Polarity dependent strongly inhomogeneous In-incorporation in GaN nanocolumns.

In this work, GaN/InGaN/GaN nanocolumns (NCs) have been grown by molecular beam epitaxy. Selective area growth (SAG) and self-organized growth (SOG) were performed simultaneously in patterned and unpatterned regions of the same substrate, respectively. The resulting structures show different tip morphologies and structural properties due to the different polarity along the growth direction, namely Ga-polar with r-plane faceted tips for the SAG NCs and N-polar with c-plane top facet for the SOG ones. When growing Ga-polar GaN/InGaN NCs, no indium is incorporated at a substrate temperature of [Formula: see text]°C. Rather, indium incorporation takes place under the same growth conditions on the N-polar NCs. The In-incorporation is investigated by means of nano x-ray fluorescence and diffraction, high-angle annular dark-field scanning transmission electron microscopy and high-resolution transmission electron microscopy.

Phase separation in single In(x)Ga(1-x)N nanowires revealed through a hard X-ray synchrotron nanoprobe.

In this work, we report on the composition, short- and long-range structural order of single molecular beam epitaxy grown In(x)Ga(1-x)N nanowires using a hard X-ray synchrotron nanoprobe. Nano-X-ray fluorescence mapping reveals an axial and radial heterogeneous elemental distribution in the single wires with Ga accumulation at their bottom and outer regions. Polarization-dependent nano-X-ray absorption near edge structure demonstrates that despite the elemental modulation, the tetrahedral order around the Ga atoms remains along the nanowires. Nano-X-ray diffraction mapping on single nanowires shows the existence of at least three different phases at their bottom: an In-poor shell and two In-rich phases. The alloy homogenizes toward the top of the wires, where a single In-rich phase is observed. No signatures of In-metallic precipitates are observed in the diffraction spectra. The In-content along the single nanowires estimated from X-ray fluorescence and diffraction data are in good agreement. A rough picture of these phenomena is briefly presented. We anticipate that this methodology will contribute to a greater understanding of the underlying growth concepts not only of nanowires but also of many nanostructures in materials science.

Spontaneous core­shell elemental distribution in In-rich In(x)Ga1-xN nanowires grown by molecular beam epitaxy.

The elemental distribution of self-organized In-rich In(x)Ga1-xN nanowires grown by plasma-assisted molecular beam epitaxy has been investigated using three different techniques with spatial resolution on the nanoscale. Two-dimensional images and elemental profiles of single nanowires obtained by x-ray fluorescence and energy-dispersive x-ray spectroscopy, respectively, have revealed a radial gradient in the alloy composition of each individual nanowire. The spectral selectivity of resonant Raman scattering has been used to enhance the signal from very small volumes with different elemental composition within single nanowires. The combination of the three techniques has provided sufficient sensitivity and spatial resolution to prove the spontaneous formation of a core­shell nanowire and to quantify the thicknesses and alloy compositions of the core and shell regions. A theoretical model based on continuum elastic theory has been used to estimate the strain fields present in such inhomogeneous nanowires. These results suggest new strategies for achieving high quality nonpolar heterostructures.

Transforming growth factor (TGF)-ß signalling is increased in rheumatoid synovium but TGF-ß blockade does not modify experimental arthritis.

