Artemisinin-based combination therapy does not measurably reduce human infectiousness to vectors in a setting of intense malaria transmission

<p>Background: Artemisinin-based combination therapy (ACT) for treating malaria has activity against immature gametocytes. In theory, this property may complement the effect of terminating otherwise lengthy malaria infections and reducing the parasite reservoir in the human population that can infect vector mosquitoes. However, this has never been verified at a population level in a setting with intense transmission, where chronically infectious asymptomatic carriers are common and cured patients are rapidly and repeatedly re-infected.</p> <p>Methods: From 2001 to 2004, malaria vector densities were monitored using light traps in three Tanzanian districts. Mosquitoes were dissected to determine parous and oocyst rates. Plasmodium falciparum sporozoite rates were determined by ELISA. Sulphadoxinepyrimethamine(SP) monotherapy was used for treatment of uncomplicated malaria in the contiguous districts of Kilombero and Ulanga throughout this period. In Rufiji district, the standard drug was changed to artesunate co-administered with SP (AS + SP) in March 2003. The effects of this change in case management on malaria parasite infection in the vectors were analysed.</p> <p>Results: Plasmodium falciparum entomological inoculation rates exceeded 300 infective bites per person per year at both sites over the whole period. The introduction of AS + SP in Rufiji was associated with increased oocyst prevalence (OR [95%CI] = 3.9 [2.9-5.3], p < 0.001), but had no consistent effect on sporozoite prevalence (OR [95%CI] = 0.9 [0.7-1.2], p = 0.5). The estimated infectiousness of the human population in Rufiji was very low prior to the change in drug policy. Emergence rates and parous rates of the vectors varied substantially throughout the study period, which affected estimates of infectiousness. The latter consequently cannot be explained by the change in drug policy.</p> <p>Conclusions: In high perennial transmission settings, only a small proportion of infections in humans are symptomatic or treated, so case management with ACT may have little impact on overall infectiousness of the human population. Variations in infection levels in vectors largely depend on the age distribution of the mosquito population. Benefits of ACT in suppressingtransmission are more likely to be evident where transmission is already low or effective vector control is widely implemented.</p&gt

RR Lyrae Stars in the Andromeda Halo from Deep Imaging with the Advanced Camera for Surveys

We present a complete census of RR Lyrae stars in a halo field of the Andromeda galaxy. These deep observations, taken as part of a program to measure the star formation history in the halo, spanned a period of 41 days with sampling on a variety of time scales, enabling the identification of short and long period variables. Although the long period variables cannot be fully characterized within the time span of this program, the enormous advance in sensitivity provided by the Advanced Camera for Surveys on the Hubble Space Telescope allows accurate characterization of the RR Lyrae population in this field. We find 29 RRab stars with a mean period of 0.594 days, 25 RRc stars with a mean period of 0.316 days, and 1 RRd star with a fundamental period of 0.473 days and a first overtone period of 0.353 days. These 55 RR Lyrae stars imply a specific frequency S_RR=5.6, which is large given the high mean metallicity of the halo, but not surprising given that these stars arise from the old, metal-poor tail of the distribution. This old population in the Andromeda halo cannot be clearly placed into one of the Oosterhoff types: the ratio of RRc/RRabc stars is within the range seen in Oosterhoff II globular clusters, the mean RRab period is in the gap between Oosterhoff types, and the mean RRc period is in the range seen in Oosterhoff I globular clusters. The periods of these RR Lyraes suggest a mean metallicity of [Fe/H]=-1.6, while their brightness implies a distance modulus to Andromeda of 24.5+/-0.1, in good agreement with the Cepheid distance.Comment: 15 pages, latex. Accepted for publication in The Astronomical Journa

Delta-like and gtl2 are reciprocally expressed, differentially methylated linked imprinted genes on mouse chromosome 12

AbstractThe distal portion of mouse chromosome 12 is imprinted. To date, however, Gtl2 is the only imprinted gene identified on chromosome 12. Gtl2 encodes multiple alternatively spliced transcripts with no apparent open reading frame. Using conceptuses with maternal or paternal uniparental disomy for chromosome 12 (UPD12), we found that Gtl2 is expressed from the maternal allele and methylated at the 5′ end of the silent paternal allele. A reciprocally imprinted gene, Delta-like (Dlk), with homology to genes involved in the Notch signalling pathway was identified 80kb upstream of Gtl2. Dlk was expressed exclusively from the paternal allele in both the embryo and placenta, but the CpG-island promoter of Dlk was completely unmethylated on both parental alleles. Rather, a paternally methylated region was identified in the last exon of the active Dlk allele. The proximity, reciprocal imprinting and methylation in this domain are reminiscent of the co-ordinately regulated Igf2–H19 imprinted domain on mouse chromosome 7. Like H19 and Igf2, Gtl2 and Dlk were found to be co-expressed in the same tissues throughout development, though not after birth. These results have implications for the regulation, function and evolution of imprinted domains

The evolution of imprinting: chromosomal mapping of orthologues of mammalian imprinted domains in monotreme and marsupial mammals.

