if it contains introns, and in translation of COX1 RNAs [Manthey, G. M.

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Scope: This review summarizes the main issues discussed during Track D, which examined the societal impact of HIV/AIDS, and responses to the epidemic by individuals, families, communities and societies worldwide. Micro- and macrolevel issues addressed included the development, implementation and evaluation of programmes for prevention and care; policy development and implementation; structural issues such as the impact of gender relations, development and migration on the development of the epidemic; and the social and economic impact of HIV/AIDS on affected societies and communities.

Recurrent Themes: Presentations provided strong evidence that peer-led, community-based programmes offer particularly effective ways of working, and that participatory research involving affected communities provides useful results for the design and evaluation of programmes and policies.

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