Determination of partial photoionisation cross sections of methyl bromide in the first autoionisation range by use of spin polarisation photoelectron spectroscopy

Schäfers F, Baig MA, Heinzmann U. Determination of partial photoionisation cross sections of methyl bromide in the first autoionisation range by use of spin polarisation photoelectron spectroscopy. Journal of Physics B: Atomic, Molecular and Optical Physics. 1983;16(1):L1-L6.Using recent experimental data on photoelectron spin polarisation combined with the high-resolution spectrum of methyl bromide, which has also been recently reported, the partial photoionisation cross sections for the ionisation of CH3Br from the 4 pi ground-state orbital into the energy degenerate continua epsilon sigma , epsilon pi and epsilon delta have been determined separately. Quantitative results, obtained for the autoionising resonances between 116 and 118 nm, are reported and discussed

Spin polarized photoelectrons with unpolarized light in normal emission from Pt(110)

Irmer N, Frentzen F, Schmiedeskamp B, Heinzmann U. Spin polarized photoelectrons with unpolarized light in normal emission from Pt(110). Surface Science. 1994;307-309(2):1114-1117.The normally emitted photoelectrons of the reconstructed (1 x 2) surface of Pt(110) caused by off-normally incoming, unpolarized light are spin polarized. Measurements have been performed with the light of a gas discharge tube and spin polarization of up to 20% has been found for the spin polarization perpendicular to the reaction plane, defined by the momenta of incoming photon and outgoing electron beam. The polarization depends significantly on a rotation of the crystal about the surface normal. The experimental data are in good agreement with theoretical calculations of Feder's group [1] based upon the theory describing the photoemission in the one-step model

High-threshold mechanosensitive ion channels blocked by a novel conopeptide mediate pressure-evoked pain

Little is known about the molecular basis of somatosensory mechanotransduction in mammals. We screened a library of peptide toxins for effects on mechanically activated currents in cultured dorsal root ganglion neurons. One conopeptide analogue, termed NMB-1 for noxious mechanosensation blocker 1, selectively inhibits (IC50 1 µM) sustained mechanically activated currents in a subset of sensory neurons. Biotinylated NMB-1 retains activity and binds selectively to peripherin-positive nociceptive sensory neurons. The selectivity of NMB-1 was confirmed by the fact that it has no inhibitory effects on voltage-gated sodium and calcium channels, or ligand-gated channels such as acid-sensing ion channels or TRPA1 channels. Conversely, the tarantula toxin, GsMTx-4, which inhibits stretch-activated ion channels, had no effects on mechanically activated currents in sensory neurons. In behavioral assays, NMB-1 inhibits responses only to high intensity, painful mechanical stimulation and has no effects on low intensity mechanical stimulation or thermosensation. Unexpectedly, NMB-1 was found to also be an inhibitor of rapid FM1-43 loading (a measure of mechanotransduction) in cochlear hair cells. These data demonstrate that pharmacologically distinct channels respond to distinct types of mechanical stimuli and suggest that mechanically activated sustained currents underlie noxious mechanosensation. NMB-1 thus provides a novel diagnostic tool for the molecular definition of channels involved in hearing and pressure-evoked pain

Clinical translation of [18F]ICMT-11 for measuring chemotherapy-induced caspase 3/7 activation in breast and lung cancer

Background: Effective anticancer therapy is thought to involve induction of tumour cell death through apoptosis and/or necrosis. [18F]ICMT-11, an isatin sulfonamide caspase-3/7-specific radiotracer, has been developed for PET imaging and shown to have favourable dosimetry, safety, and biodistribution. We report the translation of [18F]ICMT-11 PET to measure chemotherapy-induced caspase-3/7 activation in breast and lung cancer patients receiving first-line therapy. Results: Breast tumour SUVmax of [18F]ICMT-11 was low at baseline and unchanged following therapy. Measurement of M30/M60 cytokeratin-18 cleavage products showed that therapy was predominantly not apoptosis in nature. While increases in caspase-3 staining on breast histology were seen, post-treatment caspase-3 positivity values were only approximately 1%; this low level of caspase-3 could have limited sensitive detection by [18F]ICMT-11-PET. Fourteen out of 15 breast cancer patients responded to first–line chemotherapy (complete or partial response); one patient had stable disease. Four patients showed increases in regions of high tumour [18F]ICMT-11 intensity on voxel-wise analysis of tumour data (classed as PADS); response was not exclusive to patients with this phenotype. In patients with lung cancer, multi-parametric [18F]ICMT-11 PET and MRI (diffusion-weighted- and dynamic contrast enhanced-MRI) showed that PET changes were concordant with cell death in the absence of significant perfusion changes. Conclusion: This study highlights the potential use of [18F]ICMT-11 PET as a promising candidate for non-invasive imaging of caspase3/7 activation, and the difficulties encountered in assessing early-treatment responses. We summarize that tumour response could occur in the absence of predominant chemotherapy-induced caspase-3/7 activation measured non-invasively across entire tumour lesions in patients with breast and lung cancer

Atividade antimicrobiana do oleorresina de copaíba (Copaifera reticulata) frente a Staphylococcus coagulase positiva isolados de casos de otite em cães.

