Early star-forming galaxies and the reionization of the Universe

Star forming galaxies represent a valuable tracer of cosmic history. Recent observational progress with Hubble Space Telescope has led to the discovery and study of the earliest-known galaxies corresponding to a period when the Universe was only ~800 million years old. Intense ultraviolet radiation from these early galaxies probably induced a major event in cosmic history: the reionization of intergalactic hydrogen. New techniques are being developed to understand the properties of these most distant galaxies and determine their influence on the evolution of the universe.Comment: Review article appearing in Nature. This posting reflects a submitted version of the review formatted by the authors, in accordance with Nature publication policies. For the official, published version of the review, please see http://www.nature.com/nature/archive/index.htm

A multilevel analysis of neighborhood and individual effects on individual smoking and drinking in Taiwan

<p>Abstract</p> <p>Background</p> <p>We assessed direct effects of neighborhood-level characteristics and interactive effects of neighborhood-level characteristics and individual socioeconomic position on adult smoking and drinking, after consideration of individual-level characteristics in Taiwan.</p> <p>Methods</p> <p>Data on individual sociodemographic characteristics, smoking, and drinking were obtained from Taiwan Social Change Survey conducted in 1990, 1995, and 2000. The overall response rate was 67%. A total of 5883 women and men aged over 20 living in 434 neighborhoods were interviewed. Participants' addresses were geocoded and linked with Taiwan census data for measuring neighborhood-level characteristics including neighborhood education, neighborhood concentration of elderly people, and neighborhood social disorganization. The data were analyzed with multilevel binomial regression models.</p> <p>Results</p> <p>Several interaction effects between neighborhood characteristics and individual socioeconomic status (SES) were found in multilevel analyses. Our results indicated that different neighborhood characteristics led to different interaction patterns. For example, neighborhood education had a positive effect on smoking for low SES women, in contrast to a negative effect on smoking for high SES women. This result supports the hypothesis of "relative deprivation," suggesting that poor people living in affluent neighborhoods suffer from relative deprivation and relative standing. On the other hand, neighborhood social disorganization has positive effects on drinking for low SES individuals, but not for high SES individuals. These interactive effects support the hypothesis of the double jeopardy theory, suggesting that living in neighborhoods with high social disorganization will intensify the effects of individual low SES.</p> <p>Conclusion</p> <p>The findings of this study show new evidence for the effects of neighborhood characteristics on individual smoking and drinking in Taiwan, suggesting that more studies are needed to understand neighborhood effects in Asian societies.</p

The development of socio-economic health differences in childhood: results of the Dutch longitudinal PIAMA birth cohort

Background: People with higher socio-economic status (SES) are generally in better health. Less is known about when these socio-economic health differences set in during childhood and how they develop over time. The goal of this study was to prospectively study the development of socio-economic health differences in the Netherlands, and to investigate possible explanations for socio-economic variation in childhood health. Methods: Data from the Dutch Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study were used for the analyses. The PIAMA study followed 3,963 Dutch children during their first eight years of life. Common childhood health problems (i.e. eczema, asthma symptoms, general health, frequent respiratory infections, overweight, and obesity) were assessed annually using questionnaires. Maternal educational level was used to indicate SES. Possible explanatory lifestyle determinants (breastfeeding, smoking during pregnancy, smoking during the first three months, and day-care centre attendance) and biological determinants (maternal age at birth, birthweight, and older siblings) were analysed using generalized estimating equations. Results: This study shows that socio-economic differences in a broad range of health problems are already present early in life, and persist during childhood. Children from families with low socio-economic backgrounds experience more asthma symptoms (odds ratio (OR) 1.27; 95% Confidence Interval (CI) 1.08-1.49), poorer general health (OR 1.36; 95% CI 1.16-1.60), more frequent respiratory infections (OR 1.57; 95% CI 1.35-1.83), more overweight (OR 1.42; 95% CI 1.16-1.73), and more obesity (OR 2.82; 95% CI 1.80-4.41). The most important contributors to the observed childhood socio-economic health disparities are socio-economic differences in maternal age at birth, breastfeeding, and day-care centre attendance. Conclusions: Socio-economic health disparities already occur very early in life. Socio-economic disadvantage takes its toll on child health before birth, and continues to do so during childhood. Therefore, action to reduce health disparities needs to start very early in life, and should also address socio-economic differences in maternal age at birth, breastfeeding habits, and day-care centre attendance

