A central goal of evolutionary biology is to link genomic change to phenotypic evolution. The origin of new transcription factors is a special case of genomic evolution since it brings opportunities ...for novel regulatory interactions and potentially the emergence of new biological properties.
We demonstrate that a group of four homeobox gene families (Argfx, Leutx, Dprx, Tprx), plus a gene newly described here (Pargfx), arose by tandem gene duplication from the retinal-expressed Crx gene, followed by asymmetric sequence evolution. We show these genes arose as part of repeated gene gain and loss events on a dynamic chromosomal region in the stem lineage of placental mammals, on the forerunner of human chromosome 19. The human orthologues of these genes are expressed specifically in early embryo totipotent cells, peaking from 8-cell to morula, prior to cell fate restrictions; cow orthologues have similar expression. To examine biological roles, we used ectopic gene expression in cultured human cells followed by high-throughput RNA-seq and uncovered extensive transcriptional remodelling driven by three of the genes. Comparison to transcriptional profiles of early human embryos suggest roles in activating and repressing a set of developmentally-important genes that spike at 8-cell to morula, rather than a general role in genome activation.
We conclude that a dynamic chromosome region spawned a set of evolutionarily new homeobox genes, the ETCHbox genes, specifically in eutherian mammals. After these genes diverged from the parental Crx gene, we argue they were recruited for roles in the preimplantation embryo including activation of genes at the 8-cell stage and repression after morula. We propose these new homeobox gene roles permitted fine-tuning of cell fate decisions necessary for specification and function of embryonic and extra-embryonic tissues utilised in mammalian development and pregnancy.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Adeno-associated viruses (AAVs) are typically single-stranded deoxyribonucleic acid (ssDNA) encapsulated within 25-nm protein capsids. Recently, tissue-specific AAV capsids (e.g. PHP.eB) have been ...shown to enhance brain delivery in rodents via the LY6A receptor on brain endothelial cells. Here, we create a non-invasive positron emission tomography (PET) methodology to track viruses. To provide the sensitivity required to track AAVs injected at picomolar levels, a unique multichelator construct labeled with a positron emitter (Cu-64, t
= 12.7 h) is coupled to the viral capsid. We find that brain accumulation of the PHP.eB capsid 1) exceeds that reported in any previous PET study of brain uptake of targeted therapies and 2) is correlated with optical reporter gene transduction of the brain. The PHP.eB capsid brain endothelial receptor affinity is nearly 20-fold greater than that of AAV9. The results suggest that novel PET imaging techniques can be applied to inform and optimize capsid design.
Evaluations and value-based decisions are often accompanied by a feeling of confidence about whether or not the evaluation or decision is accurate. We argue that this feeling of confidence reflects ...the variation of an underlying value distribution and that this value distribution represents previously experienced values related to an object. Two preregistered experiments in which the variation of such value distributions was systematically varied provide causal evidence in favor of this hypothesis. A third preregistered experiment showed that, for natural food items with uncontrolled prior experiences, confidence in evaluations is again related to the variation of individuals' self-reported value distributions. Similarly, for choices between items, the variation of experienced values related to a choice pair influenced confidence in the perceived correctness of the choice. These findings converge with other domains of decision making showing that confidence tracks the variation of the underlying probability distribution of the evidence that a decision is based on, which in the case of value-based decisions, is informed by a value distribution reflecting priorly experienced values.
Strong size and internal density evolution of early-type galaxies between image and the present has been reported by several authors. Here we analyze samples of nearby and distant galaxies with ...dynamically measured masses in order to confirm the previous, model-dependent results and constrain the uncertainties that may play a role. Velocity dispersion ( capital sigma ) measurements are taken from the literature for 50 morphologically selected image field and cluster early-type galaxies with typical masses image. Sizes are determined with Advanced Camera for Surveys imaging. We compare the distant sample with a large sample of nearby early-type galaxies extracted from the Sloan Digital Sky Survey for which we determine sizes, masses, and densities in a consistent manner, using simulations to quantify systematic differences between the size measurements of nearby and distant galaxies. We find a highly significant difference between the image distributions of the nearby and distant samples, regardless of sample selection effects. The implied evolution in image at fixed mass between image and the present is a factor of image. This is in qualitative agreement with semianalytic models; however, the observed evolution is much faster than the predicted evolution. Our results reinforce and are quantitatively consistent with previous, photometric studies that found size evolution of up to a factor of 5 since image. A combination of structural evolution of individual galaxies through the accretion of companions and the continuous formation of early-type galaxies through increasingly gas-poor mergers is one plausible explanation of the observations.
Centrioles organize the centrosome, and accurate control of their number is critical for the maintenance of genomic integrity. Centriole duplication occurs once per cell cycle and is controlled by ...Polo-like kinase 4 (Plk4). We showed previously that Plk4 phosphorylates itself to promote its degradation by the proteasome. Here we demonstrate that this autoregulated instability controls the abundance of endogenous Plk4. Preventing Plk4 autoregulation causes centrosome amplification, stabilization of p53, and loss of cell proliferation; moreover, suppression of p53 allows growth of cells carrying amplified centrosomes. Plk4 autoregulation thus guards against genome instability by limiting centrosome duplication to once per cell cycle.
