The lincRNA HOTAIRM1, located in the HOXA genomic region, is expressed in acute myeloid leukemia, impacts prognosis in patients in the intermediate-risk cytogenetic category, and is associated with a distinctive microRNA signature.

Long non-coding RNAs (lncRNAs) are deregulated in several tumors, although their role in acute myeloid leukemia (AML) is mostly unknown.We have examined the expression of the lncRNA HOX antisense intergenic RNA myeloid 1 (HOTAIRM1) in 241 AML patients. We have correlated HOTAIRM1 expression with a miRNA expression profile. We have also analyzed the prognostic value of HOTAIRM1 expression in 215 intermediate-risk AML (IR-AML) patients.The lowest expression level was observed in acute promyelocytic leukemia (P < 0.001) and the highest in t(6;9) AML (P = 0.005). In 215 IR-AML patients, high HOTAIRM1 expression was independently associated with shorter overall survival (OR:2.04;P = 0.001), shorter leukemia-free survival (OR:2.56; P < 0.001) and a higher cumulative incidence of relapse (OR:1.67; P = 0.046). Moreover, HOTAIRM1 maintained its independent prognostic value within the favorable molecular subgroup (OR: 3.43; P = 0.009). Interestingly, HOTAIRM1 was overexpressed in NPM1-mutated AML (P < 0.001) and within this group retained its prognostic value (OR: 2.21; P = 0.01). Moreover, HOTAIRM1 expression was associated with a specific 33-microRNA signature that included miR-196b (P < 0.001). miR-196b is located in the HOX genomic region and has previously been reported to have an independent prognostic value in AML. miR-196b and HOTAIRM1 in combination as a prognostic factor can classify patients as high-, intermediate-, or low-risk (5-year OS: 24% vs 42% vs 70%; P = 0.004).Determination of HOTAIRM1 level at diagnosis provided relevant prognostic information in IR-AML and allowed refinement of risk stratification based on common molecular markers. The prognostic information provided by HOTAIRM1 was strengthened when combined with miR-196b expression. Furthermore, HOTAIRM1 correlated with a 33-miRNA signature.

Experience and intermediate-term results using the Contegra heterograft for right ventricular outflow reconstruction in adults.

OBJECTIVES: The Contegra bioprosthesis (valved heterologous bovine jugular vein) is used for reconstruction of the right ventricular outflow tract (RVOT) in congenital heart malformations and pulmonary valve replacement in different settings. Compared to pulmonary homografts, the Contegra conduit is readily available 'on the shelf'. So far, its use was mainly described in children. The aim of this study is to evaluate the feasibility and the outcome of Contegra graft implantation in the adult. METHODS: Between November 1999 and December 2007, a total of 32 Contegra grafts were implanted in 31 patients (24 men and 7 women), with a mean age of 35.7+/-10.5 years (range 18-54 years). All operations have been completed through median sternotomy with cardiopulmonary bypass. Indications included: Ross procedure for aortic valve disease (n=22); re-operation of corrected Fallot-tetralogy (n=5); isolated pulmonary valve disease (n=2); re-operation of double outlet right ventricle (DORV) (n=1); pulmonary stenosis in congenital dilated cardiomyopathy (DCM) (n=1). Conduit sizes included 22 mm (n=31), 20 mm (n=1). RESULTS: There was no hospital mortality and no valved conduit related early morbidity. In the median follow-up of 38 months (range 1-99 months) of 28 patients there was one late death, not conduit related (total mortality 3.6%). Re-operation for symptomatic graft stenosis was realised in two patients, 7 and 16 months after primo-implantation, corresponding to graft related late morbidity of 7.1%. CONCLUSIONS: In this small review of 32 operations using the Contegra graft for RVOT reconstruction in adult cardiac surgery for different indications, we observed good postoperative mid-term results concerning conduit function. Mean transpulmonary pressure gradients remain low (13.3+/-6.6 mmHg postoperative, 14.5+/-7.9 mmHg at follow-up). The use of the Contegra graft seems to be a good alternative to the homograft with low operative mortality and morbidity. Long-term outcome data are not available and further investigations must be performed to evaluate results.

