Aberrant expression of ALK and EZH2 in Merkel cell carcinoma

BACKGROUND: Distinct characteristic features categorize Merkel cell carcinoma (MCC) into two subgroups according to the Merkel cell polyomavirus infection. Many mutational studies on MCC have been carried out in recent years without identifying a prominent driver mutation. However, there is paucity reporting the expression of cancer genes at the RNA level in MCC tumors. In this study, we studied the RNA expression profiles of 26 MCC tumors, with a goal to identify prospective molecular targets that could improve the treatment strategies of MCC. METHODS: RNA expression of 50 cancer-related genes in 26 MCC tumors was analyzed by targeted amplicon based next-generation sequencing using the Ion Torrent technology and the expression compared with that of normal, non-cancerous skin samples. Sequencing data were processed using Torrent Suite Software. Expression profiles of MCV-negative and MCV-positive tumors were compared. Fluorescence in situ hybridization was performed to study ALK rearrangements and immunohistochemistry to study ALK expression in tumor tissue. RESULTS: ALK, CDKN2A, EZH2 and ERBB4 were overexpressed, and EGFR, ERBB2, PDGFRA and FGFR1 were underexpressed in MCC tumors compared to normal skin. In the MCV-negative tumors, MET, NOTCH1, FGFR3, and SMO were overexpressed and JAK3 and NPM1 were under-expressed compared to the MCV-positive tumors. CONCLUSIONS: High expression of ALK, CDKN2A and EZH2 was recorded in MCC tumors. No ALK fusion was seen by FISH analysis. Overexpression of EZH2 suggests its potential as a drug target in MCC.Peer reviewe

A method for cellulose determination

The usual metods for cellulose determinations, excepting those in which the material is decomposed by total hydrolysis, are principally methods for producing cellulose preparations. In these the non-cellulosic compounds are tried to be removed as thoroughly as possible without decomposing the cellulose. However, the preparations obtained still contain different non-cellulosic components for which corrections must be made. In the method proposed by the authors a crude cellulose preparation is produced by a relatively mild treatment, and corrections are made for crude lignin and pentosans. The main feature in producing the crude cellulose preparation is shaking the samples with 3N NaOH solution in pressure bottles in a boiling water bath. The method appears to give readable results for fodder materials. For woods the results are evidently too high, especially due to mannan in the crude cellulose

Energy Dissipation of Fast Electrons in Polymethylmetacrylate (PMMA): Towards a Universal Curve for Electron Beam Attenuation in Solids for Energies between ~0 eV and 100 keV

Wolfgang S.M. Werner, Florian Simperl, Felix Bloedorn, Julian Brunner, Johannes Kero, Alessandra Bellissimo and Olga Ridzel Spectroscopy of correlated electron pairs was employed to investigate the energy dissipation process as well as the transport and the emission of low energy electrons on a polymethylmetracylate (PMMA) surface, providing secondary electron (SE) spectra causally related to the energy loss of the primary electron. Two groups of electrons are identified in the cascade of slow electrons, corresponding to different stages in the energy dissipation process. For both groups, the characteristic lengths for attenuation due to collective excitations and momentum relaxation are quantified and are found to be distinctly different: l1=(12.0+/-2) Angstroem and l2=(61.5+/-11) Angstroem. The results strongly contradict the commonly employed model of exponential attenuation with the electron inelastic mean free path (IMFP) as characteristic length, but essentially agree with a theory used for decades in astrophysics and neutron transport, albeit with characteristic lengths expressed in units of Angstroems rather than lightyears.Comment: 6 pages 5 figure

Broadband Meter-Wavelength Observations of Ionospheric Scintillation

Intensity scintillations of cosmic radio sources are used to study astrophysical plasmas like the ionosphere, the solar wind, and the interstellar medium. Normally these observations are relatively narrow band. With Low Frequency Array (LOFAR) technology at the Kilpisj\"arvi Atmospheric Imaging Receiver Array (KAIRA) station in northern Finland we have observed scintillations over a 3 octave bandwidth. ``Parabolic arcs'', which were discovered in interstellar scintillations of pulsars, can provide precise estimates of the distance and velocity of the scattering plasma. Here we report the first observations of such arcs in the ionosphere and the first broad-band observations of arcs anywhere, raising hopes that study of the phenomenon may similarly improve the analysis of ionospheric scintillations. These observations were made of the strong natural radio source Cygnus-A and covered the entire 30-250\,MHz band of KAIRA. Well-defined parabolic arcs were seen early in the observations, before transit, and disappeared after transit although scintillations continued to be obvious during the entire observation. We show that this can be attributed to the structure of Cygnus-A. Initial results from modeling these scintillation arcs are consistent with simultaneous ionospheric soundings taken with other instruments, and indicate that scattering is most likely to be associated more with the topside ionosphere than the F-region peak altitude. Further modeling and possible extension to interferometric observations, using international LOFAR stations, are discussed.Comment: 11 pages, 17 figure

