Clinical Utility of Insulin-Like Growth Factor 1 and 2; Determination by High Resolution Mass Spectrometry

Measurement of insulin-like growth factor-1 (IGF-I) has utility for the diagnosis and management of growth disorders, but inter-assay comparison of results has been complicated by a multitude of reference standards, antibodies, detection methods, and pre-analytical preparation strategies. We developed a quantitative LC-MS method for intact IGF-I, which has advantages in throughput and complexity when compared to mass spectrometric approaches that rely on stable isotope dilution analysis of tryptic peptides. Since the method makes use of full-scan data, the assay was easily extended to provide quantitative measurement of IGF-II using the same assay protocol. The validated LC-MS assay for IGF-I and IGF-II provides accurate results across the pediatric and adult reference range and is suitable for clinical use.     

Meiofaunal responses to nutrient additions in a Mediterranean stream

1. The effects of a moderate addition of nutrients (twofold N and threefold P) were examined during a 2‐year period to determine the response to nutrient addition in a meiofaunal community inhabiting sandy patches in a Mediterranean stream. 2. The pattern of meiofaunal assemblages exhibits a high degree of intra‐ and interannual variability. This pattern alternates between periods of hydrological stability and disturbances, such as floods and droughts, which is a characteristic of Mediterranean systems. 3. A before–after–control–impact (BACI) design was used to determine the outcome of the addition by comparing an upstream non‐enriched reach with an enriched downstream reach. Analysis of the study data by means of a nonparametric permutational procedure (permanova ) showed that fertilisation had a significant effect. Density and biomass values increased in the most abundant meiofaunal groups, including microcrustaceans, oligochaetes and chironomids. Microcrustaceans were the dominant group in the permanent meiofauna. 4. We also examined differences in microcrustacean secondary production in both reaches. Ostracods and cyclopoid copepods increased their secondary production in the impacted reach as a result of the nutrient addition. 5. Our study demonstrated that moderate nutrient enrichment can affect the biomass and production of stream meiofauna, but it is still unclear whether this effect was because of autotrophic or heterotrophic pathways.     

The Ordovician-Silurian boundary stratotype: consequences of its approval by the IUGS

Lespérance, Pierre J., Barnes, Christopher R., Berry, William B. N., Boucot, Arthur J. & Mu En-zhi 1987 07 15: The Ordovician-Silurian boundary stratotype: consequences of its approval by the IUGS.
The Ordovician-Silurian stratotype at Dob's Linn, Scotland is the second systemic boundary approved by the International Union of Geological Sciences (IUGS). A review of the internationally accepted criteria required of a stratotype shows that few of these are possessed by the Dob's Linn section. The strongest attribute of the section is the presence of zonal graptolites, although the boundary is recognized primarily on a single biological event (base of acuminatus Zone) for which the evolutionary relationships of the taxa are not established. In approving this boundary proposal in 1985, which received only simple majority support within the Ordovician-Silurian Boundary Working Group (OSBWG) and which fails to meet most of the accepted prerequisites for a stratotype, the International Commission on Stratigraphy (ICS) and the IUGS have established an unfortunate precedent. It follows that future systemic boundaries need not meet the accepted standards. It raises serious questions on the assessment and voting procedures of the International Commission on Stratigraphy and on the credence accorded the recommendations developed by the International Subcommission on Stratigraphic Classification of IUGS.     

Functional contribution of cysteine residues to the human immunodeficiency virus type 1 envelope.

