Surgical impact on brain tumor invasion: A physical perspective

It is conventional strategy to treat highly malignant brain tumors initially with cytoreductive surgery followed by adjuvant radio- and chemotherapy. However, in spite of all such efforts, the patients' prognosis remains dismal since residual glioma cells continue to infiltrate adjacent parenchyma and the tumors almost always recur. On the basis of a simple biomechanical conjecture that we have introduced previously, we argue here that by affecting the 'volume-pressure' relationship and minimizing surface tension of the remaining tumor cells, gross total resection may have an inductive effect on the invasiveness of the tumor cells left behind. Potential implications for treatment strategies are discussed

Plan de trabajo y cronograma para la ejecución de actividades

Propuesta técnica que incluye el desarrollo de seis actividades que comprometen la entrega de resultados a través de siete productos principales. Las actividades entorno al cumplimiento del convenio son i) Construir la línea base de información secundaria disponible sobre biodiversidad para la cuenca del río Claro, Antioquia, que incluya, entre otros, datos sobre ecología, genética, uso, conservación, distribución, uso de hábitat, impactos e información espacial, procesos ecológicos; ii) Desarrollar un taller con actores clave en la gestión de la biodiversidad en la cuenca del río Claro, para la validación y robustecimiento de la línea base de información, así como para la identificación de vacíos de información y priorización de especies de interés, ecosistemas y temáticas, con miras a la construcción de agendas de investigación a largo plazo; iii) Construir propuestas de diseño de muestreo de la biodiversidad a diferentes niveles: especies, poblaciones, comunidades, ecosistemas, paisaje, ajustadas a las características socioecológicas de la cuenca del río Claro, para el establecimiento de plataformas de monitoreo, que incluyan además el recurso hídrico de la cuenca del río Claro, la diversidad subterránea, epígea y asociada al ecosistema cárstico; iv) Realizar al menos dos pre-salidas a la cuenca del río Claro, para el reconocimiento de las ventanas o localidades de trabajo y ajuste de las propuestas de diseño de muestreo, así como para la definición de aspectos logísticos; v) Evaluar el estado del conocimiento sobre la ecología del Jaguar ( Panthera onca ) en la cuenca del río Claro y generar una propuesta de muestreo no invasivo para conocer el estado de la diversidad genética de la especie en la región; vi) Articular la red de actores y expertos en grandes felinos para la construcción colectiva de herramientas de gestión y conservación para el Jaguar (Panthera onca).Bogotá, ColombiaCiencias Básicas de la Biodiversida

Shox2 mediates Tbx5 activity by regulating Bmp4 in the pacemaker region of the developing heart

Heart formation requires a highly balanced network of transcriptional activation of genes. The homeodomain transcription factor, Shox2, is essential for the formation of the sinoatrial valves and for the development of the pacemaking system. The elucidation of molecular mechanisms underlying the development of pacemaker tissue has gained clinical interest as defects in its patterning can be related to atrial arrhythmias. We have analyzed putative targets of Shox2 and identified the Bmp4 gene as a direct target. Shox2 interacts directly with the Bmp4 promoter in chromatin immunoprecipitation assays and activates transcription in luciferase-reporter assays. In addition, ectopic expression of Shox2 in Xenopus embryos stimulates transcription of the Bmp4 gene, and silencing of Shox2 in cardiomyocytes leads to a reduction in the expression of Bmp4. In Tbx5del/+ mice, a model for Holt-Oram syndrome, and Shox2−/− mice, we show that the T-box transcription factor Tbx5 is a regulator of Shox2 expression in the inflow tract and that Bmp4 is regulated by Shox2 in this compartment of the embryonic heart. In addition, we could show that Tbx5 acts cooperatively with Nkx2.5 to regulate the expression of Shox2 and Bmp4. This work establishes a link between Tbx5, Shox2 and Bmp4 in the pacemaker region of the developing heart and thus contributes to the unraveling of the intricate interplay between the heart-specific transcriptional machinery and developmental signaling pathways

ICA-Derived Respiration Using an Adaptive R-peak Detector

Breathing Rate (BR) plays a key role in health deterioration monitoring. Despite that, it has been neglected due to inadequate nursing skills and insufficient equipment. ECG signal, which is always monitored in a hospital ward, is affected by respiration which makes it a highly appealing way for the BR estimation. In addition, the latter requires accurate R-peak detection, which is a continuing concern because current methods are still inaccurate and miss heart beats. This study proposes a frequency domain BR estimation method which uses a novel real-time R-peak detector based on Empirical Mode Decomposition (EMD) and a blind source ICA for separating the respiratory signal. The originality of the BR estimation method is that it takes place in the frequency domain as opposed to some of the current methods which rely on a time domain analysis, making the estimation more accurate. Moreover, our novel QRS detector uses an adaptive threshold over a sliding window and differentiates large Q-peaks from R-peaks, facilitating a more accurate BR estimation. The performance of our methods was tested on real data from Capnobase dataset. An average mean absolute error of less than 0.7 breath per minute was achieved using our frequency domain method, compared to 15 breaths per minute of the time domain analysis. Moreover, our modified QRS detector shows comparable results to other published methods, achieving a detection rate over 99.80%

