Vascular dysfunction by myofibroblast activation in patients with idiopathic pulmonary fibrosis and prognostic significance

In this study, we demonstrated the importance of telomerase protein expression and determined the relationships among telomerase, endothelin-1 (ET-1) and myofibroblasts during early and late remodeling of parenchymal and vascular areas in usual interstitial pneumonia (UIP) using 27 surgical lung biopsies from patients with idiopathic pulmonary fibrosis (IPF). Telomerase+, myofibroblasts alpha-SMA+, smooth muscle cells caldesmon+, endothelium ET-1+ cellularity, and fibrosis severity were evaluated in 30 fields covering normal lung parenchyma, minimal fibrosis (fibroblastic foci), severe ( mural) fibrosis, and vascular areas of UIP by the point-counting technique and a semiquantitative score. The impact of these markers was determined in pulmonary functional tests and follow-up until death from IPF. Telomerase and ET-1 expression was significantly increased in normal and vascular areas compared to areas of fibroblast foci. Telomerase and ET-1 expression was inversely correlated with minimal fibrosis in areas of fibroblast foci and directly associated with severe fibrosis in vascular areas. Telomerase activity in minimal fibrosis areas was directly associated with diffusing capacity of the lung for oxygen/alveolar volume and ET-1 expression and indirectly associated with diffusing capacity of the lungs for carbon monoxide and severe fibrosis in vascular areas. Cox proportional hazards regression revealed a low risk of death for females with minimal fibrosis displaying high telomerase and ET-1 expression in normal areas. Vascular dysfunction by telomerase/ET-1 expression was found earlier than vascular remodeling by myofibroblast activation in UIP with impact on IPF evolution, suggesting that strategies aimed at preventing the effect of these mediators may have a greater impact on patient outcome.

Cointegration: Bayesian Significance Test

To estimate causal relationships, time series econometricians must be aware of spurious correlation, a problem first mentioned by Yule (1926). To deal with this problem, one can work either with differenced series or multivariate models: VAR (VEC or VECM) models. These models usually include at least one cointegration relation. Although the Bayesian literature on VAR/VEC is quite advanced, Bauwens et al. (1999) highlighted that "the topic of selecting the cointegrating rank has not yet given very useful and convincing results". The present article applies the Full Bayesian Significance Test (FBST), especially designed to deal with sharp hypotheses, to cointegration rank selection tests in VECM time series models. It shows the FBST implementation using both simulated and available (in the literature) data sets. As illustration, standard non informative priors are used.

Prognostic significance of NDRG1 expression in oral and oropharyngeal squamous cell carcinoma

Human N-myc downstream-regulated gene 1 (NDRG1) is a metastasis suppressor gene with several potential functions, including cell differentiation, cell cycle regulation and response to hormones, nickel and stress. The purpose of this study was to investigate the immunoexpression of NDRG1 in oral and oropharyngeal squamous cell carcinomas searching for its role in the clinical course of these tumors. We investigated immunohistochemical expression of NDRG1 protein in 412 tissue microarray cores of tumor samples from 103 patients with oral and oropharyngeal squamous cell carcinomas and in 110 paraffin-embedded surgical margin sections. The results showed NDRG1 up-regulation in 101/103 (98.1 %) tumor samples, but no expression in any normal tissue sample. Western blot assays confirmed the immunohistochemical findings, suggesting that lower levels of NDRG1 are associated with a high mortality rate. NDRG1 overexpression was related to long-term specific survival (HR = 0.38; p = 0.009), whereas the presence of lymph-node metastasis showed the opposite association with survival (HR = 2.45; p = 0.013). Our findings reinforce the idea that NDRG1 plays a metastasis suppressor role in oral and oropharyngeal squamous cell carcinomas and may be a useful marker for these tumors.

