Adrenomedullin prevents apoptosis in prostate cancer cells

The 52-aminoacid peptide adrenomedullin (AM) is expressed in the normal and malignant prostate. We have previously shown that prostate cancer cells produce and secrete AM, which acts as an autocrine growth inhibitory factor. We have evaluated in the present study the role of AM in prostate cancer cell apoptosis, induced either by serum deprivation or treatment with the chemotherapeutic agent etoposide (which acts as an inhibitor of topoisomerase II). For this purpose we over-expressed AM in PC-3, DU 145 and LNCaP cells, which were transfected with an expression vector carrying AM. We also treated the parental cell lines with synthetic AM in normal culture conditions and in conditions of induced-apoptosis. After serum removal, AM prevented apoptosis in DU 145 and PC-3 cells, but not in LNCaP cells. When treated with etoposide, AM prevented apoptosis in PC-3 and LNCaP cells, but not in DU 145 cells. Cell cycle analysis demonstrated a significant decrease in the percentage of AM-overexpressing PC-3 cells in the subG0/G1 phase after treatment with etoposide, as compared to the percentage of mock-transfected PC-3 treated cells. Western blot showed that protein levels of phosphorylated ERK1/2 increased in parental PC-3 cells after treatment with etoposide. In PC-3 cells overexpressing AM, phosphorylated ERK1/2 basal levels were lower than basal levels of parental PC-3 cells, and treatment with etoposide did not result in such an increase. Etoposide produced a significant increase in cleaved PARP in parental PC-3 cells. However, PC-3 clones overexpressing AM that were treated with etoposide only showed a mild increase in fragmented PARP. The ratio Bcl-2/Bax was reduced in parental or mock-transfected PC-3 cells after treatment with etoposide. On the contrary, this ratio was not reduced in PC-3 clones with AM overexpression that were treated with etoposide. All these data demonstrate that AM plays a protective role against induced apoptosis in prostate cancer cells. These results may have important implications in prostate cancer resistance to chemotherapeutic agents

Vegetation and soil fire damage analysis based on species distribution modeling trained with multispectral satellite data

Producción CientíficaForest managers demand reliable tools to evaluate post-fire vegetation and soil damage. In this study, we quantify wildfire damage to vegetation and soil based on the analysis of burn severity, using multitemporal and multispectral satellite data and species distribution models, particularly maximum entropy (MaxEnt). We studied a mega-wildfire (9000 ha burned) in North-Western Spain, which occurred from 21 to 27 August 2017. Burn severity was measured in the field using the composite burn index (CBI). Burn severity of vegetation and soil layers (CBIveg and CBIsoil) was also differentiated. MaxEnt provided the relative contribution of each pre-fire and post-fire input variable on low, moderate and high burn severity levels, as well as on all severity levels combined (burned area). In addition, it built continuous suitability surfaces from which the burned surface area and burn severity maps were built. The burned area map achieved a high accuracy level (κ = 0.85), but slightly lower accuracy when differentiating the three burn severity classes (κ = 0.81). When the burn severity map was validated using field CBIveg and CBIsoil values we reached lower κ statistic values (0.76 and 0.63, respectively). This study revealed the effectiveness of the proposed multi-temporal MaxEnt based method to map fire damage accurately in Mediterranean ecosystems, providing key information to forest managers.Ministerio de Economía, Industria y Competitividad (project 559 AGL2017-86075-C2-1-R)Junta de Castilla y León (project LE001P17)Ministerio de Educación, Cultura y Deporte (grants PRX17/00234 and PRX17/00133

Controlled cavity collapse: scaling laws of drop formation

The formation of transient cavities at liquid interfaces occurs in an immense variety of natural processes, among which the bursting of surface bubbles and the impact of a drop on a liquid pool are salient. The collapse of a surface liquid cavity is a well documented natural process that leads to the ejection of a thin and fast jet. Droplets generated through this process can be one order of magnitude smaller than the cavity's aperture, and they are consequently of interest in drop on demand inkjet applications. In this work, the controlled formation and collapse of a liquid cavity is analyzed, and the conditions for minimizing the resulting size and number of ejected drops are determined. The experimental and numerical models are simple and consist of a liquid reservoir, a nozzle plate with the discharge orifice, and a moving piston actuated by single half-sine-shaped pull-mode pulses. The size of the jetted droplet is described by a physical model resulting in a scaling law that is numerically and experimentally validatedRoyal Society (UF120319, URF\R\180016, and RGF\EA\180061)John Fell Oxford University Press Research Fund (0005176)EPSRC – UK (EP/P024173/1)Ministerio de Economía y Competitividad, Plan Estatal 2013–2016 Retos, project DPI2013-46485-C3-1-

Adrenomedullin inhibits prostate cancer cell proliferation through a cAMP-independent autocrine mechanism

