Inclusive V0V^0 Production Cross Sections from 920 GeV Fixed Target Proton-Nucleus Collisions

Inclusive differential cross sections $d\sigma_{pA}/dx_F$ and $d\sigma_{pA}/dp_t^2$ for the production of \kzeros, \lambdazero, and \antilambda particles are measured at HERA in proton-induced reactions on C, Al, Ti, and W targets. The incident beam energy is 920 GeV, corresponding to $\sqrt {s} = 41.6$ GeV in the proton-nucleon system. The ratios of differential cross sections \rklpa and \rllpa are measured to be $6.2\pm 0.5$ and $0.66\pm 0.07$, respectively, for \xf $\approx-0.06$. No significant dependence upon the target material is observed. Within errors, the slopes of the transverse momentum distributions $d\sigma_{pA}/dp_t^2$ also show no significant dependence upon the target material. The dependence of the extrapolated total cross sections $\sigma_{pA}$ on the atomic mass $A$ of the target material is discussed, and the deduced cross sections per nucleon $\sigma_{pN}$ are compared with results obtained at other energies.Comment: 17 pages, 7 figures, 5 table

Genome-wide methylation analysis identifies genes silenced in non-seminoma cell lines

Silencing of genes by DNA methylation is a common phenomenon in many types of cancer. However, the genome wide effect of DNA methylation on gene expression has been analysed in relatively few cancers. Germ cell tumours (GCTs) are a complex group of malignancies. They are unique in developing from a pluripotent progenitor cell. Previous analyses have suggested that non-seminomas exhibit much higher levels of DNA methylation than seminomas. The genomic targets that are methylated, the extent to which this results in gene silencing and the identity of the silenced genes most likely to play a role in the tumours’ biology have not yet been established. In this study, genome-wide methylation and expression analysis of GCT cell lines was combined with gene expression data from primary tumours to address this question. Genome methylation was analysed using the Illumina infinium HumanMethylome450 bead chip system and gene expression was analysed using Affymetrix GeneChip Human Genome U133 Plus 2.0 arrays. Regulation by methylation was confirmed by demethylation using 5-aza-2-deoxycytidine and reverse transcription–quantitative PCR. Large differences in the level of methylation of the CpG islands of individual genes between tumour cell lines correlated well with differential gene expression. Treatment of non-seminoma cells with 5-aza-2-deoxycytidine verified that methylation of all genes tested played a role in their silencing in yolk sac tumour cells and many of these genes were also differentially expressed in primary tumours. Genes silenced by methylation in the various GCT cell lines were identified. Several pluripotency-associated genes were identified as a major functional group of silenced genes

GEICO (Spanish Group for Investigation on Ovarian Cancer) treatment guidelines in ovarian cancer 2012

In 2006, under the auspices of The Spanish Research Group for Ovarian Cancer (Spanish initials GEICO), the first “Treatment Guidelines in Ovarian Cancer” were developed and then published in Clinical and Translational Oncology by Poveda Velasco et al. (Clin Transl Oncol 9(5):308–316, 2007). Almost 6 years have elapsed and over this time, we have seen some important developments in the treatment of ovarian cancer. Significant changes were also introduced after the GCIG-sponsored 4th Consensus Conference on Ovarian Cancer by Stuart et al. (Int J Gynecol Cancer 21:750–755, 2011). So we decided to update the treatment guidelines in ovarian cancer and, with this objective, a group of investigators of the GEICO group met in February 2012. This study summarizes the presentations, discussions and evidence that were reviewed during the meeting and during further discussions of the manuscript

Crystallization of BaF2 from droplets of phase separated glass evidence of a core shell structure by ASAXS

