DAAM1 and DAAM2 are co-required for myocardial maturation and sarcomere assembly

AbstractWnt ligands regulate heart morphogenesis but the underlying mechanisms remain unclear. Two Formin-related proteins, DAAM1 and 2, were previously found to bind the Wnt effector Disheveled. Here, since DAAM1 and 2 nucleate actin and mediate Wnt-induced cytoskeletal changes, a floxed-allele of Daam1 was used to disrupt its function specifically in the myocardium and investigate Wnt-associated pathways. Homozygous Daam1 conditional knockout (CKO) mice were viable but had misshapen hearts and poor cardiac function. The defects in Daam1 CKO mice were observed by mid-gestation and were associated with a loss of protrusions from cardiomyocytes invading the outflow tract. Further, these mice exhibited noncompaction cardiomyopathy (NCM) and deranged cardiomyocyte polarity. Interestingly, Daam1 CKO mice that were also homozygous for an insertion disrupting Daam2 (DKO) had stronger NCM, severely reduced cardiac function, disrupted sarcomere structure, and increased myocardial proliferation, suggesting that DAAM1 and DAAM2 have redundant functions. While RhoA was unaffected in the hearts of Daam1/2 DKO mice, AKT activity was lower than in controls, raising the issue of whether DAAM1/2 are only mediating Wnt signaling. Daam1-floxed mice were thus bred to Wnt5a null mice to identify genetic interactions. The hearts of Daam1 CKO mice that were also heterozygous for the null allele of Wnt5a had stronger NCM and more severe loss of cardiac function than Daam1 CKO mice, consistent with DAAM1 and Wnt5a acting in a common pathway. However, deleting Daam1 further disrupted Wnt5a homozygous-null hearts, suggesting that DAAM1 also has Wnt5a-independent roles in cardiac development

Measurements of Atmospheric Antiprotons

We measured atmospheric antiproton spectra in the energy range 0.2 to 3.4 GeV, at sea level and at balloon altitude in the atmospheric depth range 4.5 to 26 g/cm^2. The observed energy spectra, including our previous measurements at mountain altitude, were compared with estimated spectra calculated on various assumptions regarding the energy distribution of antiprotons that interacted with air nuclei.Comment: Accepted for publication in PL

Measurements of 0.2 to 20 GeV/n cosmic-ray proton and helium spectra from 1997 through 2002 with the BESS spectrometer

We measured low energy cosmic-ray proton and helium spectra in the kinetic energy range 0.215 - 21.5 GeV/n at different solar activities during a period from 1997 to 2002. The observations were carried out with the BESS spectrometer launched on a balloon at Lynn Lake, Canada. A calculation for the correction of secondary particle backgrounds from the overlying atmosphere was improved by using the measured spectra at small atmospheric depths ranging from 5 through 37 g/cm^2. The uncertainties including statistical and systematic errors of the obtained spectra at the top of atmosphere are 5-7 % for protons and 6-9 % for helium nuclei in the energy range 0.5 - 5 GeV/n.Comment: 27 pages, 7 Tables, 9 figures, Submitted to Astroparticle Physic

Regulation of angiogenesis by a non-canonical Wnt-Flt1 pathway in myeloid cells

Myeloid cells are a feature of most tissues. Here we show that during development, retinal myeloid cells (RMCs) produce Wnt ligands to regulate blood vessel branching. In the mouse retina, where angiogenesis occurs postnatally, somatic deletion in RMCs of the Wnt ligand transporter Wntless results in increased angiogenesis in the deeper layers. We also show that mutation of Wnt5a and Wnt11 results in increased angiogenesis and that these ligands elicit RMC responses via a non-canonical Wnt pathway. Using cultured myeloid-like cells and RMC somatic deletion of Flt1, we show that an effector of Wnt-dependent suppression of angiogenesis by RMCs is Flt1, a naturally occurring inhibitor of vascular endothelial growth factor (VEGF). These findings indicate that resident myeloid cells can use a non-canonical, Wnt-Flt1 pathway to suppress angiogenic branching

Measurement of cosmic-ray low-energy antiproton spectrum with the first BESS-Polar Antarctic flight

The BESS-Polar spectrometer had its first successful balloon flight over Antarctica in December 2004. During the 8.5-day long-duration flight, almost 0.9 billion events were recorded and 1,520 antiprotons were detected in the energy range 0.1-4.2 GeV. In this paper, we report the antiproton spectrum obtained, discuss the origin of cosmic-ray antiprotons, and use antiprotons to probe the effect of charge sign dependent drift in the solar modulation.Comment: 18 pages, 1 table, 5 figures, submitted to Physics Letters

Measurements of Primary and Atmospheric Cosmic-Ray Spectra with the BESS-TeV Spectrometer

Primary and atmospheric cosmic-ray spectra were precisely measured with the BESS-TeV spectrometer. The spectrometer was upgraded from BESS-98 to achieve seven times higher resolution in momentum measurement. We report absolute fluxes of primary protons and helium nuclei in the energy ranges, 1-540 GeV and 1-250 GeV/n, respectively, and absolute flux of atmospheric muons in the momentum range 0.6-400 GeV/c.Comment: 26 pages, 9 figures, 3 tables, Submitted to Phys. Lett.

Precise Measurements of Atmospheric Muon Fluxes with the BESS Spectrometer

The vertical absolute fluxes of atmospheric muons and muon charge ratio have been measured precisely at different geomagnetic locations by using the BESS spectrometer. The observations had been performed at sea level (30 m above sea level) in Tsukuba, Japan, and at 360 m above sea level in Lynn Lake, Canada. The vertical cutoff rigidities in Tsukuba (36.2 N, 140.1 E) and in Lynn Lake (56.5 N, 101.0 W) are 11.4 GV and 0.4 GV, respectively. We have obtained vertical fluxes of positive and negative muons in a momentum range from 0.6 to 20 GeV/c with systematic errors less than 3 % in both measurements. By comparing the data collected at two different geomagnetic latitudes, we have seen an effect of cutoff rigidity. The dependence on the atmospheric pressure and temperature, and the solar modulation effect have been also clearly observed. We also clearly observed the decrease of charge ratio of muons at low momentum side with at higher cutoff rigidity region.Comment: 35 pages, 9 figures. Submitted to Astroparticle Physic

Measurements of Proton, Helium and Muon Spectra at Small Atmospheric Depths with the BESS Spectrometer

The cosmic-ray proton, helium, and muon spectra at small atmospheric depths of 4.5 -- 28 g/cm^2 were precisely measured during the slow descending period of the BESS-2001 balloon flight. The variation of atmospheric secondary particle fluxes as a function of atmospheric depth provides fundamental information to study hadronic interactions of the primary cosmic rays with the atmosphere.Comment: 21 pages, 11 figures, 4 table

Development and Test Results of a low-β\beta Quadrupole Model for the Large Hadron Collider

A 1-m model of the high gradient 70 mm aperture superconducting low-b quadrupoles for the Large Hadron Collider (LHC) has been developed. A field gradient of 250 T/m at 1.9 K has been achieved with a peak field of 10 T in the coil. This paper describes development of the first model magnet and presents the test results