Introgression of Brown Norway \u3cem\u3eCYP4A\u3c/em\u3e Genes onto the Dahl Salt-Sensitive Background Restores Vascular Function in SS-5\u3csup\u3eBN\u3c/sup\u3e Consomic Rats

The present study tested the hypothesis that the Dahl SS (salt-sensitive) rat has vascular dysfunction due, in part, to the up-regulation of the CYP4A/20-HETE (cytochrome P450 ω-hydroxylase 4A)/20-hydroxyeicosatetraenoic acid) system. To assess the role of vascular 20-HETE, SS rats were compared with SS-5BN consomic rats, carrying CYP4A alleles on chromosome 5 from the normotensive BN (Brown Norway) introgressed on to the SS genetic background. Cerebral arteries from SS-5BN rats had less CYP4A protein than arteries from SS rats fed either NS (normal-salt, 0.4% NaCl) or HS (high-salt, 4.0% NaCl) diet. ACh (acetylcholine)-induced dilation of MCAs (middle cerebral arteries) from SS and SS-5BN rats was present in SS-5BN rats fed on either an NS or HS diet, but absent in SS rats. In SS rats fed on either diet, ACh-induced dilation was restored by acute treatment with the CYP4A inhibitor DDMS (N-methyl-sulfonyl-12,12-dibromododec-11-enamide) or the 20-HETE antagonist 20-HEDE [20-hydroxyeicosa-6(Z),15(Z)-dienoic acid]. The restored response to ACh in DDMS-treated SS rats was inhibited by L-NAME (NGnitro-L-arginine methyl ester) and unaffected by indomethacin or MS-PPOH [N-methylsulfonyl-6-(2-propargyloxyphenyl)hexanamide]. Vascular relaxation responses to the NO donor C5FeN6Na2O were intact in both SS and SS-5BN rats and unaffected by the acute addition of DDMS, indicating that the vascular dysfunction of the SS rat is due to a reduced bioavailability of NO instead of failure of the VSMCs (vascular smooth muscle cells) to respond to the vasodilator. Superoxide levels in cerebral arteries of SS-5BN rats [evaluated semi-quantitatively by DHE (dihydroethidium) fluorescence] were lower than those in the arteries of SS rats. These findings indicate that SS rats have an up-regulation of the CYP4A/20-HETE pathway resulting in elevated ROS (reactive oxygen species) and reduced NO bioavailability causing vascular dysfunction

