Evidence of Abundant Purifying Selection in Humans for Recently Acquired Regulatory Functions

Although only 5% of the human genome is conserved across mammals, a substantially larger portion is biochemically active, raising the question of whether the additional elements evolve neutrally or confer a lineage-specific fitness advantage. To address this question, we integrate human variation information from the 1000 Genomes Project and activity data from the ENCODE Project. A broad range of transcribed and regulatory nonconserved elements show decreased human diversity, suggesting lineage-specific purifying selection. Conversely, conserved elements lacking activity show increased human diversity, suggesting that some recently became nonfunctional. Regulatory elements under human constraint in nonconserved regions were found near color vision and nerve-growth genes, consistent with purifying selection for recently evolved functions. Our results suggest continued turnover in regulatory regions, with at least an additional 4% of the human genome subject to lineage-specific constraint.National Institutes of Health (U.S.) (Grant R01HG004037)National Institutes of Health (U.S.) (Grant RC1HG005334)National Science Foundation (U.S.) (CAREER Grant 0644282

Targeted Disruption of TgPhIL1 in Toxoplasma gondii Results in Altered Parasite Morphology and Fitness

The inner membrane complex (IMC), a series of flattened vesicles at the periphery of apicomplexan parasites, is thought to be important for parasite shape, motility and replication, but few of the IMC proteins that function in these processes have been identified. TgPhIL1, a Toxoplasma gondii protein that was previously identified through photosensitized labeling with 5-[125I] iodonapthaline-1-azide, associates with the IMC and/or underlying cytoskeleton and is concentrated at the apical end of the parasite. Orthologs of TgPhIL1 are found in other apicomplexans, but the function of this conserved protein family is unknown. As a first step towards determining the function of TgPhIL1 and its orthologs, we generated a T. gondii parasite line in which the single copy of TgPhIL1 was disrupted by homologous recombination. The TgPhIL1 knockout parasites have a distinctly different morphology than wild-type parasites, and normal shape is restored in the knockout background after complementation with the wild-type allele. The knockout parasites are outcompeted in culture by parasites expressing functional TgPhIL1, and they generate a reduced parasite load in the spleen and liver of infected mice. These findings demonstrate a role for TgPhIL1 in the morphology, growth and fitness of T. gondii tachyzoites

The Circumstellar Disk of the Butterfly Star in Taurus

We present a model of the circumstellar environment of the so-called ``Butterfly Star'' in Taurus (IRAS 04302+2247). The appearance of this young stellar object is dominated by a large circumstellar disk seen edge-on and the light scattering lobes above the disk. The model is based on multi-wavelength continuum observations: Millimeter maps and high-resolution near-infrared images obtained with HST/NICMOS. It was found that the disk and envelope parameters are comparable with those of the circumstellar environment of other young stellar objects. A main result is that the dust properties must be different in the circumstellar disk and in the envelope: While a grain size distribution with grain radii up to 100 micron is required to reproduce the millimeter observations of the disk, the envelope is dominated by smaller grains similar to those of the interstellar medium. Preprint with high figure quality available at: http://spider.ipac.caltech.edu/staff/swolf/homepage/public/preprints/i04302.psComment: 32 pages, 9 figure

The political economy of competitiveness and social mobility

Social mobility has become a mainstream political and media issue in recent years in the United Kingdom. This article suggests that part of the reason for this is that it can serve as a mechanism to discuss policy concerns that appear to be about social justice without questioning important aspects of neo-liberal political economy. The article charts the policy rhetoric on social mobility under both New Labour and the current Coalition Government. It is argued first that under New Labour the apparent commitment to social mobility was in fact subsumed beneath the pursuit of neo-liberal competitiveness, albeit imperfectly realised in policy. Second, the article suggests that under the Coalition Government the commitment to raising levels of social mobility has been retained and the recently published Strategy for Social Mobility promises that social mobility is what the Coalition means when it argues that the austerity programme is balanced with ‘fairness’. Third, however, the Strategy makes clear that the Coalition define social mobility in narrower terms than the previous government. It is argued here that in narrowing the definition the connection with the idea of competitiveness, while still clearly desirable for the Coalition, is weakened. Fourth, a brief analysis of the Coalition's main policy announcements provides little evidence to suggest that even the narrow definition set out in the Strategy is being seriously pursued. Fifth, the international comparative evidence suggests that any strategy aimed at genuinely raising the level of social mobility would need to give much more serious consideration to narrowing levels of inequality. Finally, it is concluded that when considered in the light of the arguments above, the Strategy for Social Mobility – and therefore ‘Fairness’ itself – is merely a discursive legitimation of the wider political economy programme of austerity

