How Hyperpolarization and the Recovery of Excitability Affect Propagation through a Virtual Anode in the Heart

Researchers have suggested that the fate of a shock-induced wave front at the edge of a “virtual anode” (a region hyperpolarized by the shock) is a key factor determining success or failure during defibrillation of the heart. In this paper, we use a simple one-dimensional computer model to examine propagation speed through a hyperpolarized region. Our goal is to test the hypothesis that rapid propagation through a virtual anode can cause failure of propagation at the edge of the virtual anode. The calculations support this hypothesis and suggest that the time constant of the sodium inactivation gate is an important parameter. These results may be significant in understanding the mechanism of the upper limit of vulnerability

O-GlcNAc modification blocks the aggregation and toxicity of the protein α-synuclein associated with Parkinson's disease.

Several aggregation-prone proteins associated with neurodegenerative diseases can be modified by O-linked N-acetyl-glucosamine (O-GlcNAc) in vivo. One of these proteins, α-synuclein, is a toxic aggregating protein associated with synucleinopathies, including Parkinson's disease. However, the effect of O-GlcNAcylation on α-synuclein is not clear. Here, we use synthetic protein chemistry to generate both unmodified α-synuclein and α-synuclein bearing a site-specific O-GlcNAc modification at the physiologically relevant threonine residue 72. We show that this single modification has a notable and substoichiometric inhibitory effect on α-synuclein aggregation, while not affecting the membrane binding or bending properties of α-synuclein. O-GlcNAcylation is also shown to affect the phosphorylation of α-synuclein in vitro and block the toxicity of α-synuclein that was exogenously added to cells in culture. These results suggest that increasing O-GlcNAcylation may slow the progression of synucleinopathies and further support a general function for O-GlcNAc in preventing protein aggregation

Anomalous spin-splitting of two-dimensional electrons in an AlAs Quantum Well

We measure the effective Lande g-factor of high-mobility two-dimensional electrons in a modulation-doped AlAs quantum well by tilting the sample in a magnetic field and monitoring the evolution of the magnetoresistance oscillations. The data reveal that |g| = 9.0, which is much enhanced with respect to the reported bulk value of 1.9. Surprisingly, in a large range of magnetic field and Landau level fillings, the value of the enhanced g-factor appears to be constant.Comment: 4 pages, 3 figure

The Carnegie Supernova Project: The Low-Redshift Survey

Supernovae are essential to understanding the chemical evolution of the Universe. Type Ia supernovae also provide the most powerful observational tool currently available for studying the expansion history of the Universe and the nature of dark energy. Our basic knowledge of supernovae comes from the study of their photometric and spectroscopic properties. However, the presently available data sets of optical and near-infrared light curves of supernovae are rather small and/or heterogeneous, and employ photometric systems that are poorly characterized. Similarly, there are relatively few supernovae whose spectral evolution has been well sampled, both in wavelength and phase, with precise spectrophotometric observations. The low-redshift portion of the Carnegie Supernova Project (CSP) seeks to remedy this situation by providing photometry and spectrophotometry of a large sample of supernovae taken on telescope/filter/detector systems that are well understood and well characterized. During a five-year program which began in September 2004, we expect to obtain high-precision u'g'r'i'BVYJHKs light curves and optical spectrophotometry for about 250 supernovae of all types. In this paper we provide a detailed description of the CSP survey observing and data reduction methodology. In addition, we present preliminary photometry and spectra obtained for a few representative supernovae during the first observing campaign.Comment: 45 pages, 13 figures, 3 tables, accepted by PAS

Carnegie Supernova Project-II: Extending the Near-Infrared Hubble Diagram for Type Ia Supernovae to z∼0.1z\sim0.1

The Carnegie Supernova Project-II (CSP-II) was an NSF-funded, four-year program to obtain optical and near-infrared observations of a "Cosmology" sample of $\sim100$ Type Ia supernovae located in the smooth Hubble flow ($0.03 \lesssim z \lesssim 0.10$). Light curves were also obtained of a "Physics" sample composed of 90 nearby Type Ia supernovae at $z \leq 0.04$ selected for near-infrared spectroscopic time-series observations. The primary emphasis of the CSP-II is to use the combination of optical and near-infrared photometry to achieve a distance precision of better than 5%. In this paper, details of the supernova sample, the observational strategy, and the characteristics of the photometric data are provided. In a companion paper, the near-infrared spectroscopy component of the project is presented.Comment: 43 pages, 10 figures, accepted for publication in PAS

The Peculiar SN 2005hk: Do Some Type Ia Supernovae Explode as Deflagrations?

