Tectonic and stratigraphic evolution based on seismic sequence stratigraphy: Central rift section of the campos basin, offshore brazil

The rift section of the Brazilian basins represent the sedimentary record associated with the first stages of Gondwana break‐up in the Early Cretaceous phase (Berriasian to Aptian). The rift succession of the Campos Basin constitutes one of the main petroleum systems of Brazil’s marginal basins. This interval contains the main source rock and important reservoirs in the Lagoa Feia Group deposits. The Lagoa Feia Group is characterized by siliciclastic, carbonate and evaporite sediments deposited during the rift and post‐rift phases. Despite the economic relevance, little is known in stratigraphic terms regarding this rift interval. To date, most studies of the Lagoa Feia Group have adopted a lithostratigraphic approach, while this study proposes a tectonostrati-graphic framework for the deep‐rift succession of the Campos Basin (Lagoa Feia Group), using the fundamentals of seismic sequence stratigraphy. This work also aims to establish a methodological and practical procedure for the stratigraphic analysis of rift basins, using seismic data and seismofacies, and focusing on tectonicstratigraphic analysis. The dataset comprised 2D seismic lines, core and lithological logs from exploration wells. Three seismic facies were identified based on reflector patterns and lithologic data from well cores, providing an improved subdivision of the pre‐, syn‐ and post‐rift stages. The syn‐rift stage was further subdivided based on the geometric patterns of the reflectors. Tectonics was the main controlling factor in the sedimentary succession, and the pattern and geometry of the seismic reflectors of the syn‐rift interval in the Campos Basin allowed the identification of three tectonic systems tracts: (i) a Rift Initiation Systems Tract; (ii) a High Tectonic Activity Systems Tract and (iii) a Low Tectonic Activity Systems Tract

Palaeocurrent directions as an indicator of Pindos foreland evolution (central and southern part), Western Greece

In order to estimate the palaeoflow direction of the submarine fans, deposited in the Internal Ionian subbasin of the Pindos Foreland, fifty-one positions along the sub-basin were selected and measurements of palaeocurrents indicators such as flute and groove marks were taken. In the studied area the main palaeoflow direction of turbidites was axial, from south to north in the southern part, and from north to south in the northern part. A minor westward palaeoflow direction is also present. These palaeoflow directions were influenced mainly by the regional tectonic activity, such as internal thrusting (Gavrovo Thrust) and differential activity of the Pindos Thrust which subdivided Pindos foreland into narrow linear sub-basins

Hepcidin Expression in Iron Overload Diseases Is Variably Modulated by Circulating Factors

Hepcidin is a regulatory hormone that plays a major role in controlling body iron homeostasis. Circulating factors (holotransferrin, cytokines, erythroid regulators) might variably contribute to hepcidin modulation in different pathological conditions. There are few studies analysing the relationship between hepcidin transcript and related protein expression profiles in humans. Our aims were: a. to measure hepcidin expression at either hepatic, serum and urinary level in three paradigmatic iron overload conditions (hemochromatosis, thalassemia and dysmetabolic iron overload syndrome) and in controls; b. to measure mRNA hepcidin expression in two different hepatic cell lines (HepG2 and Huh-7) exposed to patients and controls sera to assess whether circulating factors could influence hepcidin transcription in different pathological conditions. Our findings suggest that hepcidin assays reflect hepatic hepcidin production, but also indicate that correlation is not ideal, likely due to methodological limits and to several post-trascriptional events. In vitro study showed that THAL sera down-regulated, HFE-HH and C-NAFLD sera up-regulated hepcidin synthesis. HAMP mRNA expression in Huh-7 cells exposed to sera form C-Donors, HFE-HH and THAL reproduced, at lower level, the results observed in HepG2, suggesting the important but not critical role of HFE in hepcidin regulation

1B/(−)IRE DMT1 Expression during Brain Ischemia Contributes to Cell Death Mediated by NF-κB/RelA Acetylation at Lys310

