生物标记物之警示信号

寻找生物标记——能对阿尔茨海默氏症的侵入发出警告信号的标记物——的工作一直在进行着。而开展这项研究的目的旨在赢得对这一疾病治疗的主动权．探索阿尔茨海默氏症防治的新模式     

Conservation status of threatened fishes in Warner Basin, Oregon

Two federally listed fishes, the Foskett speckled dace and Warner sucker, are endemic to Warner Basin in south central Oregon. The Foskett speckled dace is native only to a single spring in Coleman Valley. A nearby spring was stocked with dace in 1979 and 1980, and now provides a second population. The present numbers of dace probably are at their highest levels since settlement of the region. The Warner sucker historically occurred throughout much of the Warner Valley, but its distribution and abundance have been reduced by construction of reservoirs and irrigation dams and the introduction of predatory game fishes. Lentic habitats have become dominated by introduced fishes, particularly white crappie, black crappie, and brown bullhead. The largest remaining population of Warner suckers occurs in Hart Lake, where successful reproduction was documented but there is no evidence of recruitment to the adult population.     

Retrospective evaluation of the effects of human disturbance and goldfish introduction on endangered Pahrump poolfish

Life history data for Pahrump poolfish ( Empetrichthys latos latos ) collected from 1937 to 1975 were organized and analyzed to improve our understanding of changes caused by human habitat disruption and introduced goldfish ( Carassius auratus ) at Manse Spring, Nevada. Pahrump poolfish twice demonstrated their ability to recover numerically from a population crash. The first crash followed a November 1961 introduction of a few goldfish and subsequent removal of vegetation by local ranch children intent on turning Manse Spring into a swimming hole. The second crash followed another major habitat disturbance resulting from an unsuccessful attempt to eradicate goldfish in July 1967. Each crash (1962–1963 and 1967–1968) reduced the poolfish population to fewer than 50 adults and was followed by a population recovery to more than 1000. Following the first habitat disruption, changes in poolfish population structure and poolfish diet were observed. These changes caused an increased mortality rate, resulting in disappearance or decline in relative abundance of larger poolfish size classes with a commensurate reduction in production of mature eggs by the population. We detected no additional changes in life history characteristics that could be associated with the second population crash and recovery. We concluded that removal of vegetation in the summer of 1962 and the more extreme habitat disruption and fish handling in June–July 1967 were human-induced pulse disturbances resulting in poolfish population crashes. We also concluded that the changes in poolfish life history characteristics resulted principally from press disturbances attributable to goldfish. Los datos sobre la historia de vida del pez de poza Pahrump ( Empetrichthys latos latos ), recopilados entre 1937 y 1975, fueron organizados y analizados para ayudar a entender los cambios cusados por la perturbación antropogénica del hábitat y por la introducción del carpín dorado ( Carassius auratus ) a Manse Spring, Nevada. En dos ocasiones, los peces de poza Pahrump demostraron la habilidad de reponerse numéricamente después de descensos abruptos de la población. El primero fue en noviembre de 1961, después de la introducción de algunos carpines dorados y subsecuente remoción de vegetación por niños de ranchos locales con la intención de convertir Manse Spring en una poza para nadar. El segundo descenso ocurrió luego de otra perturbación de hábitat resultado de un intento fallido por erradicar el carpín dorado en julio de 1967. Cada descenso (1962–1963 y 1967–1968) redujo la población de peces de poza a menos de 50 adultos; y fue seguido por una recuperación de la población a más de 1000. Después de la primera perturbación del hábitat y descenso en la población de peces de poza, se observaron cambios en la dieta y la estructura de la población. Aparentemente, estos cambios ocasionaron un ascenso en la tasa de mortalidad, causando la desaparición o disminución de la abundancia relativa de peces de poza de clases de mayor tamaño, con una reducción proporcional en la producción de huevos maduros. No detectamos cambios adicionales en las características de historia de vida que pudieran estar asociados con el segundo descenso y recuperación de la población. Concluimos que la remoción de vegetación en el verano de 1962, y la aún mayor perturbación del hábitat y manejo de peces en junio/julio de 1967, fueron perturbaciones inducidas por el humano a modo de “pulso” que provocaron descensos de la población de peces de poza, y que los cambios en las características de historia de vida de los peces de poza resultaron principalmente de la presión por la alteración atribuida a los carpines dorados.     

Characterization of the human cysteinyl leukotriene CysLT1 receptor.

