New Insights into X-ray Binaries

X-ray binaries are excellent laboratories to study collapsed objects. On the one hand, transient X-ray binaries contain the best examples of stellar-mass black holes while persistent X-ray binaries mostly harbour accreting neutron stars. The determination of stellar masses in persistent X-ray binaries is usually hampered by the overwhelming luminosity of the X-ray heated accretion disc. However, the discovery of high-excitation emission lines from the irradiated companion star has opened new routes in the study of compact objects. This paper presents novel techniques which exploits these irradiated lines and summarises the dynamical masses obtained for the two populations of collapsed stars: neutron stars and black holes.Comment: 12 pages, 5 figures, 2 tables, Invited review to plenary session in "Highlights of Spanish Astrophysics V", Proceedings of the VIII Scientific Meeting of the Spanish Astronomical Society (SEA) held in Santander, 7-11 July, 2008. Edited by J. Gorgas, L. J. Goicoechea, J. I. Gonzalez-Serrano, J. M. Dieg

The INT photometric H alpha Survey of the Northern Galactic Plane (IPHAS)

The Isaac Newton Telescope (INT) Photometric Hα Survey of the Northern Galactic Plane (IPHAS) is a 1800-deg2 CCD survey of the northern Milky Way spanning the latitude range −5° < b < + 5° and reaching down to r′≃ 20 (10s). Representative observations and an assessment of point-source data from IPHAS, now underway, are presented. The data obtained are Wide Field Camera images in the Hα narrow-band, and Sloan r′ and i′ broad-band filters. We simulate IPHAS (r′−Hα, r′−i′) point-source colours using a spectrophotometric library of stellar spectra and available filter transmission profiles: this defines the expected colour properties of (i) solar metallicity stars, without Hα emission, and (ii) emission-line stars. Comparisons with observations of fields in Aquila show that the simulations of normal star colours reproduce the observations well for all spectral types earlier than M. A further comparison between colours synthesized from long-slit flux-calibrated spectra and IPHAS photometry for six objects in a Taurus field confirms the reliability of the pipeline calibration. Spectroscopic follow-up of a field in Cepheus shows that sources lying above the main stellar locus in the (r′− Hα, r′−i′) plane are confirmed to be emission-line objects with very few failures. In this same field, examples of Hα deficit objects (a white dwarf and a carbon star) are shown to be readily distinguished by their IPHAS colours. The role IPHAS can play in studies of spatially resolved northern Galactic nebulae is discussed briefly and illustrated by a continuum-subtracted mosaic image of Shajn 147 (a supernova remnant, 3° in diameter). The final catalogue of IPHAS point sources will contain photometry on about 80 million objects. Used on its own, or in combination with near-infrared photometric catalogues, IPHAS is a major resource for the study of stellar populations making up the disc of the Milky Way. The eventual yield of new northern emission-line objects from IPHAS is likely to be an order of magnitude increase on the number already known

Integration of Global Signaling Pathways, cAMP-PKA, MAPK and TOR in the Regulation of FLO11

The budding yeast, Saccharomyces cerevisiae, responds to various environmental cues by invoking specific adaptive mechanisms for their survival. Under nitrogen limitation, S. cerevisiae undergoes a dimorphic filamentous transition called pseudohyphae, which helps the cell to forage for nutrients and reach an environment conducive for growth. This transition is governed by a complex network of signaling pathways, namely cAMP-PKA, MAPK and TOR, which controls the transcriptional activation of FLO11, a flocculin gene that encodes a cell wall protein. However, little is known about how these pathways co-ordinate to govern the conversion of nutritional availability into gene expression. Here, we have analyzed an integrative network comprised of cAMP-PKA, MAPK and TOR pathways with respect to the availability of nitrogen source using experimental and steady state modeling approach. Our experiments demonstrate that the steady state expression of FLO11 was bistable over a range of inducing ammonium sulphate concentration based on the preculturing condition. We also show that yeast switched from FLO11 expression to accumulation of trehalose, a STRE response controlled by a transcriptional activator Msn2/4, with decrease in the inducing concentration to complete starvation. Steady state analysis of the integrative network revealed the relationship between the environment, signaling cascades and the expression of FLO11. We demonstrate that the double negative feedback loop in TOR pathway can elicit a bistable response, to differentiate between vegetative growth, filamentous growth and STRE response. Negative feedback on TOR pathway function to restrict the expression of FLO11 under nitrogen starved condition and also with re-addition of nitrogen to starved cells. In general, we show that these global signaling pathways respond with specific sensitivity to regulate the expression of FLO11 under nitrogen limitation. The holistic steady state modeling approach of the integrative network revealed how the global signaling pathways could differentiate between multiple phenotypes

