Galaxies in the early Universe that are bright at submillimetre wavelengths (submillimetre-bright galaxies) are forming stars at a rate roughly 1,000 times higher than the Milky Way. A large fraction ...of the new stars form in the central kiloparsec of the galaxy
, a region that is comparable in size to the massive, quiescent galaxies found at the peak of cosmic star-formation history
and the cores of present-day giant elliptical galaxies. The physical and kinematic properties inside these compact starburst cores are poorly understood because probing them at relevant spatial scales requires extremely high angular resolution. Here we report observations with a linear resolution of 550 parsecs of gas and dust in an unlensed, submillimetre-bright galaxy at a redshift of z = 4.3, when the Universe was less than two billion years old. We resolve the spatial and kinematic structure of the molecular gas inside the heavily dust-obscured core and show that the underlying gas disk is clumpy and rotationally supported (that is, its rotation velocity is larger than the velocity dispersion). Our analysis of the molecular gas mass per unit area suggests that the starburst disk is gravitationally unstable, which implies that the self-gravity of the gas is stronger than the differential rotation of the disk and the internal pressure due to stellar-radiation feedback. As a result of the gravitational instability in the disk, the molecular gas would be consumed by star formation on a timescale of 100 million years, which is comparable to gas depletion times in merging starburst galaxies
.
Surface charge states of biomaterials are often important for the adsorption of cells, proteins, and foreign ions on their surfaces, which should be clarified at the atomic and electronic levels. ...First-principles calculations were performed to reveal thermodynamically stable surface atomic structures and their charge states in hydroxyapatite (HAp). Effects of aqueous environments on the surface stability were considered using an implicit solvation model. It was found that in an air atmosphere, stoichiometric {0001} and P-rich {101&cmb.macr;0} surfaces are energetically favorable, whereas in an aqueous solution, a Ca-rich {101&cmb.macr;0} surface is the most stable. This difference suggests that preferential surface structures strongly depend on chemical environments with and without aqueous solutions. Their surface potentials at zero charge were calculated to obtain the isoelectric points (pH
PZC
). pH
PZC
values for the {0001} surface and the Ca-rich {101&cmb.macr;0} surface were obtained to be 4.8 and 8.7, respectively. This indicates that in an aqueous solution at neutral pH, the {0001} and Ca-rich {101&cmb.macr;0} surfaces are negatively and positively charged, respectively. This trend agrees with experimental data from chromatography and zeta potential measurements. Our methodology based on first-principles calculations enables determining macroscopic charge states of HAp surfaces from atomic and electronic levels.
Macroscopic charge states for hydroxyapatite surfaces have been quantitatively determined using an implicit solvation model based on first-principles calculations.
Summary Objective Endochondral ossification, a conversion process from nonvascularized and hypoxic cartilage to highly vascularized bone, plays a crucial role in osteoarthritis (OA) development as ...well as in physiological skeletal growth. We have shown that hypoxia-inducible factor-2α (HIF-2α, encoded by EPAS1 ) is an extensive regulator of the endochondal ossification process. Here we review the possible signaling network regulating OA development on the axis of HIF-2α. Methods Peer reviewed publications published prior to August 2010 were searched in the Pubmed database. Articles that were relevant to HIF and molecular mechanisms of the endochondral ossification and OA were selected. Results As a trigger of OA, mechanical stress may induce the upstream NF-κB signal and HIF-2α expression in joint cartilage of mice and humans, which causes transactivation of endochondral ossification-related molecules with the most potent β-subunit partner aryl hydrocarbon nuclear translocator-like (ARNTL). In contrast to HIF-2α, HIF-1α functions to maintain cartilage via a distinct mechanism, so that the shifting of the HIFs might possibly be involved in an OA pathogenesis. Conclusion Signals on the HIF-2α axis from NF-κB signaling to the endochondral ossification-related molecules, possibly in combination with HIF-2α and ARNTL, may represent a rational therapeutic target for OA with minimal effects on physiological skeletal homeostasis.
