基于酵母水平的高通量药物筛选

随着后基因组时代的到来,越来越多的药物靶标蛋白将会被发现,基于靶标蛋白设计出的化合物也将大量涌现,高通量药物筛选日趋重要。酵母基因组的易操作性及其简单稳定的培养条件,使得该真核微生物成为一种理想的药物筛选工程细胞。本文讨论了选择酵母系统进行细胞水平筛选的优缺点,并从基于靶点和表型两种筛选模式对酵母水平的高通量药物筛选做一总结。     

The Influences of Environment, Mating Habitat, and Predation on Evolution of Pinniped Lactation Strategies

Seals have adapted their social systems and lactation strategies to marine environments that include open and ice-covered oceans, high and low productivity, extremes in seasonality, and ocean- and terrestrial-type predators. Different explanations for the variation in pinniped lactation systems have been proposed but tests of alternative hypotheses have not sufficiently accounted for phylogeny and body size. After controlling for this variation, I predicted that environment, mating habitat, and predation would yield a fuller explanation. Lactation traits, duration, pup growth rate, and fat content were significantly influenced by both body size and phylogeny, which together explained 20–69% of the variation. After controlling for this variation, initial results did not support the environment hypothesis, as no differences in lactation traits were found between species living in polar (≥60°N) versus equatorial (<60°N) environments. In contrast, seals that nurse in areas of Arctic sea ice contending with ice-hunting predators, such as polar bears, had relatively short lactation compared to species living in the Antarctic and more equatorial regions. Also, the availability of predator-free islands for terrestrial mating and parturition was related to a harem mating system, increased sexual size dimorphism (SSD), and slow juvenile growth rates, less fat in milk, and longer lactation. Using structural equation modeling, latitude and size of harems provided independent explanations for all three lactation traits. Thus, use of islands in ice-free waters, predation in Arctic ice-covered waters, and more milk fat in high-latitude seals together provided adequate explanations for the evolution of lactation diversity among pinnipeds.     

Thermal biology of African lovebirds and Australian grass parakeets

We compared aspects of the thermal biology of two groups of small parrots, of similar body mass, each derived from a range of habitat types, varying in aridity, but indigenous to either southern Africa or Australia. By accounting for phylogenetic differences, we were able to question whether arid zone species have lower metabolic rates and greater thermal tolerances than mesic species in relation to the “pre-adapted” and “post-arrival adaptation” hypotheses. Four species of African lovebird (Agapornis) and four species of Australian grass parakeet (one Neopsephotus and three Neophema species) were investigated. The Rosy-faced Lovebird (Agapornis roseicollis), Bourke's Parakeet (Neopsephotus bourkii) and the Scarlet-chested Parakeet (Neophema splendida) were categorised as arid zone species, Fischer's Lovebird (Agapornis fischeri), the Black-masked Lovebird (Agapornis personatus) and the Elegant Parakeet (Neophema elegans) as semi-arid zone species, and the Black-cheeked Lovebird (Agapornis nigrigenis) and the Turquoise Parakeet (Neophema pulchella) as mesic zone species. Conventional and phylogenetically independent statistical methods yielded no significant differences in the basal metabolic rates of birds from different habitats or between the species assemblages from Africa and Australia.     

A modified Coomassie Brilliant Blue staining method at nanogram sensitivity compatible with proteomic analysis

A more sensitive and convenient Coomassie Brilliant Blue (CBB) staining method for visualizing proteins was developed. Compared with the modifications include the supplement of 10% (v/v) methanol into the fixing solution, an increase of an additional sensitization step and CBB raised from 0.1 to 0.125%. The improved method can detect proteins at nanogram level. The improved method is more sensitive than Blue Silver and more convenient than the Silver protocol. Mass spectrometry results confirmed that it is suitable for subsequent proteomic research.     