Characterization of PAR1 and FGFR1 expression in invasive breast carcinomas: Prognostic significance

Breast cancer is the most common cause of cancer mortality among women worldwide. Among the several factors associated with breast cancer development, angiogenesis plays an essential role and has currently emerged as a potential diagnostic, prognostic and therapeutic target. Protease-activated receptor 1 (PAR1) and fibroblast growth factor receptor 1 (FGFR1) have important activities in tumor angiogenesis and progression. The aim of this study was to investigate the prognostic significance of these two receptors, hypothesising significant correlations between receptor expression in tumor angiogenesis and clinicopathological parameters customarily used in breast cancer prognosis and prediction. Formalin-fixed and paraffin-embedded samples of ductal invasive breast carcinomas were used to analyze the expression of PAR1 and FGFR1, in the tumor cells as well as in the tumor stroma, and further determine intratumoral microvessel density (iMVD) to quantify intratumoral angiogenesis. Correlations between PAR1 and FGFR1 expression in tumor cells and stroma, iMVD and several clinicopathological parameters and molecular markers used in breast cancer diagnosis have been addressed. The correlation between PAR1 and FGFR1 suggests an association of the two receptors with a more aggressive breast cancer phenotype and, consequently, a potential role during tumor progression. The results reported in the present study also emphasize the importance of microenvironmental factors in tumor progression, while precluding the positive association between iMVD and breast cancer aggressiveness.

Prognostic significance of CD24 and claudin-7 immunoexpression in ductal invasive breast cancer

This study aimed to identify the CD24 and CD44 immunophenotypes within invasive ductal breast carcinoma (I DC) subgroups defined by immunohistochesmistry markers and to determine its influence on prognosis as well as its association with the expression of Ki-67, cytokeratins (CK5 and CK 18) and claudin-7. Immunohistochemical expression of CD44 and CD24 alone or in combination was investigated in 95 IDC cases arranged in a tissue microarray (TMA). The association with subgroups defined as luminal A and B; HER2 rich and triple negative, or with the other markers and prognosis was analyzed. CD44(+)/CD24(-) and CD44(-)/CD24(+) were respectively present in 8.4% and 16.8% of the tumors, a lack of both proteins was detected in 6.3%, while CD441(-)/CD24(+) was observed in 45.3% of the tumors. Although there was no significant correlation between subgroups and different phenotypes, the CD44(+)/CD24(-) phenotype was more common in the basal subgroups but absent in HER2 tumors, whereas luminal tumors are enriched in CD44(-)/CD24(+) and CD44(+)/CD24(+) cells. The frequency of CD44(+)/CD24(-) or CD44(-)/CD24(+) was not associated with clinical characteristics or biological markers. There was also no significant association of these phenotypes with the event free (DFS) and overall survival (OS). Single CD44(+) was evident in 57.9% of the tumors and was marginally associated to grading and not to any other tumor characteristics as well as OS and DFS. CD24(+) was positive in 74.7% of the tumors, showing a significant association with estrogen receptor, progesterone receptor and Ki-67 and a marginal association with CKI8 and claudin-7. Expression of claudin-7 and Ki-67 did not associate with the cancer subgroups, while a positive association between CK18 and the luminal subgroups was found (P=0.03). CK5, CK18 and Ki-67 expression had no influence in OS or DFS. Single CD24(+) (P=0.07) and claudin-7 positivity (P=0.05) were associated with reduced time of recurrence, suggesting a contribution of these markers to aggressiveness of breast cancer.

Embryonic and Fetal Development in - Pigmy Rice Rat - Oligoryzomys sp (Rodentia, Sigmodontinae) and its Significance for Being a new Experimental Model

Oligoryzomys (Cricetidae, Sigmodontinae) is a common rodent genus from South America that includes a couple of very similar species. Related species have been used as experimental model for understanding several diseases for which these species are reservoirs. In order to provide a better understanding of the embryological aspects of this group, herein we showed data on the embryonic and fetal development in Oligoryzomys sp. Eight specimens of different stages of gestation were obtained from the Collection of the Zoology Museum of University of Sao Paulo, Brazil. Gestational ages were estimated by crown-rump-length according to Evans and Sack (1973). To address our analysis after examining the gross morphology, tissues from several organs were processed for light and scanning electron microscopy. Morphological data on the systems (nervous system, cardiorespiratory system, intestinal tract and urogenital system) were described in detail. Finally, the findings were compared with what is known about embryological aspects in other rodent species in order to establish similarities and differences during the organogenesis in different species.