Lung resistance-related protein as a predictor of clinical outcome in advanced testicular germ-cell tumours

This study was undertaken to investigate the expression and predictive value for outcome of multidrug resistance-associated (MDR) proteins P-glycoprotein (Pgp), MRP1, BCRP, and LRP, in advanced testicular germ-cell tumours (TGCT). Paraffin-embedded sections from 56 previously untreated patients with metastatic TGCT were immunostained for Pgp, MRP1, BCRP, and LRP. All patients received platinum-based chemotherapy after orchidectomy. Immunostaining was related to clinicopathological parameters, response to chemotherapy, and outcome. Strong and intermediate expressions of the different MDR-related proteins were: 27 and 41% (Pgp), 54 and 37% (MRP1), 86 and 7% (BCRP), and 14 and 29% (LRP). P-glycoprotein and MRP1 associated, respectively, to low AFP (P=0.026) and high LDH levels (P=0.014), whereas LRP expression associated with high beta-hCG levels (P=0.003) and stage IV tumours (P=0.029). No correlation was found between Pgp, MRP1, and BCRP expression and response to chemotherapy and survival. In contrast, patients with LRP-positive tumours (strong or intermediate expression) had shorter progression-free (P=0.0006) and overall survival (P=0.0116) than LRP-negative patients, even after individual log-rank adjustments by statistically associated variables. Our data suggest that a positive LRP immunostaining at the time of diagnosis in metastatic TGCT is associated with an adverse clinical outcome

Initial data release from the INT Photometric H alpha Survey of the Northern Galactic Plane (IPHAS)

The INT/WFC Photometric Hα Survey of the Northern Galactic Plane (IPHAS) is an imaging survey being carried out in Hα, r′ and i′ filters, with the Wide Field Camera (WFC) on the 2.5-m Isaac Newton Telescope (INT) to a depth of r′= 20 (10σ). The survey is aimed at revealing the large scale organization of the Milky Way and can be applied to identifying a range of stellar populations within it. Mapping emission line objects enables a particular focus on objects in the young and old stages of stellar evolution ranging from early T-Tauri stars to late planetary nebulae. In this paper we present the IPHAS Initial Data Release, primarily a photometric catalogue of about 200 million unique objects, coupled with associated image data covering about 1600 deg2 in three passbands. We note how access to the primary data products has been implemented through use of standard virtual observatory publishing interfaces. Simple traditional web access is provided to the main IPHAS photometric catalogue, in addition to a number of common catalogues (such as 2MASS) which are of immediate relevance. Access through the AstroGrid VO Desktop opens up the full range of analysis options, and allows full integration with the wider range of data and services available through the Virtual Observatory. The IDR represents the largest data set published primarily through VO interfaces to date, and so stands as an exemplar of the future of survey data mining. Examples of data access are given, including a cross-matching of IPHAS photometry with sources in the UKIDSS Galactic Plane Survey that validates the existing calibration of the best data

mTORC1 Inhibition via Rapamycin Promotes Triacylglycerol Lipolysis and Release of Free Fatty Acids in 3T3â L1 Adipocytes

