Inducers of epithelial mesenchymal transition and cancer stem cells in malignant pleural effusions

The Epithelial to Mesenchymal Transition (EMT) plays a role not only in tumor metastasis but also in tumor recurrence. This process is believed to be tightly linked to the presence of Cancer Stem Cells (CSCs) however, it is still not clear which factors could induce EMT and how it could be a source for CSCs. It has been demonstrated that Malignant Pleural Effusion (MPEs) may represent an excellent source to identify markers and molecular mechanisms involved in EMT and CSCs development. Growth factors, cell differentiation markers and molecular adhesion are involved in some of the crucial neoplastic cell events such as proliferation, metastasis, resistance to chemotherapy and EMT. In this review, we summarize the current understanding of which molecular markers can orchestrate EMT and CSCs in MPEs

HGF modulates actin cytoskeleton remodeling and contraction in testicular myoid cells

The presence of the HGF/Met system in the testicular myoid cells was first discovered by our group. However, the physiological role of this pathway remains poorly understood. We previously reported that HGF increases uPA secretion and TGF-β activation in cultured tubular fragments and that HGF is maximally expressed at Stages VII–VIII of the seminiferous epithelium cycle, when myoid cell contraction occurs. It is well known that the HGF/Met pathway is involved in cytoskeletal remodeling; moreover, the interaction of uPA with its receptor, uPAR, as well as the activation of TGF-β have been reported to be related to the actin cytoskeleton contractility of smooth muscle cells. Herein, we report that HGF induces actin cytoskeleton remodeling in vitro in isolated myoid cells and myoid cell contraction in cultured seminiferous tubules. To better understand these phenomena, we evaluated: (1) the regulation of the uPA machinery in isolated myoid cells after HGF administration; and (2) the effect of uPA or Met inhibition on HGF-treated tubular fragments. Because uPA activates latent TGF-β, the secretion of this factor was also evaluated. We found that both uPA and TGF-β activation increase after HGF administration. In testicular tubular fragments, HGF-induced TGF-β activation and myoid cell contraction are abrogated by uPA or Met inhibitor administratio

BDNF/TrkB axis activation promotes epithelial-mesenchymal transition in idiopathic pulmonary fibrosis

Background: Neurotrophins (NT) belongs to a family of growth factors which promotes neurons survival and differentiation. Increasing evidence show that NT and their receptor are expressed in lung tissues suggesting a possible role in lung health and disease. Here we investigated the expression and functional role of the TrkB/BDNF axis in idiopathic pulmonary fibrotic lung (myo)fibroblasts. Methods: Lung fibroblast were isolated from IPF patients and characterized for the expression of mesenchymal markers in comparison to normal lung fibroblasts isolated from non-IPF controls. Results: BDNF treatment promoted mesenchymal differentiation and this effect was counteracted by the TrkB inhibitor K252a. In this regard, we showed that K252a treatment was able to control the expression of transcription factors involved in epithelial to mesenchymal transition (EMT). Accordingly, K252a treatment reduced matrix metalloproteinase-9 enzyme activity and E-cadherin expression while increased cytoplasmic β-catenin expression. Conclusions: Our results suggest that BDNF/TrkB axis plays a role in EMT promoting the acquisition of (myo)fibroblast cell phenotype in IPF. Targeting BDNF/TrkB seems to represent a viable approach in order to prevent EMT dependent lung fibrosis

Alzheimer's Disease Promotion by Obesity: Induced Mechanisms—Molecular Links and Perspectives

The incidence of AD is increasing in parallel with the increase in life expectancy. At the same time the prevalence of metabolic syndrome and obesity is reaching epidemic proportions in western populations. Stress is one of the major inducers of visceral fat and obesity development, underlying accelerated aging processes. Adipose tissue is at present considered as an active endocrine organ, producing important mediators involved in metabolism regulation as well as in inflammatory mechanisms. Insulin and leptin resistance has been related to the dysregulation of energy balance and to the induction of a chronic inflammatory status which have been recognized as important cofactors in cognitive impairment and AD initiation and progression. The aim of this paper is to disclose the correlation between the onset and progression of AD and the stress-induced changes in lifestyle, leading to overnutrition and reduced physical activity, ending with metabolic syndrome and obesity. The involved molecular mechanisms will be briefly discussed, and advisable guide lines for the prevention of AD through lifestyle modifications will be proposed

