Yin-Yang1 is required for epithelial-to-mesenchymal transition and regulation of Nodal signaling during mammalian gastrulation

AbstractThe ubiquitously expressed Polycomb Group protein Yin-Yang1 (YY1) is believed to regulate gene expression through direct binding to DNA elements found in promoters or enhancers of target loci. Additionally, YY1 contains diverse domains that enable a plethora of protein–protein interactions, including association with the Oct4/Sox2 pluripotency complex and Polycomb Group silencing complexes. To elucidate the in vivo role of YY1 during gastrulation, we generated embryos with an epiblast specific deletion of Yy1. Yy1 conditional knockout (cKO) embryos initiate gastrulation, but both primitive streak formation and ingression through the streak is severely impaired. These streak descendants fail to repress E-Cadherin and are unable to undergo an appropriate epithelial to mesenchymal transition (EMT). Intriguingly, overexpression of Nodal and concomitant reduction of Lefty2 are observed in Yy1 cKO embryos, suggesting that YY1 is normally required for proper Nodal regulation during gastrulation. Furthermore, definitive endoderm is specified but fails to properly integrate into the outer layer. Although anterior neuroectoderm is specified, mesoderm production is severely restricted. We show that YY1 directly binds to the Lefty2 locus in E7.5 embryos and that pharmacological inhibition of Nodal signaling partially restores mesoderm production in Yy1 cKO mutant embryos. Our results reveal critical requirements for YY1 during several important developmental processes, including EMT and regulation of Nodal signaling. These results are the first to elucidate the diverse role of YY1 during gastrulation in vivo

Creation of the two isoforms of rodent NKG2D was driven by a B1 retrotransposon insertion

The mouse gene for the natural killer (NK) cell-activating receptor Nkg2d produces two protein isoforms, NKG2D-S and NKG2D-L, which differ by 13 amino acids at the N-terminus and have different signalling capabilities. These two isoforms are produced through differential splicing, but their regulation has not been investigated. In this study, we show that rat Nkg2d has the same splicing pattern as that of the mouse, and we mapped transcriptional start sites in both species. We found that the splice forms arise from alternative promoters and that the NKG2D-L promoter is derived from a rodent B1 retrotransposon that inserted before mouse–rat divergence. This B1 insertion is associated with loss of a nearby splice acceptor site that subsequently allowed creation of the short NKG2D isoform found in mouse but not human. Transient reporter assays indicate that the B1 element is a strong promoter with no inherent lymphoid tissue-specificity. We have also identified different binding sites for the ETS family member GABP within both the mouse and rat B1 elements that are necessary for high-promoter activity and for full Nkg2d-L expression. These findings demonstrate that a retroelement insertion has led to gene-regulatory change and functional diversification of rodent NKG2D

From Earth to Orbit: An assessment of transportation options

The report assesses the requirements, benefits, technological feasibility, and roles of Earth-to-Orbit transportation systems and options that could be developed in support of future national space programs. Transportation requirements, including those for Mission-to-Planet Earth, Space Station Freedom assembly and operation, human exploration of space, space science missions, and other major civil space missions are examined. These requirements are compared with existing, planned, and potential launch capabilities, including expendable launch vehicles (ELV's), the Space Shuttle, the National Launch System (NLS), and new launch options. In addition, the report examines propulsion systems in the context of various launch vehicles. These include the Advanced Solid Rocket Motor (ASRM), the Redesigned Solid Rocket Motor (RSRM), the Solid Rocket Motor Upgrade (SRMU), the Space Shuttle Main Engine (SSME), the Space Transportation Main Engine (STME), existing expendable launch vehicle engines, and liquid-oxygen/hydrocarbon engines. Consideration is given to systems that have been proposed to accomplish the national interests in relatively cost effective ways, with the recognition that safety and reliability contribute to cost-effectiveness. Related resources, including technology, propulsion test facilities, and manufacturing capabilities are also discussed

