Genetic studies of human evolution require high-quality contiguous ape genome assemblies that are not guided by the human reference. We coupled long-read sequence assembly and full-length ...complementary DNA sequencing with a multiplatform scaffolding approach to produce ab initio chimpanzee and orangutan genome assemblies. By comparing these with two long-read de novo human genome assemblies and a gorilla genome assembly, we characterized lineage-specific and shared great ape genetic variation ranging from single- to mega-base pair-sized variants. We identified ~17,000 fixed human-specific structural variants identifying genic and putative regulatory changes that have emerged in humans since divergence from nonhuman apes. Interestingly, these variants are enriched near genes that are down-regulated in human compared to chimpanzee cerebral organoids, particularly in cells analogous to radial glial neural progenitors.
Adult Leydig cell steroidogenesis is dependent on LH but fetal Leydig cells can function independently of gonadotropin stimulation. To identify factors that may be involved in regulation of fetal ...Leydig cells expressed sequence tag libraries from fetal and adult testes were compared, and fetal-specific genes identified. The ACTH receptor melanocortin type 2 receptor (Mc2r) was identified within this fetal-specific group. Subsequent real-time PCR studies confirmed that Mc2r was expressed in the fetal testis at 100-fold higher levels than in the adult testis. Incubation of fetal or neonatal testes with ACTH in vitro stimulated testosterone production more than 10-fold, although ACTH had no effect on testes from animals aged 20 d or older. The steroidogenic response of fetal and neonatal testes to a maximally stimulating dose of human chorionic gonadotropin was similar to the response shown to ACTH. The ED50 for ACTH, measured in isolated fetal and neonatal testicular cells, was 5 × 10−10 m and the lowest dose of ACTH eliciting a response was 2 × 10−11 m. Circulating ACTH levels in fetal mice were around 8 × 10−11 m. Neither α-MSH nor γ-MSH had any effect on androgen production in vitro at any age. Fetal testosterone levels were normal in mice that lack circulating ACTH (proopiomelanocortin-null) indicating that ACTH is not essential for fetal Leydig cell function. Results show that both LH and ACTH can regulate testicular steroidogenesis during fetal development in the mouse and suggest that fetal Leydig cells, but not adult Leydig cells, are sensitive to ACTH stimulation.
Developmental changes in the expression of 18 Leydig cell-specific mRNA species were measured by real-time polymerase chain
reaction to partially characterize the developmental phenotype of the cells ...in the mouse and to identify markers of adult
Leydig cell differentiation. Testicular interstitial webs were isolated from mice between birth and adulthood. Five developmental
patterns of gene expression were observed. Group 1 contained mRNA species encoding P450 side chain cleavage (P450 scc ), P450 c17 , relaxin-like factor (RLF), glutathione S-transferase 5-5 (GST5-5), StAR protein, LH receptor, and epoxide hydrolase (EH);
group 2 contained 3β-hydroxysteroid dehydrogenase (3β-HSD) VI, 17β-hydroxysteroid dehydrogenase (17β-HSD) III, vascular cell
adhesion molecule 1, estrogen sulfotransferase, and prostaglandin D (PGD)-synthetase; group 3 contained patched and thrombospondin
2 (TSP2); group 4 contained 5α-reductase 1 and 3α-hydroxysteroid dehydrogenase; group 5 contained sulfonylurea receptor 2
and 3β-HSD I. Group 1 contained genes that were expressed in fetal and adult Leydig cells and which increased in expression
around puberty toward a maximum in the adult. Group 2 contained genes expressed only in the adult Leydig cell population.
Group 3 contained genes with predominant fetal/neonatal expression in the interstitial tissue. Group 4 contained genes with
a peak of expression around puberty, whereas genes in group 5 show little developmental change in expression. Highest mRNA
levels in descending order were RLF , P450 c17 , EH , 17β-HSD III , PGD-synthetase , GST5-5 , and P450 scc . Results identify five genes expressed in the mouse adult Leydig cell population, but not in the fetal population, and one
gene ( TSP2 ) that may be expressed only in the fetal Leydig cell population. The developmental pattern of gene expression suggests that
three distinct phases of adult Leydig cell differentiation occur.
