Andrea Markus - Academia.edu (original) (raw)

Papers by Andrea Markus

Nucleic Acids Research, 2006

Molecular Biology Reports, 2013

Journal of Molecular Medicine, 2002

Molecular and cellular biology, 2005

The BRCT domain is a highly conserved module found in many proteins that participate in DNA damag... more The BRCT domain is a highly conserved module found in many proteins that participate in DNA damage checkpoint regulation, DNA repair, and cell cycle control. Here we describe the cloning, characterization, and targeted mutagenesis of Brctx, a novel gene with a BRCT motif. Brctx was found to be expressed ubiquitously in adult tissues and during development, with the highest levels found in testis. Brctx-deficient mice develop normally, show no pathological abnormalities, and are fertile. BRCTx binds to the C terminus of hRAD18 in yeast two-hybrid and immunoprecipitation assays and colocalizes with this protein in the nucleus. Despite this, Brctx-deficient murine embryonic fibroblasts (MEFs) do not show overt sensitivity to DNA-damaging agents. MEFs from Brctx-deficient embryos grow at a similar rate to wild-type MEF CD4/CD8 expressions, and the cell cycle parameters of thymocytes from wild-type and Brctx knockout animals are indistinguishable. Intriguingly, the BRCT domain of BRCTx i...

The International Journal of Biochemistry & Cell Biology, 2009

Resveratrol is a polyphenolic flavonoid with potent antioxidant activity. It is found in a divers... more Resveratrol is a polyphenolic flavonoid with potent antioxidant activity. It is found in a diversity of plants, notably berry fruit, and is attracting increased attention due to its health benefits, especially in common age-related diseases such as cancer, type 2 diabetes, cardiovascular disease, and neurological conditions. Resveratrol has positive effects on metabolism and can increase the lifespan of various organisms. Its effects arise from its capacity to interact with multiple molecular targets involved in diverse intracellular pathways. Most well known is the ability of resveratrol to activate sirtuins, a class of NAD(+)-dependent deacetylases that affect multiple transcription factors and other protein targets. More potent sirtuin activators have now been discovered by large-scale screening programs. Resveratrol and the new compounds are the subject of clinical trials to determine their consumer safety and suitability for the prevention and treatment of most common diseases of aging.

Neuropharmacology, 2008

Changes in the levels of angiotensin-converting enzyme (ACE) have been found in brains of schizop... more Changes in the levels of angiotensin-converting enzyme (ACE) have been found in brains of schizophrenia patients, suggesting a possible involvement of angiotensin in the illness. Prepulse inhibition (PPI) is a measure of sensorimotor gating and is disrupted in patients with schizophrenia. In a previous study, a reduction of ACE activity, either in ACE knockout mice or after ACE inhibitor treatment, markedly inhibited the disruption of PPI caused by the dopamine receptor agonist, apomorphine. ACE is not specific for the angiotensin system and, therefore, in the present study we assessed pharmacological regulation of PPI in two other, more specific genetic mouse models of altered angiotensin activity. We used renin-enhancer knockout (REKO) mice, which display reduced renin activity, and neuron-specific enolase (NSE)-AT 1A mice, which selectively over-express angiotensin AT 1A receptors in the brain. Treatment of these mice with apomorphine, the dopamine releaser, amphetamine or the NMDA receptor antagonist, MK-801, significantly disrupted PPI. There was, however, no difference in these effects between the genotypes. These data suggest that genetically induced changes in the activity of the angiotensin system do not alter regulation of PPI in mice. Our previous results on the effects of reduced ACE activity could be explained by mechanisms other than angiotensin, such as effects on enkephalin or bradykinin metabolism.

The Journal of Pathology, 1996

The chromosomal translocation t(2;13)(q35;q14) has been reported in alveolar paediatric rhabdomyo... more The chromosomal translocation t(2;13)(q35;q14) has been reported in alveolar paediatric rhabdomyosarcoma. The rearrangement leads to the juxtaposition of the PAX-3 and FORKHEAD genes and the production of a fusion protein with putative transcriptional regulatory activity. The diagnostic potential of this translocation has been examined using a reverse transcription polymerase chain reaction (RT-PCR) assay to detect translocations in both fresh-frozen and archival formalin-fixed, paraffin-embedded rhabdomyosarcoma. A total of 25 tumours and one cell line were examined. PAX-3-FORKHEAD chimeric mRNAs were amplified by PCR in 8 of 15 cases of alveolar rhabdomyosarcoma. Translocations were detectable in both fresh-frozen tissues (4 of 7) and paraffin-embedded tumours (3 of 7) and in the alveolar rhabdomyosarcoma cell line. Our study confirms that the t(2;13) translocation is not present in embryonal rhabdomyosarcomas, but can be detected in nearly half of alveolar rhabdomyosarcomas, whether fresh-frozen or paraffin-embedded. The PCR-based t(2;13) translocation assay can aid in the diagnosis of rhabdomyosarcoma, but cannot replace a careful histopathological evaluation. It may contribute in further characterizing an otherwise undifferentiated small cell tumour, where it may be indicative of clinical behaviour.

