Exploring the Universe with Metal-Poor Stars

The early chemical evolution of the Galaxy and the Universe is vital to our understanding of a host of astrophysical phenomena. Since the most metal-poor Galactic stars (with metallicities down to [Fe/H]\sim-5.5) are relics from the high-redshift Universe, they probe the chemical and dynamical conditions of the Milky Way and the origin and evolution of the elements through nucleosynthesis. They also provide constraints on the nature of the first stars, their associated supernovae and initial mass function, and early star and galaxy formation. The Milky Way's dwarf satellites contain a large fraction (~30%) of the known most metal-poor stars that have chemical abundances that closely resemble those of equivalent halo stars. This suggests that chemical evolution may be universal, at least at early times, and that it is driven by massive, energetic SNe. Some of these surviving, ultra-faint systems may show the signature of just one such PopIII star; they may even be surviving first galaxies. Early analogs of the surviving dwarfs may thus have played an important role in the assembly of the old Galactic halo whose formation can now be studied with stellar chemistry. Following the cosmic evolution of small halos in simulations of structure formation enables tracing the cosmological origin of the most metal-poor stars in the halo and dwarf galaxies. Together with future observations and additional modeling, many of these issues, including the reionization history of the Milky Way, may be constrained this way. The chapter concludes with an outlook about upcoming observational challenges and ways forward is to use metal-poor stars to constrain theoretical studies.Comment: 34 pages, 11 figures. Book chapter to appear in "The First Galaxies - Theoretical Predictions and Observational Clues", 2012 by Springer, eds. V. Bromm, B. Mobasher, T. Wiklin

The role of cell death in the pathogenesis of autoimmune disease: HMGB1 and microparticles as intercellular mediators of inflammation

Cell death is critical to normal homeostasis, although this process, when increased aberrantly, can lead to the production of pro-inflammatory mediators promoting autoimmunity. Two novel intercellular mediators of inflammation generated during cell death are high mobility group box 1 (HMGB1) protein and microparticles (MPs). HMGB1 is a nuclear protein that functions in transcription when inside the nucleus but takes on pro-inflammatory properties when released during cell death. Microparticles are small, membrane-bound structures that extrude from cells when they die and contain cell surface proteins and nuclear material from their parent cells. MPs circulate widely throughout the vasculature and mediate long-distance communication between cells. Both MPs and HMGB1 have been implicated in the pathogenesis of a broad spectrum of inflammatory diseases, including the prototypic autoimmune conditions systemic lupus erythematosus and rheumatoid arthritis. Given their range of activity and association with active disease, both structures may prove to be targets for effective therapy in these and other disorders

Identification of diarrheagenic Escherichia coli isolated from infants and children in Dar es Salaam, Tanzania

<p>Abstract</p> <p>Background</p> <p>Relatively few studies have been done in Tanzania to detect and classify diarrheagenic <it>Escherichia coli </it>(DEC) strains among children with diarrhea. This study aimed at investigating DEC among children in Dar es Salaam aged less than five years hospitalized due to acute/persistent diarrhea.</p> <p>Methods</p> <p>DEC were isolated from stool samples collected from two hundred and eighty children with acute/persistent diarrhea at Muhimbili National Hospital and Ilala and Mwananyamala Municipal Hospitals in Dar es Salaam. A multiplex PCR system method was used to detect a species specific gene for <it>E.coli </it>and ten different virulence genes for detection of five pathogroups of DEC namely enteroaggregative- (EAEC), enteropathogenic- (EPEC), enterotoxigenic- (ETEC), enteroinvasive- (EIEC) and enterohemorghagic- <it>Escherichia coli </it>(EHEC).</p> <p>Results</p> <p>Sixty-four patients (22.9%) harbored DEC. Forty-one of them (14.6%) were categorized as EAEC. Most of the EAEC (82.9%) were classified as typical EAEC possessing the <it>aggR </it>gene, and 92.6% carried the <it>aat </it>gene. Isolates from thirteen patients were EPEC (4.6%) and most of these (92.3%) were typical EPEC with both <it>eae </it>and <it>bfpA </it>genes. Ten isolates were identified as ETEC (3.6%) with only the heat stable toxin; either <it>st1a </it>or <it>st1b </it>but not both. Age wise, EAEC and EPEC were significantly more prevalent among the age group 0–6 months (p < 0.05). Genes for EHEC (<it>stx</it>₁and <it>stx</it>₂) and EIEC <it>(ial</it>) were not detected in this study group.</p> <p>Conclusion</p> <p>The results show a high proportion of DEC among Tanzanian children with diarrhea, with typical EAEC and typical EPEC predominating. The use of primers for both variants of ST1 (st1a and st1b) increased the sensitivity for detection of ETEC strains.</p

Sprouted Innervation into Uterine Transplants Contributes to the Development of Hyperalgesia in a Rat Model of Endometriosis