Sirtuin-1 (SIRT1) and SIRT6, NAD
-dependent Class III protein deacetylases, are putative anti-aging enzymes, down-regulated in patients with chronic obstructive pulmonary disease (COPD), which is ...characterized by the accelerated ageing of the lung and associated with increased oxidative stress. Here, we show that oxidative stress (hydrogen peroxide) selectively elevates microRNA-34a (miR-34a) but not the related miR-34b/c, with concomitant reduction of SIRT1/-6 in bronchial epithelial cells (BEAS2B), which was also observed in peripheral lung samples from patients with COPD. Over-expression of a miR-34a mimic caused a significant reduction in both mRNA and protein of SIRT1/-6, whereas inhibition of miR-34a (antagomir) increased these sirtuins. Induction of miR-34a expression with H
O
was phosphoinositide-3-kinase (PI3K) dependent as it was associated with PI3Kα activation as well as phosphatase and tensin homolog (PTEN) reduction. Importantly, miR-34a antagomirs increased SIRT1/-6 mRNA levels, whilst decreasing markers of cellular senescence in airway epithelial cells from COPD patients, suggesting that this process is reversible. Other sirtuin isoforms were not affected by miR-34a. Our data indicate that miR-34a is induced by oxidative stress via PI3K signaling, and orchestrates ageing responses under oxidative stress, therefore highlighting miR-34a as a new therapeutic target and biomarker in COPD and other oxidative stress-driven aging diseases.
Abstract
We present a study using the Karl G. Jansky Very Large Array (VLA) of 12CO J = 1−0 emission in three strongly lensed submillimetre-selected galaxies (SMMJ16359, SMMJ14009 and SMMJ02399) at z ...= 2.5-2.9. These galaxies span L
IR = 1011-1013L⊙, offering an opportunity to compare the interstellar medium of luminous infrared galaxies and ultraluminous infrared galaxies at high redshift. We estimate molecular gas masses in the range of 2-40 × 109M⊙ using a method that assumes canonical underlying brightness temperature (T
b) ratios for star-forming and non-star-forming gas phases and a maximal star formation efficiency. A more simplistic method - using X
CO = 0.8 and the measured T
b ratios - yields gas masses twice as high. In SMMJ14009 we find , indicative of warm, star-forming gas, possibly influenced by the central active galactic nucleus (AGN). We set a gas mass limit of 3σ < 6 × 108M⊙ for the Lyman break galaxy, A2218 #384, located in the same field as SMMJ16359 at z = 2.515. Finally, we use the rest-frame ∼115GHz free-free flux densities for SMMJ14009 and SMMJ02399 - measurements tied directly to the photoionization rate of massive stars, and made possible by VLA's bandwidth - to estimate star formation rates (SFRs) of 400-600M⊙yr−1 and to estimate the fraction of L
IR due to AGN.
Panchromatic observations of the best candidate hyperluminous infrared galaxies from the widest Herschel extragalactic imaging survey have led to the discovery of at least four intrinsically luminous ...z = 2.41 galaxies across an approximately 100 kpc region-a cluster of starbursting protoellipticals. Via subarcsecond interferometric imaging we have measured accurate gas and star formation surface densities. The two brightest galaxies span ~3 kpc FWHM in submillimeter/radio continuum and CO J = 4-3, and double that in CO J = 1-0. The broad CO line is due partly to the multitude of constituent galaxies and partly to large rotational velocities in two counter-rotating gas disks-a scenario predicted to lead to the most intense starbursts, which will therefore come in pairs. The disks have M sub(dyn) of several x 10 super(11) M sub(middot in circle) and gas fractions of ~40%. Velocity dispersions are modest so the disks are unstable, potentially on scales commensurate with their radii: these galaxies are undergoing extreme bursts of star formation, not confined to their nuclei, at close to the Eddington limit. Their specific star formation rates place them gap 5x above the main sequence, which supposedly comprises large gas disks like these. Their high star formation efficiencies are difficult to reconcile with a simple volumetric star formation law. N-body and dark matter simulations suggest that this system is the progenitor of a B(inary)-type gap 10 super(14.6)-M sub(mid dot in circle) cluster.