The Spitzer Gould Belt Survey of Large Nearby Interstellar Clouds: Discovery of A Dense Embedded Cluster in the Serpens-Aquila Rift

We report the discovery of a nearby, embedded cluster of young stellar objects, associated filamentary infrared dark cloud, and 4.5 mu m shock emission knots from outflows detected in Spitzer IRAC mid-infrared imaging of the Serpens-Aquila Rift obtained as part of the Spitzer Gould Belt Legacy Survey. We also present radial velocity measurements of the region from molecular line observations obtained with the Submillimeter Array (SMA) that suggest the cluster is comoving with the Serpens Main embedded cluster to the north. We therefore assign it 3 degrees the same distance, 260 pc. The core of the new cluster, which we call Serpens South, is composed of an unusually large fraction of protostars (77%) at high mean surface density (> 430 pc(-2)) and short median nearest neighbor spacing (3700 AU). We perform basic cluster structure characterization using nearest neighbor surface density mapping of the YSOs and compare our findings to other known clusters with equivalent analyses available in the literature.Astronom

Systematic Molecular Differentiation in Starless Cores

(Abridged) We present evidence that low-mass starless cores, the simplest units of star formation, are systematically differentiated in their chemical composition. Molecules including CO and CS almost vanish near the core centers, where the abundance decreases by one or two orders of magnitude. At the same time, N2H+ has a constant abundance, and the fraction of NH3 increases toward the core center. Our conclusions are based on a study of 5 mostly-round starless cores (L1498, L1495, L1400K, L1517B, and L1544), which we have mappedin C18O(1-0), C17O(1-0), CS(2-1), C34S(2-1), N2H+(1-0), NH3(1,1) and (2,2), and the 1.2 mm continuum. For each core we have built a model that fits simultaneously the radial profile of all observed emission and the central spectrum for the molecular lines. The observed abundance drops of CO and CS are naturally explained by the depletion of these molecules onto dust grains at densities of 2-6 10^4 cm-3. N2H+ seems unaffected by this process up to densities of several 10^5, while the NH3 abundance may be enhanced by reactions triggered by the disappearance of CO from the gas phase. With the help of our models, we show that chemical differentiation automatically explains the discrepancy between the sizes of CS and NH3 maps, a problem which has remained unexplained for more than a decade. Our models, in addition, show that a combination of radiative transfer effects can give rise to the previously observed discrepancy in the linewidth of these two tracers. Although this discrepancy has been traditionally interpreted as resulting from a systematic increase of the turbulent linewidth with radius, our models show that it can arise in conditions of constant gas turbulence.Comment: 25 pages, 9 figures, accepted by Ap

Electronic response of aligned multishell carbon nanotubes

We report calculations of the effective electronic response of aligned multishell carbon nanotubes. A local graphite-like dielectric tensor is assigned to every point of the multishell tubules, and the effective transverse dielectric function of the composite is computed by solving Maxwell's equations. Calculations of both real and imaginary parts of the effective dielectric function are presented, for various values of the filling fraction and the ratio of the internal and external radii of hollow tubules. Our full calculations indicate that the experimentally measured macroscopic dielectric function of carbon nanotube materials is the result of a strong electromagnetic coupling between the tubes, which cannot be accounted for with the use of simplified effective medium theories. The presence of surface plasmons is investigated, and both optical absorption cross sections and energy-loss spectra of aligned tubules are calculated.Comment: 4 pages, 4 figures, to appear in Phys. Rev.

