Chemical composition of modern and fossil hippopotamid teeth and implications for paleoenvironmental reconstructions and enamel formation : part 2, alkaline earth elements as tracers of watershed hydrochemistry and provenance

This study demonstrates that alkaline earth elements in enamel of hippopotamids, in particular Ba and Sr, are tracers for water provenance and hydrochemistry in terrestrial settings. The studied specimens are permanent premolar and molar teeth found in modern and fossil lacustrine sediments of the Western Branch of the East African Rift system (Lake Kikorongo, Lake Albert, and Lake Malawi) and from modern fluvial environments of the Nile River. Concentrations in enamel vary by two orders of magnitude for Ba (120–9336 μg g−1) as well as for Sr (9–2150 μg g−1). The variations are partially induced during post-mortem alteration and during amelogenesis, but the major contribution originates ultimately from the variable water chemistry in the habitats of the hippopotamids which is controlled by the lithologies and weathering processes in the watershed areas. Amelogenesis causes a distinct distribution of MgO, Ba and Sr in modern and fossil enamel, in that element concentrations increase along profiles from the outer rim towards the enamel–dentin junction by a factor of 1.3–1.9. These elements are well correlated in single specimens, thus suggesting that their distribution is determined by a common, single process, which can be described by closed system Rayleigh crystallization of bioapatite in vivo. Enamel from most hippopotamid specimens has Sr/Ca and Ba/Ca which are typical for herbivores. However, Ba/Sr ranges from 0.1 to 3 and varies on spatial and temporal scales. Thus, Sr concentrations and Ba/Sr in enamel differentiate between habitats having basaltic mantle rocks or Archean crustal rocks as the ultimate sources of Sr and Ba. This provenance signal is modulated by climate change. In Miocene to Pleistocene enamel from the Lake Albert region, Ba/Sr decreases systematically with time from 2 to 0.5. This trend can be correlated with changes in climate from humid to arid, in vegetation from C3 to C4 biomass as well as with increasing evaporation of the lake water. The most plausible explanation is that Ba mobility decreased with increasing aridification due to preferential deposition with clay and Fe-oxide-hydroxide or barite on the watershed of Lake Albert

Alteraciones en la proliferación celular y muerte celular programada tipo apoptosis en muestras de carcinoma de células escamosas de mucosa oral

56 p.El carcinoma de células escamosas de la cavidad oral (CCECO) representa el 90% de las neoplasias malignas bucales. La carcinogénesis oral se ha vinculado a daños genéticos no letales, especialmente en secuencias de genes supresores de tumores y oncogenes. Estas mutaciones y otros mecanismos permiten a las células proliferar a un ritmo que supera la muerte celular, especialmente la de tipo apoptosis. Este desbalance se debe tanto al aumento en la proliferación como a una disminución de la muerte celular. Así, la desregulación de la muerte celular tipo apoptosis también juega un rol fundamental en el proceso de carcinogénesis.El objetivo del presente estudio fue analizar la posible desregulación de proliferación tumoral (determinada mediante la expresión de marcadores de proliferación tumoral) y muerte celular tipo apoptosis en el CCECO. Se estudiaron 5 muestras correspondientes a biopsias incisionales de CCECO obtenidas de la Unidad de Diagnostico Oral e Histopatología de las Clínicas Odontológicas de la Facultad de Ciencias de la Salud, Universidad de Talca. Éstas fueron sometidas a análisis inmunohistoquímico para el antígeno de proliferación celular nuclear (PCNA) y el gen supresor de tumores p53. Las muestras fueron analizadas adicionalmente con el método histoquímico de detección de Regiones Organizadoras de Nucléolos (Técnica AgNOR). La posible muerte celular tipo apoptosis fue determinada mediante el método de TUNEL (TdT-mediated dUTP Nick-End Labeling). Los resultados de nuestro estudio confirman que el CCECO presenta una desregulación de procesos celulares básicos, específicamente: 1) Aumento de la proliferación celular 2) Presencia de genes supresores de tumores mutados (p53) 3) Alteración en el patrón de maduración epitelial, manifestado por una alteración en la expresión normal de células TUNEL+ en el epitelio./ABSTRACT:Oral squamous cell carcinoma (OSCC) represents the 90% of the oral malignant neoplasms. The oral carcinogenesis has been related to non-lethal genetic damage, especially in tumor-supressor genes and oncogenes. These mutations and other deregulated mechanisms results in an increased cellular proliferation rate that overtake the cell death rate, the latter one is additionally decreased. Therefore, cell death deregulation, specially apoptotic cell death, plays a fundamental role in the oral carcinogenesis.The principal aim of the present study was to analyze the possible deregulation of cellular proliferation (determined by proliferation markers) and the apoptotic cell death in OSCC. We analyzed five samples of incisional biobsies of OSCC from the “Unidad de Diagnostico Oral e Histopatología de las Clínicas Odontológicas de la Facultad de Ciencias de la Salud, Universidad de Talca”. Immunohistochemistry for the proliferating celular nuclear antigen (PCNA) and the p53 tumor suppressor gene was performed. Additionally, nucleolar organizer regions (AgNORs) were analyzed histochemically and DNA fragmentation was determined by the TUNEL (TdT-mediated dUTP Nick- End Labeling) method.Our results confirm that OSCC present deregulation of basic cellular processes, specifically: 1) Increase in cell proliferation 2) Mutation of tumor suppressor genes 3) Alteration in normal epithelial differentiation, evidenced by altered expression of TUNEL+ cell

