Anisotropy of anomalous dispersion in X-ray diffraction

Polarization-dependent resonant Bragg diffraction in crystals is investigated both theoretically and experimentally. In order to describe the effects of anisotropic anomalous dispersion on intensity and polarization of kinematically diffracted X-radiation, a general scattering model is developed on the basis of site-symmetry-compatible second-rank scattering-factor tensors for the absorbing atoms. For conventional four-circle single-crystal diffractometry it is shown that intensity and polarization of the diffracted beam can be predicted as functions of both crystal orientation and polarization of the incident radiation. In principle, anisotropy of anomalous dispersion may affect any reflection. In particular, it can give rise to the observation of intensities for reflections being systematically extinct by space-group symmetry. Both effects are discussed. Experimental proof of the model's validity was obtained by synchrotron-radiation X-ray diffraction measurements of mainly `forbidden' reflections in cubic cuprite, Cu2O and tetragonal rutile type TiO2 and MnF2. The experiments were carried out at the respective K-absorption edges of the cations using different instruments at HASYLAB/DESY during dedicated mode of DORIS II (3.78 GeV). Significant anisotropy of anomalous dispersion due to excitation of K electrons into p states was observed in each case, allowing studies of the dependence of `forbidden' reflection intensities on both radiation energy and rotation ([Psi]) around the scattering vector h. Comparison of the observations with the analytical intensity functions derived from the scattering model shows full agreement on a relative scale. For cuprite, estimates of the anisotropies of the real and imaginary components of the anomalous dispersion of Cu were obtained from the allowed reflection 330. The values derived from two different experiments (energies) are f' = -0.56, -0.35 and f'' = -0.23, 0.0 electrons, respectively

Interplay of inequivalent atomic positions in resonant x-ray diffraction of Fe3BO6

'Forbidden' Bragg reflections of iron orthoborate Fe3BO6 were studied theoretically and experimentally in the vicinity of the iron K edge. Their energy spectra are explained as resulting from the interference of x-rays scattered from two inequivalent crystallographic sites occupied by iron ions. This particular structure property gives rise to complex azimuthal dependences of the reflection intensities in the pre-edge region as they result from the interplay of site specific dipole-quadrupole and quadrupole-quadrupole resonant scattering. Also evidenced is an isotropic character of the absorption spectrum. Self-absorption correction to the diffraction data, as well as possible contributions of thermal vibrations and magnetic order, are discussed. Particular care is given to extracting clean spectra from the data, and it is demonstrated that excellent results can be obtained even from measurements that appear corrupted by several effects such as poor crystal quality and multiple scattering.Comment: 12 page

Polarization Dependence of Anomalous X-ray Scattering in Orbital Ordered Manganites

In order to determine types of the orbital ordering in manganites, we study theoretically the polarization dependence of the anomalous X-ray scattering which is caused by the anisotropy of the scattering factor. The general formulae of the scattering intensity in the experimental optical system is derived and the atomic scattering factor is calculated in the microscopic electronic model. By using the results, the X-ray scattering intensity in several types of the orbital ordering is numerically calculated as a function of azimuthal and analyzer angles.Comment: 9 pages, 7 figure

Emerging role of caldesmon in cancer: A potential biomarker for colorectal cancer and other cancers

Colorectal cancer (CRC) is a devastating disease, mainly because of metastasis. As a result, there is a need to better understand the molecular basis of invasion and metastasis and to identify new biomarkers and therapeutic targets to aid in managing these tumors. The actin cytoskeleton and actin-binding proteins are known to play an important role in the process of cancer metastasis because they control and execute essential steps in cell motility and contractility as well as cell division. Caldesmon (CaD) is an actin-binding protein encoded by the CALD1 gene as multiple transcripts that mainly encode two protein isoforms: High-molecular-weight CaD, expressed in smooth muscle, and low-molecular weight CaD (l-CaD), expressed in nonsmooth muscle cells. According to our comprehensive review of the literature, CaD, particularly l-CaD, plays a key role in the development, metastasis, and resistance to chemoradiotherapy in colorectal, breast, and urinary bladder cancers and gliomas, among other malignancies. CaD is involved in many aspects of the carcinogenic hallmarks, including epithelial mesenchymal transition via transforming growth factor-beta signaling, angiogenesis, resistance to hormonal therapy, and immune evasion. Recent data show that CaD is expressed in tumor cells as well as in stromal cells, such as cancerassociated fibroblasts, where it modulates the tumor microenvironment to favor the tumor. Interestingly, CaD undergoes selective tumor-specific splicing, and the resulting isoforms are generally not expressed in normal tissues, making these transcripts ideal targets for drug design. In this review, we will analyze these features of CaD with a focus on CRC and show how the currently available data qualify CaD as a potential candidate for targeted therapy in addition to its role in the diagnosis and prognosis of cancer

