Effect of dietary omega-3 fatty acids on castrate-resistant prostate cancer and tumor-associated macrophages.

BackgroundM2-like macrophages are associated with the pathogenesis of castrate-resistant prostate cancer (CRPC). We sought to determine if dietary omega-3 fatty acids (ω-3 FAs) delay the development and progression of CRPC and inhibit tumor-associated M2-like macrophages.MethodsMycCap cells were grown subcutaneously in immunocompetent FVB mice. Mice were castrated when tumors reached 300 mm2. To study effects of dietary ω-3 FAs on development of CRPC, ω-3 or ω-6 diets were started 2 days after castration and mice sacrificed after early regrowth of tumors. To study ω-3 FA effects on progression of CRPC, tumors were allowed to regrow after castration before starting the diets. M2 (CD206+) macrophages were isolated from allografts to examine ω-3 FA effects on macrophage function. Omega-3 fatty acid effects on androgen-deprived RAW264.7 M2 macrophages were studied by RT-qPCR and a migration/ invasion assay.ResultsThe ω-3 diet combined with castration lead to greater MycCap tumor regression (tumor volume reduction: 182.2 ± 33.6 mm3) than the ω-6 diet (tumor volume reduction: 148.3 ± 35.2; p = 0.003) and significantly delayed the time to CRPC (p = 0.006). Likewise, the ω-3 diet significantly delayed progression of established castrate-resistant MycCaP tumors (p = 0.003). The ω-3 diet (as compared to the ω-6 diet) significantly reduced tumor-associated M2-like macrophage expression of CSF-1R in the CRPC development model, and matrix metallopeptidase-9 (MMP-9) and vascular endothelial growth factor (VEGF) in the CRPC progression model. Migration of androgen-depleted RAW264.7 M2 macrophages towards MycCaP cells was reversed by addition of docosahexaenoic acid (ω-3).ConclusionsDietary omega-3 FAs (as compared to omega-6 FAs) decreased the development and progression of CRPC in an immunocompetent mouse model, and had inhibitory effects on M2-like macrophage function. Clinical trials are warranted evaluating if a fish oil-based diet can delay the time to castration resistance in men on androgen deprivation therapy, whereas further preclinical studies are warranted evaluating fish oil for more advanced CRPC

Rhomboid family member 2 regulates cytoskeletal stress-associated Keratin 16.

Keratin 16 (K16) is a cytoskeletal scaffolding protein highly expressed at pressure-bearing sites of the mammalian footpad. It can be induced in hyperproliferative states such as wound healing, inflammation and cancer. Here we show that the inactive rhomboid protease RHBDF2 (iRHOM2) regulates thickening of the footpad epidermis through its interaction with K16. K16 expression is absent in the thinned footpads of irhom2-/- mice compared with irhom2+/+mice, due to reduced keratinocyte proliferation. Gain-of-function mutations in iRHOM2 underlie Tylosis with oesophageal cancer (TOC), characterized by palmoplantar thickening, upregulate K16 with robust downregulation of its type II keratin binding partner, K6. By orchestrating the remodelling and turnover of K16, and uncoupling it from K6, iRHOM2 regulates the epithelial response to physical stress. These findings contribute to our understanding of the molecular mechanisms underlying hyperproliferation of the palmoplantar epidermis in both physiological and disease states, and how this 'stress' keratin is regulated

Aplicaciones del Laser Holmiun en Urología

Introducción: El laser es una tecnología de amplias aplicaciones industriales, biológicas y de investigación que se logra con grandes cantidades de energía transformada en radiación electromagnéti­ca que emite finalmente haces de luz produciendo un efecto fototérmico o fotoacústico. En el caso del láser Holmiun debido a su amplia longitud de onda (2120nm) permite realizar distintos procedimien­tos como la ablación y corte de tejidos, litotripsia y vapori­zación tisular. Objetivo: Presentar los tratamientos mínima­mente invasivos mediante laser Holmium (New Star®, 18W), en distintos padecimientos urológicos realizados hasta la fecha en el país. Material y Métodos: Se presentan los 10 primeros casos de cirugías endourológicas con el laser Holmium realizadas entre julio de 2011 y diciembre de 2012 en el Sanatorio Adventista de Asunción, principalmente litotripcias como nefrolitotripsia percutánea, ureterolitotripcia distal y proximal, nefrolitotripcia vía retrograda mediante uso de ureteroscopio flexible, cistolitotripsia y la cervicotomía vesical y uretrotomía interna, todos ellos em­pleando un equipo de laser Holmium de 18W. Resultados: Se realizaron un caso de nefrolitotripsia percutánea, dos litotripsias caliciales vía retrograda, seis uretero-litotripsias distales y una cistolitotripsia. En tres casos de uretero-litotripsia se requirió de uretrotomía por estrechez uretral bulbar y de anastomosis uretrovesical. Un caso de ureterolitotripsia fue reintervenido por los fragmentos residuales. No hubo perforaciones de mucosas y las retropulsiones fueron mínimas. Se efectuó uretrografía retrógrada de control y calibraciones uretrales en los casos de uretrotomía y de la cervicotomía con láser. Se ejecutaron radiografías simples de las vías urinarias en cistolitotripsia, ureterolitotripsia y nefrolitotripsia percutánea y retrograda, todos ellos mostrando  mejorías  anatómicas. Conclusiones: El laser Holmium es una herramienta que posee un excelente perfil de eficacia y seguridad. Se destaca su generalización en los últimos años para el manejo de las patologías obstructivas del tracto urinario y de la enferme­dad litiásica, de la cual actualmente se constituye como el “estándar de oro”. El campo de la endourología constituye un área primordial para el urólogo general, por lo cual el adiestramiento y empleo de la tecnología laser, constituye uno de los mayores retos en la forma­ción profesional del mismo ya que ha permitido incorporar el  endoscopio flexible  que abarca la totalidad del tracto urinario

