Photometry of supernovae in an image series : methods and application to the Supernova Legacy Survey (SNLS)

We present a technique to measure lightcurves of time-variable point sources on a spatially structured background from imaging data. The technique was developed to measure light curves of SNLS supernovae in order to infer their distances. This photometry technique performs simultaneous PSF photometry at the same sky position on an image series. We describe two implementations of the method: one that resamples images before measuring fluxes, and one which does not. In both instances, we sketch the key algorithms involved and present the validation using semi-artificial sources introduced in real images in order to assess the accuracy of the supernova flux measurements relative to that of surrounding stars. We describe the methods required to anchor these PSF fluxes to calibrated aperture catalogs, in order to derive SN magnitudes. We find a marginally significant bias of 2 mmag of the after-resampling method, and no bias at the mmag accuracy for the non-resampling method. Given surrounding star magnitudes, we determine the systematic uncertainty of SN magnitudes to be less than 1.5 mmag, which represents about one third of the current photometric calibration uncertainty affecting SN measurements. The SN photometry delivers several by-products: bright star PSF flux mea- surements which have a repeatability of about 0.6%, as for aperture measurements; we measure relative astrometric positions with a noise floor of 2.4 mas for a single-image bright star measurement; we show that in all bands of the MegaCam instrument, stars exhibit a profile linearly broadening with flux by about 0.5% over the whole brightness range.Comment: Accepted for publication in A&A. 20 page

Differing roles of autophagy in HIV-associated neurocognitive impairment and encephalitis with implications for morphine co-exposure

We investigated the role of autophagy in HIV-infected subjects with neurocognitive impairment (NCI) ± HIV encephalitis (HIVE), many of which had a history of polysubstance abuse/dependence, using post-mortem brain tissues to determine whether differences in autophagy related factors may be more associated with NCI or NCI-encephalitis. Using qRT-PCR, we detected significant differences in gene expression levels with SQSTM1, LAMP1 higher in HIV-infected subjects without NCI while ATG5, SQSTM1 were then lower in HIV infection/NCI and ATG7, SQSTM1 being higher in NCI-HIVE. Immunohistochemical labeling of these autophagy associated proteins (also including Beclin 1 and LC3B) in Iba1-positive microglial cells showed generally higher immunoreactivity in the NCI and NCI-HIVE groups with more focal vs. diffuse patterns of expression in the NCI-HIVE group. Furthermore, analysis of microarray data from these same subjects found significantly higher levels of LAMP1 in NCI-HIVE compared to uninfected subjects in the basal ganglia. Finally, we tested the effect of supernatant from HIV-1-infected microglia and HIV-1 Tat protein in combination with morphine on neurons in vitro and found opposing events with both significant inhibition of autophagic flux and reduced dendrite length for morphine and supernatant treatment while Tat and morphine exposure resulted in lower autophagic activity at an earlier time point and higher levels in the later. These results suggest autophagy genes and their corresponding proteins may be differentially regulated at the transcriptional, translational, and post-translational levels in the brain during various stages of the HIV disease and that infected individuals exposed to morphine can experience mixed signaling of autophagic activity which could lead to more severe NCI than those without opioid use

Diet, Genetics, and Disease: A Focus on the Middle East and North Africa Region

The Middle East and North Africa (MENA) region suffers a drastic change from a traditional diet to an industrialized diet. This has led to an unparalleled increase in the prevalence of chronic diseases. This review discusses the role of nutritional genomics, or the dietary signature, in these dietary and disease changes in the MENA. The diet-genetics-disease relation is discussed in detail. Selected disease categories in the MENA are discussed starting with a review of their epidemiology in the different MENA countries, followed by an examination of the known genetic factors that have been reported in the disease discussed, whether inside or outside the MENA. Several diet-genetics-disease relationships in the MENA may be contributing to the increased prevalence of civilization disorders of metabolism and micronutrient deficiencies. Future research in the field of nutritional genomics in the MENA is needed to better define these relationships

High density of unrepaired genomic ribonucleotides leads to Topoisomerase 1-mediated severe growth defects in absence of ribonucleotide reductase

Cellular levels of ribonucleoside triphosphates (rNTPs) are much higher than those of deoxyribonucleoside triphosphates (dNTPs), thereby influencing the frequency of incorporation of ribonucleoside monophosphates (rNMPs) by DNA polymerases (Pol) into DNA. RNase H2-initiated ribonucleotide excision repair (RER) efficiently removes single rNMPs in genomic DNA. However, processing of rNMPs by Topoisomerase 1 (Top1) in absence of RER induces mutations and genome instability. Here, we greatly increased the abundance of genomic rNMPs in Saccharomyces cerevisiae by depleting Rnr1, the major subunit of ribonucleotide reductase, which converts ribonucleotides to deoxyribonucleotides. We found that in strains that are depleted of Rnr1, RER-deficient, and harbor an rNTP-permissive replicative Pol mutant, excessive accumulation of single genomic rNMPs severely compromised growth, but this was reversed in absence of Top1. Thus, under Rnr1 depletion, limited dNTP pools slow DNA synthesis by replicative Pols and provoke the incorporation of high levels of rNMPs in genomic DNA. If a threshold of single genomic rNMPs is exceeded in absence of RER and presence of limited dNTP pools, Top1-mediated genome instability leads to severe growth defects. Finally, we provide evidence showing that accumulation of RNA/DNA hybrids in absence of RNase H1 and RNase H2 leads to cell lethality under Rnr1 depletion

Functional morphological imaging of autism spectrum disorders: Current position and theories proposed

AbstractAutism is a pervasive disorder of childhood development. Polymorphous clinical profiles combining various degrees of communication and social interaction with restricted and stereotyped behaviour are grouped under the heading of ‘autism spectrum disorders’ (ASD). Many teams are trying to pick out the underlying cerebral abnormalities in order to understand the neuronal networks involved in relationships with others. Here we review the morphological, spectroscopic and functional abnormalities in the amygdala-hippocampal circuit, the caudate nuclei, the cerebellum, and the frontotemporal regions, which have been described in subjects with ASD. White matter abnormalities have also been described in diffusion tensor imaging, leading to suspected damage to the subjacent neural networks, such as mirror neurones or the social brain

Water Dynamics Around Proteins: T- and R-States of Hemoglobin and Melittin

The water dynamics, as characterized by the local hydrophobicity (LH), is investigated for tetrameric hemoglobin and dimeric melittin. For the T0 to R0 transition in Hb it is found that LH provides additional molecular-level insight into the Perutz mechanism, i.e., the breaking and formation of salt bridges at the alpha1 / beta2 and alpha2 / beta1 interface is accompanied by changes in LH. For Hb in cubic water boxes with 90 Aengstroem and 120 Aengstroem edge length it is observed that following a decrease in LH as a consequence of reduced water density or change of water orientation at the protein/water interface the alpha / beta interfaces are destabilized; this is a hallmark of the Perutz stereochemical model for the T to R transition in Hb. The present work thus provides a dynamical view of the classical structural model relevant to the molecular foundations of Hb function. For dimeric melittin, earlier results by Cheng and Rossky (Nature, 1998, 392, 696-699) are confirmed and interpreted on the basis of LH from simulations in which the protein structure is frozen. For the flexible melittin dimer the changes in the local hydration can be as much as 30 % than for the rigid dimer, reflecting the fact that protein and water dynamics are coupled