Proliferation of Tau 304-380 Fragment Aggregates through Autocatalytic Secondary Nucleation.

The self-assembly of the protein tau into neurofibrillary tangles is one of the hallmarks of Alzheimer's disease and related tauopathies. Still, the molecular mechanism of tau aggregation is largely unknown. This problem may be addressed by systematically obtaining reproducible in vitro kinetics measurements under quiescent conditions in the absence of triggering substances. Here, we implement this strategy by developing protocols for obtaining an ultrapure tau fragment (residues 304-380 of tau441) and for performing spontaneous aggregation assays with reproducible kinetics under quiescent conditions. We are thus able to identify the mechanism of fibril formation of the tau 304-380 fragment at physiological pH using fluorescence spectroscopy and mass spectrometry. We find that primary nucleation is slow, and that secondary processes dominate the aggregation process once the initial aggregates are formed. Moreover, our results further show that secondary nucleation of monomers on fibril surfaces dominates over fragmentation of fibrils. Using separate isotopes in monomers and fibrils, through mass spectroscopy measurements, we verify the isotope composition of the intermediate oligomeric species, which reveals that these small aggregates are generated from monomer through secondary nucleation. Our results provide a framework for understanding the processes leading to tau aggregation in disease and for selecting possible tau forms as targets in the development of therapeutic interventions in Alzheimer's disease

Remoción de sulfuros presentes en el agua residual del proceso de curtido mediante cavitación hidrodinámica

(HC), um processo de oxidação avançada, analisado a partir de diferentes parâmetros de funcionamento como o pH inicial da pressão de águas residuais e da entrada para um tempo de resposta fixo de 90 minutos; parâmetros de projeto foram estabelecidos através da utilização de dois protótipos, variando o número e o diâmetro dos furos no ponto de estrangulamento com o objetivo de determinar as condições ideais para o tratamento deste tipo de contaminante do reator a águas residuais. Obteve um máximo de afastamento de 32,6% da concentração inicial de enxofre sem aplicar qualquer catalisador ou reagente químico; da mesma forma um análise custo-benefício devido a eficiência da tecnologia aplicada em comparação com a energia necessária pelo reator utilizado, mostrando uma diminuição de 198% do custo total do tratamento atual. Finalmente, cavitação hidrodinâmica é uma tecnologia sustentável para o indústria de curtimento de couro.El sulfuro presente en el agua residual de la industria del curtido de cueros proviene de la operación de pelambre (depilado de la piel) en concentraciones que afectan significativamente la calidad del agua del cuerpo receptor debido a la toxicidad del vertimiento produciendo la mortandad de flora y fauna, responsable de la presencia de olores desagradables en el cauce y la notable disminución del oxígeno disuelto en el agua del afluente. En la presente investigación, la remoción de sulfuro es evaluada empleando la técnica cavitación hidrodinámica (CH), un proceso de oxidación avanzada analizado desde diferentes parámetros de operación como pH inicial del agua residual y presión de entrada para un tiempo de reacción fijo de 90 minutos; parámetros de diseño fueron establecidos mediante el uso de dos prototipos, variando el número y diámetro de orificios en el punto de estrangulamiento con el objetivo de determinar las condiciones óptimas del reactor para el tratamiento de este tipo de contaminante en las aguas residuales. Se obtuvo una remoción máxima del 32,6 % de la concentración inicial de sulfuro sin aplicar algún tipo de catalizador o reactivo químico; de igual modo se realizó un análisis costobeneficio debido a la eficiencia de la tecnología aplicada en comparación con la energía requerida por el reactor empleado, donde se observa una disminución del 198 % del costo total del tratamiento actual. Finalmente, la cavitación hidrodinámica es una tecnología sustentable para la industria del curtido de cueros.Sulfide present in the wastewater from industrial tanneries is resulting from unhairing (depilated of the skin) in concentrations that affects significantly the water system due to its toxicity, producing the mortality of flora and fauna, responsible for the presence of unpleasant odors in the riverbed and decreasing the dissolve oxygen in the water of the receiver stream. In the present research, removal of sulfide is evaluated using hydrodynamic cavitation (HC). An advanced technology is analyzed by different parameters as initial pH solution and inlet pressure, set in two prototypes established for a reaction time of 90 minutes. Design parameters as number and diameter of holes in the constriction are estimated according on the degradation extent with the objective of knowing best reactor characteristics for wastewater treatment applying this technique. A maximum extent of sulfide oxidation of 32.6% was reached without using any further reagents; cost – benefit analysis had been discussed in the present investigation due to the enhance of cavitation hydrodynamic reached compared with the energy required by the reactor observing a shortfall of 198% related with the conventional treatment, HC was found as a sustainable technology for tannery industries

