Hyperacetylation in prostate cancer induces cell cycle aberrations, chromatin reorganization and altered gene expression profiles.

Histone acetylation is a fundamental mechanism in the regulation of local chromatin conformation and gene expression. Research has focused on the impact of altered epigenetic environments on the expression of specific genes and their pathways. However, changes in histone acetylation also have a global impact on the cell. In this study we used digital texture analysis to assess global chromatin patterns following treatment with trichostatin A (TSA) and have observed significant alterations in the condensation and distribution of higher-order chromatin, which were associated with altered gene expression profiles in both immortalised normal PNT1A prostate cell line and androgen-dependent prostate cancer cell line LNCaP. Furthermore, the extent of TSA-induced disruption was both cell cycle and cell line dependent. This was illustrated by the identification of sub-populations of prostate cancer cells expressing high levels of H3K9 acetylation in the G2/M phase of the cell cycle that were absent in normal cell populations. In addition, the analysis of enriched populations of G1 cells showed a global decondensation of chromatin exclusively in normal cells.

Immunobiosensor detection of domoic acid as a screening test in bivalve molluscs: Comparison with liquid chromatography-based analysis

A rapid and sensitive immuno-based screening method was developed to detect domoic acid (DA) present in extracts of shellfish species using a surface plasmon resonance-based optical biosensor. A rabbit polyclonal antibody raised against DA was mixed with standard or sample extracts and allowed to interact with DA immobilized onto a sensor chip surface. The characterization of the antibody strongly suggested high cross-reactivity with DA and important isomers of the toxin. The binding of this antibody to the sensor chip surface was inhibited in the presence of DA in either standard solutions or sample extracts. The DA chip surface proved to be highly stable, achieving approximately 800 analyses per chip without any loss of surface activity. A single analytical cycle (sample injection, chip regeneration, and system wash) took 10 min to complete. Sample analysis (scallops, mussels, cockles, oysters) was achieved by simple extraction with methanol. These extracts were then filtered and diluted before analysis. Detection limits in the ng/g range were achieved by the assay; however, the assay parameters chosen allowed the test to be performed most accurately at the European Union's official action limit for DA of 20 mu g/g. At this concentration, intra- and interassay variations were measured for a range of shellfish species and ranged from 4.5 to 7.4% and 2.3 to 9.7%, respectively.

From the UV to the static-field limit: rates and scaling laws of intense-field ionization of helium

We present high-accuracy calculations of ionization rates of helium at UV (195 nm) wavelengths. The data are obtained from full-dimensionality integrations of the helium-laser time-dependent Schrödinger equation. Comparison is made with our previously obtained data at 390 nm and 780 nm. We show that scaling laws introduced by Parker et al extend unmodified from the near-infrared limit into the UV limit. Static-field ionization rates of helium are also obtained, again from time-dependent full-dimensionality integrations of the helium Schrödinger equation. We compare the static-field ionization results with those of Scrinzi et al and Themelis et al, who also treat the full-dimensional helium atom, but with time-independent methods. Good agreement is obtained.

The vegetation and climate history of the last glacial cycle in a new pollen record from Lake Fimon (southern Alpine foreland, N-Italy)

The sediments of Like Fimon N Italy contain the first continuous archive of the Late Pleistocene environmental and climate history of the southern Alpine foreland We present here the detailed palynological record of the interval between Termination II and the List Glacial Maximum The age-depth model is obtained by radiocarbon dating in the uppermost part of the record Downward we con elated major forest expansion and contraction events to isotopic events in the Greenland Ice core records via a stepping-stone approach involving intermediate correlation to isotopic events dated by TIMS U/Th in Alpine and Apennine stalagmites and to pollen records from mime cores of the Iberian margin Modelled ages obtained by Bayesian analysis of deposition are thoroughly consistent with actual ages with maximum offset of +/- 1700 years Sharp expansion of broad-leaved temperate forest and of sudden water table rise mark the onset of the Last Interglacial after a treeless steppe phase at the end of penultimate glaciation This event is actually a two-step process which matches the two step rise observed in the isotopic record of the nearby Antro del Corchia stalagmite respectively dated to 132 5 +/- 2 5 and 129 +/- 1 5 ka At the interglacial decline mixed oak forests were replaced by oceanic mixed forests the latter persisting further for 7 ka till the end of the Eemian succession Warm-temperate woody species are still abundant at the Eemian end corroborating a steep gradient between central Europe and the Alpine divide at the inception of the last glacial After a stadial phase marked by moderate forest decline a new expansion of warm broad leaved forests interrupted by minor events and followed by mixed oceanic forests can be identified with the north-alpine Saint Germain I The spread of beech during the oceanic phase is a valuable circumalpine marker The subsequent stadial-interstadial succession lacking the telocratic oceanic phase is also consistent with the evidence at the north alpine foreland The Middle Wurmian (full glacial) is marked by persistence of mixed forests dominated by conifers but with significant lime and other broad leaved species A major Arboreal Pollen decrease is observed at modelled age of 38 7 +/- 0 5 ka (larch expansion and last occurrence of lime) which his been related to Heinrich Event 4 The evidence of afforestation persisting south of the Alps throughout most of MIS 3 contrasts with a boreal and continental landscape known for the northern alpine foreland pointing to a sharp rainfall boundary at the Alpine divide and to southern air circulation This is in agreement with the Alpine paleoglaciological record and is supported by the pressure and rainfall patterns designed by mesoscale paleoclimate simulations Strenghtening the continental high pressure during the full glacial triggered cyclogenesis in the middle latitude eastern Europe and orographic rainfall in the eastern Alps and the Balkanic mountains thus allowing forests development at current sea level altitudes (C) 2010 Elsevier Ltd All rights reserved

RNA polymerase I-specific subunits promote polymerase clustering to enhance the rRNA gene transcription cycle.

RNA polymerase I (Pol I) produces large ribosomal RNAs (rRNAs). In this study, we show that the Rpa49 and Rpa34 Pol I subunits, which do not have counterparts in Pol II and Pol III complexes, are functionally conserved using heterospecific complementation of the human and Schizosaccharomyces pombe orthologues in Saccharomyces cerevisiae. Deletion of RPA49 leads to the disappearance of nucleolar structure, but nucleolar assembly can be restored by decreasing ribosomal gene copy number from 190 to 25. Statistical analysis of Miller spreads in the absence of Rpa49 demonstrates a fourfold decrease in Pol I loading rate per gene and decreased contact between adjacent Pol I complexes. Therefore, the Rpa34 and Rpa49 Pol I–specific subunits are essential for nucleolar assembly and for the high polymerase loading rate associated with frequent contact between adjacent enzymes. Together our data suggest that localized rRNA production results in spatially constrained rRNA production, which is instrumental for nucleolar assembly.

The tumor suppressor gene DLEC1 is frequently silenced by DNA methylation in hepatocellular carcinoma and induces G1 arrest in cell cycle

Background/Aims: The chromosome locus 3p21.3 is a