Analyses of Sweet Receptor Gene (Tas1r2) and Preference for Sweet Stimuli in Species of Carnivora

The extent to which taste receptor specificity correlates with, or even predicts, diet choice is not known. We recently reported that the insensitivity to sweeteners shown by species of Felidae can be explained by their lacking of a functional Tas1r2 gene. To broaden our understanding of the relationship between the structure of the sweet receptors and preference for sugars and artificial sweeteners, we measured responses to 12 sweeteners in 6 species of Carnivora and sequenced the coding regions of Tas1r2 in these same or closely related species. The lion showed no preference for any of the 12 sweet compounds tested, and it possesses the pseudogenized Tas1r2. All other species preferred some of the natural sugars, and their Tas1r2 sequences, having complete open reading frames, predict functional sweet receptors. In addition to preferring natural sugars, the lesser panda also preferred 3 (neotame, sucralose, and aspartame) of the 6 artificial sweeteners. Heretofore, it had been reported that among vertebrates, only Old World simians could taste aspartame. The observation that the lesser panda highly preferred aspartame could be an example of evolutionary convergence in the identification of sweet stimul

Biochemical enrichment and biophysical characterization of a taste receptor for L-arginine from the catfish, Ictalurus puntatus

BACKGROUND: The channel catfish, Ictalurus punctatus, is invested with a high density of cutaneous taste receptors, particularly on the barbel appendages. Many of these receptors are sensitive to selected amino acids, one of these being a receptor for L-arginine (L-Arg). Previous neurophysiological and biophysical studies suggested that this taste receptor is coupled directly to a cation channel and behaves as a ligand-gated ion channel receptor (LGICR). Earlier studies demonstrated that two lectins, Ricinus communis agglutinin I (RCA-I) and Phaseolus vulgaris Erythroagglutinin (PHA-E), inhibited the binding of L-Arg to its presumed receptor sites, and that PHA-E inhibited the L-Arg-stimulated ion conductance of barbel membranes reconstituted into lipid bilayers. RESULTS: Both PHA-E and RCA-I almost exclusively labeled an 82–84 kDa protein band of an SDS-PAGE of solubilized barbel taste epithelial membranes. Further, both rhodamine-conjugated RCA-I and polyclonal antibodies raised to the 82–84 kDa electroeluted peptides labeled the apical region of catfish taste buds. Because of the specificity shown by RCA-I, lectin affinity was chosen as the first of a three-step procedure designed to enrich the presumed LGICR for L-Arg. Purified and CHAPS-solubilized taste epithelial membrane proteins were subjected successively to (1), lectin (RCA-I) affinity; (2), gel filtration (Sephacryl S-300HR); and (3), ion exchange chromatography. All fractions from each chromatography step were evaluated for L-Arg-induced ion channel activity by reconstituting each fraction into a lipid bilayer. Active fractions demonstrated L-Arg-induced channel activity that was inhibited by D-arginine (D-Arg) with kinetics nearly identical to those reported earlier for L-Arg-stimulated ion channels of native barbel membranes reconstituted into lipid bilayers. After the final enrichment step, SDS-PAGE of the active ion channel protein fraction revealed a single band at 82–84 kDa which may be interpreted as a component of a multimeric receptor/channel complex. CONCLUSIONS: The data are consistent with the supposition that the L-Arg receptor is a LGICR. This taste receptor remains active during biochemical enrichment procedures. This is the first report of enrichment of an active LGICR from the taste system of vertebrata

Near-Infrared Spectroscopy of Molecular Filaments in the Reflection Nebula NGC 7023

We present near-infrared spectroscopy of fluorescent molecular hydrogen (H_2) emission from molecular filaments in the reflection nebula NGC 7023. We derive the relative column densities of H_2 rotational-vibrational states from the measured line emission and compare these results with several model photodissociation regions covering a range of densities, incident UV-fields, and excitation mechanisms. Our best-fit models for one filament suggest, but do not require, either a combination of different densities, suggesting clumps of 10^6 cm^{-3} in a 10^4 - 10^5 cm^{-3} filament, or a combination of fluorescent excitation and thermally-excited gas, perhaps due to a shock from a bipolar outflow. We derive densities and UV fields for these molecular filaments that are in agreement with previous determinations.Comment: ApJ accepted, 26 pages including 5 embedded figures, uses AASTEX. Also available at http://www-astronomy.mps.ohio-state.edu/~martini/pubs.htm

Spitzer observations of the Massive star forming complex S254-S258: structure and evolution

