影像化合物PiB可用于辨认人脑的淀粉样蛋白斑

据美国BIOCOMPARE科技新闻网（2007／3／21）报道，马萨诸塞综合医院（MGH）的研究人员证实，一种名为PittsburghcompoundB（简称PiB）的荧光物质可用于辨认人脑的淀粉样蛋白斑。

桥粒蛋白斑菲素蛋白1的1个新的纯合突变(888delC)导致的外胚层发育不良-皮肤脆性综合征

We report an unusual case of an inherited disorder of the desmosomal protein plakophilin 1, resulting in ectodermal dysplasia-skin fragility syndrome. The affected 6-year-old boy had red skin at birth and subsequently developed skin fragility, progressive plantar keratoderma, nail dystrophy, and alopecia. Skin biopsy revealed widening of intercellular spaces in the epidermis and a reduced number of small, poorly formed desmosomes. Mutation analysis of the plakophilin 1 gene PKP1 revealed a homozygous deletion of C at nucleotide 888 within exon 5. This mutation differs from the PKP1 gene pathology reported in 8 previously published individuals with this rare genodermatosis. However, all cases show similar clinical features, highlighting the importance of functional plakophilin 1 in maintaining desmosomal adhesion in skin, as well as the role of this protein in aspects of ectodermal development.

新试验药物可“溶解”轻中度阿尔茨海默病的淀粉样蛋白斑

一项Ⅱ期临床研究的中期结果显示，一种作用于淀粉样蛋白的单克隆抗体能安全有效地“溶解”轻中度阿尔茨海默病患者大脑中的淀粉样蛋白斑。该种名为LY2062430的试验药物是一种单克隆抗体，研究显示，静脉注射该抗体可使淀粉样蛋白的血清浓度明显降低，因为它具有与淀粉样蛋白结合的能力。

清除老年痴呆症小鼠小胶质细胞可以防止神经元丢失但并不调节β-淀粉样蛋白的病理改变

除了β-淀粉样蛋白斑和tau蛋白过度磷酸化引起的神经元纤维缠结外,神经炎症被认为是阿尔茨海默病（Alzheimer disease,AD）的另一个重要病理特征。炎症在阿尔茨海默氏病的特征性表现为反应性星形胶质细胞和活化的小胶质细胞在淀粉样蛋白斑周围聚集,提示活化的小胶质细胞在疾病的发病机制中发挥了作用。在健康成年小鼠,小胶质细胞的生存依赖于集落刺激因子1受体（colony-stimulating factor 1 receptor,CSF1R）的信号,

Purification and Antimicrobial Activity of Antimicrobial Protein from Brown-spotted Grouper, Epinephelus fario

Antimicrobial proteins and peptides had been found from a wide variety of organisms in the last few years These molecules have attracted much research interest because of their biochemical diversity, broad specificity on anti-viral, anti-bacterial, anti-fungi, anti-protozoan parasites, anti-tumoural, and wound-healing effects. Antimicrobial proteins and peptides play key roles in innate immunity. They interact directly with bacteria and kill them. The brown-spotted grouper, Epinephelusfario, is an important marine fish cultured in southem China. Recently, bacteria and virus have caused high mortality in E. fario cultures, but its endogenous antimicrobial peptides and proteins have not been explored. An antimicrobial component was found from the skin homogenate of E. fario. After the skin homogenate was digested with trypsin, its antimicrobial activity was lost, which showed that the antimicrobial component is a protein. The antimicrobial protein （Efap） was purified from the skin homogenate of E. fario by successive ion-exchange and gel filtration chromatography. Efap was demonstrated to be single protein band by SDS-PAGE, with the apparent molecular weight of 41 kD. Efap exhibited antimicrobial activity both for the Gram-positive bacteria, Staphylococcus aureus, Micrococcus luteus and Bacillus subtilis, and for the Gram-negative bacteria, Vibrio alginolyticus, Vibrio parahaemolyticus, Vibrio fluvialis, Pasteurella multocida, Aeromonas hydrophila, Eschrrichiu coli, and Pseudomonas aeruginosa. Except A. hydrophila, P. aeruginosa, and E. coli （MIC〉20 mol/L）, most of the tested Gram-negative bacteria were sensitive to Efap （MIC〈20 mol/L）. Interestingly, Efap showed potent antimicrobial activity against Gram-positive bacteria S. aureus （MIC 5-10 mol/L） but comparatively weak antimicrobial activity against M. luteus and B. subtilis. The broad antimicrobial activities of Efap suggest that it contributes to the innate host defence of E. fario.

设计的自组装肽通过促进神经元分化和旁分泌作用使神经干细胞移植治疗阿尔茨海默病的效果最大化

阿尔茨海默病（Alzheimer’s disease,AD）的神经病理学标志包括细胞外β-淀粉样蛋白（amyloid-βpeptide,Aβ）沉积形成的淀粉样蛋白斑和神经元丢失。神经干细胞（neural stem cell,NSC）治疗正成为各种神经系统退行性疾病的细胞替代疗法。然而,退行性疾病的病损区环境不利于移植细胞的存活与分化。

Elementary study of differential expression of total soluble proteins in different life phases of Porphyra yezoensis

Total soluble proteins of different life stages, filamentous sporophytes cultivated in high temperatures, and blade gametophytes harvested in different seasons, were identified by SDS-PAGE. The types and amounts of expressed proteins also varied amongst the samples. The fewest soluble proteins were present in filamentous sporophytes. There were more types and amounts of soluble protein in conchospores than in filamentous sporophytes, but fewer than in bulgy sporophytes. More types of protein were detected in filamentous sporophytes cultivated in high temperatures than in those growing in normal situations. The most types and amounts of protein were found in blade gametophytes in all samples. Blade gametophytes harvested last year and stored at -20 ℃ showed only minor differences in expression of proteins when compared with those harvested in different seasons.

