3,410 research outputs found

    Coatomer-bound Cdc42 regulates dynein recruitment to COPI vesicles

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    Cytoskeletal dynamics at the Golgi apparatus are regulated in part through a binding interaction between the Golgi-vesicle coat protein, coatomer, and the regulatory GTP-binding protein Cdc42 (Wu, W.J., J.W. Erickson, R. Lin, and R.A. Cerione. 2000. Nature. 405:800–804; Fucini, R.V., J.L. Chen, C. Sharma, M.M. Kessels, and M. Stamnes. 2002. Mol. Biol. Cell. 13:621–631). The precise role of this complex has not been determined. We have analyzed the protein composition of Golgi-derived coat protomer I (COPI)–coated vesicles after activating or inhibiting signaling through coatomer-bound Cdc42. We show that Cdc42 has profound effects on the recruitment of dynein to COPI vesicles. Cdc42, when bound to coatomer, inhibits dynein binding to COPI vesicles whereas preventing the coatomer–Cdc42 interaction stimulates dynein binding. Dynein recruitment was found to involve actin dynamics and dynactin. Reclustering of nocodazole-dispersed Golgi stacks and microtubule/dynein-dependent ER-to-Golgi transport are both sensitive to disrupting Cdc42 mediated signaling. By contrast, dynein-independent transport to the Golgi complex is insensitive to mutant Cdc42. We propose a model for how proper temporal regulation of motor-based vesicle translocation could be coupled to the completion of vesicle formation

    Concentrated Perchlorate at the Mars Phoenix Landing Site: Evidence for Thin Film Liquid Water on Mars

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    NASA\u27s Phoenix mission, which landed on the northern plains of Mars in 2008, returned evidence of the perchlorate anion distributed evenly throughout the soil column at the landing site. Here, we use spectral data from Phoenix\u27s Surface Stereo Imager to map the distribution of perchlorate salts at the Phoenix landing site, and find that perchlorate salt has been locally concentrated into subsurface patches, similar to salt patches that result from aqueous dissolution and redistribution on Earth. We propose that thin films of liquid water are responsible for translocating perchlorate from the surface to the subsurface, and for concentrating it in patches. The thin films are interpreted to result from melting of minor ice covers related to seasonal and long-term obliquity cycles

    Pair-instability and super-luminous supernova discoveries at z = 2.05, z = 2.50, and z = 3.90

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    We present the discovery of three super-luminous supernovae (SLSNe) at z = 2 - 4 as part of our survey to detect ultraviolet-luminous supernova at z > 2. SLSNe are ≥10 times more luminous than normal supernova types, reaching peak luminosities of ≳10^(44) erg s^(−1). A small subset of SLSNe (type SLSN-R) exhibit a slow evolution, and thus enormous integrated energies (≳10^(51) erg), consistent with the radiative decay of several solar masses of 56 Ni. SLSN-R are believed to be the deaths of very massive stars, ∼140 - 260 M_⊙, that are theorized to result in pair-instability supernovae. Two of the high redshift SLSNe presented here are consistent with the behavior of SLSN-R out to the extent in which their light curves are sampled, with the third event being consistent with the more rapid fade of the type II-L SLSN SN 2008es at z = 0.205. SLSNe are extremely rare locally but are expected to have been more common in the early Universe and as members of the first generation of stars to form after the Big Bang, the Population III stars. The high intrinsic luminosity of SLSNe and their detectability using our image-stacking technique out to z ∼ 6 provide the first viable route to detect and study the deaths of massive Population III stars which are expected to form in pristine gas at redshifts as low as z ∼ 2

    β-D-N4-hydroxycytidine (NHC) Inhibits SARS-CoV-2 Through Lethal Mutagenesis But Is Also Mutagenic To Mammalian Cells

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    Mutagenic ribonucleosides can act as broad-based antiviral agents. They are metabolized to the active ribonucleoside triphosphate form and concentrate in the genomes of RNA viruses during viral replication. β-D-N 4-hydroxycytidine (NHC, the initial metabolite of molnupiravir) is more than 100-fold more active than ribavirin or favipiravir against SARS-CoV-2, with antiviral activity correlated to the level of mutagenesis in virion RNA. However, NHC also displays host mutational activity in an animal cell culture assay, consistent with RNA and DNA precursors sharing a common intermediate of a ribonucleoside diphosphate. These results indicate that highly active mutagenic ribonucleosides may hold risk for the host
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