The aim of this study was to analyse the distribution of regulatory and inhibitory mothers against decapentaplegic homologue (Smad) proteins as markers of active transforming growth factor (TGF)-ß signalling in rheumatoid arthritis (RA) synovial tissue and to investigate the effect of TGF-ß blockade in the development and progression of collagen-induced arthritis. The expression of Smad proteins in synovial tissues from RA, osteoarthritic and healthy controls was analysed by immunohistochemistry. Arthritis was induced in DBA/1 mice by immunization with chicken type-II collagen (CII). TGF-ß was blocked in vivo with the specific peptide p17 starting at the time of immunization or on the day of arthritis onset. T cell population frequencies and specific responses to CII were analysed. The expression of cytokines and transcription factors was quantified in spleen and joint samples. Statistical differences between groups were compared using the Mann-Whitney U-test or one-way analysis of variance (anova) using the Kruskal-Wallis test. p-Smad-2/3 and inhibitory Smad-7 expression were detected in RA and control tissues. In RA, most lymphoid infiltrating cells showed nuclear p-Smad-2/3 without Smad-7 expression. Treatment with TGF-ß antagonist did not affect clinical severity, joint inflammation and cartilage damage in collagen-induced arthritis. Frequency of T cell subsets, mRNA levels of cytokines and transcription factors, specific proliferation to CII, serum interleukin (IL)-6 and anti-CII antibodies were comparable in p17 and phosphate-buffered saline (PBS)-treated groups. The pattern of Smad proteins expression demonstrates active TGF-ß signalling in RA synovium. However, specific TGF-ß blockade does not have a significant effect in the mice model of collagen-induced arthritis.

Hard X-ray nanoprobe investigations of the subtissue metal distributions within Daphnia magna.

The unique potential of nanoscale elemental imaging of major/minor and trace-level elemental distributions within thin biological tissue sections of the ecotoxicological model organism Daphnia magna is demonstrated by synchrotron radiation nano-X-ray fluorescence (nano-XRF). The applied highly specialized sample preparation method, coupled with the high spatial resolution (∼180 nm) and high X-ray photon flux (6 × 10(11) photons/s) available at the European Synchrotron Radiation Facility (ESRF) ID22NI beamline proved to be critical for the high-quality visualization of (trace-)metal distributions on the submicron level within the target structures of interest. These include the branchial sacs on the thoracic appendages (epipodites) of D. magna, which are osmoregulatory regions where ion exchange occurs. For the main element of interest (Zn), detection limits of 0.7 ppm (3 ag) was reached in fast-scanning mode using an acquisition time of 0.3 s/pixel. As demonstrated, synchrotron radiation nano-XRF revealed the elemental distributions of Ca, Fe, and Zn within this osmoregulatory region on the submicron scale, aiding the exploration of possible detoxification mechanisms of Zn within D. magna at the subtissue level.

Biomedical applications of the ESRF synchrotron-based microspectroscopy platform.

Very little is known about the sub-cellular distribution of metal ions in cells. Some metals such as zinc, copper and iron are essential and play an important role in the cell metabolism. Dysfunctions in this delicate housekeeping may be at the origin of major diseases. There is also a prevalent use of metals in a wide range of diagnostic agents and drugs for the diagnosis or treatment of a variety of disorders. This is becoming more and more of a concern in the field of nanomedicine with the increasing development and use of nanoparticles, which are suspected of causing adverse effects on cells and organ tissues. Synchrotron-based X-ray and Fourier-transformed infrared microspectroscopies are developing into well-suited sub-micrometer analytical tools for addressing new problems when studying the role of metals in biology. As a complementary tool to optical and electron microscopes, developments and studies have demonstrated the unique capabilities of multi-keV microscopy: namely, an ultra-low detection limit, large penetration depth, chemical sensitivity and three-dimensional imaging capabilities. More recently, the capabilities have been extended towards sub-100nm lateral resolutions, thus enabling sub-cellular chemical imaging. Possibilities offered by these techniques in the biomedical field are described through examples of applications performed at the ESRF synchrotron-based microspectroscopy platform (ID21 and ID22 beamlines).

Nano-X-ray absorption spectroscopy of single Co-implanted ZnO nanowires.

We report on the local structure of single Co-implanted ZnO nanowires studied using a hard X-ray nanoprobe. X-ray fluorescence maps show uniform Zn and Co distributions along the wire within the length scale of the beam size. The X-ray fluorescence data allow the estimation of the Co content within the nanowire. Polarization dependent X-ray absorption near edge structure shows no structural disorder induced neither in the radial nor axial directions of the implanted nanowires after subsequent annealing. Co2+ ions occupy Zn sites into the wurtzite ZnO lattice. Extended X-ray absorption fine structure data reveal high structural order in the host lattice without distortion in their interatomic distances, confirming the recovery of the radiation damaged ZnO structure through thermal annealing.

