Crystal structure of the M1 protein-binding domain of the influenza A virus nuclear export protein (NEP/NS2)

During influenza virus infection, viral ribonucleoproteins (vRNPs) are replicated in the nucleus and must be exported to the cytoplasm before assembling into mature viral particles. Nuclear export is mediated by the cellular protein Crm1 and putatively by the viral protein NEP/NS2. Proteolytic cleavage of NEP defines an N-terminal domain which mediates RanGTP-dependent binding to Crm1 and a C-terminal domain which binds to the viral matrix protein M1. The 2.6 A crystal structure of the C-terminal domain reveals an amphipathic helical hairpin which dimerizes as a four-helix bundle. The NEP-M1 interaction involves two critical epitopes: an exposed tryptophan (Trp78) surrounded by a cluster of glutamate residues on NEP, and the basic nuclear localization signal (NLS) of M1. Implications for vRNP export are discussed.     

Candida albicans and Saccharomyces cerevisiae cell wall mannans produce fever in rats: role of nitric oxide and cytokines

Mannan components of C. albicans (5 mg/kg, i.p.) and S. cerevisiae (2.5 mg/kg, i.p.) cell walls produced pyrogenic responses which were completely inhibited by indomethacin (5 mg/kg, s.c.) pretreatment in rats. A non-selective NOS inhibitor, L-NAME (10 mg/kg, s.c.), also inhibited the pyrogenic effectiveness of C. albicans mannan, whereas it was ineffective on the fever induced by S. cerevisiae mannan. A selective elevation in the serum TNF-alpha levels was observed at the initial phase of the fever due to S. cerevisiae mannan, whereas there was no significant change on the serum levels of TNF-alpha, IL-1beta and IFN-gamma during the latent period or at the initial phase of the fever induced by C. albicans mannan. Injections of N-linked and/or O-linked oligomannosides of the either mannan did not cause any significant change in the body temperature and serum cytokine levels. These data suggest that the mannan components of C. albicans and S. cerevisiae cell walls produce a prostaglandin-dependent fever in rats. The initial signal for fever seems to be different for each mannan. Data also indicate that integrity of the mannans is necessary for the pyrogenic response.     

Soil inorganic carbon storage pattern in China

Soils with pedogenic carbonate cover about 30% (3.44 × 10⁶ km²) of China, mainly across its arid and semiarid regions in the Northwest. Based on the second national soil survey (1979–1992), total soil inorganic carbon (SIC) storage in China was estimated to be 53.3±6.3 PgC (1 Pg=10¹⁵ g) to the depth investigated to 2 m. Soil inorganic carbon storages were 4.6, 10.6, 11.1, and 20.8 Pg for the depth ranges of 0–0.1, 0.1–0.3, 0.3–0.5, and 0.5–1 m, respectively. Stocks for 0.1, 0.3, 0.5, and 1 m of depth accounted for 8.7%, 28.7%, 49.6%, and 88.9% of total SIC, respectively. In contrast with soil organic carbon (SOC) storage, which is highest under 500–800 mm yr⁻¹ of mean precipitation, SIC storage peaks where mean precipitation is <400 mm yr⁻¹. The amount and vertical distribution of SIC was related to climate and land cover type. Content of SIC in each incremental horizon was positively related with mean annual temperature and negatively related with mean annual precipitation, with the magnitude of SIC content across land cover types showing the following order: desert, grassland >shrubland, cropland >marsh, forest, meadow. Densities of SIC increased generally with depth in all ecosystem types with the exception of deserts and marshes where it peaked in intermediate layers (0.1–0.3 m for first and 0.3–0.5 m for latter). Being an abundant component of soil carbon stocks in China, SIC dynamics and the process involved in its accumulation or loss from soils require a better understanding.     

小黄皮叶挥发油的化学成分

利用水蒸气蒸馏法提取小黄皮叶挥发油,运用毛细管气相色谱-质谱联用法对挥发油进行了分析,分离出40个峰,鉴定了其中的37种成分,所鉴定成分占挥发油总量的99.87%,其主要化学成分为单萜及倍半萜类化合物。     

利用恒河婴猴模型对肠道病毒71型传播感染特征的生物学分析

本文在前期工作基础上,进一步对肠道病毒71型(EV71)从恒河婴猴的感染个体向其他未感染个体传播的可能性及相关生物学特性做了初步分析.通过喷雾形式经呼吸道感染1~2月龄恒河婴猴(A组);在观察临床症状同时,于感染后第7天,取该组动物粪便处理后,将上清液以喷雾形式经呼吸道感染新的婴猴个体(B组),随后对该次代感染个体进行...     

EV71灭活疫苗（人二倍体细胞）在恒河猴婴猴模型中的免疫保护性分析

肠道病毒71型作为引起儿童群体常见传染性手足口病（HFMD）的主要病原,具有导致少量感染个体出现脑炎等神经系统病变以及相关心肺功能衰竭的病理学特性．因此其预防性疫苗的研发具有重要的公共卫生意义．在前期工作的基础上,一种EV71灭活病毒疫苗（人二倍体细胞）在本研究中基于恒河猴婴猴模型进行了相应的免疫保护性分析．以160EU剂量对2～3月龄婴猴进行0,4周免疫后,动物在第4周接受了剂量为10。～CCID50的病毒经呼吸道的攻击．对病毒攻击后动物在14天内的临床症状、血液生物学、器官病原学分布以及病理学检测的动态观察表明,经疫苗免疫的动物未出现对照动物所具有的特征性临床表现,其血液生物学及病理学检测均无异常．同时,器官病原学分布亦呈阴性．结合动物中和抗体的明确增长及对照动物的综合表现分析,本文的工作证实了该EV71灭活病毒疫苗（人二倍体细胞）在恒河猴婴猴体内的免疫保护性．     

