A knowledge-based scoring function for protein-ligand interactions: Probing the reference state

Knowledge-based scoring functions have recently emerged as an alternative and very promising way of ranking protein-ligand complexes with known 3D structure according to their binding affinities. Theses implified potential-based approaches use the structural information stored in databases of protein-ligand complexes to derive atom pair interaction potentials also known as potentials of mean force (PMF). The derived PMF depend on the definition of a suitable reference state. The reference states vary among suggested knowledge-based scoring functions. Therefore, we attempt here to shed some light on the influence of different reference state definitions on the predictive power of a knowledge-based scoring function that has been introduced by us very recently [J. Med. Chem., 42 (1999) 791]. It is shown that a reference state that implicitly and more comprehensively accounts for protein and ligand solvation gives the most consistent scoring results for four test sets of diverse protein-ligand complexes taken from the Brookhaven Protein Data Bank. It is also shown that a reference sphere radius of at least 7–8 Å is needed to effectively capture solvation effects that are treated implicitly in the scoring function.     

适于人表皮组织蛋白质组分析的双向电泳技术

 【目的】 建立适于人表皮组织的双向电泳技术,并应用质谱技术对人表皮组织蛋白质组进行初步分析?【方法】 利用组织匀浆法制备人表皮组织总蛋白?固相pH 梯度胶条进行双向电泳?PDQuest 7.4软件比较和分析电泳图谱,利用质谱技术鉴定部分蛋白斑点?【结果】 成功建立了适用于人表皮组织蛋白质组分析的双向电泳技术,获得和比较了人表皮组织双向电泳四种染色图谱?人表皮组织的蛋白质在pH5～8范围内分布均匀,分子量集中在15～100 ku之间?银染图谱获得的蛋白斑点数为586±14;对质谱兼容的几种染色方法进行比较分析,结果表明Neuhoff 胶体考染更适合于人表皮组织蛋白质的双向电泳分析,其在上样量为350 μg时蛋白斑点数达394±9,匹配率为85.53%?利用基质辅助激光解析电离飞行时间质谱技术成功获得了Neuhoff 胶体考染的两个蛋白斑点的肽质量指纹图谱,并鉴定为Caspase 14 前体和27 ku热激蛋白1?【结论】建立的表皮组织双向电泳技术及其图谱可为皮肤蛋白质组学研究提供参考,为人皮肤蛋白质组学平台的构建奠定良好基础?     

Effect of cyclopropenoid fatty acids on the hepatic microsomal mixed-function-oxidase system and aflatoxin metabolism in rabbits

Male New Zealand weanling rabbits were fed a diet containing 0·25% cyclopropenoid fatty acids for 28 days. Compared with the controls, the rabbits given cyclopropenoid fatty acids showed retarded growth, some moderate liver histological damage, altered hepatic mixed-function-oxidase activities and minor variations in in vitro [¹⁴C]aflatoxin B₁ metabolism. In in vitro assays the major hepatic metabolite of aflatoxin B₁ (AFB₁) was aflatoxicol (AFL) and the major AFL metabolite was AFB₁. Minor amounts of aflatoxin M₁ and a metabolite believed to be AFL-M₁ were formed. The similarity of this AFB₁ metabolite pattern to that in rainbow trout, taken together with the apparent absence of AFB₁ detoxification products is consistent with the sensitivity of both species to the acute effects of AFB₁.     

Silicosis in slate pencil workers: I. An environmental and medical study

An environmental and medical survey was undertaken in the slate-pencil industry in the central part of India. The industrial hygiene survey revealed that concentrations of free silica dust were very high. The medical survey, involving 593 workers, revealed that the prevalence of silicosis in this industry was 54.6%. Of these, 17.7% of workers had conglomerate silicosis (progressive massive fibrosis, PMF). The radiologic appearance of simple and conglomerate silicosis resembled closely the simple pneumoconiosis and progressive massive fibrosis (PMF) among other occupational groups exposed to free silica and also found in coal workers. The pulmonary lesions were detectable after a relatively short duration of exposure. The short latent period of development and the high prevalence of silicosis observed among these workers are related to exposure to high concentrations of siliceous dust in the work environment.     