The biological roles of nucleic acid methylation, other than at the C5-position of cytosines in CpG dinucleotides, are still not well understood. Here, we report genetic evidence for a critical role ...for the putative DNA demethylase NMAD-1 in regulating meiosis in C. elegans. nmad-1 mutants have reduced fertility. They show defects in prophase I of meiosis, which leads to reduced embryo production and an increased incidence of males due to defective chromosomal segregation. In nmad-1 mutant worms, nuclear staging beginning at the leptotene and zygotene stages is disorganized, the cohesin complex is mislocalized at the diplotene and diakinesis stages, and chromosomes are improperly condensed, fused, or lost by the end of diakinesis. RNA sequencing of the nmad-1 germline revealed reduced induction of DNA replication and DNA damage response genes during meiosis, which was coupled with delayed DNA replication, impaired DNA repair and increased apoptosis of maturing oocytes. To begin to understand how NMAD-1 regulates DNA replication and repair, we used immunoprecipitation and mass spectrometry to identify NMAD-1 binding proteins. NMAD-1 binds to multiple proteins that regulate DNA repair and replication, including topoisomerase TOP-2 and co-localizes with TOP-2 on chromatin. Moreover, the majority of TOP-2 binding to chromatin depends on NMAD-1. These results suggest that NMAD-1 functions at DNA replication sites to regulate DNA replication and repair during meiosis.
We attempted to determine the effect of universal adhesive application time on dentin bond performance in different etching modes based on shear bond strength (SBS) tests and surface free energy ...(SFE) measurements. The five universal adhesives used were Adhese Universal (AU), Clearfil Universal Bond Quick (CQ), G-Premio Bond (GP), Scotchbond Universal (SU), and Tokuyama Universal Bond (TU). Bovine dentin specimens were divided into four groups of 10 for each adhesive. SBS and SFE were determined after applying the following surface treatments: 1) self-etch (SE) mode with immediate air blowing after adhesive application (IA treatment), 2) SE mode with prolonged application time (PA treatment), 3) etch-and-rinse (ER) mode with IA treatment, and 4) ER mode with PA treatment. Bonded specimens were subjected to SBS testing. The SFE of adhesive-treated dentin surfaces was measured after rinsing with acetone and water. Three-way analysis of variance revealed that dentin SBS values (
<0.001) were significantly influenced by the factors of adhesive type and application duration, but the factor of pre-etching was not significant (
0.985). The manufacturer's instructions require longer application times for AU and SU, which showed significantly lower SBS values in IA than in PA treatment in both etching modes. However, the difference in the other adhesives was not significant between the IA and PA treatments in either etching mode. The total SFE (γ
) was dependent on the adhesive and etching mode. The γ
value of the initial group (SiC paper ground group) at baseline was 69.5 (mN·m
) and that of the pre-etching group at baseline was 30.6 (mN·m
). For all the adhesives, γ
in SE mode showed significantly higher values than in ER mode, regardless of the application time. In SE mode, almost all universal adhesives tested showed lower γ
values in PA treatment than in IA treatment. For ER mode, all the adhesives showed significantly higher γ
values than those of the pre-etching baseline, regardless of the application time. Most adhesives did not show any significant differences in γ
values between IA and PA treatments, regardless of etching mode.