Although the envelope gene of human immunodeficiency virus type 1 shows considerable strain variability, cysteine residues of the envelope protein are strongly conserved, suggesting that they are important to the envelope structure. We constructed and analyzed mutants of a biologically active molecular clone of human immunodeficiency virus type 1 in which different cysteines were replaced by other amino acids in order to determine their functional importance. Substitution of cysteines 296 and 331, on either side of a region recognized by type-specific neutralizing antibodies, or on either side (residues 418 and 445) of a region important for CD4 binding, resulted in noninfectious mutants. These mutants were blocked early in the viral life cycle. Their gp160 envelope precursor polypeptides were poorly cleaved, and CD4 binding was also strongly impaired. Similar substitutions in the first variable region (residue 131) or between the first and second variable regions (residue 196) also gave noninfectious mutant virus, but here the block was late in the virus life cycle; these mutants were defective for syncytium formation. Substitution of cys386, between the neutralization and CD4 binding regions, resulted in a virus which retained infectivity but which spread much more slowly than the wild type. As with the cys131 and cys196 mutants, the cys386 mutant appeared to be defective in syncytium formation. These results show that all seven of the tested cysteines are vital for envelope function and suggest that this is likely true for all envelope cysteines. The results further show that regions important for CD4 binding, proteolytic cleavage recognition, and syncytium formation are all multiple and distributed over a relatively large part of the gp120 and therefore are likely dependent on protein tertiary structure.     

Dosimetric mapping in BIORACK on IML2

Seven detector packages consisting of plastic nuclear track detectors, nuclear emulsions and thermoluminescence dosimeters were exposed in different locations inside BIORACK during the IML2 mission. The detectors supplement each other in their registration characteristics and cover well the different contributions of the space radiations to the dose. In this report, results are given on total dose measurements, cosmic ray flux and neutron dose. Total doses differ by up to a factor of 1.5 and heavy ion fluxes by more than a factor of 6 in the different locations. The results are compared with those of previous missions. The mission equivalent dose for the astronauts was calculated from the measurements to be 3.8 mSv.     

Coordinated mRNA and Protein Expression of Human LAMP-1 in Induction of Melanogenesis After UV-B Exposure and Co-Transfection of Human Tyrosinase and TRP-1 cDNAs

In order to better understand the cascade of melanogenic events in melanocytes, this report has introduced our two recent approaches for the expression of melanogenesis/or melanosome-associated genes and encoded proteins in melanocytes (melanoma cells) after repeated exposure to UV -B and after cotransfection of two human genes, i.e., tyrosinase and tyrosinase-related protein-1 (TRP-1). Repeated exposure of UV B (2.5–5.0 mJ/cm²) caused not only upregulation of tyrosinase and TRP-1 genes but also coordinated increase in the gene and protein synthesis expression of Lamp-1 (lysosome-associated membrane protein-1). When COS-7 kidney cells and amelanotic melanoma (C32 and SKMEL-24) and melanotic melanoma (G361 and SK-MEL-23) cells were exposed to cotransfection of human tyrosinase and TRP-1 cDNAs, there was also an increased expression of Lamp-1 mRNA and protein along with tyrosinase activation and new melanin synthesis. Importantly, single transfectants of human tyrosinase cDNA revealed marked cellular degeneration, whereas this degeneration was not seen in single transfectants of TRP-1 cDNA or cotransfectants of human tyrosinase and TRP-1 cDNAs, indicating that TRP-1 prevented, along with Lamp-1, programmed death of melanocytes after transfection of tyrosinase gene. The coordinated expression of TRP-1 and Lamp-1 was further confirmed by antisense oligodeoxynucleotide hybridization experiment against Lamp-1 gene, showing the decreased expression of TRP-1 as identified by three different types of anti-TRP-1 monoclonal antibodies. We propose therefore that human tyrosinase and TRP-l, when activated or expressed together, will coordinate to upregulate the mRNA expression and protein synthesis of Lamp-1. The Lamp-1 molecules will, in turn, cover the inner surface of melanosomal membrane, together with TRP-1 molecules, thus protecting the melanosomal membrane from toxic melanin intermediates generated during melanogenesis in the presence of active tyrosinase. In contrast, the expression of other lysosome-related proteins, e.g., β-galactosidase and CD63 is not stimulated in new melanogenesis.     