Results of 1/4-Scale Experiments. Vapor Simulant And Liquid Jet A Tests

A quarter-scale engineering model of the center wing tank (CWT) of a 747-100 was constructed. This engineering model replicated the compartmentalization, passageways, and venting to the atmosphere. The model was designed to scale the fluid dynamical and combustion aspects of the explosion, not the structural failure of the beams or spars. The effect of structural failure on combustion was examined by using model beams and spars with deliberately engineered weak connections to the main tank structure. The model was filled with a simulant fuel (a mixture of propane and hydrogen) and ignited with a hot wire. The simulant fuel was chosen on the basis of laboratory testing to model the combustion characteristics (pressure rise and flame speed) of Jet A vapor created by a Jet A liquid layer at 50C at an altitude of 13.8 kft. A series of experiments was carried out in this model in order to: (a) investigate combustion in a CWT geometry; and (b) provide guidance to the TWA 800 crash investigation. The results of the experiments were observed with high-speed film, video, and still cameras, fast and slow pressure sensors, thermocouples, photodetectors, and motion sensors. A special pseudo-schlieren system was used to visualize flame propagation within the tank. This report describes the test program, facility, instrumentation, the first 30 experiments, comparisons between experiments, and performance of the instrumentation; then examines the significance of these results to the TWA 800 crash investigation. The key results of this study are: Flame Motion: The motion of flame was dominated by the effects of turbulence created by jetting through the passageways and vent stringers. A very rapid combustion event (lasting 10 to 20 ms) occurred once the flame traveled outside of the ignition bay and interacted with the turbulent flow. Most of the gas within the tank was burned during this rapid event. Compartments: The combustion time decreased with an increasing number of compartments (bays) within the tank. With six bays, combustion took only 100 to 150 ms to be completed from the time of ignition until the end of the rapid combustion phase. The total combustion event was three to four times shorter with compartments than without. Venting: Venting to the outside of the tank through the model vent stringers had a negligible effect on the combustion progress or on the peak pressure reached at the end of the burn. Ignition Location: Variation of the ignition location produced distinctive pressure loads on the structural components. Liquid Fuel: Lofting of a cold liquid fuel layer was produced by the combustion-induced gas motion. Although this spray of liquid eventually ignited and burned, it did not contribute to the pressure loading. Structural Failure: Structural failure resulted in flame acceleration, decreasing the overall combustion time. TWA 800 Investigation: The pressure loads were sufficiently high, up to 4 bar, and the combustion events were sufficiently short, that the forward portion (spanwise beam 3, front spar) of the CWT structure would fail as a direct consequence of the explosion. A combination of pressure loads was produced in some tests consistent with the TWA 800 wreckage. Replica tests, structural modeling, and sensitivity studies on fuel concentration are needed before any conclusions can be drawn about probable ignition locations. Cargo Bay: Tests with a simplified model of a half-full cargo bay indicated that repeated pressure waves with an amplitude of 1 bar or less are produced when an explosion scenario similar to TWA 800 is tested. Future Testing: Future studies should include replica tests, tests with Jet A vapor and warm liquid Jet A layers, and sensitivity tests to examine ignition location, fuel concentration, and vent area perturbations. Summary: Explosion tests in a 747-100 CWT model reveal that a very complex pattern of combustion occurs due the interaction of the flame and the flow-generated turbulence. A wide range of structural load patterns occur, depending on the location of the ignition source. Some of these load patterns are consistent with damage believed to be associated with the initial explosion event in TWA 800. Sensitivity of the loading to the ignition location indicates that narrowing down the ignition location in TWA 800 may be possible. However, the complexity of the combustion and structural failure processes in the actual center wing tank mandates extremely careful consideration of the uncertainties that enter into this process

The source structure of 0642+449 detected from the CONT14 observations

The CONT14 campaign with state-of-the-art VLBI data has observed the source 0642+449 with about one thousand observables each day during a continuous observing period of fifteen days, providing tens of thousands of closure delays---the sum of the delays around a closed loop of baselines. The closure delay is independent of the instrumental and propagation delays and provides valuable additional information about the source structure. We demonstrate the use of this new "observable" for the determination of the structure in the radio source 0642+449. This source, as one of the defining sources in the second realization of the International Celestial Reference Frame (ICRF2), is found to have two point-like components with a relative position offset of -426 microarcseconds in right ascension and -66 microarcseconds in declination. The two components are almost equally bright with a flux-density ratio of 0.92. The standard deviation of closure delays for source 0642+449 was reduced from 139 ps to 90 ps by using this two-component model. Closure delays larger than one nanosecond are found to be related to the source structure, demonstrating that structure effects for a source with this simple structure could be up to tens of nanoseconds. The method described in this paper does not rely on a priori source structure information, such as knowledge of source structure determined from direct (Fourier) imaging of the same observations or observations at other epochs. We anticipate our study to be a starting point for more effective determination of the structure effect in VLBI observations.Comment: 14 pages, 13 figures, Accepted by Astronomical Journal on 12 Jul, 201