Signaling by mTOR complex 1 (mTORC1) promotes anabolic cellular processes in response to growth factors, nutrients, and hormonal cues. Numerous clinical trials employing the mTORC1 inhibitor rapamycin (aka sirolimus) to immunoâ suppress patients following organ transplantation have documented the development of hypertriglyceridemia and elevated serum free fatty acids (FFA). We therefore investigated the cellular role of mTORC1 in control of triacylglycerol (TAG) metabolism using cultured murine 3T3â L1 adipocytes. We found that treatment of adipocytes with rapamycin reduced insulinâ stimulated TAG storage ~50%. To determine whether rapamycin reduces TAG storage by upregulating lipolytic rate, we treated adipocytes in the absence and presence of rapamycin and isoproterenol, a β2â adrenergic agonist that activates the cAMP/protein kinase A (PKA) pathway to promote lipolysis. We found that rapamycin augmented isoproterenolâ induced lipolysis without altering cAMP levels. Rapamycin enhanced the isoproterenolâ stimulated phosphorylation of hormone sensitive lipase (HSL) on Serâ 563 (a PKA site), but had no effect on the phosphorylation of HSL S565 (an AMPK site). Additionally, rapamycin did not affect the isoproterenolâ mediated phosphorylation of perilipin, a protein that coats the lipid droplet to initiate lipolysis upon phosphorylation by PKA. These data demonstrate that inhibition of mTORC1 signaling synergizes with the βâ adrenergicâ cAMP/PKA pathway to augment phosphorylation of HSL to promote hormoneâ induced lipolysis. Moreover, they reveal a novel metabolic function for mTORC1; mTORC1 signaling suppresses lipolysis, thus augmenting TAG storage.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141428/1/lipd1089.pd

mTOR: from growth signal integration to cancer, diabetes and ageing

In all eukaryotes, the target of rapamycin (TOR) signalling pathway couples energy and nutrient abundance to the execution of cell growth and division, owing to the ability of TOR protein kinase to simultaneously sense energy, nutrients and stress and, in metazoans, growth factors. Mammalian TOR complex 1 (mTORC1) and mTORC2 exert their actions by regulating other important kinases, such as S6 kinase (S6K) and Akt. In the past few years, a significant advance in our understanding of the regulation and functions of mTOR has revealed the crucial involvement of this signalling pathway in the onset and progression of diabetes, cancer and ageing.National Institutes of Health (U.S.)Howard Hughes Medical InstituteWhitehead Institute for Biomedical ResearchJane Coffin Childs Memorial Fund for Medical Research (Postdoctoral Fellowship)Human Frontier Science Program (Strasbourg, France

Global urban environmental change drives adaptation in white clover.

Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale

Expression of multidrug resistance proteins P-glycoprotein, multidrug resistance protein 1, breast cancer resistance protein and lung resistance related protein in locally advanced bladder cancer treated with neoadjuvant chemotherapy: biological and clinical implications.

PURPOSE: Resistance to chemotherapy is a major obstacle to overcome in the conservative treatment of patients with locally advanced bladder cancer (LABC). We investigated the predictive value of the response to neoadjuvant chemotherapy (NACT) and prognosis of the expression of multidrug resistance (MDR) related proteins, P-glycoprotein (P-gp), multidrug resistance protein 1 (MRP1), breast cancer resistance protein (BCRP) and lung resistance related protein/major vault protein (LRP/MVP) in LABC. MATERIALS AND METHODS: Using immunohistochemistry we studied the expression of MDR proteins in tumors from 83 patients with LABC treated with NACT using a bladder sparing approach. Expression was related to the response to NACT, bladder preservation and prognosis. RESULTS: P-gp, MRP1, BCRP and LRP/MVP were expressed at high levels in 53%, 59%, 28% and 70% of cases, respectively. P-gp expression correlated with shorter progression-free survival (p = 0.04) but not with overall survival. Surprisingly MRP1 expression correlated with a higher response (p = 0.005) and a higher probability of bladder preservation following NACT (p = 0.001). BCRP did not show any prognostic impact. High LRP/MVP expression was significantly associated with a worse response to NACT and a decreased probability of bladder preservation (p = 0.035). CONCLUSIONS: Our data suggest that MRP1 and LRP/MVP may be useful in combination with other clinicopathological prognostic factors for selecting patients with LABC to be candidates for bladder preservation after NACT. A large prospective study is warranted to confirm the prognostic value of these MDR proteins