55 research outputs found
Possible function of the protein bound to nuclear complementary RNA
It was demonstrated that individual renal endothelial dilatory function of the healthy rat predicts susceptibility to subsequent renal damage induced by 5/6 nephrectomy. In addition, it is reported that myocardial infarction (MI) that was performed upon unilateral nephrectomy (UNx) induced highly variable renal damage. Therefore, whether the variability in renal damage after MI could be explained by the variation in individual renal endothelial function before the induction of injury was studied. Endothelium-dependent relaxation to acetylcholine was investigated in vitro in small arteries that were isolated from the extirpated kidney at UNx. MI was induced 1 wk after UNx by ligation of the left coronary artery. Proteinuria and systolic BP were evaluated weekly for 16 wk thereafter using metabolic cages and the tail-cuff method, respectively. Upon termination of the study, focal glomerulosclerosis was evaluated by histology as an additional marker of renal damage. After MI, nephrectomized male Wistar rats (n = 15) gradually developed variable proteinuria, ranging from 20 to 507 mg/24 h at week 16, with an average systolic BP of 131 +/- 7 mmHg. The individual renal endothelial function of the healthy rats predicted the extent of renal damage in terms of proteinuria (r = -0.62, P = 0.008) and focal glomerulosclerosis (r = -0.70, P = 0.003). The individual level of renal endothelial function in the healthy rat is able to predict the severity of renal damage that is induced by MI. Further exploration of the underlying mechanisms may lead to discovery of preventive renoprotective therapies
Author index for volume 286
Susceptibility to renal injury varies among individuals. Previously, we found that individual endothelial function of healthy renal arteries in vitro predicted severity of renal damage after 5/6 nephrectomy. Here we hypothesized that individual differences in endothelial function in vitro and renal perfusion in vivo predict the severity of renal damage in a model of adriamycin-induced nephropathy. In three separate studies, the following baseline parameters were measured in healthy male Wistar rats: (1) acetylcholine (ACh)-induced relaxation in small renal arteries in vitro (n = 16) and the contribution of prostaglandins, nitric oxide (NO) and endothelium-dependent hyperpolarizing factor (EDHF) to the relaxation; (2) glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) in spontaneously voiding rats in vivo (n = 16) and (3) the acute effect of the NO-synthase inhibitor N(G)-nitro-l-arginine methyl ester (L-NAME, n = 12) on renal blood flow (RBF) as compared to vehicle infusion (n = 9). Following these measurements, adriamycin (1.75 mg/kg i.v.) was injected and subsequent renal damage after 6 weeks was related to the baseline parameters. Total ACh-induced (r = 0.51, P <0.05) and EDHF-mediated relaxation (r = 0.68, P <0.05), as well as ERPF (r = 0.66, P <0.01), positively correlated with the severity of proteinuria 6 weeks after injection. In contrast, pronounced baseline NO-mediated dilation was associated with lower proteinuria (r = 0.71, P <0.01). Nevertheless, an acute L-NAME infusion, strongly reducing RBF by 22 +/- 8%, during adriamycin administration provided protection against the development of proteinuria. Individual animals with pronounced baseline endothelial dilatory ability measured in vitro and high ERPF in vivo are vulnerable to renal damage after the adriamycin injection. Acute inhibition of NO during adriamycin administration, resulting in a decrease of RBF, protects against renal injury, probably by limiting the delivery of the drug to the kidney. Therefore, interindividual variability in renal haemodynamics might be crucially involved in susceptibility to nephrotoxic renal damag
The Realm and Frontiers of Mycosis Fungoides
Objectives Chronic renal failure (CRF) is associated with altered systemic arterial tone and hypertension. Myogenic constriction and endothelium-derived hyperpolarizing factor (EDHF)-dependent relaxation represent major vasoregulatory mechanisms in small systemic arteries. Elevated myogenic response and impaired EDHF might participate in the development of essential hypertension; however, their role in CRF-related hypertension is unknown. We investigated whether myogenic response and EDHF are altered in subtotally nephrectornized (sNX) rats and whether these changes are modifiable by chronic treatment with angiotensin-converting enzyme (ACE) inhibitor. Methods In a pressure arteriograph, myogenic constriction and EDHF-mediated relaxation were evaluated in small mesenteric arteries isolated from male Wistar rats 15 weeks after either sham operation (n = 7) (SHAM), sNX (n = 12) or sNX followed by 9 weeks of treatment with lisinopril (sNX + LIS, 2.5 mg/kg, n = 13). Results Surprisingly, myogenic response was reduced in hypertensive CRF rats (maximal myogenic tone: 37 +/- 2 and 18 +/- 4%, P <0.01; peak myogenic index: -0.80 +/- 0.08 and -0.40 +/- 0.12%/mmHg, P <0.05 in SHAM and sNX respectively). At the same time EDHF-mediated relaxation was also impaired (maximal response: 92 +/- 2 and 77 +/- 5%, P <0.01; pD(2): 6.5 +/- 0.1 and 5.9 +/- 0.1, P <0.05). Both myogenic response and EDHF were inversely related to the severity of renal failure and restored by treatment with lisinopril to levels found in SHAM animals. Conclusion Major constrictive (myogenic) and dilatory (EDHF) mechanisms of small systemic arteries are impaired in hypertensive CRF rats. These alterations do not seem to participate in the development of hypertension, being rather directly related to the severity of renal impairment. Both systemic vascular changes might be restored by renoprotective treatment with ACE inhibitor
A systematic variation of the stellar initial mass function in early-type galaxies
Much of our knowledge of galaxies comes from analysing the radiation emitted
by their stars. It depends on the stellar initial mass function (IMF)
describing the distribution of stellar masses when the population formed.