ALMA Observations of the Largest Proto-Planetary Disk in the Orion Nebula, 114-426: A CO Silhouette

We present ALMA observations of the largest protoplanetary disk in the Orion Nebula, 114-426. Detectable 345 GHz (856 micron) dust continuum is produced only in the 350 AU central region of the ~1000 AU diameter silhouette seen against the bright H-alpha background in HST images. Assuming optically thin dust emission at 345 GHz, a gas-to-dust ratio of 100, and a grain temperature of 20 K, the disk gas-mass is estimated to be 3.1 +/- 0.6 Jupiter masses. If most solids and ices have have been incorporated into large grains, however, this value is a lower limit. The disk is not detected in dense-gas tracers such as HCO+ J=4-3, HCN J=4-3, or CS =7-6. These results may indicate that the 114-426 disk is evolved and depleted in some light organic compounds found in molecular clouds. The CO J=3-2 line is seen in absorption against the bright 50 to 80 K background of the Orion A molecular cloud over the full spatial extent and a little beyond the dust continuum emission. The CO absorption reaches a depth of 27 K below the background CO emission at VLSR ~6.7 km/s about 0.52 arcseconds (210 AU) northeast and 12 K below the background CO emission at VLSR ~ 9.7 km/s about 0.34 arcseconds (140 AU) southwest of the suspected location of the central star, implying that the embedded star has a mass less than 1 Solar mass .Comment: 20 pages, 4 figure

ALMA Observations of the Orion Proplyds

We present ALMA observations of protoplanetary disks ("proplyds") in the Orion Nebula Cluster. We imaged 5 individual fields at 856um containing 22 HST-identified proplyds and detected 21 of them. Eight of those disks were detected for the first time at submillimeter wavelengths, including the most prominent, well-known proplyd in the entire Orion Nebula, 114-426. Thermal dust emission in excess of any free-free component was measured in all but one of the detected disks, and ranged between 1-163 mJy, with resulting disk masses of 0.3-79 Mjup. An additional 26 stars with no prior evidence of associated disks in HST observations were also imaged within the 5 fields, but only 2 were detected. The disk mass upper limits for the undetected targets, which include OB stars, theta1Ori C and theta1Ori F, range from 0.1-0.6 Mjup. Combining these ALMA data with previous SMA observations, we find a lack of massive (>3 Mjup) disks in the extreme-UV dominated region of Orion, within 0.03 pc of O-star theta1Ori C. At larger separations from theta1Ori C, in the far-UV dominated region, there is a wide range of disk masses, similar to what is found in low-mass star forming regions. Taken together, these results suggest that a rapid dissipation of disk masses likely inhibits potential planet formation in the extreme-UV dominated regions of OB associations, but leaves disks in the far-UV dominated regions relatively unaffected.Comment: ApJ, in pres

Construyendo un nuevo relato sobre el territorio provincial: La cátedra de Geografía Económica en la Universidad Nacional de Córdoba (1957-1968)

