Solar Carbon Monoxide, Thermal Profiling, and the Abundances of C, O, and their Isotopes

A solar photospheric "thermal profiling" analysis is presented, exploiting the infrared rovibrational bands of carbon monoxide (CO) as observed with the McMath-Pierce Fourier transform spectrometer (FTS) at Kitt Peak, and from above the Earth's atmosphere by the Shuttle-borne ATMOS experiment. Visible continuum intensities and center-limb behavior constrained the temperature profile of the deep photosphere, while CO center-limb behavior defined the thermal structure at higher altitudes. The oxygen abundance was self consistently determined from weak CO absorptions. Our analysis was meant to complement recent studies based on 3-D convection models which, among other things, have revised the historical solar oxygen (and carbon) abundance downward by a factor of nearly two; although in fact our conclusions do not support such a revision. Based on various considerations, an oxygen abundance of 700+/-100 ppm (parts per million relative to hydrogen) is recommended; the large uncertainty reflects the model sensitivity of CO. New solar isotopic ratios also are reported for 13C, 17O, and 18O.Comment: 90 pages, 19 figures (some with parts "a", "b", etc.); to be published in the Astrophysical Journal Supplement

Expression of androgen receptor splice variants in clinical breast cancers

Published: November 05, 2015The importance of androgen receptor (AR) signaling is increasingly being recognized in breast cancer, which has elicited clinical trials aimed at assessing the efficacy of androgen deprivation therapy (ADT) for metastatic disease. In prostate cancer, resistance to ADT is frequently associated with the emergence of androgen-independent splice variants of the AR (AR variants, AR-Vs) that lack the LBD and are constitutively active. Women with breast cancer may be prone to a similar phenomenon. Herein, we show that in addition to the prototypical transcript, the AR gene produces a diverse range of AR-V transcripts in primary breast tumors. The most frequently and highly expressed variant was AR-V7 (exons 1/2/3/CE3), which was detectable at the mRNA level in > 50% of all breast cancers and at the protein level in a subset of ERα-negative tumors. Functionally, AR-V7 is a constitutively active and ADT-resistant transcription factor that promotes growth and regulates a transcriptional program distinct from AR in ERα-negative breast cancer cells. Importantly, we provide ex vivo evidence that AR-V7 is upregulated by the AR antagonist enzalutamide in primary breast tumors. These findings have implications for treatment response in the ongoing clinical trials of ADT in breast cancer.Theresa E. Hickey, Connie M. Irvine, Heidi Dvinge, Gerard A. Tarulli, Adrienne R. Hanson, Natalie K. Ryan, Marie A. Pickering, Stephen N. Birrell, Dong Gui Hu, Peter I. Mackenzie, Roslin Russell, Carlos Caldas, Ganesh V. Raj, Scott M. Dehm, Stephen R. Plymate, Robert K. Bradley, Wayne D. Tilley, Luke A. Selt

Hormonal response to lipid and carbohydrate meals during the acute postprandial period

<p>Abstract</p> <p>Background</p> <p>Optimizing the hormonal environment during the postprandial period in favor of increased anabolism is of interest to many active individuals. Data are conflicting regarding the acute hormonal response to high fat and high carbohydrate feedings. Moreover, to our knowledge, no studies have compared the acute hormonal response to ingestion of lipid and carbohydrate meals of different size.</p> <p>Methods</p> <p>We compared the hormonal response to lipid and carbohydrate meals of different caloric content during the acute postprandial period. Nine healthy men (22 ± 2 years) consumed in a random order, cross-over design one of four meals/beverages during the morning hours in a rested and fasted state: dextrose at 75 g (300 kcals), dextrose at 150 g (600 kcals), lipid at 33 g (300 kcals), lipid at 66 g (600 kcals). Blood samples were collected Pre meal, and at 0.5 hr, 1 hr, 2 hr, and 3 hr post meal. Samples were assayed for testosterone, cortisol, and insulin using ELISA techniques. Area under the curve (AUC) was calculated for each variable, and a 4 × 5 ANOVA was used to further analyze data.</p> <p>Results</p> <p>A meal × time effect (p = 0.0003) was noted for insulin, with values highest for the dextrose meals at the 0.5 hr and 1 hr times, and relatively unaffected by the lipid meals. No interaction (p = 0.98) or meal (p = 0.39) effect was noted for testosterone, nor was an interaction (p = 0.99) or meal (p = 0.65) effect noted for cortisol. However, a time effect was noted for both testosterone (p = 0.04) and cortisol (p < 0.0001), with values decreasing during the postprandial period. An AUC effect was noted for insulin (p = 0.001), with values higher for the dextrose meals compared to the lipid meals (p < 0.05). No AUC effect was noted for testosterone (p = 0.85) or cortisol (p = 0.84).</p> <p>Conclusions</p> <p>These data indicate that 1) little difference is noted in serum testosterone or cortisol during the acute postprandial period when healthy men consume lipid and dextrose meals of different size; 2) Both testosterone and cortisol experience a drop during the acute postprandial period, which is similar to what is expected based on the normal diurnal variation--feeding with lipid or dextrose meals does not appear to alter this pattern; 3) dextrose meals of either 75 g or 150 g result in a significant increase in serum insulin, in particular at 0.5 hr and 1 hr post-ingestion; 4) lipid meals have little impact on serum insulin.</p