Consequently knowledge of the IMF is critical to virtually every aspect of
galaxy evolution. More than half a century after the first IMF determination,
no consensus has emerged on whether it is universal in different galaxies.
Previous studies indicated that the IMF and the dark matter fraction in galaxy
centres cannot be both universal, but they could not break the degeneracy
between the two effects. Only recently indications were found that massive
elliptical galaxies may not have the same IMF as our Milky Way. Here we report
unambiguous evidence for a strong systematic variation of the IMF in early-type
galaxies as a function of their stellar mass-to-light ratio, producing
differences up to a factor of three in mass. This was inferred from detailed
dynamical models of the two-dimensional stellar kinematics for the large
Atlas3D representative sample of nearby early-type galaxies spanning two orders
of magnitude in stellar mass. Our finding indicates that the IMF depends
intimately on a galaxy's formation history.Comment: 4 pages, 2 figures, LaTeX. Accepted for publication as a Nature
Letter. More information about our Atlas3D project is available at
http://purl.org/atlas3
First spectroscopic observations of the galaxies that reionized the Universe
Low-mass galaxies in the early universe are believed to be the building
blocks of present-day galaxies. These fledgling systems likely played a pivotal
role in cosmic reionization, a major phase transition from neutral Hydrogen to
ionized plasma around 600-800 Myr after the Big Bang. However, these galaxies
have eluded comprehensive spectroscopic studies owing to their extreme
faintness. Here we report the first spectroscopic analysis of 8 ultra-faint
galaxies during the epoch of reionization with absolute magnitudes between
M to mag (down to 0.005 ). The
combination of ultra-deep NIRSpec (Near-Infrared Spectrograph) observations and
the strong gravitational lensing boost of Abell~2744 allow us to derive the
first spectroscopic constraints on the prevalence of faint galaxies and their
ionizing properties during the Universe's first billion years. We find that
faint galaxies are prodigious producers of ionizing photons with log(/ Hz erg) =, a factor of 4 larger than canonical
values. This means that the total rate of ionizing photons produced by galaxies
exceeds that needed for reionization, even for modest values of escape fraction
( =5%). These findings provide robust evidence that faint galaxies
were the main drivers of cosmic reionization at .Comment: 29 pages, 7 figures, 2 table
The Hubble Space Telescope Wide Field Camera 3 Early Release Science data: Panchromatic Faint Object Counts for 0.2-2 microns wavelength
We describe the Hubble Space Telescope (HST) Wide Field Camera 3 (WFC3) Early
Release Science (ERS) observations in the Great Observatories Origins Deep
Survey (GOODS) South field. The new WFC3 ERS data provide calibrated, drizzled
mosaics in the UV filters F225W, F275W, and F336W, as well as in the near-IR
filters F098M (Ys), F125W (J), and F160W (H) with 1-2 HST orbits per filter.
Together with the existing HST Advanced Camera for Surveys (ACS) GOODS-South
mosaics in the BViz filters, these panchromatic 10-band ERS data cover 40-50
square arcmin at 0.2-1.7 {\mu}m in wavelength at 0.07-0.15" FWHM resolution and
0.090" Multidrizzled pixels to depths of AB\simeq 26.0-27.0 mag (5-{\sigma})
for point sources, and AB\simeq 25.5-26.5 mag for compact galaxies.
