Telomerase activity in plasma cell dyscrasias

Activation of telomerase is essential for in vitro cellular immortalization and tumorigenesis. In the present study, we investigated telomerase activation and its implications in plasma cell dyscrasias including monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM) and plasma cell leukaemia (PCL). All 5 patients with MGUS exhibited normal levels of telomerase activity in their plasma cells. Elevated telomerase activity was found in the samples from 21/27 patients with MM and 4/4 with PCL. In addition, 4 myeloma cell lines all expressed high levels of telomerase activity. The expression of telomerase reverse transcriptase (hTERT) and telomerase RNA template (hTER) was positively associated with the levels of telomerase activity in MM/PCL. Tankyrase expression was upregulated, concomitant with the induction of hTERT and activation of telomerase in MM/PCL. The present findings indicate that MGUS cells may not be immortalized and that activation of telomerase plays a role in the malignant transformation from MGUS to MM. © 2001 Cancer Research Campaign http://www.bjcancer.co

The benthic fauna of the Åland archipelago 2013

In the summer of 2013 a study of the benthic fauna in the Åland archipelago was conducted. The aim was to obtain an overview of the benthic fauna in the region and to describe changes over time (2006 vs. 2013). In total, 39 stations were sampled for zoobenthos and hydrography. Twenty-seven of the stations in this study were also sampled in 2006, while the remaining 12 stations have been sampled in studies prior to 2006. The 39 stations were located around the main island of Åland and the depth of the stations ranged between 5 and 37 meters. Since the previous baseline-study in 2006 there has been a decrease in abundance and an increase in the average weight of the individuals at sheltered stations. At exposed stations an increase in biomass, number of species and average weight of the individuals was found. Macoma balthica increased in abundance at exposed stations. No marked changes in the overall length distribution of M. balthica were found between 2006 and 2013. However, at some stations, especially those in connection with Lumparn, there were some indications pointing towards reproductive disturbance among M. balthica. In 2013 the ecological status was good or high at the majority of the stations. Only three stations located north of Lumparn embayment had a moderate or worse ecological status. Other findings in this study largely support the results of the ecological status classification. The situation at some of the stations in the Lumparn area is a cause of concern. However, at the station Ål Bergö somewhat contradicting findings were found. While the ecological status in 2013 was good, the oxygen level in the bottom water was below the limit of hypoxia (2mg/l). Special attention should be given to the Lumparn area as well as the area around Ål Bergö in future studies. A revision of the exposure classification can give better representation of large scale changes in the benthic fauna communities of Åland. Therefore, a proposition on exposure class classification to be used in future baseline studies is also given in this report

Identification of a new cholesterol-binding site within the IFN-γ receptor that is required for signal transduction.

The cytokine interferon-gamma (IFN-γ) is a master regulator of innate and adaptive immunity involved in a broad array of human diseases that range from atherosclerosis to cancer. IFN-γ exerts it signaling action by binding to a specific cell surface receptor, the IFN-γ receptor (IFN-γR), whose activation critically depends on its partition into lipid nanodomains. However, little is known about the impact of specific lipids on IFN-γR signal transduction activity. Here, a new conserved cholesterol (chol) binding motif localized within its single transmembrane domain is identified. Through direct binding, chol drives the partition of IFN-γR2 chains into plasma membrane lipid nanodomains, orchestrating IFN-γR oligomerization and transmembrane signaling. Bioinformatics studies show that the signature sequence stands for a conserved chol-binding motif presented in many mammalian membrane proteins. The discovery of chol as the molecular switch governing IFN-γR transmembrane signaling represents a significant advance for understanding the mechanism of lipid selectivity by membrane proteins, but also for figuring out the role of lipids in modulating cell surface receptor function. Finally, this study suggests that inhibition of the chol-IFNγR2 interaction may represent a potential therapeutic strategy for various IFN-γ-dependent diseases

Measurement of the proton and deuteron structure functions, F2p and F2d, and of the ratio sigma(L)/sigma(T)

