Evolution and functional divergence of the anoctamin family of membrane proteins

Our study suggests that anoctamins have evolved by series of duplication events, and that they are constrained by purifying selection. In addition we identified a number of protein domains, and amino acid residues which contribute to predicted functional divergence. Hopefully, this work will facilitate future functional characterization of the anoctamin membrane protein family

Spectroscopy of Quasar Candidates from SDSS Commissioning Data

The Sloan Digital Sky Survey has obtained images in five broad-band colors for several hundred square degrees. We present color-color diagrams for stellar objects, and demonstrate that quasars are easily distinguished from stars by their distinctive colors. Follow-up spectroscopy in less than ten nights of telescope time has yielded 22 new quasars, 9 of them at $z> 3.65$, and one with $z = 4.75$, the second highest-redshift quasar yet known. Roughly 80% of the high-redshift quasar candidates selected by color indeed turn out to be high-redshift quasars.Comment: 4 pages, 3 figures, to appear in the proceedings of "After the Dark Ages: When Galaxies were Young (the Universe at 2<z<5)", 9th Annual October Astrophysics Conference in Marylan

Spectroscopic Target Selection in the Sloan Digital Sky Survey: The Quasar Sample

We describe the algorithm for selecting quasar candidates for optical spectroscopy in the Sloan Digital Sky Survey. Quasar candidates are selected via their non-stellar colors in "ugriz" broad-band photometry, and by matching unresolved sources to the FIRST radio catalogs. The automated algorithm is sensitive to quasars at all redshifts lower than z=5.8. Extended sources are also targeted as low-redshift quasar candidates in order to investigate the evolution of Active Galactic Nuclei (AGN) at the faint end of the luminosity function. Nearly 95% of previously known quasars are recovered (based on 1540 quasars in 446 square degrees). The overall completeness, estimated from simulated quasars, is expected to be over 90%, whereas the overall efficiency (quasars:quasar candidates) is better than 65%. The selection algorithm targets ultraviolet excess quasars to i^*=19.1 and higher-redshift (z>3) quasars to i^*=20.2, yielding approximately 18 candidates per square degree. In addition to selecting ``normal'' quasars, the design of the algorithm makes it sensitive to atypical AGN such as Broad Absorption Line quasars and heavily reddened quasars.Comment: 62 pages, 15 figures (8 color), 8 tables. Accepted by AJ. For a version with higher quality color figures, see http://archive.stsci.edu/sdss/quasartarget/RichardsGT_qsotarget.preprint.p

Hydroxysteroid (17 beta) dehydrogenase 12 is essential for metabolic homeostasis in adult mice

Hydroxysteroid 17-beta dehydrogenase 12 (HSD17B12) is suggested to be involved in the elongation of very long chain fatty acids. Previously, we have shown a pivotal role for the enzyme during mouse development. In the present study we generated a conditional Hsd17b12 knockout (HSD17B12cKO) mouse model by breeding mice homozygous for a floxed Hsd17b12 allele with mice expressing the tamoxifen-inducible Cre recombinase at the ROSA26 locus. Gene inactivation was induced by administering tamoxifen to adult mice. The gene inactivation led to a 20% loss of body weight within six days, associated with drastic reduction in both white (83% males, 75% females) and brown (65% males, 60% females) fat, likely due to markedly reduced food and water intake. Furthermore, the knockout mice showed sickness behavior and signs of liver toxicity, specifically microvesicular hepatic steatosis and increased serum alanine aminotransferase (4.6-fold in males, 7.7-fold in females). The hepatic changes were more pronounced in females than males. Pro-inflammatory cytokines, such as interleukin 6 (IL-6), IL-17 and granulocyte-colony stimulating factor were increased in the HSD17B12cKO mice indicating inflammatory response. Serum lipidomics study showed an increase in the amount of dihydroceramides, despite the dramatic overall loss of lipids. In line with the proposed role for HSD17B12 in the fatty acid elongation, we observed accumulation of ceramides, dihydroceramides, hexosylceramides and lactosylceramides with shorter than 18-carbon fatty acid side chains in the serum. The results indicate that HSD17B12 is essential for proper lipid homeostasis, and HSD17B12 deficiency rapidly results in fatal systemic inflammation and lipolysis in adult mice.Peer reviewe

The Discovery of a Second Field Methane Brown Dwarf from Sloan Digital Sky Survey Commissioning Data

