We report the discovery of a brown dwarf on an eccentric orbit and with a semimajor axis that places it in the brown dwarf desert region around the star HD 191760. The star has a spectral type of ...G3IV/V and a metallicity (Fe/H) of 0.29 dex. HD 191760 adds to the small number of metal-rich stars with brown dwarf companions. The brown dwarf (HD 191760b) is found to have an orbital period of 505.57 ± 0.40 d and semimajor axis of 1.35 ± 0.01 au, placing it firmly in the brown dwarf desert. The eccentricity of HD 191760b is found to be 0.63 ± 0.01, meaning it reaches as close as 0.5 au from the host star. Dynamical simulations indicate that no inner planets could reside at separations beyond ∼0.17 au due to the disastrous gravity imposed by HD 191760b. In addition to these first results, we also refine the orbits found for the exoplanets around the stars HD 48265, HD 143361 and HD 154672. All one-planet solutions are in agreement with those previously published by the Magellan Planet Search.
The aim of this experiment was to localize the mRNA and protein of ghrelin and its active receptor, growth hormone secretagogue 1A (GHS-R1A), within the reproductive tract of dairy cattle. Ghrelin is ...an orexigenic hormone that has been identified as a potent regulator of energy homeostasis. Recent evidence suggests that ghrelin may also serve as a metabolic signal to the reproductive tract. Ghrelin and GHS-R1A have been identified in the reproductive tract of several species, including humans, mice, and rats. However, ghrelin and GHS-R1A expression have not been described within bovine reproductive tissues. Therefore, the ampulla, isthmus, uterine body, corpus luteum, and follicles were harvested from 3 Holstein heifers (15.91±0.07mo of age) immediately following exsanguination. Duodenum and hypothalamus were collected as positive controls for ghrelin and GHS-R1A, respectively. Tissues were fixed in 10% formalin and embedded in paraffin for microscopy. Additional samples were stored at −80°C for detection of mRNA. Ghrelin and GHS-R1A mRNA and protein were observed in all tissue types within the reproductive tract of dairy heifers; however, expression appeared to be cell specific. Furthermore, ghrelin protein appeared to be localized to the cytoplasm, whereas GHS-R1A protein was found on the plasma membrane. Within the reproductive tissues, ghrelin mRNA and protein were most abundantly expressed in the ampulla of the oviduct. Concentrations of GHS-R1A were lower than those of ghrelin but differed between tissues. This is one of the first studies to provide molecular evidence for the presence of ghrelin and GHS-R1A within the entire reproductive tract. However, implications for fertility remain to be determined.
Phosphorylated osteopontin peptides suppress crystallization by inhibiting the growth of calcium oxalate crystals.
Osteopontin isolated from human urine uropontin (uOPN) is a potent inhibitor of ...calcium oxalate (CaOx) monohydrate (COM) crystallization. However, specific structural features responsible for its effects on CaOx crystallization were not previously known. The present studies were designed to define molecular features responsible for interactions of uOPN with COM crystals and the inhibition of crystallization.
Peptides and phosphopeptides with sequences corresponding to potential crystal binding domains within the protein sequence of osteopontin were synthesized. Then the effects of these peptides on COM crystal growth and crystal aggregation were investigated and their secondary structures analyzed.
Growth of COM crystals was inhibited by ∼50% at 1000 nmol/L concentrations by the two unmodified peptides with the closest clustering of aspartic acid residues. Growth was not inhibited by the other two unmodified peptides, with aspartic residues more evenly distributed within their sequences. Phosphorylation markedly increased inhibition of COM crystal growth, so that each of the four phosphorylated peptides inhibited growth by at least 50% at concentrations of ≤200 nmol/L. Phosphorylation of these peptides did not cause changes in secondary structure that would favor interaction with COM crystal surfaces.
These studies of synthetic peptides identify molecular features within the osteopontin molecule that contribute to the inhibition of one aspect of COM crystallization. The inhibition of crystal growth induced by phosphorylation appears to result from altered local patterns of charge density, since conformational changes favoring interaction with crystals were not caused by phosphorylation.
Abstract Objectives The objectives were to determine the time course for ovarian failure in rats caused by 4-vinylcyclohexene diepoxide (VCD) and develop a model for ovarian cancer in which ovarian ...neoplasms were chemically induced in an animal that was follicle depleted, but retained residual ovarian tissue. Methods Initially, female Fisher 344 rats were treated with VCD (to induce ovarian failure) or vehicle control (sesame oil). Three or 6 months after treatment, ovaries were collected and processed for histological evaluation for confirmation of ovarian failure. A further set of female rats was assigned to four groups exposed to combinations of vehicle control, VCD and/or DMBA (directly applied to the ovary) in a novel model for examining early stages of ovarian neoplasia. Results Three and 6 months following VCD dosing there was a significant reduction of ovarian weight and follicle number. Treatment with DMBA subsequent to VCD resulted in tumors in 42% of animals at 3 months and 57% at 5 months. All neoplasms were classified Sertoli–Leydig cell tumors (SLCT). No tumor occurred in animals treated with vehicle or DMBA alone. Conclusions These studies demonstrate that the VCD-treated rat can be used as a model for peri- and post-menopause. DMBA induction of ovarian neoplasms was greater in those rats treated with VCD. Whether this increase was due to tumor initiation by VCD or was the result of ovarian failure cannot be distinguished from these results. This represents the only animal model to date for sex cord stromal tumors.
