Erbin:LAP家族的新成员

Erbin(ErbB2结构蛋白）是LAP家族新成员,它的N末端有16个富含亮氨酸的重复序列（LRR）,在LRR后有一个LRR样的结构域,C末端含有PDZ结构域,实验证明Erbin通过其PDZ结构域与ErbB2结合。在上皮和神经元等级性细胞中,Erbin对ErbB2的定位或定向转移具有重要作用,并可增加ErbB2在细胞表面的表达量。Erbin作为支架蛋白还参与了细胞骨架的形成。     

Inhibition of NF-κB by MG132 through ER stress-mediated induction of LAP and LIP

Proteasome inhibitor MG132 blocks activation of NF-κB by preventing degradation of IκB. In this report, we propose an alternative mechanism by which MG132 inhibits cytokine-triggered NF-κB activation. We found that MG132 induced endoplasmic reticulum (ER) stress, and attenuation of ER stress blunted the suppressive effect of MG132 on NF-κB. Through ER stress, MG132 up-regulated C/EBPβ mRNA transiently and caused sustained accumulation of its translational products liver activating protein (LAP) and liver-enriched inhibitory protein (LIP), both of which were identified as suppressors of NF-κB. Our results disclosed a novel mechanism underlying inhibition of NF-κB by MG132.     

LAP proteins: what's up with epithelia?

How cells maintain their overall shape and size, and the related question of how proteins and other molecules reach and stay at their specific subcellular locations, are among the most difficult and exciting problems in cell biology. Three recent studies have made a significant contribution to this area by identifying new proteins, called LAP proteins, that have critical functions in maintaining the shape and apical-basal polarity of epithelial cells.     

LEM4/ANKLE-2 deficiency impairs post-mitotic re-localization of BAF,LAP2α and LaminA to the nucleus,causes nuclear envelope instability in telophase and leads to hyperploidy in HeLa cells

The human LEM-domain protein family is involved in fundamental aspects of nuclear biology. The LEM-domain interacts with the barrier-to-autointegration factor (BAF), which itself binds DNA. LEM-domain proteins LAP2, emerin and MAN1 are proteins of the inner nuclear membrane; they have important functions: maintaining the integrity of the nuclear lamina and regulating gene expression at the nuclear periphery.LEM4/ANKLE-2 has been proposed to participate in nuclear envelope reassembly after mitosis and to mediate dephosphorylation of BAF through binding to phosphatase PP2A. Here, we used CRISPR/Cas9 to create several cell lines deficient in LEM4/ANKLE-2. By using time-lapse video microscopy, we show that absence of this protein severely compromises the post mitotic re-association of the nuclear proteins BAF, LAP2α and LaminA to chromosomes. These defects give rise to a strong mechanical instability of the nuclear envelope in telophase and to a chromosomal instability leading to increased number of hyperploid cells. Reintroducing LEM4/ANKLE-2 in the cells by transfection could efficiently restore the telophase association of BAF and LAP2α to the chromosomes. This rescue phenotype was abolished for N- or C-terminally truncated mutants that had lost the capacity to bind PP2A. We demonstrate also that, in addition to binding to PP2A, LEM4/ANKLE-2 binds BAF through its LEM-domain, providing further evidence for a generic function of this domain as a principal interactor of BAF.     

A –308 deletion of the tomato LAP promoters is able to direct flower-specific and MeJA-induced expression in transgenic plants

Tomato and potato leucine aminopeptidase (LAP) mRNAs are induced in response to mechanical wounding and the wound signal molecules, ABA and jasmonic acid. Here, we report the isolation of two LAP genes, LAP17.1A and LAP17.2, from tomato. Functional analysis in transgenic tomato and potato plants show that fusions of the corresponding 5 non-coding regions to the gusA gene are constitutively expressed in flowers and induced in leaves upon wounding or by treatment with methyl jasmonate (MeJA). Comparison of the 5 non-coding regions of the two genes revealed a region from –317 to –3 relative to the ATG, which is strongly conserved in both promoters. This 0.3 kb proximal promoter fragment is sufficient to direct flower-specific and MeJA-inducible GUS activity in transgenic potato plants, and thus contains a MeJA-responsive element that mediates induction by MeJA. Dimeric TGACG motifs or G-box elements similar to those found in other MeJA-inducible genes are not observed in this region, which suggests that a different DNA sequence is involved in MeJA induction of the LAP genes.     