Análisis de los factores inmunohistopatológicos (receptores hormonales, estrógenos, progesterona y ERB-2) asociados al pronóstico del cáncer de mama en la población de Barranquilla (2004- 2005)

Resumen Objetivo: Estudiar los patrones de expresión de los receptores de estrógenos, progestagenos y erb-2 en 85 pacientes atendidas en dos laboratorios de patología de Barranquilla. De Julio del 2004 a diciembre del 2005. Material y metodos: Estudio Descriptivo de corte. Se utilizaron 85 muestras incluidas en parafina de pacientes con diagnóstico de cáncer de mama para lo cual, se realizaron estudios inmunohistoquimicos con técnicas de peroxidasa – antiperoxidasa, se utilizaron anticuerpos monoclonales Dako contra estrógenos, progestágenos y ebr-2. Resultados: Se observó carcinoma in situ (4), cáncer mesenquimal (1), carcinoma lobulillar (1) y resto carcinomas ductales infiltrantes grados I, II y III. La inmunohistoquímica mostró positividad para estrógeno y progestágeno a nivel intracelular en 73 casos y negativos para erb-2, 11 fueron negativos para estrógeno y progestágeno, uno fue positivo para ebr-2. Conclusiones: 1. El carcinoma ductal infiltrante grado II y III fue la forma histológica que se presentó con mayor frecuencia (80) casos. 2. El 88,23 % de los casos fueron estrógeno y progestágeno positivos. 3. La relación entre el componente histológico y receptores hormonales positivos, sugieren buen pronóstico. Palabras claves: Cáncer de mama, receptores de estrógenos, receptores de progesterona, ERB-2. Abstract Objectives: To study the patterns of expression of the estrogen, progestagens and erb-2 receptors in 85 patients attended in two pathology laboratories from Barranquilla, from July 2004 to December 2005 Material and methods: This is a descriptive study of cohort. 104 cases were reviewed and 18 were excluded by lack of data. Inmunohistochemistry studies with techniques of peroxidase - antiperoxidase were made, for which Dako monoclonals antibodies against estrogens, progestagens and ebr-2 were used. Results: Four neoplasias were classified as carcinoma in situ, one mesenquimal cancer, one lobulillar carcinoma and the others were infiltrating ductal carcinomas grade I, II and III. The immunohistochemistry studies showed positivity for estrogens and progestagen at the intracellular level in 73 cases and negativity to erb-2, 11 were negative for both estrogen and progestagen and one was positive to ebr-2. Conclusions: 1.The infiltrating ductal carcinoma grades II and III were the histological presentation that appears most frequently (80) cases. 2. 88.03 % of the cases were positive for estrogens and progestagens. 3. The relation between the histological component and the hormonal receptors positivity, suggests a good prognosis. Key words: Breast cancer, estrogen receptors, progestagen receptors, ERB-2, prognosis

Epigallocatechin gallate (EGCG) reduces the intensity of pancreatic amyloid fibrils in human islet amyloid polypeptide (hIAPP) transgenic mice

The formation of amyloid fibrils by human islet amyloid polypeptide protein (hIAPP) has been implicated in pancreas dysfunction and diabetes. However, efficient treatment options to reduce amyloid fibrils in vivo are still lacking. Therefore, we tested the effect of epigallocatechin gallate (EGCG) on fibril formation in vitro and in vivo. To determine the binding of hIAPP and EGCG, in vitro interaction studies were performed. To inhibit amyloid plaque formation in vivo, homozygous (tg/tg), hemizygous (wt/tg), and control mice (wt/wt) were treated with EGCG. EGCG bound to hIAPP in vitro and induced formation of amorphous aggregates instead of amyloid fibrils. Amyloid fibrils were detected in the pancreatic islets of tg/tg mice, which was associated with disrupted islet structure and diabetes. Although pancreatic amyloid fibrils could be detected in wt/tg mice, these animals were non-diabetic. EGCG application decreased amyloid fibril intensity in wt/tg mice, however it was ineffective in tg/tg animals. Our data indicate that EGCG inhibits amyloid fibril formation in vitro and reduces fibril intensity in non-diabetic wt/tg mice. These results demonstrate a possible in vivo effectiveness of EGCG on amyloid formation and suggest an early therapeutical application

Surface-Catalyzed Secondary Nucleation Dominates the Generation of Toxic IAPP Aggregates.