Endometriosis is an enigmatic painful disorder whose pain symptoms remain difficult to alleviate in large part because the disorder is defined by extrauteral endometrial growths whose contribution to pain is poorly understood. A rat model (ENDO) involves autotransplanting on abdominal arteries uterine segments that grow into vascularized cysts that become innervated with sensory and sympathetic fibers. ENDO rats exhibit vaginal hyperalgesia. We used behavioral, physiological, and immunohistochemical methods to test the hypothesis that cyst innervation contributes to the development of this hyperalgesia after transplant. Rudimentary sensory and sympathetic innervation appeared in the cysts at two weeks, sprouted further and more densely into the cyst wall by four weeks, and matured by six weeks post-transplant. Sensory fibers became abnormally functionally active between two and three weeks post-transplant, remaining active thereafter. Vaginal hyperalgesia became significant between four and five weeks post-transplant, and stabilized after six to eight weeks. Removing cysts before they acquired functional innervation prevented vaginal hyperalgesia from developing, whereas sham cyst removal did not. Thus, abnormally-active innervation of ectopic growths occurs before hyperalgesia develops, supporting the hypothesis. These findings suggest that painful endometriosis can be classified as a mixed inflammatory/neuropathic pain condition, which opens new avenues for pain relief. The findings also have implications beyond endometriosis by suggesting that functionality of any transplanted tissue can be influenced by the innervation it acquires

How to do a grounded theory study: a worked example of a study of dental practices

<p>Abstract</p> <p>Background</p> <p>Qualitative methodologies are increasingly popular in medical research. Grounded theory is the methodology most-often cited by authors of qualitative studies in medicine, but it has been suggested that many 'grounded theory' studies are not concordant with the methodology. In this paper we provide a worked example of a grounded theory project. Our aim is to provide a model for practice, to connect medical researchers with a useful methodology, and to increase the quality of 'grounded theory' research published in the medical literature.</p> <p>Methods</p> <p>We documented a worked example of using grounded theory methodology in practice.</p> <p>Results</p> <p>We describe our sampling, data collection, data analysis and interpretation. We explain how these steps were consistent with grounded theory methodology, and show how they related to one another. Grounded theory methodology assisted us to develop a detailed model of the process of adapting preventive protocols into dental practice, and to analyse variation in this process in different dental practices.</p> <p>Conclusions</p> <p>By employing grounded theory methodology rigorously, medical researchers can better design and justify their methods, and produce high-quality findings that will be more useful to patients, professionals and the research community.</p

Expression of SPIG1 Reveals Development of a Retinal Ganglion Cell Subtype Projecting to the Medial Terminal Nucleus in the Mouse

Visual information is transmitted to the brain by roughly a dozen distinct types of retinal ganglion cells (RGCs) defined by a characteristic morphology, physiology, and central projections. However, our understanding about how these parallel pathways develop is still in its infancy, because few molecular markers corresponding to individual RGC types are available. Previously, we reported a secretory protein, SPIG1 (clone name; D/Bsp120I #1), preferentially expressed in the dorsal region in the developing chick retina. Here, we generated knock-in mice to visualize SPIG1-expressing cells with green fluorescent protein. We found that the mouse retina is subdivided into two distinct domains for SPIG1 expression and SPIG1 effectively marks a unique subtype of the retinal ganglion cells during the neonatal period. SPIG1-positive RGCs in the dorsotemporal domain project to the dorsal lateral geniculate nucleus (dLGN), superior colliculus, and accessory optic system (AOS). In contrast, in the remaining region, here named the pan-ventronasal domain, SPIG1-positive cells form a regular mosaic and project exclusively to the medial terminal nucleus (MTN) of the AOS that mediates the optokinetic nystagmus as early as P1. Their dendrites costratify with ON cholinergic amacrine strata in the inner plexiform layer as early as P3. These findings suggest that these SPIG1-positive cells are the ON direction selective ganglion cells (DSGCs). Moreover, the MTN-projecting cells in the pan-ventronasal domain are apparently composed of two distinct but interdependent regular mosaics depending on the presence or absence of SPIG1, indicating that they comprise two functionally distinct subtypes of the ON DSGCs. The formation of the regular mosaic appears to be commenced at the end of the prenatal stage and completed through the peak period of the cell death at P6. SPIG1 will thus serve as a useful molecular marker for future studies on the development and function of ON DSGCs

Prisoners in Their Habitat? Generalist Dispersal by Habitat Specialists: A Case Study in Southern Water Vole (Arvicola sapidus)

