Discrete clouds of neutral gas between the galaxies M31 and M33.

Spiral galaxies must acquire gas to maintain their observed level of star formation beyond the next few billion years. A source of this material may be the gas that resides between galaxies, but our understanding of the state and distribution of this gas is incomplete. Radio observations of the Local Group of galaxies have revealed hydrogen gas extending from the disk of the galaxy M31 at least halfway to M33. This feature has been interpreted to be the neutral component of a condensing intergalactic filament, which would be able to fuel star formation in M31 and M33, but simulations suggest that such a feature could also result from an interaction between both galaxies within the past few billion years (ref. 5). Here we report radio observations showing that about 50 per cent of this gas is composed of clouds, with the rest distributed in an extended, diffuse component. The clouds have velocities comparable to those of M31 and M33, and have properties suggesting that they are unrelated to other Local Group objects. We conclude that the clouds are likely to be transient condensations of gas embedded in an intergalactic filament and are therefore a potential source of fuel for future star formation in M31 and M33.

Intraorifice sealing of gutta-percha obturated root canals to prevent coronal microleakage.

A study was conducted to evaluate Cavit, Intermediate Restorative Material, and Super-EBA as intraorifice filling materials to prevent coronal microleakage. Root canal instrumentation and obturation was done on 74 extracted single-rooted teeth. Three and one-half millimeters of the gutta-percha was removed from the coronal aspect of the root canal and replaced with one of the three filling materials. The teeth were suspended in scintillation vials containing trypticase soy broth, and human saliva was added to the pulp chambers. Microbial penetration was detected as an increase in turbidity of the broth corresponding to bacterial growth. At the end of 90 days, the results showed that 15% of the Cavit-filled orifices leaked, whereas 35% of the Intermediate Restorative Material and Super-EBA-filled orifices leaked. The gutta-percha obturated root canals that received an intraorifice filling material leaked significantly less than the obturated, unsealed control group--all of which leaked in < 49 days.

Exome sequencing reveals novel and recurrent mutations with clinical impact in blastic plasmacytoid dendritic cell neoplasm.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a very rare disease that currently lacks genomic and genetic biomarkers to assist in its clinical management. We performed whole-exome sequencing (WES) of three BPDCN cases. Based on these data, we designed a resequencing approach to identify mutations in 38 selected genes in 25 BPDCN samples. WES revealed 37-99 deleterious gene mutations per exome with no common affected genes between patients, but with clear overlap in terms of molecular and disease pathways (hematological and dermatological disease). We identified for the first time deleterious mutations in IKZF3, HOXB9, UBE2G2 and ZEB2 in human leukemia. Target sequencing identified 29 recurring genes, ranging in prevalence from 36% for previously known genes, such as TET2, to 12-16% for newly identified genes, such as IKZF3 or ZEB2. Half of the tumors had mutations affecting either the DNA methylation or chromatin remodeling pathways. The clinical analysis revealed that patients with mutations in DNA methylation pathway had a significantly reduced overall survival (P=0.047). We provide the first mutational profiling of BPDCN. The data support the current WHO classification of the disease as a myeloid disorder and provide a biological rationale for the incorporation of epigenetic therapies for its treatment.

MicroRNA signatures in B-cell lymphomas.

Accurate lymphoma diagnosis, prognosis and therapy still require additional markers. We explore the potential relevance of microRNA (miRNA) expression in a large series that included all major B-cell non-Hodgkin lymphoma (NHL) types. The data generated were also used to identify miRNAs differentially expressed in Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL) samples. A series of 147 NHL samples and 15 controls were hybridized on a human miRNA one-color platform containing probes for 470 human miRNAs. Each lymphoma type was compared against the entire set of NHLs. BL was also directly compared with DLBCL, and 43 preselected miRNAs were analyzed in a new series of routinely processed samples of 28 BLs and 43 DLBCLs using quantitative reverse transcription-polymerase chain reaction. A signature of 128 miRNAs enabled the characterization of lymphoma neoplasms, reflecting the lymphoma type, cell of origin and/or discrete oncogene alterations. Comparative analysis of BL and DLBCL yielded 19 differentially expressed miRNAs, which were confirmed in a second confirmation series of 71 paraffin-embedded samples. The set of differentially expressed miRNAs found here expands the range of potential diagnostic markers for lymphoma diagnosis, especially when differential diagnosis of BL and DLBCL is required.

Mantle cell lymphoma: transcriptional regulation by microRNAs.

Mantle cell lymphoma (MCL) pathogenesis is still partially unexplained. We investigate the importance of microRNA (miRNA) expression as an additional feature that influences MCL pathway deregulation and may be useful for predicting patient outcome. Twenty-three MCL samples, eight cell lines and appropriate controls were screened for their miRNAs and gene expression profiles and DNA copy-number changes. MCL patients exhibit a characteristic signature that includes 117 miRNA (false discovery rate <0.05). Combined analysis of miRNAs and the gene expression profile, paired with bioinformatics target prediction (miRBase and TargetScan), revealed a series of genes and pathways potentially targeted by a small number of miRNAs, including essential pathways for lymphoma survival such as CD40, mitogen-activated protein kinase and NF-kappaB. Functional validation in MCL cell lines demonstrated NF-kappaB subunit nuclear translocation to be regulated by the expression of miR-26a. The expression of 12 selected miRNAs was studied by quantitative PCR in an additional series of 54 MCL cases. Univariate analysis identified a single miRNA, miR-20b, whose lack of expression distinguished cases with a survival probability of 56% at 60 months. In summary, using a novel bioinformatics approach, this study identified miRNA changes that contribute to MCL pathogenesis and markers of potential utility in MCL diagnosis and clinical prognostication.

Mean velocity of circumferential fiber shortening in prolapsed mitral leaflet syndrome.

In 26 patients with mitral valve prolapse, ventricular function was evaluated by mean velocity of circumferential fiber shortening (MVCF) as measured along the basilar, middle and apical axes. Significantly increased rates of MVCF were found in patients with mitral prolapse along the basilar axis (1.75 +/- 0.23 circ/sec) and middle axis (2.09 +/- 0.34 cir/sec) (P less than 0.025 and P less than 0.05, respectively). Patients with mitral valve prolapse and regurgitation demonstrated a significant increase in MVCF along the basilar axes (1.72 +/- 0.15 cir/sec) (P less than 0.05). Asynergy apperars to have a negative effect on the MVCF along the middle axis. The MVCF was found not to be related to clinical findings, symptoms or electrocardiographic changes. The mechanism for the increase in MVCF in patients with mitral valve prolapse remains unsettled.