10 research outputs found
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The scope of science for the International Polar Year, 2007-2008
The International Polar Year 2007““2008 will be the largest internationally coordinated research programme in 50 years. It will be an intensive period of interdisciplinary science focused on the Arctic and the Antarctic. IPY 2007““2008 research activities were assembled from the ideas of researchers in more than 60 countries. A total of 228 projects have been endorsed by the ICSU/WMO Joint Committee for IPY 2007““2008. These projects have a strong interdisciplinary emphasis and address the six themes as well as education and outreach objectives. IPY projects will exploit new technological and logistical capabilities and strengthen international coordination of research. They aim to attract, engage and develop a new generation of researchers and raise the awareness, interest and understanding of polar residents, educators, students, the general public and decision makers worldwide. IPY projects will collect a broad-ranging set of samples, data and information which will be made available to an unprecedented degree. IPY 2007““2008 aims to leave a legacy of enhanced observational systems, facilities and infrastructure. The observational networks to be established during IPY include integrated ocean observing systems in both the Arctic and Southern Oceans, coordinated acquisition of satellite data products from multiple space agencies and observational systems for astronomy, sun““earth physics, atmospheric chemistry, meteorology, ecosystems, permafrost, glaciers and geophysics. Many observing systems within IPY will be developed within the framework of existing international global observing systems
A review of the development of international science cooperation in the Arctic with a focus on IASC activities and its science priority projects (review)
In the brief review of the development of international science cooperation in the Arctic, a survey of the main historical events in the development of circumarctic science cooperation was given. It was pointed out that this development was closely linked to the geopolitical situation, as was the founding of the International Arctic Science Committee (IASC). A further survey of the IASC, its organisation, and with an emphasis on the science planning process and the science priority projects under development within IASC was given. This planning would then reach a milestone at the International Conference for Arctic Research Planning, organised by IASC, and held 5-9 December 1995 at Dartmouth College, Hanover, USA. This was a science planning conference bringing together both leading arctic scientists, science managers, and representatives from funding agencies and users
The pioneer factor activity of c-Myb involves recruitment of p300 and induction of histone acetylation followed by acetylation-induced chromatin dissociation
Background
The concept of pioneer transcription factors is emerging as an essential part of the epigenetic regulation, taking place during cell development and differentiation. However, the precise molecular mechanism underlying pioneer factor activity remains poorly understood. We recently reported that the transcription factor c-Myb acts as a pioneer factor in haematopoiesis, and a point mutation in its DNA binding domain, D152V, is able to abrogate this function.
Results
Here, we show that specific histone modifications, including H3K27ac, prevent binding of c-Myb to histone tails, representing a novel effect of histone modifications, namely restricting binding of a pioneer factor to chromatin. Furthermore, we have taken advantage of the pioneer-defect D152V mutant to investigate mechanisms of c-Myb’s pioneer factor activity. We show that c-Myb-dependent transcriptional activation of a gene in inaccessible chromatin relies on c-Myb binding to histones, as well as on c-Myb interacting with the histone acetyltransferase p300. ChIP assays show that both wild type and the D152V mutant of c-Myb bind to a selected target gene at its promoter and enhancer, but only wild-type c-Myb causes opening and activation of the locus. Enhancement of histone acetylation restores activation of the same gene in the absence of c-Myb, suggesting that facilitating histone acetylation is a crucial part of the pioneer factor function of c-Myb.
Conclusions
We suggest a pioneer factor model in which c-Myb binds to regions of closed chromatin and then recruits histone acetyltransferases. By binding to histones, c-Myb facilitates histone acetylation, acting as a cofactor for p300 at c-Myb bound sites. The resulting H3K27ac leads to chromatin opening and detachment of c-Myb from the acetylated chromatin. We propose that the latter phenomenon, acetylation-induced chromatin dissociation, represents a mechanism for controlling the dynamics of pioneer factor binding to chromatin
MOESM3 of The pioneer factor activity of c-Myb involves recruitment of p300 and induction of histone acetylation followed by acetylation-induced chromatin dissociation
Additional File 3: Figure S3. Isolated nuclei were extracted with 0.1% TX-100 and increasing NaCl concentrations, and soluble (S) and insoluble (P) nuclear fractions analysed by western blotting using anti-Ty antibodies to visualize c-Myb and c-Myb D152V. Densitometric analysis of salt extractions are shown in upper row for c-Myb (middle row) and c-Myb D152V (bottom row)
MOESM1 of The pioneer factor activity of c-Myb involves recruitment of p300 and induction of histone acetylation followed by acetylation-induced chromatin dissociation
Additional File 1: Figure S1. Peptide arrays containing 384 histone tail modification combinations incubated with GST-c-Myb-R3 (left) or GST-c-Myb-R3-D152V (right) and detected with anti-GST primary antibody
MOESM2 of The pioneer factor activity of c-Myb involves recruitment of p300 and induction of histone acetylation followed by acetylation-induced chromatin dissociation
Additional File 2: Figure S2. The same experiment as shown in Fig. 3, but here RNA was analysed for expression of lysozyme (LYZ, Gallus gallus (Chicken)) measured by qRT-PCR. The values of RNA expression were normalized to the relative amount of the reference gene hprt
Magnetic resonance volumetry: prediction of subjective memory complaints and mild cognitive impairment, and associations with genetic and cardiovascular risk factors
Background/Aims: Subjective memory complaints (SMC) are strong predictors of mild cognitive impairment (MCI) and subsequent Alzheimer’s disease. Our aims were to see if fully automated cerebral MR volume measurements could distinguish subjects with SMC and MCI from controls, and if probable parental late-onset Alzheimer’s disease (LOAD), apolipoprotein E ε4 genotype, total plasma homocysteine, and cardiovascular risk factors were associated with MR volumetric findings.
Methods: 198 stroke-free subjects comprised the control (n =58), the SMC (n = 25) and the MCI (n = 115) groups. Analysis of covariance and receiver operating
characteristic curve was used to see if MR volumetry distinguished subjects with SMC and MCI from controls.
Results: Subjects with SMC and MCI had significantly larger lateral ventricles and smaller hippocampal volumes than controls. The area under the curve in subjects with SMC and MCI compared to that of controls was less than 0.68 for all volumes of
intracranial structures. There was an interaction between sex and probable parental LOAD for hippocampal volume, with a significant association between probable parental LOAD and hippocampal volume in women.
Conclusions: Fully automated MR volumetry can distinguish
subjects with SMC and MCI from controls in a general population, but insufficiently to assume
a clear clinical role. Research on sporadic LOAD might benefit from a sex-specific search for
genetic risk factors