Revisiting the expression and function of follicle-stimulation hormone receptor in human umbilical vein endothelial cells

Expression of follicle-stimulation hormone receptor (FSHR) is confined to gonads and at low levels to some extragonadal tissues like human umbilical vein endothelial cells (HUVEC). FSH-FSHR signaling was shown to promote HUVEC angiogenesis and thereafter suggested to have an influential role in pregnancy. We revisited hereby the expression and functionality of FSHR in HUVECs angiogenesis, and were unable to reproduce the FSHR expression in human umbilical cord, HUVECs or immortalized HUVECs (HUV-ST). Positive controls as granulosa cells and HEK293 cells stably transfected with human FSHR cDNA expressed FSHR signal. In contrast to positive control VEGF, FSH treatment showed no effects on tube formation, nitric oxide production, wound healing or cell proliferation in HUVEC/HUV-ST. Thus, it remains open whether the FSH-FSHR activation has a direct regulatory role in the angiogenesis of HUVECs.</p

Analyses of plant products in greater detail

The customary Weende system for food analysis is biologically defective and even misleading. The authors have used an analysis scheme in which the conventional crude fibre determination is replaced by the determination of the total of the vegetable cell wall substances. This fraction is called membrane substances. The crude fibre is an arbitrary fragment of this total. E.g. in spruce wood the crude fibre forms about 80 % of the total of the membrane substances, and in wheat bran about 50 %. In addition the fraction »membrane substances» is divided into 4 subtractions: cellulose, pentosans, lignin, and other membrane substances. Further, a fraction called valuable carbohydrates is determined by subtracting from 100 the percentages of water, ash, crude protein, crude fat, and membane substances. This scheme has been applied to the investigation of 44 different plant products. A critical examination of the methods used has been included

Asthma and mode of birth delivery: A study in 5-year-old Dutch twins.

Several studies report caesarean section (CS) to be a risk factor for childhood asthma. We used data from a large cohort of 5-year-old twins to examine the relationship between mode of birth delivery and asthma. The extent to which an infant is exposed to maternal vaginal flora may protect against the risk of developing asthma. Therefore, we expect a lower rate of asthma in twins born by vaginal delivery (VD) than those born by CS, and a lower rate of asthma in first-born twins compared to second-born twins by VD. Information on mode of delivery was obtained at the time of birth in a survey completed by the mother shortly after delivery. Information on history of asthma diagnosis by a physician was obtained by parental report when the twins were 5 years old. Complete data were available for 6330 first-born and 5438 second-born twins from birth cohorts 1991-2000. Full term first-born twins born by CS had a significantly higher risk of asthma compared to those born by VD, odds ratio = 1.59 (95% CI = 1.23-2.06). No significant differences were observed between CS and VD first-born twins when gestational age was less than 37 weeks, and no significant differences were observed between CS and VD second-born twins at any gestational age. No differences in asthma prevalence were found between first- and second-born twins both born by VD. CS may increase the risk of asthma to full term infants, however, the underlying mechanism is unclear

Simulated seasonal impact on middle atmospheric ozone from high-energy electron precipitation related to pulsating aurorae

Recent simulation studies have provided evidence that a pulsating aurora (PsA) associated with high-energy electron precipitation is having a clear local impact on ozone chemistry in the polar middle mesosphere. However, it is not clear if the PsA is frequent enough to cause longer-term effects of measurable magnitude. There is also an open question of the relative contribution of PsA-related energetic electron precipitation (PsA EEP) to the total atmospheric forcing by solar energetic particle precipitation (EPP). Here we investigate the PsA-EEP impact on stratospheric and mesospheric odd hydrogen, odd nitrogen, and ozone concentrations. We make use of the Whole Atmosphere Community Climate Model and recent understanding on PsA frequency, latitudinal and magnetic local time extent, and energy-flux spectra. Analysing an 18-month time period covering all seasons, we particularly look at PsA-EEP impacts at two polar observation stations located at opposite hemispheres: Tromsø in the Northern Hemisphere (NH) and Halley Research Station in the Southern Hemisphere (SH). We find that PsA EEP can have a measurable impact on ozone concentration above 30 km altitude, with ozone depletion by up to 8 % seen in winter periods due to PsA-EEP-driven NOx enhancement. We also find that direct mesospheric NOx production by high-energy electrons (E> 100 keV) accounts for about half of the PsA-EEP-driven upper stratospheric ozone depletion. A larger PsA-EEP impact is seen in the SH where the background dynamical variability is weaker than in the NH. Clearly indicated from our results, consideration of polar vortex dynamics is required to understand PsA-EEP impacts seen at ground observation stations, especially in the NH. We conclude that PsA-EEP has the potential to make an important contribution to the total EPP forcing; thus, it should be considered in atmospheric and climate simulations.publishedVersio