Variability of stellar granulation and convective blueshift with spectral type and magnetic activity. I. K and G main sequence stars

In solar-type stars, the attenuation of convective blueshift by stellar magnetic activity dominates the RV variations over the low amplitude signal induced by low mass planets. Models of stars that differ from the Sun will require a good knowledge of the attenuation of the convective blueshift to estimate its impact on the variations. It is therefore crucial to precisely determine not only the amplitude of the convective blueshift for different types of stars, but also the dependence of this convective blueshift on magnetic activity, as these are key factors in our model producing the RV. We studied a sample of main sequence stars with spectral types from G0 to K2 and focused on their temporally averaged properties: the activity level and a criterion allowing to characterise the amplitude of the convective blueshift. We find the differential velocity shifts of spectral lines due to convection to depend on the spectral type, the wavelength (this dependence is correlated with the Teff and activity level), and on the activity level. This allows us to quantify the dependence of granulation properties on magnetic activity for stars other than the Sun. The attenuation factor of the convective blueshift appears to be constant over the considered range of spectral types. We derive a convective blueshift which decreases towards lower temperatures, with a trend in close agreement with models for Teff lower than 5800 K, but with a significantly larger global amplitude. We finally compare the observed RV variation amplitudes with those that could be derived from our convective blueshift using a simple law and find a general agreement on the amplitude. Our results are consistent with previous results and provide, for the first time, an estimation of the convective blueshift as a function of Teff, magnetic activity, and wavelength, over a large sample of G and K main sequence stars

Spin Gaps in High Temperature Superconductors

The phenomenology and theory of spin gap effects in high temperature superconductors is summarized. It is argued that the spin gap behavior can only be explained by a model of charge 0 spin 1/2 fermions which become paired into singlets and that there are both theoretical and experimental reasons for believing that the pairing is greatly enhanced in the bilayer structure of the $YBa_2Cu_3O_{6+x}$ system. This article will appear in the Proceedings of the Stanford Conference on Spectroscopies in Novel Superconductors. To obtain postscript files containing the figures send mail to [email protected]: 9 pages, revtex. To obtain figures contact [email protected]

Superconducting Order Parameter Symmetry in Multi-layer Cuprates

We discuss the allowed order parameter symmetries in multi-layer cuprates and their physical consequences using highly non-specific forms of the inter- and intra-plane interactions. Within this framework, the bi-layer case is discussed in detail with particular attention paid to the role of small orthorhombic distortions as would derive from the chains in YBCO or superlattice effects in BSCCO. In the orthorhombic bi-layer case the (s,-s) state is of special interest, since for a wide range of parameters this state exhibits pi phase shifts in corner Josephson junction experiments. In addition, its transition temperature is found to be insensitive to non-magnetic inter-plane disorder, as would be present at the rare earth site in YBCO, for example. Of particular interest, also, are the role of van Hove singularities which are seen to stabilize states with d_{x^2 - y^2}-like symmetry, (as well as nodeless s-states) and to elongate the gap functions along the four van Hove points, thereby leading to a substantial region of gaplessness. We find that d_{x^2 - y^2}-like states are general solutions for repulsive interactions; they possess the fewest number of nodes and therefore the highest transition temperatures. In this way, they should not be specifically associated with a spin fluctuation driven pairing mechanism.Comment: REVTeX documentstyle, 34 pages, 10 figures include

Fanconi-BRCA pathway mutations in childhood T-cell acute lymphoblastic leukemia

BRCA2 (also known as FANCD1) is a core component of the Fanconi pathway and suppresses transformation of immature T-cells in mice. However, the contribution of Fanconi-BRCA pathway deficiency to human T-cell acute lymphoblastic leukemia (T-ALL) remains undefined. We identified point mutations in 9 (23%) of 40 human T-ALL cases analyzed, with variant allele fractions consistent with heterozygous mutations early in tumor evolution. Two of these mutations were present in remission bone marrow specimens, suggesting germline alterations. BRCA2 was the most commonly mutated gene. The identified Fanconi-BRCA mutations encode hypomorphic or null alleles, as evidenced by their inability to fully rescue Fanconi-deficient cells from chromosome breakage, cytotoxicity and/or G2/M arrest upon treatment with DNA cross-linking agents. Disabling the tumor suppressor activity of the Fanconi-BRCA pathway is generally thought to require biallelic gene mutations. However, all mutations identified were monoallelic, and most cases appeared to retain expression of the wild-type allele. Using isogenic T-ALL cells, we found that BRCA2 haploinsufficiency induces selective hypersensitivity to ATR inhibition, in vitro and in vivo. These findings implicate Fanconi-BRCA pathway haploinsufficiency in the molecular pathogenesis of T-ALL, and provide a therapeutic rationale for inhibition of ATR or other druggable effectors of homologous recombination

PRC2 loss induces chemoresistance by repressing apoptosis in T cell acute lymphoblastic leukemia