四环素牙比色条的制作及其临床应用

目的：制作和应用四环素牙比色条比色修复四环素牙列患者的部分缺失牙，再现天然四环素牙色彩。方法：根据四环素牙颜色程度的不同，用Vita瓷粉制作四环素牙比色条，用以在四环素牙患者缺失牙修复临床中比色。结果：用四环素牙比色四环素牙患者选色，制作163个单位烤瓷冠桥，患者感到颜色满意。结论：四环素牙比色条方便了医技之间的沟通，更加准确地表达四环素牙颜色的信息，从而取得烤瓷冠桥色彩再现的效果。     

Clinical significance of microcytosis in patients with primary myelofibrosis

Microcytosis is a relatively frequent finding in primary myelofibrosis (PMF); however its prognostic significance is unknown. We identified factors associated with microcytosis in PMF and measured its impact on outcomes. Among 725 patients with PMF, 140 (19%) showed microcytosis. In multivariate analysis, factors associated with microcytosis were absence of prior therapy, low iron, low transferrin saturation (satTF), and splenomegaly. Among 375 untreated patients, low satTF and splenomegaly were associated with microcytosis. Overall, microcytosis was associated with a higher risk of transformation to leukemia (p = 0.03), but not shorter leukemia-free survival. Microcytosis in PMF may be related to dysregulation of iron homeostasis.     

3023 Mayo Clinic Patients With Myeloproliferative Neoplasms: Risk-Stratified Comparison of Survival and Outcomes Data Among Disease Subgroups

Objective

To document the Mayo Clinic decades-long experience with myeloproliferative neoplasms (MPNs) and provide mature risk-stratified survival data and disease complication estimates.

Orange juice decreases low-density lipoprotein cholesterol in hypercholesterolemic subjects and improves lipid transfer to high-density lipoprotein in normal and hypercholesterolemic subjects

Orange juice (OJ) is regularly consumed worldwide, but its effects on plasma lipids have rarely been explored. This study hypothesized that consumption of OJ concentrate would improve lipid levels and lipid metabolism, which are important in high-density lipoprotein (HDL) function in normolipidemic (NC) and hypercholesterolemic (HCH) subjects. Fourteen HCH and 31 NC adults consumed 750 mL/day OJ concentrate (1:6 OJ/water) for 60 days. Eight control subjects did not consume OJ for 60 days. Plasma was collected before and on the last day for biochemical analysis and an in vitro assay of transfers of radioactively labeled free-cholesterol, cholesteryl esters, phospholipids, and triglycerides from lipoprotein-like nanoemulsions to HDL. Orange juice consumption decreased low-density lipoprotein cholesterol (160 ± 17 to 141 ± 26 mg/dL, P < .01) in the HCH group but not in the NC group. HDL-cholesterol and triglycerides remained unchanged in both groups. Free-cholesterol transfer to HDL increased (HCH: 4.4 ± 2 to 5.6 ± 1%, NC: 3.2 ± 2 to 6.2 ± 1%, P< .05) whereas triglyceride (HCH 4.9 ± 1 to 3.1 ± 1%, NC 4.4 ± 1 to 3.4 ± 1%, P< .05) and phospholipid (HCH 21.6 ± 2 to 18.6 ± 3%, NC 20.2 ± 2 to 18.4 ± 2%, P < .05) transfers decreased in both groups. Cholesteryl-ester transfer decreased only in HCH (3.6 ± 1 to 3.1 ± 1%, P < .05), but not in NC. In control subjects, plasma lipids and transfers were unaltered for 60 days. Thus, by decreasing atherogenic low-density lipoprotein cholesterol in HCH and increasing HDL ability to take up free cholesterol in HCH and NC, OJ may be beneficial to both groups as free-cholesterol transfer to HDL is crucial for cholesterol esterification and reverse cholesterol transport.