Three ant species nest obligately in the swollen-thorn domatia of the African ant-plant Vachellia (Acacia) drepanolobium, a model system for the study of ant-defence mutualisms and species ...coexistence. Here we report on the characteristic fungal communities generated by these ant species in their domatia. First, we describe behavioural differences between the ant species when presented with a cultured fungal isolate in the laboratory. Second, we use DNA metabarcoding to show that each ant species has a distinctive fungal community in its domatia, and that these communities remain characteristic of the ant species over two Kenyan sampling locations separated by 190 km. Third, we find that DNA extracted from female alates of Tetraponera penzigi and Crematogaster nigriceps contained matches for most of the fungal metabarcodes from those ant species' domatia, respectively. Fungal hyphae and other debris are also visible in sections of these alates' infrabuccal pockets. Collectively, our results indicate that domatium fungal communities are associated with the ant species occupying the tree. To the best of our knowledge, this is the first record of such ant-specific fungal community-level differences on the same myrmecophytic host species. These differences may be shaped by ant behaviour in the domatia, and by ants vectoring fungi when they disperse to establish new colonies. The roles of the fungi with respect to the ants and their host plant remain to be determined.
Early observations indicated that the Earth's Van Allen radiation belts could be separated into an inner zone dominated by high-energy protons and an outer zone dominated by high-energy electrons. ...Subsequent studies showed that electrons of moderate energy (less than about one megaelectronvolt) often populate both zones, with a deep 'slot' region largely devoid of particles between them. There is a region of dense cold plasma around the Earth known as the plasmasphere, the outer boundary of which is called the plasmapause. The two-belt radiation structure was explained as arising from strong electron interactions with plasmaspheric hiss just inside the plasmapause boundary, with the inner edge of the outer radiation zone corresponding to the minimum plasmapause location. Recent observations have revealed unexpected radiation belt morphology, especially at ultrarelativistic kinetic energies (more than five megaelectronvolts). Here we analyse an extended data set that reveals an exceedingly sharp inner boundary for the ultrarelativistic electrons. Additional, concurrently measured data reveal that this barrier to inward electron radial transport does not arise because of a physical boundary within the Earth's intrinsic magnetic field, and that inward radial diffusion is unlikely to be inhibited by scattering by electromagnetic transmitter wave fields. Rather, we suggest that exceptionally slow natural inward radial diffusion combined with weak, but persistent, wave-particle pitch angle scattering deep inside the Earth's plasmasphere can combine to create an almost impenetrable barrier through which the most energetic Van Allen belt electrons cannot migrate.
Long-read sequence assembly of the gorilla genome Gordon, David; Huddleston, John; Chaisson, Mark J. P. ...
Science (American Association for the Advancement of Science),
04/2016, Letnik:
352, Številka:
6281
Journal Article
Recenzirano
Odprti dostop
Accurate sequence and assembly of genomes is a critical first step for studies of genetic variation. We generated a high-quality assembly of the gorilla genome using single-molecule, real-time ...sequence technology and a string graph de novo assembly algorithm. The new assembly improves contiguity by two to three orders of magnitude with respect to previously released assemblies, recovering 87% of missing reference exons and incomplete gene models. Although regions of large, high-identity segmental duplications remain largely unresolved, this comprehensive assembly provides new biological insight into genetic diversity, structural variation, gene loss, and representation of repeat structures within the gorilla genome. The approach provides a path forward for the routine assembly of mammalian genomes at a level approaching that of the current quality of the human genome.
We present an analysis of magnetic field and suprathermal electron measurements from the Mars Global Surveyor (MGS) spacecraft that reveals isolated magnetic structures filled with Martian ...atmospheric plasma located downstream from strong crustal magnetic fields with respect to the flowing solar wind. The structures are characterized by magnetic field enhancements and rotations characteristic of magnetic flux ropes, and characteristic ionospheric electron energy distributions with angular distributions distinct from surrounding regions. These observations indicate that significant amounts of atmosphere are intermittently being carried away from Mars by a bulk removal process: the top portions of crustal field loops are stretched through interaction with the solar wind and detach via magnetic reconnection. This process occurs frequently and may account for as much as 10% of the total present‐day ion escape from Mars.
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