Parton Distributions for Event Generators

In this paper, conventional Global QCD analysis is generalized to produce parton distributions optimized for use with event generators at the LHC. This optimization is accomplished by combining the constraints due to existing hard-scattering experimental data with those from anticipated cross sections for key representative SM processes at LHC (by the best available theory) as joint input to the global analyses. The PDFs obtained in these new type of global analyses using matrix elements calculated in any given order will be best suited to work with event generators of that order, for predictions at the LHC. This is most useful for LO event generators at present. Results obtained from a few candidate PDF sets (labeled as CT09MCS, CT09MC1 and CT09MC2) for LO event generators produced in this way are compared with those from other approaches.Comment: 35 pages, 19 figures, and 4 table

Electric Field Control of Spin Transport

Spintronics is an approach to electronics in which the spin of the electrons is exploited to control the electric resistance R of devices. One basic building block is the spin-valve, which is formed if two ferromagnetic electrodes are separated by a thin tunneling barrier. In such devices, R depends on the orientation of the magnetisation of the electrodes. It is usually larger in the antiparallel than in the parallel configuration. The relative difference of R, the so-called magneto-resistance (MR), is then positive. Common devices, such as the giant magneto-resistance sensor used in reading heads of hard disks, are based on this phenomenon. The MR may become anomalous (negative), if the transmission probability of electrons through the device is spin or energy dependent. This offers a route to the realisation of gate-tunable MR devices, because transmission probabilities can readily be tuned in many devices with an electrical gate signal. Such devices have, however, been elusive so far. We report here on a pronounced gate-field controlled MR in devices made from carbon nanotubes with ferromagnetic contacts. Both the amplitude and the sign of the MR are tunable with the gate voltage in a predictable manner. We emphasise that this spin-field effect is not restricted to carbon nanotubes but constitutes a generic effect which can in principle be exploited in all resonant tunneling devices.Comment: 22 pages, 5 figure

Search for K_S K_L in psi'' decays

K_S K_L from psi'' decays is searched for using the psi'' data collected by BESII at BEPC, the upper limit of the branching fraction is determined to be B(psi''--> K_S K_L) < 2.1\times 10^{-4} at 90% C. L. The measurement is compared with the prediction of the S- and D-wave mixing model of the charmonia, based on the measurements of the branching fractions of J/psi-->K_S K_L and psi'-->K_S K_L.Comment: 5 pages, 1 figur

Occult hepatitis B virus infection: diagnosis, implications and management?

Occult hepatitis B virus (HBV) infection is generally defined as the detection of HBV-DNA in the serum or liver tissue of patients who test negative for hepatitis B surface antigen. In most cases, occult HBV infection is related to low level HBV infection with subdetectable levels of HBsAg and not infection with HBV variants that cannot express S proteins or produce S proteins with aberrant epitopes that are not detected by conventional serological assays. Prevalence of occult HBV infection is related to the overall prevalence of HBV infection in that country, being more common in persons with prior exposure to HBV. Occult HBV infection has been found in a substantial proportion of patients with cirrhosis and hepatocellular carcinoma but other causes of liver disease are frequently present. Future studies should focus on delineating the pathogenic role of occult HBV infection and the basis for failure to detect circulating hepatitis B surface antigen.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75344/1/j.1440-1746.2004.03657.x.pd

Basic Amino Acid Mutations in the Nuclear Localization Signal of Hibiscus Chlorotic Ringspot Virus p23 Inhibit Virus Long Distance Movement

10.1371/journal.pone.0074000PLoS ONE89-POLN

Complete experimental toolbox for alignment-free quantum communication

Quantum communication employs the counter-intuitive features of quantum physics to perform tasks that are im- possible in the classical world. It is crucial for testing the foundations of quantum theory and promises to rev- olutionize our information and communication technolo- gies. However, for two or more parties to execute even the simplest quantum transmission, they must establish, and maintain, a shared reference frame. This introduces a considerable overhead in communication resources, par- ticularly if the parties are in motion or rotating relative to each other. We experimentally demonstrate how to circumvent this problem with the efficient transmission of quantum information encoded in rotationally invariant states of single photons. By developing a complete toolbox for the efficient encoding and decoding of quantum infor- mation in such photonic qubits, we demonstrate the fea- sibility of alignment-free quantum key-distribution, and perform a proof-of-principle alignment-free entanglement distribution and violation of a Bell inequality. Our scheme should find applications in fundamental tests of quantum mechanics and satellite-based quantum communication.Comment: Main manuscript: 7 pages, 3 figures; Supplementary Information: 7 pages, 3 figure