In the vertebrate central nervous system (CNS), mutual antagonism between posteriorly expressed
Gbx2 and anteriorly expressed
Otx2 positions the midbrain/hindbrain boundary (MHB), but does not induce ...MHB organizer genes such as
En,
Pax2/5/8 and
Wnt1. In the CNS of the cephalochordate amphioxus,
Otx is also expressed anteriorly, but
En,
Pax2/5/8 and
Wnt1 are not expressed near the caudal limit of
Otx, raising questions about the existence of an MHB organizer in amphioxus. To investigate the evolutionary origins of the MHB, we cloned the single amphioxus
Gbx gene. Fluorescence in situ hybridization showed that, as in vertebrates, amphioxus
Gbx and the
Hox cluster are on the same chromosome. From analysis of linked genes, we argue that during evolution a single ancestral
Gbx gene duplicated fourfold in vertebrates, with subsequent loss of two duplicates. Amphioxus
Gbx is expressed in all germ layers in the posterior 75% of the embryo, and in the CNS, the
Gbx and
Otx domains abut at the boundary between the cerebral vesicle (forebrain/midbrain) and the hindbrain. Thus, the genetic machinery to position the MHB was present in the protochordate ancestors of the vertebrates, but is insufficient for induction of organizer genes. Comparison with hemichordates suggests that anterior
Otx and posterior
Gbx domains were probably overlapping in the ancestral deuterostome and came to abut at the MHB early in the chordate lineage before MHB organizer properties evolved.
Re-ionization of the intergalactic medium occurred in the early Universe at redshift z ≈ 6-11, following the formation of the first generation of stars. Those young galaxies (where the bulk of stars ...formed) at a cosmic age of less than about 500 million years (z ≲ 10) remain largely unexplored because they are at or beyond the sensitivity limits of existing large telescopes. Understanding the properties of these galaxies is critical to identifying the source of the radiation that re-ionized the intergalactic medium. Gravitational lensing by galaxy clusters allows the detection of high-redshift galaxies fainter than what otherwise could be found in the deepest images of the sky. Here we report multiband observations of the cluster MACS J1149+2223 that have revealed (with high probability) a gravitationally magnified galaxy from the early Universe, at a redshift of z = 9.6 ± 0.2 (that is, a cosmic age of 490 ± 15 million years, or 3.6 per cent of the age of the Universe). We estimate that it formed less than 200 million years after the Big Bang (at the 95 per cent confidence level), implying a formation redshift of ≲14. Given the small sky area that our observations cover, faint galaxies seem to be abundant at such a young cosmic age, suggesting that they may be the dominant source for the early re-ionization of the intergalactic medium.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Opsin proteins covalently bind to small molecular chromophores and each protein-chromophore complex is sensitive to particular wavelengths of light. Multiple opsins with different wavelength ...absorbance peaks are required for color vision. Comparing opsin responses is challenging at low light levels, explaining why color vision is often lost in nocturnal species. Here, we investigated opsin evolution in 27 phylogenetically diverse insect species including several transitions between photic niches (nocturnal, diurnal, and crepuscular). We find widespread conservation of five distinct opsin genes, more than commonly considered. These comprise one c-opsin plus four r-opsins (long wavelength sensitive or LWS, blue sensitive, ultra violet UV sensitive and the often overlooked Rh7 gene). Several recent opsin gene duplications are also detected. The diversity of opsin genes is consistent with color vision in diurnal, crepuscular, and nocturnal insects. Tests for positive selection in relation to photic niche reveal evidence for adaptive evolution in UV-sensitive opsins in day-flying insects in general, and in LWS opsins of day-flying Lepidoptera specifically.
The Swift-BAT Hard X-Ray Transient Monitor Krimm, H. A.; Holland, S. T.; Corbet, R. H. D. ...
The Astrophysical journal. Supplement series,
11/2013, Letnik:
209, Številka:
1
Journal Article
Recenzirano
Odprti dostop
The Swift/Burst Alert Telescope (BAT) hard X-ray transient monitor provides near real-time coverage of the X-ray sky in the energy range 15-50 keV. The BAT observes 88% of the sky each day with a ...detection sensitivity of 5.3 mCrab for a full-day observation and a time resolution as fine as 64 s. The three main purposes of the monitor are (1) the discovery of new transient X-ray sources, (2) the detection of outbursts or other changes in the flux of known X-ray sources, and (3) the generation of light curves of more than 900 sources spanning over eight years. The primary interface for the BAT transient monitor is a public Web site. Between 2005 February 12 and 2013 April 30, 245 sources have been detected in the monitor, 146 of them persistent and 99 detected only in outburst. Among these sources, 17 were previously unknown and were discovered in the transient monitor. In this paper, we discuss the methodology and the data processing and filtering for the BAT transient monitor and review its sensitivity and exposure.We provide a summary of the source detections and classify them according to the variability of their light curves. Finally, we review all new BAT monitor discoveries. For the new sources that are previously unpublished, we present basic data analysis and interpretations.
A suboptimal early-life environment, due to poor nutrition or stress during pregnancy, can influence lifelong phenotypes in the progeny. Epigenetic factors are thought to be key mediators of these ...effects. We show that protein restriction in mice from conception until weaning induces a linear correlation between growth restriction and DNA methylation at ribosomal DNA (rDNA). This epigenetic response remains into adulthood and is restricted to rDNA copies associated with a specific genetic variant within the promoter. Related effects are also found in models of maternal high-fat or obesogenic diets. Our work identifies environmentally induced epigenetic dynamics that are dependent on underlying genetic variation and establishes rDNA as a genomic target of nutritional insults.
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