The aggregation of the human islet amyloid polypeptide (IAPP) is associated with diabetes type II. A quantitative understanding of this connection at the molecular level requires that the aggregation mechanism of IAPP is resolved in terms of the underlying microscopic steps. Here we have systematically studied recombinant IAPP, with amidated C-terminus in oxidised form with a disulphide bond between residues 3 and 7, using thioflavin T fluorescence to monitor the formation of amyloid fibrils as a function of time and IAPP concentration. We used global kinetic analyses to connect the macroscopic measurements of aggregation to the microscopic mechanisms, and show that the generation of new aggregates is dominated by the secondary nucleation of monomers on the fibril surface. We then exposed insulinoma cells to aliquots extracted from different time points of the aggregation process, finding the highest toxicity at the midpoint of the reaction, when the secondary nucleation rate reaches its maximum. These results identify IAPP oligomers as the most cytotoxic species generated during IAPP aggregation, and suggest that compounds that target secondary nucleation of IAPP could be most effective as therapeutic candidates for diabetes type II

Comparación plan de estudios programa administración de empresas Uniminuto y Columbus State University

Realizar comparaciones entre los modelos educativos enfocándonos en las asignaturas que se enseñan a los estudiantes de la Corporación Universitaria Minuto de Dios y Columbus State University (CSU), es un proceso que se inicia con el conocimiento de la malla curricular de las dos Universidades para intentar así, identificar cuáles serían las asignaturas con mayor similitud en Columbus, sin embargo los enfoques que se manejan son diferentes, teniendo en cuenta que la demanda y población a la cual se dirigen, por razones económicas, condiciones sociales y características de los estudiantes, como también el mercado laboral que ofrece el entorno

The global abundance of tree palms

Aim Palms are an iconic, diverse and often abundant component of tropical ecosystems that provide many ecosystem services. Being monocots, tree palms are evolutionarily, morphologically and physiologically distinct from other trees, and these differences have important consequences for ecosystem services (e.g., carbon sequestration and storage) and in terms of responses to climate change. We quantified global patterns of tree palm relative abundance to help improve understanding of tropical forests and reduce uncertainty about these ecosystems under climate change. Location Tropical and subtropical moist forests. Time period Current. Major taxa studied Palms (Arecaceae). Methods We assembled a pantropical dataset of 2,548 forest plots (covering 1,191 ha) and quantified tree palm (i.e., ≥10 cm diameter at breast height) abundance relative to co‐occurring non‐palm trees. We compared the relative abundance of tree palms across biogeographical realms and tested for associations with palaeoclimate stability, current climate, edaphic conditions and metrics of forest structure. Results On average, the relative abundance of tree palms was more than five times larger between Neotropical locations and other biogeographical realms. Tree palms were absent in most locations outside the Neotropics but present in >80% of Neotropical locations. The relative abundance of tree palms was more strongly associated with local conditions (e.g., higher mean annual precipitation, lower soil fertility, shallower water table and lower plot mean wood density) than metrics of long‐term climate stability. Life‐form diversity also influenced the patterns; palm assemblages outside the Neotropics comprise many non‐tree (e.g., climbing) palms. Finally, we show that tree palms can influence estimates of above‐ground biomass, but the magnitude and direction of the effect require additional work. Conclusions Tree palms are not only quintessentially tropical, but they are also overwhelmingly Neotropical. Future work to understand the contributions of tree palms to biomass estimates and carbon cycling will be particularly crucial in Neotropical forests

Consistent patterns of common species across tropical tree communities

Trees structure the Earth’s most biodiverse ecosystem, tropical forests. The vast number of tree species presents a formidable challenge to understanding these forests, including their response to environmental change, as very little is known about most tropical tree species. A focus on the common species may circumvent this challenge. Here we investigate abundance patterns of common tree species using inventory data on 1,003,805 trees with trunk diameters of at least 10 cm across 1,568 locations1,2,3,4,5,6 in closed-canopy, structurally intact old-growth tropical forests in Africa, Amazonia and Southeast Asia. We estimate that 2.2%, 2.2% and 2.3% of species comprise 50% of the tropical trees in these regions, respectively. Extrapolating across all closed-canopy tropical forests, we estimate that just 1,053 species comprise half of Earth’s 800 billion tropical trees with trunk diameters of at least 10 cm. Despite differing biogeographic, climatic and anthropogenic histories7, we find notably consistent patterns of common species and species abundance distributions across the continents. This suggests that fundamental mechanisms of tree community assembly may apply to all tropical forests. Resampling analyses show that the most common species are likely to belong to a manageable list of known species, enabling targeted efforts to understand their ecology. Although they do not detract from the importance of rare species, our results open new opportunities to understand the world’s most diverse forests, including modelling their response to environmental change, by focusing on the common species that constitute the majority of their trees.Publisher PDFPeer reviewe