The molecular mechanisms responsible for increasing iron and neurodegeneration in brain ischemia are an interesting area of research which could open new therapeutic approaches. Previous evidence has shown that activation of nuclear factor kappa B (NF-κB) through RelA acetylation on Lys310 is the prerequisite for p50/RelA-mediated apoptosis in cellular and animal models of brain ischemia. We hypothesized that the increase of iron through a NF-κB-regulated 1B isoform of the divalent metal transporter-1 (1B/DMT1) might contribute to post-ischemic neuronal damage. Both in mice subjected to transient middle cerebral artery occlusion (MCAO) and in neuronally differentiated SK-N-SH cells exposed to oxygen-glucose-deprivation (OGD), 1A/DMT1 was only barely expressed while the 1B/DMT1 without iron-response-element (−IRE) protein and mRNA were early up-regulated. Either OGD or over-expression of 1B/(−)IRE DMT1 isoform significantly increased iron uptake, as detected by total reflection X-ray fluorescence, and iron-dependent cell death. Iron chelation by deferoxamine treatment or (−)IRE DMT1 RNA silencing displayed significant neuroprotection against OGD which concomitantly decreased intracellular iron levels. We found evidence that 1B/(−)IRE DMT1 was a target gene for RelA activation and acetylation on Lys310 residue during ischemia. Chromatin immunoprecipitation analysis of the 1B/DMT1 promoter showed there was increased interaction with RelA and acetylation of H3 histone during OGD exposure of cortical neurons. Over-expression of wild-type RelA increased 1B/DMT1 promoter-luciferase activity, the (−)IRE DMT1 protein, as well as neuronal death. Expression of the acetylation-resistant RelA-K310R construct, which carried a mutation from lysine 310 to arginine, but not the acetyl-mimic mutant RelA-K310Q, down-regulated the 1B/DMT1 promoter, consequently offering neuroprotection. Our data showed that 1B/(−)IRE DMT1 expression and intracellular iron influx are early downstream responses to NF-κB/RelA activation and acetylation during brain ischemia and contribute to the pathogenesis of stroke-induced neuronal damage

A computational model of liver iron metabolism

Iron is essential for all known life due to its redox properties; however, these same properties can also lead to its toxicity in overload through the production of reactive oxygen species. Robust systemic and cellular control are required to maintain safe levels of iron, and the liver seems to be where this regulation is mainly located. Iron misregulation is implicated in many diseases, and as our understanding of iron metabolism improves, the list of iron-related disorders grows. Recent developments have resulted in greater knowledge of the fate of iron in the body and have led to a detailed map of its metabolism; however, a quantitative understanding at the systems level of how its components interact to produce tight regulation remains elusive. A mechanistic computational model of human liver iron metabolism, which includes the core regulatory components, is presented here. It was constructed based on known mechanisms of regulation and on their kinetic properties, obtained from several publications. The model was then quantitatively validated by comparing its results with previously published physiological data, and it is able to reproduce multiple experimental findings. A time course simulation following an oral dose of iron was compared to a clinical time course study and the simulation was found to recreate the dynamics and time scale of the systems response to iron challenge. A disease state simulation of haemochromatosis was created by altering a single reaction parameter that mimics a human haemochromatosis gene (HFE) mutation. The simulation provides a quantitative understanding of the liver iron overload that arises in this disease. This model supports and supplements understanding of the role of the liver as an iron sensor and provides a framework for further modelling, including simulations to identify valuable drug targets and design of experiments to improve further our knowledge of this system

Iron metabolism and toxicity

Iron is an essential nutrient with limited bioavailability. When present in excess, iron poses a threat to cells and tissues, and therefore iron homeostasis has to be tightly controlled. Iron's toxicity is largely based on its ability to catalyze the generation of radicals, which attack and damage cellular macromolecules and promote cell death and tissue injury. This is lucidly illustrated in diseases of iron overload, such as hereditary hemochromatosis or transfusional siderosis, where excessive iron accumulation results in tissue damage and organ failure. Pathological iron accumulation in the liver has also been linked to the development of hepatocellular cancer. Here we provide a background on the biology and toxicity of iron and the basic concepts of iron homeostasis at the cellular and systemic level. In addition, we provide an overview of the various disorders of iron overload, which are directly linked to iron's toxicity. Finally, we discuss the potential role of iron in malignant transformation and cancer. © 2004 Elsevier Inc. All rights reserved