Slowly cycling Rho kinase-dependent actomyosin cross-bridge slippage explains intrinsic high compliance of detrusor smooth muscle

Biological soft tissues are viscoelastic because they display timeindependent pseudoelasticity and time-dependent viscosity. However, there is evidence that the bladder may also display plasticity, defined as an increase in strain that is unrecoverable unless work is done by the muscle. In the present study, an electronic lever was used to induce controlled changes in stress and strain to determine whether rabbit detrusor smooth muscle (rDSM) is best described as viscoelastic or viscoelastic plastic. Using sequential ramp loading and unloading cycles, stress-strain and stiffness-stress analyses revealed that rDSM displayed reversible viscoelasticity, and that the viscous component was responsible for establishing a high stiffness at low stresses that increased only modestly with increasing stress compared with the large increase produced when the viscosity was absent and only pseudoelasticity governed tissue behavior. The study also revealed that rDSM underwent softening correlating with plastic deformation and creep that was reversed slowly when tissues were incubated in a Ca2+ -containing solution. Together, the data support a model of DSM as a viscoelastic-plastic material, with the plasticity resulting from motor protein activation. This model explains the mechanism of intrinsic bladder compliance as slipping cross bridges, predicts that wall tension is dependent not only on vesicle pressure and radius but also on actomyosin cross-bridge activity, and identifies a novel molecular target for compliance regulation, both physiologically and therapeutically

The Spitzer c2d Survey Of Nearby Dense Cores. XI. Infrared And Submillimeter Observations Of CB130

We present new observations of the CB130 region composed of three separate cores. Using the Spitzer Space Telescope, we detected a Class 0 and a Class II object in one of these, CB130-1. The observed photometric data from Spitzer and ground-based telescopes are used to establish the physical parameters of the Class 0 object. Spectral energy distribution fitting with a radiative transfer model shows that the luminosity of the Class 0 object is 0.14-0.16 L-circle dot, which is low for a protostellar object. In order to constrain the chemical characteristics of the core having the low-luminosity object, we compare our molecular line observations to models of lines including abundance variations. We tested both ad hoc step function abundance models and a series of self-consistent chemical evolution models. In the chemical evolution models, we consider a continuous accretion model and an episodic accretion model to explore how variable luminosity affects the chemistry. The step function abundance models can match observed lines reasonably well. The best-fitting chemical evolution model requires episodic accretion and the formation of CO2 ice from CO ice during the low-luminosity periods. This process removes C from the gas phase, providing a much improved fit to the observed gas-phase molecular lines and the CO2 ice absorption feature. Based on the chemical model result, the low luminosity of CB130-1 is explained better as a quiescent stage between episodic accretion bursts rather than being at the first hydrostatic core stage.NASA 1224608, 1288664, 1407, NNX07AJ72G, 1279198, 1288806, 1342425NSF AST-0607793, AST-0708158Korea government (MEST) 2009-0062866Ministry of Education, Science and Technology 2010-0008704Astronom

The Herschel Digit Survey Of Weak-Line T Tauri Stars: Implications For Disk Evolution And Dissipation

As part of the "Dust, Ice, and Gas In Time (DIGIT)" Herschel Open Time Key Program, we present Herschel photometry (at 70, 160, 250, 350, and 500 mu m) of 31 weak-line T Tauri star (WTTS) candidates in order to investigate the evolutionary status of their circumstellar disks. Of the stars in our sample, 13 had circumstellar disks previously known from infrared observations at shorter wavelengths, while 18 of them had no previous evidence for a disk. We detect a total of 15 disks as all previously known disks are detected at one or more Herschel wavelengths and two additional disks are identified for the first time. The spectral energy distributions (SEDs) of our targets seem to trace the dissipation of the primordial disk and the transition to the debris disk regime. Of the 15 disks, 7 appear to be optically thick primordial disks, including 2 objects with SEDs indistinguishable from those of typical Classical T Tauri stars, 4 objects that have significant deficit of excess emission at all IR wavelengths, and 1 "pre-transitional" object with a known gap in the disk. Despite their previous WTTS classification, we find that the seven targets in our sample with optically thick disks show evidence for accretion. The remaining eight disks have weaker IR excesses similar to those of optically thin debris disks. Six of them are warm and show significant 24 mu m Spitzer excesses, while the last two are newly identified cold debris-like disks with photospheric 24 mu m fluxes, but significant excess emission at longer wavelengths. The Herschel photometry also places strong constraints on the non-detections, where systems with F-70/F-70,(*) greater than or similar to 5-15 and L-disk/L-* greater than or similar to 10(-3) to 10(-4) can be ruled out. We present preliminary models for both the optically thick and optically thin disks and discuss our results in the context of the evolution and dissipation of circumstellar disks.NASA through JPL/CaltechNASA through the Sagan Fellowship ProgramEuropean Commission PERG06-GA-2009-256513Agence Nationale pour la Recherche (ANR) of France ANR-2010-JCJC-0504-01CFHT 11AH96Astronom

