不同术式的经内镜下行乳头括约肌切开术（EST）对肠胆反流的影响

目的：目前认为,十二指肠胆道反流是引起胆道反复感染,进而导致胆道结石再发和胆道狭窄的原因之一。近年来应用以内镜下逆行胆胰管造影术（endoscopicretrogradecholangiopancreatography,ERCP）为基础的微创治疗胆总管结束的技术开展颇为广泛。它主要包括ERCP、Oddi括约肌切开术（endoscopicsphincterotomy,EST）、十二指肠乳头球囊扩张术（endoscopicpapillarybal—Iondilation,EPBD）、胆管结石碎石取石术、胆总管支架植入术和鼻胆管引流术六大技术。本文主要研究了采用不同术式的EST,即EST中切口和EST小切口＋EPBD术,在术后早期对患者十二指肠胆道反流的影响。方法：63例胆总管结石患者,男30例,女33例,予行经内镜下逆行的胆胰管造影（ERCP）后分别采用不同术式EST,术后安放胆总管引流管。术后l周留取胆汁采用口服核素和测定胆汁中的胃蛋白酶I、II的浓度,对十二指肠胆道反流进行定量和定性的测定。结果：EST中切口术组、EST小切口＋球囊扩张（EPBD）组分别与无EST组相比,年龄和性别无统计学意义（P=0．07,P=0．416）。行EST中切开和小切开＋球囊扩张患者胆汁中的锝计数明显高于无EST组,且这两组不同术式的患者锝计数存在显著的统计学差异（P〈0．05）。行EST中切口者、EST小切口＋球囊扩张术者胆汁中的PGII质量浓度明显低于无EST组（P〈0．05）,但是EST中切口者和EST小切口＋球囊扩张术后两组间胆汁中PGII的质量浓度无统计学差异。结论：行EST中切口取胆总管结石的患者在手术早期较易发生十二指肠胆道的反流。因此,建议对于胆总管结石患者尽量选择行EST小切口＋球裳扩张术（EPBD）的手术方式。     

Fluid Shear Stress on Endothelial Cells Modulates Mechanical Tension across VE-Cadherin and PECAM-1

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A survey of aspartate-phenylalanine and glutamate-phenylalanine interactions in the protein data bank: searching for anion-π pairs

Protein structures are stabilized using noncovalent interactions. In addition to the traditional noncovalent interactions, newer types of interactions are thought to be present in proteins. One such interaction, an anion-π pair, in which the positively charged edge of an aromatic ring interacts with an anion, forming a favorable anion-quadrupole interaction, has been previously proposed [Jackson, M. R., et al. (2007) J. Phys. Chem. B111, 8242-8249]. To study the role of anion-π interactions in stabilizing protein structure, we analyzed pairwise interactions between phenylalanine (Phe) and the anionic amino acids, aspartate (Asp) and glutamate (Glu). Particular emphasis was focused on identification of Phe-Asp or -Glu pairs separated by less than 7 ? in the high-resolution, nonredundant Protein Data Bank. Simplifying Phe to benzene and Asp or Glu to formate molecules facilitated in silico analysis of the pairs. Kitaura-Morokuma energy calculations were performed on roughly 19000 benzene-formate pairs and the resulting energies analyzed as a function of distance and angle. Edgewise interactions typically produced strongly stabilizing interaction energies (-2 to -7.3 kcal/mol), while interactions involving the ring face resulted in weakly stabilizing to repulsive interaction energies. The strongest, most stabilizing interactions were identified as preferentially occurring in buried residues. Anion-π pairs are found throughout protein structures, in helices as well as β strands. Numerous pairs also had nearby cation-π interactions as well as potential π-π stacking. While more than 1000 structures did not contain an anion-π pair, the 3134 remaining structures contained approximately 2.6 anion-π pairs per protein, suggesting it is a reasonably common motif that could contribute to the overall structural stability of a protein.     

Tandem SAM domain structure of human Caskin1: a presynaptic, self-assembling scaffold for CASK

The synaptic scaffolding proteins CASK and Caskin1 are part of the fibrous mesh of proteins that organize the active zones of neural synapses. CASK binds to a region of Caskin1 called the CASK interaction domain (CID). Adjacent to the CID, Caskin1 contains two tandem sterile α motif (SAM) domains. Many SAM domains form polymers so they are good candidates for forming the fibrous structures seen in the active zone. We show here that the SAM domains of Caskin1 form a new type of SAM helical polymer. The Caskin1 polymer interface exhibits a remarkable segregation of charged residues, resulting in a high sensitivity to ionic strength in?vitro. The Caskin1 polymers can be decorated with CASK proteins, illustrating how these proteins may work together to organize the cytomatrix in active zones.     

苎麻光合生理生态特性研究

以大田栽培的苎麻植株为材料,用TPS-2便携式光合作用测定系统测定自然条件下生长的苎麻叶片的光合气体交换参数,以及光响应曲线和CO2响应曲线,并通过回归和相关法分析探讨净光合速率与主要生理、生态因子间的关系.结果表明:(1)苎麻叶片的净光合速率(Pn)日变化曲线呈现双峰型,2个光合峰高度接近,其净光合速率具有典型的午休"现象;蒸腾速率(Tr)日变化曲线呈现单峰型,其走势与气孔导度(Gs)日变化一致.(2)苎麻叶片光合作用的光饱和点(LSP)为1 568.5μmol?m-2?s-1,光补偿点(LCP)为54.18μmol?m-2?s-1,表观量子效率(AQY)为0.025 8 mol?mol-1;而其CO2补偿点(CCP)、饱和点(CSP)和羧化效率(CE)分别为49.25、1 746.9μmol?mol-1和0.045;因此,苎麻属于喜光性阳生植物,且对强光有一定的耐受能力.(3)苎麻叶片Pn日变化的主要限制因子是胞间CO2浓度(Ci),主要决定生理因子是气孔导度(Gs).     

