Caveolin-1 expression is elevated in claudin-low mammary tumor cells

<p>Abstract</p> <p>Background</p> <p>Caveolin-1 is a scaffolding protein found in plasma membrane invaginations known as caveolae. Caveolin-1 can regulate a number of intracellular processes such as signal transduction, cholesterol metabolism and vesicular transport. With respect to breast cancer caveolin-1 has been observed in both tumor cells and stromal cells surrounding tumors however most of the recent research has focused on how the loss of caveolin-1 in the stromal cells surrounding the tumor alters the tumor microenvironment.</p> <p>Methods</p> <p>Caveolin-1 expression was evaluated in (1) mammary tumors induced by the transgenic overexpression of the type I insulin-like growth factor receptor (IGF-IR), (2) mammary tumors that became independent of IGF-IR signalling and acquired a claudin-low genotype, (3) two murine mammary epithelial tumor cell lines and (4) two murine mammary claudin-low tumor cell lines.</p> <p>Results</p> <p>We found that mammary tumors induced by IGF-IR overexpression expressed low levels of caveolin-1 while mammary tumors that became independent of IGF-IR signalling expressed considerably higher levels of caveolin-1. Interestingly, pockets of caveolin-1 positive cells could be observed in some of the IGF-IR-induced mammary tumors and these caveolin-1 positive cells were associated with tumor cells that expressed basal cytokeratins (cytokeratins 5 and 14). This caveolin-1 expression pattern was maintained in the murine mammary tumor cell lines in that the epithelial mammary tumor cell lines expressed little or no caveolin-1 while the claudin-low cell lines expressed caveolin-1.</p> <p>Conclusions</p> <p>Our model indicates that mammary tumor cells with epithelial characteristics lack caveolin-1 while mesenchymal tumor cells express caveolin-1 suggesting that caveolin-1 may serve as a marker of mammary tumor cells with mesenchymal characteristics such as claudin-low breast tumors.</p

3-Acetyl­benzoic acid

In the crystal structure of the title compound, C9H8O3, essentially planar mol­ecules [the carboxyl group makes a dihedral angle of 4.53 (7)° with the plane of the ring, while the acid group forms a dihedral angle of 3.45 (8)° to the ring] aggregate by centrosymmetric hydrogen-bond pairing of ordered carboxyl groups. This yields dimers which have two orientations in a unit cell, creating a herringbone pattern. In addition, two close C—H⋯O inter­molecular contacts exist: one is between a methyl H atom and the ketone of a symmetry-related mol­ecule and the other involves a benzene H atom and the carboxyl group O atom of another mol­ecule. The crystal studied was a non-merohedral twin with twin law [100, 00, 0] and a domain ratio of 0.8104(14): 0.1896(14)

Intervening Mgii absorption systems from the SDSS DR12 quasar spectra

We present the catalogue of the Mg II absorption systems detected at a high significance level using an automated search algorithm in the spectra of quasars from the twelfth data release of the Sloan Digital Sky Survey. A total of 266,433 background quasars were searched for the presence of absorption systems in their spectra. The continuum modelling for the quasar spectra was performed using a mean filter. A pseudo-continuum derived using a median filter was used to trace the emission lines. The absorption system catalogue contains 39,694 Mg II systems detected at a 6.0, 3.0σ level respectively for the two lines of the doublet. The catalogue was constrained to an absorption line redshift of 0.35 6 z2796 6 2.3. The rest-frame equivalent width of the λ2796 line ranges between 0.2 6 Wr 6 6.2 ˚A. Using Gaussian-noise only simulations we estimate a false positive rate of 7.7 per cent in the catalogue. We measured the number density ∂N2796/∂z of Mg II absorbers and find evidence for steeper evolution of the systems with Wr > 1.2 ˚A at low redshifts (z2796 6 1.0), consistent with other earlier studies. A suite of null tests over the redshift range 0.5 6 z2796 6 1.5 was used to study the presence of systematics and selection effects like the dependence of the number density evolution of the absorption systems on the properties of the background quasar spectra. The null tests do not indicate the presence of any selection effects in the absorption catalogue if the quasars with spectral signal-to-noise level less than 5.0 are removed. The resultant catalogue contains 36,981 absorption systems. The Mg II absorption catalogue is publicly available