Adrenomedullin (AM) is a multifunctional peptide expressed in the normal and malignant prostate, and in prostate cancer cells. To elucidate the potential role of AM in prostate cancer, we have transfected the human AM gene into PC-3, DU 145, and LNCaP prostate cancer cells. Northern blot, Western blot, and radioimmunoassay techniques confirmed an increase in the synthesis and secretion of the 6kDa mature peptide, in the AM-transfected clones. Proliferation and cell cycle assays demonstrated that AM overexpression inhibited cell proliferation in PC-3 and LNCaP cells through a G0/G1 cell cycle arrest, but not in DU 145 cells. In vivo growth assays also confirmed that, at least in PC-3, AM produced a very significant reduction of tumor volume. In addition, the three cell lines expressed the CL/RCP/RAMP-2 receptor complex by RT-PCR, which suggests that AM peptide acts through an autocrine loop in prostate cancer cells. Although cAMP elevation is the most common pathway involved in AM signalling, stimulation of PC-3, DU 145, and LNCaP with synthetic AM did not increase intracellular cAMP. However, short-term stimulation of PC-3 cells with synthetic AM increased ERK1/2 activation. On the contrary, long-term stimulation, or AM overexpression, caused a reduction in the basal activation of ERK1/2. In summary, our results demonstrate that AM (either overexpressed or exogenously added) causes an inhibition of prostate cancer cell growth. This inhibition does not depend on changes in intracellular cAMP levels, but may be related to ERK1/2 activation

Low and high Reynolds number flows inside Taylor cones

Liquid motions inside Taylor cones exhibit interesting features which are not well understood yet. In addition to the flow rate injected through the electrified needle to which the conical meniscus is anchored, the action of the tangential electrical stress on the cone surface induces a recirculating meridional motion, towards the apex along the generatrix and away from it along the axis. Sometimes, a vigorous swirl is observed. The characteristic value of the liquid velocity is found to be highly dependent on both the electrical conductivity and the viscosity of the liquid, so that the Reynolds number of the liquid flow varies from very small values (creeping flow) for the case of highly conducting and viscous liquids to relatively large values for liquids with sufficiently low values of the liquid conductivity and viscosity. Theoretical conical flows for low and high values of the Reynolds number show qualitatively good agreement with photographs of real flows inside Taylor cones. In particular, the existence of a vigorous swirl which is observed in the electrospraying of paraffins and other poorly conducting and low viscosity liquids can be explained as bifurcation of a primarily nonswirling meridional flow when the Reynolds number reaches a critical value.Comisión Interministerial de Ciencia y Tecnología PB96-0679-C02-0

A new device for the generation of microbubbles

In this paper we present a new method for the production of bubble-liquid suspensions (from now on BLS) composed of micron-sized bubbles and with gas to liquid volume ratios larger than unity. We show that the BLS gas fraction ʎ=Qg and Q1 , being Qg and Q1 the flow rates of gas and liquid, respectively, is controlled by a dimensionless parameter which accounts for the ratio of the gas pressure inside the device to the liquid viscous pressure drop from the orifices where the liquid is injected to the exit, where the BLS is obtained. This parameter permits the correct scaling of the BLS gas volume fraction of all the experiments presented

Enhancement of the stability of the flow focusing technique for low-viscosity liquids

Article number 115039We propose a modified flow focusing configuration to produce low-viscosity microjets at much smaller flow rates than those reached by the standard configuration. In the modified flow focusing device, a sharpened rod blocks the recirculation cell appearing in the tapering liquid meniscus for low flow rates, which considerably improves its stability. We measured the minimum flow rates attainable with the modified configuration and compared the results with the corresponding values for the standard technique. For moderate and large applied pressure drops, the minimum flow rate reached with the modified configuration was about five times smaller than its counterpart in the standard configuration. The Weber numbers of the jets produced with the modified flow focusing configuration were considerably smaller than those with the standard technique. Numerical simulations were conducted to show how the presence of the inner rod substantially changes the flow pattern in the liquid meniscus.Ministerio de Ciencia y Educación, Junta de Extremadura y Junta de Andalucía (España) DPI2010-21103, GR10047 y P08-TEP-0412

Adrenomedullin and proadrenomedullin N-terminal 20 peptide in the normal prostate and in prostate carcinoma

There is increasing evidence for the important role played by regulatory peptides in the physiology of the normal and neoplastic prostate. Adrenomedullin (AM) and pro-adrenomedullin N-terminal 20 peptide (PAMP) are recently discovered regulatory peptides widely expressed in the normal prostate and in prostate carcinoma. AM is produced in secretory, stroma, and endothelial cells and in neurons of the prostate ganglia. PAMP is only produced by neuroendocrine cells. The expression of AM mRNA is regulated by androgens in the rat prostate. The number of neuroendocrine cells expressing PAMP is increased in prostate carcinoma after androgen deprivation, which shows that this peptide could regulate androgen-independent prostate tumor growth. However, the roles of AM and PAMP in the normal prostate and in prostate carcinoma are yet to be elucidated