The Canis Major Dwarf Galaxy

Recent observational evidence suggests that the Sagittarius dwarf galaxy represents the only major ongoing accretion event in the Galactic halo, accounting for the majority of stellar debris identified there. This paper summarizes the recent discovery of another potential Milky Way accretion event, the Canis Major dwarf galaxy. This dwarf satellite galaxy is found to lie just below the Galactic plane and appears to be on an equatorial orbit. Unlike Sagittarius, which is contributing to the Galactic halo, the location and eventual demise of Canis Major suggests that it represents a building block of the thick disk.Comment: Refereed contribution to "Structure & Dynamics in the Local Universe, a workshop to honour Brent Tully's 60th birthday", Nov 2003. 4 pages + 2 figures (quality reduced due to size restrictions). To appear in PAS

A Vast Thin Plane of Co-rotating Dwarf Galaxies Orbiting the Andromeda Galaxy

Dwarf satellite galaxies are thought to be the remnants of the population of primordial structures that coalesced to form giant galaxies like the Milky Way. An early analysis noted that dwarf galaxies may not be isotropically distributed around our Galaxy, as several are correlated with streams of HI emission, and possibly form co-planar groups. These suspicions are supported by recent analyses, and it has been claimed that the apparently planar distribution of satellites is not predicted within standard cosmology, and cannot simply represent a memory of past coherent accretion. However, other studies dispute this conclusion. Here we report the existence (99.998% significance) of a planar sub-group of satellites in the Andromeda galaxy, comprising approximately 50% of the population. The structure is vast: at least 400 kpc in diameter, but also extremely thin, with a perpendicular scatter <14.1 kpc (99% confidence). Radial velocity measurements reveal that the satellites in this structure have the same sense of rotation about their host. This finding shows conclusively that substantial numbers of dwarf satellite galaxies share the same dynamical orbital properties and direction of angular momentum, a new insight for our understanding of the origin of these most dark matter dominated of galaxies. Intriguingly, the plane we identify is approximately aligned with the pole of the Milky Way's disk and is co-planar with the Milky Way to Andromeda position vector. The existence of such extensive coherent kinematic structures within the halos of massive galaxies is a fact that must be explained within the framework of galaxy formation and cosmology.Comment: Published in the 3rd Jan 2013 issue of Nature. 19 pages, 4 figures, 1 three-dimensional interactive figure. To view and manipulate the 3-D figure, an Adobe Reader browser plug-in is required; alternatively save to disk and view with Adobe Reade

The PAndAS Field of Streams: stellar structures in the Milky Way halo toward Andromeda and Triangulum

We reveal the highly structured nature of the Milky Way stellar halo within the footprint of the PAndAS photometric survey from blue main sequence and main sequence turn-off stars. We map no fewer than five stellar structures within a heliocentric range of ~5 to 30 kpc. Some of these are known (the Monoceros Ring, the Pisces/Triangulum globular cluster stream), but we also uncover three well-defined stellar structures that could be, at least partly, responsible for the so-called Triangulum/Andromeda and Triangulum/Andromeda 2 features. In particular, we trace a new faint stellar stream located at a heliocentric distance of ~17 kpc. With a surface brightness of \Sigma_V ~ 32-32.5 mag/arcsec^2, it follows an orbit that is almost parallel to the Galactic plane north of M31 and has so far eluded surveys of the Milky Way halo as these tend to steer away from regions dominated by the Galactic disk. Investigating our follow-up spectroscopic observations of PAndAS, we serendipitously uncover a radial velocity signature from stars that have colors and magnitudes compatible with the stream. From the velocity of eight likely member stars, we show that this stellar structure is dynamically cold, with an unresolved velocity dispersion that is lower than 7.1 km/s at the 90-percent confidence level. Along with the width of the stream (300-650 pc), its dynamics points to a dwarf-galaxy-accretion origin. The numerous stellar structures we can map in the Milky Way stellar halo between 5 and 30 kpc and their varying morphology is a testament to the complex nature of the stellar halo at these intermediate distances.Comment: 11 pages, 8 figures, accepted for publication in the ApJ, Figure 3 is the money plo

Therapeutic Rescue of Misfolded Mutants: Validation of Primary High Throughput Screens for Identification of Pharmacoperone Drugs