Low-level APC mutational mosaicism is the underlying cause in a substantial fraction of unexplained colorectal adenomatous polyposis cases

BACKGROUND: In 30-50% of patients with colorectal adenomatous polyposis, no germline mutation in the known genes APC, causing familial adenomatous polyposis, MUTYH, causing MUTYH-associated polyposis, or POLE or POLD1, causing polymerase-proofreading-associated polyposis can be identified, although a hereditary aetiology is likely. This study aimed to explore the impact of APC mutational mosaicism in unexplained polyposis. METHODS: To comprehensively screen for somatic low-level APC mosaicism, high-coverage next-generation sequencing of the APC gene was performed using DNA from leucocytes and a total of 53 colorectal tumours from 20 unrelated patients with unexplained sporadic adenomatous polyposis. APC mosaicism was assumed if the same loss-of-function APC mutation was present in ≥2 anatomically separated colorectal adenomas/carcinomas per patient. All mutations were validated using diverse methods. RESULTS: In 25% (5/20) of patients, somatic mosaicism of a pathogenic APC mutation was identified as underlying cause of the disease. In 2/5 cases, the mosaic level in leucocyte DNA was slightly below the sensitivity threshold of Sanger sequencing; while in 3/5 cases, the allelic fraction was either very low (0.1-1%) or no mutations were detectable. The majority of mosaic mutations were located outside the somatic mutation cluster region of the gene. CONCLUSIONS: The present data indicate a high prevalence of pathogenic mosaic APC mutations below the detection thresholds of routine diagnostics in adenomatous polyposis, even if high-coverage sequencing of leucocyte DNA alone is taken into account. This has important implications for both routine work-up and strategies to identify new causative genes in this patient group

Matrix gla protein in xenopus laevis: molecular cloning, tissue distribution, and evolutionary considerations

Matrix Gla protein (MGP) belongs to the family of vitamin K-dependent, Gla-containing proteins and in higher vertebrates, is found in the extracellular matrix of mineralized tissues and soft tissues. MGP synthesis is highly regulated at the transcription and posttranscription levels and is now known to be involved in the regulation of extracellular matrix calcification and maintenance of cartilage and soft tissue integrity during growth and development. However, its mode of action at the molecular level remains unknown. Because there is a large degree of conservation between amino,acid sequences of shark and human MGP, the function of MGP probably has been conserved throughout evolution. Given the complexity of the mammalian system, the study of MGP in a lower vertebrate might be advantageous to relate the onset of MGP expression with specific events during development. Toward this goal, MGP was purified from Xenopus long bones and its N-terminal amino acid sequence was determined and used to clone the Xenopus MGP complementary DNA (cDNA) by a mixture of reverse-transcription (RT)- and 5'- rapid amplification of cDNA ends (RACE)-polymerase chain reaction (PCR). MGP messenger RNA (mRNA) was present in all tissues analyzed although predominantly expressed in Xenopus bone and heart and its presence was detected early in development at the onset of chondrocranium development and long before the appearance of the first calcified structures and metamorphosis. These results show that in this system, as in mammals, MGP may be required to delay or prevent mineralization of cartilage and soft tissues during the early stages of development and indicate that Xenopus is an adequate model organism to further study MGP function during growth and development.NATO/CRG940751/SA5.2.05, Praxis XXI/BIA 469/94, (NIH; grant AR 25921) (Praxis XXI/BPD/18816) (Praxis XXI/BICJ-2985