Study of metallic components of historical organ pipes using synchrotron radiation X-ray microfluorescence imaging and grazing incidence X-ray diffraction.

A comparative study of the composition and microstructure of two different brass alloys from reed pipes, one from a Spanish baroque organ and the other from a modern one, was carried out. This study allowed us to determine the procedure followed to produce the brass used to make ancient reed pipes. Moreover the distribution and correlation of lead and other trace elements present into the main component of the brass, the copper and zinc phases, of the historical tongues and shallots were established. This chemical composition was compared with that of a tongue from a twentieth-century organ. The whole study was accomplished using a combination of laboratory and synchrotron radiation techniques. X-ray fluorescence was the technique used to obtain elemental and chemical imaging of the main phases and the trace elements at a sub-micrometer scale.

X-ray absorption near-edge structure of GaN with high Mn concentration grown on SiC.

By means of x-ray absorption near-edge structure (XANES) several Ga(1-x)Mn(x)N (0.03

Zap-70-independent Ca(2+) mobilization and Erk activation in Jurkat T cells in response to T-cell antigen receptor ligation.

The tyrosine kinase ZAP-70 has been implicated as a critical intermediary between T-cell antigen receptor (TCR) stimulation and Erk activation on the basis of the ability of dominant negative ZAP-70 to inhibit TCR-stimulated Erk activation, and the reported inability of anti-CD3 antibodies to activate Erk in ZAP-70-negative Jurkat cells. However, Erk is activated in T cells receiving a partial agonist signal, despite failing to activate ZAP-70. This discrepancy led us to reanalyze the ZAP-70-negative Jurkat T-cell line P116 for its ability to support Erk activation in response to TCR/CD3 stimulation. Erk was activated by CD3 cross-linking in P116 cells. However, this response required a higher concentration of anti-CD3 antibody and was delayed and transient compared to that in Jurkat T cells. Activation of Raf-1 and MEK-1 was coincident with Erk activation. Remarkably, the time course of Ras activation was comparable in the two cell lines, despite proceeding in the absence of LAT tyrosine phosphorylation in the P116 cells. CD3 stimulation of P116 cells also induced tyrosine phosphorylation of phospholipase C-gamma1 (PLCgamma1) and increased the intracellular Ca(2+) concentration. Protein kinase C (PKC) inhibitors blocked CD3-stimulated Erk activation in P116 cells, while parental Jurkat cells were refractory to PKC inhibition. The physiologic relevance of these signaling events is further supported by the finding of PLCgamma1 tyrosine phosphorylation, Erk activation, and CD69 upregulation in P116 cells on stimulation with superantigen and antigen-presenting cells. These results demonstrate the existence of two pathways leading to TCR-stimulated Erk activation in Jurkat T cells: a ZAP-70-independent pathway requiring PKC and a ZAP-70-dependent pathway that is PKC independent.

New cryogenic environment for beamline ID22 at the European Synchrotron Radiation Facility.

A compact minicryostat has been well adapted on the hard x-ray microprobe ID22 of the European Synchrotron Radiation Facility. For variable low-temperature investigations, its special technical design provides precise scanning microscopy and allows easy access for multiple detection modes. Based on x-ray excited optical luminescence technique on the micrometer scale, details of the equipment, its temperature calibration, and typical results are described. Data collections from InAs quantum heterostructures support the excellent thermal performance of the novel cryogenic device.

First report of a patient with a mixoploidy 47,XXX/94,XXXXXX.