How was it for you? Experiences of participatory design in the UK health service

Improving co-design methods implies that we need to understand those methods, paying attention to not only the effect of method choices on design outcomes, but also how methods affect the people involved in co-design. In this article, we explore participants' experiences from a year-long participatory health service design project to develop ‘Better Outpatient Services for Older People’. The project followed a defined method called experience-based design (EBD), which represented the state of the art in participatory service design within the UK National Health Service. A sample of participants in the project took part in semi-structured interviews reflecting on their involvement in and their feelings about the project. Our findings suggest that the EBD method that we employed was successful in establishing positive working relationships among the different groups of stakeholders (staff, patients, carers, advocates and design researchers), although conflicts remained throughout the project. Participants' experiences highlighted issues of wider relevance in such participatory design: cost versus benefit, sense of project momentum, locus of control, and assumptions about how change takes place in a complex environment. We propose tactics for dealing with these issues that inform the future development of techniques in user-centred healthcare design

Star Clusters in the Nearby Late-Type Galaxy NGC 1311

Ultraviolet, optical and near infrared images of the nearby (D ~ 5.5 Mpc) SBm galaxy NGC 1311, obtained with the Hubble Space Telescope, reveal a small population of 13 candidate star clusters. We identify candidate star clusters based on a combination of their luminosity, extent and spectral energy distribution. The masses of the cluster candidates range from ~1000 up to ~100000 Solar masses, and show a strong positive trend of larger mass with increasing with cluster age. Such a trend follows from the fading and dissolution of old, low-mass clusters, and the lack of any young super star clusters of the sort often formed in strong starbursts. The cluster age distribution is consistent with a bursting mode of cluster formation, with active episodes of age ~10 Myr, ~100 Myr and ~1 Gyr. The ranges of age and mass we probe are consistent with those of the star clusters found in quiescent Local Group dwarf galaxies.Comment: 21 pages, 11 figures, accepted by A

Inter-Strain Epigenomic Profiling Reveals a Candidate IAP Master Copy in C3H Mice.

Insertions of endogenous retroviruses cause a significant fraction of mutations in inbred mice but not all strains are equally susceptible. Notably, most new Intracisternal A particle (IAP) ERV mutagenic insertions have occurred in C3H mice. We show here that strain-specific insertional polymorphic IAPs accumulate faster in C3H/HeJ mice, relative to other sequenced strains, and that IAP transcript levels are higher in C3H/HeJ embryonic stem (ES) cells compared to other ES cells. To investigate the mechanism for high IAP activity in C3H mice, we identified 61 IAP copies in C3H/HeJ ES cells enriched with H3K4me3 (a mark of active promoters) and, among those tested, all are unmethylated in C3H/HeJ ES cells. Notably, 13 of the 61 are specific to C3H/HeJ and are members of the non-autonomous 1Δ1 IAP subfamily that is responsible for nearly all new insertions in C3H. One copy is full length with intact open reading frames and hence potentially capable of providing proteins i

Modulation of NTC frequencies by Pc5 ULF pulsations : experimental test of the generation mechanism and magnetoseismology of the emitting surface

Nonthermal continuum (NTC) radiation is believed to be emitted by the conversion of an electrostatic wave into an electromagnetic one, which takes place at the Earth's magnetic equator. It is generally accepted that the frequency of the electrostatic wave at the source meets a local characteristic frequency placed in between two multiples of the electron cyclotron frequency, fce, which results in emission of a narrow band frequency element. In an event on 14 August 2003, we compare oscillations of the central frequency of distinct NTC frequency elements observed from Cluster orbiting near perigee, with simultaneous Pc5 Ultra Low Frequency (ULF) pulsations in the magnetic field observed from the same platform. The latter magnetic perturbations are interpreted as magnetohydrodynamic poloidal waves, where fundamental and second harmonic modes coexist. The NTC oscillation and the fundamental wave have similar periods, but are phase shifted by a quarter of period. From the correlation between both signals, and the proximity of the NTC source (localized via triangulation) with Cluster, we infer that the poloidal perturbations are spatially uniform between the source and the satellites. From the phase shift between signals, we conclude that the electrostatic wave which converts into NTC is mainly governed by the plasma density, affected by movements of the magnetic field lines. Furthermore, we demonstrate that the observations can be used to perform a magnetoseismology of the emitting surface. The results show a steepening of the plasmapause density profile near the satellites, which can be responsible for the generation of NTC emission