Normal forms, stability and splitting of invariant manifolds I. Gevrey Hamiltonians

In this paper, we give a new construction of resonant normal forms with a small remainder for near-integrable Hamiltonians at a quasi-periodic frequency. The construction is based on the special case of a periodic frequency, a Diophantine result concerning the approximation of a vector by independent periodic vectors and a technique of composition of periodic averaging. It enables us to deal with non-analytic Hamiltonians, and in this first part we will focus on Gevrey Hamiltonians and derive normal forms with an exponentially small remainder. This extends a result which was known for analytic Hamiltonians, and only in the periodic case for Gevrey Hamiltonians. As applications, we obtain an exponentially large upper bound on the stability time for the evolution of the action variables and an exponentially small upper bound on the splitting of invariant manifolds for hyperbolic tori, generalizing corresponding results for analytic Hamiltonians.

Normal forms, stability and splitting of invariant manifolds II. Finitely differentiable Hamiltonians

This paper is a sequel to ``Normal forms, stability and splitting of invariant manifolds I. Gevrey Hamiltonians", in which we gave a new construction of resonant normal forms with an exponentially small remainder for near-integrable Gevrey Hamiltonians at a quasi-periodic frequency, using a method of periodic approximations. In this second part we focus on finitely differentiable Hamiltonians, and we derive normal forms with a polynomially small remainder. As applications, we obtain a polynomially large upper bound on the stability time for the evolution of the action variables and a polynomially small upper bound on the splitting of invariant manifolds for hyperbolic tori.

Vancomycin-intermediate Staphylococcus aureus selected during vancomycin therapy of experimental endocarditis are not detected by culture-based diagnostic procedures and persist after treatment arrest.

OBJECTIVES: Laboratory detection of vancomycin-intermediate Staphylococcus aureus (VISA) and their heterogeneous VISA (hVISA) precursors is difficult. Thus, it is possible that vancomycin failures against supposedly vancomycin-susceptible S. aureus are due to undiagnosed VISA or hVISA. We tested this hypothesis in experimental endocarditis.¦METHODS: Rats with aortic valve infection due to the vancomycin-susceptible (MIC 2 mg/L), methicillin-resistant S. aureus M1V2 were treated for 2 days with doses of vancomycin that mimicked the pharmacokinetics seen in humans following intravenous administration of 1 g of the drug every 12 h. Half of the treated animals were killed 8 h after treatment arrest and half 3 days thereafter. Population analyses were done directly on vegetation homogenates or after one subculture in drug-free medium to mimic standard diagnostic procedures.¦RESULTS: Vancomycin cured 14 of 26 animals (54%; P<0.05 versus controls) after 2 days of treatment. When vegetation homogenates were plated directly on vancomycin-containing plates, 6 of 13 rats killed 8 h after treatment arrest had positive cultures, 1 of which harboured hVISA. Likewise, 6 of 13 rats killed 3 days thereafter had positive valve cultures, 5 of which harboured hVISA. However, one subculture of vegetations in drug-free broth was enough to revert all the hVISA phenotypes to the susceptible pattern of the parent. Thus, vancomycin selected for hVISA during therapy of experimental endocarditis due to vancomycin-susceptible S. aureus. These hVISA were associated with vancomycin failure. The hVISA phenotype persisted in vivo, even after vancomycin arrest, but was missed in vitro after a single passage of the vegetation homogenate on drug-free medium.¦CONCLUSIONS: hVISA might escape detection in clinical samples if they are subcultured before susceptibility tests.

Liver, Gastrointestinal, and Cardiac Toxicity in Intermediate Hepatocellular Carcinoma Treated With PRECISION TACE With Drug-Eluting Beads: Results From the PRECISION V Randomized Trial.