Leaf cuticular alkanes of Solanum subg. Leptostemonum Dunal (Bitter) of some northeast Brazilian species: Composition and taxonomic significance

Solanum subgenus Leptostemonum (Dunal) Bitter comprises approximately 450 species, of which 110, including 58 endemics, occur in Brazil, which is recognized as one of the centers of diversity of the group. Due the great morphological plasticity and its large number of species, several taxonomic treatments have been proposed for the genus Solanum, but its infrageneric classification is problematic. The aim of this study was to analyze the alkane composition of the leaf epicuticular waxes of nine species of the subgenus Leptostemonum to evaluate the chemotaxonomic potential of the alkanes. As results, were identified in nine species thirty-one alkanes, including iso- and anteiso-alkanes. The major constituent of wax in most species was tritriacontane. Hentriacontane was the main constituent of Solanum paraibanum and Solanum torvum, and penta-triacontane was predominant in different populations of Solanum stramonifolium. The phenetic analysis of nine species based on the distribution profile of alkanes (Euclidean distance and UPGMA method) show three clusters with distinct main homolog. The profiles of alkanes showed some qualitative taxonomic value for species analyzed, although, a larger number of representative samples of this subgenus must be investigated. (C) 2012 Elsevier Ltd. All rights reserved.

Tectonic implications of the 1419 Ma Nova Guarita mafic intrusives paleomagnetic pole (Amazonian Craton) on the longevity of Nuna

The Nuna supercontinent was probably assembled in the Paleoproterozoic, but its paleogeography and the timing for its demise are stills matter of debate. A paleomagnetic and geochronological study carried out on the Mesoproterozoic Nova Guarita dyke swarm (northern Mato Grosso State, SW Amazonian Craton) provides additional constraints on the duration of this supercontinent. Paleomagnetic AF and thermal treatment revealed south/southwest (northeast) magnetic directions with downward (upward) inclinations for 19 analyzed sites. These directions are carried by PSD magnetite with high unblocking temperatures as indicated by additional magnetic tests, including thermomagnetic curves, hysteresis loops and the progressive acquisition of isothermal remanence in selected samples. A positive contact test with the host granite in one of the studied dykes further attests to the primary origin of the characteristic magnetic component. A mean site direction was calculated at D-m = 220.5 degrees, I-m = 45.9 degrees (alpha(95) = 6.5 degrees, K = 27.7), which yielded a paleomagnetic pole located at 245.9 degrees E, 47.9 degrees S (A(95) = 7.0 degrees). Ar-40/Ar-39 dating carried out on biotites from four analyzed dykes yielded well-defined plateau ages with a mean of 1418.5 +/- 3.5 Ma. The Nova Guarita pole precludes a long-lived Nuna configuration in which Laurentia, Baltica, North China, and Amazonia formed a long and continuous block as previously proposed for the Paleoproterozoic. It is nevertheless fully compatible with a SAMBA (Amazonia-Baltica) link at Mesoproterozoic times. (C) 2011 Elsevier B.V. All rights reserved.

Contribution to the stratigraphy of the onshore Paraíba Basin, Brazil

Several publications have contributed to improve the stratigraphy of the Paraíba Basin in northeastern Brazil. However, the characterization and distribution of sedimentary units in onshore areas of this basin are still incomplete, despite their significance for reconstructing the tectono-sedimentary evolution of the South American passive margin. This work provides new information to differentiate among lithologically similar strata, otherwise entirely unrelated in time. This approach included morphological, sedimentological and stratigraphic descriptions based on surface and sub-surface data integrated with remote sensing, optically stimulated luminescence dating, U+Th/He dating of weathered goethite, and heavy mineral analysis. Based on this study, it was possible to show that Cretaceous units are constrained to the eastern part of the onshore Paraíba Basin. Except for a few outcrops of carbonatic rocks nearby the modern coastline, deposits of this age are not exposed to the surface in the study area. Instead, the sedimentary cover throughout the basin is constituted by mineralogically and chronologically distinctive deposits, inserted in the Barreiras Formation and mostly in the Post-Barreiras Sediments, of early/middle Miocene and Late Pleistocene-Holocene ages, respectively. The data presented in this work support tectonic deformation as a factor of great relevance to the distribution of the sedimentary units of the Paraíba Basin.

