p21 is decreased in polycystic kidney disease and leads to increased epithelial cell cycle progression: roscovitine augments p21 levels.

BackgroundAutosomal dominant polycystic kidney disease (ADPKD) is a common genetic disease with few treatment options other than renal replacement therapy. p21, a cyclin kinase inhibitor which has pleiotropic effects on the cell cycle, in many cases acts to suppress cell cycle progression and to prevent apoptosis. Because defects in cell cycle arrest and apoptosis of renal tubular epithelial cells occur in PKD, and in light of earlier reports that polycystin-1 upregulates p21 and that the cyclin-dependent kinase inhibitor roscovitine arrests progression in a mouse model, we asked whether (1) p21 deficiency might underlie ADPKD and (2) the mechanism of the salutary roscovitine effect on PKD involves p21.Methodsp21 levels in human and animal tissue samples as well as cell lines were examined by immunoblotting and/or immunohistochemisty. Apoptosis was assessed by PARP cleavage. p21 expression was attenuated in a renal tubular epithelial cell line by antisense methods, and proliferation in response to p21 attenuation and to roscovitine was assessed by the MTT assay.ResultsWe show that p21 is decreased in human as well as a non-transgenic rat model of ADPKD. In addition, hepatocyte growth factor, which induces transition from a cystic to a tubular phenotype, increases p21 levels. Furthermore, attenuation of p21 results in augmentation of cell cycle transit in vitro. Thus, levels of p21 are inversely correlated with renal tubular epithelial cell proliferation. Roscovitine, which has been shown to arrest progression in a murine model of PKD, increases p21 levels and decreases renal tubular epithelial cell proliferation, with no affect on apoptosis.ConclusionThe novelty of our study is the demonstration in vivo in humans and rat models of a decrement of p21 in cystic kidneys as compared to non-cystic kidneys. Validation of a potential pathogenetic model of increased cyst formation due to enhanced epithelial proliferation and apoptosis mediated by p21 suggests a mechanism for the salutary effect of roscovitine in ADPKD and supports further investigation of p21 as a target for future therapy

QZ Serpentis: A Dwarf Nova with a 2-Hour Orbital Period and an Anomalously Hot, Bright Secondary Star

We present spectroscopy and time-series photometry of the dwarf nova QZ Ser. The spectrum shows a rich absorption line spectrum of type K4 +- 2. K-type secondary stars are generally seen in dwarf novae with orbital periods P-orb around 6 h, but in QZ Ser the absorption radial velocities show an obvious modulation (semi-amplitude 207(5) km/s) at P-orb = 119.752(2) min, much shorter than typical for such a relatively warm and prominent secondary spectrum. The H-alpha emission-line velocity is modulated at the same period and roughly opposite phase. Time-series photometry shows flickering superposed on a modulation with two humps per orbit, consistent with ellipsoidal variation of the secondary's light. QZ Ser is a second example of a relatively short-period dwarf nova with a surprisingly warm secondary. Model calculations suggest that the secondary is strongly enhanced in helium, and had already undergone significant nuclear evolution when mass transfer began. Several sodium absorption features in the secondary spectrum are unusually strong, which may indicate that the present-day surface was the site of CNO-cycle hydrogen burning in the past.Comment: 11 pages, 3 postscript figures, 1 jpeg greyscale figure. Accepted for publication in PAS

Trapped Ar isotopes in meteorite ALH 84001 indicate Mars did not have a thick ancient atmosphere

Water is not currently stable in liquid form on the martian surface due to the present mean atmospheric pressure of ∼7 mbar and mean global temperature of ∼220 K. However, geomorphic features and hydrated mineral assemblages suggest that Mars’ climate was once warmer and liquid water flowed on the surface. These observations may indicate a substantially more massive atmosphere in the past, but there have been few observational constraints on paleoatmospheric pressures. Here we show how the [superscript 40]Ar/[superscript 36]Ar ratios of trapped gases within martian meteorite ALH 84001 constrain paleoatmospheric pressure on Mars during the Noachian era [∼4.56–3.8 billion years (Ga)]. Our model indicates that atmospheric pressures did not exceed ∼1.5 bar during the first 400 million years (Ma) of the Noachian era, and were <400 mbar by 4.16 Ga. Such pressures of CO[subscript 2] are only sufficient to stabilize liquid water on Mars’ surface at low latitudes during seasonally warm periods. Other greenhouse gases like SO[superscript 2] and water vapor may have played an important role in intermittently stabilizing liquid water at higher latitudes following major volcanic eruptions or impact events.United States. National Aeronautics and Space Administration. Mars Fundamental Research Program (Grant MFRP05-0108)Ann and Gordon Getty Foundatio

