Synergism between the Two Membranes of the Blood-brain Barrier: Glucose and Amino Acid Transport

Brain capillary endothelial cells, which are connected by extensive tight junctions and are polarized into luminal (blood-facing) and abluminal (brain-facing) plasma membrane domains, form the blood-brain barrier (BBB). The polar distribution of transport proteins mediates glucose and amino acid (AA) homeostasis in the brain. The ability to isolate the luminal and abluminal membranes has permitted the study of each side of the BBB separately in vitro and yielded new information on BBB function. The two membranes have different characteristics. Facilitative transporters were found on both membranes in a position to permit the bidirectional transport of glucose, almost all amino acids and taurine. Na+-dependent transporters were only found on abluminal membranes. The Na+-dependent transporters on the abluminal side are capable of removing virtually all amino acids including acidic AA from the extracellular fluid of brain (ECF). The presence of Na+-dependent carriers on the abluminal membrane provides a mechanism by which the concentrations of AA, glucose and taurine in the ECF of brain may be maintained at optimal levels under physiological and pathophysiological circumstances. Facilitative carriers for glutamine (n) and glutamate (xg-) are found only in the luminal membrane of the BBB. This organization allows the net removal of acidic and nitrogen-rich AA from brain, and explains the low rate of glutamate and glutamine penetration into the central nervous system. The presence of a g-glutamyl cycle at the luminal membrane and Na+-dependent AA transporters at the abluminal membrane may serve to modulate movement of AA from blood to brain. The g-glutamyl cycle is expected to generate pyroglutamate within the endothelial cells. Pyroglutamate stimulates Na+-dependent AA transporters at the abluminal membrane thereby reducing net influx of AA the to brain. It is now clear the BBB may actively participate in the regulation of the AA content of the brain as well as contributing to the control of brain osmolarity

The Oldest Stars of the Extremely Metal-Poor Local Group Dwarf Irregular Galaxy Leo A

We present deep Hubble Space Telescope single-star photometry of Leo A in B, V, and I. Our new field of view is offset from the centrally located field observed by Tolstoy et al. (1998) in order to expose the halo population of this galaxy. We report the detection of metal-poor red horizontal branch stars, which demonstrate that Leo A is not a young galaxy. In fact, Leo A is as least as old as metal-poor Galactic Globular Clusters which exhibit red horizontal branches, and are considered to have a minimum age of about 9 Gyr. We discuss the distance to Leo A, and perform an extensive comparison of the data with stellar isochrones. For a distance modulus of 24.5, the data are better than 50% complete down to absolute magnitudes of 2 or more. We can easily identify stars with metallicities between 0.0001 and 0.0004, and ages between about 5 and 10 Gyr, in their post-main-sequence phases, but lack the detection of main-sequence turnoffs which would provide unambiguous proof of ancient (>10 Gyr) stellar generations. Blue horizontal branch stars are above the detection limits, but difficult to distinguish from young stars with similar colors and magnitudes. Synthetic color-magnitude diagrams show it is possible to populate the blue horizontal branch in the halo of Leo A. The models also suggest ~50% of the total astrated mass in our pointing to be attributed to an ancient (>10 Gyr) stellar population. We conclude that Leo A started to form stars at least about 9 Gyr ago. Leo A exhibits an extremely low oxygen abundance, of only 3% of Solar, in its ionized interstellar medium. The existence of old stars in this very oxygen-deficient galaxy illustrates that a low oxygen abundance does not preclude a history of early star formation.Comment: 44 pages, 18 figures, accepted for publication in the August 2002 issue of AJ. High resolution figures is available at http://www.astro.spbu.ru/staff/dio/preprints.htm

A Near-Infrared Stellar Census of the Blue Compact Dwarf Galaxy VII~Zw~403

We present near-infrared single-star photometry for the low-metallicity Blue Compact Dwarf galaxy VII~Zw~403. We achieve limiting magnitudes of F110W~$\approx$~25.5 and F160W~$\approx$~24.5 using one of the NICMOS cameras with the HST equivalents of the ground-based J and H filters. The data have a high photometric precision (0.1 mag) and are $>95$% complete down to magnitudes of about 23, far deeper than previous ground-based studies in the near-IR. The color-magnitude diagram contains about 1000 point sources. We provide a preliminary transformation of the near-IR photometry into the ground system...Comment: Accepted for publication by the AJ, preprint has 49 pages, 2 tables, and 16 figure

A Stellar Population Gradient in VII Zw 403 - Implications for the Formation of Blue Compact Dwarf Galaxies

We present evidence for the existence of an old stellar halo in the Blue Compact Dwarf galaxy VII Zw 403. VII Zw 403 is the first Blue Compact Dwarf galaxy for which a clear spatial segregation of the resolved stellar content into a "core-halo" structure is detected. Multicolor HST/WFPC2 observations indicate that active star formation occurs in the central region, but is strikingly absent at large radii. Instead, a globular-cluster-like red giant branch suggests the presence of an old (> 10 Gyr) and metal poor (=-1.92) stellar population in the halo. While the vast majority of Blue Compact Dwarf galaxies has been recognized to possess halos of red color in ground-based surface photometry, our observations of VII Zw 403 establish for the first time a direct correspondence between a red halo color and the presence of old, red giant stars. If the halos of Blue Compact Dwarf galaxies are all home to such ancient stellar populations, then the fossil record conflicts with delayed-formation scenarios for dwarfs.Comment: Accepted for publication in the Ap