Insulin-like growth factors and insulin control a multifunctional signalling network of significant importance in cancer

Insulin-like growth factor (IGF) and insulin (INS) proteins regulate key cellular functions through a complex interacting multi-component molecular network, known as the IGF/INS axis. We describe how dynamic and multilayer interactions give rise to the multifunctional role of the IGF/INS axis. Furthermore, we summarise the importance of the regulatory IGF/INS network in cancer, and discuss the possibilities and limitations of therapies targeting the IGF/INS axis with reference to ongoing clinical trials concerning the blockage of IGF1R in several types of cancer

IGFBP-rP1, a potential molecule associated with colon cancer differentiation

<p>Abstract</p> <p>Background</p> <p>In our previous studies, we have demonstrated that insulin-like growth factor binding protein-related protein1 (IGFBP-rP1) played its potential tumor suppressor role in colon cancer cells through apoptosis and senescence induction. In this study, we will further uncover the role of IGFBP-rP1 in colon cancer differentiation and a possible mechanism by revealing responsible genes.</p> <p>Results</p> <p>In normal colon epithelium, immunohistochemistry staining detected a gradient IGFBP-rP1 expression along the axis of the crypt. IGFBP-rP1 strongly expressed in the differentiated cells at the surface of the colon epithelium, while weakly expressed at the crypt base. In colon cancer tissues, the expression of IGFBP-rP1 correlated positively with the differentiation status. IGFBP-rP1 strongly expressed in low grade colorectal carcinoma and weakly expressed in high grade colorectal carcinoma. In vitro, transfection of PcDNA3.1(IGFBP-rP1) into RKO, SW620 and CW2 cells induced a more pronounced anterior-posterior polarity morphology, accompanied by upregulation with alkaline phosphatase (AKP) activity. Upregulation of carcino-embryonic antigen (CEA) was also observed in SW620 and CW2 transfectants. The addition of IGFBP-rP1 protein into the medium could mimic most but not all effects of IGFBP-rP1 cDNA transfection. Seventy-eight reproducibly differentially expressed genes were detected in PcDNA3.1(IGFBP-rP1)-RKO transfectants, using Affymetrix 133 plus 2.0 expression chip platform. Directed Acyclic Graph (DAG) of the enriched GO categories demonstrated that differential expression of the enzyme regulator activity genes together with cytoskeleton and actin binding genes were significant. IGFBP-rP1 could upreguate Transgelin (TAGLN), downregulate SRY (sex determining region Y)-box 9(campomelic dysplasia, autosomal sex-reversal) (SOX9), insulin receptor substrate 1(IRS1), cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) (CDKN2B), amphiregulin(schwannoma-derived growth factor) (AREG) and immediate early response 5-like(IER5L) in RKO, SW620 and CW2 colon cancer cells, verified by Real time Reverse Transcription Polymerase Chain Reaction (rtRT-PCR). During sodium butyrate-induced Caco2 cell differentiation, IGFBP-rP1 was upregulated and the expression showed significant correlation with the AKP activity. The downregulation of IRS1 and SOX9 were also induced by sodium butyrate.</p> <p>Conclusion</p> <p>IGFBP-rP1 was a potential key molecule associated with colon cancer differentiation. Downregulation of IRS1 and SOX9 may the possible key downstream genes involved in the process.</p

State of the Art Review: Emerging Therapies: The Use of Insulin Sensitizers in the Treatment of Adolescents with Polycystic Ovary Syndrome (PCOS)

PCOS, a heterogeneous disorder characterized by cystic ovarian morphology, androgen excess, and/or irregular periods, emerges during or shortly after puberty. Peri- and post-pubertal obesity, insulin resistance and consequent hyperinsulinemia are highly prevalent co-morbidities of PCOS and promote an ongoing state of excess androgen. Given the relationship of insulin to androgen excess, reduction of insulin secretion and/or improvement of its action at target tissues offer the possibility of improving the physical stigmata of androgen excess by correction of the reproductive dysfunction and preventing metabolic derangements from becoming entrenched. While lifestyle changes that concentrate on behavioral, dietary and exercise regimens should be considered as first line therapy for weight reduction and normalization of insulin levels in adolescents with PCOS, several therapeutic options are available and in wide use, including oral contraceptives, metformin, thiazolidenediones and spironolactone. Overwhelmingly, the data on the safety and efficacy of these medications derive from the adult PCOS literature. Despite the paucity of randomized control trials to adequately evaluate these modalities in adolescents, their use, particularly that of metformin, has gained popularity in the pediatric endocrine community. In this article, we present an overview of the use of insulin sensitizing medications in PCOS and review both the adult and (where available) adolescent literature, focusing specifically on the use of metformin in both mono- and combination therapy