The muon-proton and muon-deuteron inclusive deep inelastic scattering cross sections were measured in the kinematic range 0.002 < x < 0.60 and 0.5 < Q2 < 75 GeV2 at incident muon energies of 90, 120, 200 and 280 GeV. These results are based on the full data set collected by the New Muon Collaboration, including the data taken with a small angle trigger. The extracted values of the structure functions F2p and F2d are in good agreement with those from other experiments. The data cover a sufficient range of y to allow the determination of the ratio of the longitudinally to transversely polarised virtual photon absorption cross sections, R= sigma(L)/sigma(T), for 0.002 < x < 0.12 . The values of R are compatible with a perturbative QCD prediction; they agree with earlier measurements and extend to smaller x.Comment: In this replacement the erroneously quoted R values in tables 3-6 for x>0.12, and R1990 values in tables 5-6 for all x, have been corrected, and the cross sections in tables 3-4 have been adapted. Everything else, including the structure functions F2, remained unchanged. 22 pages, LateX, including figures, with two .sty files, and three separate f2tab.tex files for the F2-tables. Accepted for publication in Nucl.Phys.B 199

An intronic deletion in megakaryoblastic leukemia 1 is associated with hyperproliferation of B cells in triplets with Hodgkin lymphoma

Megakaryoblastic leukemia 1 (MKL1) is a coactivator of serum response factor and together regulate transcription of actin cytoskeleton genes. MKL1 is associated with hematologic malignancies and immunodeficiency, but its role in B cells is unexplored. Here we examined B cells from monozygotic triplets with an intronic deletion in MKL1, two of whom were previously treated for Hodgkin lymphoma. To investigate MKL1 and B cell responses in HL pathogenesis, we generated Epstein Barr virus-transformed lymphoblastoid cell lines from the triplets and two controls. While cells from the Hodgkin lymphoma treated patients had a phenotype close to healthy controls, cells from the undiagnosed triplet had increased MKL1 mRNA, increased MKL1 protein, and elevated expression of MKL1-dependent genes. This was associated with elevated actin content, increased cell spreading, decreased expression of CD11a integrin molecules, and delayed aggregation. Moreover, cells from the undiagnosed triplet proliferated faster, displayed a higher proportion of cells with hyperploidy, and formed large tumors in vivo. This phenotype was reversible by inhibiting MKL1 activity. Interestingly, cells from the triplet treated for Hodgkin lymphoma in 1985 contained two subpopulations: one with high expression of CD11a that behaved like control cells and the other with low expression of CD11a that formed large tumors in vivo similar to cells from the undiagnosed triplet. This implies that pre-malignant cells had re-emerged a long time after treatment. Together, these data suggest that dysregulated MKL1 activity participates in B cell transformation and Hodgkin lymphoma pathogenesis

Germline and somatic JAK2 mutations and susceptibility to chronic myeloproliferative neoplasms

Myeloproliferative neoplasms (MPNs) are a group of closely related stem-cell-derived clonal proliferative diseases. Most cases are sporadic but first-degree relatives of MPN patients have a five- to seven-fold increased risk for developing an MPN. The tumors of most patients carry a mutation in the Janus kinase 2 gene (JAK2V617F). Recently, three groups have described a strong association of JAK2 germline polymorphisms with MPN in patients positive for JAK2V617F. The somatic mutation occurs primarily on one particular germline JAK2 haplotype, which may account for as much as 50% of the risk to first-degree relatives. This finding provides new directions for unraveling the pathogenesis of MPN

Suicide in cancer patients in South East England from 1996 to 2005: a population-based study

BACKGROUND: Studies from around the world have shown that suicide risk is increased in cancer patients, but no previous detailed analysis has been carried out in England

Large enhancement of deuteron polarization with frequency modulated microwaves

We report a large enhancement of 1.7 in deuteron polarization up to values of 0.6 due to frequency modulation of the polarizing microwaves in a two liters polarized target using the method of dynamic nuclear polarization. This target was used during a deep inelastic polarized muon-deuteron scattering experiment at CERN. Measurements of the electron paramagnetic resonance absorption spectra show that frequency modulation gives rise to additional microwave absorption in the spectral wings. Although these results are not understood theoretically, they may provide a useful testing ground for the deeper understanding of dynamic nuclear polarization.Comment: 10 pages, including the figures coming in uuencoded compressed tar files in poltar.uu, which also brings cernart.sty and crna12.sty files neede