In this paper, we describe: a) the scientific rationale, and the data taking
plus reduction procedures of the panchromatic 10-band ERS mosaics; b) the
procedure of generating object catalogs across the 10 different ERS filters,
and the specific star-galaxy separation techniques used; and c) the reliability
and completeness of the object catalogs from the WFC3 ERS mosaics. The
excellent 0.07-0.15" FWHM resolution of HST/WFC3 and ACS makes star- galaxy
separation straightforward over a factor of 10 in wavelength to AB\simeq 25-26
mag from the UV to the near-IR, respectively.Comment: 51 pages, 71 figures Accepted to ApJS 2011.01.2
Observations of the High Redshift Universe
(Abridged) In these lectures aimed for non-specialists, I review progress in
understanding how galaxies form and evolve. Both the star formation history and
assembly of stellar mass can be empirically traced from redshifts z~6 to the
present, but how the various distant populations inter-relate and how stellar
assembly is regulated by feedback and environmental processes remains unclear.
I also discuss how these studies are being extended to locate and characterize
the earlier sources beyond z~6. Did early star-forming galaxies contribute
significantly to the reionization process and over what period did this occur?
Neither theory nor observations are well-developed in this frontier topic but
the first results presented here provide important guidance on how we will use
more powerful future facilities.Comment: To appear in `First Light in Universe', Saas-Fee Advanced Course 36,
Swiss Soc. Astrophys. Astron. in press. 115 pages, 64 figures (see
http://www.astro.caltech.edu/~rse/saas-fee.pdf for hi-res figs.) For lecture
ppt files see
http://obswww.unige.ch/saas-fee/preannouncement/course_pres/overview_f.htm
The KMOS3D Survey: Demographics and Properties of Galactic Outflows at z=0.6-2.7
We present a census of ionized gas outflows in 599 normal galaxies at redshift 0.6 < z < 2.7, mostly based on integral field spectroscopy of H alpha, [N II], and [S II] line emission. The sample fairly homogeneously covers the main sequence of star-forming galaxies with masses 9.0 < log(M-*/M-circle dot) < 11.7, and probes into the regimes of quiescent galaxies and starburst outliers. About one-third exhibits the high-velocity component indicative of outflows, roughly equally split into winds driven by star formation (SF) and active galactic nuclei (AGNs). The incidence of SF-driven winds correlates mainly with SF properties. These outflows have typical velocities of similar to 450 km s(-1), local electron densities of n(e) similar to 380 cm(-3), modest mass loading factors of similar to 0.1-0.2 at all galaxy masses, and energetics compatible with momentum driving by young stellar populations. The SF-driven winds may escape from log(M-*/M-circle dot) less than or similar to 10.3 galaxies, but substantial mass, momentum, and energy in hotter and colder outflow phases seem required to account for low galaxy formation efficiencies in the low-mass regime. Faster AGN-driven outflows (similar to 1000-2000 km s(-1)) are commonly detected above log(M-*/M-circle dot) similar to 10.7, in up to similar to 75% of log(M-*/M-circle dot) greater than or similar to 11.2 galaxies. The incidence, strength, and velocity of AGN-driven winds strongly correlates with stellar mass and central concentration. Their outflowing ionized gas appears denser (n(e) similar to 1000 cm(-3)), and possibly compressed and shock-excited. These winds have comparable mass loading factors as the SF-driven winds but carry similar to 10 (similar to 50) times more momentum (energy). The results confirm our previous findings of high-duty-cycle, energy-driven outflows powered by AGN above the Schechter mass, which may contribute to SF quenching.E.S.W. and J.T.M. acknowledge
support by the Australian Research Council Center of
Excellence for All Sky Astrophysics in Three Dimensions
(ASTRO 3D), through project number CE170100013. D.J.W.
and M.F. acknowledge the support of the Deutsche Forschungsgemeinschaft via Project ID 3871/1-1 and 3871/1-2.
G.B.B. acknowledges support from the Cosmic Dawn Center,
which is funded by the Danish National Research Foundation
Commentary on the Special Issue on the Impact of Myogenic Tone in Health and Disease Preface
Autoregulation is a vital homeostatic mechanism that helps maintain constant delivery of oxygen to organs despite fluctuations in arteriolar pressure. Autoregulation of blood flow to elevations in pressure is largely mediated by the myogenic response of small arteries and arterioles which constrict in response to elevations in distending pressure. There is now general agreement that the myogenic response is an intrinsic property of vascular smooth muscle cells in the vessel wall that involves depolarization and calcium influx through L-type voltage-gated calcium channels (VGCC), calcium/calmodulin-dependent phosphorylation of myosin light chain kinase and actin myosin-based contraction. Despite intensive investigation, however, the mechanotransduction events that initiate the myogenic response and the signaling pathways involved remain uncertain. This special issue on the Impact of Myogenic Tone in Health and Disease includes 9 papers that address current thought regarding the molecular mechanisms underlying myogenic control of vascular tone in the renal, cerebral and coronary circulations and the evidence that impairments in the myogenic response contribute to the development of vascular and end organ damage associated with hypertension, diabetes and aging
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