pH Modulation of Efflux Pump Activity of Multi-Drug Resistant Escherichia coli: Protection During Its Passage and Eventual Colonization of the Colon

BACKGROUND:Resistance Nodulation Division (RND) efflux pumps of Escherichia coli extrude antibiotics and toxic substances before they reach their intended targets. Whereas these pumps obtain their energy directly from the proton motive force (PMF), ATP-Binding Cassette (ABC) transporters, which can also extrude antibiotics, obtain energy from the hydrolysis of ATP. Because E. coli must pass through two pH distinct environments of the gastrointestinal system of the host, it must be able to extrude toxic agents at very acidic and at near neutral pH (bile salts in duodenum and colon for example). The herein described study examines the effect of pH on the extrusion of ethidium bromide (EB). METHODOLOGY/PRINCIPAL FINDINGS:E. coli AG100 and its tetracycline induced progeny AG100(TET) that over-expresses the acrAB efflux pump were evaluated for their ability to extrude EB at pH 5 and 8, by our recently developed semi-automated fluorometric method. At pH 5 the organism extrudes EB without the need for metabolic energy (glucose), whereas at pH 8 extrusion of EB is dependent upon metabolic energy. Phe-Arg beta-naphtylamide (PAbetaN), a commonly assumed inhibitor of RND efflux pumps has no effect on the extrusion of EB as others claim. However, it does cause accumulation of EB. Competition between EB and PAbetaN was demonstrated and suggested that PAbetaN was preferentially extruded. A K(m) representing competition between PAbetaN and EB has been calculated. CONCLUSIONS/SIGNIFICANCE:The results suggest that E. coli has two general efflux systems (not to be confused with a distinct efflux pump) that are activated at low and high pH, respectively, and that the one at high pH is probably a putative ABC transporter coded by msbA, which has significant homology to the ABC transporter coded by efrAB of Enterococcus faecalis, an organism that faces similar challenges as it makes its way through the toxic intestinal system of the host

Melanism in Peromyscus Is Caused by Independent Mutations in Agouti

Identifying the molecular basis of phenotypes that have evolved independently can provide insight into the ways genetic and developmental constraints influence the maintenance of phenotypic diversity. Melanic (darkly pigmented) phenotypes in mammals provide a potent system in which to study the genetic basis of naturally occurring mutant phenotypes because melanism occurs in many mammals, and the mammalian pigmentation pathway is well understood. Spontaneous alleles of a few key pigmentation loci are known to cause melanism in domestic or laboratory populations of mammals, but in natural populations, mutations at one gene, the melanocortin-1 receptor (Mc1r), have been implicated in the vast majority of cases, possibly due to its minimal pleiotropic effects. To investigate whether mutations in this or other genes cause melanism in the wild, we investigated the genetic basis of melanism in the rodent genus Peromyscus, in which melanic mice have been reported in several populations. We focused on two genes known to cause melanism in other taxa, Mc1r and its antagonist, the agouti signaling protein (Agouti). While variation in the Mc1r coding region does not correlate with melanism in any population, in a New Hampshire population, we find that a 125-kb deletion, which includes the upstream regulatory region and exons 1 and 2 of Agouti, results in a loss of Agouti expression and is perfectly associated with melanic color. In a second population from Alaska, we find that a premature stop codon in exon 3 of Agouti is associated with a similar melanic phenotype. These results show that melanism has evolved independently in these populations through mutations in the same gene, and suggest that melanism produced by mutations in genes other than Mc1r may be more common than previously thought

