The Response of Caenorhabditis elegans to Hydrogen Sulfide and Hydrogen Cyanide

Hydrogen sulfide (H2S), an endogenously produced small molecule, protects animals from various stresses. Recent studies demonstrate that animals exposed to H2S are long lived, resistant to hypoxia, and resistant to ischemia–reperfusion injury. We performed a forward genetic screen to gain insights into the molecular mechanisms Caenorhabditis elegans uses to appropriately respond to H2S. At least two distinct pathways appear to be important for this response, including the H2S-oxidation pathway and the hydrogen cyanide (HCN)-assimilation pathway. The H2S-oxidation pathway requires two distinct enzymes important for the oxidation of H2S: the sulfide:quinone reductase sqrd-1 and the dioxygenase ethe-1. The HCN-assimilation pathway requires the cysteine synthase homologs cysl-1 and cysl-2. A low dose of either H2S or HCN can activate hypoxia-inducible factor 1 (HIF-1), which is required for C. elegans to respond to either gas. sqrd-1 and cysl-2 represent the entry points in the H2S-oxidation and HCN-assimilation pathways, respectively, and expression of both of these enzymes is highly induced by HIF-1 in response to both H2S and HCN. In addition to their role in appropriately responding to H2S and HCN, we found that cysl-1 and cysl-2 are both essential mediators of innate immunity against fast paralytic killing by Pseudomonas. Furthermore, in agreement with these data, we showed that growing worms in the presence of H2S is sufficient to confer resistance to Pseudomonas fast paralytic killing. Our results suggest the hypoxia-independent hif-1 response in C. elegans evolved to respond to the naturally occurring small molecules H2S and HCN

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

Dealing with mobility: Understanding access anytime, anywhere

The rapid and accelerating move towards the adoption and use of mobile technologies has increasingly provided people and organisations with the ability to work away from the office and on the move. The new ways of working afforded by these technologies are often characterised in terms of access to information and people ‘anytime, anywhere’. This paper presents a study of mobile workers that highlights different facets of access to remote people and information, and different facets of anytime, anywhere. Four key factors in mobile work are identified from the study: the role of planning, working in ‘dead time’, accessing remote technological and informational resources, and monitoring the activities of remote colleagues. By reflecting on these issues, we can better understand the role of technology and artefact use in mobile work and identify the opportunities for the development of appropriate technological solutions to support mobile workers

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

Decoherence of electron spin qubits in Si-based quantum computers

Direct phonon spin-lattice relaxation of an electron qubit bound by a donor impurity or quantum dot in SiGe heterostructures is investigated. The aim is to evaluate the importance of decoherence from this mechanism in several important solid-state quantum computer designs operating at low temperatures. We calculate the relaxation rate $1/T_1$ as a function of [100] uniaxial strain, temperature, magnetic field, and silicon/germanium content for Si:P bound electrons. The quantum dot potential is much smoother, leading to smaller splittings of the valley degeneracies. We have estimated these splittings in order to obtain upper bounds for the relaxation rate. In general, we find that the relaxation rate is strongly decreased by uniaxial compressive strain in a SiGe-Si-SiGe quantum well, making this strain an important positive design feature. Ge in high concentrations (particularly over 85%) increases the rate, making Si-rich materials preferable. We conclude that SiGe bound electron qubits must meet certain conditions to minimize decoherence but that spin-phonon relaxation does not rule out the solid-state implementation of error-tolerant quantum computing.Comment: 8 figures. To appear in PRB-July 2002. Revisions include: some references added/corrected, several typos fixed, a few things clarified. Nothing dramati

Do the photometric colors of Type II-P Supernovae allow accurate determination of host galaxy extinction?

We present infrared photometry of SN 1999em, plus optical photometry, infrared photometry, and optical spectroscopy of SN 2003hn. Both objects were Type II-P supernovae. The V-[RIJHK] color curves of these supernovae evolved in a very similar fashion until the end of plateau phase. This allows us to determine how much more extinction the light of SN 2003hn suffered compared to SN 1999em. Since we have an estimate of the total extinction suffered by SN 1999em from model fits of ground-based and space-based spectra as well as photometry of SN 1999em, we can estimate the total extinction and absolute magnitudes of SN 2003hn with reasonable accuracy. Since the host galaxy of SN 2003hn also produced the Type Ia SN 2001el, we can directly compare the absolute magnitudes of these two SNe of different types.Comment: 24 pages, 6 figure

Optical and Infrared Photometry of the Type Ia Supernovae 1999da, 1999dk, 1999gp, 2000bk, and 2000ce

We present BVRI photometry of the Type Ia supernovae 1999da, 1999dk, 1999gp, 2000bk, and 2000ce, plus infrared photometry of three of these. These objects exhibit the full range of decline rates of Type Ia supernovae. Combined optical and infrared data show that families of V - infrared color curves can be used to derive the host extinction (A_V) of these objects. Existing data do not yet allow us to construct these loci for all color indices and supernova decline rates, but the V-K color evolution is sufficiently uniform that it allows the determination of host extinction over a wide range of supernova decline rates to an accuracy of roughly +/- 0.1 mag. We introduce a new empirical parameter, the mean I-band flux 20 to 40 days after maximum light, and show how it is directly related to the decline rate.Comment: 53 pages, 18 figures, accepted for publication in the Astronomical Journal (scheduled for the September 2001 issue