Paleogeographic Reconstructions in the Mediterranean : A Paleomagnetic Study of Jurassic Sediments From Sardinia

The paleogeography and tectonic history of the Corsica-Sardinia block and the opening of the Liguro-Proven\ue7al ocean since Oligocene times is based on a wealth of geologic, geophysical, and paleomagnetic studies and relatively well understood (Gattacceca et al. 2007, Vigliotti and Langenheim 1995). Conversely, the paleogeography of Sardinia and the surrounding regions during the Mesozoic is much less clear due to the absence of paleomagnetic data, except for a single study on Jurassic sediments from eastern Sardinia (Horner and Lowrie 1981). Consequently, pre-Oligocene deformations of Sardinia remain virtually undated. Recent paleomagnetic studies of dykes of Late Carboniferous and Permian age as well as Permian sediments have revealed significant counterclockwise rotations between Northern, Central and Southern Sardinia (Emmer et al., 2005). The geodynamic context these rotational movements are related to, however, is still far from being clear. In an attempt to contribute to better time constraints for tectonic motions within Sardinia, a total of 208 oriented core samples from 24 sites of predominantly Jurassic age have been collected from the Nurra region (1), the Gulf of Orosei (2) and the Tacchi region (3). Unfortunately, samples taken from the northwest of Sardinia (1) proved to be too weakly magnetized and did not yield any stable directions. Primary directions of magnetization, passing the reversal test, were recovered from regions (2) and (3), yielding overall mean directions of D=284.8\ub0, I=46.6\ub0 (N=36, \u3b195=9.9, k=32.1) and D=267.0\ub0, I=49.9\ub0 (N=68, \u3b195=12.3, k=13.5) for the Gulf of Orosei and the Tacchi region, respectively. Taking into account error limits, these directions are not significantly different from each other and confirm and expand the limited data set of Horner and Lowrie (1981). Based on these new results, we conclude that no post-Jurassic deformation has affected the region. This suggests that the counterclockwise rotations previously observed in Permian rocks by Emmer et al. must be pre-Jurassic in age and cannot be related to subduction rollback tectonics during the Oligocene to Miocene as suggested by Helbig et al. (2006)

Paleomagnetic data from Late Paleozoic dykes of Sardinia: evidence for block rotations and implications for the intra-Pangea megashear system

Paleomagnetic studies of dyke swarms from the Variscan belt of Europe can be used to reconstruct internal postorogenic rotations within the fold belt. Here we present paleomagnetic data from 13 late Variscan dykes from Sardinia ranging in age from 298\ub15 to 270\ub110 Ma. The dykes can be grouped on the basis of their different directions in strike in a northern, a central-eastern and a south-eastern province. Paleomagnetic component directions have been obtained using thermal and alternating field demagnetization techniques, which give reproducible results. The paleomagnetic mean directions differ significantly between northern Sardinia and south-eastern and central-eastern Sardinia, the latter two regions yielding statistically similar paleomagnetic mean directions. These results indicate that Sardinia fragmented into two, arguably three, crustal blocks after emplacement of the dykes, which experienced differential relative rotations, as is also indicated by the differences in overall strike directions. The determination of timing, sense, and magnitude of these rotations has major implications for the reconstruction of the geodynamic evolution of the region in post-Carboniferous times. We argue that the observed block rotations occurred during the Permian as the result of post-Variscan intra-Pangea mobility possibly related to the transformation of an Early Permian Pangea B to a Late Permian Pangea A. \ua9 2014. American Geophysical Union. All Rights Reserved

In situ quantification of HER2–protein tyrosine kinase 6 (PTK6) protein–protein complexes in paraffin sections from breast cancer tissues

BACKGROUND: Protein tyrosine kinase 6 (PTK6; breast tumour kinase) is overexpressed in up to 86% of the invasive breast cancers, and its association with the oncoprotein human epidermal growth factor receptor 2 (HER2) was shown in vitro by co-precipitation. Furthermore, expression of PTK6 in tumours is linked with the expression of HER2. METHOD AND RESULTS: In this study, we used the proximity ligation assay (PLA) technique on formalin-fixed paraffin sections from eighty invasive breast carcinoma tissue specimens to locate PTK6-HER2 protein-protein complexes. Proximity ligation assay signals from protein complexes were assessed quantitatively, and expression levels showed a statistically significant association with tumour size (P=0.015) and course of the cancer disease (P=0.012). CONCLUSION: Protein tyrosine kinase 6 forms protein complexes with HER2 in primary breast cancer tissues, which can be visualised by use of the PLA technique. Human epidermal growth factor receptor 2-PTK6 complexes are of prognostic relevance

A paleomagnetic study of Permian and Triassic rocks from the Toulon-Cuers Basin, SE France: Evidence for intra-Pangea block rotations in the Permian

