BIOCHEMICAL TAXONOMY OF MARINE PHYTOPLANKTON BY ELECTROPHORESIS OF ENZYMES. I. THE CENTRIC DIATOMS THALASSIOSIRA PSEUDONANA AND T. FLUVIATILIS1,2

Diatom systematics depends almost entirely upon structure of the silica shell. It is not known to what extent the taxonomic species, as defined by shell structure, corresponds to the genetic species—i.e., to the reproductively isolated population. As an approach to this problem, we report here a comparison of enzymes by electrophoresis. We have examined the genetic constitution of a number of clones of (presumably) the same species for each of 2 closely related, centric diatom species: Thalassiosira pseudonana Hasle and Heimdal and T. fluviatilis Hustedt. The 4 clones of T. fluviatilis form a distinct group, clearly separated from all the T. pseudonana clones. Within T. pseudonana, 4 estuarine clones and one reef clone form a group that is distinctly different from 4 oceanic clones. A single clone of T. pseudonana from the Continental Slope waters is intermediate between these 2 groups and probably shares genes with both groups, indicating that the 2 T. pseudonana groups are not genetically isolated. We conclude that i) within groups, isolates are closely related even though they originated from different continents; and, ii) T. pseudonana is subdivided into ecological races.     

TBX2 acts as a potent transcriptional silencer of tumour suppressor genes through interaction with the CoREST complex to sustain the proliferation of breast cancers

Chromosome 17q23 amplification occurs in 20% of primary breast tumours and is associated with poor outcome. The TBX2 gene is located on 17q23 and is often over-expressed in this breast tumour subset. TBX2 is an anti-senescence gene, promoting cell growth and survival through repression of Tumour Suppressor Genes (TSGs), such as NDRG1 and CST6. Previously we found that TBX2 cooperates with the PRC2 complex to repress several TSGs, and that PRC2 inhibition restored NDRG1 expression to impede cellular proliferation. Here, we now identify CoREST proteins, LSD1 and ZNF217, as novel interactors of TBX2. Genetic or pharmacological targeting of CoREST emulated TBX2 loss, inducing NDRG1 expression and abolishing breast cancer growth in vitro and in vivo. Furthermore, we uncover that TBX2/CoREST targeting of NDRG1 is achieved by recruitment of TBX2 to the NDRG1 promoter by Sp1, the abolishment of which resulted in NDRG1 upregulation and diminished cancer cell proliferation. Through ChIP-seq we reveal that 30% of TBX2-bound promoters are shared with ZNF217 and identify novel targets repressed by TBX2/CoREST; of these targets a lncRNA, LINC00111, behaves as a negative regulator of cell proliferation. Overall, these data indicate that inhibition of CoREST proteins represents a promising therapeutic intervention for TBX2-addicted breast tumours.     

ATM phosphorylates histone H2AX in response to DNA double-strand breaks

A very early step in the response of mammalian cells to DNA double-strand breaks is the phosphorylation of histone H2AX at serine 139 at the sites of DNA damage. Although the phosphatidylinositol 3-kinases, DNA-PK (DNA-dependent protein kinase), ATM (ataxia telangiectasia mutated), and ATR (ATM and Rad3-related), have all been implicated in H2AX phosphorylation, the specific kinase involved has not yet been identified. To definitively identify the specific kinase(s) that phosphorylates H2AX in vivo, we have utilized DNA-PKcs-/- and Atm-/- cell lines and mouse embryonic fibroblasts. We find that H2AX phosphorylation and nuclear focus formation are normal in DNA-PKcs-/- cells and severely compromised in Atm-/- cells. We also find that ATM can phosphorylate H2AX in vitro and that ectopic expression of ATM in Atm-/- fibroblasts restores H2AX phosphorylation in vivo. The minimal H2AX phosphorylation in Atm-/- fibroblasts can be abolished by low concentrations of wortmannin suggesting that DNA-PK, rather than ATR, is responsible for low levels of H2AX phosphorylation in the absence of ATM. Our results clearly establish ATM as the major kinase involved in the phosphorylation of H2AX and suggest that ATM is one of the earliest kinases to be activated in the cellular response to double-strand breaks.     

Information-Theoretic Analysis of Neural Coding

We describe an approach to analyzing single- and multiunit (ensemble) discharge patterns based on information-theoretic distance measures and on empirical theories derived from work in universal signal processing. In this approach, we quantify the difference between response patterns, whether time-varying or not, using information-theoretic distance measures. We apply these techniques to single- and multiple-unit processing of sound amplitude and sound location. These examples illustrate that neurons can simultaneously represent at least two kinds of information with different levels of fidelity. The fidelity can persist through a transient and a subsequent steady-state response, indicating that it is possible for an evolving neural code to represent information with constant fidelity.