Survey of Academic Field Experiences (SAFE): Trainees Report Harassment and Assault

Little is known about the climate of the scientific fieldwork setting as it relates to gendered experiences, sexual harassment, and sexual assault. We conducted an internet-based survey of field scientists (N = 666) to characterize these experiences. Codes of conduct and sexual harassment policies were not regularly encountered by respondents, while harassment and assault were commonly experienced by respondents during trainee career stages. Women trainees were the primary targets; their perpetrators were predominantly senior to them professionally within the research team. Male trainees were more often targeted by their peers at the research site. Few respondents were aware of mechanisms to report incidents; most who did report were unsatisfied with the outcome. These findings suggest that policies emphasizing safety, inclusivity, and collegiality have the potential to improve field experiences of a diversity of researchers, especially during early career stages. These include better awareness of mechanisms for direct and oblique reporting of harassment and assault and, the implementation of productive response mechanisms when such behaviors are reported. Principal investigators are particularly well positioned to influence workplace culture at their field sites.     

Primate milk: proximate mechanisms and ultimate perspectives

To understand the evolutionary forces that have shaped primate lactation strategies, it is important to understand the proximate mechanisms of milk synthesis and their ecological and phylogenetic contexts. The lactation strategy of a species has four interrelated dimensions: the frequency and duration of nursing bouts, the period of lactation until weaning, the number and sex ratio of infants that a mother rears simultaneously, and the composition and yield of the milk that mothers synthesize. Milk synthesis, arguably the most physiologically costly component of rearing infants, remains the least studied. Energy transfer becomes energetically less efficient, transitioning from placental support to milk synthesis just as the energy requirements for infant growth, development, and behavioral activity substantially increase. Here we review primate lactation biology and milk synthesis, integrating studies from anthropology, biology, nutrition, animal science, immunology, and biochemistry, to identify the derived and ancestral features of primate milks and enhance our understanding of primate life history.     

E. coli chaperones DnaK,Hsp33 and Spy inhibit bacterial functional amyloid assembly

Amyloid formation is an ordered aggregation process, where β-sheet rich polymers are assembled from unstructured or partially folded monomers. We examined how two Escherichia coli cytosolic chaperones, DnaK and Hsp33, and a more recently characterized periplasmic chaperone, Spy, modulate the aggregation of a functional amyloid protein, CsgA. We found that DnaK, the Hsp70 homolog in E. coli, and Hsp33, a redox-regulated holdase, potently inhibited CsgA amyloidogenesis. The Hsp33 anti-amyloidogenesis activity was oxidation dependent, as oxidized Hsp33 was significantly more efficient than reduced Hsp33 at preventing CsgA aggregation. When soluble CsgA was seeded with preformed amyloid fibers, neither Hsp33 nor DnaK were able to efficiently prevent soluble CsgA from adopting the amyloid conformation. Moreover, both DnaK and Hsp33 increased the time that CsgA was reactive with the amyloid oligomer conformation-specific A11 antibody. Since CsgA must also pass through the periplasm during secretion, we assessed the ability of the periplasmic chaperone Spy to inhibit CsgA polymerization. Like DnaK and Hsp33, Spy also inhibited CsgA polymerization in vitro. Overexpression of Spy resulted in increased chaperone activity in periplasmic extracts and in reduced curli biogenesis in vivo. We propose that DnaK, Hsp33 and Spy exert their effects during the nucleation stages of CsgA fibrillation. Thus, both housekeeping and stress induced cytosolic and periplasmic chaperones may be involved in discouraging premature CsgA interactions during curli biogenesis.Key words: chaperone, curli, functional amyloid, CsgA, DnaK, Hsp33, Spy     

核心组蛋白的融合表达和纯化

目的:克隆核心组蛋白H2A、H2B、H3和H4的基因,表达并纯化组蛋白与谷胱甘肽S-转移酶(GST)的融合蛋白。方法:用PCR方法从乳腺文库中扩增核心组蛋白H2A、H2B、H3和H4的编码序列,分别将其以正确相位与pGEX-KG载体中的GST编码序列融合,得到重组质粒pGST-H2A、pGST-H2B、pGST-H3和pGST-H4,分别转化大肠杆菌BL21,表达融合蛋白GST-H2A、GST-H2B、GST-H3和GST-H4;用谷胱甘肽-Sepharose 4B亲和纯化融合蛋白;用Western印迹检测融合蛋白的表达及纯化。结果:分别构建了核心组蛋白H2A、H2B、H3和H4的融合表达载体;Western印迹检测表明,融合蛋白GST-H2A、GST-H2B、GST-H3和GST-H4获得表达及纯化。结论:表达并纯化了H2A、H2B、H3和H4的融合蛋白,为进一步研究核心组蛋白的功能奠定了基础。