Oogenesis: Single cell development and differentiation

AbstractOocytes express a unique set of genes that are essential for their growth, for meiotic recombination and division, for storage of nutrients, and for fertilization. We have utilized the newly sequenced genome of Strongylocentrotus purpuratus to identify genes that help the oocyte accomplish each of these tasks. This study emphasizes four classes of genes that are specialized for oocyte function: (1) Transcription factors: many of these factors are not significantly expressed in embryos, but are shared by other adult tissues, namely the ovary, testis, and gut. (2) Meiosis: A full set of meiotic genes is present in the sea urchin, including those involved in cohesion, in synaptonemal complex formation, and in meiotic recombination. (3) Yolk uptake and storage: Nutrient storage for use during early embryogenesis is essential to oocyte function in most animals; the sea urchin accomplishes this task by using the major yolk protein and a family of accessory proteins called YP30. Comparison of the YP30 family members across their conserved, tandem fasciclin domains with their intervening introns reveals an incongruence in the evolution of its major clades. (4) Fertilization: This set of genes includes many of the cell surface proteins involved in sperm interaction and in the physical block to polyspermy. The majority of these genes are active only in oocytes, and in many cases, their anatomy reflects the tandem repeating interaction domains essential for the function of these proteins. Together, the expression profile of these four gene classes highlights the transitions of the oocyte from a stem cell precursor, through stages of development, to the clearing and re-programming of gene expression necessary to transition from oocyte, to egg, to embryo

Evaluation of Vascular Control Mechanisms Utilizing Video Microscopy of Isolated Resistance Arteries of Rats

This protocol describes the use of in vitro television microscopy to evaluate vascular function in isolated cerebral resistance arteries (and other vessels), and describes techniques for evaluating tissue perfusion using Laser Doppler Flowmetry (LDF) and microvessel density utilizing fluorescently labeled Griffonia simplicifolia (GS1) lectin. Current methods for studying isolated resistance arteries at transmural pressures encountered in vivo and in the absence of parenchymal cell influences provide a critical link between in vivo studies and information gained from molecular reductionist approaches that provide limited insight into integrative responses at the whole animal level. LDF and techniques to selectively identify arterioles and capillaries with fluorescently-labeled GS1 lectin provide practical solutions to enable investigators to extend the knowledge gained from studies of isolated resistance arteries. This paper describes the application of these techniques to gain fundamental knowledge of vascular physiology and pathology in the rat as a general experimental model, and in a variety of specialized genetically engineered designer rat strains that can provide important insight into the influence of specific genes on important vascular phenotypes. Utilizing these valuable experimental approaches in rat strains developed by selective breeding strategies and new technologies for producing gene knockout models in the rat, will expand the rigor of scientific premises developed in knockout mouse models and extend that knowledge to a more relevant animal model, with a well understood physiological background and suitability for physiological studies because of its larger size

The unique chemistry of Eastern Mediterranean water masses selects for distinct microbial communities by depth

Peer reviewedPublisher PD

History of Foster Care Among Homeless Adults with Mental Illness in Vancouver, British Columbia: A Precursor to Trajectories of Risk

Background It is well documented that a disproportionate number of homeless adults have childhood histories of foster care placement(s). This study examines the relationship between foster care placement as a predictor of adult substance use disorders (including frequency, severity and type), mental illness, vocational functioning, service use and duration of homelessness among a sample of homeless adults with mental illness. We hypothesize that a history of foster care predicts earlier, more severe and more frequent substance use, multiple mental disorder diagnoses, discontinuous work history, and longer durations of homelessness. Methods This study was conducted using baseline data from two randomized controlled trials in Vancouver, British Columbia for participants who responded to a series of questions pertaining to out-of-home care at 12 months follow-up (n = 442). Primary outcomes included current mental disorders; substance use including type, frequency and severity; physical health; duration of homelessness; vocational functioning; and service use. Results In multivariable regression models, a history of foster care placement independently predicted incomplete high school, duration of homelessness, discontinuous work history, less severe types of mental illness, multiple mental disorders, early initiation of drug and/or alcohol use, and daily drug use. Conclusions This is the first Canadian study to investigate the relationship between a history of foster care and current substance use among homeless adults with mental illness, controlling for several other potential confounding factors. It is important to screen homeless youth who exit foster care for substance use, and to provide integrated treatment for concurrent disorders to homeless youth and adults who have both psychiatric and substance use problems