Plasmodium falciparum Antigens on the Surface of the Gametocyte-Infected Erythrocyte

BACKGROUND: The asexual blood stages of the human malaria parasite Plasmodium falciparum produce highly immunogenic polymorphic antigens that are expressed on the surface of the host cell. In contrast, few studies have examined the surface of the gametocyte-infected erythrocyte. METHODOLOGY/PRINCIPAL FINDINGS: We used flow cytometry to detect antibodies recognising the surface of live cultured erythrocytes infected with gametocytes of P. falciparum strain 3D7 in the plasma of 200 Gambian children. The majority of children had been identified as carrying gametocytes after treatment for malaria, and each donated blood for mosquito-feeding experiments. None of the plasma recognised the surface of erythrocytes infected with developmental stages of gametocytes (I-IV), but 66 of 194 (34.0%) plasma contained IgG that recognised the surface of erythrocytes infected with mature (stage V) gametocytes. Thirty-four (17.0%) of 200 plasma tested recognised erythrocytes infected with trophozoites and schizonts, but there was no association with recognition of the surface of gametocyte-infected erythrocytes (odds ratio 1.08, 95% C.I. 0.434-2.57; P = 0.851). Plasma antibodies with the ability to recognise gametocyte surface antigens (GSA) were associated with the presence of antibodies that recognise the gamete antigen Pfs 230, but not Pfs48/45. Antibodies recognising GSA were associated with donors having lower gametocyte densities 4 weeks after antimalarial treatment. CONCLUSIONS/SIGNIFICANCE: We provide evidence that GSA are distinct from antigens detected on the surface of asexual 3D7 parasites. Our findings suggest a novel strategy for the development of transmission-blocking vaccines

The COS Absorption Survey of Baryon Harbors (CASBaH): Warm-hot Circumgalactic Gas Reservoirs Traced by Ne VIII Absorption

We survey the highly ionized circumgalactic media (CGM) of 29 blindly selected galaxies at 0.49 < z_(gal) < 1.44 based on high-S/N ultraviolet spectra of z > 1 QSOs and the galaxy database from the COS Absorption Survey of Baryon Harbors (CASBaH). We detect the Ne VIII doublet in nine of the galaxies, and for gas with N(Ne VIII) > 10^13.3 cm^-2 (> 10^13.5 cm^-2), we derive a Ne VIII covering fraction f_c = 75 +15/-25% (44 +22/-20%) within impact parameter (rho) < 200 kpc of M_* = 10^(9.5-11.5) Msol galaxies and f_c = 70 +16/-22% (f_c = 42 +20/-17%) within rho < 1.5 virial radii. We estimate the mass in Ne VIII-traced gas to be M_gas(Ne VIII) > 10^9.5 Msol (Z/Zsol)^-1, or 6-20% of the expected baryonic mass if the Ne VIII absorbers have solar metallicity. Ionizing Ne VII to Ne VIII requires 207 eV, and photons with this energy are scarce in the CGM. However, for the median halo mass and redshift of our sample, the virial temperature is close to the peak temperature for the Ne VIII ion, and the Ne VIII-bearing gas is plausibly collisionally ionized near this temperature. Moreover, we find that photoionized Ne VIII requires cool and low-density clouds that would be highly underpressured (by approximately two orders of magnitude) relative to the putative, ambient virialized medium, complicating scenarios where such clouds could survive. Thus, more complex (e.g., non-equilibrium) models may be required; this first statistical sample of Ne VIII absorber/galaxy systems will provide stringent constraints for future CGM studies.Comment: Published in ApJL, Volume 877, Issue 2, Article L2

