P3 cap modified Phe*-Ala series BACE inhibitors

With the aim of reducing molecular weight and adjusting log D value of BACE inhibitors to more favorable range for BBB penetration and better bioavailability, we synthesized and evaluated several series of P3 cap modified BACE inhibitors obtained via replacement of the P3NHBoc moiety as seen in 3 with other polar functional groups such as amino, hydroxyl and fluorine. Several promising inhibitors emerging from this P3 cap SAR study (e.g., 15 and 19) demonstrated good enzyme inhibitory potencies (BACE-1 IC(50) <50 nM) and whole cell activities (IC(50) approximately 1 microM).     

尿酸酶－鲁米诺化学发光传感器

研制了依赖于鲁米诺化学发光反应和固定化尿酸酶柱的测定血清尿酸的生物传感器。其测定血清样品响应时间47s。测定每份样品需时1．5min,样品体积17μl。工作曲线的线性范围1~20mg／dl。批内不精密度3．22％～4.36％,批间6.18%～7．8%。测定值回收率为93％～109％。与医院常规酶试剂盘方法比较相关系数r=0.9909。固定化尿酸酶柱室温使用,4℃冰箱保存,连续使用5个半月测定样品2000次以上,仍保持原酶柱活力的94%。     

金门岛北部海域浮游植物的季节变动及与环境的关联

采用2013—2014年四季度月在金门岛北部海域获取的浮游植物及环境因子监测数据, 分析该区浮游植物的群落结构和季节变化及其与温度、盐度、悬浮物、营养盐、叶绿素等的关系, 初步探讨涉海工程建设对浮游植物群落的潜在影响。结果显示, 鉴定出的浮游植物隶属3门43属82种(不含未定种), 群落构成以硅藻为主, 其次是甲藻, 蓝藻仅1种。物种组成的季节差异较大, 3月物种贫乏, 1月次之, 7月和11月最丰富。四季丰度平均为47.09×103 cells/L, 1月丰度最高, 7月次之, 11月最低, 3月高于11月少许。四季优势种均为硅藻, 13个优势种分别为柔弱几内亚藻(Guinardia delicatula)、短角弯角藻(Ecampia zoodicaus)、骨条藻(Skeletonema spp.)、具槽帕拉藻(Paralia sulcata)、微小海链藻(Thalassiosira exigua)、标志星杆藻(Asterionella notula)、旋链角毛藻(Chaetoceros curvisetus)、新月菱形藻(Nitzchia closterium)、派格棍形藻(Bacillaria paxillifera)、异常角毛藻(Chaetoceros abmormis)、小细柱藻(Leptocylindrus minutum)、宽角曲舟藻(Pleurosigma angulatum)和美丽曲舟藻(Pleurosigma formosum)。不同季节优势种有一定程度交错, 仅在单季占优的有6种, 有2/3在3个以上季节出现, 具槽帕拉藻、骨条藻为四季优势种。浮游植物物种多样性和均匀度总体较好, 群落结构稳定。与毗邻海区相比, 本区物种丰富度偏低, 丰度高于毗邻海区, 种类组成相似, 优势种却有较大差别。Pearson相关分析表明, 溶解无机氮及活性磷酸盐仅在1月与丰度存在极显著的正相关, 是促使丰度为四季最高的原因。涉海工程施工产生的悬浮物和冲击波是影响浮游植物群落的主要因素, 大量海洋工程建设案例表明, 施工期造成的浮游植物丰度下降趋势和优势种更替混乱在工程结束后能得以恢复。     

The epithelial-mesenchymal transition generates cells with properties of stem cells

The epithelial-mesenchymal transition (EMT) is a key developmental program that is often activated during cancer invasion and metastasis. We here report that the induction of an EMT in immortalized human mammary epithelial cells (HMLEs) results in the acquisition of mesenchymal traits and in the expression of stem-cell markers. Furthermore, we show that those cells have an increased ability to form mammospheres, a property associated with mammary epithelial stem cells. Independent of this, stem cell-like cells isolated from HMLE cultures form mammospheres and express markers similar to those of HMLEs that have undergone an EMT. Moreover, stem-like cells isolated either from mouse or human mammary glands or mammary carcinomas express EMT markers. Finally, transformed human mammary epithelial cells that have undergone an EMT form mammospheres, soft agar colonies, and tumors more efficiently. These findings illustrate a direct link between the EMT and the gain of epithelial stem cell properties.     

Retina dorsal/ventral patterning by Xenopus TBX3.

Although it is well known that patterning in the retina of vertebrates is essential for retina formation and for the retinotopic projection of axons in the embryo, knowledge of molecular and cellular mechanisms of retina patterning is limited. We have previously identified the Xenopus Tbx3 gene (XTbx3) which is expressed in the dorsal retina but not in the ventral retina in Xenopus embryos [H. Li, C. Tierney, L. Wen, J. Y. Wu, and Y. Rao (1997) Development 124, 603-615; M.-L. He, L. Wen, C. E. Campbell, J. Y. Wu, and Y. Rao (1999) Proc. Natl. Acad. Sci. USA 96, 10212-10217]. Dosage-sensitive phenotypes in humans suggest that the manipulation of the amount and location of its products could be informative for understanding its normal function. Here we report that ectopic expression of Tbx3 by mRNA injection suppressed formation of the ventral retina. Furthermore, Tbx3 injection led to inhibition of molecular markers for the ventral retina including Pax-2 and netrin, indicating that Tbx3 plays an important role in retina dorsal/ventral patterning in vertebrates by inhibition of gene expression for ventral retina specification.     