西藏色季拉山暗针叶林苔藓多样性及林窗干扰的影响

为了解西藏色季拉山暗针叶林苔藓多样性及林窗干扰的影响,在过去工作积累的基础上研究了色季拉山西坡5块样地内不同林内环境(林窗、林缘和林下)地面、腐木和树附生苔藓生物量特征。结果表明, 地面生单位面积苔藓植物生物量储量最高,平均910.10 g/m²,其次为腐木生(221.90 g/m²),树附生的最低(53.59 g/m²)。林窗地面生苔藓单位面积生物量最高,均值为360.47 g/m²,其次为林下(305.51 g/m²),最小为林缘(244.11 g/m²);林窗、林缘和林下间的地面生苔藓单位面积生物量差异显著(P＜0.05)。沿海拔梯度,林窗苔藓单位面积生物量表现出先增加后减少的趋势。因此,在西藏色季拉山暗针叶林内,林窗对地面生苔藓单位面积生物量有显著影响。     

Role of the extracellular domain of human herpesvirus 7 glycoprotein B in virus binding to cell surface heparan sulfate proteoglycans.

In an attempt to identify the human herpesvirus 7 (HHV-7) envelope protein(s) involved in cell surface binding, the extracellular domain of the HHV-7 glycoprotein B (gB) homolog protein was cloned and expressed as a fusion product with the Fc domain of human immunoglobulin G heavy chain gamma1 (gB-Fc) in an eukaryotic cell system. Indirect immunofluorescence followed by flow cytometric analysis revealed specific binding of gB-Fc to the membrane of SupT1 cells but not to other CD4+ T-lymphoblastoid cell lines, such as Jurkat or PM1, clearly indicating that gB-Fc did not bind to the CD4 molecule. This was also suggested by the ability of gB-Fc to bind to CD4-negative fibroblastoid Chinese hamster ovary (CHO) cells. The binding was abrogated by enzymatic removal of cell surface heparan sulfate proteoglycans by heparinase and heparitinase but not by treatment with condroitinase ABC. In addition, binding of the gB-Fc fusion protein to CHO cells was severely impaired in the presence of soluble heparin, as well as when heparan sulfate-deficient mutant CHO cells were used. Consistent with these findings, soluble heparin was found to block HHV-7 infection and syncytium formation in the SupT1 cell line. Although the CD4 antigen is a critical component of the receptor for the T-lymphotropic HHV-7, these findings suggest that heparin-like molecules also play an important role in HHV-7-cell surface interactions required for infection and that gB represents one of the HHV-7 envelope proteins involved in the adsorption of virus-to-cell surface proteoglycans.     

高含量、低用量颗粒剂防治玉米螟的研究

1973—1977年,作者研究了防治玉米螟颗粒剂的“高含量、低用量”问题,即在单位面积上有效成分用量相等下,探讨逐步提高颗粒剂中有效成分含量而又按比例减少单位面积上颗粒剂用量的防治效果的相关性。结果证明,在相当大的范围内,高含量、低用量可以代替低含量、高用量。每亩用辛硫磷4克时,1.6%颗炷剂每亩用0.5斤与0.1%颗粒剂每亩用8斤均可获80%左右相似的防治效果;每亩用对硫磷40克时,8%颗粒剂每亩用1斤与1%颗粒剂每亩用8斤均可获90%以上防治效果。对地亚农和二氯苯醚菊酯试验亦获类似结果。 颗粒剂应用这一改革,有利于成品化和机械施药,并可显著降低防治成本。 同时,还做了室内毒力测定及在玉米上残效作用测定,以验证田间防治效果。 近二十年来,国内、外一直把颗粒剂做为防治玉米心叶期玉米螟(`Ostrinia nubilalis`` Hübner)的有效手段。我国自五十年代末已开始研究和应用滴滴涕、六六六等颗粒剂防治玉米螟,获得了高于六六六药液灌心的防治效果(邱式邦等,1961;邱式邦等,1963;慕立义,1963)。但由于颗粒剂用量大、费用高而未能成批生产。土法生产、群制群用的颗粒剂亦存在着缺点:(1)加工时不但造粒、选粒用工多,而且粒度、有效成分的含量及在载体上的分布均难以规格化,药效不够稳定;(2)加工所用的毒剂均为农药制剂。如用乳油、除乳化剂及有机溶剂被浪费外,往往还引起玉米的药害;如用粉剂,则不能渗入载体内部,不耐雨水冲洗而降低残效;(3)由于颗粒剂不规格化和单位面积用量大而不利于机械施药。因此,多年来生产上迫切需要高效、低毒、低残毒、价廉和利于机械施药的成品颗粒剂以代替土法生产的颗粒剂。