Accurate detection of uniparental disomy and microdeletions by SNP array analysis in myelodysplastic syndromes with normal cytogenetics.

Progress in the management of patients with myelodysplastic syndromes (MDS) has been hampered by the inability to detect cytogenetic abnormalities in 40-60% of cases. We prospectively analyzed matched pairs of bone marrow and buccal cell (normal) DNA samples from 51 MDS patients by single nucleotide polymorphism (SNP) arrays, and identified somatically acquired clonal genomic abnormalities in 21 patients (41%). Among the 33 patients with normal bone marrow cell karyotypes, 5 (15%) had clonal, somatically acquired aberrations by SNP array analysis, including 4 with segmental uniparental disomies (UPD) and 1 with three separate microdeletions. Each abnormality was detected more readily in CD34+ cells than in unselected bone marrow cells. Paired analysis of bone marrow and buccal cell DNA from each patient was necessary to distinguish true clonal genomic abnormalities from inherited copy number variations and regions with apparent loss of heterozygosity. UPDs affecting chromosome 7q were identified in two patients who had a rapidly deteriorating clinical course despite a low-risk International Prognostic Scoring System score. Further studies of larger numbers of patients will be needed to determine whether 7q UPD detected by SNP array analysis will identify higher risk MDS patients at diagnosis, analogous to those with 7q cytogenetic abnormalities

Monitoring SO2 emission at the Soufriere Hills Volcano: implications for changes in erruptive conditions

FLWINinfo:eu-repo/semantics/publishe

Polydiacetylenic nanofibers as new siRNA vehicles for in vitro and in vivo delivery

Polydiacetylenic nanofibers (PDA-Nfs) obtained by photopolymerization of surfactant 1 were optimized for intracellular delivery of small interfering RNAs (siRNAs). PDA-Nfs/siRNA complexes efficiently silenced the oncogene Lim-1 in the renal cancer cells 786-O in vitro. Intraperitoneal injection of PDA-Nfs/siLim1 downregulated Lim-1 in subcutaneous tumor xenografts obtained with 786-O cells in nude mice. Thus, PDA-Nfs represent an innovative system for in vivo delivery of siRNAs

Increased entropy of signal transduction in the cancer metastasis phenotype

Studies into the statistical properties of biological networks have led to important biological insights, such as the presence of hubs and hierarchical modularity. There is also a growing interest in studying the statistical properties of networks in the context of cancer genomics. However, relatively little is known as to what network features differ between the cancer and normal cell physiologies, or between different cancer cell phenotypes. Based on the observation that frequent genomic alterations underlie a more aggressive cancer phenotype, we asked if such an effect could be detectable as an increase in the randomness of local gene expression patterns. Using a breast cancer gene expression data set and a model network of protein interactions we derive constrained weighted networks defined by a stochastic information flux matrix reflecting expression correlations between interacting proteins. Based on this stochastic matrix we propose and compute an entropy measure that quantifies the degree of randomness in the local pattern of information flux around single genes. By comparing the local entropies in the non-metastatic versus metastatic breast cancer networks, we here show that breast cancers that metastasize are characterised by a small yet significant increase in the degree of randomness of local expression patterns. We validate this result in three additional breast cancer expression data sets and demonstrate that local entropy better characterises the metastatic phenotype than other non-entropy based measures. We show that increases in entropy can be used to identify genes and signalling pathways implicated in breast cancer metastasis. Further exploration of such integrated cancer expression and protein interaction networks will therefore be a fruitful endeavour.Comment: 5 figures, 2 Supplementary Figures and Table

Photopolymerized micelles of diacetylene amphiphile: physical characterization and cell delivery properties:

A series of polydiacetylene (PDA) - based micelles were prepared from diacetylenic surfactant bearing polyethylene glycol, by increasing UV-irradiation times. These polymeric lipid micelles were analyzed by physicochemical methods, electron microscopy and NMR analysis. Cellular delivery of fluorescent dye suggests that adjusting the polymerization state is vital to reach the full in vitro potential of PDA-based delivery system

T-Lymphoblastic Lymphoma Cells Express High Levels of BCL2, S1P1, and ICAM1, Leading to a Blockade of Tumor Cell Intravasation

The molecular events underlying the progression of T-lymphoblastic lymphoma (T-LBL) to acute T-lymphoblastic leukemia (T-ALL) remain elusive. In our zebrafish model, concomitant overexpression of bcl-2 with Myc accelerated T-LBL onset while inhibiting progression to T-ALL. The T-LBL cells failed to invade the vasculature and showed evidence of increased homotypic cell-cell adhesion and autophagy. Further analysis using clinical biopsy specimens revealed autophagy and increased levels of BCL2, S1P1, and ICAM1 in human T-LBL compared with T-ALL. Inhibition of S1P1 signaling in T-LBL cells led to decreased homotypic adhesion in vitro and increased tumor cell intravasation in vivo. Thus, blockade of intravasation and hematologic dissemination in T-LBL is due to elevated S1P1 signaling, increased expression of ICAM1, and augmented homotypic cell-cell adhesion.Stem Cell and Regenerative Biolog

Fracture and damage localization in volcanic edifice rocks from El Hierro, Stromboli and Tenerife

© 2018 The Author(s). We present elastic wave velocity and strength data from a suite of three volcanic rocks taken from the volcanic edifices of El Hierro and Tenerife (Canary Islands, Spain), and Stromboli (Aeolian Islands, Italy). These rocks span a range of porosity and are taken from volcanoes that suffer from edifice instability. We measure elastic wave velocities at known incident angles to the generated through-going fault as a function of imposed strain, and examine the effect of the damage zone on P-wave velocity. Such data are important as field measurements of elastic wave tomography are key tools for understanding volcanic regions, yet hidden fractures are likely to have a significant effect on elastic wave velocity. We then use elastic wave velocity evolution to calculate concomitant crack density evolution which ranges from 0 to 0.17: highest values were correlated to the damage zone in rocks with the highest initial porosity

Cardiac Dysfunction, Congestion and Loop Diuretics: their Relationship to Prognosis in Heart Failure

Background: Diuretics are the mainstay of treatment for congestion but concerns exist that they adversely affect prognosis. We explored whether the relationship between loop diuretic use and outcome is explained by the underlying severity of congestion amongst patients referred with suspected heart failure. Method and Results: Of 1190 patients, 712 had a left ventricular ejection fraction (LVEF) ≤50 %, 267 had LVEF >50 % with raised plasma NTproBNP (>400 ng/L) and 211 had LVEF >50 % with NTproBNP ≤400 ng/L; respectively, 72 %, 68 % and 37 % of these groups were treated with loop diuretics including 28 %, 29 % and 10 % in doses ≥80 mg furosemide equivalent/day. Compared to patients with cardiac dysfunction (either LVEF ≤50 % or NT-proBNP >400 ng/L) but not taking a loop diuretic, those taking a loop diuretic were older and had more clinical evidence of congestion, renal dysfunction, anaemia and hyponatraemia. During a median follow-up of 934 (IQR: 513–1425) days, 450 patients were hospitalized for HF or died. Patients prescribed loop diuretics had a worse outcome. However, in multi-variable models, clinical, echocardiographic (inferior vena cava diameter), and biochemical (NTproBNP) measures of congestion were strongly associated with an adverse outcome but not the use, or dose, of loop diuretics. Conclusions: Prescription of loop diuretics identifies patients with more advanced features of heart failure and congestion, which may account for their worse prognosis. Further research is needed to clarify the relationship between loop diuretic agents and outcome; imaging and biochemical measures of congestion might be better guides to diuretic dose than symptoms or clinical signs