The Stellar Content of NGC 6789, A Blue Compact Dwarf Galaxy in the Local Void

We find that NGC6789 is the most nearby example of a Blue Compact Dwarf galaxy known to date. With the help of WFPC2 aboard the Hubble Space Telescope, we resolve NGC6789 into over 15,000 point sources in the V and I bands. The young stars of NGC6789 are found exclusively near the center of the galaxy. The red giant population identified at large galacticentric radii yields a distance of about 3.6 Mpc, a stellar metallicity [Fe/H] of about -2, and a minimum age of about 1 Gyr. Despite its isolated location in the Local Void,its low metallicity, and its active star formation, the properties of NGC6789 are clearly not those of a galaxy in formation.Comment: 8 pages, 4 figures, ApJL Accepte

"On the Spot": travelling artists and Abolitionism, 1770-1830

Until recently the visual culture of Atlantic slavery has rarely been critically scrutinised. Yet in the first decades of the nineteenth century slavery was frequently represented by European travelling artists, often in the most graphic, sometimes voyeuristic, detail. This paper examines the work of several itinerant artists, in particular Augustus Earle (1793-1838) and Agostino Brunias (1730–1796), whose very mobility along the edges of empire was part of a much larger circulatory system of exchange (people, goods and ideas) and diplomacy that characterised Europe’s Age of Expansion. It focuses on the role of the travelling artist, and visual culture more generally, in the development of British abolitionism between 1770 and 1830. It discusses the broad circulation of slave imagery within European culture and argues for greater recognition of the role of such imagery in the abolitionist debates that divided Britain. Furthermore, it suggests that the epistemological authority conferred on the travelling artist—the quintessential eyewitness—was key to the rhetorical power of his (rarely her) images. Artists such as Earle viewed the New World as a boundless source of fresh material that could potentially propel them to fame and fortune. Johann Moritz Rugendas (1802-1858), on the other hand, was conscious of contributing to a global scientific mission, a Humboldtian imperative that by the 1820s propelled him and others to travel beyond the traditional itinerary of the Grand Tour. Some artists were implicated in the very fabric of slavery itself, particularly those in the British West Indies such as William Clark (working 1820s) and Richard Bridgens (1785-1846); others, particularly those in Brazil, expressed strong abolitionist sentiments. Fuelled by evangelical zeal to record all aspects of the New World, these artists recognised the importance of representing the harsh realities of slave life. Unlike those in the metropole who depicted slavery (most often in caustic satirical drawings), many travelling artists believed strongly in the evidential value of their images, a value attributed to their global mobility. The paper examines the varied and complex means by which visual culture played a significant and often overlooked role in the political struggles that beset the period

Breast cancer family history and allele-specific DNA methylation in the Legacy Girls Study

Family history, a well-established risk factor for breast cancer, can have both genetic and environmental contributions. Shared environment in families as well as epigenetic changes that also may be influenced by shared genetics and environment may also explain familial clustering of cancers. Epigenetic regulation, such as DNA methylation, can change the activity of a DNA segment without a change in the sequence; environmental exposures experienced across the life course can induce such changes. However, genetic-epigenetic interactions, detected as methylation quantitative trait loci (mQTLs; a.k.a. meQTLs) and haplotype-dependent allele-specific methylation (hap-ASM), can also contribute to inter-individual differences in DNA methylation patterns. To identify differentially methylated regions (DMRs) associated with breast cancer susceptibility, we examined differences in white blood cell DNA methylation in 29 candidate genes in 426 girls (ages 6-13 years) from the LEGACY Girls Study, 239 with and 187 without a breast cancer family history (BCFH). We measured methylation by targeted massively parallel bisulfite sequencing (bis-seq) and observed BCFH DMRs in two genes: ESR1 (Δ4.9%, P = 0.003) and SEC16B (Δ3.6%, P = 0.026), each of which has been previously implicated in breast cancer susceptibility and pubertal development. These DMRs showed high inter-individual variability in methylation, suggesting the presence of mQTLs/hap-ASM. Using single nucleotide polymorphisms data in the bis-seq amplicon, we found strong hap-ASM in SEC16B (with allele specific-differences ranging from 42% to 74%). These findings suggest that differential methylation in genes relevant to breast cancer susceptibility may be present early in life, and that inherited genetic factors underlie some of these epigenetic differences

Circulating growth factor concentrations and breast cancer risk: a nested case-control study of IGF-1, IGFBP-3, and breast cancer in a family-based cohort

Background Insulin-like growth factor 1 (IGF-1) and binding protein 3 (IGFBP-3) are associated with breast cancer in women at average risk of cancer. Less is known whether these biomarkers also predict risk in women with breast cancer family history. Methods We conducted a nested case-control study within the New York site of the Breast Cancer Family Registry (BCFR, n = 80 cases, 156 controls), a cohort enriched for breast cancer family history. Using conditional logistic regression, we estimated the association between IGF-1 and IGFBP-3 levels and breast cancer risk and examined whether this risk differed by predicted absolute breast cancer risk based on pedigree models. Results The overall association between IGF-1 or IGFBP-3 elevation (≥ median in controls) and breast cancer risk was elevated, but not statistically significant (IGF-1 OR = 1.37, 95% CI = 0.66–2.85; IGFBP-3 OR = 1.62, 95% CI = 0.81–3.24). Women with elevated predicted absolute 10-year risk ≥ 3.4% and elevated IGFBP-3 (≥ median) had more than a 3-fold increased risk compared to women with lower predicted absolute 10-year risk (< 3.4%) and low IGFBP-3 (OR = 3.47 95% CI = 1.04–11.6). Conclusions These data offer some support that the overall magnitude of the associations between IGF-1 and IGFBP3 seen in average risk cohorts may be similar in women enriched with a strong breast cancer family history