Habitat specialists inhabiting scarce and scattered habitat patches pose interesting questions related to dispersal such as how specialized terrestrial mammals do to colonize distant patches crossing hostile matrices. We assess dispersal patterns of the southern water vole (Arvicola sapidus), a habitat specialist whose habitat patches are distributed through less than 2% of the study area (overall 600 km2) and whose populations form a dynamic metapopulational network. We predict that individuals will require a high ability to move through the inhospitable matrix in order to avoid genetic and demographic isolations. Genotypes (N = 142) for 10 microsatellites and sequences of the whole mitochondrial Control Region (N = 47) from seven localities revealed a weak but significant genetic structure partially explained by geographic distance. None of the landscape models had a significant effect on genetic structure over that of the Euclidean distance alone and no evidence for efficient barriers to dispersal was found. Contemporary gene flow was not severely limited for A. sapidus as shown by high migration rates estimates (>10%) between non-neighbouring areas. Sex-biased dispersal tests did not support differences in dispersal rates, as shown by similar average axial parent-offspring distances, in close agreement with capture-mark-recapture estimates. As predicted, our results do not support any preferences of the species for specific landscape attributes on their dispersal pathways. Here, we combine field and molecular data to illustrate how a habitat specialist mammal might disperse like a habitat generalist, acquiring specific long-distance dispersal strategies as an adaptation to patchy, naturally fragmented, heterogeneous and unstable habitats

Problems of multi-species organisms: endosymbionts to holobionts

The organism is one of the fundamental concepts of biology and has been at the center of many discussions about biological individuality, yet what exactly it is can be confusing. The definition that we find generally useful is that an organism is a unit in which all the subunits have evolved to be highly cooperative, with very little conflict. We focus on how often organisms evolve from two or more formerly independent organisms. Two canonical transitions of this type—replicators clustered in cells and endosymbiotic organelles within host cells—demonstrate the reality of this kind of evolutionary transition and suggest conditions that can favor it. These conditions include co-transmission of the partners across generations and rules that strongly regulate and limit conflict, such as a fair meiosis. Recently, much attention has been given to associations of animals with microbes involved in their nutrition. These range from tight endosymbiotic associations like those between aphids and Buchnera bacteria, to the complex communities in animal intestines. Here, starting with a reflection about identity through time (which we call “Theseus’s fish”), we consider the distinctions between these kinds of animal–bacteria interactions and describe the criteria by which a few can be considered jointly organismal but most cannot

Attentional bias retraining in cigarette smokers attempting smoking cessation (ARTS): study protocol for a double bline randomised controlled trial

YesSmokers attend preferentially to cigarettes and other smoking-related cues in the environment, in what is known as an attentional bias. There is evidence that attentional bias may contribute to craving and failure to stop smoking. Attentional retraining procedures have been used in laboratory studies to train smokers to reduce attentional bias, although these procedures have not been applied in smoking cessation programmes. This trial will examine the efficacy of multiple sessions of attentional retraining on attentional bias, craving, and abstinence in smokers attempting cessation. This is a double-blind randomised controlled trial. Adult smokers attending a 7-session weekly stop smoking clinic will be randomised to either a modified visual probe task with attentional retraining or placebo training. Training will start 1 week prior to quit day and be given weekly for 5 sessions. Both groups will receive 21 mg transdermal nicotine patches for 8–12 weeks and withdrawal-orientated behavioural support for 7 sessions. Primary outcome measures are the change in attentional bias reaction time and urge to smoke on the Mood and Physical Symptoms Scale at 4 weeks post-quit. Secondary outcome measures include differences in withdrawal, time to first lapse and prolonged abstinence at 4 weeks post-quit, which will be biochemically validated at each clinic visit. Follow-up will take place at 8 weeks, 3 months and 6 months post-quit. This is the first randomised controlled trial of attentional retraining in smokers attempting cessation. This trial could provide proof of principle for a treatment aimed at a fundamental cause of addiction.National Institute for Health Research (NIHR) Doctoral Research Fellowship (DRF) awarded to RB (DRF-2009-02-15

Drivers of reef shark abundance and biomass in the Solomon Islands

Remote island nations face a number of challenges in addressing concerns about shark population status, including access to rigorously collected data and resources to manage fisheries. At present, very little data are available on shark populations in the Solomon Islands and scientific surveys to document shark and ray diversity and distribution have not been completed. We aimed to provide a baseline of the relative abundance and diversity of reef sharks and rays and assess the major drivers of reef shark abundance/biomass in the Western Province of the Solomon Islands using stereo baited remote underwater video. On average reef sharks were more abundant than in surrounding countries such as Fiji and Indonesia, yet below that of remote islands without historical fishing pressure, suggesting populations are relatively healthy but not pristine. We also assessed the influence of location, habitat type/complexity, depth and prey biomass on reef shark abundance and biomass. Location was the most important factor driving reef shark abundance and biomass with two times the abundance and a 43% greater biomass of reef sharks in the more remote locations, suggesting fishing may be impacting sharks in some areas. Our results give a much needed baseline and suggest that reef shark populations are still relatively unexploited, providing an opportunity for improved management of sharks and rays in the Solomon Islands