O objetivo do presente trabalho foi investigar o potencial antimicrobiano do oleorresina de Copaifera reticulata Ducke em isolados de Staphylococcus coagulase positiva (SCP) provenientes de casos de otite externa em cães. O método de microdiluição em caldo foi utilizado para determinação da concentração inibitória mínima (CIM) e concentração bactericida mínima (CBM) de oleorresina de copaíba. Em adição, foi determinado o perfil de suscetibilidade aos antimicrobianos dos isolados de SCP pelo método de difusão em ágar. Oito classes de antimicrobianos foram usadas para o cálculo de multirresistência antimicrobiana. A determinação da composição química do oleorresina de copaíba foi realizada por cromatografia em fase gasosa acoplada à espectrometria de massas (GC/MS), sendo que β-cariofileno, β-bisaboleno e (E)-a-bergamoteno foram os compostos majoritários. O oleorresina de copaíba demonstrou CIM90 de 0,164mg/mL e CBM90 de 1,31mg/mL. A multirresistência foi verificada em 27% das cepas testadas. Os resultados sugerem que o oleorresina de copaíba exerceu atividade bacteriostática e bactericida mesmo em cepas multirresistentes de Staphylococcus coagulase-positiva

Bone mineral density, pulmonary function, chronological age, and age at diagnosis in children and adolescents with cystic fibrosis

AbstractObjectiveTo assess bone mineral density in patients with cystic fibrosis (CF), and to correlate it with possible intervening variables.MethodsChildren and adolescents diagnosed with CF, aged 6 to 18 years, followed at the outpatient clinic were included in the study. First, demographic data were collected and, subsequently, patients underwent a spirometric test. All patients answered the Cystic Fibrosis Quality of Life Questionnaire (CFQ) and underwent the six-minute walk test (6MWT) and bone densitometry (DXA).ResultsA total of 25 CF patients were included, of which 56% were males. The mean age was 12.3±3.4 years; mean height was 149.2±14.4 cm; and mean weight was 44.4±13.9 kg. Most results on pulmonary function and bone mineral density (BMD) were within normal limits. The mean forced expiratory volume in one second (FEV) was 92.5±23.6 (% of predicted), mean forced vital capacity (FVC) was 104.4±21.3 (% of predicted), and1 mean BMD z-score was 0.1±1.0. BMD was moderately correlated with FEV (r = 0.43, p = 0.03) and FVC (r = 0.57, p = 0.003). Regarding chronological age and age at diagnosis, a moderate and inverse correlation was also found (r = −0.55, p = 0.004; r = −0.57, p = 0.003, respectively). However, no significant correlations were found with the data from CFQ, 6MWT, and body mass index.ConclusionMost patients had BMD within normal limits and presented a positive correlation with pulmonary function, as well as a negative correlation with chronological age and age at diagnosis

Loss of CX3CR1 increases accumulation of inflammatory monocytes and promotes gliomagenesis

The most abundant populations of non-neoplastic cells in the glioblastoma (GBM) microenvironment are resident microglia, macrophages and infiltrating monocytes from the blood circulation. The mechanisms by which monocytes infiltrate into GBM, their fate following infiltration, and their role in GBM growth are not known. Here we tested the hypothesis that loss of the fractalkine receptor CX3CR1 in microglia and monocytes would affect gliomagenesis. Deletion of Cx3cr1 from the microenvironment resulted in increased tumor incidence and shorter survival times in glioma-bearing mice. Loss of Cx3cr1 did not affect accumulation of microglia/macrophages in peri-tumoral areas, but instead indirectly promoted the trafficking of CD11b+CD45hiCX3CR1lowLy-6ChiLy-6G-F4/80-/low circulating inflammatory monocytes into the CNS, resulting in their increased accumulation in the perivascular area. Cx3cr1-deficient microglia/macrophages and monocytes demonstrated upregulation of IL1{beta} expression that was inversely proportional to Cx3cr1 gene dosage. The Proneural subgroup of the TCGA GBM patient dataset with high IL1{beta} expression showed shorter survival compared to patients with low IL1{beta}. IL1{beta} promoted tumor growth and increased the cancer stem cell phenotype in murine and human Proneural glioma stem cells (GSCs). IL1{beta} activated the p38 MAPK signaling pathway and expression of monocyte chemoattractant protein (MCP-1/CCL2) by tumor cells. Loss of Cx3cr1 in microglia in a monocyte-free environment had no impact on tumor growth and did not alter microglial migration. These data suggest that enhancing signaling to CX3CR1 or inhibiting IL1{beta} signaling in intra-tumoral macrophages can be considered as potential strategies to decrease the tumor-promoting effects of monocytes in Proneural GBM

Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations.

Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10(-9)). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma