IPS-1 Is Essential for the Control of West Nile Virus Infection and Immunity

The innate immune response is essential for controlling West Nile virus (WNV) infection but how this response is propagated and regulates adaptive immunity in vivo are not defined. Herein, we show that IPS-1, the central adaptor protein to RIG-I-like receptor (RLR) signaling, is essential for triggering of innate immunity and for effective development and regulation of adaptive immunity against pathogenic WNV. IPS-1^−/− mice exhibited increased susceptibility to WNV infection marked by enhanced viral replication and dissemination with early viral entry into the CNS. Infection of cultured bone-marrow (BM) derived dendritic cells (DCs), macrophages (Macs), and primary cortical neurons showed that the IPS-1-dependent RLR signaling was essential for triggering IFN defenses and controlling virus replication in these key target cells of infection. Intriguingly, infected IPS-1^−/− mice displayed uncontrolled inflammation that included elevated systemic type I IFN, proinflammatory cytokine and chemokine responses, increased numbers of inflammatory DCs, enhanced humoral responses marked by complete loss of virus neutralization activity, and increased numbers of virus-specific CD8+ T cells and non-specific immune cell proliferation in the periphery and in the CNS. This uncontrolled inflammatory response was associated with a lack of regulatory T cell expansion that normally occurs during acute WNV infection. Thus, the enhanced inflammatory response in the absence of IPS-1 was coupled with a failure to protect against WNV infection. Our data define an innate/adaptive immune interface mediated through IPS-1-dependent RLR signaling that regulates the quantity, quality, and balance of the immune response to WNV infection.     

Phenotypic selection in natural populations: what limits directional selection?

Studies of phenotypic selection document directional selection in many natural populations. What factors reduce total directional selection and the cumulative evolutionary responses to selection? We combine two data sets for phenotypic selection, representing more than 4,600 distinct estimates of selection from 143 studies, to evaluate the potential roles of fitness trade-offs, indirect (correlated) selection, temporally varying selection, and stabilizing selection for reducing net directional selection and cumulative responses to selection. We detected little evidence that trade-offs among different fitness components reduced total directional selection in most study systems. Comparisons of selection gradients and selection differentials suggest that correlated selection frequently reduced total selection on size but not on other types of traits. The direction of selection on a trait often changes over time in many temporally replicated studies, but these fluctuations have limited impact in reducing cumulative directional selection in most study systems. Analyses of quadratic selection gradients indicated stabilizing selection on body size in at least some studies but provided little evidence that stabilizing selection is more common than disruptive selection for most traits or study systems. Our analyses provide little evidence that fitness trade-offs, correlated selection, or stabilizing selection strongly constrains the directional selection reported for most quantitative traits.     

Enhancement of Hypophysectomy-Induced Dopamine Receptor Hypersensitivity in Male Rats by Chronic Haloperidol Administration

It has been reported that hypophysectomy (HYPOX) would antagonize the development of a neuroleptic-induced dopamine receptor hypersensitivity, and suggested that the neuroleptic-induced dopamine receptor hypersensitivity may be mediated by the neuroleptic-induced hyperprolactinemia. Conversely, we and others have reported on the ability of HYPOX animals to develop a neuroleptic-induced dopamine receptor hypersensitivity. The present study was undertaken to define the possible role(s) of prolactin in the modulation of striatal dopamine receptor sensitivity. The data from these studies indicate: that HYPOX alone will result in the development of a striatal dopamine receptor hypersensitivity; that the HYPOX-induced dopamine receptor hypersensitivity could be increased by the chronic administration and withdrawal of haloperidol; that administration of prolactin to HYPOX rats would partially antagonize the development of the neuroleptic-induced dopamine receptor hypersensitivity; and that the administration of prolactin alone had minimal effects on the apomorphine-induced behavior or neurochemistry of the HYPOX animals. These results suggest that the neuroleptics do not require the presence of a pituitary secretion (specifically, prolactin) to induce a striatal dopamine receptor hypersensitivity; however, they do indicate that a pituitary secretion, perhaps prolactin, may have the ability to modulate striatal dopamine sensitivity.     

天童常绿阔叶树种栲树生殖个体大小及其生殖构件特征

对浙江天童木荷-栲树林内的常绿阔叶树种栲树(Castanopsis fargesii Franch.)的生殖个体大小、生殖构件的分布及其动态变化特征进行了研究。结果表明, 该地区栲树生殖个体的胸径在17~50 cm 间, 平均胸径为31. 2±8.0 cm, 平均年龄约36.3±6.6 年;林缘附近的生殖个体小于木荷-林内。相对稳定的群落和比较丰富的土壤养分条件有利于生殖枝数量和花序数量的增多。栲树生殖个体的数量在两年中变化较大, 部分栲树个体可以在连续年份中生殖。从枝系水平分析:在持续生殖的栲树个体上, 生殖枝数量有明显变化, 并非所有的生殖枝在两年中都可开花或结果, 保持连续生殖的枝系约占48.2%。栲树果序枝数量在连续年份有明显差异(p < 0.01), 而且果序枝上的幼蕾数、果实数量及结实率等都有明显差异(p < 0.05)。     

