Identification of Thymosin β4 as an effector of Hand1-mediated vascular development

The bHLH transcription factor Hand1 (Heart and neural crest-derived transcript-1) has a fundamental role in cardiovascular development; however, the molecular mechanisms have not been elucidated. In this paper we identify Thymosin β4 (Tβ4/Tmsb4x), which encodes an actin monomer-binding protein implicated in cell migration and angiogenesis, as a direct target of Hand1. We demonstrate that Hand1 binds an upstream regulatory region proximal to the promoter of Tβ4 at consensus Thing1 and E-Box sites and identify both activation and repression of Tβ4 by Hand1, through direct binding within either non-canonical or canonical E-boxes, providing new insight into gene regulation by bHLH transcription factors. Hand1-mediated activation of Tβ4 is essential for yolk sac vasculogenesis and embryonic survival, and administration of synthetic TB4 partially rescues yolk sac capillary plexus formation in Hand1-null embryos. Thus, we identify an in vivo downstream target of Hand1 and reveal impaired yolk sac vasculogenesis as a primary cause of early embryonic lethality following loss of this critical bHLH factor

Low-speed wind-tunnel test of a STOL supersonic-cruise fighter concept

A wind-tunnel investigation was conducted to examine the low-speed static stability and control characteristics of a 0.10 scale model of a STOL supersonic cruise fighter concept. The concept, referred to as a twin boom fighter, was designed as a STOL aircraft capable of efficient long range supersonic cruise. The configuration name is derived from the long twin booms extending aft of the engine to the twin vertical tails which support a high center horizontal tail. The propulsion system features a two dimensional thrust vectoring exhaust nozzle which is located so that the nozzle hinge line is near the aircraft center of gravity. This arrangement is intended to allow large thrust vector angles to be used to obtain significant values of powered lift, while minimizing pitching moment trim changes. Low speed stability and control information was obtained over an angle of attack range including the stall. A study of jet induced power effects was included

Simulation of the Hydrologic-Economic Flow System in an Agricultural Area

Like the allocation of water resources among water users, the distribution of allocated water to the subusers requires an estimate of the economic costs and benefits from a number of distribution alternatives. The most satisfactory solution maximizes the benefit cost ratio. This study is based on the premise that equitable water distribution to agricultural subusers can be more easily accomplished through the use of a technique to predict the marginal value of agricultural water. A hydro-economic model is formulated to distribute the water supply to the crops and to determine the unit value of water for the given supply. By incrementing the supply, the marginal value of water for a given cropping pattern is determined. Water is in short supply if the potential evapotranspiration of all the crops can not be satisfied. The link between the economic and hydrologic system is the production function which is the relationship between the actual evapotranspiration and the yield of the crop. Other variables affecting crop production are assumed to be relatively constant. The simulation model is applied to a prototype system to demonstrate the applicability of the model to management and planning problems. The model provides a means of determining the marginal value of water in water short years where potential evapotranspiration of all crops can not be met

Salt Loading from Efflorescence and Suspended Sediments in the Price River Basin

Salinity control is a major component of water management in arid climates and irrigated areas and one of particular concern in the Colorado River Basin. The alts enter the water as it flows over land or moves through the soil or geologic formations. The principal salt collection processes are 1) dissolution from the soil surface during runoff events, 2) transpiration of soil water leaving salt residuals, 3) efflorescence left by evaporating seepage and then dissolved by subsequent runoff, 4) dissolution with weathering of fixed bed channels, 5) salts released by sediments entering the channel from sheet, gulley, and bank erosion, and 6) deep percolation through saline aquifer reaching the stream as base flow. This study examined processes 3 and 5. Salt efflorescence was examined by field observation and instrumentation, laboratory experiments, and mathematical modeling. The field data showed near saturation conditions of sodium sulfate waters below crusts of densities between 0.14 and 0.36 g/cm^2 and which formed over abouta 10-day period following channel cleaning by storm runoff. Laboratory data on salt crusting in soil columns were also used in developing a model which when applied to the Price River Basin estimated that no more than 7.5 percent of the total salt loading comes from salt efflorescence being carried away in the stream flow. The conditions favorable to the accumulation of salt efflorescence are highly saline water just below the soil surface and a source of heat for vaporizing the water. Salt release from suspended sediments was studied by laboratory experimentation with sediment material obtained from various locations in the Price River Basin. The Buckinham Pi Theorem was employed to derive relationships expressing the EC of a sediment water system as a function o fthe controlling factors. The results were presented in two salt release equations, one excluding the effect of initial EC and the other providing for initially saline solutions. The salt release equations were incorporated into an adapted version of the Watershed Erosion and Sediment Transport (WEST) model and applied to a small tributary of Coal Creek. Extrapolation to the entire Price River Basin led to an estimate that about 0.50 percent of the total annual salt load is released from suspened sediments. This study concludes that surface salt sources produce a relatvely small fraction of the total loading. Future studies need to go underground. They need to quantify and examine the flow lines of water movement from mountain source and valley floow recharge areas to points of emergence as base flow in the larger stream channels. They need to investigate the aquifers and their soluble salt content