Propuesta metodológica para la elaboración de la linea base de la biodiversidad de la cuenca del río claro, Antioquia, a partir de información secundaria

La cuenca del río Claro es considerada como uno de los ecosistemas más importantes de la región hidrográfica del río Grande del Magdalena. Es una región única a nivel biológico por su riqueza en especies endémicas, como resultado del aislamiento que por millones de años tuvieron las especies que allí han habitado, de cambios en las coberturas de los bosques y en la distribución de las especies, así como por las alteraciones geológicas en el área durante el Pleistoceno, lo que ha conferido a la zona la denominación de refugio del Pleistoceno. Esta condición ha desencadenado la formación de suelos cársticos, fruto de la erosión de los suelos generada por millones de años, influyendo de forma representativa en el tipo de biota que allí se encuentra. Con el objetivo de construir una visión amplia de las múltiples dimensiones del conocimiento de la biodiversidad en la cuenca del río Claro, el Instituto Humboldt, propone la construcción de una línea base que articule las diferentes fuentes de información disponibles, en un proceso sistemático y riguroso, fundamentado en una revisión extensa y detallada, y siguiendo estándares de calidad y excelencia en términos de los resultados esperados. Con este fin, se han identificado siete componentes temáticos (Análisis espacial y administración de datos, Dinámica y funcionamiento de ecosistemas, Genética de la conservación, Calidad del recurso hídrico, Vertebrados e invertebrados terrestres y acuáticos, Insectos y Flora), agrupando aquellos enfocados a nivel de especies y aquellos relacionados con otros niveles y aspectos de la biodiversidad.Bogotá, ColombiaCiencias Básicas de la Biodiversida

Heritability of seed weight in Maritime pine, a relevant trait in the transmission of environmental maternal effects

Quantitative seed provisioning is an important life-history trait with strong effects on offspring phenotype and fitness. As for any other trait, heritability estimates are vital for understanding its evolutionary dynamics. However, being a trait in between two generations, estimating additive genetic variation of seed provisioning requires complex quantitative genetic approaches for distinguishing between true genetic and environmental maternal effects. Here, using Maritime pine as a long-lived plant model, we quantified additive genetic variation of cone and seed weight (SW) mean and SW within-individual variation. We used a powerful approach combining both half-sib analysis and parent-offspring regression using several common garden tests established in contrasting environments to separate G, E and G x E effects. Both cone weight and SW mean showed significant genetic variation but were also influenced by the maternal environment. Most of the large variation in SW mean was attributable to additive genetic effects (h(2) = 0.55-0.74). SW showed no apparent G x E interaction, particularly when accounting for cone weight covariation, suggesting that the maternal genotypes actively control the SW mean irrespective of the amount of resources allocated to cones. Within-individual variation in SW was low (12%) relative to between-individual variation (88%), and showed no genetic variation but was largely affected by the maternal environment, with greater variation in the less favourable sites for pine growth. In summary, results were very consistent between the parental and the offspring common garden tests, and clearly indicated heritable genetic variation for SW mean but not for within-individual variation in SW.This study was financed by the Spanish National Research Grants RTA2007-100 and AGL2012-40151 (FENOPIN), both co-financed by EU-FEDER. The progeny trials and the clonal seed orchards are part of the experimental set up of the Maritime pine breeding programme developed by the Centro de Investigacion Forestal de Lourizan, Xunta de Galicia.Spanish National Research Grant RTA2007-100Spanish National Research Grant AGL2012-40151 (FENOPIN)EU-FEDERPeer reviewe

Pyogenic spondylitis

Pyogenic spondylitis is a neurological and life threatening condition. It encompasses a broad range of clinical entities, including pyogenic spondylodiscitis, septic discitis, vertebral osteomyelitis, and epidural abscess. The incidence though low appears to be on the rise. The diagnosis is based on clinical, radiological, blood and tissue cultures and histopathological findings. Most of the cases can be treated non-operatively. Surgical treatment is required in 10–20% of patients. Anterior decompression, debridement and fusion are generally recommended and instrumentation is acceptable after good surgical debridement with postoperative antibiotic cover

Mineralogical and geochemical analysis of Fe-phases in drill-cores from the Triassic Stuttgart Formation at Ketzin CO₂ storage site before CO₂ arrival