Chemical composition of modern and fossil Hippopotamid teeth and implications for paleoenvironmental reconstructions and enamel formation - Part 2: Alkaline earth elements as tracers of watershed hydrochemistry and provenance [Discussion paper]

For reconstructing environmental change in terrestrial realms the geochemistry of fossil bioapatite in bones and teeth is among the most promising applications. This study demonstrates that alkaline earth elements in enamel of Hippopotamids, in particular Ba and Sr are tracers for water provenance and hydrochemistry. The studied specimens are molar teeth from Hippopotamids found in modern and fossil lacustrine settings of the Western Branch of the East African Rift system (Lake Kikorongo, Lake Albert, and Lake Malawi) and from modern fluvial environments of the Nile River. Concentrations in enamel vary by ca. two orders of magnitude for Ba (120–9336 μg g−1) as well as for Sr (9–2150 μg g−1). Concentration variations in enamel are partly induced during post-mortem alteration and during amelogenesis, but the major contribution originates from the variable water chemistry in the habitats of the Hippopotamids which is dominated by the lithologies and weathering processes in the watershed areas. Amelogenesis causes a distinct distribution of Ba and Sr in modern and fossil enamel, in that element concentrations increase along profiles from the outer rim towards the enamel-dentin junction by a factor of 1.3–1.5. These elements are well correlated with MgO and Na2O in single specimens, thus suggesting that their distribution is determined by a common, single process. Presuming that the shape of the tooth is established at the end of the secretion process and apatite composition is in equilibrium with the enamel fluid, the maturation process can be modeled by closed system Rayleigh crystallization. Enamel from many Hippopotamid specimens has Sr/Ca and Ba/Ca which are typical for herbivores, but the compositions extend well into the levels of plants and carnivores. Within enamel from single specimens these element ratios covary and provide a specific fingerprint of the Hippopotamid habitat. All specimens together, however, define subparallel trends with different Ba/Sr ranging from 0.1 to 3. This ratio varies on spatial and temporal scales and traces provenance signals as well as the fractionation of the elements in the hydrological cycle. Thus, Sr concentrations and Ba/Sr in enamel differentiate between habitats having basaltic or Archean crustal rocks as the ultimate sources of Sr and Ba. The provenance signal is modulated by climate change. In Miocene to Pleistocene enamel from the Lake Albert region, Ba/Sr decreases systematically with time from about 2 to 0.5. This trend can be correlated with changes in climate from humid to arid in vegetation from C3 to C4 biomass as well as with increasing evaporation of the lake water. The most plausible explanation is that with time, Ba mobility decreased relative to that of Sr. This can arise if preferential adsorption of Ba to clay and Fe-oxide-hydroxide is related to increasing aridification. Additionally, weathering solutions and lake water can become increasingly alkaline and barite becomes stable. In this case, Ba will be preferentially deposited on the watershed of Lake Albert and rivers with low Ba/Sr will feed the habitats of the Hippopotamids

Azaporphine guest-host complexes in solution and gas-phase: evidence for partially filled nanoprisms and exchange reactions

Supramolecular guest-host complexes comprising various azaporphines stacked in a coordination nanoprism consisting of tris(4-pyridyl)triazines as panels{,} 1{,}4-bis(pyridyl)benzenes as pillars and (en)Pd as hinges were synthesized according to the procedure of Fujita and coworkers and characterized as ions in the gas-phase by high-resolution electrospray ionization mass spectrometry and collision induced dissociation as well as in solution by analytical ultracentrifugation. Apart from fully filled nanoprisms we have also prepared and observed partially filled as well as empty congeners in aqueous solutions. Upon mixing room temperature solutions of two types of nanoprisms{,} we observe that azaporphine guest exchange reactions occur on a timescale of minutes{,} indicating that the formation of the guest-host complexes is reversible

Roadmap to Gigahertz Organic Transistors

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Determinación del efecto quimiopreventivo de quercetina en un modelo de carcinogénesis oral en ratones CF-1 expuestos a 4-nitroquinolina 1- oxido