Calcium oxalate monohydrate (COM) crystals are the major mineral component of most kidney stones, and thus have an important role in chronic human disease. However, the physicochemical mechanisms ...leading to calcium oxalate (CaOx) stone disease are only partially defined. As spontaneous precipitation of CaOx is rare under renal conditions, an alternative pathway for CaOx crystallization seems necessary to resolve this central issue. We performed kinetic studies using the dual constant composition method to simultaneously analyze the crystallization of COM and brushite, the form of calcium phosphate that is most readily formed in the typical slightly acidic urinary milieu. These studies were supported by parallel analysis by scanning electron and atomic force microscopy. In these studies, mineralization of a thermodynamically stable phase (COM) was induced by the presence of brushite, a more readily precipitated inorganic phase. Furthermore, once formed, the COM crystals grew at the expense of brushite crystals causing the dissolution of the brushite crystals. These studies show that brushite may play crucial roles in the formation of COM crystals. The definition of these two roles for brushite thereby provides physicochemical explanations for the initiation of COM crystallization and also for the relative paucity of calcium phosphate detected in the majority of CaOx renal stones.
Contribution of human uropontin to inhibition of calcium oxalate crystallization. Uropontin (UP) is known to inhibit the growth and nucleation of calcium oxalate monohydrate (COM) crystals, and it ...also impedes attachment of calcium oxalate crystals to cultured renal epithelial cells. However, its role in normal defense against renal crystallization, and in pathogenesis of nephrolithiasis is unclear. In this study we determined the effect of UP on aggregation of COM crystals as well as the inhibitory activity of UP on COM crystal growth and nucleation in a series of normal subjects, in order to assess the potential of UP as an important urinary inhibitor. The mean urinary excretion of UP measured by ELISA was 185 ± 12 nmol/24 hr (mean ± SEM) with a mean urine UP concentration of 131 ± 13nM. Uropontin isolated by immunoaffinity chromatography was a very potent inhibitor of COM crystal aggregation, with a mean UP concentration of 28 ± 4nM required for a 50% reduction in aggregation. The kDa for COM crystal growth inhibition determined from Langmuir type isotherms was 21 ± 3nM and the concentration required for 50% reduction in COM crystal growth rate was 16 ± 2 nM. Inhibition of secondary nucleation was measured at a single concentration of 200nM, which reduced the nucleation rate to 42 ± 3% of control. Using a theoretical model of growth and aggregation inhibition at varying urine flow rates, we showed that inhibitory activity of UP would be significant for all subjects over a wide range of urine flow rates. Overall, UP is a potent inhibitor of COM aggregation as well as growth and nucleation. The urinary concentration of UP is in the range in which its contribution to inhibition of growth and aggregation are likely to be substantial. Thus, UP appears to be an important natural defense against renal crystallizations and nephrolithiasis.
To investigate the role of the thick ascending limb (TAL) Na(+)-K(+)-2Cl- cotransporter in regulation of water excretion, we have prepared a peptide-derived polyclonal antibody based on the cloned ...cDNA sequence of the rat type 1 bumetanide-sensitive cotransporter, BSC-1 (also termed "NKCC-2"). Immunoblots revealed a single broad 161-kDa band in membrane fractions of rat renal outer medulla and cortex but not from rat colon or parotid gland. A similar protein was labeled in mouse kidney. Immunoperoxidase immunohistochemistry in rat kidney revealed labeling restricted to the medullary and cortical TAL segments. Because long-term regulation of urinary concentrating ability may depend on regulation of Na(+)-K(+)-2Cl- cotransporter abundance, we used immunoblotting to evaluate the effects of several in vivo factors on expression levels of BSC-1 protein in rat kidney outer medulla. Chronic oral saline loading with 0.16 M NaCl markedly increased BSC-1 abundance. However, long-term vasopressin infusion or thirsting of rats did not affect BSC-1 abundance. Chronic furosemide infusion caused a 9-kDa upward shift in apparent molecular mass and an apparent increase in expression level. These results support the previous identification of BSC-1 as the TAL Na(+)-K(+)-2Cl- transporter and demonstrate that the expression of this transporter is regulated.
It is evident that in the last decade or so, a vast amount of new information has become available concerning the various 5-HT receptor types and their characteristics. This derives from two main ...research approaches, operational pharmacology, using selective ligands (both agonists and antagonists), and, more recently, molecular biology. Although the scientific community continues to deliberate about the hierarchy of criteria for neurotransmitter receptor characterisation, there seems good agreement between the two approaches regarding 5-HT receptor classification. In addition, the information regarding transduction mechanisms and second messengers is also entirely consistent. Thus, on the basis of these essential criteria for receptor characterisation and classification, there are at least three main groups or classes of 5-HT receptor: 5-HT1, 5-HT2, and 5-HT3. Each group is not only operationally but also structurally distinct, with each receptor group having its own distinct transducing system. The more recently identified 5-HT4 receptor almost undoubtedly represents a fourth 5-HT receptor class on the basis of operational and transductional data, but this will only be definitively shown when the cDNA for the receptor has been cloned and the amino acid sequence of the protein is known. Although those 5-HT receptors that have been fully characterised and classified to date (and, hence, named with confidence) would seem to mediate the majority of the actions of 5-HT throughout the mammalian body, not all receptors for 5-HT are fully encompassed within our scheme of classification. These apparent anomalies must be recognised and need further study. They may or may not represent new groups of 5-HT receptor or subtypes of already known groups of 5-HT receptor. Even though the cDNAs for the 5-ht1E, 5-ht1F, 5-ht5, 5-ht6, and 5-ht7 receptors have been cloned and their amino acid sequence defined, more data are necessary concerning their operational and transductional characteristics before one can be confident of the suitability of their appellations. Therefore, it is important to rationalise in concert all of the available data from studies involving both operational approaches of the classical pharmacological type and those from molecular and cellular biology.
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