Study of the L-2,L-3 edges of 3d transition metals by X-ray absorption spectroscopy

WOS: 000261693900103In the soft X-rays energy region, near edge X-ray absorption fine structure (NEXAFS) spectra are generally recorded by monitoring yield signals of secondary particles. These secondary particles, electrons or fluorescence photons, follow from the decay of the core hole excited in the primary absorption process. In general the yield signals are, to a good approximation, proportional to the absorption coefficient. However, in several applications it would be desirable to measure the absorption coefficient quantitatively. To derive the absorption coefficient quantitatively from a yield spectrum, one needs to know the escape depth of the emitted electrons (Ne) of the applied yield technique in the material of interest. Since this quantity is difficult to calculate, it is unknown for most materials. In this paper we present the first results of our systematic investigation of the total electron-yield (TEY) escape depth of the 3d transition metals (Fe, Co and Cu). In addition our results gave important information on the variation of the TEY escape depth with the filling of the 3d band. (C) 2008 Elsevier B.V. All rights reserved.Department of Energy, Office of Basic Energy Science; SSRL University of Cukurova; DOE Cooperative Research ProgramThe authors express their thanks to Curtis Troxel for his support at the Stanford Synchrotron Radiation Laboratory (SSRL), where the NEXAFS experiments have been carried out. SSRL is supported by the Department of Energy, Office of Basic Energy Science. Support by SSRL University of Cukurova and the DOE Cooperative Research Program for SESAME project is acknowledged by Y.U

Ancient DNA analysis reveals high frequency of European lactase persistence allele (T-13910) in medieval Central Europe

Ruminant milk and dairy products are important food resources in many European, African, and Middle Eastern societies. These regions are also associated with derived genetic variants for lactase persistence. In mammals, lactase, the enzyme that hydrolyzes the milk sugar lactose, is normally down-regulated after weaning, but at least five human populations around the world have independently evolved mutations regulating the expression of the lactase-phlorizin-hydrolase gene. These mutations result in a dominant lactase persistence phenotype and continued lactase tolerance in adulthood. A single nucleotide polymorphism (SNP) at C/T-13910 is responsible for most lactase persistence in European populations, but when and where the T-13910 polymorphism originated and the evolutionary processes by which it rose to high frequency in Europe have been the subject of strong debate. A history of dairying is presumed to be a prerequisite, but archaeological evidence is lacking. In this study, DNA was extracted from the dentine of 36 individuals excavated at a medieval cemetery in Dalheim, Germany. Eighteen individuals were successfully genotyped for the C/T-13910 SNP by molecular cloning and sequencing, of which 13 (72%) exhibited a European lactase persistence genotype: 44% CT, 28% TT. Previous ancient DNA-based studies found that lactase persistence genotypes fall below detection levels in most regions of Neolithic Europe. Our research shows that by AD 1200, lactase persistence frequency had risen to over 70% in this community in western Central Europe. Given that lactase persistence genotype frequency in present-day Germany and Austria is estimated at 71-80%, our results suggest that genetic lactase persistence likely reached modern levels before the historic population declines associated with the Black Death, thus excluding plague-associated evolutionary forces in the rise of lactase persistence in this region. This new evidence sheds light on the dynamic evolutionary history of the European lactase persistence trait and its global cultural implications

Epigenetic Regulation of iASPP-p63 Feedback Loop in Cutaneous Squamous Cell Carcinoma

Keratinocyte skin cancer, comprising cutaneous squamous (cSCC) and basal cell carcinoma, is the most common malignancy in the United Kingdom. P53 is frequently mutated in cSCC. iASPP is a key inhibitor of p53 and NF-kappa B signaling pathways and has been documented as highly expressed in several types of human cancer. We have previously identified an autoregulatory feedback loop between iASPP and p63, which is critical in epidermal homeostasis. We hypothesized a potential role for dysregulation of this axis in the pathogenesis of keratinocyte malignancies. Immunostaining of 116 cSCC clinical samples revealed increased iASPP and Delta Np63 expression, but also highlighted a significant alteration of iASPP cellular localization, with consequent deregulation of its function. Expression patterns, functionality, and gene and microRNA expression analysis were further investigated in 10 cSCC cell lines. Our data suggest that while direct effects of iASPP and p63 upon each other's expression are maintained in cSCC, epigenetic dysregulation of the feedback loop occurs at the microRNA level by a previously unreported mechanism controlling p63 expression. We demonstrate that this autoregulatory feedback loop controls cell migration in cSCC by blocking epithelial-mesenchymal transition and promoting proliferation, and provides future directions for clinical biomarker and therapeutic target discovery in cutaneous SCC

Comprehensive Analysis of VEGFR2 Expression in HPV-Positive and -Negative OPSCC Reveals Differing VEGFR2 Expression Patterns

Simple Summary:& nbsp;Up to 50% of oropharyngeal squamous cell carcinomas (OPSCC) are associated with human papillomavirus type 16 (HPV16), the annual incidence of which is steadily increasing. HPV-positive and -negative OPSCC exhibit a different biology, which is characterized by distinct mutation signatures and expression patterns. It is known that VEGFR2 is commonly overexpressed in HNSCC, but the influence of HPV on VEGFR2 in OPSCC is still unknown, although VEGFR2 has emerged as a promising target in tumor therapy. The aim of our study was to evaluate whether HPV exerts specific effects on VEGFR2 expression in OPSCC and thus possibly on the regulation of vascularization. Interestingly, while HPV-negative carcinoma upregulates VEGFR2 in tumor cells, in HPV-positive carcinoma VEGFR2 is upregulated in tumor-supporting blood vessels. HPV-positive OPSCC with high VEGFR2 expression is associated with poor prognosis, supporting the prognostic significance of deregulated VEGF signaling for OPSCC patients. VEGF signaling regulated by the vascular endothelial growth factor receptor 2 (VEGFR2) plays a decisive role in tumor angiogenesis, initiation and progression in several tumors including HNSCC. However, the impact of HPV-status on the expression of VEGFR2 in OPSCC has not yet been investigated, although HPV oncoproteins E6 and E7 induce VEGF-expression. In a series of 56 OPSCC with known HPV-status, VEGFR2 expression patterns were analyzed both in blood vessels from tumor-free and tumor-containing regions and within tumor cells by immunohistochemistry using densitometry. Differences in subcellular colocalization of VEGFR2 with endothelial, tumor and stem cell markers were determined by double-immunofluorescence imaging. Immunohistochemical results were correlated with clinicopathological data. HPV-infection induces significant downregulation of VEGFR2 in cancer cells compared to HPV-negative tumor cells (p = 0.012). However, with respect to blood vessel supply, the intensity of VEGFR2 staining differed only in HPV-positive OPSCC and was upregulated in the blood vessels of tumor-containing regions (p < 0.0001). These results may suggest different routes of VEGFR2 signaling depending on the HPV-status of the OPSCC. While in HPV-positive OPSCC, VEGFR2 might be associated with increased angiogenesis, in HPV-negative tumors, an autocrine loop might regulate tumor cell survival and invasion.</p