High Mobility Group Protein N5 (HMGN5) and Lamina-associated Polypeptide 2α (LAP2α) Interact and Reciprocally Affect Their Genome-wide Chromatin Organization

The interactions of nuclear lamins with the chromatin fiber play an important role in regulating nuclear architecture and chromatin function; however, the full spectrum of these interactions is not known. We report that the N-terminal domain of the nucleosome-binding protein HMGN5 interacts with the C-terminal domain of the lamin-binding protein LAP2α and that these proteins reciprocally alter their interaction with chromatin. Chromatin immunoprecipitation analysis of cells lacking either HMGN5 or LAP2α reveals that loss of either protein affects the genome-wide distribution of the remaining partner. Our study identifies a new functional link between chromatin-binding and lamin-binding proteins.     

Qualitative and quantitative determination of major saponins in Paris and Trillium by HPLC-ELSD and HPLC–MS/MS

High-performance liquid chromatographic (HPLC) with evaporative light scattering detection (ELSD) and HPLC with electrospray ionization multistage tandem mass spectrometry (HPLC–ESI-MSⁿ) were used to identify and quantify steroid saponins in Paris and Trillium plants. The content of the known saponins such as Paris I, II, III, V, VI, VII, H, gracillin and protodioscin in Paris and Trillium plants was determined simultaneously using the developed HPLC-ELSD method. Furthermore, other 12 steroid saponins were identified by HPLC–ESI(+/−)-MSⁿ detection. In the end, a developed analytical procedure was proved to be a reliable and rapid method for the quality control of Paris and Trillium plants. In addition, the alternative resources for Paris yunnanensis used as a traditional Chinese medicine were discovered according to the hierarchical clustering analysis of the saponin fraction of these plants.     

HALS与LAP用于直肠癌根治术患者的临床疗效及其对血清炎性因子水平的影响

目的:探讨手辅助腹腔镜手术(hand-assisted laparoscopic surgery,HALS)与全腹腔镜手术(laparoscopic surgery,LAP)用于直肠癌根治术患者的临床疗效及其对血清炎性因子水平的影响。方法:选取2013年3月～2018年3月在我院行直肠癌根治术的患者61例进行回顾性分析,按照手术方式不同分为手辅助腹腔镜手术组(HALS组)和全腹腔镜手术组(LAP组)。比较两组患者的手术相关指标、术后恢复指标和治疗前后血清炎性因子水平的变化。结果:HALS组的手术时间、术中出血量和副损伤显著低于LAP组(P0.05),两组中转开腹率相比无统计学差异(P0.05);两组患者术后肠功能恢复时间、进食时间、下床时间和住院时间比较均无显著性差异(P0.05);两组患者术后1 h和术后1 d血清白细胞介素-10(interleukin-10, IL-10)、C-反应蛋白(C reactive protein,CRP)和α肿瘤坏死因子(Tumor Necrosis Factor-α,TNF-α)水平均较术前显著升高,且HALS组显著低于LAP组(P0.05),术后1 w血清IL-10、CRP和TNF-α水平与术前相比无统计学差异(P0.05)。结论:HALS直肠癌根治术对患者的手术创伤小,炎性反应轻,且不影响患者的预后,利于患者的康复。     

Preparation and conformational analysis of C-glycosyl β- and β/β-peptides

Ten C-glycosyl β²- and β/β²-peptides with three to eight amino acid residues have been prepared. Solution and solid-phase peptide syntheses were employed to assemble β²-amino acids in which C-glycosylic substituents are attached to the C-2 position of β-amino acids. Conformational analysis of the C-glycosyl β²-peptides using NMR and CD spectra indicates that the tripeptide can form a helical secondary structure. Besides, helix directions of the C-glycosyl β/β²-peptides are governed by the configuration at the α-carbon of the peptide backbone that originates from the stereocenter of the C-glycosyl β²-amino acids.     

IFN-α/β and autophagy

Hepatitis C virus (HCV) infects approximately 130 million people worldwide. The clinical sequelae of this chronic disease include cirrhosis, functional failure and carcinoma of the liver. HCV induces autophagy, a fundamental cellular process for maintaining homeostasis and mediating innate immune response, and also inhibits autophagic protein degradation and suppresses antiviral immunity. In addition to this ploy, the HCV serine protease composed of the viral non-structural proteins 3/4A (NS3/4A) can enzymatically digest two cellular proteins, mitochondria-associated anti-viral signaling protein (MAVS) and Toll/interleukin-1 receptor domain containing adaptor inducing IFN-β (TRIF). Since these two proteins are the adaptor molecules in the retinoic acid-inducible gene I (RIG-I) and TLR3 pathways, respectively, their cleavage has been suggested as a pivotal mechanism by which HCV blunts the IFN-α/β signaling and antiviral responses. Thus far, how HCV perturbs autophagy and copes with IFN-α/β in the liver remains unclear.     

