bif1, a new BMP signaling inhibitor, regulates embryonic hematopoiesis in the zebrafish.

Hematopoiesis maintains the entire blood system, and dysregulation of this process can lead to malignancies (leukemia), immunodeficiencies or red blood cell diseases (anemia, polycythemia vera). We took advantage of the zebrafish model that shares most of the genetic program involved in hematopoiesis with mammals to characterize a new gene of unknown function, si:ch73-299h12.2, which is expressed in the erythroid lineage during primitive, definitive and adult hematopoiesis. This gene, required during primitive and definitive erythropoiesis, encodes a C2H2 zinc-finger protein that inhibits BMP signaling. We therefore named this gene blood-inducing factor 1 and BMP inhibitory factor 1 (bif1). We identified a bif1 ortholog in Sinocyclocheilus rhinocerous, another fish, and in the mouse genome. Both genes also inhibit BMP signaling when overexpressed in zebrafish. In conclusion, we have deorphanized a new zebrafish gene of unknown function: bif1 codes for a zinc-finger protein that inhibits BMP signaling and also regulates primitive erythropoiesis and definitive hematopoiesis

Silica Vesicle Nanovaccine Formulations Stimulate Long-Term Immune Responses to the Bovine Viral Diarrhoea Virus E2 Protein

Bovine Viral Diarrhoea Virus (BVDV) is one of the most serious pathogen, which causes tremendous economic loss to the cattle industry worldwide, meriting the development of improved subunit vaccines. Structural glycoprotein E2 is reported to be a major immunogenic determinant of BVDV virion. We have developed a novel hollow silica vesicles (SV) based platform to administer BVDV-1 Escherichia coli-expressed optimised E2 (oE2) antigen as a nanovaccine formulation. The SV-140 vesicles (diameter 50 nm, wall thickness 6 nm, perforated by pores of entrance size 16 nm and total pore volume of 0.934 cm(3)g(-1)) have proven to be ideal candidates to load oE2 antigen and generate immune response. The current study for the first time demonstrates the ability of freeze-dried (FD) as well as non-FD oE2/SV140 nanovaccine formulation to induce long-term balanced antibody and cell mediated memory responses for at least 6 months with a shortened dosing regimen of two doses in small animal model. The in vivo ability of oE2 (100 mu g)/SV-140 (500 mu g) and FD oE2 (100 mu g)/SV-140 (500 mu g) to induce long-term immunity was compared to immunisation with oE2 (100 mu g) together with the conventional adjuvant Quil-A from the Quillaja saponira (10 mu g) in mice. The oE2/SV-140 as well as the FD oE2/SV-140 nanovaccine generated oE2-specific antibody and cell mediated responses for up to six months post the final second immunisation. Significantly, the cell-mediated responses were consistently high in mice immunised with oE2/SV-140 (1,500 SFU/million cells) at the six-month time point. Histopathology studies showed no morphological changes at the site of injection or in the different organs harvested from the mice immunised with 500 mu g SV-140 nanovaccine compared to the unimmunised control. The platform has the potential for developing single dose vaccines without the requirement of cold chain storage for veterinary and human applications

Timed patterns: TCOZ to timed automata

Abstract. The integrated logic-based modeling language, Timed Communicating Object Z (TCOZ), is well suited for presenting complete and coherent requirement models for complex real-time systems. However, the challenge is how to verify the TCOZ models with tool support, especially for analyzing timing properties. Specialized graph-based modeling technique, Timed Automata (TA), has powerful mechanisms for designing real-time models using multiple clocks and has well developed automatic tool support. One weakness of TA is the lack of high level composable graphical patterns to support systematic designs for complex systems. The investigation of possible links between TCOZ and TA may benefit both techniques. For TCOZ, TA’s tool support can be reused to check timing properties. For TA, a set of composable graphical patterns can be defined based on the semantics of the TCOZ constructs, so that those patterns can be re-used in a generic way. This paper firstly defines the composable TA graphical patterns, and then presents sound transformation rules and a tool for projecting TCOZ specifications into TA. A case study of a railroad crossing system is demonstrated

