Inhibition of Endosteal Vascular Niche Remodeling Rescues Hematopoietic Stem Cell Loss in AML

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Two new species of Staurotheca Allman, 1888 (Cnidaria, Hydrozoa, Sertulariidae) from the Scotia Sea (Antarctica)

Two new species of the genus Staurotheca Allman, 1888 have been studied (Staurotheca cornuta sp. nov. and Staurotheca multifurcata sp. nov). The material, from the Scotia Ridge area (Antarctica), was collected in 1986/1987 by the Spanish Antarctic expedition “Antártida 8611”. Each species is described and figured, and its systematic position among allied species is noted. Data concerning autecology and geographical distribution for each species are given. A comparative table listing the main features of the known species of the genus is included. Finally, a general survey of the geographical and bathymetrical distribution of the known species of the genus is presented. Accepted: 1 September 1998     

<Emphasis Type="Italic">atonal</Emphasis>- and <Emphasis Type="Italic">achaete-scute</Emphasis>-related genes in the annelid <Emphasis Type="Italic">Platynereis dumerilii</Emphasis>: insights into the evolution of neural basic-Helix-Loop-Helix genes

Background  

Functional studies in model organisms, such as vertebrates and Drosophila, have shown that basic Helix-loop-Helix (bHLH) proteins have important roles in different steps of neurogenesis, from the acquisition of neural fate to the differentiation into specific neural cell types. However, these studies highlighted many differences in the expression and function of orthologous bHLH proteins during neural development between vertebrates and Drosophila. To understand how the functions of neural bHLH genes have evolved among bilaterians, we have performed a detailed study of bHLH genes during nervous system development in the polychaete annelid, Platynereis dumerilii, an organism which is evolutionary distant from both Drosophila and vertebrates.     

Identification of in vitro phosphorylation sites in the Arabidopsis thaliana somatic embryogenesis receptor‐like kinases

The Arabidopsis thaliana somatic embryogenesis receptor‐like kinase (SERK) family consists of five leucine‐rich repeat receptor‐like kinases (LRR‐RLKs) with diverse functions such as brassinosteroid insensitive 1 (BRI1)‐mediated brassinosteroid perception, development and innate immunity. The autophosphorylation activity of the kinase domains of the five SERK proteins was compared and the phosphorylated residues were identified by LC‐MS/MS. Differences in autophosphorylation that ranged from high activity of SERK1, intermediate activities for SERK2 and SERK3 to low activity for SERK5 were noted. In the SERK1 kinase the C‐terminally located residue Ser‐562 controls full autophosphorylation activity. Activation loop phosphorylation, including that of residue Thr‐462 previously shown to be required for SERK1 kinase activity, was not affected. In vivo SERK1 phosphorylation was induced by brassinosteroids. Immunoprecipitation of CFP‐tagged SERK1 from plant extracts followed by MS/MS identified Ser‐303, Thr‐337, Thr‐459, Thr‐462, Thr‐463, Thr‐468, and Ser‐612 or Thr‐613 or Tyr‐614 as in vivo phosphorylation sites of SERK1. Transphosphorylation of SERK1 by the kinase domain of the main brassinosteroid receptor BRI1 occurred only on Ser‐299 and Thr‐462. This suggests both intra‐ and intermolecular control of SERK1 kinase activity. Conversely, BRI1 was transphosphorylated by the kinase domain of SERK1 on Ser‐887. BRI1 kinase activity was not required for interaction with the SERK1 receptor in a pull down assay.     

A non-tree-based comprehensive study of metazoan Hox and ParaHox genes prompts new insights into their origin and evolution

Background  

Hox and the closely-related ParaHox genes, which emerged prior to the divergence between cnidarians and bilaterians, are the most well-known members of the ancient genetic toolkit that controls embryonic development across all metazoans. Fundamental questions relative to their origin and evolutionary relationships remain however unresolved. We investigate here the evolution of metazoan Hox and ParaHox genes using the HoxPred program that allows the identification of Hox genes without the need of phylogenetic tree reconstructions.     