Use of ETC-1002 to treat hypercholesterolemia in patients with statin intolerance

BackgroundOnce-daily, oral ETC-1002 reduces low-density lipoprotein cholesterol (LDL-C) and has beneficial effects on other cardiometabolic risk factors but has not been examined in statin intolerant patients.ObjectivesTo study the efficacy and safety of ETC-1002 (a novel LDL-C–lowering agent) in patients with hypercholesterolemia and a history of statin intolerance.MethodsPatients intolerant to at least 1 statin were entered into this multicenter, double-blind, 8-week trial. Participants were required to have a history of muscle complaints that developed during statin treatment and resolved within 4 weeks of statin discontinuation. Patients (n = 56) were randomized in a 2:1 ratio to ETC-1002 60 mg daily or placebo. The ETC-1002 dose was increased at 2-week intervals to 120 mg, 180 mg, and 240 mg. The primary end point was the percentage change from baseline to week 8 in calculated LDL-C.ResultsETC-1002 reduced LDL-C 28.7% more than placebo (95% confidence interval, −35.4 to −22.1; P < .0001). ETC-1002 significantly reduced non–high-density lipoprotein cholesterol, total cholesterol, apolipoprotein B, and high-sensitivity C-reactive protein. Triglycerides and high-density lipoprotein cholesterol did not change with ETC-1002 treatment. Sixty-two percent of patients receiving ETC-1002 and none in the placebo group achieved the 2004 National Cholesterol Education Program Adult Treatment Panel III LDL-C goal (P < .0001). Muscle-related adverse events occurred with similar frequency in the placebo and ETC-1002 treatment groups, causing no discontinuations in ETC-1002–treated patients.ConclusionsETC-1002 appears to be effective at reducing LDL-C and was well tolerated in patients with statin-associated muscle complaints. Longer and larger studies are required to confirm the absence of muscle side effects

Green and brown bridges between weeds and crops reveal novel Diaporthe species in Australia

Diaporthe (syn. Phomopsis) species are well-known saprobes, endophytes or pathogens on a range of plants. Several species have wide host ranges and multiple species may sometimes colonise the same host species. This study describes eight novel Diaporthe species isolated from live and/or dead tissue from the broad acre crops lupin, maize, mungbean, soybean and sunflower, and associated weed species in Queensland and New South Wales, as well as the environmental weed bitou bush (Chrysanthemoides monilifera subsp. rotundata) in eastern Australia. The new taxa are differentiated on the basis of morphology and DNA sequence analyses based on the nuclear ribosomal internal transcribed spacer region, and part of the translation elongation factor-1α and ß-tubulin genes. The possible agricultural significance of live weeds and crop residues ('green bridges') as well as dead weeds and crop residues ('brown bridges') in aiding survival of the newly described Diaporthe species is discussed

Three-Terminal Si-Based Negative Differential Resistance Circuit Element with Adjustable Peak-to-Valley Current Ratios Using a Monolithic Vertical Integration

Si-based resonant bipolar transistors are demonstrated by the monolithic vertical integration of Si-based resonant interband tunnel diodes atop the emitter of Si/SiGe heterojunction bipolar transistors ~HBTs! on a silicon substrate. In the common emitter configuration, IC versus VCE shows negative differential resistance characteristics. The resulting characteristics are adjustable peak-to-valley current ratios, including infinite and negative values, and tailorable peak current densities by the control of the HBT base current under room temperature operation. With the integrated RITD-HBT combination, latching properties which are the key operating principle for high-speed mixed-signal, memory, and logic circuitry, are experimentally demonstrated