A search for 21 cm HI absorption in AT20G compact radio galaxies

We present results from a search for 21 cm associated HI absorption in a sample of 29 radio sources selected from the Australia Telescope 20 GHz survey. Observations were conducted using the Australia Telescope Compact Array Broadband Backend, with which we can simultaneously look for 21 cm absorption in a redshift range of 0.04 < z < 0.08, with a velocity resolution of 7 km/s . In preparation for future large-scale H I absorption surveys we test a spectral-line finding method based on Bayesian inference. We use this to assign significance to our detections and to determine the best-fitting number of spectral-line components. We find that the automated spectral-line search is limited by residuals in the continuum, both from the band-pass calibration and spectral-ripple subtraction, at spectral-line widths of \Deltav_FWHM > 103 km/s . Using this technique we detect two new absorbers and a third, previously known, yielding a 10 per cent detection rate. Of the detections, the spectral-line profiles are consistent with the theory that we are seeing different orientations of the absorbing gas, in both the host galaxy and circumnuclear disc, with respect to our line-of-sight to the source. In order to spatially resolve the spectral-line components in the two new detections, and so verify this conclusion, we require further high-resolution 21 cm observations (~0.01 arcsec) using very long baseline interferometry.Comment: 16 pages, 8 figures and 5 tables; accepted for publication in MNRAS (version 2 based on proof corrections

A connexin/ifi30 pathway bridges HSCs with their niche to dampen oxidative stress

Reactive oxygen species (ROS) represent a by-product of metabolism and their excess is toxic for hematopoietic stem and progenitor cells (HSPCs). During embryogenesis, a small number of HSPCs are produced from the hemogenic endothelium, before they colonize a transient organ where they expand, for example the fetal liver in mammals. In this study, we use zebrafish to understand the molecular mechanisms that are important in the caudal hematopoietic tissue (equivalent to the mammalian fetal liver) to promote HSPC expansion. High levels of ROS are deleterious for HSPCs in this niche, however this is rescued by addition of antioxidants. We show that Cx41.8 is important to lower ROS levels in HSPCs. We also demonstrate a new role for ifi30, known to be involved in the immune response. In the hematopoietic niche, Ifi30 can recycle oxidized glutathione to allow HSPCs to dampen their levels of ROS, a role that could be conserved in human fetal liver

Hapln1b, a central organizer of the ECM, modulates kit signaling to control developmental hematopoiesis in zebrafish

During early vertebrate development, hematopoietic stem and progenitor cells (HSPCs) are produced in hemogenic endothelium located in the dorsal aorta, before they migrate to a transient niche where they expand to the fetal liver and the caudal hematopoietic tissue, in mammals and zebrafish, respectively. In zebrafish, previous studies have shown that the extracellular matrix (ECM) around the aorta must be degraded to enable HSPCs to leave the aortic floor and reach blood circulation. However, the role of the ECM components in HSPC specification has never been addressed. In this study, hapln1b, a key component of the ECM, was specifically expressed in hematopoietic sites in the zebrafish embryo. Gain- and loss-of-function experiments all resulted in the absence of HSPCs in the early embryo, showing that hapln1b is necessary, at the correct level, to specify HSPCs in the hemogenic endothelium. Furthermore, the expression of hapln1b was necessary to maintain the integrity of the ECM through its link domain. By combining functional analyses and computer modeling, we showed that kitlgb interacts with the ECM to specify HSPCs. The findings show that the ECM is an integral component of the microenvironment and mediates the cytokine signaling that is necessary for HSPC specification

