73 research outputs found

    Mechano-Electric Feedback in the Fish Heart

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    Mechanoelectric feedback (MEF) describes the modulation of electrical activity by mechanical activity. This may occur via the activation of mechanosensitive ion channels (MSCs). MEF has not previously been investigated in fish ventricular tissue even though fish can greatly increase ventricular end diastolic volume during exercise which should therefore provide a powerful mechanical stimulus for MEF.When the ventricles of extrinsically paced, isolated working trout hearts were dilated by increasing afterload, monophasic action potential (MAP) duration was significantly shortened at 25% repolarisation, unaltered at 50% repolarisation and significantly lengthened at 90% repolarisation. This observation is consistent with the activation of cationic non-selective MSCs (MSC(NS)s). We then cloned the trout ortholog of TRPC1, a candidate MSC(NS) and confirmed its presence in the trout heart.Our results have validated the use of MAP technology for the fish heart and suggest that, in common with amphibians and mammals, MEF operates in fish ventricular myocardium, possibly via the activation of mechanosensitive TRPC1 ion channels

    A preliminary study of the variation of phytoplankton absorption coefficients in the northern South China Sea

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    The temporal and spatial variabilities of phytoplankton absorption coefficients (a(ph)(lambda)) and their relationships with physical processes in the northern South China Sea were examined., based on in situ data collected from two cruise surveys during May 14 to 25 2001. and November 2 to 21, 2002. Significant changes in the surface water in a,h values and B/R ratios (a(ph)(440)/a(ph)(675)) were observed in May, which were caused by a phytoplankton bloom on the inner shelf stimulated by a large river plume due to heavy precipitation. This is consistent with the observed one order of magnitude elevation of chlorophyll a and a shift from a pico/nano dominated phytoplankton community to one dominated by micro-algae. Enhanced vertical mixing due to strengthened northeast monsoon in November has been observed to result in higher surface a(ph)(675) (0.002-0.006 m(-1) higher) and less pronounced subsurface maximum on the outer shelf/slope in November as compared with that in May. Measurements of a(ph) and B/R ratios from three transects in November revealed a highest surface a(ph)(675) immediately outside the mouth of the Zhujiang (Pearl) River Estuary, whereas lower a(ph)(675) and higher B/R ratios were featured in the outer shelf/slope waters, demonstrating the respective influence of the Zhujiang River plume and the oligotrophic water of the South China Sea. The difference in spectral shapes of phytoplankton absorption (measured by B/R ratios and bathochromic shifts) on these three transects infers that picoprocaryotes are the major component of the phytoplankton community on the outer shelf/slope rather than on the inner shelf. A regional tuning of the phytoplankton absorption spectral model (Carder et al., 1999) was attempted, demonstrating a greater spatial variation than temporal variation in the lead parameter a(0)(lambda). It was thus implicated that region-based parameterization of ocean color remote sensing algorithms in the northern South China Sea was mandatory.National Basic Research Program of China [2009CB421200, 2009CB421201]; National Natural Science Foundation of China [40821063]; High-Tech R&D Program of China [2006AA09A302, 2008AA09Z108

    Hystricognathy vs Sciurognathy in the Rodent Jaw: A New Morphometric Assessment of Hystricognathy Applied to the Living Fossil Laonastes (Diatomyidae)

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    While exceptional for an intense diversification of lineages, the evolutionary history of the order Rodentia comprises only a limited number of morphological morphotypes for the mandible. This situation could partly explain the intense debates about the taxonomic position of the latest described member of this clade, the Laotian rock rat Laonastes aenigmamus (Diatomyidae). This discovery has re-launched the debate on the definition of the Hystricognathi suborder identified using the angle of the jaw relative to the plane of the incisors. Our study aims to end this ambiguity. For clarity, it became necessary to revisit the entire morphological diversity of the mandible in extant and extinct rodents. However, current and past rodent diversity brings out the limitations of the qualitative descriptive approach and highlights the need for a quantitative approach. Here, we present the first descriptive comparison of the masticatory apparatus within the Ctenohystrica clade, in combining classic comparative anatomy with morphometrical methods. First, we quantified the shape of the mandible in rodents using 3D landmarks. Then, the analysis of osteological features was compared to myological features in order to understand the biomechanical origin of this morphological diversity. Among the morphological variation observed, the mandible of Laonastes aenigmamus displays an intermediate association of features that could be considered neither as sciurognathous nor as hystricognathous

    Pathologic and Phenotypic Alterations in a Mouse Expressing a Connexin47 Missense Mutation That Causes Pelizaeus-Merzbacher–Like Disease in Humans

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    Gap junction channels are intercellular conduits that allow diffusional exchange of ions, second messengers, and metabolites. Human oligodendrocytes express the gap junction protein connexin47 (Cx47), which is encoded by the GJC2 gene. The autosomal recessive mutation hCx47M283T causes Pelizaeus-Merzbacher–like disease 1 (PMLD1), a progressive leukodystrophy characterized by hypomyelination, retarded motor development, nystagmus, and spasticity. We introduced the human missense mutation into the orthologous position of the mouse Gjc2 gene and inserted the mCx47M282T coding sequence into the mouse genome via homologous recombination in embryonic stem cells. Three-week-old homozygous Cx47M282T mice displayed impaired rotarod performance but unchanged open-field behavior. 10-15-day-old homozygous Cx47M282T and Cx47 null mice revealed a more than 80% reduction in the number of cells participating in glial networks after biocytin injections into oligodendrocytes in sections of corpus callosum. Homozygous expression of mCx47M282T resulted in reduced MBP expression and astrogliosis in the cerebellum of ten-day-old mice which could also be detected in Cx47 null mice of the same age. Three-month-old homozygous Cx47M282T mice exhibited neither altered open-field behavior nor impaired rotarod performance anymore. Adult mCx47M282T expressing mice did not show substantial myelin alterations, but homozygous Cx47M282T mice, additionally deprived of connexin32, which is also expressed in oligodendrocytes, died within six weeks after birth and displayed severe myelin defects accompanied by astrogliosis and activated microglia. These results strongly suggest that PMLD1 is caused by the loss of Cx47 channel function that results in impaired panglial coupling in white matter tissue

    Monoclonal Antibody and Fusion Protein Biosimilars Across Therapeutic Areas: A Systematic Review of Published Evidence

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