We present extensive u'g'r'i'BVRIYJHKs photometry and optical spectroscopy of SN 2005hk. These data reveal that SN 2005hk was nearly identical in its observed properties to SN 2002cx, which has been called ``the most peculiar known type Ia supernova.'' Both supernovae exhibited high ionization SN 1991T-like pre-maximum spectra, yet low peak luminosities like SN 1991bg. The spectra reveal that SN 2005hk, like SN 2002cx, exhibited expansion velocities that were roughly half those of typical type Ia supernovae. The R and I light curves of both supernovae were also peculiar in not displaying the secondary maximum observed for normal type Ia supernovae. Our YJH photometry of SN 2005hk reveals the same peculiarity in the near-infrared. By combining our optical and near-infrared photometry of SN 2005hk with published ultraviolet light curves obtained with the Swift satellite, we are able to construct a bolometric light curve from ~10 days before to ~60 days after B maximum. The shape and unusually low peak luminosity of this light curve, plus the low expansion velocities and absence of a secondary maximum at red and near-infrared wavelengths, are all in reasonable agreement with model calculations of a 3D deflagration which produces ~0.25 M_sun of 56Ni.Comment: Accepted by PASP, to appear in April 2007 issue, 63 pages, 16 figures, 11 table

BVRI Light Curves for 29 Type Ia Supernovae

BVRI light curves are presented for 27 Type Ia supernovae discovered during the course of the Calan/Tololo Survey and for two other SNe Ia observed during the same period. Estimates of the maximum light magnitudes in the B, V, and I bands and the initial decline rate parameter m15(B) are also given.Comment: 17 pages, figures and tables are not included (contact first author if needed), to appear in the Astronomical Journa

The metabolic adaptation evoked by arginine enhances the effect of radiation in brain metastases

Selected patients with brain metastases (BM) are candidates for radiotherapy. A lactatogenic metabolism, common in BM, has been associated with radioresistance. We demonstrated that BM express nitric oxide (NO) synthase 2 and that administration of its substrate l-arginine decreases tumor lactate in BM patients. In a placebo-controlled trial, we showed that administration of l-arginine before each fraction enhanced the effect of radiation, improving the control of BM. Studies in preclinical models demonstrated that l-arginine radiosensitization is a NO-mediated mechanism secondary to the metabolic adaptation induced in cancer cells. We showed that the decrease in tumor lactate was a consequence of reduced glycolysis that also impacted ATP and NAD+ levels. These effects were associated with NO-dependent inhibition of GAPDH and hyperactivation of PARP upon nitrosative DNA damage. These metabolic changes ultimately impaired the repair of DNA damage induced by radiation in cancer cells while greatly sparing tumor-infiltrating lymphocytes.Fil: Marullo, Rossella. Cornell University; Estados UnidosFil: Castro, Monica. Universidad de Buenos Aires; ArgentinaFil: Yomtoubian, Shira. Cornell University; Estados UnidosFil: Nieves Calvo Vidal, M.. Cornell University; Estados UnidosFil: Revuelta, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Krumsiek, Jan. Cornell University; Estados UnidosFil: Nicholas, Andrew P.. Cornell University; Estados UnidosFil: Cresta Morgado, Pablo. Universidad de Buenos Aires; ArgentinaFil: Yang, ShaoNing. Cornell University; Estados UnidosFil: Medina, Vanina Araceli. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Roth, Berta María Cristina. Universidad de Buenos Aires; ArgentinaFil: Bonomi, Marcelo. Ohio State University; Estados UnidosFil: Keshari, Kayvan R.. Memorial Sloan Kettering Cancer Center; Estados UnidosFil: Mittal, Vivek. Cornell University; Estados UnidosFil: Navigante, Alfredo Hugo. Universidad de Buenos Aires; ArgentinaFil: Cerchietti, Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Oncología "Ángel H. Roffo"; Argentin

Lipidomic Analysis of Arabidopsis T-DNA Insertion Lines Leads to Identification and Characterization of C-Terminal Alterations in FATTY ACID DESATURASE 6

Article states that mass-spectrometry-based screening of lipid extracts of wounded and unwounded leaves from a collection of 364 Arabidopsis thaliana T-DNA insertion lines produced lipid profiles that were scored on the number and significance of their differences from the leaf lipid profiles of wild-type plants. The analysis identified Salk_109175C, which displayed alterations in leaf chloroplast glycerolipid composition, including a decreased ratio between two monogalactosyldiacylglycerol (MGDG) molecular species, MGDG(18:3/16:3) and MGDG(18:3/18:3)

Immortalized Mouse Inner Ear Cell Lines Demonstrate a Role for Chemokines in Promoting the Growth of Developing Statoacoustic Ganglion Neurons

The target-derived factors necessary for promoting initial outgrowth from the statoacoustic ganglion (SAG) to the inner ear have not been fully characterized. In the present study, conditioned medium from embryonic Immortomouse inner ear cell lines that maintain many characteristics of developing inner ear sensory epithelia were screened for neurite-promoting activity. Conditioned medium found to be positive for promoting SAG neurite outgrowth and neuronal survival was then tested for the presence of chemokines, molecules that have not previously been investigated for promoting SAG outgrowth. One candidate molecule, monocyte chemotactic protein 1 (MCP-1), was detected in the conditioned medium and subsequently localized to mouse hair cells by immunocytochemistry. In vitro studies demonstrated that function-blocking MCP-1 antibodies decreased the amount of SAG neurite outgrowth induced by the conditioned medium and that subsequent addition of MCP-1 protein was able to promote outgrowth when added to the antibody-treated conditioned medium. The use of the Immortomouse cell lines proved valuable in identifying this candidate cofactor that promotes outgrowth of early-stage SAG nerve fibers and is expressed in embryonic hair cells.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41388/1/10162_2005_Article_13.pd