The identification of a massive shear zone separating Gondwana from Laurasia during late Palaeozoic times is one of the prerequisites for the controversial Pangea B to A transition. Here we present new paleomagnetic data from Permian and Triassic sediments and volcanic rocks from the Toulon-Cuers basin, SE France, likely to be situated within this intra-Pangea shear zone. A total of 150 samples from 14 sites were collected in the field; 108 samples yielded reliable paleomagnetic component directions based on stepwise thermal demagnetization up to maximum temperatures of 690C. After removal of an initial viscous magnetic component from room temperature up to 200C, a second component of reverse polarity, oriented to the south-and-up, was identified in almost all samples of Permian age. The Triassic samples behave similarly, with the notable difference that here, two polarities of magnetization are present. Positive field tests suggest the primary character of this characteristic magnetization. The latitudes of the resulting Early to Mid Permian paleopoles agree well with the corresponding segment of the apparent polar wander path (APWP) for Europe, whereas the longitudes are strung out along a small circle segment, indicating relative rotations between the sampled regions and stable Europe. The Triassic poles, instead, plot close to the Triassic segment of the European APWP and provide an upper time limit for the observed rotations. These results suggest a wrench faulting event associated with intra-Pangea crustal instability and transformation during the Permian

Observation of the geology and geomorphology of the 1999 Marsokhod test site

The Marsokhod rover returned data from six stations that were used to decipher the geomorphology and geology of a region not previously visited by members of the geomorphology field team. Satellite images and simulated descent images provided information about the regional setting. The landing zone was on an alluvial apron flanking a mountain block to the west and a playa surface to the east. Rover color images, infrared spectra analysis of the mountains, and the apron surface provided insight into the rock composition of the nearby mountains. From the return data the geomorphology team interpreted the region to consist of compressionally deformed, ancient marine sediments and igneous rocks exposed by more recent extensional tectonics. Unconsolidated alluvial materials blanket the lower flanks of the mountains. Bn ancient shoreline cut into alluvial material marks a high stand of water during a past, wetter climate period. Playa sediments floor a present-day, seasonally, dry lake. Observations made by the rover using panoramic and close-up (hand specimens-scale) image data and color scene data confirmed the presence of boulders, cobbles, and fines of various provinces. Rover traverses to sites identified as geologically distinct, such as fan, channel, shoreline, and playa, provided useful clues to the geologic interpretations. Analysis of local rocks was given concert only through comparison with distant geologic features. These results demonstrated the importance of a multifaceted approach to site interpretation through comparison of interpretations derived by differing geologic techniques

Observations of the geology and geomorphology of the 1999 Marsokhod test site

The Marsokhod rover returned data from six stations that were used to decipher the geomorphology and geology of a region not previously visited by members of the geomorphology field team. Satellite images and simulated descent images provided information about the regional setting. The landing zone was on an alluvial apron flanking a mountain block to the west and playa surface to the east. Rover color images, infrared spectra analysis of the mountains, and the apron surface provided insight into the rock composition of the nearby mountains. From the return data the geomorphology team interpreted the region to consist of compressionally deformed, ancient marine sediments and igneous rocks exposed by more recent extensional tectonics. Unconsolidated alluvial materials blanket the lower flanks of the mountains. An ancient shoreline cut into alluvial material marks a high stand of water during a past, wetter climate period. Playa sediments floor a present-day, seasonally, dry lake. Observations made by the rover using panoramic and close-up (hand specimens—scale) image data and color scene data confirmed the presence of boulders, cobbles, and fines of various provinces. Rover traverses to sites identified as geologically distinct, such as a fan, channel, shoreline, and playa, provided useful clues to the geologic interpretations. Analysis of local rocks was given context only through comparison with distant geologic features. These results demonstrated the importance of a multifaceted approach to site interpretation through comparison of interpretations derived by differing geologic techniques

Array comparative genomic hybridisation (aCGH) analysis of premenopausal breast cancers from a nuclear fallout area and matched cases from Western New York

High-resolution array comparative genomic hybridisation (aCGH) analysis of DNA copy number aberrations (CNAs) was performed on breast carcinomas in premenopausal women from Western New York (WNY) and from Gomel, Belarus, an area exposed to fallout from the 1986 Chernobyl nuclear accident. Genomic DNA was isolated from 47 frozen tumour specimens from 42 patients and hybridised to arrays spotted with more than 3000 BAC clones. In all, 20 samples were from WNY and 27 were from Belarus. In total, 34 samples were primary tumours and 13 were lymph node metastases, including five matched pairs from Gomel. The average number of total CNAs per sample was 76 (range 35–134). We identified 152 CNAs (92 gains and 60 losses) occurring in more than 10% of the samples. The most common amplifications included gains at 8q13.2 (49%), at 1p21.1 (36%), and at 8q24.21 (36%). The most common deletions were at 1p36.22 (26%), at 17p13.2 (26%), and at 8p23.3 (23%). Belarussian tumours had more amplifications and fewer deletions than WNY breast cancers. HER2/neu negativity and younger age were also associated with a higher number of gains and fewer losses. In the five paired samples, we observed more discordant than concordant DNA changes. Unsupervised hierarchical cluster analysis revealed two distinct groups of tumours: one comprised predominantly of Belarussian carcinomas and the other largely consisting of WNY cases. In total, 50 CNAs occurred significantly more commonly in one cohort vs the other, and these included some candidate signature amplifications in the breast cancers in women exposed to significant radiation. In conclusion, our high-density aCGH study has revealed a large number of genetic aberrations in individual premenopausal breast cancer specimens, some of which had not been reported before. We identified a distinct CNA profile for carcinomas from a nuclear fallout area, suggesting a possible molecular fingerprint of radiation-associated breast cancer

