Chemical weathering and provenance evolution of Holocene–Recent sediments from the Western Indus Shelf, Northern Arabian Sea inferred from physical and mineralogical properties

We present a multi-proxy mineral record based on X-ray diffraction and diffuse reflectance spectrophotometry analysis for two cores from the western Indus Shelf in order to reconstruct changing weathering intensities, sediment transport, and provenance variations since 13 ka. Core Indus-10 is located northwest of the Indus Canyon and exhibits fluctuations in smectite/(illite + chlorite) ratios that correlate with monsoon intensity. Higher smectite/(illite + chlorite) and lower illite crystallinity, normally associated with stronger weathering, peaked during the Early–Mid Holocene, the period of maximum summer monsoon. Hematite/goethite and magnetic susceptibility do not show clear co-variation, although they both increase at Indus-10 after 10 ka, as the monsoon weakened. At Indus-23, located on a clinoform just west of the canyon, hematite/goethite increased during a period of monsoon strengthening from 10 to 8 ka, consistent with increased seasonality and/or reworking of sediment deposited prior to or during the glacial maximum. After 2 ka terrigenous sediment accumulation rates in both cores increased together with redness and hematite/goethite, which we attribute to widespread cultivation of the floodplain triggering reworking, especially after 200 years ago. Over Holocene timescales sediment composition and mineralogy in two localities on the high-energy shelf were controlled by varying degrees of reworking, as well as climatically modulated chemical weathering

Prenatal Programming of Metabolic Syndrome in the Common Marmoset Is Associated With Increased Expression of 11β-Hydroxysteroid Dehydrogenase Type 1

OBJECTIVE: Recent studies in humans and animal models of obesity have shown increased adipose tissue activity of 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), which amplifies local tissue glucocorticoid concentrations. The reasons for this 11beta-HSD1 dysregulation are unknown. Here, we tested whether 11beta-HSD1 expression, like the metabolic syndrome, is "programmed" by prenatal environmental events in a nonhuman primate model, the common marmoset monkey. RESEARCH DESIGN AND METHODS: We used a "fetal programming" paradigm where brief antenatal exposure to glucocorticoids leads to the metabolic syndrome in the offspring. Pregnant marmosets were given the synthetic glucocorticoid dexamethasone orally for 1 week in either early or late gestation, or they were given vehicle. Tissue 11beta-HSD1 and glucocorticoid receptor mRNA expression were examined in the offspring at 4 and 24 months of age. RESULTS: Prenatal dexamethasone administration, selectively during late gestation, resulted in early and persistent elevations in 11beta-HSD1 mRNA expression and activity in the liver, pancreas, and subcutaneous-but not visceral-fat. The increase in 11beta-HSD1 occurred before animals developed obesity or overt features of the metabolic syndrome. In contrast to rodents, in utero dexamethasone exposure did not alter glucocorticoid receptor expression in metabolic tissues in marmosets. CONCLUSIONS: These data suggest that long-term upregulation of 11beta-HSD1 in metabolically active tissues may follow prenatal "stress" hormone exposure and indicates a novel mechanism for fetal origins of adult obesity and the metabolic syndrome

Using Quantitative Spectroscopic Analysis to Determine the Properties and Distances of Type II-Plateau Supernovae: SNe 2005cs and 2006bp

We analyze the Type II Plateau supernovae (SN II-P) 2005cs and 2006bp with the non-LTE model atmosphere code CMFGEN. We fit 13 spectra in the first month for SN 2005cs and 18 for SN 2006bp. {\sl Swift} ultraviolet photometry and ground-based optical photometry calibrate each spectrum. Our analysis shows both objects were discovered less than 3 days after they exploded, making these the earliest SN II-P spectra ever studied. They reveal broad and very weak lines from highly-ionized fast ejecta with an extremely steep density profile. We identify He{\sc ii} 4686\AA emission in the SN 2006bp ejecta. Days later, the spectra resemble the prototypical Type II-P SN 1999em, which had a supergiant-like photospheric composition. Despite the association of SN 2005cs with possible X-ray emission, the emergent UV and optical light comes from the photosphere, not from circumstellar emission. We surmise that the very steep density fall-off we infer at early times may be a fossil of the combined actions of the shock wave passage and radiation driving at shock breakout. Based on tailored CMFGEN models, the direct-fitting technique and the Expanding Photosphere Method both yield distances and explosion times that agree within a few percent. We derive a distance to NGC 5194, the host of SN 2005cs, of 8.9$\pm$0.5 Mpc and 17.5$\pm$0.8 Mpc for SN 2006bp in NGC 3953. The luminosity of SN 2006bp is 1.5 times that of SN 1999em, and 6 times that of SN 2005cs. Reliable distances to Type II-P supernovae that do not depend on a small range in luminosity provide an independent route to the Hubble Constant and improved constraints on other cosmological parameters.Comment: 27 pages, 16 figures, 11 tables, accepted to ApJ, high-resolution of the paper available at http://hermes.as.arizona.edu/~luc/snIIP/sn05cs_06bp.ps.g