Crystallization of BaF2 from droplets of phase separated glass evidence of a core shell structure by ASAXS Armin Hoell, Vikram Singh Raghuwanshi, Christian Bocker, Andreas Herrmann, Christian Rüssel and Thomas Höche Glasses with the mol compositions 1.88 Na2O 15.04 K2O 7.52 Al2O3 69.56 SiO2 6.00 BaF2 and 1.88 Na2O 15.03 K2O 7.52 Al2O3 69.52 SiO2 6.00 BaF2 0.05 SmF3 were studied using X ray diffraction, transmission electron microscopy, and anomalous small angle X ray scattering ASAXS . While the glass doped with samarium showed liquid liquid phase separation of droplets with sizes of around 100 nm, the glass without samarium did not. The samples were annealed at 580 C or at 600 C which led to the crystallization of cubic BaF2. The X ray diffraction patterns showed strongly broadened lines. Hence, the BaF2 crystals possess sizes in the nm range. ASAXS gave evidence of a core shell structure. In agreement with earlier studies, it is assumed that the shell acts as a diffusion barrier that hinders crystal growth. Surprisingly, the cores and shells from the crystallization of the homogeneous glass and from the second glass, which is Sm doped and shows liquid liquid phase separation, both possess similar dimensions, even though the origin of the barrier is very different. The doped samples show long luminescence lifetimes of nearly 5 ms at a wavelength of 600 nm, which is nearly as long as those in fluoride phosphate glasse

A subset of morphologically distinct mammary myoepithelial cells lacks corresponding immunophenotypic markers

INTRODUCTION: Immunostaining for smooth muscle actin (SMA) is commonly used to elucidate mammary myoepithelial (ME) cells, whose presence or absence is a reliable criterion for differentiating in situ and invasive carcinomas. However, some morphologically distinct ME cells fail to stain for SMA. This study intended to assess whether these SMA-negative cells also lack the expression of other ME cell markers. METHODS: Hematoxylin/eosin and SMA immunostained sections from 175 breast cancer patients were examined. Three cases were found to harbor ducts that showed morphologically distinct ME cell layers, but showed no SMA immunostaining in at least one-third of the layer or the entire layer. Eight additional consecutive sections from each case were stained for SMA, using a black chromogen, and each was then re-stained for one of eight additional markers supposed to exclusively or preferentially stain ME cells, using a red chromogen. SMA-negative ME cells were re-examined for the expression of other markers. RESULTS: SMA-negative ME cells in two cases also failed to display immunoreactivity for other markers, including calponin, CD10, smooth muscle myosin heavy chain, protease inhibitor 5 (maspin), Wilms' tumor-1, and cytokeratins 5, 14, and 17 (CK5, CK14, and CK17). However, in one case SMA-negative ME cells displayed immunoreactivities for maspin, CK5, CK14, and CK17. The distribution of these ME cells is independent of ductal size, length, and architecture. CONCLUSIONS: A subset of morphologically identifiable ME cells lack the expression of nine corresponding immunophenotypic markers, suggesting that ME cells might also be subject to different normal and pathological alterations

Heteromeric clusters of ubiquitinated ER-shaping proteins drive ER-phagy

Membrane-shaping proteins characterized by reticulon homology domains play an important part in the dynamic remodelling of the endoplasmic reticulum (ER). An example of such a protein is FAM134B, which can bind LC3 proteins and mediate the degradation of ER sheets through selective autophagy (ER-phagy)1. Mutations in FAM134B result in a neurodegenerative disorder in humans that mainly affects sensory and autonomic neurons2. Here we report that ARL6IP1, another ER-shaping protein that contains a reticulon homology domain and is associated with sensory loss3, interacts with FAM134B and participates in the formation of heteromeric multi-protein clusters required for ER-phagy. Moreover, ubiquitination of ARL6IP1 promotes this process. Accordingly, disruption of Arl6ip1 in mice causes an expansion of ER sheets in sensory neurons that degenerate over time. Primary cells obtained from Arl6ip1-deficient mice or from patients display incomplete budding of ER membranes and severe impairment of ER-phagy flux. Therefore, we propose that the clustering of ubiquitinated ER-shaping proteins facilitates the dynamic remodelling of the ER during ER-phagy and is important for neuronal maintenance.</p

SCFAs Induce Mouse Neutrophil Chemotaxis through the GPR43 Receptor

Short chain fatty acids (SCFAs) have recently attracted attention as potential mediators of the effects of gut microbiota on intestinal inflammation. Some of these effects have been suggested to occur through the direct actions of SCFAs on the GPR43 receptor in neutrophils, though the precise role of this receptor in neutrophil activation is still unclear. We show that mouse bone marrow derived neutrophils (BMNs) can chemotax effectively through polycarbonate filters towards a source of acetate, propionate or butyrate. Moreover, we show that BMNs move with good speed and directionality towards a source of propionate in an EZ-Taxiscan chamber coated with fibrinogen. These effects of SCFAs were mimicked by low concentrations of the synthetic GPR43 agonist phenylacetamide-1 and were abolished in GPR43−/− BMNs. SCFAs and phenylacetamide-1 also elicited GPR43-dependent activation of PKB, p38 and ERK and these responses were sensitive to pertussis toxin, indicating a role for Gi proteins. Phenylacetamide-1 also elicited rapid and transient activation of Rac1/2 GTPases and phosphorylation of ribosomal protein S6. Genetic and pharmacological intervention identified important roles for PI3Kγ, Rac2, p38 and ERK, but not mTOR, in GPR43-dependent chemotaxis. These results identify GPR43 as a bona fide chemotactic receptor for neutrophils in vitro and start to define important elements in its signal transduction pathways