The Structure of the [Zn_In - V_P] Defect Complex in Zn Doped InP

We study the structure, the formation and binding energies and the transfer levels of the zinc-phosphorus vacancy complex [Zn_In - V_P] in Zn doped p-type InP, as a function of the charge, using plane wave ab initio DFT-LDA calculations in a 64 atom supercell. We find a binding energy of 0.39 eV for the complex, which is neutral in p-type material, the 0/-1 transfer level lying 0.50 eV above the valence band edge, all in agreement with recent positron annihilation experiments. This indicates that, whilst the formation of phosphorus vacancies (V_P) may be involved in carrier compensation in heavily Zn doped material, the formation of Zn-vacancy complexes is not. Regarding the structure: for charge states Q=+6 to -4 the Zn atom is in an sp^2 bonded DX position and electrons added/removed go to/come from the remaining dangling bonds on the triangle of In atoms. This reduces the effective vacancy volume monatonically as electrons are added to the complex, also in agreement with experiment. The reduction occurs through a combination of increased In-In bonding and increased Zn-In electrostatic attraction. In addition, for certain charge states we find complex Jahn-Teller behaviour in which up to three different structures, (with the In triangle dimerised, antidimerised or symmetric) are stable and are close to degenerate. We are able to predict and successfully explain the structural behaviour of this complex using a simple tight binding model.Comment: 10 pages text (postscript) plus 8 figures (jpeg). Submitted to Phys. Rev.

Nonlinear vertical oscillations of a particle in a sheath of a rf discharge

A new simple method to measure the spatial distribution of the electric field in the plasma sheath is proposed. The method is based on the experimental investigation of vertical oscillations of a single particle in the sheath of a low-pressure radio-frequency discharge. It is shown that the oscillations become strongly nonlinear and secondary harmonics are generated as the amplitude increases. The theory of anharmonic oscillations provides a good qualitative description of the data and gives estimates for the first two anharmonic terms in an expansion of the sheath potential around the particle equilibrium.Comment: 11 pages, 4 figure

Movement of Escherichia coli in soil as applied in irrigation water.

The US Food and Drug Administration (FDA) has proposed that If irrigation water exceeds 235 colony-forming units (CFU) of E. coli /100 ml in any one sample or 126 CFU/100 ml in the average of any five consecutive samples, growers would have to cease using that water in any way that directly contacts the surface of fresh produce (FDA 2013). The FDA has proposed that these E. coli levels are an indication of high risk of bacterial contamination of fresh onion (Allium cepa L.) bulbs regardless of the irrigation system. If onion irrigation exceeds 235 CFU, it is not known whether the contaminated water applied by furrow or drip irrigation actually reaches the onion bulb. Soil could filter E. coli and other bacteria before irrigation water reaches onion bulbs. ?Vaquero? onions were grown on Owyhee silt loam. In our preliminary studies reported here, well water free of E. coli was applied to onions through drip irrigation or through furrow irrigation. A second water source was intentionally enriched with E. coli by being run across a pasture and recaptured prior to use. Furrow and drip irrigation were used to apply this water containing 218 to >2400 MPN/100ml for 11+ hours per irrigation. E. coli was monitored in the soil water at the end of irrigation cycles through direct sampling of the soil. Soil water was also sampled using sterile soil solution capsules (SSSC) to sample E. coli in the soil water that moved into place, to differentiate the movement of soil water from the soil water already in place. Soil water measurements were made adjacent to the water source, half way to the bulbs, and immediately adjacent to the onion bulbs. For furrow irrigation with ditch water the E. coli counts in the soil next to the onion bulbs was only 0% and 21% of the counts in the irrigation water following the first and second irrigations, respectively. During subsequent furrow irrigations, the E. coli counts in the soil water next to the onion bulbs exceeded the counts in the irrigation water. For drip irrigation with ditch water, the E. coli counts in the soil solution next to the onion bulbs remained very low. The soil water sampled by the SSSC adjacent to the onion bulbs drip-irrigated with ditch water also had very low E. coli counts