104 p.El cáncer es un problema de salud pública a nivel mundial, afectando por igual a países desarrollados, como a los en vías en desarrollo. El cáncer orofaríngeo es una de las neoplasias más prevalentes (5,7%), afectando anualmente aproximadamente a 400.000 personas. En particular el carcinoma de células escamosas de la cavidad oral (CCECO) representa el 80% de estas neoplasias. El tratamiento de este tipo de cáncer es sumamente costoso y radical, lo que conlleva graves secuelas para el paciente durante toda su vida. La detección temprana de esta neoplasia es la mejor alternativa para impedir estas consecuencias.Quercetina es uno de los flavonoides más comunes y ampliamente distribuido en frutas y hortalizas. Es un potente antioxidante, que podría inducir respuestas celulares que contribuyan a disminuir la severidad de las neoplasias, convirtiéndolo en un candidato a ser un agente quimiopreventivo. Sin embargo, en la literatura se han reportado que la quercetina podría tener efectos oxidantes in vitro y que las dosis necesarias para obtener efectos antioxidantes in vivo son difícilmente aplicables.El objetivo de este estudio fue determinar el posible efecto quimiopreventivo de quercetina en CCECO inducido por 4-NQO. Para esto se utilizó un modelo de carcinogénesis químico murino determinando el efecto de quercetina sobre las lesiones preneoplásicas y neoplásicas, nivel de lipoperoxidación y glutatión reducido en sangre de ratones tratados. Además, se evaluó el potencial efecto tóxico del compuesto en cultivos celulares de fibroblastos pulmonares (MCR-5).Quercetina a bajas concentraciones previene la disminución de la viabilidad celular causada por 4-NQO, pero no mejora la sobrevida, ni la incidencia, ni la severidad de las lesiones preneoplásicas y de CCECO de ratones tratados con 4-NQO. Además mantiene bajos los niveles de GSH sanguíneo en ratones expuestos a 4-NQO y quercetina. Se concluye que Quercetina no presenta un efecto quimiopreventivo sobre las lesiones en la mucosa lingual de ratones sometidos a carcinogénesis experimental inducida por 4-NQO./ ABSTRACT: Cancer is a worldwide public health problem, affecting both developed and developing countries. Oropharyngeal cancer is one of the most prevalent carcinomas (5.7%), affecting approximately 400000 individuals annually. Squamous cell carcinoma of the oral cavity (SCCOC) represents 80% of these tumors. Treatment of this type of cancer is extremely expensive and radical, and has serious consequences for the patient throughout their lives. Early detection of this neoplasm is the best alternative to prevent these consequences. Quercetin is one of the most common and widely distributed flavonoids in fruits and vegetables. It is a powerful antioxidant which could induce cellular responses that might contribute to reduce the severity of tumors, making it a candidate as a chemopreventive agent. However, the scientific reports indicates that Quercetin may have oxidant effects in vitro and that the doses required for in vivo antioxidant effects are hardly applicable.The objetive of this study was to determine the potential chemopreventive effect of Quercetin over 4-NQO induced SCCOC in mice. We determined the effect of Quercetin on preneoplastic and neoplastic lesions, lipoperoxidation levels and reduced glutathione levels in the blood of treated animals. Additionally, the potential toxic effects on lung fibroblast cell cultures (MCR-5) was assessed. Quercetin at low concentrations prevent the decrease of cell viability caused by 4-NQO, but does not improve survival, nor the incidence or severity of preneoplastic lesions and SCCOC in mice treated with 4-NQO. Quercetin also maintains low blood GSH levels in CF-1 mice exposed to 4-NQO and quercetin. We conclude, that Quercetin has no chemopreventive effect on lesions in the lingual mucosa in mice subjected to experimental carcinogenesis with 4-NQO

Defining Criteria for Guiding Cancer Patients to Find a Reputable Complementary Medicine Provider: Results of a Literature Review and a Consensus Procedure

Purpose: Even in cases of positive evidence for complementary medicine (CM) therapies, it is still difficult for cancer patients to identify reputable providers. The aim of this study was to develop and evaluate a criteria list to provide guidance to cancer patients seeking a reputable CM provider. Methods: The design combined a literature review, an expert consensus procedure (n=15) and an assessment from three stakeholder perspectives (patients (n=18), CM providers (n=26) and oncology physicians (n=20)). Results: A total of 30 existing CM criteria were extracted from the literature, and 12 more were added by the experts. The main challenge was to define criteria that could easily be applied by the patients. A final comprehensive list of 8 criteria guiding cancer patients to find a reputable CM provider was developed. Conclusion: Health professionals and cancer information services might find the criteria list helpful when aiming to strengthen patients' awareness of quality-related factors associated with CM providers. The criteria developed might be helpful when standards are established for quality assurance in CM in oncology

Expresion de cambios histopatologicos reaccionales, pre-neoplasicos y/o neoplasicos en el epitelio de la mucosa lingual de ratones cf-1 expuestos a 4-nitroquinolina-1-oxido.

