Analysis of HSC activity and compensatory Hox gene expression profile in Hoxb cluster mutant fetal liver cells

Overexpression of Hoxb4 in bone marrow cells promotes expansion of hematopoietic stem cell (HSC) populations in vivo and in vitro, indicating that this homeoprotein can activate the genetic program that determines self-renewal. However, this function cannot be solely attributed to Hoxb4 because Hoxb4(-/-) mice are viable and have an apparently normal HSC number. Quantitative polymerase chain reaction analysis showed that Hoxb4(-/-) c-Kit(+) fetal liver cells expressed moderately higher levels of several Hoxb cluster genes than control cells, raising the possibility that normal HSC activity in Hoxb4(-/-) mice is due to a compensatory up-regulation of other Hoxb genes. In this study, we investigated the competitive repopulation potential of HSCs lacking Hoxb4 alone, or in conjunction with 8 other Hoxb genes. Our results show that Hoxb4(-/-) and Hoxb1-b9(-/-) fetal liver cells retain full competitive repopulation potential and the ability to regenerate all myeloid and lymphoid lineages. Quantitative Hox gene expression profiling in purified c-KIt(+) Hoxb1-bg(-/-) fetal liver cells revealed an interaction between the Hoxa, b, and c clusters with variation in expression levels of Hoxa4, -a11, and -c4. Together, these studies show a complex network of genetic interactions between several Hox genes in primitive hematopoietic cells and demonstrate that HSCs lacking up to 30% of the active Hox genes remain fully competent.

HoxA cluster is haploinsufficient for activity of hematopoietic stem and progenitor cells

Functional compensation between homeodomain proteins has hindered the ability to unravel their role in hematopoiesis using single gene knockouts. Because HoxB genes are dispensable for hematopoiesis, and most HoxA genes are expressed an order of magnitude higher than other cluster genes in hematopoietic stem cell (HSC)-enriched populations, we hypothesize that maintenance of HoxA cluster expression is important for adult hematopoiesis and that global decrease of HoxA gene expression levels affects steady-state hematopoiesis.

A Cluster Randomized Controlled Trial of an Adapted U.S. Model of Pharmaceutical Care for Nursing Home Residents in Northern Ireland (Fleetwood Northern Ireland Study): A Cost-Effectiveness Analysis

OBJECTIVES: To evaluate the cost-effectiveness of an adapted U.S. model of pharmaceutical care to improve psychoactive prescribing for nursing home residents in Northern Ireland (Fleetwood NI Study).
DESIGN: Economic evaluation alongside a cluster randomized controlled trial.
SETTING: Nursing homes in NI randomized to intervention (receipt of the adapted model of care; n511) or control (usual care continued; n511).
PARTICIPANTS: Residents aged 65 and older who provided informed consent (N5253; 128 intervention, 125 control) and who had full resource use data at 12 months.
INTERVENTION: Trained pharmacists reviewed intervention home residents’ clinical and prescribing information for 12 months, applied an algorithm that guided them in assessing the appropriateness of psychoactive medication, and worked with prescribers (general practitioners) to make changes. The control homes received usual care in which there was no pharmacist intervention.
MEASUREMENTS: The proportion of residents prescribed one or more inappropriate psychoactive medications (according to standardized protocols), costs, and a cost-effectiveness acceptability curve. The latter two outcomes are the focus for this article.
RESULTS: The proportions of residents receiving inappropriate psychoactive medication at 12 months in the intervention and control group were 19.5% and 50.4%, respectively. The mean cost of healthcare resources used per resident per year was $4,923 (95% con?dence interval.

The synthesis and electronic structure of a novel [NiS4Fe2(CO)(6)] radical cluster: Implications for the active site of the [NiFe] hydrogenases

A novel [Ni'S-4'Fe-2(CO)(6)] cluster (1: 'S-4'=(CH3C6H3S2)(2)(CH2)(3)) has been synthesised, structurally characterised and has been shown to undergo a chemically reversible reduction process at -1.31 V versus Fc(+)/Fc to generate the EPR-active monoanion 1(-). Multifrequency Q-, X- and S-band EPR spectra of Ni-61-enriched 1(-) show a well-resolved quartet hyperfine splitting in the low-field region due to the interaction with a single Ni-61 (I = 3/2) nucleus. Simulations of the EPR spectra require the introduction of a single angle of non-coincidence between g, and A(1), and g(3) and A(3) to reproduce all of the features in the S- and X-band spectra. This behaviour provides a rare example of the detection and measurement of non-coincidence effects from frozen-solution EPR spectra without the need for single-crystal measurements, and in which the S-band experiment is sensitive to the non-coincidence. An analysis of the EPR spectra of 1(-) reveals a 24% Ni contribution to the SOMO in 1(-), supporting a delocalisation of the spin-density across the NiFe2 cluster. This observation is supported by IR spectroscopic results which show that the CO stretching frequencies, v(CO), shift to lower frequency by about 70 cm(-1) when 1 is reduced to 1(-). Density functional calculations provide a framework for the interpretation of the spectroscopic properties of 1(-) and suggest that the SOMO is delocalised over the whole cluster, but with little S-centre participation. This electronic structure contrasts with that of the Ni-A, -B, -C and -L forms of [NiFe] hydrogenase in which there is considerable S participation in the SOMO.