Estimated Ultraviolet Radiation Doses in Wetlands in Six National Parks

Ultraviolet-B radiation (UV-B, 280–320-nm wavelengths) doses were estimated for 1024 wetlands in six national parks: Acadia (Acadia), Glacier (Glacier), Great Smoky Mountains (Smoky), Olympic (Olympic), Rocky Mountain (Rocky), and Sequoia/Kings Canyon (Sequoia). Estimates were made using ground-based UV-B data (Brewer spectrophotometers), solar radiation models, GIS tools, field characterization of vegetative features, and quantification of DOC concentration and spectral absorbance. UV-B dose estimates were made for the summer solstice, at a depth of 1 cm in each wetland. The mean dose across all wetlands and parks was 19.3 W-h m⁻² (range of 3.4–32.1 W-h m⁻²). The mean dose was lowest in Acadia (13.7 W-h m⁻²) and highest in Rocky (24.4 W-h m⁻²). Doses were significantly different among all parks. These wetland doses correspond to UV-B flux of 125.0 μW cm⁻² (range 21.4–194.7 μW cm⁻²) based on a day length, averaged among all parks, of 15.5 h. Dissolved organic carbon (DOC), a key determinant of water-column UV-B flux, ranged from 0.6 (analytical detection limit) to 36.7 mg C L⁻¹ over all wetlands and parks, and reduced potential maximal UV-B doses at 1-cm depth by 1%–87 %. DOC concentration, as well as its effect on dose, was lowest in Sequoia and highest in Acadia (DOC was equivalent in Acadia, Glacier, and Rocky). Landscape reduction of potential maximal UV-B doses ranged from zero to 77% and was lowest in Sequoia. These regional differences in UV-B wetland dose illustrate the importance of considering all aspects of exposure in evaluating the potential impact of UV-B on aquatic organisms.     

功能矫形前伸青春期大鼠下颌后翼外肌MyoD、myogenin的表达

目的：探讨＂应力-生长（改建）＂在细胞水平上的体现,为功能矫形治疗和矫治效果的保持提供新思路和实验依据。方法：本实验选用20只4周龄,雄性SD大鼠随机分为8组。其中实验组大鼠经戊巴比妥麻醉后佩戴上颌斜面导板,对照组未佩用。依据时间不同又分为四组：1d,7d,14d,21d。采用RT-PCR技术分析各组大鼠翼外肌组织中肌分化相关基因MyoD、myogenin mRNA的表达变化。结果：未施加功能矫形力的大鼠翼外肌组织MyoD表达伴随其生长发育呈现递减趋势,实验组在第7 d出现表达上调。同时,力学刺激后实验组动物myogenin的表达与对照组相比较在14 d组出现明显上调。结论：功能矫形力作用于翼外肌组织可以诱导MyoD和myogenin的表达上调进而诱导成肌细胞的分化。     

Isolation and characterization of a Mr = 110,000 glycoprotein localized to the hepatocyte bile canaliculus

A Mr = 110,000 glycoprotein, GP 110, was partially purified using wheat germ agglutinin-Sepharose affinity chromatography from a bile canalicular-enriched membrane fraction denoted N2u of rat liver. This fraction was subjected to preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis and the Mr = 110,000 polypeptide was excised and used as an immunogen in rabbits. The antisera were found to specifically recognize a Mr = 110,000 polypeptide, named GP 110, in the N2u membrane fraction. In isolated hepatocytes, GP 110 was readily accessible to cell surface iodination catalyzed by lactoperoxidase at 4 degrees C and was judged by immunoprecipitation studies to contain about 2% of total radioactivity incorporated into externally oriented proteins of the cell. Immunoprecipitated GP 110 was shown by two-dimensional polyacrylamide gel electrophoresis to migrate with an approximate pI of 4.9. Indirect immunofluorescence on frozen liver sections demonstrated that GP 110 was primarily localized in the bile canaliculus. In corroborative studies employing subcellular fractionation, it was found that GP 110 was enriched nearly 19-fold in P2, a plasma membrane fraction primarily derived from the sinusoidal domain, and 44-fold in N2u. In contrast, only low levels of GP 110 were present in endoplasmic reticulum, mitochondrial, cytosolic, and nuclear-enriched fractions of liver. The physiological function of GP 110 is as yet unknown; antisera to it did not immunoprecipitate other known bile canalicular proteins of similar molecular weights. GP 110 was found to be extensively glycosylated relative to other known membrane proteins; approximately 33% of the apparent molecular weight appear to be carbohydrate. In agreement, limited removal of N-linked carbohydrate chains indicated that there are approximately eight chains/GP 110 polypeptide. Neuraminidase treatment of GP 110 resulted in a desialylated Mr = 85,000 polypeptide suggesting that the majority of carbohydrate chains on GP 110 are of the complex type.     

120 例初治、年轻、中高/ 高危弥漫大B细胞淋巴瘤的临床分析

目的:探讨初治、年轻、中高/高危弥漫大B细胞淋巴瘤(diffuse large B cell lymphoma,DLBCL)的临床特征、治疗措施及预后影响因素。方法:回顾性分析2006年1月至2014年5月军事医学科学院附属医院淋巴瘤科收治的年龄≤60岁、年龄调整的国际预后指数(aa IPI)评分≥2分的初治DLBCL病例,进行疗效及预后相关因素的分析。结果:共收集到资料完整的DLBCL病例120例,中位随访28(4-106)个月,3年PFS率53.25%,OS率61.52%。单因素分析结果显示B症状、治疗方案及近期疗效、自体移植对无进展生存(PFS)及总体生存(OS)率的影响有统计学意义。多因素分析结果显示治疗方案、自体造血干细胞移植是影响PFS、OS率的独立影响因素。结论:年轻、中高/高危DLBCL具有高度异质性,病理细胞来源、Ki-67等在本组病例中未见显著预后意义,有待临床进一步探索。