Experimental Cell Research, 2006

Annals of the New York Academy of Sciences, 2007

The natural polyphenol resveratrol stimulates sirtuins and extends lifespan. Here resveratrol inh... more The natural polyphenol resveratrol stimulates sirtuins and extends lifespan. Here resveratrol inhibited expression of replicative senescence marker INK4a in human dermal fibroblasts, and 47 of 19,000 genes from microarray experiments were differentially expressed. These included genes for growth, cell division, cell signaling, apoptosis, and transcription. Genes involved in Ras and ubiquitin pathways, Ras-GRF1, RAC3, and UBE2D3, were downregulated. The changes suggest resveratrol might alter sirtuin-regulated downstream pathways, rather than sirtuin activity. Serum deprivation and high confluency caused nuclear translocation of the SIRT1-regulated transcription factor FOXO3a. Our data indicate resveratrol's actions might cause FOXO recruitment to the nucleus.

$Research paper thumbnail of Scanning X-ray diffraction on cardiac tissue: automatized data analysis and processing$

Journal of Synchrotron Radiation, 2017

A scanning X-ray diffraction study of cardiac tissue has been performed, covering the entire cros... more A scanning X-ray diffraction study of cardiac tissue has been performed, covering the entire cross section of a mouse heart slice. To this end, moderate focusing by compound refractive lenses to micrometer spot size, continuous scanning, data acquisition by a fast single-photon-counting pixel detector, and fully automated analysis scripts have been combined. It was shown that a surprising amount of structural data can be harvested from such a scan, evaluating the local scattering intensity, interfilament spacing of the muscle tissue, the filament orientation, and the degree of anisotropy. The workflow of data analysis is described and a data analysis toolbox with example data for general use is provided. Since many cardiomyopathies rely on the structural integrity of the sarcomere, the contractile unit of cardiac muscle cells, the present study can be easily extended to characterize tissue from a diseased heart.

The expression of the (pro)renin receptor (ATP6AP2) in late gestational human tissues suggests th... more The expression of the (pro)renin receptor (ATP6AP2) in late gestational human tissues suggests that the prorenin-angiotensin system (RAS) might influence pregnancy outcome. Here w e characterized the RAS in term fetal membranes (amnion and chorion), decidua and placenta (n = 38) from women undergoing elective cesarean section (non-labouring) or following spontaneous delivery (after labour), and myometrium (n = 16) from elective or emergency cesarean (labouring) deliveries. RT-qPCR was used to quantify prorenin (REN), AGT, ACE, ACE2, AGTR1, AGTR2, ATP6AP2 and MAS1 mRNAs, and immunohistochemistry was used to localize prorenin, AGT, ACE, ACE2 and AGTR1 proteins. In myometrium, mRNAs for downstream signalling proteins (ZBTB16, TGFB1 and PTGS2) were also measured. ACE and AGT mRNA levels were higher in labouring myometrium (P < 0.05), consistent with elevated production of angiotensin II (Ang II), which, by the upregulation of PTGS2 occurring in labour (P = 0.022), could influence labour. In amnion, expression of all RAS component mRNAs, except ATP6AP2, was low. After labour amnion showed lower ACE (P = 0.014) and higher AGTR2 (P = 0.01) mRNA levels. In decidua, RAS components other than AGTR1 and AGTR2 were abundant. Amnion and chorion exhibited higher immunostaining of AGT and prorenin than expected from their low mRNA levels, suggesting that these proteins could have been originated from decidua, where the cognate genes are more active. In placenta, prorenin and AGT were localized to syncytiotrophoblasts and ACE was localized to fetal capillary endothelial cells, while ACE2 distribution was diffuse. AGTR1 mRNA and protein expression was high in the placenta. We propose that ACE in fetal vessels could contribute Ang II to the fetus, while ACE2 in syncytiotrophoblasts might convert placental or maternal circulating Ang II to angiotensin-(1–7), which might then be supplied to the maternal bloodstream. In conclusion, the abundance and distribution of intrauterine RAS components suggest diverse roles for this local RAS in pregnancy.

Rhabdomyosarcomas bear a morphological and genetic resemblance to developing skeletal muscle. Apa... more Rhabdomyosarcomas bear a morphological and genetic resemblance to developing skeletal muscle. Apart from myogenic marker genes (bHLH factors, myosin, actin), cell adhesion molecules such as N-cadherin and N-CAM have been reported to be expressed both in rhabdomyosarcomas and during myogenesis. The present study demonstrates the expression of another cadherin, cadherin-11, in rhabdomyosarcomas and during differentiation of myoblasts in vitro: cadherin-11, a predominantly mesenchymal cell adhesion molecule, is highly expressed in embryonal rhabdomyosarcomas and alveolar rhabdomyosarcomas, which do not bear the Pax-3-FKHR fusion previously described. Cadherin-11 is down-regulated in normal skeletal muscle and after myotube formation in vitro. The results of this study suggest that cadherin-11 might be involved in myogenesis and that rhabdomyosarcomas may re-express or fail to down-regulate cadherin-11. Since alveolar rhabdomyosarcomas bearing the t(2;13) translocation do not express cadherin-11, it is postulated that Pax-3 and cadherin-11 might be linked and involved in the same myogenic pathway.