We report the discovery of a second field methane brown dwarf from the commissioning data of the Sloan Digital Sky Survey (SDSS). The object, SDSS J134646.45-003150.4 (SDSS 1346-00), was selected because of its very red color and stellar appearance. Its spectrum between 0.8-2.5 mic is dominated by strong absorption bands of H_2O and CH_4 and closely mimics those of Gliese 229B and SDSS 162414.37+002915.6 (SDSS 1624+00), two other known methane brown dwarfs. SDSS 1346-00 is approximately 1.5 mag fainter than Gliese 229B, suggesting that it lies about 11 pc from the sun. The ratio of flux at 2.1 mic to that at 1.27 mic is larger for SDSS 1346-00 than for Gliese 229B and SDSS 1624+00, which suggests that SDSS 1346-00 has a slightly higher effective temperature than the others. Based on a search area of 130 sq. deg. and a detection limit of z* = 19.8, we estimate a space density of 0.05 pc^-3 for methane brown dwarfs with T_eff ~ 1000 K in the 40 pc^3 volume of our search. This estimate is based on small-sample statistics and should be treated with appropriate caution.Comment: 9 pages, 3 figures, AASTeX, to appear in ApJ Letters, authors list update

The SEGUE Stellar Parameter Pipeline. I. Description and Initial Validation Tests

We describe the development and implementation of the SEGUE (Sloan Extension for Galactic Exploration and Understanding) Stellar Parameter Pipeline (SSPP). The SSPP derives, using multiple techniques, radial velocities and the fundamental stellar atmospheric parameters (effective temperature, surface gravity, and metallicity) for AFGK-type stars, based on medium-resolution spectroscopy and $ugriz$ photometry obtained during the course of the original Sloan Digital Sky Survey (SDSS-I) and its Galactic extension (SDSS-II/SEGUE). The SSPP also provides spectral classification for a much wider range of stars, including stars with temperatures outside of the window where atmospheric parameters can be estimated with the current approaches. This is Paper I in a series of papers on the SSPP; it provides an overview of the SSPP, and initial tests of its performance using multiple data sets. Random and systematic errors are critically examined for the current version of the SSPP, which has been used for the sixth public data release of the SDSS (DR-6).Comment: 64 pages, 8 tables, 12 figures, submitted to the Astronomical Journa

Photometric Redshifts of Quasars

We demonstrate that the design of the Sloan Digital Sky Survey (SDSS) filter system and the quality of the SDSS imaging data are sufficient for determining accurate and precise photometric redshifts (``photo-z''s) of quasars. Using a sample of 2625 quasars, we show that photo-z determination is even possible for z<=2.2 despite the lack of a strong continuum break that robust photo-z techniques normally require. We find that, using our empirical method on our sample of objects known to be quasars, approximately 70% of the photometric redshifts are correct to within delta z = 0.2; the fraction of correct photometric redshifts is even better for z>3. The accuracy of quasar photometric redshifts does not appear to be dependent upon magnitude to nearly 21st magnitude in i'. Careful calibration of the color-redshift relation to 21st magnitude may allow for the discovery of on the order of 10^6 quasars candidates in addition to the 10^5 quasars that the SDSS will confirm spectroscopically. We discuss the efficient selection of quasar candidates from imaging data for use with the photometric redshift technique and the potential scientific uses of a large sample of quasar candidates with photometric redshifts.Comment: 29 pages, 8 figures, submitted to A

Accurate isolation and detection of circulating tumor cells using enrichment-free multiparametric high resolution imaging