OBJECTIVE. The purpose of our study was to evaluate hepatic, gastrointestinal, and cardiac toxicity after PRECISION transarterial chemoembolization (TACE) with drug-eluting beads (DEB) versus conventional TACE with doxorubicin in the treatment of intermediate-stage hepatocellular carcinoma (HCC).SUBJECTS AND METHODS. Two hundred twelve patients (185 men and 27 women; mean age, 67 years) were randomized to TACE with DEB or conventional TACE. The majority of patients (67% in both groups) presented in a more advanced stage. Safety was measured by rate of adverse events (Southwest Oncology Group criteria) and changes in laboratory parameters. Cardiotoxicity was assessed with left ventricular ejection fraction (LVEF) mainly on MRI or echocardiography.RESULTS. The mean maximum postchemoembolization alanine transaminase increase in the DEB group was 50% less than in the conventional TACE group (p < 0.001) and 41% less in respect to aspartate transaminase (p < 0.001). End-of-study values returned to approximately baseline levels but with greater variability in conventional TACE patients. Treatment-emergent adverse events in the hepatobiliary system organ class occurred in 16.1% of DEB group patients compared with 25% of conventional TACE patients. There were fewer liver toxicity events in the DEB group. There was a small but statistically significant difference in mean change from baseline in LVEF between the two groups of 4 percentage points for the conventional TACE group (95% CI, 0.71-7.3; p = 0.018).CONCLUSION. PRECISION TACE with DEB loaded with doxorubicin offers a safe therapy option for intermediate-stage HCC, even in patients with more advanced liver disease.

Monoclonal antibody against carcinoembryonic antigen (CEA) identifies two new forms of crossreacting antigens of molecular weight 90,000 and 160,000 in normal granulocytes.

Two new forms of non-specific crossreacting antigens (NCAs) were identified in the Nonidet P40 (NP-40) extracts of normal granulocytes by precipitation with the monoclonal antibody (MAb) 192 directed against carcinoembryonic antigen (CEA) and already known to crossreact with the perchloric acid soluble NCA-55. The NP-40 soluble NCAs recognized by MAb 192 have apparent mol. wts of 90,000 and 160,000 in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Both NCAs appear to consist of a single monomeric polypeptide chain, since they have the same electrophoretic mobility in SDS-PAGE under reduced and non-reduced conditions. When granulocytes were extracted with perchloric acid instead of NP-40, only the 55,000 mol. wt antigen, corresponding to the previously described NCA-55, was precipitated by MAb 192. Furthermore, it was shown that NCA-55 is not a degradation product of NCA-90 or NCA-160 due to the perchloric acid treatment because exposure to perchloric acid of NCA preparations purified from NP-40 extracts did not change their apparent mol. wts in SDS-PAGE. It was also shown that NCA-160 is not a granulocytic form of CEA because it was not precipitated by the MAb 35 reacting exclusively with CEA. Immunocytochemical studies of granulocytes and macrophages showed that MAb 192 stained both types of cells whereas MAb 47 stained only the granulocytes and MAb 35 none of these cells. In granulocytes both MAbs reacted with antigens associated with granules and also present at the periphery of the nucleus as well as in the Golgi apparatus. The NCA-90 identified by MAb 192 was found by sequential immunodepletion to be antigenically distinct from the NCA-95 precipitated by MAb 47. The epitope recognized by MAb 192 on CEA and NCA molecules appears to be on the peptidic moiety because the antigens deglycosylated by the enzyme Endo F were still precipitated by this MAb. Taken together, the results indicate that MAb 192 identifies two novel forms of NCA (NCA-90 and NCA-160) in NP-40 extracts of granulocytes, which are distinct from CEA and the previously described NCA-55 and NCA-95 identified by MAbs 192 and 47, respectively, in perchloric acid extracts of granulocytes.

Experiències catalanes, angleses i irlandeses en el millorament de l’accès a l’habitatge

El Grup de Recerca d´Accés a l´Habitatge de la Universitat Rovira i Virgili ha portat a terme durant l´any 2011 una sèrie d´activitats gràcies a l´ajuda concedida per la convocatòria de l´AGAUR PBR-DGR 2010, que ha donat suport al Grup tant de forma directa (per exemple, en viatges i dietes) com indirecta (gràcies a l´ajuda prestada per la Sra. Helaine Cristina Madeira Santos, becària de suport al Grup de Recerca, que ha portat a terme tasques de coordinació i investigació). Així, el Grup ha portat a terme tasques d´investigació (per exemple, la signatura d´un Conveni amb l’Agència de l’Habitatge de Catalunya amb la finalitat de portar a terme en el termini de 3 anys l’elaboració d´un marc legislatiu sobre les tinences intermitges en el Dret català); tasques de formació (gràcies a la participació en Congressos i Jornades); esta coordinant una xarxa sobre grups d´habitatge (per exemple, mitjançant un Congrés internacional sobre habitatge celebrat a Granada); ha publicat llibres i articles científics (per exemple, la publicació dels treballs presentats en les III Jornades Internacionals de Housing de 2010); i finalment cal destacar que l´activitat del Grup ha tingut un gran impacte en els mitjans de comunicació. Tot aquest treball ha permès al Grup arribar a unes conclusions sobre el status quo de l´habitatge a Espanya, per exemple les mancances del mercat d´habitatge en propietat i en lloguer i els aspectes que cal reformar quant al règim tributari i processal d´aquestes formes de tinença immobiliària. La principal conclusió, però, és la necessitat de regular noves formes d´entendre la tinença de la terra tot seguint els models ja presents en altres països europeus (principalment, Anglaterra i Irlanda), com la propietat compartida i la propietat temporal, figures en les quals està aprofundint actualment el Grup de recerca.

