179 research outputs found

    Multiproxy investigation of the last 2,000 years BP marine paleoenvironmental record along the western Spitsbergen margin

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    A reconstruction of the last 2,000 years BP of environmental and oceanographic changes on the western margin of Spitsbergen was performed using a multidisciplinary approach including the fossil assemblages of diatoms, planktic and benthic foraminifera and calcareous nannofossils and the use of geochemistry (X-ray fluorescence spectroscopy, X-ray diffraction). We identified two warm periods (2,000–1,600 years BP and 1,300–700 years BP) that were associated with the Roman Warm Period and the Medieval Warm Period that alternate with colder oceanic conditions and sea ice coverage occurred during the Dark Ages (1,600–1,300 years BP) and the beginning of the Little Ice Age. During the Medieval Warm Period the occurrence of ice-rafted debris and Aulocoseira spp., a specific diatom genus commonly associated with continental freshwater, suggests significant runoff of meltwaters from local glaciers

    Stratigraphic framework of the late Miocene Pisco Formation at Cerro Los Quesos (Ica Desert, Peru)

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    The enormous concentration of marine vertebrates documented within the Pisco Formation is unique for Peru and South America and places this unit among the prime fossil Lagerstätten for Miocene to Pliocene marine mammals worldwide. In order to provide a robust stratigraphic framework for the fossil-bearing locality of Cerro Los Quesos, this study presents a 1:10,000 scale geological map covering an area of about 21 km2, a detailed measured section spanning 290 m of strata, and a refined chronostratigraphy for the studied succession well constrained by diatom biostratigraphy and high-resolution 40Ar/39Ar isotopic dating of three interbedded ash layers. Within the apparently monotonous, diatomite-dominated sedimentary section, the Pisco Formation has been subdivided into six local members, with stratigraphic control over the different outcrops facilitated by the establishment of a detailed marker bed stratigraphy based on fifteen readily distinguishable sediment layers of different nature

    Facies analysis, stratigraphy and marine vertebrate assemblage of the lower Miocene Chilcatay Formation at Ullujaya (Pisco basin, Peru)

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    This paper is the first integrated account of the sedimentology, stratigraphy and vertebrate paleontology for the marine strata of the Chilcatay Formation exposed at Ullujaya, Pisco basin (southern Peru). An allostratigraphic framework for the investigated strata was established using geological mapping (1:4,000 scale) and conventional sedimentary facies analysis and resulted in recognition of two unconformity-bounded allomembers (designated Ct1 and Ct2 in ascending order). The chronostratigraphic framework is well constrained by integration of micropaleontological data and isotope geochronology and indicates deposition during the early Miocene. The marine vertebrate fossil assemblage is largely dominated by cetaceans (odontocetes), whereas isolated teeth and spines indicate a well-diversified elasmobranch assemblage. Our field surveys, conducted to evaluate the paleontological sensitivity of the investigated strata, indicate that vertebrate remains only came from a rather restricted stratigraphic interval of the Ct1 allomember and reveal the high potential for these sediments to yield abundant and scientifically significant fossil assemblages

    Role of the p53/p21 system in the response of human colon carcinoma cells to Doxorubicin