Functional rescue of misfolded mutant receptors by small non-peptide molecules has been demonstrated. These small, target-specific molecules (pharmacological chaperones or "pharmacoperones") serve as molecular templates, promote correct folding and allow otherwise misfolded mutants to pass the scrutiny of the cellular quality control system (QCS) and be expressed at the plasma membrane (PM) where they function similarly to wild type (WT) proteins. In the case of the gonadotropin releasing hormone receptor (GnRHR), drugs that rescue one mutant typically rescue many mutants, even if the mutations are located at distant sites (extracellular loops, intracellular loops, transmembrane helices). This increases the value of these drugs. These drugs are typically identified, post hoc, from "hits" in screens designed to detect antagonists or agonists. The therapeutic utility of pharmacoperones has been limited due to the absence of screens that enable identification of pharmacoperones per se.We describe a generalizable primary screening approach for pharmacoperone drugs based on measurement of gain of activity in stable HeLa cells stably expressing the mutants of two different model G-protein coupled receptors (GPCRs) (hGnRHR[E(90)K] or hV2R[L(83)Q]). These cells turn off expression of the receptor mutant gene of interest in the presence of tetracycline and its analogs, which provides a convenient means to identify false positives.The methods described and characterized here provide the basis of novel primary screens for pharmacoperones that detect drugs that rescue GPCR mutants of specific receptors. This approach will identify structures that would have been missed in screens that were designed to select only agonists or antagonists. Non-antagonistic pharmacoperones have a therapeutic advantage since they will not compete for endogenous agonists and may not have to be washed out once rescue has occurred and before activation by endogenous or exogenous agonists

Risk Factors for Cardiovascular Disease and Diet of Urban and Rural Dwellers in Northern Nigeria

Over the last 30 years, cardiovascular diseases (CVDs), including stroke and myocardial infarction, have increased in developing countries. Serum lipids and diet of the Fulani, a rural Nigerian population, were previously studied. Despite their consumption of a diet rich in saturated fat, the overall blood lipid profiles of Fulani men and women are generally favourable. However, Fulani males in the same study had mean serum levels of homocysteine, an emerging risk factor for CVD, that exceeded the upper limit of the homocysteine reference range. The authors were interested in knowing if these findings in the Fulani nomads were representative of the biochemical parameters of CVD risk in other ethnic groups in the same region of Nigeria. To address this question, the nutrient content of diets of 55 men, aged 20-75 years, and 77 women, aged 20-70 years, who were inhabitants of a large urban centre in northern Nigeria, was assessed, and their serum levels of total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, and homocysteine were determined. These data were compared with those of the same rural Fulani population studied previously. Urban subjects consumed more calories than rural subjects (men: 2,061 vs 1,691 kcal; women: 1,833 vs 1,505 kcal) and had a significantly higher mean body mass index (BMI) and percentage of body fat than rural subjects. Both urban males and females had carbohydrate intakes that were greater than those of Fulani pastoralists (men: 56% vs 33% total calories; women: 51% vs 38% total calories), but had a significantly lower dietary intake of total fat and saturated fat (men: 36% vs 51% of total calories; women: 40% vs 51% of total calories). With the exception of HDL-cholesterol levels, which were significantly lower in the rural population, the blood lipid profiles of rural subjects were more favourable compared to those of urban subjects. Both urban and rural males had homocysteine levels above the upper limit of the reference range for healthy adults (urban males-12.7\u3bcmol/L; rural males-15.2 \u3bcmol/L). The dietary intakes of folate and vitamin B12 were lower for rural Fulani subjects, and this was reflected in their significantly lower serum concentrations of these two vitamins. Results of this study suggest that, although the lipid profiles of urban and rural men and women in northern Nigeria indicate a relatively low risk for CVD, their elevated serum homocysteine levels are a cause for concern. The high homocysteine levels among rural men and women could be explained in part at least by their marginal status with respect to folate and vitamin B12

AN ULTRA-FAINT GALAXY CANDIDATE DISCOVERED in EARLY DATA from the MAGELLANIC SATELLITES SURVEY

We report a new ultra-faint stellar system found in Dark Energy Camera data from the first observing run of the Magellanic Satellites Survey (MagLiteS). MagLiteS J0644-5953 (Pictor II or Pic II) is a low surface brightness (μ = 28.5+1 -1 mag arcsec-2 within its half-light radius) resolved overdensity of old and metal-poor stars located at a heliocentric distance of 45+5 -4 kpc. The physical size (r1/2 = 46+15 -11) and low luminosity (Mv = -3.2+0.4 -0.5 mag) of this satellite are consistent with the locus of spectroscopically confirmed ultra-faint galaxies. MagLiteS J0644-5953 (Pic II) is located 11.3+3.1 -0.9 kpc from the Large Magellanic Cloud (LMC), and comparisons with simulation results in the literature suggest that this satellite was likely accreted with the LMC. The close proximity of MagLiteS J0644-5953 (Pic II) to the LMC also makes it the most likely ultra-faint galaxy candidate to still be gravitationally bound to the LM