Significance of non‐sinking particulate organic carbon and dark CO2 fixation to heterotrophic carbon demand in the mesopelagic northeast Atlantic

[EN] It is generally assumed that sinking particulate organic carbon (POC) constitutes the main source of organic carbon supply to the deep ocean's food webs. However, a major discrepancy between the rates of sinking POC supply (collected with sediment traps) and the prokaryotic organic carbon demand (the total amount of carbon required to sustain the heterotrophic metabolism of the prokaryotes; i.e., production plus respiration, PCD) of deep-water communities has been consistently reported for the dark realm of the global ocean. While the amount of sinking POC flux declines exponentially with depth, the concentration of suspended, buoyant non-sinking POC (nsPOC; obtained with oceanographic bottles) exhibits only small variations with depth in the (sub)tropical Northeast Atlantic. Based on available data for the North Atlantic we show here that the sinking POC flux would contribute only 4–12% of the PCD in the mesopelagic realm (depending on the primary production rate in surface waters). The amount of nsPOC potentially available to heterotrophic prokaryotes in the mesopelagic realm can be partly replenished by dark dissolved inorganic carbon fixation contributing between 12% to 72% to the PCD daily. Taken together, there is evidence that the mesopelagic microheterotrophic biota is more dependent on the nsPOC pool than on the sinking POC supply. Hence, the enigmatic major mismatch between the organic carbon demand of the deep-water heterotrophic microbiota and the POC supply rates might be substantially smaller by including the potentially available nsPOC and its autochthonous production in oceanic carbon cycling models.

Pyrochlore der Pegmatit-Provinz Nazareno, Brasilien

Zusammenfassung:Mit Hilfe einer neuen Formel für die Minerale der Pyrochlor-Gruppe werden sämtliche Endglieder der Na-Ca-Mikrolithe und der Ba-haltigen Mikrolithe aus der Pegmatit-Provinz Nazareno beschrieben: Die Na-reichsten Proben haben nahezu die Idealzusammensetzung eines idealen Pyrochlors, d.h. . Die Ca-reichsten Varietäten weisen maximal auf, wobei der Besetzungsanteil des Ca am A2+ ca. 93% beträgt. Die Ba-haltigen Mikrolithe sind durch eine Defektstruktur gekennzeichnet, wobei für das mögliche Endglied kein Beispiel in den Daten vorliegt. Das Endglied mit dem geringsten Defektcharakter hat folgende Stöchiometrie:

Sedimentology and tectonic history of late Archaean sedimentary successions in Zimbabwe

ZusammenfassungSpätarchaische Sedimentgesteine (ca. 2,65 Milliarden Jahre alt) wurden in Grünsteingürteln des Simbabwe Kratons untersucht. In dem Belingwe Grünsteingürtel ist granitoides Grundgebirge von einer allochthonen Einheit aus vulkanischen Gesteinen und Vorlandbeckensedimenten überlagert. Die sedimentäre Abfolge besteht aus Flachwasserkalken und Turbiditen. Unterschiedliche Faziestypen der Kalksteine sind in sedimentäre Verflachungszyklen angeordnet. Eustatische Meeresspiegelschwankungen werden als Ursache der zyklischen Sedimentation angenommen. Sedimentologische, geochemische und strukturelle Analysen zeigen die Bedeutung horizontal-tektonischer Prozesse für die Entstehung dieses Grünsteingürtels an.Sedimentgesteine des Midlands Grünsteingürtels lagern zwischen ozeanischen, mafischen Vulkaniten und kontinentalen, granitoiden Gneisen. Die Art der Abfolge sedimentärer Fazies, beginnend mit Turbiditen und überlagert von flachmarinen Schelfsedimenten und alluvialen Ablagerungen, sowie geologische und geochemische Hinweise aus den benachbarten Gesteinsserien lassen auf Ablagerung während der Kollision zwischen einem ozeanischen Plateau/Inselbogen und einem kontinentalen Krustenfragmentes schließen.In dem Bindura-Shamva Grünsteingürtel können zwei Sedimentgesteinseinheiten unterschieden werden, eine alluvial—flachmarine Abfolge und eine tiefmarin—fluviatile Abfolge. Extensionstektonik verursachte wahrscheinlich die Bildung des Sedimentbeckens. Die spätere Phase der Beckenbildung war jedoch ähnlich jener in modernen Vorlandbecken.Schichtparallele Eisensteinhorizonte sind häufig entlang von Sediment-Vulkanit-Kontakten zu finden. Diese Gesteine werden als silifizierte und von Sulfiden imprägnierte Scherzonen interpretiert. Syntektonische hydrothermale Alteration von Gesteinen entlang der Störungszonen führte zur Bildung dieser 'tektonischen Eisensteine'.