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    BACKGROUND: Colon adenocarcinomas are refractory to a number of widely used anticancer agents. Multifactorial mechanisms have been implicated in this intrinsically resistant phenotype, including deregulation of cell death pathways. In this regard, the p53 protein has a well established role in the control of tumor cell response to DNA damaging agents; however, the relationship between p53-driven genes and drug sensitivity remains controversial. The present study investigates the role of the p53/p21 system in the response of human colon carcinoma cells to treatment with the cytotoxic agent doxorubicin (DOX) and the possibility to modify the therapeutic index of DOX by modulation of p53 and/or p21 protein levels. METHODS: The relationship between p53 and p21 protein levels and the cytotoxic effect of DOX was investigated, by MTT assay and western blot analysis, in HCT116 (p53-positive) and HT29 (p53-negative) colon cancer cells. We then assessed the effects of DOX in two isogenic cell lines derived from HCT116 by abrogating the expression and/or function of p53 and p21 (HCT116-E6 and HCT116 p21-/-, respectively). Finally, we evaluated the effect of pre-treatment with the piperidine nitroxide Tempol (TPL), an agent that was reported to induce p21 expression irrespective of p53 status, on the cytotoxicity of DOX in the four cell lines. Comparisons of IC50 values and apoptotic cell percentages were performed by ANOVA and Bonferroni's test for independent samples. C.I. calculations were performed by the combination Index method. RESULTS: Our results indicate that, in the colon carcinoma cell lines tested, sensitivity to DOX is associated with p21 upregulation upon drug exposure, and DOX cytotoxicity is potentiated by pre-treatment with TPL, but only in those cell lines in which p21 can be upregulated. CONCLUSIONS: p21 induction may significantly contribute to the response of colon adenocarcinomas cells to DOX treatment; and small molecules that can exploit p53-independent pathways for p21 induction, such as TPL, may find a place in chemotherapeutic protocols for the clinical management of colorectal cancer, where p53 function is often lost, due to genetic or epigenetic defects or to post-transcriptional inactivating mechanisms

    Ultraviolet Irradiation Induces the Accumulation of Chondroitin Sulfate, but Not Other Glycosaminoglycans, in Human Skin

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    Ultraviolet (UV) light alters cutaneous structure and function. Prior work has shown loss of dermal hyaluronan after UV-irradiation of human skin, yet UV exposure increases total glycosaminoglycan (GAG) content in mouse models. To more fully describe UV-induced alterations to cutaneous GAG content, we subjected human volunteers to intermediate-term (5 doses/week for 4 weeks) or single-dose UV exposure. Total dermal uronyl-containing GAGs increased substantially with each of these regimens. We found that UV exposure substantially increased dermal content of chondroitin sulfate (CS), but not hyaluronan, heparan sulfate, or dermatan sulfate. UV induced the accumulation of both the 4-sulfated (C4S) and 6-sulfated (C6S) isoforms of CS, but in distinct distributions. Next, we examined several CS proteoglycan core proteins and found a significant accumulation of dermal and endothelial serglycin, but not of decorin or versican, after UV exposure. To examine regulation in vitro, we found that UVB in combination with IL-1α, a cytokine upregulated by UV radiation, induced serglycin mRNA in cultured dermal fibroblasts, but did not induce the chondroitin sulfate synthases. Overall, our data indicate that intermediate-term and single-dose UVB exposure induces specific GAGs and proteoglycan core proteins in human skin in vivo. These molecules have important biologic functions and contribute to the cutaneous response to UV

    Biological evaluation of alginate-based hydrogels, with antimicrobial features by Ce(III) incorporation, as vehicles for a bone substitute

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    In this work three different hydrogels were developed to associate, as vehicles, with the synthetic bone substitute GR-HA. One based on an alginate matrix (Alg); a second on a mixture of alginate and chitosan (Alg/Ch); and a third on alginate and hyaluronate (Alg/HA), using Ca2+ ions as cross-linking agents. The hydrogels, as well as the respective injectable bone substitutes (IBSs), were fully characterized from the physical-chemical point of view. Weight change studies proved that all hydrogels were able to swell and degrade within 72 hours at pH 7.4 and 4.0, being Alg/HA the hydrogel with the highest degradation rate (80%). Rheology studies demonstrated that all hydrogels are non-Newtonian viscoelastic fluids, and injectability tests showed that IBSs presented low maximum extrusion forces, as well as quite stable average forces. In conclusion, the studied hydrogels present the necessary features to be successfully used as vehicles of GR-HA, particularly the hydrogel Alg/HA.The authors would like to acknowledge the financial support from FCT (Fundacao para a Ciencia e a Tecnologia) through the grant SFRH/BD/76237/2011 and project ENMED/0002/2010, from FEDER funds through the program COMPETE-Programa Operacional Factores de Competitividade-under the project PEst-C/EME/UI0285/2011, as well as to the project I&DT BIOMAT&CELL n. 1372
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