Assessment of Metabolome Annotation Quality: A Method for Evaluating the False Discovery Rate of Elemental Composition Searches

BACKGROUND: In metabolomics researches using mass spectrometry (MS), systematic searching of high-resolution mass data against compound databases is often the first step of metabolite annotation to determine elemental compositions possessing similar theoretical mass numbers. However, incorrect hits derived from errors in mass analyses will be included in the results of elemental composition searches. To assess the quality of peak annotation information, a novel methodology for false discovery rates (FDR) evaluation is presented in this study. Based on the FDR analyses, several aspects of an elemental composition search, including setting a threshold, estimating FDR, and the types of elemental composition databases most reliable for searching are discussed. METHODOLOGY/PRINCIPAL FINDINGS: The FDR can be determined from one measured value (i.e., the hit rate for search queries) and four parameters determined by Monte Carlo simulation. The results indicate that relatively high FDR values (30-50%) were obtained when searching time-of-flight (TOF)/MS data using the KNApSAcK and KEGG databases. In addition, searches against large all-in-one databases (e.g., PubChem) always produced unacceptable results (FDR >70%). The estimated FDRs suggest that the quality of search results can be improved not only by performing more accurate mass analysis but also by modifying the properties of the compound database. A theoretical analysis indicates that FDR could be improved by using compound database with smaller but higher completeness entries. CONCLUSIONS/SIGNIFICANCE: High accuracy mass analysis, such as Fourier transform (FT)-MS, is needed for reliable annotation (FDR <10%). In addition, a small, customized compound database is preferable for high-quality annotation of metabolome data

Proteotypic classification of spontaneous and transgenic mammary neoplasms

INTRODUCTION: Mammary tumors in mice are categorized by using morphologic and architectural criteria. Immunolabeling for terminal differentiation markers was compared among a variety of mouse mammary neoplasms because expression of terminal differentiation markers, and especially of keratins, provides important information on the origin of neoplastic cells and their degree of differentiation. METHODS: Expression patterns for terminal differentiation markers were used to characterize tumor types and to study tumor progression in transgenic mouse models of mammary neoplasia (mice overexpressing Neu (Erbb2), Hras, Myc, Notch4, SV40-TAg, Tgfa, and Wnt1), in spontaneous mammary carcinomas, and in mammary neoplasms associated with infection by the mouse mammary tumor virus (MMTV). RESULTS: On the basis of the expression of terminal differentiation markers, three types of neoplasm were identified: first, simple carcinomas composed exclusively of cells with a luminal phenotype are characteristic of neoplasms arising in mice transgenic for Neu, Hras, Myc, Notch4, and SV40-TAg; second, 'complex carcinomas' displaying luminal and myoepithelial differentiation are characteristic of type P tumors arising in mice transgenic for Wnt1, neoplasms arising in mice infected by the MMTV, and spontaneous adenosquamous carcinomas; and third, 'carcinomas with epithelial to mesenchymal transition (EMT)' are a characteristic feature of tumor progression in Hras-, Myc-, and SV40-TAg-induced mammary neoplasms and PL/J and SJL/J mouse strains, and display de novo expression of myoepithelial and mesenchymal cell markers. In sharp contrast, EMT was not detected in papillary adenocarcinomas arising in BALB/cJ mice, spontaneous adenoacanthomas, neoplasms associated with MMTV-infection, or in neoplasms arising in mice transgenic for Neu and Wnt1. CONCLUSIONS: Immunohistochemical profiles of complex neoplasms are consistent with a stem cell origin, whereas simple carcinomas might originate from a cell committed to the luminal lineage. In addition, these results suggest that the initiating oncogenic events determine the morphologic features associated with cancer progression because EMT is observed only in certain types of neoplasm