低心血管疾病风险选择性环氧合酶-2抑制剂的虚拟筛选

摘要 目的：寻找具有血栓素A2受体（Thromboxane A2 receptor,TP）抑制作用的选择性环氧合酶-2（Cyclooxygenase-2,COX-2）抑制剂,以期降低其心血管疾病风险。方法：本研究从公开数据库中获取了512种TP抑制剂,通过分子对接、分子动力学模拟和ADMET预测,筛选出化合物TP84。结果：分子对接结果显示,与先前获批的选择性COX-2抑制剂罗非昔布相比,TP84对COX-2的亲和力更高,对环氧合酶-1（Cyclooxygenase-1,COX-1）的亲和力更低;分子动力学模拟进一步表明,模拟过程中TP84与COX-1的结合不稳定,而TP84能稳定结合COX-2,与COX-2的结合自由能是COX-1的3倍;此外,根据ADMET预测,TP84的药物化学、吸收、分布、代谢、排泄和毒性处于类药物候选物的可接受范围内。结论：TP84是一种潜在的低心血管疾病风险选择性COX-2抑制剂。     

Assessment of blue-stain resistance according to the EN 152 and a reverse test method using visual and computer-aided techniques

A computer technique for assessing blue-stained coated wood has been implemented for evaluating the discoloration of coatings and analysing the interior wood staining of samples subjected to testing according to European Standard EN 152. The comparison of visual assessment and computer-evaluated percentages of blue staining is based on a combination of correlation measures, principal components and cluster analysis. It appears difficult to imitate human evaluation with image processing, since computer ratings represent exact percentages, while subjective evaluations do not. Additionally, more specific techniques for exploring fungal growth in coated wood have been described. As EN 152 was specifically developed for testing efficacy of wood preservatives, a modified test methodology was elaborated for testing the efficacy of wood coatings, called here as the EN 152-reverse method. Furthermore three-dimensional (3D) reconstruction is validated as a tool for in-depth analysis of blue-stain disfigurement. This 3D visualisation indicates important differences in fungal infestation and proves its suitability for blue-stain resistance testing.     

Rapid pre-screening of cervical smears as a method of internal quality control in a cervical screening programme

Objective:  To evaluate the performance of rapid pre-screening (RPS) as a method of internal quality control in the cytopathological examination of cervical smears for cervical cancer screening.
Methods:  The sample consisted of 6135 cervical smears submitted to RPS and routine screening (RS) methods. The smears classified as negative in RPS and RS were considered final diagnoses, and were not, therefore, submitted to any additional review. The smears identified as suspect or unsatisfactory according to RPS were analysed separately by two different cytologists irrespective of the diagnosis reached in RS. Smears considered abnormal or unsatisfactory at RS were also reviewed. When both cytologists issued concordant diagnoses, this was considered the final diagnosis. Discordant results were analysed by a third cytologist and a consensus meeting was held to define the final diagnosis.
Results:  Taking abnormalities detected by RS as the denominator, RPS had a sensitivity of 63.0% for the detection of all abnormal smears and 96.7% for high grade squamous intraepithelial lesion (HSIL). When compared with the final diagnosis, sensitivity of RPS for all abnormal smears was 74.9% and for HSIL 95.0%. Of the 529 abnormal smears confirmed in the final diagnosis, 2.15% were detected only by the RPS.
Conclusion:  RPS is an effective alternative method of internal quality control with high sensitivity for the detection of more severe lesions. It also permits monitoring of the laboratory rate of false-negative results, and allows constant evaluation of the performance both of the pre-screening and RS cytologists.     

Design and effectiveness of a novel trap for capturing nesting songbirds

ABSTRACT Capturing songbirds at their nests can be challenging and time consuming. Although traps designed for capturing songbirds at their nests have been described in the literature, few are effective for capturing species with open‐cup nests. We describe a cylindrical trap designed to capture songbirds at nests up to 2 m above ground in grasses, forbs, shrubs, and small saplings. The nest trap is constructed using a rigid hoop, two pieces of mist net, three stakes, and twist ties. We used this trap to capture female Dickcissels (Spiza americana) and female Indigo Buntings (Passerina cyanea) at their nests, with success rates of 85% (N= 196) and 60–73% (N= 16), respectively. Trapping success was comparable to that using other passerine nest trap designs. Nest abandonment after trapping attempts was rare and similar to that reported in previous studies. Our nest trap is lightweight, easy to make, versatile enough to use in a variety of grassland and shrub habitats, and easily carried and deployed in the field.