We present Spitzer-IRAC, NOAO 2.1meter-Flamingos, Keck-NIRC, and FCRAO-SEQUOIA observations of the massive star forming complex S254-S258, covering an area of 25x20 arc-minutes. Using a combination of the IRAC and NIR data, we identify and classify the young stellar objects (YSO) in the complex. We detect 510 sources with near or mid IR-excess, and we classify 87 Class I, and 165 Class II sources. The YSO are found in clusters surrounded by isolated YSO in a low-density distributed population. The ratio of clustered to total YSO is 0.8. We identify six new clusters in the complex. One of them, G192.63-00, is located around the ionizing star of the HII region S255. We hypothesize that the ionizing star of S255 was formed in this cluster. We also detect a southern component of the cluster in HII region S256. The cluster G192.54-0.15, located inside HII region S254 has a VLSR of 17 km/s with respect to the main cloud, and we conclude that it is located in the background of the complex. The structure of the molecular cloud is examined using 12CO and 13CO, as well as a near-IR extinction map. The main body of the molecular cloud has VLSR between 5 and 9 km/s. The arc-shaped structure of the molecular cloud, following the border of the HII regions, and the high column density in the border of the HII regions support the idea that the material has been swept up by the expansion of the HII regions.Comment: Accepted for publication in The Astrophysical Journa

The Chandra XBootes Survey - III: Optical and Near-IR Counterparts

The XBootes Survey is a 5-ks Chandra survey of the Bootes Field of the NOAO Deep Wide-Field Survey (NDWFS). This survey is unique in that it is the largest (9.3 deg^2), contiguous region imaged in X-ray with complementary deep optical and near-IR observations. We present a catalog of the optical counterparts to the 3,213 X-ray point sources detected in the XBootes survey. Using a Bayesian identification scheme, we successfully identified optical counterparts for 98% of the X-ray point sources. The optical colors suggest that the optically detected galaxies are a combination of z<1 massive early-type galaxies and bluer star-forming galaxies whose optical AGN emission is faint or obscured, whereas the majority of the optically detected point sources are likely quasars over a large redshift range. Our large area, X-ray bright, optically deep survey enables us to select a large sub-sample of sources (773) with high X-ray to optical flux ratios (f_x/f_o>10). These objects are likely high redshift and/or dust obscured AGN. These sources have generally harder X-ray spectra than sources with 0.1<f_x/f_o<10. Of the 73 X-ray sources with no optical counterpart in the NDWFS catalog, 47 are truly optically blank down to R~25.5 (the average 50% completeness limit of the NDWFS R-band catalogs). These sources are also likely to be high redshift and/or dust obscured AGN.Comment: 19 pages, 13 figures, ApJ accepted. Catalog can be found at: http://www.noao.edu/noao/noaodeep or ftp://archive.noao.edu/pub/catalogs/xbootes

Pseudogenization of a Sweet-Receptor Gene Accounts for Cats' Indifference toward Sugar

Although domestic cats (Felis silvestris catus) possess an otherwise functional sense of taste, they, unlike most mammals, do not prefer and may be unable to detect the sweetness of sugars. One possible explanation for this behavior is that cats lack the sensory system to taste sugars and therefore are indifferent to them. Drawing on work in mice, demonstrating that alleles of sweet-receptor genes predict low sugar intake, we examined the possibility that genes involved in the initial transduction of sweet perception might account for the indifference to sweet-tasting foods by cats. We characterized the sweet-receptor genes of domestic cats as well as those of other members of the Felidae family of obligate carnivores, tiger and cheetah. Because the mammalian sweet-taste receptor is formed by the dimerization of two proteins (T1R2 and T1R3; gene symbols Tas1r2 and Tas1r3), we identified and sequenced both genes in the cat by screening a feline genomic BAC library and by performing PCR with degenerate primers on cat genomic DNA. Gene expression was assessed by RT-PCR of taste tissue, in situ hybridization, and immunohistochemistry. The cat Tas1r3 gene shows high sequence similarity with functional Tas1r3 genes of other species. Message from Tas1r3 was detected by RT-PCR of taste tissue. In situ hybridization and immunohistochemical studies demonstrate that Tas1r3 is expressed, as expected, in taste buds. However, the cat Tas1r2 gene shows a 247-base pair microdeletion in exon 3 and stop codons in exons 4 and 6. There was no evidence of detectable mRNA from cat Tas1r2 by RT-PCR or in situ hybridization, and no evidence of protein expression by immunohistochemistry. Tas1r2 in tiger and cheetah and in six healthy adult domestic cats all show the similar deletion and stop codons. We conclude that cat Tas1r3 is an apparently functional and expressed receptor but that cat Tas1r2 is an unexpressed pseudogene. A functional sweet-taste receptor heteromer cannot form, and thus the cat lacks the receptor likely necessary for detection of sweet stimuli. This molecular change was very likely an important event in the evolution of the cat's carnivorous behavior

Suppressed radio emission in supercluster galaxies: enhanced ram pressure in merging clusters?