Tectonic geomorphology and active strain of the Northern Apennines mountain front

The Northern Apennines (NA) chain is the expression of the active plate margin between Europe and Adria. Given the low convergence rates and the moderate seismic activity, ambiguities still occur in defining a seismotectonic framework and many different scenarios have been proposed for the mountain front evolution. Differently from older models that indicate the mountain front as an active thrust at the surface, a recently proposed scenario describes the latter as the frontal limb of a long-wavelength fold (> 150 km) formed by a thrust fault tipped around 17 km at depth, and considered as the active subduction boundary. East of Bologna, this frontal limb is remarkably very straight and its surface is riddled with small, but pervasive high- angle normal faults. However, west of Bologna, some recesses are visible along strike of the mountain front: these perturbations seem due to the presence of shorter wavelength (15 to 25 km along strike) structures showing both NE and NW-vergence. The Pleistocene activity of these structures was already suggested, but not quantitative reconstructions are available in literature. This research investigates the tectonic geomorphology of the NA mountain front with the specific aim to quantify active deformations and infer possible deep causes of both short- and long-wavelength structures. This study documents the presence of a network of active extensional faults, in the foothills south and east of Bologna. For these structures, the strain rate has been measured to find a constant throw-to-length relationship and the slip rates have been compared with measured rates of erosion. Fluvial geomorphology and quantitative analysis of the topography document in detail the active tectonics of two growing domal structures (Castelvetro - Vignola foothills and the Ghiardo plateau) embedded in the mountain front west of Bologna. Here, tilting and river incision rates (interpreted as that long-term uplift rates) have been measured respectively at the mountain front and in the Enza and Panaro valleys, using a well defined stratigraphy of Pleistocene to Holocene river terraces and alluvial fan deposits as growth strata, and seismic reflection profiles relationships. The geometry and uplift rates of the anticlines constrain a simple trishear fault propagation folding model that inverts for blind thrust ramp depth, dip, and slip. Topographic swath profiles and the steepness index of river longitudinal profiles that traverse the anti- clines are consistent with stratigraphy, structures, aquifer geometry, and seismic reflection profiles. Available focal mechanisms of earthquakes with magnitude between Mw 4.1 to 5.4, obtained from a dataset of the instrumental seismicity for the last 30 years, evidence a clear vertical separation at around 15 km between shallow extensional and deeper compressional hypocenters along the mountain front and adjacent foothills. In summary, the studied anticlines appear to grow at rates slower than the growing rate of the longer- wavelength structure that defines the mountain front of the NA. The domal structures show evidences of NW-verging deformation and reactivations of older (late Neogene) thrusts. The reconstructed river incision rates together with rates coming from several other rivers along a 250 km wide stretch of the NA mountain front and recently available in the literature, all indicate a general increase from Middle to Late Pleistocene. This suggests focusing of deformation along a deep structure, as confirmed by the deep compressional seismicity. The maximum rate is however not constant along the mountain front, but varies from 0.2 mm/yr in the west to more than 2.2 mm/yr in the eastern sector, suggesting a similar (eastward-increasing) trend of the apenninic subduction.