Quantitative assessment of DNA fragmentation and beta-amyloid deposition in insular cortex and midfrontal gyrus from patients with Alzheimer's disease

It has been suggested that the neurodegeneration that occurs with Alzheimer's disease (AD) may result from apoptosis, a process of programmed cell death. Neuronal injury, induced by abnormal aggregates of beta-amyloid peptide, has been identified as an apoptotic trigger. In the present study, brain tissue samples were obtained from the insular cortex (INS) and midfrontal gyrus (MFG) of Alzheimer subjects and age-matched, nondemented controls. Tissue sections from all samples were alternately stained by an in situ TUNEL assay to identify 3' termini DNA strand breaks characteristic of apoptosis or immunohistochemically for beta-amyloid deposition in senile plaques. The incidence of DNA fragmentation detected in pyramidal neurons was relatively infrequent overall, but was significantly higher in AD compared to controls. AD subjects consistently exhibited a dense accumulation of plaques, with a twofold greater concentration in MFG as INS. There was no significant difference in pyramidal cell number regardless of subject or brain region. Taken together, our results indicate that the TUNEL assay may be revealing cell damage rather than cell loss. Our finding of a moderate correlation between the incidence of TUNEL-positive cells and plaque density implicates beta-amyloid as one of multiple factors provoking cell injury in AD. A notable contribution of this study is the identification of distinctive neuropathologies co-occurring in two brain regions interconnected with each other and with limbic and cortical areas typically damaged during AD.     

Local Effect of Enhancer of Zeste-Like Reveals Cooperation of Epigenetic and cis-Acting Determinants for Zygotic Genome Rearrangements

In the ciliate Paramecium tetraurelia, differentiation of the somatic nucleus from the zygotic nucleus is characterized by massive and reproducible deletion of transposable elements and of 45,000 short, dispersed, single-copy sequences. A specific class of small RNAs produced by the germline during meiosis, the scnRNAs, are involved in the epigenetic regulation of DNA deletion but the underlying mechanisms are poorly understood. Here, we show that trimethylation of histone H3 (H3K27me3 and H3K9me3) displays a dynamic nuclear localization that is altered when the endonuclease required for DNA elimination is depleted. We identified the putative histone methyltransferase Ezl1 necessary for H3K27me3 and H3K9me3 establishment and show that it is required for correct genome rearrangements. Genome-wide analyses show that scnRNA-mediated H3 trimethylation is necessary for the elimination of long, repeated germline DNA, while single copy sequences display differential sensitivity to depletion of proteins involved in the scnRNA pathway, Ezl1- a putative histone methyltransferase and Dcl5- a protein required for iesRNA biogenesis. Our study reveals cis-acting determinants, such as DNA length, also contribute to the definition of germline sequences to delete. We further show that precise excision of single copy DNA elements, as short as 26 bp, requires Ezl1, suggesting that development specific H3K27me3 and H3K9me3 ensure specific demarcation of very short germline sequences from the adjacent somatic sequences.     

Deep sequencing reveals clonal evolution patterns and mutation events associated with relapse in B-cell lymphomas

Background

Molecular mechanisms associated with frequent relapse of diffuse large B-cell lymphoma (DLBCL) are poorly defined. It is especially unclear how primary tumor clonal heterogeneity contributes to relapse. Here, we explore unique features of B-cell lymphomas - VDJ recombination and somatic hypermutation - to address this question.

Results

We performed high-throughput sequencing of rearranged VDJ junctions in 14 pairs of matched diagnosis-relapse tumors, among which 7 pairs were further characterized by exome sequencing. We identify two distinctive modes of clonal evolution of DLBCL relapse: an early-divergent mode in which clonally related diagnosis and relapse tumors diverged early and developed in parallel; and a late-divergent mode in which relapse tumors developed directly from diagnosis tumors with minor divergence. By examining mutation patterns in the context of phylogenetic information provided by VDJ junctions, we identified mutations in epigenetic modifiers such as KMT2D as potential early driving events in lymphomagenesis and immune escape alterations as relapse-associated events.

Conclusions

Altogether, our study for the first time provides important evidence that DLBCL relapse may result from multiple, distinct tumor evolutionary mechanisms, providing rationale for therapies for each mechanism. Moreover, this study highlights the urgent need to understand the driving roles of epigenetic modifier mutations in lymphomagenesis, and immune surveillance factor genetic lesions in relapse.

Electronic supplementary material

The online version of this article (doi:10.1186/s13059-014-0432-0) contains supplementary material, which is available to authorized users.