The structure of protostellar envelopes derived from submillimeter continuum images

High dynamic range imaging of submillimeter dust emission from the envelopes of eight young protostars in the Taurus and Perseus star-forming regions has been carried out using the SCUBA submillimeter camera on the James Clerk Maxwell Telescope. Good correspondence between the spectral classifications of the protostars and the spatial distributions of their dust emission is observed, in the sense that those with cooler spectral energy distributions also have a larger fraction of the submillimeter flux originating in an extended envelope compared with a disk. This results from the cool sources having more massive envelopes rather than warm sources having larger disks. Azimuthally-averaged radial profiles of the dust emission are used to derive the power-law index of the envelope density distributions, p (defined by rho proportional to r^-p), and most of the sources are found to have values of p consistent with those predicted by models of cloud collapse. However, the youngest protostars in our sample, L1527 and HH211-mm, deviate significantly from the theoretical predictions, exhibiting values of p somewhat lower than can be accounted for by existing models. For L1527 heating of the envelope by shocks where the outflow impinges on the surrounding medium may explain our result. For HH211-mm another explanation is needed, and one possibility is that a shallow density profile is being maintained in the outer envelope by magnetic fields and/or turbulence. If this is the case star formation must be determined by the rate at which the support is lost from the cloud, rather than the hydrodynamical properties of the envelope, such as the sound speed.Comment: Accepted for publication in the Astrophysical Journa

A shallow though extensive H2 2.12 micron imaging survey of Taurus-Auriga-Perseus: I. NGC1333, L1455, L1448 and B1

We discuss wide-field near-IR imaging of the NGC1333, L1448, L1455 and B1 star forming regions in Perseus. The observations have been extracted from a much larger narrow-band imaging survey of the Taurus-Auriga-Perseus complex. These H2 2.12 micron observations are complemented by broad-band K imaging, mid-IR imaging and photometry from the Spitzer Space Telescope, and published submillimetre CO J=3-2 maps of high-velocity molecular outflows. We detect and label 85 H2 features and associate these with 26 molecular outflows. Three are parsec-scale flows, with a mean flow lobe length exceeding 11.5 arcmin. 37 (44%) of the detected H2 features are associated with a known Herbig-Haro object, while 72 (46%) of catalogued HH objects are detected in H2 emission. Embedded Spitzer sources are identified for all but two of the 26 molecular outflows. These candidate outflow sources all have high near-to-mid-IR spectral indices (mean value of alpha ~ 1.4) as well as red IRAC 3.6-4.5 micron and IRAC/MIPS 4.5-24.0 micron colours: 80% have [3.6]-[4.5] > 1.0 and [4.5]-[24] > 1.5. These criteria - high alpha and red [4.5]-[24] and [3.6]-[4.5] colours - are powerful discriminants when searching for molecular outflow sources. However, we find no correlation between alpha and flow length or opening angle, and the outflows appear randomly orientated in each region. The more massive clouds are associated with a greater number of outflows, which suggests that the star formation efficiency is roughly the same in each region.Comment: 23 pages (including Appoendix); 11 main text figures, 5 colour appendix figs uploaded as gifs; accepted by MNRAS; for higher-resolution figures please visit http://www.jach.hawaii.edu/~cdavis

Defining functional DNA elements in the human genome

With the completion of the human genome sequence, attention turned to identifying and annotating its functional DNA elements. As a complement to genetic and comparative genomics approaches, the Encyclopedia of DNA Elements Project was launched to contribute maps of RNA transcripts, transcriptional regulator binding sites, and chromatin states in many cell types. The resulting genome-wide data reveal sites of biochemical activity with high positional resolution and cell type specificity that facilitate studies of gene regulation and interpretation of noncoding variants associated with human disease. However, the biochemically active regions cover a much larger fraction of the genome than do evolutionarily conserved regions, raising the question of whether nonconserved but biochemically active regions are truly functional. Here, we review the strengths and limitations of biochemical, evolutionary, and genetic approaches for defining functional DNA segments, potential sources for the observed differences in estimated genomic coverage, and the biological implications of these discrepancies. We also analyze the relationship between signal intensity, genomic coverage, and evolutionary conservation. Our results reinforce the principle that each approach provides complementary information and that we need to use combinations of all three to elucidate genome function in human biology and disease