Interbreedings between Karyotypic Alpine Races of the Common Shrew Sorex-Araneus (Insectivora, Mammalia)

Controlled interbreedings were performed between distinct chromosomal races or forms of Sorex araneus coming from populations of Swiss and French Alps. Four mating pairs including homozygous individuals of the Vaud race, the Valais race, the Intermediate Vaud-Acrocentric form and the Acrocentric form have led to several heterozygous hybrid litters. The karyotypes of the parents were determined from cultures of cartilaginous cells. The karyotypes of the offsprings were determined with a classical method. The production of hybrids between different races suggests the absence of postmating barrier between the Vaud race and the Intermediate form, the Acrocentric form and the Intermediate form, the Acrocentric form and the Valais race.

‘A tiger that wants to become a lion’: Violent forms of agency among youth in Cape Verde

Cape Verdean prison population raised 100% in the last ten years: in this paper I offer an interpretation of this disturbing figure, addressing the issue of young offenders and children in conflict with the law, the perception of youth crime in Cape Verde, and how the government has recently dealt with these issues. Cape Verde currently deploys a repressive approach to the issue of youth crime: in this draconian context, I will follow the application of policies and laws targeting juvenile delinquents as well as the public and media discourse on the issue. At the same time, through interviews with younger inmates in prisons and institutions, I will relocate young offenders’ behavior and activity within their wider social context, providing urgently needed data on the cultural and social dimensions of juvenile offending and violence.

ParA2, a Vibrio cholerae chromosome partitioning protein, forms left-handed helical filaments on DNA.

Most bacterial chromosomes contain homologs of plasmid partitioning (par) loci. These loci encode ATPases called ParA that are thought to contribute to the mechanical force required for chromosome and plasmid segregation. In Vibrio cholerae, the chromosome II (chrII) par locus is essential for chrII segregation. Here, we found that purified ParA2 had ATPase activities comparable to other ParA homologs, but, unlike many other ParA homologs, did not form high molecular weight complexes in the presence of ATP alone. Instead, formation of high molecular weight ParA2 polymers required DNA. Electron microscopy and three-dimensional reconstruction revealed that ParA2 formed bipolar helical filaments on double-stranded DNA in a sequence-independent manner. These filaments had a distinct change in pitch when ParA2 was polymerized in the presence of ATP versus in the absence of a nucleotide cofactor. Fitting a crystal structure of a ParA protein into our filament reconstruction showed how a dimer of ParA2 binds the DNA. The filaments formed with ATP are left-handed, but surprisingly these filaments exert no topological changes on the right-handed B-DNA to which they are bound. The stoichiometry of binding is one dimer for every eight base pairs, and this determines the geometry of the ParA2 filaments with 4.4 dimers per 120 A pitch left-handed turn. Our findings will be critical for understanding how ParA proteins function in plasmid and chromosome segregation.

Two functional forms of the Xenopus laevis estrogen receptor translated from a single mRNA species.

Steroid receptors are nuclear proteins that regulate gene transcription in a ligand-dependent manner. Over-expression of the Xenopus estrogen receptor in a vaccinia virus-derived expression system revealed that the receptor localized exclusively in the nucleus of the infected cells, irrespective of the presence or absence of the ligand. Furthermore, two forms of the receptor were produced, a full-length and a N-terminal truncated version, which are translated from a single mRNA species by the use of two AUG within the same reading frame. These 66- and 61-kDa receptors were also observed after in vitro translation of the mRNA as well as in primary Xenopus hepatocytes. Both forms are potent estrogen-dependent transcriptional activators in transient transfection experiments, as well as in in vitro transcription assays.