Levels of cytokines (IL-1beta, IL-2, IL-6, IL-8, TNF-alpha) and trace elements (Zn, Cu) in breast milk from mothers of preterm and term infants

It has been well documented that human milk contains several immunomodulator components which are important during infant period when the newborn's immune system is still under development. In this study, we aim at examining levels of cytokines, zinc (Zn), and copper (Cu) in milk from mothers of premature and mature infants, and comparing changes during lactation periods consequently. Milk was collected from total of 40 mothers (group M: mothers of mature infants, n = 20; group PM: mothers of premature infants, n = 20) from four lactation stages: colostrum (0-7 days), transitional (7-14 days), mature milk (21 days), and mature milk (2nd month). Levels of cytokines (interleukin [IL]-lbeta, IL-2, IL-6, IL-8, tumor necrosis factor-alpha [TNF-alpha]) were determined by chemiluminesence method, whereas atomic absorption spectrophotometer was used for the determination of Zn and Cu levels. Cytokine levels were determined to be high in colostrum and transient milk from mothers of full-term infants, whereas their levels were reduced drastically in the 21st day and the 2nd month milk (P < .01, P < .001). Similar trends were observed in milk from mothers of premature infants, but cytokine levels were significantly lower in colostrum compared to colostrum from mothers of mature infants (P < .01). The differences in cytokine levels were continuous in transient milk (P < .05) and mature milk (21 days) (P < .05), whereas there was no statistically significant differences between milk from both groups of mothers in the 2nd month (P > .05). Zn levels in milk from mothers of premature infants were significantly lower compared to the ones from mothers of mature infants (P < .01) and these differences continued through the 2nd month. Although Cu levels were lower in milk from mothers of premature infants, there was no statistically significant difference except colostrum (P > .05). Our results clearly demonstrate that the level of immunomodulating agents such as cytokines and trace elements in milk from mothers of premature infants is less than the level of the same agents in milk from mothers of full-term infants. Although there are commercially available products for infant feeding, human milk is still the best natural nutrient for newborns. Therefore, when premature infants are breastfed, necessary precautions such as supplemantary diets must be considered for possible infections and risks related with immune system deficiency.     

Characterization of microsatellite DNA markers in a critically endangered species,Mekong giant catfish,Pangasianodon gigas

Microsatellite DNA markers for a critically endangered Mekong giant catfish (Pangasianodon gigas Roberts and Vidthayanon, 1991) were developed from fin clips collected from captive fish using (GT)₁₅ probe. The number of alleles per locus ranged from two to four. The expected heterozygosities ranged from 0.13 to 0.68. Also, these primers were successfully amplified in four closely related species, Pangasius bocourti, Pangasius conchophilus, Pangasius larnaudii and Pangasius sanitwongsei with the number of alleles per locus ranged from 1 to 13, 1 to 16, 1 to 12 and 1 to 4, respectively. These markers should prove to be very useful for the evaluation of genetic diversity for this species and other related Pangasius species.     

Mutations in RIPK4 cause the autosomal-recessive form of popliteal pterygium syndrome

The autosomal-recessive form of popliteal pterygium syndrome, also known as Bartsocas-Papas syndrome, is a rare, but frequently lethal disorder characterized by marked popliteal pterygium associated with multiple congenital malformations. Using Affymetrix 250K SNP array genotyping and homozygosity mapping, we mapped this malformation syndrome to chromosomal region 21q22.3. Direct sequencing of RIPK4 (receptor-interacting serine/threonine kinase protein 4) showed a homozygous transversion (c.362T>A) that causes substitution of a conserved isoleucine with asparagine at amino acid position 121 (p.Ile121Asn) in the serine/threonine kinase domain of the protein. Additional pathogenic mutations-a homozygous transition (c.551C>T) that leads to a missense substitution (p.Thr184Ile) at a conserved position and a homozygous one base-pair insertion mutation (c.777_778insA) predicted to lead to a premature stop codon (p.Arg260ThrfsX14) within the kinase domain-were observed in two families. Molecular modeling of the kinase domain showed that both the Ile121 and Thr184 positions are critical for the protein's stability and kinase activity. Luciferase reporter assays also demonstrated that these mutations are critical for the catalytic activity of RIPK4. RIPK4 mediates activation of the nuclear factor-κB (NF-κB) signaling pathway and is required for keratinocyte differentiation and craniofacial and limb development. The phenotype of Ripk4(-/-) mice is consistent with the human phenotype presented herein. Additionally, the spectrum of malformations observed in the presented families is similar, but less severe than the conserved helix-loop-helix ubiquitous kinase (CHUK)-deficient human fetus phenotype; known as Cocoon syndrome; this similarity indicates that RIPK4 and CHUK might function via closely related pathways to promote keratinocyte differentiation and epithelial growth.     

茎花葱臭木化学成分的研究

从茎花葱臭木种子中分离得到5个化合物,经理化与波谱分析鉴定为β-谷甾醇(1)、没食子酸乙酯(2)、胡萝卜苷(3)、1-O-β-D-吡喃葡萄糖基-(2S,3S,4R,8Z)-2-N-(2 ′-羟基二十四烷酰氨基)十八二氧鞘氨-8-烯(4)和2,3,2″,3″-四氢穗花杉双黄酮(5).这5个化合物均首次从该植物中分离得到.其中化合物5进行细胞毒活性测试,没有显示抑制活性.