SN 2002cx: The Most Peculiar Known Type Ia Supernova

We present photometric and spectroscopic observations of supernova (SN) 2002cx, which reveal it to be unique among all observed type Ia supernovae (SNe Ia). SN 2002cx exhibits a SN 1991T-like premaximum spectrum, a SN 1991bg-like luminosity, and expansion velocities roughly half those of normal SNe Ia. Photometrically, SN 2002cx has a broad peak in the $R$ band and a plateau phase in the $I$ band, and slow late-time decline. The $(B - V)$ color evolution is nearly normal, but the $(V - R)$ and $(V - I)$ colors are very red. Early-time spectra of SN 2002cx evolve very quickly and are dominated by lines from Fe-group elements; features from intermediate-mass elements (Ca, S, Si) are weak or absent. Mysterious emission lines are observed around 7000 \AA\ at about 3 weeks after maximum brightness. The nebular spectrum of SN 2002cx is also unique, consisting of narrow iron and cobalt lines. The observations of SN 2002cx are inconsistent with the observed spectral/photometric sequence, and provide a major challenge to our understanding of SNe Ia. No existing theoretical model can successfully explain all observed aspects of SN 2002cx.Comment: 60 pages, 12 figures. A high resolution PostScript version is available at http://astro.berkeley.edu/~weidong/sn2002cx.p

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

The Mechanism of Mammalian Pexophagy

The mechanism of mammalian pexophagy is poorly understood. Although ubiquitination is thought to be involved in the process, the upstream and downstream effectors of ubiquitination remain elusive. Specifically, the E3 ligase responsible for mediating ubiquitination is not known, the site(s) of ubiquitination on the peroxisomal membrane are not known, and the key autophagy receptor which binds ubiquitin at the surface of the peroxisome is not known. In the first chapter of this thesis, I introduce the peroxisome and the key players in general autophagy, as well as in the selective autophagy of the peroxisome. In the second chapter, I explain the reagents and techniques used in this thesis. In the third chapter, I identify and characterize the peroxisomal E3 ubiquitin ligase PEX2 as the causative agent for mammalian pexophagy, identify two peroxisomal membrane proteins which are ubiquitinated by PEX2, and identify NBR1 as the primary receptor in PEX2-mediated pexophagy. In the fourth chapter, I examine the regulation of PEX2 and demonstrate how a key metabolic stimulus, protein restriction, initiates signaling through the mTORC1 pathway which leads to pexophagy in cultured cells as well as in a mouse model. Finally, I conclude my thesis with a discussion on my findings and some general thoughts on the current state of the field.Ph.D.2019-02-16 00:00:0

Open Mouth Operations

Abstract This paper explains how central bank statements, rather than open market operations, can be used to implement monetary policy. In the extreme, policy instruments can be held constant, and yet interest rates will evolve along the path desired by the central bank. We show how the recent implementation of monetary policy in New Zealand works in this way. Using announcement data from New Zealand, we find that open mouth operations lead to large changes in interest rates across all maturities, and these changes cannot be explained by open market operations. Implications are drawn for monetary policy in other jurisdictions

Glyceryl Trinitrate Inhibits Hypoxia/Reoxygenation-Induced Apoptosis in the Syncytiotrophoblast of the Human Placenta : Therapeutic Implications for Preeclampsia

Damage of the placenta resulting from ischemia-reperfusion is important to the pathophysiology of preeclampsia. Here we investigated whether low concentrations of glyceryl trinitrate (GTN), a nitric oxide mimetic with anti-apoptotic properties, inhibit hypoxia/reoxygenation-induced apoptosis in the syncytiotrophoblast of chorionic villous explants from human placentas. Compared with villi analyzed immediately after delivery or maintained under normoxic conditions, villi exposed to a 6-hour cycle of hypoxia/reoxygenation exhibited greater numbers of syncytiotrophoblasts with terminal dUTP nick-end labeling (TUNEL)-positive nuclei in the syncytiotrophoblast. This increased number of TUNEL-positive nuclei was paralleled by higher levels of 4-hydroxynonenal (marker of lipid peroxidation), nitrotyrosine residues, and active caspase-3 and polyADP-ribose polymerase expression. Morphological analysis of explants exposed to hypoxia/reoxygenation revealed apoptotic and aponecrotic features similar to those of chorionic villi from preeclamptic pregnancies. Treatment with GTN during the hy-poxia/reoxygenation cycle blocked the increases in the number of TUNEL-positive nuclei and in the levels of 4-hydroxynonenal, nitrotyrosine, and active caspase-3. Incubation with GTN also attenuated the hypoxia/reoxygenation-induced polyADP-ribose polymerase expression and the apoptotic and aponecrotic morphological alterations. These results suggest that small concentrations of nitric oxide protect chorionic villi from hypoxia/reoxygenation-induced damage and provide a rationale for the use of low doses of nitric oxide mimetics in the treatment and/or prevention of preeclampsia