热带爪蛙LAP家族基因在胚胎早期发育中的表达图式

LAP家族蛋白含有特征性的富含亮氨酸的重复序列和PDZ结构域.在脊椎动物和无脊椎动物中,LAP家族基因在细胞极性、上皮组织的动态平衡与肿瘤抑制等的调控中具有重要作用.在脊椎动物中,这一家族基因包括4个成员：densin,erbin,scribble和lano.本研究根据热带爪蟾（Xenopus tropicalis）的基因组与EST序列,推测了其LAP家族的4个基因,克隆了其基因片段并研究了它们在胚胎发育中的表达图式.爪蛙的LAP蛋白在结构上与其他脊椎动物中的同源蛋白相似.这4个基因均有母源性表达,在卵裂期胚胎动物极细胞中表达较强,到原肠胚期在动物帽细胞中可检测到.在胚胎发育晚期,这些基因在上皮细胞中表达较广,包括神经上皮、耳泡、视泡和前肾.上述结果表明,LAP基因可能参与调控爪蛙早期发育中的上皮细胞极性和形态发生.在爪蛙胚胎头部,erbin和lano具有相似的时空表达图式,这表明二者在体内的功能可能是相关的.     

Isolation and synthesis of trans- and cis-(−)-clovamides and their deoxy analogues from the bark of Dalbergia melanoxylon

N-(3′,4′-Dihydroxy-trans-cinnamoyl)-3-(3,4-dihydroxyphenyl)-L-alanine [(?)-clovamide], the major phenolic metabolite (0.1%) in the bark of Dalbergia melanoxylon, is associated with minor proportions of its cis-isomer, and similar pairs of geometrical isomers of their deoxy analogues N-(4′-hydroxycinnamoyl)-3-(3,4-dihydroxyphenyl)-L-alanine and N-(4′-hydroxycinnamoyl)-3-(4-hydroxyphenyl)-L-alanine. (?)-Trans-clovamide is synthesized by direct condensation of the acid chloride of caffeic acid with L-DOPA. Diagnostic CD spectra of these compounds and ¹³C spectra of (?)-trans- and (?)-cis-clovamides are recorded.     

Visual learning and memory of Drosophila melanogaster wild type CS and the mutants dunce1, amnesiac, turnip and rutabaga

Dunce¹, amnesiac, turnip and rutabaga, mutants of Drosophila melanogaster deficient in olfactory learning and/or memory, were tested for visual learning ability and memory. All these mutants are able to learn conditioned visual information, but not as well as the corresponding wildtype CS. Memory of all four mutants is reduced during the first 30 min after training, but indistinguishable from that of the wildtype two hours after conditioning.     

Obtaining and characterization of “Holospora curviuscula” and Holospora obtusa, bacterial symbionts of the macronuclei of Paramecium bursaria and Paramecium caudatum

The symbionts of the macronuclei of Paramecium bursaria and P. caudatum, “Holospora curviuscula” 02AZ16 and H. obtusa 88Ti, respectively, were obtained and investigated. The 16S rDNA nucleotide sequences of “Holospora curviuscula” were obtained for the first time. The differences in 16S rDNA (3.4%) suggest their classification within the genus Holospora. Molecular phylogenetic analysis of the symbionts revealed that these intranuclear symbionts of the ciliates belonged to the order Rickettsiales, forming within a compact cluster of related species.     

Wnt/β-catenin signaling and disease

The WNT signal transduction cascade controls myriad biological phenomena throughout development and adult life of all animals. In parallel, aberrant Wnt signaling underlies a wide range of pathologies in humans. In this Review, we provide an update of the core Wnt/β-catenin signaling pathway, discuss how its various components contribute to disease, and pose outstanding questions to be addressed in the future.     

5′-Monohydroxyphylloquinone from Anacystis and Euglena

The monohydroxy analogue of phylloquinone found in Anacystis nidulans and Euglena gracilis has been characterized as 5′-monohydroxyphylloquinone by MS analysis.