Understanding the Geometry of Astrophysical Magnetic Fields

Faraday rotation measurements have provided an invaluable technique with which to measure the properties of astrophysical magnetized plasmas. Unfortunately, typical observations provide information only about the density-weighted average of the magnetic field component parallel to the line of sight. As a result, the magnetic field geometry along the line of sight, and in many cases even the location of the rotating material, is poorly constrained. Frequently, interpretations of Faraday rotation observations are dependent upon underlying models of the magnetic field being probed (e.g., uniform, turbulent, equipartition). However, we show that at sufficiently low frequencies, specifically below roughly 13 (RM/rad m^-2)^(1/4) (B/G)^(1/2) MHz, the character of Faraday rotation changes, entering what we term the ``super-adiabatic regime'' in which the rotation measure is proportional to the integrated absolute value of the line-of-sight component of the field. As a consequence, comparing rotation measures at high frequencies with those in this new regime provides direct information about the geometry of the magnetic field along the line of sight. Furthermore, the frequency defining the transition to this new regime, nu_SA, depends directly upon the local electron density and magnetic field strength where the magnetic field is perpendicular to the line of sight, allowing the unambiguous distinction between Faraday rotation within and in front of the emission region. Typical values of nu_SA range from 10 kHz to 10 GHz, depending upon the details of the Faraday rotating environment. In particular, for resolved AGN, including the black holes at the center of the Milky Way (Sgr A*) and M81, nu_SA ranges from roughly 10 MHz to 10 GHz, and thus can be probed via existing and up-coming ground-based radio observatories.Comment: 13 pages, 5 figures, submitted to Ap

Developing Financial Benchmarks for Critical Access Hospitals

This study developed and applied benchmarks for five indicators included in the CAH Financial Indicators Report, an annual, hospital-specific report distributed to all critical access hospitals (CAHs). An online survey of Chief Executive Officers and Chief Financial Officers was used to establish benchmarks. Indicator values for 2004, 2005, and 2006 were calculated for 421 CAHs and hospital performance was compared to the benchmarks. Although many hospitals performed better than benchmark on one indicator in 1 year, very few performed better than benchmark on all five indicators in all 3 years. The probability of performing better than benchmark differed among peer groups

Treatment with ETC-1002 alone and in combination with ezetimibe lowers LDL cholesterol in hypercholesterolemic patients with or without statin intolerance

BackgroundETC-1002 is an oral, once-daily, first-in-class medication being developed to treat hypercholesterolemia.ObjectivesTo compare 2 doses of ETC-1002, alone or combined with ezetimibe 10 mg (EZE), vs EZE monotherapy for lowering low-density lipoprotein cholesterol (LDL-C).MethodsThis phase 2b, multicenter, double-blind trial-evaluated hypercholesterolemic patients (LDL-C, 130 to 220 mg/dL) with (n = 177) or without (n = 171) muscle-related intolerance to ≥2 statins; 1 at lowest approved dose. Subjects were randomized to 12-week treatment with ETC-1002 120 mg or ETC-1002 180 mg alone, EZE alone, ETC-1002 120 mg plus EZE, or ETC-1002 180 mg plus EZE.ResultsEZE alone lowered LDL-C by 21%, whereas ETC-1002 monotherapy with 120 mg or 180 mg reduced LDL-C by 27% (P = .0008 vs EZE) and 30% (P < .0001 vs EZE), respectively. The combination of ETC-1002, 120 mg or 180 mg plus EZE reduced LDL-C by 43% and 48%, respectively (both P < .0001 vs EZE). ETC-1002 alone or combined with EZE also reduced non–high-density lipoprotein cholesterol, total cholesterol, apolipoprotein B, LDL particle number, and high-sensitivity C-reactive protein compared with EZE alone. Across all treatment groups, statin-intolerant patients reported more muscle-related adverse events than did statin-tolerant patients. ETC-1002 was safe and well tolerated, and rates of muscle-related adverse events were similar in all treatment groups.ConclusionsIn patients with and without statin intolerance, daily treatment with ETC-1002 120 mg and 180 mg alone or with EZE reduced LDL-C more than EZE alone and had a similar tolerability profile (NCT01941836)