Contribution of tectonic processes to the exhumation of the Cycladic blueschist unit, Greece and Turkey

In dieser Studie werden strukturgeologische, metamorphe und geochronologische Daten benutzt, um eine Quantifizierung tektonischer Prozesse vorzunehmen, die für die Exhumierung der Kykladischen Blauschiefereinheit in der Ägäis und der Westtürkei verantwortlich waren. Bei den beiden tektonischen Prozessen handelt es sich um: (1) Abschiebungstektonik und (2) vertikale duktile Ausdünnung. Eine finite Verformungsanalyse an Proben der Kykladischen Blauschiefereinheit ermöglicht eine Abschätzung des Beitrags von vertikaler duktiler Ausdünnung an der gesamten Exhumierung. Kalkulationen mit einem eindimensionalen, numerischen Model zeigt, daß vertikale duktile Ausdünnung nur ca. 10% an der gesamten Exhumierung ausmacht. Kinematische, metamorphe und geochronologische Daten erklären die tektonische Natur und die Evolution eines extensionalen Störungssystems auf der Insel Ikaria in der östlichen Ägäis. Thermobarometrische Daten lassen erkennen, daß das Liegende des Störungssystems aus ca. 15 km Tiefe exhumiert wurde. Sowohl Apatit- und Zirkonspaltspurenalter als auch Apatit (U-Th)/He-Alter zeigen, daß sich das extensionale Störungssystem zwischen 11-3 Ma mit einer Geschwindigkeit von ca. 7-8 km/Ma bewegte. Spät-Miozäne Abschiebungen trugen zur Exhumierung der letzten ~5-15 km der Hochdruckgesteine bei. Ein Großteil der Exhumierung der Kykladischen Blauschiefereinheit muß vor dem Miozän stattgefunden haben. Dies wird durch einen Extrusionskeil erklärt, der ca. 30-35 km der Kykladischen Blauschiefereinheit in der Westtürkei exhumierte. 40Ar/39Ar und 87Rb/86Sr Datierungen an Myloniten des oberen Abschiebungskontakts zwischen der Selçuk Decke und der darunterliegenden Ampelos/Dilek Decke der Kykladischen Blauschiefereinheit als auch des unteren Überschiebungskontakts zwischen der Ampelos/Dilek Decke und den darunterliegenden Menderes Decken zeigt, daß sich beide mylonitische Zonen um ca. ~35 Ma formten, was die Existenz eines Spät-Eozänen/Früh-Oligozänen Extrusionskeils beweist.

InSAR deformation measurements of the earthquake cycle in transcurrent tectonic domains, analytical and analog modeling

I applied the SBAS-DInSAR method to the Mattinata Fault (MF) (Southern Italy) and to the Doruneh Fault System (DFS) (Central Iran). In the first case, I observed limited internal deformation and determined the right lateral kinematic pattern with a compressional pattern in the northern sector of the fault. Using the Okada model I inverted the observed velocities defining a right lateral strike slip solution for the MF. Even if it fits the data within the uncertainties, the modeled slip rate of 13-15 mm yr-1 seems too high with respect to the geological record. Concerning the Western termination of DFS, SAR data confirms the main left lateral transcurrent kinematics of this fault segment, but reveal a compressional component. My analytical model fits successfully the observed data and quantifies the slip in ~4 mm yr-1 and ~2.5 mm yr-1 of pure horizontal and vertical displacement respectively. The horizontal velocity is compatible with geological record. I applied classic SAR interferometry to the October–December 2008 Balochistan (Central Pakistan) seismic swarm; I discerned the different contributions of the three Mw > 5.7 earthquakes determining fault positions, lengths, widths, depths and slip distributions, constraining the other source parameters using different Global CMT solutions. A well constrained solution has been obtained for the 09/12/2008 aftershock, whereas I tested two possible fault solutions for the 28-29/10/08 mainshocks. It is not possible to favor one of the solutions without independent constraints derived from geological data. Finally I approached the study of the earthquake-cycle in transcurrent tectonic domains using analog modeling, with alimentary gelatins like crust analog material. I successfully joined the study of finite deformation with the earthquake cycle study and sudden dislocation. A lot of seismic cycles were reproduced in which a characteristic earthquake is recognizable in terms of displacement, coseismic velocity and recurrence time.