IntroductionThe reliable and accurate detection of rare circulating tumor cells (CTCs) from cancer patient blood samples promises advantages in both research and clinical applications. Numerous CTC detection methods have been explored that rely on either the physical properties of CTCs such as density, size, charge, and/or their antigen expression profiles. Multiple factors can influence CTC recovery including blood processing method and time to processing. This study aimed to examine the accuracy and sensitivity of an enrichment-free method of isolating leukocytes (AccuCyte® system) followed by immunofluorescence staining and high-resolution imaging (CyteFinder® instrument) to detect CTCs.MethodHealthy human blood samples, spiked with cancer cells from cancer cell lines, as well as blood samples obtained from 4 subjects diagnosed with cancer (2 pancreatic, 1 thyroid, and 1 small cell lung) were processed using the AccuCyte-CyteFinder system to assess recovery rate, accuracy, and reliability over a range of processing times.ResultsThe AccuCyte-CyteFinder system was highly accurate (95.0%) at identifying cancer cells in spiked-in samples (in 7.5 mL of blood), even at low spiked-in numbers of 5 cells with high sensitivity (90%). The AccuCyte-CyteFinder recovery rate (90.9%) was significantly higher compared to recovery rates obtained by density gradient centrifugation (20.0%) and red blood cell lysis (52.0%). Reliable and comparable recovery was observed in spiked-in samples and in clinical blood samples processed up to 72 hours post-collection. Reviewer analysis of images from spiked-in and clinical samples resulted in high concordance (R-squared value of 0.998 and 0.984 respectively).DiscussionThe AccuCyte-CyteFinder system is as an accurate, sensitive, and clinically practical method to detect and enumerate cancer cells. This system addresses some of the practical logistical challenges in incorporating CTCs as part of routine clinical care. This could facilitate the clinical use of CTCs in guiding precision, personalized medicine

High-Redshift Quasars Found in Sloan Digital Sky Survey Commissioning Data II: The Spring Equatorial Stripe

This is the second paper in a series aimed at finding high-redshift quasars from five-color (u'g'r'i'z') imaging data taken along the Celestial Equator by the Sloan Digital Sky Survey (SDSS) during its commissioning phase. In this paper, we present 22 high-redshift quasars (z>3.6) discovered from ~250 deg^2 of data in the spring Equatorial Stripe, plus photometry for two previously known high-redshift quasars in the same region of sky. Our success rate of identifying high-redshift quasars is 68%. Five of the newly discovered quasars have redshifts higher than 4.6 (z=4.62, 4.69, 4.70, 4.92 and 5.03). All the quasars have i* < 20.2 with absolute magnitude -28.8 < M_B < -26.1 (h=0.5, q_0=0.5). Several of the quasars show unusual emission and absorption features in their spectra, including an object at z=4.62 without detectable emission lines, and a Broad Absorption Line (BAL) quasar at z=4.92.Comment: 28 pages, AJ in press (Jan 2000), final version with minor changes; high resolution finding charts available at http://www.astro.princeton.edu/~fan/paper/qso2.htm

Exploring the Ion Channel TRPV2 and Testicular Macrophages in Mouse Testis

The cation channel TRPV2 is known to be expressed by murine macrophages and is crucially involved in their functionality. Macrophages are frequent cells of the mouse testis, an immune-privileged and steroid-producing organ. TRPV2 expression by testicular macrophages and possible changes associated with age or inflammation have not been investigated yet. Therefore, we studied testes of young adult and old wild-type (WT) and AROM(+) mice, i.e., transgenic mice overexpressing aromatase. In these animals, inflammatory changes are described in the testis, involving active macrophages, which increase with age. This is associated with impaired spermatogenesis and therefore AROM(+) mice are a model for male infertility associated with sterile inflammation. In WT animals, testicular TRPV2 expression was mapped to interstitial CD206(+) and peritubular MHC II+ macrophages, with higher levels in CD206(+) cells. Expression levels of TRPV2 and most macrophage markers did not increase significantly in old mice, with the exception of CD206. As the number of TRPV2(+) testicular macrophages was relatively small, their possible involvement in testicular functions and in aging in WT mice remains to be further studied. In AROM(+) testis, TRPV2 was readily detected and levels increased significantly with age, together with macrophage markers and TNF-alpha. TRPV2 co-localized with F4/80 in macrophages and further studies showed that TRPV2 is mainly expressed by unusual CD206(+)MHC II+ macrophages, arising in the testis of these animals. Rescue experiments (aromatase inhibitor treatment and crossing with ER alpha KO mice) restored the testicular phenotype and also abolished the elevated expression of TRPV2, macrophage and inflammation markers. This suggests that TRPV2(+) macrophages of the testis are part of an inflammatory cascade initiated by an altered sex hormone balance in AROM(+) mice. The changes in testis are distinct from the described alterations in other organs of AROM(+), such as prostate and spleen. When we monitored TRPV2 levels in another immune-privileged organ, namely the brain, we found that levels of TRPV2 were not elevated in AROM(+) and remained stable during aging. In the adrenal, which similar to the testis produces steroids, we found slight, albeit not significant increases in TRPV2 in both AROM(+) and WT mice, which were associated with age. Thus, the changes in the testis are specific for this organ