BACKGROUND: The evolution of genomic imprinting, the parental-origin specific expression of genes, is the subject of much debate. There are several theories to account for how the mechanism evolved including the hypothesis that it was driven by the evolution of X-inactivation, or that it arose from an ancestrally imprinted chromosome. RESULTS: Here we demonstrate that mammalian orthologues of imprinted genes are dispersed amongst autosomes in both monotreme and marsupial karyotypes. CONCLUSION: These data, along with the similar distribution seen in birds, suggest that imprinted genes were not located on an ancestrally imprinted chromosome or associated with a sex chromosome. Our results suggest imprinting evolution was a stepwise, adaptive process, with each gene/cluster independently becoming imprinted as the need arose.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Age Constraints for an M31 Globular Cluster from Main Sequence Photometry

We present a color-magnitude diagram (CMD) of the globular cluster SKHB-312 in the Andromeda galaxy (M31), obtained with the Advanced Camera for Surveys on the Hubble Space Telescope. The cluster was included in deep observations taken to measure the star formation history of the M31 halo. Overcoming a very crowded field, our photometry of SKHB-312 reaches V ~ 30.5 mag, more than 1 mag below the main sequence turnoff. These are the first observations to allow a direct age estimate from the turnoff in an old M31 cluster. We analyze its CMD and luminosity function using a finely-spaced grid of isochrones that have been calibrated using observations of Galactic clusters taken with the same camera and filters. The luminosity difference between the subgiant and horizontal branches is ~0.2 mag smaller in SKHB-312 than in the Galactic clusters 47 Tuc and NGC 5927, implying SKHB-312 is 2-3 Gyr younger. A quantitative comparison to isochrones yields an age of 10 +2.5/-1 Gyr

Marsupial chromosome DNA content and genome size assessed from flow karyotypes: invariable low autosomal GC content.

Extensive chromosome homologies revealed by cross-species chromosome painting between marsupials have suggested a high level of genome conservation during evolution. Surprisingly, it has been reported that marsupial genome sizes vary by more than 1.2 Gb between species. We have shown previously that individual chromosome sizes and GC content can be measured in flow karyotypes, and have applied this method to compare four marsupial species. Chromosome sizes and GC content were calculated for the grey short-tailed opossum (2n = 18), tammar wallaby (2n = 16), Tasmanian devil (2n = 14) and fat-tailed dunnart (2n = 14), resulting in genome sizes of 3.41, 3.31, 3.17 and 3.25 Gb, respectively. The findings under the same conditions allow a comparison between the four species, indicating that the genomes of these four species are 1-8% larger than human. We show that marsupial genomes are characterized by a low GC content invariable between autosomes and distinct from the higher GC content of the marsupial × chromosome

Far-Ultraviolet Emission from Elliptical Galaxies at z=0.33

We present far-ultraviolet (far-UV) images of the rich galaxy cluster ZwCl1358.1+6245, taken with the Space Telescope Imaging Spectrograph on board the Hubble Space Telescope (HST). When combined with archival HST observations, our data provide a measurement of the UV-to-optical flux ratio in 8 early-type galaxies at z=0.33. Because the UV flux originates in a population of evolved, hot, horizontal branch (HB) stars, this ratio is potentially one of the most sensitive tracers of age in old populations -- it is expected to fade rapidly with lookback time. We find that the UV emission in these galaxies, at a lookback time of 3.9 Gyr, is significantly weaker than it is in the current epoch, yet similar to that in galaxies at a lookback time of 5.6 Gyr. Taken at face value, these measurements imply different formation epochs for the massive ellipticals in these clusters, but an alternative explanation is a "floor" in the UV emission due to a dispersion in the parameters that govern HB morphology.Comment: 4 pages, Latex. 2 figures. Uses corrected version of emulateapj.sty and apjfonts.sty (included). Accepted for publication in ApJ Letter

The Dearth of UV-Bright Stars in M32: Implications for Stellar Evolution Theory

Using the Space Telescope Imaging Spectrograph on the Hubble Space Telescope, we have obtained deep far-ultraviolet images of the compact elliptical galaxy M32. When combined with earlier near-ultraviolet images of the same field, these data enable the construction of an ultraviolet color-magnitude diagram of the hot horizontal branch (HB) population and other hot stars in late phases of stellar evolution. We find few post-asymptotic giant branch (PAGB) stars in the galaxy, implying that these stars either cross the HR diagram more rapidly than expected, and/or that they spend a significant fraction of their time enshrouded in circumstellar material. The predicted luminosity gap between the hot HB and its AGB-Manque (AGBM) progeny is less pronounced than expected, especially when compared to evolutionary tracks with enhanced helium abundances, implying that the presence of hot HB stars in this metal-rich population is not due to (Delta Y)/(Delta Z) > 4. Only a small fraction (~2%) of the HB population is hot enough to produce significant UV emission, yet most of the UV emission in this galaxy comes from the hot HB and AGBM stars, implying that PAGB stars are not a significant source of UV emission even in those elliptical galaxies with a weak UV excess.Comment: Accepted for publication in The Astrophysical Journal. Latex, 18 pages, 18 black & white figures, in emulate-ApJ format. Figures 11 & 16 have been degraded due to size constraints; the high-quality version of the paper is at http://www.stsci.edu/~tbrown/research/m32fuv.pd