Temperature and odors profoundly affect the behavior of animals. Transient receptor potential channel, subfamily A, member 1 (TRPA1) functions as a polymodal nociceptor for sensing both vital ...environmental cues in insects. Mosquitoes are recognized as disease vectors, and many efforts have been devoted to investigations of their host-seeking behaviors and repellents. However, the physiological characteristics of mosquito TRPA1 have not been systematically studied. We identified multiple alternative splice variants of the TrpA1 gene from Anopheles gambiae, Anopheles stephensi, Aedes aegypti and Culex pipiens pallens mosquitoes. And we performed comparative analyses of the responses of mosquito TRPA1s to heat or chemical stimuli with calcium-imaging and whole-cell patch-clamp methods. Comparison of TRPA1 among four mosquito species from different thermal niches revealed that TRPA1 of Culex pipiens pallens inhabiting the temperate zone had a lower temperature threshold for heat-evoked activation, which was supported by the in vivo heat-avoidance test. Notably, the chemosensitivity of mosquito TRPA1 channels revealed differences not only between variants but also among species. Moreover, we discovered three novel mosquito TRPA1 agonists. Thermal niches selection and evolutionary trajectories significantly affect the functional properties of mosquito TRPA1, which represents a hallmark of the behaviors that may permit the design of improved mosquito control methods.
Apple (Malus × domestica Borkh.) is a perennial woody plant that undergoes a period of dormancy (in cv. Jonathan between late September and mid-December) to survive freezing temperatures of winter. ...DORMANCY-ASSOCIATED MADS-BOX (DAM) genes play important roles in the regulation of growth cessation and terminal bud formation in peach. To understand the role of DAM orthologs in apple, we isolated and characterized four DAM-like genes (designated as MdDAMa, MdDAMb, MdDAMc, and MdDAMd) and monitored their expression in apical buds throughout the season by real-time quantitative polymerase chain reaction analyses. The transcription of MdDAMa peaked in October and that of MdDAMc was elevated from August to October, whereas MdDAMb and MdDAMd were practically undetectable. The tandemly arranged genes MdDAMa/MdDAMb and MdDAMc/MdDAMd were localized to chromosomes 16 and 8, respectively. Based on these observations, we infer that MdDAMa and MdDAMc acted in a dominant fashion on each locus and were correlated with the period of endodormancy.
The position of recombination events established along chromosomes in early prophase I and the chromosome remodeling that takes place in late prophase I are intrinsically linked steps of meiosis that ...need to be tightly regulated to ensure accurate chromosome segregation and haploid gamete formation. Here, we show that RAD-51 foci, which form at the sites of programmed meiotic DNA double-strand breaks (DSBs), exhibit a biased distribution toward off-centered positions along the chromosomes in wild-type
, and we identify two meiotic roles for chromatin-associated protein HIM-17 that ensure normal chromosome remodeling in late prophase I. During early prophase I, HIM-17 regulates the distribution of DSB-dependent RAD-51 foci and crossovers on chromosomes, which is critical for the formation of distinct chromosome subdomains (short and long arms of the bivalents) later during chromosome remodeling. During late prophase I, HIM-17 promotes the normal expression and localization of protein phosphatases GSP-1/2 to the surface of the bivalent chromosomes and may promote GSP-1 phosphorylation, thereby antagonizing Aurora B kinase AIR-2 loading on the long arms and preventing premature loss of sister chromatid cohesion. We propose that HIM-17 plays distinct roles at different stages during meiotic progression that converge to promote normal chromosome remodeling and accurate chromosome segregation.
Pigs and humans have shared influenza A viruses (IAV) since at least 1918, and many interspecies transmission events have been documented since that time. However, despite this interplay, relatively ...little is known regarding IAV circulating in swine around the world compared with the avian and human knowledge base. This gap in knowledge impedes our understanding of how viruses adapted to swine or man impacts the ecology and evolution of IAV as a whole and the true impact of swine IAV on human health. The pandemic H1N1 that emerged in 2009 underscored the need for greater surveillance and sharing of data on IAV in swine. In this paper, we review the current state of IAV in swine around the world, highlight the collaboration between international organizations and a network of laboratories engaged in human and animal IAV surveillance and research, and emphasize the need to increase information in high‐priority regions. The need for global integration and rapid sharing of data and resources to fight IAV in swine and other animal species is apparent, but this effort requires grassroots support from governments, practicing veterinarians and the swine industry and, ultimately, requires significant increases in funding and infrastructure.
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