The tendency of mitochondria to undergo or resist BCL2-controlled apoptosis (so-called mitochondrial priming) is a powerful predictor of response to cytotoxic chemotherapy. Fully exploiting this finding will require unraveling the molecular genetics underlying phenotypic variability in mitochondrial priming. Here, we report that mitochondria) apoptosis resistance in T cell acute lymphoblastic leukemia (T-ALL) is mediated by inactivation of polycomb repressive complex 2 (PRC2). In T-ALL clinical specimens, loss-of-function mutations of PRC2 core components (EZH2, FED, or SUZ12) were associated with mitochondrial apoptosis resistance. In T-ALL cells, PRC2 depletion induced resistance to apoptosis induction by multiple chemotherapeutics with distinct mechanisms of action. PRC2 loss induced apoptosis resistance via transcriptional up-regulation of the LIM domain transcription factor CRIP2 and downstream up-regulation of the mitochondrial chaperone TRAP1. These findings demonstrate the importance of mitochondrial apoptotic priming as a prognostic factor in T-ALL and implicate mitochondrial chaperone function as a molecular determinant of chemotherapy response

Genomic analyses identify recurrent MEF2D fusions in acute lymphoblastic leukemia

Chromosomal rearrangements are initiating events in acute lymphoblastic leukaemia (ALL). Here using RNA sequencing of 560 ALL cases, we identify rearrangements between MEF2D (myocyte enhancer factor 2D) and five genes (BCL9, CSF1R, DAZAP1, HNRNPUL1 and SS18) in 22 B progenitor ALL (B-ALL) cases with a distinct gene expression profile, the most common of which is MEF2DBCL9. Examination of an extended cohort of 1,164 B-ALL cases identified 30 cases with MEF2D rearrangements, which include an additional fusion partner, FOXJ2; thus, MEF2D-rearranged cases comprise 5.3% of cases lacking recurring alterations. MEF2D-rearranged ALL is characterized by a distinct immunophenotype, DNA copy number alterations at the rearrangement sites, older diagnosis age and poor outcome. The rearrangements result in enhanced MEF2D transcriptional activity, lymphoid transformation, activation of HDAC9 expression and sensitive to histone deacetylase inhibitor treatment. Thus, MEF2D-rearranged ALL represents a distinct form of high-risk leukaemia, for which new therapeutic approaches should be considered.This work was supported in part by the American Lebanese Syrian Associated Charities of St. Jude Children’s Research Hospital; by a Stand Up to Cancer Innovative Research Grant and St. Baldrick’s Foundation Scholar Award (to C.G.M.); by a St. Baldrick’s Consortium Award (S.P.H.), by a Leukemia and Lymphoma Society Specialized Center of Research grant (S.P.H. and C.G.M.), by a Lady Tata Memorial Trust Award (I.I.), by a Leukemia and Lymphoma Society Special Fellow Award and Alex’s Lemonade Stand Foundation Young Investigator Awards (K.R.), by an Alex’s Lemonade Stand Foundation Award (M.L.) and by National Cancer Institute Grants CA21765 (St Jude Cancer Center Support Grant), U01 CA157937 (C.L.W. and S.P.H.), U24 CA114737 (to Dr Gastier-Foster), NCI Contract HHSN261200800001E (to Dr Gastier-Foster), U10 CA180820 (ECOG-ACRIN Operations) and CA180827 (E.P.); U10 CA180861 (C.D.B. and G.M.); U24 CA196171 (The Alliance NCTN Biorepository and Biospecimen Resource); CA145707 (C.L.W. and C.G.M.); and grants to the COG: U10 CA98543 (Chair’s grant and supplement to support the COG ALL TARGET project), U10 CA98413 (Statistical Center) and U24 CA114766 (Specimen Banking). This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under Contract Number HHSN261200800001E

X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes

X-linked intellectual disability (XLID) is a clinically and genetically heterogeneous disorder. During the past two decades in excess of 100 X-chromosome ID genes have been identified. Yet, a large number of families mapping to the X-chromosome remained unresolved suggesting that more XLID genes or loci are yet to be identified. Here, we have investigated 405 unresolved families with XLID. We employed massively parallel sequencing of all X-chromosome exons in the index males. The majority of these males were previously tested negative for copy number variations and for mutations in a subset of known XLID genes by Sanger sequencing. In total, 745 X-chromosomal genes were screened. After stringent filtering, a total of 1297 non-recurrent exonic variants remained for prioritization. Co-segregation analysis of potential clinically relevant changes revealed that 80 families (20%) carried pathogenic variants in established XLID genes. In 19 families, we detected likely causative protein truncating and missense variants in 7 novel and validated XLID genes (CLCN4, CNKSR2, FRMPD4, KLHL15, LAS1L, RLIM and USP27X) and potentially deleterious variants in 2 novel candidate XLID genes (CDK16 and TAF1). We show that the CLCN4 and CNKSR2 variants impair protein functions as indicated by electrophysiological studies and altered differentiation of cultured primary neurons from Clcn4−/− mice or after mRNA knock-down. The newly identified and candidate XLID proteins belong to pathways and networks with established roles in cognitive function and intellectual disability in particular. We suggest that systematic sequencing of all X-chromosomal genes in a cohort of patients with genetic evidence for X-chromosome locus involvement may resolve up to 58% of Fragile X-negative cases

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]