TTC5 is required to prevent apoptosis of acute myeloid leukemia stem cells

Using a screening strategy, we identified the tetratricopeptide repeat (TPR) motif protein, Tetratricopeptide repeat domain 5 (TTC5, also known as stress responsive activator of p300 or Strap) as required for the survival of human acute myeloid leukemia (AML) cells. TTC5 is a stress-inducible transcription cofactor known to interact directly with the histone acetyltransferase EP300 to augment the TP53 response. Knockdown (KD) of TTC5 induced apoptosis of both murine and human AML cells, with concomitant loss of clonogenic and leukemia-initiating potential; KD of EP300 elicited a similar phenotype. Consistent with the physical interaction of TTC5 and EP300, the onset of apoptosis following KD of either gene was preceded by reduced expression of BCL2 and increased expression of pro-apoptotic genes. Forced expression of BCL2 blocked apoptosis and partially rescued the clonogenic potential of AML cells following TTC5 KD. KD of both genes also led to the accumulation of MYC, an acetylation target of EP300, and the form of MYC that accumulated exhibited relative hypoacetylation at K148 and K157, residues targeted by EP300. In view of the ability of excess cellular MYC to sensitize cells to apoptosis, our data suggest a model whereby TTC5 and EP300 cooperate to prevent excessive accumulation of MYC in AML cells and their sensitization to cell death. They further reveal a hitherto unappreciated role for TTC5 in leukemic hematopoiesis

Amino acids and amino sugars in calcified tissues of portunid crabs

Amino acid and amino sugar in calcified tissues of portunid crab

The role of advocacy in promoting better child health

Child health professionals play a crucial role in advocating for children and it is incumbent on all who work with them to observe and enforce the maintenance of children's rights. In this article we summarise what advocacy is, its importance for child health and briefly how to go about it. Finally, we provide three differing examples of how advocacy has been used to improve the health of children

Recent ν\nus from IceCube

IceCube is a 1 km$^3$ neutrino detector now being built at the South Pole. Its 4800 optical modules will detect Cherenkov radiation from charged particles produced in neutrino interactions. IceCube will search for neutrinos of astrophysical origin, with energies from 100 GeV up to $10^{19}$ eV. It will be able to separate $\nu_e$, $\nu_\mu$ and $\nu_\tau$. In addition to detecting astrophysical neutrinos, IceCube will also search for neutrinos from WIMP annihilation in the Sun and the Earth, look for low-energy (10 MeV) neutrinos from supernovae, and search for a host of exotic signatures. With the associated IceTop surface air shower array, it will study cosmic-ray air showers. IceCube construction is now 50% complete. After presenting preliminary results from the partial detector, I will discuss IceCube's future plans.Comment: Invited talk presented at Neutrino 2008; 7 page

Long-Term Trends in Calcifying Plankton and pH in the North Sea

Relationships between six calcifying plankton groups and pH are explored in a highly biologically productive and data-rich area of the central North Sea using time-series datasets. The long-term trends show that abundances of foraminiferans, coccolithophores, and echinoderm larvae have risen over the last few decades while the abundances of bivalves and pteropods have declined. Despite good coverage of pH data for the study area there is uncertainty over the quality of this historical dataset; pH appears to have been declining since the mid 1990s but there was no statistical connection between the abundance of the calcifying plankton and the pH trends. If there are any effects of pH on calcifying plankton in the North Sea they appear to be masked by the combined effects of other climatic (e.g. temperature), chemical (nutrient concentrations) and biotic (predation) drivers. Certain calcified plankton have proliferated in the central North Sea, and are tolerant of changes in pH that have occurred since the 1950s but bivalve larvae and pteropods have declined. An improved monitoring programme is required as ocean acidification may be occurring at a rate that will exceed the environmental niches of numerous planktonic taxa, testing their capacities for acclimation and genetic adaptation

Circular No. 48, 1903. Oregon Short Line Railroad.

Circular concerning the annual meeting of the National Educational Association

MERLIN observations of relativistic ejections from GRS 1915+105

We present high resolution MERLIN radio images of multiple relativistic ejections from GRS 1915+105 in 1997 October / November. The observations were made at a time of complex radio behaviour, corresponding to multiple optically-thin outbursts and several days of rapid radio flux oscillations. The radio imaging resolved four major ejection events from the system. As previously reported from earlier VLA observations of the source, we observe apparent superluminal motions resulting from intrinsically relativistic motions of the ejecta. However, our measured proper motions are significantly greater than those observed on larger angular scales with the VLA. Under the assumption of an intrinsically symmetric ejection, we can place an upper limit on the distance to GRS 1915+105 of 11.2 +/- 0.8 kpc. Solutions for the velocities unambiguously require a higher intrinsic speed by about 0.1c than that derived from the earlier VLA observations, whilst the angle to the line-of-sight is not found to be significantly different. At a distance of 11 kpc, we obtain solutions of v = 0.98 (-0.05,+0.02)c and theta = 66 +/- 2 degrees. The jet also appears to be curved on a scale which corresponds to a period of around 7 days. We observe significant evolution of the linear polarisation of the approaching component, with large rotations in position angle and a general decrease in fractional polarisation. The power input into the formation of the jet is very large, >10^38 erg/s at 11 kpc for a pair plasma. If the plasma contains a cold proton for each electron, then the mass outflow rate, >10^18 g/sec is comparable to inflow rates previously derived from X-ray spectral fits.Comment: 14 pages, 7 figures. Accepted for publication in MNRA

Sedimentation study, Environmental Monitoring and Operations Guidance System (EMOGS), Kings Bay, Georgia and Florida : Phase III--FY 1989

Repeated side-scan sonar and multi-frequency bathymetric surveys, accompanied by accurate, high resolution, and repeatable navigation, were conducted in the vicinity of a tidal inlet to define the length and time scales associated with bedforms and channel shoaling in a structured tidal inlet. The study site, St. Mary's entrance channel along the Georgia/Florida border (Fig. I), has a dredged channel approximately 46-52 feet in depth, bordered by a large ebb tidal delta. The tidal inlet serves Cumberland Sound, Kings Bay, and associated waterways, providing a large discharge of water from the inlet that creates bedforms and channel shoaling, given the abundance of sand-sized sediment in the vicinity. The jettied inlet produces flows tht are predominately tidally-driven, whereas farther offshore the driving forces consist predominately of waves and storm-generated flows. In the channel reaches (Table 1) between these two areas, combined wave-steady flows are present, creating a myriad of scales of bedforms and shoaling patterns. This study was designed to elucidate the time and space scales of these variable bedforms and shoaling patterns, emphasizing the difference in these scales between the three different flow regimes. The results provide an important data base for quantifying shoaling processes and mechanisms in tidal inlet channels.Funding was provided by the National Oceanic Atmospheric Administration under Sea Grant No. NA860A-D-SG090