Reactive iron (Fe) oxides and sheet silicate-bound Fe in reservoir rocks may affect the subsurface storage of CO2 through several processes by changing the capacity to buffer the acidification by CO2 and the permeability of the reservoir rock: (1) the reduction of three-valent Fe in anoxic environments can lead to an increase in pH, (2) under sulphidic conditions, Fe may drive sulphur cycling and lead to the formation of pyrite, and (3) the leaching of Fe from sheet silicates may affect silicate diagenesis. In order to evaluate the importance of Fe-reduction on the CO2 reservoir, we analysed the Fe geochemistry in drill-cores from the Triassic Stuttgart Formation (Schilfsandstein) recovered from the monitoring well at the CO2 test injection site near Ketzin, Germany. The reservoir rock is a porous, poorly to moderately cohesive fluvial sandstone containing up to 2–4 wt% reactive Fe. Based on a sequential extraction, most Fe falls into the dithionite-extractable Fe-fraction and Fe bound to sheet silicates, whereby some Fe in the dithionite-extractable Fe-fraction may have been leached from illite and smectite. Illite and smectite were detected in core samples by X-ray diffraction and confirmed as the main Fe-containing mineral phases by X-ray absorption spectroscopy. Chlorite is also present, but likely does not contribute much to the high amount of Fe in the silicate-bound fraction. The organic carbon content of the reservoir rock is extremely low (<0.3 wt%), thus likely limiting microbial Fe-reduction or sulphate reduction despite relatively high concentrations of reactive Fe-mineral phases in the reservoir rock and sulphate in the reservoir fluid. Both processes could, however, be fuelled by organic matter that is mobilized by the flow of supercritical CO2 or introduced with the drilling fluid. Over long time periods, a potential way of liberating additional reactive Fe could occur through weathering of silicates due to acidification by CO2

Protein alterations associated with temozolomide resistance in subclones of human glioblastoma cell lines

Temozolomide (TMZ) is the standard chemotherapeutic agent for human malignant glioma, but intrinsic or acquired chemoresistance represents a major obstacle to successful treatment of this highly lethal group of tumours. Obtaining better understanding of the molecular mechanisms underlying TMZ resistance in malignant glioma is important for the development of better treatment strategies. We have successfully established a passage control line (D54-C10) and resistant variants (D54-P5 and D54-P10) from the parental TMZ-sensitive malignant glioma cell line D54-C0. The resistant sub-cell lines showed alterations in cell morphology, enhanced cell adhesion, increased migration capacities, and cell cycle arrests. Proteomic analysis identified a set of proteins that showed gradual changes in expression according to their 50% inhibitory concentration (IC50). Successful validation was provided by transcript profiling in another malignant glioma cell line U87-MG and its resistant counterparts. Moreover, three of the identified proteins (vimentin, cathepsin D and prolyl 4-hydroxylase, beta polypeptide) were confirmed to be upregulated in high-grade glioma. Our data suggest that acquired TMZ resistance in human malignant glioma is associated with promotion of malignant phenotypes, and our reported molecular candidates may serve not only as markers of chemoresistance but also as potential therapeutic targets in the treatment of TMZ-resistant human malignant glioma, providing a platform for future investigations

Sensory Experience Differentially Modulates the mRNA Expression of the Polysialyltransferases ST8SiaII and ST8SiaIV in Postnatal Mouse Visual Cortex

Polysialic acid (PSA) is a unique carbohydrate composed of a linear homopolymer of α-2,8 linked sialic acid, and is mainly attached to the fifth immunoglobulin-like domain of the neural cell adhesion molecule (NCAM) in vertebrate neural system. In the brain, PSA is exclusively synthesized by the two polysialyltransferases ST8SiaII (also known as STX) and ST8SiaIV (also known as PST). By modulating adhesive property of NCAM, PSA plays a critical role in several neural development processes such as cell migration, neurite outgrowth, axon pathfinding, synaptogenesis and activity-dependent plasticity. The expression of PSA is temporally and spatially regulated during neural development and a tight regulation of PSA expression is essential to its biological function. In mouse visual cortex, PSA is downregulated following eye opening and its decrease allows the maturation of GABAergic synapses and the opening of the critical period for ocular dominance plasticity. Relatively little is known about how PSA levels are regulated by sensory experience and neuronal activity. Here, we demonstrate that while both ST8SiaII and ST8SiaIV mRNA levels decrease around the time of eye opening in mouse visual cortex, only ST8SiaII mRNA level reduction is regulated by sensory experience. Using an organotypic culture system from mouse visual cortex, we further show that ST8SiaII gene expression is regulated by spiking activity and NMDA-mediated excitation. Further, we show that both ST8SiaII and ST8SiaIV mRNA levels are positively regulated by PKC-mediated signaling. Therefore, sensory experience-dependent ST8SiaII gene expression regulates PSA levels in postnatal visual cortex, thus acting as molecular link between visual activity and PSA expression