We present a 16 years old female with a chromosomal mixoploidy and multiple phenotypic anomalies. Peripheral blood G-band karyotype was 47,XXX and her skin fibroblast karyotype revealed a mosaic with a 47,XXX cell line in 88% of metaphases and a 94,XXXXXX cell line in 12% of metaphases, consistent with a hypertetraploidy. The most prominent clinical signs were: short stature, left upper limb asymmetry, senile-like appearance, generalized hypertrichosis, and small hands and feet. Radiological examination showed bone dysplasia. The result of molecular studies demonstrated that the patient inherited the two X chromosomes from the mother and one from the father, indicating that her 47,XXX trisomy resulted from an oogenesis error in the first meiotic division. The 94,XXXXXX cell line was likely the result of a cytokinesis error. To our knowledge, this is the first documented patient with a trisomy and a hypertetraploidy.

ETP-46321, a dual p110α/δ class IA phosphoinositide 3-kinase inhibitor modulates T lymphocyte activation and collagen-induced arthritis.

Class IA phosphoinositide 3-kinases (PI3Ks) are essential to function of normal and tumor cells, and to modulate immune responses. T lymphocytes express high levels of p110α and p110δ class IA PI3K. Whereas the functioning of PI3K p110δ in immune and autoimmune reactions is well established, the role of p110α is less well understood. Here, a novel dual p110α/δ inhibitor (ETP-46321) and highly specific p110α (A66) or p110δ (IC87114) inhibitors have been compared concerning T cell activation in vitro, as well as the effect on responses to protein antigen and collagen-induced arthritis in vivo. In vitro activation of naive CD4(+) T lymphocytes by anti-CD3 and anti-CD28 was inhibited more effectively by the p110δ inhibitor than by the p110α inhibitor as measured by cytokine secretion (IL-2, IL-10, and IFN-γ), T-bet expression and NFAT activation. In activated CD4(+) T cells re-stimulated through CD3 and ICOS, IC87114 inhibited Akt and Erk activation, and the secretion of IL-2, IL-4, IL-17A, and IFN-γ better than A66. The p110α/δ inhibitor ETP-46321, or p110α plus p110δ inhibitors also inhibited IL-21 secretion by differentiated CD4(+) T follicular (Tfh) or IL-17-producing (Th17) helper cells. In vivo, therapeutic administration of ETP-46321 significantly inhibited responses to protein antigen as well as collagen-induced arthritis, as measured by antigen-specific antibody responses, secretion of IL-10, IL-17A or IFN-γ, or clinical symptoms. Hence, p110α as well as p110δ Class IA PI3Ks are important to immune regulation; inhibition of both subunits may be an effective therapeutic approach in inflammatory autoimmune diseases like rheumatoid arthritis.

Möbius sequence, hypogenitalism, cerebral, and skeletal malformations in two brothers.

Two brothers born to a healthy, consanguineous Spanish couple have a syndrome of Möbius sequence with involvement of cranial nerves V, VI, VII, IX, and XII, central nervous system malformations; characteristic face with creased earlobes, short philthrum, and a short, arched upper lip, skeletal anomalies with short sternum and delayed bone maturation, hypogenitalism, and profound mental retardation. We suggest that this is a new multiple congenital anomalies condition and mental retardation (MCA/MR) syndrome with autosomic recessive inheritance.

Familial deletion of 22q11.2.

We present a mother and her son, both carrying a deletion of chromosome 22q.11.2. They manifest clinical heterogeneity. The mother has schizophrenia, an IQ of 70. Tetralogy of Fallot, a hypernasal voice, but does not have the characteristic facies. Her son has mild psychomotor developmental delay. Tetralogy of Fallot and mild facial features characteristic of VCFS.

X-linked hydrocephalus: another two families with an L1 mutation.

X-linked hydrocephalus is a variable condition caused by mutations in the gene encoding for L1CAM. This gene is located at Xq28. Clinically the spectrum ranges from males with lethal congenital hydrocephalus to mild/moderate mental retardation and spastic paraplegia. Few carrier females show minimal signs of the syndrome. Although most cases are familial, de novo situations have been reported. We report two new families with the syndrome and a L1 mutation. Family 1 has two patients and family 2 a single patient. Clinical diagnosis in all three affected boys was beyond doubt. Prenatal testing through chorionic villus biopsy is possible only with a demonstrated L1 mutation. In lethal sporadic cases neuropathology is very important in order to evaluate for features of the syndrome. We stress the importance of further clinical reports including data on neuropathology and DNA analysis in order to further understand the mechanisms involved in this disorder.