Soil N forms and gross transformation rates in Chinese subtropical forests dominated by different tree species

Background and aims

Knowledge related to extent of differing soil N forms and N transformation rates in subtropical southern China is severely limited. Accordingly, the purpose of this study was to investigate if and how tree species of different foliage types (coniferous, deciduous, and evergreen broadleaved) influence N forms and microbial biomass carbon (MBC) and microbial biomass nitrogen (MBN) content as well as gross N transformation rates in the organic and mineral soils of three distinct subtropical forests in China.

Methods

Chloroform fumigation extraction was used to determine MBC and MBN content while ¹⁵N-isotope dilution techniques were used to measure gross N transformation rates. Canonical correspondence analysis (CCA) was used to quantify relationships between soil chemical characteristics and changes in soil N transformation rates.

Results

Soil N forms, MBC and MBN content, and N transformation rates were found to be significantly different between tree species. Deciduous forest soil exhibited the highest N transformation rates. Soil N transformation rates were closely associated with total soil C and N and MBC and MBN content.

Conclusions

Soil substrate quantity and soil microbial activity play a more important role in soil N transformation processes than does soil quality in China’s subtropical forests. Tree species type should therefore be taken into account when trying to determine ecosystem N cycling.     

Meiotic Chromosome Behavior in a Human Male t（8;15） Carrier

Reciprocal translocation is one of the most common structural chromosomal rearrangements in human beings; it is widely recognized to be associated with male infertility. This association is mainly based on the abnormal chromosome behavior of the translocated chromosomes and sex chromosomes during meiosis prophase I in reciprocal translocation carriers. However, the underlying mechanisms are not completely known. Here we report a reciprocal translocation carrier of t（8;15）, who is oligozoospermic due to apoptosis of primary spermatocytes and to premature germ cell desquamation from seminiferous tubules. Further analysis showed abnormal synapsis and recombination frequency in this patient, indicating a connection between chromosome behavior and apoptosis of primary spermatocytes. We also compared these observations with recently reported findings on spermatogenesis defects in reciprocal translocation carriers, and discuss the possible mechanisms underlying both common and unique phenotypes of reciprocal translocations involving different chromosomes with the aim of further understanding the regulation of human spermatogenesis.     

Synthesis and anti-HCV activity evaluation of anilinoquinoline derivatives

Hepatitis C virus (HCV) infection is a main cause of chronic liver disease, leading to liver cirrhosis and hepatocellular carcinoma (HCC). The objective of our research was to develop effective agents against viral replication. Here, we have synthesized a series of anilinoquinoline derivatives. Based on a cell-based HCV replicon system, we observed that 2-(3'-nitroanilino)quinoline (18) exhibited anti-HCV activity with a 50% effective concentration (EC(50)) value of 7μM and a selective index (SI) value of 10. In addition, compound 18 possessed the inhibitory effect on HCV NS3/4A protease activity. Therefore, we concluded that the compound 18 possessed a potent activity against HCV replication and could provide as a new lead compound as anti-HCV inhibitor.     

Difference in sodium spatial distribution in the shoot of two canola cultivars under saline stress

Among different mechanisms of salt resistance, regulation of ion distribution among various tissues and intracellular compartmentation are of great importance. In this study, we investigated the effects of salt stress on growth, photosynthesis, and Na(+) accumulation and distribution in leaf apoplast and symplast of two canola (Brassica napus L.) cultivars (NYY 1 and BZY 1). The results showed that the declines in shoot dry mass, leaf water potential and net photosynthetic rate of BZY 1 (salt sensitive) were higher than those of NYY 1 (salt resistant) in response to salt stress. Stomatal limitation to photosynthesis was mainly affected under moderate salinity, whereas the reduction in assimilation rate under severe salt stress was due to both stomatal and non-stomatal limitations. We also found that more Na(+) was distributed to leaf veins in NYY 1 than in BZY 1; simultaneously, less Na(+) accumulated in the leaf blade in NYY 1 than in BZY 1. The percentage of Na(+) in the leaf symplast in NYY 1 was markedly lower than that in BZY 1. Also, Na(+) diffusion in leaves through apoplastic and symplastic pathways of BZY 1 was stronger than that in NYY 1, and the transpiration rate in BZY 1, especially at the leaf edges, decreased more than in NYY 1. Our results showed that NYY 1 accumulated less Na(+) in the shoot, especially in leaf blades, and confined Na(+) to the apoplast to avoid leaf salt toxicity, which could be one reason for the higher resistance of NYY 1 than BZY 1 plants to salt stress.     

Pollen size strongly correlates with stigma depth among Pedicularis species

Darwin proposed that pollen size should be positively correlated with stigma depth rather than style length among species given that pollen tubes first enter the stigma autotrophically, then grow through the style heterotrophically. However, studies often show a positive relationship between pollen size and style length.Five floral traits were observed to be correlated among42 bumblebee-pollinated Pedicularis species(Orobanchaceae) in which stigmas are distinct from styles. The phylogenetic independent contrast analysis revealed that pollen grain volume was more strongly correlated with stigma depth than with style length, consistent with Darwin's functional hypothesis between pollen size and stigma depth.