En este trabajo, nos proponemos específicamente abordar la relación entre la conformación de la Cátedra de Geografía Económica y Social en la Facultad de Ciencias Económicas de la UNC y el contexto político y económico nacional y provincial durante el período (1957-1985), en el cual la Ciudad de Córdoba se expande y consolida como polo industrial. Se intentará mostrar en qué medida esta Cátedra aportó a la promoción del desarrollo industrial provincial y a la elaboración de una narrativa que plantea a Córdoba como una región industrial pujante en el contexto nacional. Para poder identificar este proceso, primeramente se realizará un análisis del contexto histórico en el cual surge y se desarrolla esta cátedra, para luego realizar un estudio comparativo de los programas de la materia vigentes entre 1957 y 1985, haciendo foco en las continuidades y rupturas en las fundamentaciones de los mismos, sus principales unidades temáticas y la bibliografía seleccionada. Así, se pretende recuperar, a partir de la lectura crítica de las perspectivas teórico-epistemológicas, cuáles fueron las concepciones políticas y territoriales sobre la Provincia de Córdoba sostenidas en ese espacio académico durante el período señalado.inscripcionjornadas.wix.comFil: Ricci, Carolina Paula. Universidad Nacional de Córdoba. Facultad de Filosofía y Humanidades. Escuela de Historia; Argentina.Fil: Ricci, Carolina Paula. Universidad Nacional de Córdoba. Facultad de Filosofía y Humanidades. Departamento de Geografía; Argentina.Fil: Maldonado, Rita. Universidad Nacional de Córdoba. Facultad de Filosofía y Humanidades. Escuela de Historia; Argentina.Fil: Maldonado, Rita. Universidad Nacional de Córdoba. Facultad de Filosofía y Humanidades. Departamento de Geografía; Argentina.Otras Geografía Económica y Socia

ALMA Observations of Asymmetric Molecular Gas Emission from a Protoplanetary Disk in the Orion Nebula

We present Atacama Large Millimeter/submillimeter Array (ALMA) observations of molecular line emission from d216-0939, one of the largest and most massive protoplanetary disks in the Orion Nebula Cluster (ONC). We model the spectrally resolved HCO$^+$ (4--3), CO (3--2), and HCN (4--3) lines observed at 0\farcs5 resolution to fit the temperature and density structure of the disk. We also weakly detect and spectrally resolve the CS (7--6) line but do not model it. The abundances we derive for CO and HCO$^+$ are generally consistent with expected values from chemical modeling of protoplanetary disks, while the HCN abundance is higher than expected. We dynamically measure the mass of the central star to be $2.17\pm0.07\,M_\odot$ which is inconsistent with the previously determined spectral type of K5. We also report the detection of a spatially unresolved high-velocity blue-shifted excess emission feature with a measurable positional offset from the central star, consistent with a Keplerian orbit at $60\pm20\,\mathrm{au}$. Using the integrated flux of the feature in HCO$^+$ (4--3), we estimate the total H$_2$ gas mass of this feature to be at least $1.8-8\,M_\mathrm{Jupiter}$, depending on the assumed temperature. The feature is due to a local temperature and/or density enhancement consistent with either a hydrodynamic vortex or the expected signature of the envelope of a forming protoplanet within the disk.Comment: 19 pages, 12 figures, accepted for publication in A

A Submillimeter Array Survey of Protoplanetary Disks in the Orion Nebula Cluster

We present the full results of our 3-year long Submillimeter Array survey of protoplanetary disks in the Orion Nebula Cluster. We imaged 23 fields at 880 microns and 2 fields at 1330 microns, covering an area of ~6.5 arcmin^2 and containing 67 disks. We detected 42 disks with fluxes between 6-135 mJy and at rms noise levels between 0.6 to 5.3 mJy/beam. Thermal dust emission above any free-free component was measured in 40 of the 42 detections, and the inferred disk masses range from 0.003-0.07 Msolar. We find that disks located within 0.3 pc of theta^1 Ori C have a truncated mass distribution, while disks located beyond 0.3 pc have masses more comparable to those found in low-mass star forming regions. The disk mass distribution in Orion has a distance dependence, with a derived relationship max(M_(disk)) = 0.046Msolar(d/0.3pc)^0.33 for the maximum disk masses. We found evidence of grain growth in disk 197-427, the only disk detected at both 880 microns and 1330 microns with the SMA. Despite the rapid erosion of the outer parts of the Orion disks by photoevaporation, the potential for planet formation remains high in this massive star forming region, with approximately 18% of the surveyed disks having masses greater than or equal to 0.01 Msolar within 60 AU.Comment: Accepted for publication in ApJ, 36 pages, 10 figure