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

On the Origin and Evolution of Life in the Galaxy

A simple stochastic model for evolution, based upon the need to pass a sequence of n critical steps (Carter 1983, Watson 2008) is applied to both terrestrial and extraterrestrial origins of life. In the former case, the time at which humans have emerged during the habitable period of the Earth suggests a value of n = 4. Progressively adding earlier evolutionary transitions (Maynard Smith and Szathmary, 1995) gives an optimum fit when n = 5, implying either that their initial transitions are not critical or that habitability began around 6 Ga ago. The origin of life on Mars or elsewhere within the Solar System is excluded by the latter case and the simple anthropic argument is that extraterrestrial life is scarce in the Universe because it does not have time to evolve. Alternatively, the timescale can be extended if the migration of basic progenotic material to Earth is possible. If extra transitions are included in the model to allow for Earth migration, then the start of habitability needs to be even earlier than 6 Ga ago. Our present understanding of Galactic habitability and dynamics does not exclude this possibility. We conclude that Galactic punctuated equilibrium (Cirkovic et al. 2009), proposed as a way round the anthropic problem, is not the only way of making life more common in the Galaxy.Comment: See http://www.astrobiologysociety.org/index.ph

A systematic review of the use of virtual reality and its effects on cognition in individuals with neurocognitive disorders

Introduction: Virtual reality (VR) interventions are increasingly used in individuals with brain injuries. The objective of this study was to determine the effects of VR on overall cognitive functioning in individuals with neurocognitive disorders (NCDs). Methods: Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review of the published literature on immersive and nonimmersive VR technologies targeting cognition in minor and major NCDs was conducted: (PROSPERO registration number: CRD42019121953). Results: A total of 22 studies were included in the review, for an aggregated sample of 564 individuals with NCDs. Most of the studies were conducted on patients who had stroke (27.3%), followed by mild cognitive impairment (22.7%) and Alzheimer's disease (13.6%). VR interventions used for cognitive rehabilitation suggested to improve cognition (e.g. memory, dual tasking, and visual attention), and secondarily to psychological functioning (e.g. reduction of anxiety, higher levels of well-being, and increased use of coping strategies). Conclusion: VR interventions are useful to improve cognition and psychological symptoms in NCDs

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

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

Foxp3 expression is associated with aggressiveness in differentiated thyroid carcinomas

OBJECTIVES: Forkhead box P3 (FoxP3) expression has been observed in human cancer cells but has not yet been reported in thyroid cells. We investigated the prognostic significance of both FoxP3 expression and intratumoral FoxP3+ lymphocyte infiltration in differentiated thyroid carcinoma cells. METHODS: We constructed a tissue microarray with 385 thyroid tissues, including 266 malignant tissues (from 253 papillary thyroid carcinomas and 13 follicular carcinomas), 114 benign lesions, and 5 normal thyroid tissues. RESULTS: We determined the expression of FoxP3 in both tumor cells and tumor-infiltrating lymphocytes using immunohistochemical techniques. Cellular expression of FoxP3 was evident in 71% of benign and 91.9% of malignant tissues. The nuclear and cytoplasmic expression patterns were quantified separately. A multivariate logistic regression analysis indicated that cytoplasmic FoxP3 expression is an independent risk factor for thyroid malignancy. Cytoplasmic FoxP3 staining was inversely correlated with patient age. Nuclear FoxP3 staining was more intense in younger patients and in tumors presenting with metastasis at diagnosis. FoxP3+ lymphocytes were more frequent in tumors smaller than 2 cm, those without extrathyroidal invasion, and in patients with concurrent chronic lymphocytic thyroiditis. CONCLUSIONS: We demonstrated FoxP3 expression in differentiated thyroid carcinoma cells and found evidence that this expression may exert an important influence on several features of tumor aggressiveness

Characterizing a collective and dynamic component of chromatin immunoprecipitation enrichment profiles in yeast

Background: Recent chromatin immunoprecipitation (ChIP) experiments in fly, mouse, and human have revealed the existence of high-occupancy target (HOT) regions or “hotspots” that show enrichment across many assayed DNA-binding proteins. Similar co-enrichment observed in yeast so far has been treated as artifactual, and has not been fully characterized. Results: Here we reanalyze ChIP data from both array-based and sequencing-based experiments to show that in the yeast S. cerevisiae, the collective enrichment phenomenon is strongly associated with proximity to noncoding RNA genes and with nucleosome depletion. DNA sequence motifs that confer binding affinity for the proteins are largely absent from these hotspots, suggesting that protein-protein interactions play a prominent role. The hotspots are condition-specific, suggesting that they reflect a chromatin state or protein state, and are not a static feature of underlying sequence. Additionally, only a subset of all assayed factors is associated with these loci, suggesting that the co-enrichment cannot be simply explained by a chromatin state that is universally more prone to immunoprecipitation. Conclusions: Together our results suggest that the co-enrichment patterns observed in yeast represent transcription factor co-occupancy. More generally, they make clear that great caution must be used when interpreting ChIP enrichment profiles for individual factors in isolation, as they will include factor-specific as well as collective contributions

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

A xylose-stimulated xylanase–xylose binding protein chimera created by random nonhomologous recombination

Additional file 3. Hot spot residues at the protein–protein interface between the XBP and XynA domains by molecular dynamics simulations