Hydrodynamics of polar liquid crystals

Starting from a microscopic definition of an alignment vector proportional to the polarization, we discuss the hydrodynamics of polar liquid crystals with local $C_{\infty v}$-symmetry. The free energy for polar liquid crystals differs from that of nematic liquid crystals ($D_{\infty h}$) in that it contains terms violating the ${\bf{n}}\to -{\bf{n}}$ symmetry. First we show that these $\mathcal{Z}_2$-odd terms induce a general splay instability of a uniform polarized state in a range of parameters. Next we use the general Poisson-bracket formalism to derive the hydrodynamic equations of the system in the polarized state. The structure of the linear hydrodynamic modes confirms the existence of the splay instability.Comment: 9 pages, corrected typos, added references, revised content, to appear in PR

Single-Receiver GPS Phase Bias Resolution

Existing software has been modified to yield the benefits of integer fixed double-differenced GPS-phased ambiguities when processing data from a single GPS receiver with no access to any other GPS receiver data. When the double-differenced combination of phase biases can be fixed reliably, a significant improvement in solution accuracy is obtained. This innovation uses a large global set of GPS receivers (40 to 80 receivers) to solve for the GPS satellite orbits and clocks (along with any other parameters). In this process, integer ambiguities are fixed and information on the ambiguity constraints is saved. For each GPS transmitter/receiver pair, the process saves the arc start and stop times, the wide-lane average value for the arc, the standard deviation of the wide lane, and the dual-frequency phase bias after bias fixing for the arc. The second step of the process uses the orbit and clock information, the bias information from the global solution, and only data from the single receiver to resolve double-differenced phase combinations. It is called "resolved" instead of "fixed" because constraints are introduced into the problem with a finite data weight to better account for possible errors. A receiver in orbit has much shorter continuous passes of data than a receiver fixed to the Earth. The method has parameters to account for this. In particular, differences in drifting wide-lane values must be handled differently. The first step of the process is automated, using two JPL software sets, Longarc and Gipsy-Oasis. The resulting orbit/clock and bias information files are posted on anonymous ftp for use by any licensed Gipsy-Oasis user. The second step is implemented in the Gipsy-Oasis executable, gd2p.pl, which automates the entire process, including fetching the information from anonymous ft

Communications Biophysics

Contains research objectives, summary of six research projects and reports on three research projects.National Institutes of Health (Grant 2 P01 MH-04737-06)Joint Services Electronics Programs (U. S. Army, U.S. Navy, and U.S. Air Force) under Contract DA 36-039-AMC-03200(E)National Science Foundation (Grant GK-835)National Aeronautics and Space Administration (Grant NsG-496)National Institutes of Health (Grant 5 ROI NB-05462-03

Meteorite evidence for partial differentiation and protracted accretion of planetesimals.

Modern meteorite classification schemes assume that no single planetary body could be source of both unmelted (chondritic) and melted (achondritic) meteorites. This dichotomy is a natural outcome of formation models assuming that planetesimal accretion occurred nearly instantaneously. However, it has recently been proposed that the accretion of many planetesimals lasted over ≳1 million years (Ma). This could have resulted in partially differentiated internal structures, with individual bodies containing iron cores, achondritic silicate mantles, and chondritic crusts. This proposal can be tested by searching for a meteorite group containing evidence for these three layers. We combine synchrotron paleomagnetic analyses with thermal, impact, and collisional evolution models to show that the parent body of the enigmatic IIE iron meteorites was such a partially differentiated planetesimal. This implies that some chondrites and achondrites simultaneously coexisted on the same planetesimal, indicating that accretion was protracted and that apparently undifferentiated asteroids may contain melted interiors

Communications Biophysics

Contains research objectives and reports on two research projects.National Institutes of Health (Grant 2 PO1 GM-14941-01)Joint Services Electronics Programs (U. S. Army, U.S. Navy, and U.S. Air Force) under Contract DA 28-043-AMC-02536(E)National Aeronautics and Space Administration (Grant NsG-496)National Institutes of Health (Grant 2 RO1 NB-05462-04)National Institutes of Health (Grant 1 TO1 GM-01555-01