Paleomagnetic Evidence of Vertical Axis Block Rotations from the Mesozoic of Northern Chile

We present paleomagnetic results for three Mesozoic formations from northern Chile: La Ternera Formation (Upper Triassic), Quebrada Monardes Formation (Upper Jurassic); Cerrillos Formation (Upper Cretaceous). Results from the Cerrillos are divided into eastern (Cuesta El Gao (CEG)) and western (Elisa De Bordo (EBD)) localities. Most specimens from La Ternera volcanic and sedimentary rocks are mag­netically stable, as shown by alternating field and thermal demagnetization. More complicated but still reliable results were obtained from Quebrada Monardes red beds. Normal and reverse polarities are present in both units; means of both populations are antiparallel at 95% confi­dence. The Quebrada Monardes Formation also yields positive conglomerate and fold tests. Paleomagnetic poles for La Ternera and Quebrada- Monardes are 60.9S, 218.3E (A95, 7.8°), and 66.9S, 191.6E (A95, 12.7°), respectively. Com­parison with appropriate reference poles shows that this region of Chile has undergone about 25° of clockwise rotation, with negligible lati­tudinal transport. Cerrillos CEG results are less reliable and possibly complicated by remag- netization during emplacement of early Tertiary intrusives. Most Cerrillos EDB specimens are stable, but marked increase in scatter upon un­folding suggests remagnetization. Results for the Cerrillos CEG locality, which is contiguous to the sampling area of the La Ternera and Que­brada Monardes formations, show only about half the rotation of those two units, suggesting that rotation commenced after deposition of the Que­brada Monardes rocks in the Late Jurassic and was approximately half complete by the time Cer­rillos CEG rocks acquired their magnetization. Cerrillos EDB results come from an area approxi­mately 40 km to the west; these show roughly 45° of clockwise rotation. Dispersion is very low between EDB sites, suggesting that secular vari­ation may not be completely averaged. Neverthe­less, the great difference in direct:ion between the two Cerrillos localities suggests that they lie in different structural blocks

Steric Shielding of Surface Epitopes and Impaired Immune Recognition Induced by the Ebola Virus Glycoprotein

Many viruses alter expression of proteins on the surface of infected cells including molecules important for immune recognition, such as the major histocompatibility complex (MHC) class I and II molecules. Virus-induced downregulation of surface proteins has been observed to occur by a variety of mechanisms including impaired transcription, blocks to synthesis, and increased turnover. Viral infection or transient expression of the Ebola virus (EBOV) glycoprotein (GP) was previously shown to result in loss of staining of various host cell surface proteins including MHC1 and β1 integrin; however, the mechanism responsible for this effect has not been delineated. In the present study we demonstrate that EBOV GP does not decrease surface levels of β1 integrin or MHC1, but rather impedes recognition by steric occlusion of these proteins on the cell surface. Furthermore, steric occlusion also occurs for epitopes on the EBOV glycoprotein itself. The occluded epitopes in host proteins and EBOV GP can be revealed by removal of the surface subunit of GP or by removal of surface N- and O- linked glycans, resulting in increased surface staining by flow cytometry. Importantly, expression of EBOV GP impairs CD8 T-cell recognition of MHC1 on antigen presenting cells. Glycan-mediated steric shielding of host cell surface proteins by EBOV GP represents a novel mechanism for a virus to affect host cell function, thereby escaping immune detection

A Model of Environmental Transport of Heavy Metals Originating From Stack Derived Particulate Emission in Semi-Arid Regions