Prognostic value of protein tyrosine kinase 6 (PTK6) for long-term survival of breast cancer patients

The cytoplasmic tyrosine kinase PTK6 (BRK) shows elevated expression in approximately two-thirds of primary breast tumours, and is implicated in EGF receptor-dependent signalling and epithelial tumorigenesis. Using immunohistochemistry, we performed a retrospective study on 426 archival breast cancer samples from patients with long-term follow-up and compared the protein expression levels of PTK6, the HER receptors, Sam68 (a substrate of PTK6), and signalling proteins including MAP kinase (MAPK), phosphorylated MAPK (P-MAPK), and PTEN. We show that PTK6 expression is of significant prognostic value in the outcome of breast carcinomas. In multivariate analysis, the disease-free survival of patients of ⩾240 months was directly associated with the protein expression level of PTK6 (P⩽0.001), but was also inversely associated with nodal status (P⩽0.001) and tumour size (P⩽0.01). PTK6 expression in tumour tissue significantly correlated (P⩽0.05) with the expression of PTEN, MAPK, P-MAPK, and Sam68. To investigate whether these correlations may be due to molecular interactions between PTK6 and these proteins, we used protein extracts from the T47D cell line for immunoprecipitation and western blot analysis. By this, interactions could be demonstrated between PTK6 and MAPK, P-MAPK, HER2/neu, HER3, HER4, PTEN, and Sam68. On the basis of these results, we suggest that PTK6 may serve as a future target for the development of novel treatments in breast cancer

PTK (protein tyrosine kinase)-6 and HER2 and 4, but not HER1 and 3 predict long-term survival in breast carcinomas

The HER receptors are of therapeutic and prognostic significance in breast cancer, and their function is modulated by cytoplasmic tyrosine kinases like PTK6 (brk). We performed a retrospective study on archival breast cancer samples from patients with long follow-up and compared the protein expression between individual HERs and between HERs and the PTK6. Univariate and multivariate analyses were used to study the prognostic value of parameters. Metastases-free survival of patients for longer than 240 months was inversely associated (P⩽0.05) with nodal status, tumour size, and oestrogen receptor status, but was also directly associated with high protein expression levels of HER4 and PTK6 in Kaplan–Meier analysis. In multivariate analysis for metastases-free survival of >240 months, the stepwise selected parameters were tumour size (relative risk 3.1), PTK6 expression (0.4), and number of positive lymph nodes (1.2). Furthermore, we demonstrated a timedependence of the prognostic value attributed to the parameters. The HER receptors (HER2,4), but not PTK6, were independent prognostic markers for metastases-free survival at 60 months, whereas at 240 months PTK6 is the strongest prognostic marker. We demonstrate that PTK6 is a prognostic marker of metastases-free survival in breast cancer, and is independent of the classical morphological and molecular markers of lymph node involvement, tumour size, and HER2 status

Tumor heterogeneity in neoplasms of breast, colon, and skin

<p>Abstract</p> <p>Background</p> <p>Different cell subpopulations in a single tumor may show diverse capacities for growth, differentiation, metastasis formation, and sensitivity to treatments. Thus, heterogeneity is an important feature of tumors. However, due to limitations in experimental and analytical techniques, tumor heterogeneity has rarely been studied in detail.</p> <p>Presentation of the hypothesis</p> <p>Different tumor types have different heterogeneity patterns, thus heterogeneity could be a characteristic feature of a particular tumor type.</p> <p>Testing the hypothesis</p> <p>We applied our previously published mathematical heterogeneity model to decipher tumor heterogeneity through the analysis of genetic copy number aberrations revealed by array CGH data for tumors of three different tissues: breast, colon, and skin. The model estimates the number of subpopulations present in each tumor. The analysis confirms that different tumor types have different heterogeneity patterns. Computationally derived genomic copy number profiles from each subpopulation have also been analyzed and discussed with reference to the multiple hypothetical relationships between subpopulations in origin-related samples.</p> <p>Implications of the hypothesis</p> <p>Our observations imply that tumor heterogeneity could be seen as an independent parameter for determining the characteristics of tumors. In the context of more comprehensive usage of array CGH or genome sequencing in a clinical setting our study provides a new way to realize the full potential of tumor genetic analysis.</p