The cysteinyl leukotrienes-leukotriene C4(LTC4), leukotriene D4(LTD4) and leukotriene E4(LTE4)-are important mediators of human bronchial asthma. Pharmacological studies have determined that cysteinyl leukotrienes activate at least two receptors, designated CysLT1 and CysLT2. The CysLT1-selective antagonists, such as montelukast (Singulair), zafirlukast (Accolate) and pranlukast (Onon), are important in the treatment of asthma. Previous biochemical characterization of CysLT1 antagonists and the CysLT1 receptor has been in membrane preparations from tissues enriched for this receptor. Here we report the molecular and pharmacological characterization of the cloned human CysLT1 receptor. We describe the functional activation (calcium mobilization) of this receptor by LTD4 and LTC4, and competition for radiolabelled LTD4 binding to this receptor by the cysteinyl leukotrienes and three structurally distinct classes of CysLT1-receptor antagonists. We detected CysLT1-receptor messenger RNA in spleen, peripheral blood leukocytes and lung. In normal human lung, expression of the CysLT1-receptor mRNA was confined to smooth muscle cells and tissue macrophages. Finally, we mapped the human CysLT1-receptor gene to the X chromosome.     

Ontogenetic changes in relative levels of cyclic AMP-dependent and cyclic GMP-dependent protein kinases in prostates, epididymides and testes from guinea-pigs.

Changes in relative levels of cyclic AMP-dependent protein kinase (A-PK) and cyclic GMP-dependent protein kinase (G-PK) in prostates, epidymides and testes from guinea-pigs were examined at 3 different ages. During postnatal development, a decrease in the ratio of the 2 classes of protein kinases was seen in prostates, whereas increases of the ratios of the enzymes were found in epididymides and testes.     

Interleukin-2 signals during priming are required for secondary expansion of CD8+ memory T cells

Although interleukin-2 (IL-2) was initially characterized as the primary T-cell growth factor following in vitro activation, less is known about its role in shaping T-cell responses to acute infections in vivo. The use of IL-2- or IL-2-receptor-deficient mice is problematic owing to their early development of autoimmunity, attributable to the central role of IL-2 in the generation, maintenance and function of CD4+CD25+ regulatory T cells. To bypass these inherent difficulties, we have studied the effect of IL-2 on T-cell responses to acute infections by adopting a mixed chimaera strategy in which T cells lacking the high-affinity IL-2 receptor could be studied in an otherwise healthy mouse containing a full complement of regulatory T cells. Here we show that although IL-2 signalling to pathogen-specific CD8+ T cells affects the number of developing effector and memory cells very little, it is required for the generation of robust secondary responses. This is not due to an altered T-cell-receptor repertoire development or selection, and does not reflect an acute requirement for IL-2 during secondary activation and expansion. Rather, we demonstrate a previously unappreciated role for IL-2 during primary infection in programming the development of CD8+ memory T cells capable of full secondary expansion. These results have important implications for the development of vaccination or immunotherapeutic strategies aimed at boosting memory T-cell function.     

Winter forest soil respiration controlled by climate and microbial community composition

Most terrestrial carbon sequestration at mid-latitudes in the Northern Hemisphere occurs in seasonal, montane forest ecosystems. Winter respiratory carbon dioxide losses from these ecosystems are high, and over half of the carbon assimilated by photosynthesis in the summer can be lost the following winter. The amount of winter carbon dioxide loss is potentially susceptible to changes in the depth of the snowpack; a shallower snowpack has less insulation potential, causing colder soil temperatures and potentially lower soil respiration rates. Recent climate analyses have shown widespread declines in the winter snowpack of mountain ecosystems in the western USA and Europe that are coupled to positive temperature anomalies. Here we study the effect of changes in snow cover on soil carbon cycling within the context of natural climate variation. We use a six-year record of net ecosystem carbon dioxide exchange in a subalpine forest to show that years with a reduced winter snowpack are accompanied by significantly lower rates of soil respiration. Furthermore, we show that the cause of the high sensitivity of soil respiration rate to changes in snow depth is a unique soil microbial community that exhibits exponential growth and high rates of substrate utilization at the cold temperatures that exist beneath the snow. Our observations suggest that a warmer climate may change soil carbon sequestration rates in forest ecosystems owing to changes in the depth of the insulating snow cover.     

The arrangement of the three cone classes in the living human eye

Human colour vision depends on three classes of receptor, the short- (S), medium- (M), and long- (L) wavelength-sensitive cones. These cone classes are interleaved in a single mosaic so that, at each point in the retina, only a single class of cone samples the retinal image. As a consequence, observers with normal trichromatic colour vision are necessarily colour blind on a local spatial scale. The limits this places on vision depend on the relative numbers and arrangement of cones. Although the topography of human S cones is known, the human L- and M-cone submosaics have resisted analysis. Adaptive optics, a technique used to overcome blur in ground-based telescopes, can also overcome blur in the eye, allowing the sharpest images ever taken of the living retina. Here we combine adaptive optics and retinal densitometry to obtain what are, to our knowledge, the first images of the arrangement of S, M and L cones in the living human eye. The proportion of L to M cones is strikingly different in two male subjects, each of whom has normal colour vision. The mosaics of both subjects have large patches in which either M or L cones are missing. This arrangement reduces the eye's ability to recover colour variations of high spatial frequency in the environment but may improve the recovery of luminance variations of high spatial frequency.