The environmental influence on the 1.4 GHz continuum radio emission of galaxies is analyzed in a 600 deg2 region of the local Universe containing the Shapley Supercluster (SSC). Galaxies in the FLASH and 6dFGS redshift surveys are cross-identified with NVSS radio sources, selected in a subsample doubly complete in volume and luminosity. Environmental effects are studied through a smoothed density field (normalized with random catalogs with the same survey edges and redshift selection function) and the distance to the nearest cluster (R/r200, where r200 is the virial radius, whose relation to the aperture velocity dispersion is quantified). The fraction of high radio loudness (R_K=L_radio/L_K) galaxies in the 10 Mpc Abell 3558 cluster complex at the core of the SSC (SSC-CR) is half as large than elsewhere. In the SSC-CR, R_K is anti-correlated with the density of the large-scale environment and correlated with R/r200: central brightest cluster galaxies (BCGs) in the SSC-CR are 10x less radio-loud than BCGs elsewhere, with signs of suppressed radio loudness in the SSC-CR also present beyond the BCGs, out to at least 0.3 r200. This correlation is nearly as strong as the tight correlation of L_K with R/r200 (K-luminosity segregation), inside the SSC-CR. The suppression of radio loudness in SSC-CR BCGs can be attributed to cluster-cluster mergers that destroy the cool core and thus the supply of gas to the central AGN. We analytically demonstrate that the low radio loudness of non-BCG galaxies within SSC-CR clusters cannot be explained by direct major galaxy mergers or rapid galaxy flyby collisions, but by the loss of gas supply through the enhanced ram pressure felt when these galaxies cross the shock front between the 2 merging clusters and are later subjected to the stronger wind from the 2nd cluster.Comment: Version consolidated with Erratum A&A 499, 4

PARP-1 regulates DNA repair factor availability.

PARP-1 holds major functions on chromatin, DNA damage repair and transcriptional regulation, both of which are relevant in the context of cancer. Here, unbiased transcriptional profiling revealed the downstream transcriptional profile of PARP-1 enzymatic activity. Further investigation of the PARP-1-regulated transcriptome and secondary strategies for assessing PARP-1 activity in patient tissues revealed that PARP-1 activity was unexpectedly enriched as a function of disease progression and was associated with poor outcome independent of DNA double-strand breaks, suggesting that enhanced PARP-1 activity may promote aggressive phenotypes. Mechanistic investigation revealed that active PARP-1 served to enhance E2F1 transcription factor activity, and specifically promoted E2F1-mediated induction of DNA repair factors involved in homologous recombination (HR). Conversely, PARP-1 inhibition reduced HR factor availability and thus acted to induce or enhance BRCA-ness . These observations bring new understanding of PARP-1 function in cancer and have significant ramifications on predicting PARP-1 inhibitor function in the clinical setting

Perspectives from deductible plan enrollees: plan knowledge and anticipated care-seeking changes

<p>Abstract</p> <p>Background</p> <p>Consumer directed health care proposes that patients will engage as informed consumers of health care services by sharing in more of their medical costs, often through deductibles. We examined knowledge of deductible plan details among new enrollees, as well as anticipated care-seeking changes in response to the deductible.</p> <p>Methods</p> <p>In a large integrated delivery system with a range of deductible-based health plans which varied in services included or exempted from deductible, we conducted a mixed-method, cross-sectional telephone interview study.</p> <p>Results</p> <p>Among 458 adults newly enrolled in a deductible plan (71% response rate), 51% knew they had a deductible, 26% knew the deductible amount, and 6% knew which medical services were included or exempted from their deductible. After adjusting for respondent characteristics, those with more deductible-applicable services and those with lower self-reported health status were significantly more likely to know they had a deductible. Among those who knew of their deductible, half anticipated that it would cause them to delay or avoid medical care, including avoiding doctor's office visits and medical tests, even services that they believed were medically necessary. Many expressed concern about their costs, anticipating the inability to afford care and expressing the desire to change plans.</p> <p>Conclusion</p> <p>Early in their experience with a deductible, patients had limited awareness of the deductible and little knowledge of the details. Many who knew of the deductible reported that it would cause them to delay or avoid seeking care and were concerned about their healthcare costs.</p