Executive Summary

Distinct epicardial gene regulatory programs drive development and regeneration of the zebrafish heart

Unlike the adult mammalian heart, which has limited regenerative capacity, the zebrafish heart fully regenerates following injury. Reactivation of cardiac developmental programs is considered key to successfully regenerating the heart, yet the regulation underlying the response to injury remains elusive. Here, we compared the transcriptome and epigenome of the developing and regenerating zebrafish epicardia. We identified epicardial enhancer elements with specific activity during development or during adult heart regeneration. By generating gene regulatory networks associated with epicardial development and regeneration, we inferred genetic programs driving each of these processes, which were largely distinct. Loss of Hif1ab, Nrf1, Tbx2b, and Zbtb7a, central regulators of the regenerating epicardial network, in injured hearts resulted in elevated epicardial cell numbers infiltrating the wound and excess fibrosis after cryoinjury. Our work identifies differences between the regulatory blueprint deployed during epicardial development and regeneration, underlining that heart regeneration goes beyond the reactivation of developmental programs

Functional MRI Assessment of Renal Fibrosis in Rat Models

poster abstractIntroduction Renal fibrosis is a common consequence of chronic kidney diseases which affects a large population. Therefore, it is important to establish imaging based noninvasive biomarkers to monitor the progression or regression of renal fibrosis instead of biopsy. Magnetic resonance imaging (MRI) could provide both high spatial resolution and excellent tissue contrast for visualization of kidney morphology. Moreover, MRI is capable of assessing pseudo perfusion (Df) and perfusion fraction (Pf) with intra-voxel incoherent motion (IVIM) imaging (1), tissue oxygenation with T2* mapping (2), macromolecular composition with T1rho imaging (3) and kidney function (eGFR) with dynamic contrast enhanced (DCE) imaging (4). This study is aimed to evaluate the sensitivity of these MRI techniques to the renal fibrotic changes in a rat model. Methods A total of 4 rats were scanned at early (2-5 days) and late (25-35 days) time points after surgical intervention (unilateral ureteral obstruction to induce renal fibrosis) on a Siemens Tim Trio 3T scanner using an 80mm inner diameter 8-channel rat body coil (RAPID, USA) under a stable anesthetized condition. Axial images of 80mm FOV, 2mm slice thick and sub-millimeter in-place resolution were acquired for different functional MRI techniques with following parameters, respectively: IVIM with10 b-values of 0 - 750 s/mm2. T2*: with 10 TEs of 8 - 66 ms; T1rho: with 9 TSL times of 5 - 80 ms; DCE: with150 dynamic measurements at a temporal resolution of 1.01 s. before and after a 15s injection of 1.1 ml GD-DTPA through rat tail with a power injector. Functional data were processed and analyzed using custom MATLAB programs or analysis tools installed in the MRI console workstation. Results Figure 1 shows an anatomical image of the obstructed (R) and healthy (L) rat kidneys. Figures 2-4 show example T1rho map, IVIM Df map, and T2* map, respectively. Quantitative results based on ROI measurements are summarized in table 1. Changes consistent with the expected progression of fibrosis were observed in the obstructed kidney (R) while the healthy kidney (L) and muscle region remained stable. Figure 5 shows the DCE-MRI images at baseline as well as 45s, 95s and 240s after contrast infusion. The timing and intensity of signal changes are clearly different between two kidneys. Quantitative results of DCE-MRI data and comparison with PET study is reported in a separate abstract. Discussion High quality anatomical and functional images of rat kidney can be obtained on a clinical 3.0T MR scanner with dedicated small animal coils and optimized imaging techniques. The findings suggest that IVIM, T2*, T1rho and DCE can be used to assess and monitor different aspects of physiological changes in kidney fibrosis

The role of thymosin-?4 in kidney disease

Therapies which modulate inflammation and fibrosis have the potential to reduce the morbidity and mortality associated with chronic kidney disease. A promising avenue may be manipulating thymosin-?4, a naturally-occurring peptide which is the major G-actin sequestering protein in mammalian cells and a regulator of inflammation and fibrosis. Thymosin-?4 is already being tested in clinical trials for heart disease and wound healing. In this editorial, we outline the evidence that thymosin-?4 may also have therapeutic benefit in chronic kidney disease