Mothers' views on feeding infants around the time of weaning

OBJECTIVE: To describe women's views about aspects of infants' diets around the time of weaning, making comparisons with national guidelines. DESIGN: A survey of women with a 9-month-old child. SETTING: Adelaide, South Australia. SUBJECTS: Five hundred and five women who joined a longitudinal study during pregnancy. RESULTS: Sources of information varied, with written material most commonly used (37%). Cows' milk was considered suitable as the main drink for weaned infants by 14% of women. There were divergent views about the suitability of eggs, with many women concerned about allergy. The majority of women (84%) viewed fruit juice as suitable although many qualified their response, often by stating that fruit juice should be diluted. Almost all women considered the amount of sugar mattered, primarily because of tooth decay, and that salt mattered although the reason was often uncertain. It was widely believed (77%) that additives in food could cause health problems, in particular hyperactivity and allergies, and half of the women reported avoiding specific foods because of concerns about allergies. Many women thought that giving their child food that was high in fat would encourage a liking for ‘junk’ food or lead to fatness in adulthood. CONCLUSIONS: There is considerable diversity in the views women express about aspects of infant feeding that have been the subject of guidelines. Further health promotion efforts are needed to achieve greater consistency with recommendations and to address other concerns women have. This will entail greater engagement with parents and shared development of responses.Ruth B Walker, Jennifer A Conn, Michael J Davies and Vivienne M Moor

Interrogation of IDH1 Status in Gliomas by Fourier Transform Infrared Spectroscopy

Mutations in the isocitrate dehydrogenase 1 (IDH1) gene are found in a high proportion of diffuse gliomas. The presence of the IDH1 mutation is a valuable diagnostic, prognostic and predictive biomarker for the management of patients with glial tumours. Techniques involving vibrational spectroscopy, e.g., Fourier transform infrared (FTIR) spectroscopy, have previously demonstrated analytical capabilities for cancer detection, and have the potential to contribute to diagnostics. The implementation of FTIR microspectroscopy during surgical biopsy could present a fast, label-free method for molecular genetic classification. For example, the rapid determination of IDH1 status in a patient with a glioma diagnosis could inform intra-operative decision-making between alternative surgical strategies. In this study, we utilized synchrotron-based FTIR microanalysis to probe tissue microarray sections from 79 glioma patients, and distinguished the positive class (IDH1-mutated) from the IDH1-wildtype glioma, with a sensitivity and specificity of 82.4% and 83.4%, respectively. We also examined the ability of attenuated total reflection (ATR)-FTIR spectroscopy in detecting the biomolecular events and global epigenetic and metabolic changes associated with mutations in the IDH1 enzyme, in blood serum samples collected from an additional 72 brain tumour patients. Centrifugal filtration enhanced the diagnostic ability of the classification models, with balanced accuracies up to ~69%. Identification of the molecular status from blood serum prior to biopsy could further direct some patients to alternative treatment strategies

Quality Control Autophagy Degrades Soluble ERAD-Resistant Conformers of the Misfolded Membrane Protein GnRHR

Molecular chaperones triage misfolded proteins via action as substrate selectors for quality control (QC) machines that fold or degrade clients. Herein, the endoplasmic reticulum (ER) associated Hsp40 JB12 is reported to participate in partitioning mutant conformers of GnRHR, a G-protein coupled receptor, between ER-associated degradation (ERAD) and a novel ERQC-autophagy pathway for membrane proteins. ERQC-autophagy degrades E90K-GnRHR because pools of its partially folded and detergent soluble degradation intermediates are resistant to ERAD. S168R-GnRHR is globally misfolded and disposed of via ERAD, but inhibition of p97, the protein retrotranslocation motor, shunts S168R-GnRHR from ERAD to ERQC autophagy. Partially folded and grossly misfolded forms of GnRHR associate with JB12 and Hsp70. Elevation of JB12 promotes ERAD of S168R-GnRHR, with E90K-GnRHR being resistant. E90K-GnRHR elicits association of the Vps34 autophagy initiation complex with JB12. Interaction between ERassociated Hsp40s and the Vps34 complex permits the selective degradation of ERAD-resistant membrane proteins via ERQC-autophagy

The SFA Business Review Vol. 3 No. 3

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