77 p.INTRODUCCIÓN: El cáncer oral es una enfermedad que afecta a 400.000 personas cada año. El CCECO representa aproximadamente el 90% de los casos. El desarrollo de modelos de carcinogénesis experimental en animales juega un papel fundamental para su estudio y el desarrollo de terapias. OBJETIVO: Inducir cambios histopatológicos reaccionales, pre-neoplásicos y/o neoplásicos en el epitelio de la mucosa lingual de ratones CF-1 al exponerlos a 4- nitroquinolina-1-oxido (4-NQO). MATERIALES Y MÉTODOS: Se aplicó una solución de 4NQO más propilenglicol diluido en el agua de bebida a 20 ratones, a una concentración de 100 μg/ml y se mantuvo un grupo control de igual tamaño solo con agua y propilenglicol. Esta sustancia se aplicó por un periodo de 16 semanas, después del cual se suspendió, esperando hasta las 28 semanas para realizar la biopsia de la lengua. Se analizó la presentación de lesiones clínicas (leucoplasia, eritroplasia y lesiones mixtas). Se procesó la totalidad de la lengua para estudio histopatológico de hematoxilina-eosina convencional, buscando la presencia de focos de lesiones reaccionales, pre-neoplásicos y neoplásicos. RESULTADOS: Se encontró un total de 58 lesiones macroscópicamente detectables, localizadas principalmente en la zona dorsal-medial de la lengua, de apariencia leucoplásica, de tamaños < a 1 mm hasta 3 mm, y de forma sésil. En el estudio histopatológico, las lesiones de mayor incidencia, en orden decreciente, fueron las hiperqueratosis, la hiperplasia, el carcinoma invasor y la displasia severa o CA in situ. CONCLUSIÓN: El 4-nitroquinolina 1-óxido es capaz de inducir cambios histopatológicos reaccionales, pre-neoplásicos y neoplásicos en el epitelio de la mucosa lingual de ratones CF-1 en forma similar a otros modelos animales ya sea de otras especies o cepa

Altered splicing of the BIN1 muscle-specific exon in humans and dogs with highly progressive centronuclear myopathy

Amphiphysin 2, encoded by BIN1, is a key factor for membrane sensing and remodelling in different cell types. Homozygous BIN1 mutations in ubiquitously expressed exons are associated with autosomal recessive centronuclear myopathy (CNM), a mildly progressive muscle disorder typically showing abnormal nuclear centralization on biopsies. In addition, misregulation of BIN1 splicing partially accounts for the muscle defects in myotonic dystrophy (DM). However, the muscle-specific function of amphiphysin 2 and its pathogenicity in both muscle disorders are not well understood. In this study we identified and characterized the first mutation affecting the splicing of the muscle-specific BIN1 exon 11 in a consanguineous family with rapidly progressive and ultimately fatal centronuclear myopathy. In parallel, we discovered a mutation in the same BIN1 exon 11 acceptor splice site as the genetic cause of the canine Inherited Myopathy of Great Danes (IMGD). Analysis of RNA from patient muscle demonstrated complete skipping of exon 11 and BIN1 constructs without exon 11 were unable to promote membrane tubulation in differentiated myotubes. Comparative immunofluorescence and ultrastructural analyses of patient and canine biopsies revealed common structural defects, emphasizing the importance of amphiphysin 2 in membrane remodelling and maintenance of the skeletal muscle triad. Our data demonstrate that the alteration of the muscle-specific function of amphiphysin 2 is a common pathomechanism for centronuclear myopathy, myotonic dystrophy, and IMGD. The IMGD dog is the first faithful model for human BIN1-related CNM and represents a mammalian model available for preclinical trials of potential therapies

Influence of Compensating Defect Formation on the Doping Efficiency and Thermoelectric Properties of Cu_(2-y)Se_(1–x)Br_x

The superionic conductor Cu_(2−δ)Se has been shown to be a promising thermoelectric at higher temperatures because of very low lattice thermal conductivities, attributed to the liquid-like mobility of copper ions in the superionic phase. In this work, we present the potential of copper selenide to achieve a high figure of merit at room temperature, if the intrinsically high hole carrier concentration can be reduced. Using bromine as a dopant, we show that reducing the charge carrier concentration in Cu_(2−δ)Se is in fact possible. Furthermore, we provide profound insight into the complex defect chemistry of bromine doped Cu_(2−δ)Se via various analytical methods and investigate the consequential influences on the thermoelectric transport properties. Here, we show, for the first time, the effect of copper vacancy formation as compensating defects when moving the Fermi level closer to the valence band edge. These compensating defects provide an explanation for the often seen doping inefficiencies in thermoelectrics via defect chemistry and guide further progress in the development of new thermoelectric materials