The anti-epileptic drug Valproic Acid (VPA) inhibits steroidogenesis in bovine theca and granulosa cells in vitro

Valproic acid (VPA) is used widely to treat epilepsy and bipolar disorder. Women undergoing VPA treatment reportedly have an increased incidence of polycystic ovarian syndrome (PCOS)-like symptoms including hyperandrogenism and oligo- or amenorrhoea. To investigate potential direct effects of VPA on ovarian steroidogenesis we used primary bovine theca (TC) and granulosa (GC) cells maintained under conditions that preserve their 'follicular' phenotype. Effects of VPA (7.8-500 µg/ml) on TC were tested with/without LH. Effects of VPA on GC were tested with/without FSH or IGF analogue. VPA reduced (P99% decrease; P<0.0001) with lesser effects on LHR, STAR, CYP11A1 and HSD3B1 mRNA (<90% decrease; P<0.05). VPA only reduced TC progesterone secretion induced by the highest (luteinizing) LH dose tested; TC number was unaffected by VPA. At higher concentrations (125-500 µg/ml) VPA inhibited basal, FSH- and IGF-stimulated estradiol secretion (P<0.0001) by GC without affecting progesterone secretion or cell number. VPA reversed FSH-induced upregulation of CYP19A1 and HSD17B1 mRNA abundance (P<0.001). The potent histone deacetylase (HDAC) inhibitors trichostatin A and scriptaid also suppressed TC androstenedione secretion and granulosal cell oestrogen secretion suggesting that the action of VPA reflects its HDAC inhibitory properties. In conclusion, these findings refute the hypothesis that VPA has a direct stimulatory action on TC androgen output. On the contrary, VPA inhibits both LH-dependent androgen production and FSH/IGF-dependent estradiol production in this in vitro bovine model, likely by inhibition of HDAC

Targeting lysyl oxidase reduces peritoneal fibrosis

Abdominal surgery and disease cause persistent abdominal adhesions, pelvic pain, infertility and occasionally, bowel obstruction. Current treatments are ineffective and the aetiology is unclear, although excessive collagen deposition is a consistent feature. Lysyl oxidase (Lox) is a key enzyme required for crosslinking and deposition of insoluble collagen, so we investigated whether targeting Lox might be an approach to reduce abdominal adhesions.Female C57Bl/6 mice were treated intraperitoneally with multiwalled carbon nanotubes (NT) to induce fibrosis, together with chemical (ß-aminoproprionitrile-BAPN) or miRNA Lox inhibitors, progesterone or dexamethasone. Fibrotic lesions on the diaphragm, and expression of fibrosis-related genes in abdominal wall peritoneal mesothelial cells (PMC) were measured. Effects of BAPN and dexamethasone on collagen fibre alignment were observed by TEM. Isolated PMC were cultured with interleukin-1 alpha (IL-1α) and progesterone to determine effects on Lox mRNA in vitro.NT-induced fibrosis and collagen deposition on the diaphragm was ameliorated by BAPN, Lox miRNA, or steroids. BAPN and dexamethasone disrupted collagen fibres. NT increased PMC Lox, Col1a1, Col3a1 and Bmp1 mRNA, which was inhibited by steroids. Progesterone significantly inhibited IL-1α induced Lox expression by PMC in vitro.Our results provide proof-of-concept that targeting peritoneal Lox could be an effective approach in ameliorating fibrosis and adhesion development