The birth place of the type Ic supernova 2007gr

We report our attempts to locate the progenitor of the peculiar Type Ic SN 2007gr in Hubble Space Telescope (HST) preexplosion images of the host galaxy, NGC 1058. Aligning adaptive optics Altair/NIRI imaging of SN 2007gr from the Gemini ( North) Telescope with the preexplosion HST WFPC2 images, we identify the supernova (SN) position on the HST frames with an accuracy of 20 mas. Although nothing is detected at the SN position, we show that it lies on the edge of a bright source 134 +/- 23 mas (6.9 pc) from its nominal center. On the basis of its luminosity, we suggest that this object is possibly an unresolved, compact, and coeval cluster and that the SN progenitor was a cluster member, although we note that model profile fitting favors a single bright star. We find two solutions for the age of this assumed cluster: 7 -/+ 0.5 Myr and 20 - 30 Myr, with turnoff masses of 28 +/- M-circle dot and 12 - 9 M-circle dot, respectively. Preexplosion ground-based K- band images marginally favor the younger cluster 4 age/higher turnoff mass. Assuming the SN progenitor was a cluster member, the turnoff mass provides the best estimate for its initial mass. More detailed observations, after the SN has faded, should determine whether the progenitor was indeed part of a cluster and, if so, allow an age estimate to within similar to 2 Myr, thereby favoring either a high-mass single star or lower-mass interacting binary progenitor.

The progenitor of SN 2005cs in the Whirlpool Galaxy

The progenitor of SN 2005cs, in the galaxy M51, is identified in pre-explosion Hubble Space Telescope (HST) Advanced Camera for Surveys (ACS) Wide Field Channel (WFC) imaging. Differential astrometry, with post-explosion ACS High Resolution Channel (HRC) F555W images, permitted the identification of the progenitor with an accuracy of 0.006 arcsec. The progenitor was detected in the F814W pre-explosion image with I = 23.3 +/- 0.2, but was below the detection thresholds of the F435W and F555W images, with B

The chemical composition of two supergiants in the dwarf irregular galaxy WLM

The chemical composition of two stars in WLM has been determined from high-quality Ultraviolet-Visual Echelle Spectrograph (UVES) data obtained at the VLT-UT2. The model atmospheres analysis shows that they have the same metallicity, [Fe/H] = - 0.38 +/- 0.20 (+/- 0.29). Reliable magnesium abundances are determined from several lines of two ionization states in both stars resulting in [Mg/Fe] = - 0.24 +/- 0.16 (+/- 0.28). This result suggests that the [alpha(Mg)/Fe] ratio in WLM may be suppressed relative to solar abundances ( also supported by differential abundances relative to similar stars in NGC 6822 and the Small Magellanic Cloud [SMC]). The absolute Mg abundance, [Mg/H] = -0.62, is high relative to what is expected from the nebulae though, where two independent spectroscopic analyses of the H II regions in WLM yield [O/H] = - 0.89. Intriguingly, the oxygen abundance determined from the O I lambda6158 feature in one WLM star is [O/H] = - 0.21 +/- 0.10 (+/- 0.05), corresponding to 5 times higher than the nebular oxygen abundance. This is the first time that a significant difference between stellar and nebular oxygen abundances has been found, and currently, there is no simple explanation for this difference. The two stars are massive supergiants with distances that clearly place them in WLM. They are young ( less than or equal to 10 Myr) and should have a similar composition to the ISM. Additionally, differential abundances suggest that the O/Fe ratio in the WLM star is consistent with similar stars in NGC 6822 and the SMC, galaxies where the average stellar oxygen abundances are in excellent agreement with the nebular results. If the stellar abundances reflect the true composition of WLM, then this galaxy lies well above the metallicity-luminosity relationship for dwarf irregular galaxies. It also suggests that WLM is more chemically evolved than currently interpreted from its color-magnitude diagram. The similarities between the stars in WLM and NGC 6822 suggest that these two galaxies may have had similar star formation histories.

Gemini observations of Wolf-Rayet stars in the Local Group starburst galaxy IC 10

We present Gemini-N GMOS and CFHT MOS spectroscopy of Wolf-Rayet candidates in the Local Group dwarf galaxy IC 10 that were previously identified by Massey et al. and Royer et al. From the present spectroscopic survey, the WC/WN ratio for IC 10 remains unusually high, given its low metallicity, although none of the WC9 stars suspected from narrow-band imaging are confirmed. Our spectroscopy confirms 9 newly discovered Wolf-Rayet candidates from Royer et al., whilst spectral types of 14 Wolf-Rayet stars previously observed by Massey & Armandroff are refined here. In total, there are 26 spectroscopically confirmed Wolf-Rayet stars in IC 10. All but one of the fourteen WC stars are WC4-6 stars, the exception being # 10 from Massey et al., a broad-lined, apparently single WC7 star. There are a total of eleven WN stars, which are predominantly early WN3-4 stars, but include a rare WN10 star, # 8 from Royer et al. # 5 from Massey et al. is newly identified as a transition WN/C star. Consequently, the WC/WN ratio for IC10 is 14/11similar to1.3, unusually high for a metal-poor galaxy. Re-evaluating recent photometric data of Massey & Holmes, we suggest that the true WC/WN ratio may not be as low as similar to0.3. Finally, we present ground-based finding charts for all confirmed WR stars, plus HST/WFPC2 charts for twelve cases.