A second family with Micro syndrome.

We present the cases of two sisters, daughters of healthy, non-consanguineous parents, who have a clinical syndrome characterized by microcephaly, cortical dysplasia, ventriculomegaly, hypoplasia of the corpus callosum, hypogenesis of the cerebellar vermis, cataracts, microphthalmia, optic nerve atrophy, retinal coloboma, weight and height below 3rd centile, severe mental retardation, no speech, inability to sit, no sphincter control and a spastic tetraparesis. The facies are mildly dysmorphic, but not distinctive. No metabolic, nor chromosomal anomalies were found. The cases are very similar to, but not identical, to those described by Warburg et al [Am J Med Genet (1993) 147:1309-1312] as Micro syndrome.

[Corpus callosum agenesis and epileptic seizures]. / Agenesia del cuerpo calloso y crisis epilépticas.

INTRODUCTION: The corpus callosum is the major neopallial connection between the two cerebral hemispheres. The corpus callosum agenesis (CCA) is found in 14% of CNS malformations. The diagnosis is based on neuroimaging procedures (ultrasonography, CT, MRI). The CCA is usually associated with facial dysmorphia, developmental delay and epileptic seizures. Two casuistic are studied, one with necropsies material and another with CCA patients alive, on which CCA was frequently associated with other CNS malformations, in order to establish the circumstances in which the epileptic seizures have been observed. DEVELOPMENT: It is commonly admitted that the presenting signs or symptoms in individuals with CCA are due to concurrent brain abnormalities and that isolated CCA is essentially asymptomatic. The CCA is a common component in some malformative syndromes, frequent in another, and occasional in many of them. The CCA has been reported in many chromosomal aberrations and less frequently in inborn errors of metabolism and neurocutaneous diseases. In the casuistic studies of 73 patients alive, 25 (39%) have presented epileptic fits: in 24 of them the CCA was associated to another brain abnormalities; in 17 cases, the first seizures was recorded during the first year, in 6 cases between 1 and 3 years and in cases after 2 years: the type of epileptic seizures is variable: neonatal convulsions in 4 cases, infantile spasms in 5, unilateral fits in 3, and partial seizures in 1 case. In the necropsies casuistic with 26 CCA cases, 6 (23%) suffered epileptic fits, all with another malformations of the CNS; in 3 the onset of the seizures was during the newborn period, 2 had infantile spasms during the first years and 1 case generalized seizures during the second year. CONCLUSIONS: 1. Epileptic seizures were observed in 23%-39% of the CCA cases studied. 2. All cases with CCA, except for one, have also another brain abnormality. 3. In 70% of the cases, the onset of the fits takes place during the first year. 4. The type of seizures is variable with predominance of infantile spasms and unilateral seizures.

Formation of nanostructures in Eu3+ doped glass-ceramics: an XAS study.

We describe the results of x-ray absorption experiments carried out to deduce structural and chemical information in Eu(3+) doped, transparent, oxyfluoride glass and nanostructured glass-ceramic samples. The spectra were measured at the Pb and Eu-L(III) edges. The Eu environment in the glass samples is observed to be similar to that of EuF(3). Complementary x-ray diffraction experiments show that thermal annealing creates ß-PbF(2) type nanocrystals. X-ray absorption indicates that Eu ions act as seeds in the nanocrystal formation. There is evidence of interstitial fluorine atoms around Eu ions as well as Eu dimers. X-ray absorption at the Pb-L(III) edge shows that after the thermal treatment most lead atoms form a PbO amorphous phase and that only 10% of the lead atoms remain available to form ß-PbF(2) type nanocrystals. Both x-ray diffraction and absorption point to a high Eu content in the nanocrystals. Our study suggests new approaches to the oxyfluoride glass-ceramic synthesis in order to further improve their properties.