Vascular endothelial growth factor-A165b restores normal glomerular water permeability in a diphtheria-toxin mouse model of glomerular injury

BACKGROUND/AIMS:Genetic cell ablation using the human diphtheria toxin receptor (hDTR) is a new strategy used for analysing cellular function. Diphtheria toxin (DT) is a cytotoxic protein that leaves mouse cells relatively unaffected, but upon binding to hDTR it ultimately leads to cell death. We used a podocyte-specific hDTR expressing (Pod-DTR) mouse to assess the anti-permeability and cyto-protective effects of the splice isoform vascular endothelial growth factor (VEGF-A165b). METHODS:The Pod-DTR mouse was crossed with a mouse that over-expressed VEGF-A165b specifically in the podocytes (Neph-VEGF-A165b). Wild type (WT), Pod-DTR, Neph-VEGF-A165b and Pod-DTR X Neph-VEGF-A165b mice were treated with several doses of DT (1, 5, 100, and 1,000 ng/g bodyweight). Urine was collected and the glomerular water permeability (LpA/Vi) was measured ex vivo after 14 days. Structural analysis and podocyte marker expression were also assessed. RESULTS: Pod-DTR mice developed an increased glomerular LpA/Vi 14 days after administration of DT (all doses), which was prevented when the mice over-expressed VEGF-A165b. No major structural abnormalities, podocyte ablation or albuminuria was observed in Pod-DTR mice, indicating this to be a mild model of podocyte disease. However, a change in expression and localisation of nephrin within the podocytes was observed, indicating disruption of the slit diaphragm in the Pod-DTR mice. This was prevented in the Pod-DTR X Neph-VEGF-A165b mice. CONCLUSION: Although only a mild model of podocyte injury, over-expression of the anti-permeability VEGF-A165b isoform in the podocytes of Pod-DTR mice had a protective effect. Therefore, this study further highlights the therapeutic potential of VEGF-A165b in glomerular disease

The COS-Halos Survey: Physical Conditions and Baryonic Mass in the Low-Redshift Circumgalactic Medium

We analyze the physical conditions of the cool, photoionized (T $\sim 10^4$ K) circumgalactic medium (CGM) using the COS-Halos suite of gas column density measurements for 44 gaseous halos within 160 kpc of $L \sim L^*$ galaxies at $z \sim 0.2$. These data are well described by simple photoionization models, with the gas highly ionized (n$_{\rm HII}$/n$_{\rm H} \gtrsim 99\%$) by the extragalactic ultraviolet background (EUVB). Scaling by estimates for the virial radius, R$_{\rm vir}$, we show that the ionization state (tracked by the dimensionless ionization parameter, U) increases with distance from the host galaxy. The ionization parameters imply a decreasing volume density profile n$_{\rm H}$ = (10$^{-4.2 \pm 0.25}$)(R/R$_{\rm vir})^{-0.8\pm0.3}$. Our derived gas volume densities are several orders of magnitude lower than predictions from standard two-phase models with a cool medium in pressure equilibrium with a hot, coronal medium expected in virialized halos at this mass scale. Applying the ionization corrections to the HI column densities, we estimate a lower limit to the cool gas mass M$_{\rm CGM}^{\rm cool} > 6.5 \times 10^{10}$ M$_{\odot}$ for the volume within R $<$ R$_{\rm vir}$. Allowing for an additional warm-hot, OVI-traced phase, the CGM accounts for at least half of the baryons purported to be missing from dark matter halos at the 10$^{12}$ M$_{\odot}$ scale.Comment: 19 pages, 12 Figures, and a 37-page Appendix with 36 additional figures. Accepted to ApJ June 21 201