Disrupted lymph node and splenic stroma in mice with induced inflammatory melanomas is associated with impaired recruitment of T and dendritic cells

International audienceMigration of dendritic cells (DC) from the tumor environment to the T cell cortex in tumor-draining lymph nodes (TDLN) is essential for priming naïve T lymphocytes (TL) to tumor antigen (Ag). We used a mouse model of induced melanoma in which similar oncogenic events generate two phenotypically distinct melanomas to study the influence of tumor-associated inflammation on secondary lymphoid organ (SLO) organization. One tumor promotes inflammatory cytokines, leading to mobilization of immature myeloid cells (iMC) to the tumor and SLO; the other does not. We report that inflammatory tumors induced alterations of the stromal cell network of SLO, profoundly altering the distribution of TL and the capacity of skin-derived DC and TL to migrate or home to TDLN. These defects, which did not require tumor invasion, correlated with loss of fibroblastic reticular cells in T cell zones and in impaired production of CCL21. Infiltrating iMC accumulated in the TDLN medulla and the splenic red pulp. We propose that impaired function of the stromal cell network during chronic inflammation induced by some tumors renders spleens non-receptive to TL and TDLN non-receptive to TL and migratory DC, while the entry of iMC into these perturbed SLO is enhanced. This could constitute a mechanism by which inflammatory tumors escape immune control. If our results apply to inflammatory tumors in general, the demonstration that SLO are poorly receptive to CCR7-dependent migration of skin-derived DC and naïve TL may constitute an obstacle for proposed vaccination or adoptive TL therapies of their hosts

A genome-wide association scan in admixed Latin Americans identifies loci influencing facial and scalp hair features

We report a genome-wide association scan in over 6,000 Latin Americans for features of scalp hair (shape, colour, greying, balding) and facial hair (beard thickness, monobrow, eyebrow thickness). We found 18 signals of association reaching genome-wide significance (P values 5 × 10−8 to 3 × 10−119), including 10 novel associations. These include novel loci for scalp hair shape and balding, and the first reported loci for hair greying, monobrow, eyebrow and beard thickness. A newly identified locus influencing hair shape includes a Q30R substitution in the Protease Serine S1 family member 53 (PRSS53). We demonstrate that this enzyme is highly expressed in the hair follicle, especially the inner root sheath, and that the Q30R substitution affects enzyme processing and secretion. The genome regions associated with hair features are enriched for signals of selection, consistent with proposals regarding the evolution of human hair

Evidence for the Role of Horizontal Transfer in Generating pVT1, a Large Mosaic Conjugative Plasmid from the Clam Pathogen, Vibrio tapetis

The marine bacterium Vibrio tapetis is the causative agent of the brown ring disease, which affects the clam Ruditapes philippinarum and causes heavy economic losses in North of Europe and in Eastern Asia. Further characterization of V. tapetis isolates showed that all the investigated strains harbored at least one large plasmid. We determined the sequence of the 82,266 bp plasmid pVT1 from the CECT4600T reference strain and analyzed its genetic content. pVT1 is a mosaic plasmid closely related to several conjugative plasmids isolated from Vibrio vulnificus strains and was shown to be itself conjugative in Vibrios. In addition, it contains DNA regions that have similarity with several other plasmids from marine bacteria (Vibrio sp., Shewanella sp., Listonella anguillarum and Photobacterium profundum). pVT1 contains a number of mobile elements, including twelve Insertion Sequences or inactivated IS genes and an RS1 phage element related to the CTXphi phage of V. cholerae. The genetic organization of pVT1 underscores an important role of horizontal gene transfer through conjugative plasmid shuffling and transposition events in the acquisition of new genetic resources and in generating the pVT1 modular organization. In addition, pVT1 presents a copy number of 9, relatively high for a conjugative plasmid, and appears to belong to a new type of replicon, which may be specific to Vibrionaceae and Shewanelleacae