低热量饮食可防痴呆

美国研究人员在动物研究中发现，总热量减少30%的低碳水化合物饮食，可以防止老年痴呆症恶化。在本研究中所使用实验动物经过基因设计，脑部会产生淀粉样蛋白斑（淀粉样蛋白斑是典型的老化副产品，可见于患老年痴呆症患者的脑部）。

Identification of Z-OTU protein during zebrafish oogenesis and early embryogenesis

Zebrafish（Danio rerio） Z-OTU,containing OTU and TUDOR domains,was predicted to be a member of OTU-related protease,a family of the deubiquitylating enzymes（DUBs）.A previous report from our laboratory clearly describes the expression patterns of z-otu mRNA.Here,we characterized the Z-OTU protein during zebrafish oogenesis and early embryogenesis.After prokaryotic expression,the recombinant protein of the OTU domain and GST was purified and injected into rabbits to obtain the polyclonal antibody-anti-Z-OTU,which was used for immunohistochemistry in zebrafish ovaries and embryos.Interestingly,obvious differences existed between the expression patterns of z-otu mRNA and its protein during oogenesis and early embryogenesis.In stage I oocytes,z-otu mRNA was detected in cytoplasm while its protein existed in the germinal vesicle.In addition,its protein was distributed during entire oogenesis,while mRNA was not detected in oocytes at stage IV or mature oocytes.The z-otu mRNA disappeared after midblastula transition（MBT） and its protein gradually decreased after this stage.We inferred that Z-OTU protein,like other OTU-related protease with DUB activity,was required for germinal vesicle breakdown of oocytes during meiosis,germinal vesicle migration,and embryo cleavage maintenance.

Purification and Photodynamic Bioactivity of Phycoerythrin and Phycocyanin from Porphyra yezoensis Ueda

Phycoerythrin and phycocyanin were purified from Porphyra yezoensis Ueda with their bioactivity determined in this study. Continuous precipitation with ammonium sulfate at different concentrations(10%, 20%, 40% and 50%) increased the purity(A564:A280) of phycoerythrin to 1.49, 3.92 fold of the raw extract(0.38) and the purity(A615:A280) of phycocyanin to 0.70, 3.33 fold of the raw extract(0.21). Two more times of chromatography with hydroxylapatites finally made the purity of phycoerythrin and phycocyanin reach 5.50, 14.47 fold of the raw extract, and 5.10, 24.29 fold of the raw extract, respectviely. The yield of high purity phycoerythrin and phycocyanin were 0.21% and 0.09% of dried P. yezoensis blade, respectively. The photodynamic cytotoxic experiment showed that both phycoerythrin and phycocyanin inhibited the growth of liver tumor cells significantly. It was found that 250 mg L-1 purified phycoerythrin and phycocyanin inhibited the growth of hepatocellular carcinoma cells 24 h after laser-irradiation by 80% and 59%, respectively, and 100 mg L-1 purified phycoerythrin and phycocyanin induced the apoptosis of 31.54% and 32.54% of the cells, respectively, 8 h after photodynamic therapy. Oue findings demonstrated that P. yezoensis can serve as photosensitizer(phycoerythrin and phycocyanin) producer.

Cloning and Analysis of Calmodulin Gene from Porphyra yezoensis Ueda (Bangiales, Rhodophyta)

In order to understand the mechanisms of signal transduction and anti-desiccation mechanisms of Porphyra yezoensis, cDNA and its genomic sequence of Calmodulin gene (CaM) was cloned by the technique of polymerase chain reaction (PCR) based on the analysis of P. yezoensis ESTs from dbEST database. The result shows that the full-length cDNA of CaM consists of 603 bps including an ORF encoding for 151 amino acids and a terminate codon UGA, while the length of genomic sequence is 1231 bps including 2 exons and 1 intron. The average GC content of the coding region is 58.77%, while the GC content of the third position of this gene is as high as 82.23%. Four Ca2+ binding sites (EF-hand) are found in this gene. The predicted molecular mass of the deduced peptide is 16688.72 Da and the pI is 4.222. By aligning with known CaM genes, the similarity of CaM gene sequence with homologous genes in Chlamydomonas incerta and Chlamydomonas reinhardtii is 72.7% and 72.2% respectively, and the similarity of the deduced amino acid sequence of CaM gene with homologous genes in C. incerta and C. reinhardtii are both 71.5%. This is the first report on CaM from a species of Rhodophyta.

Characterization and Diagnostic Use of a Monoclonal Antibody for VP28 Envelope Protein of White Spot Syndrome Virus

The gene encoding the VP28 envelope protein of White spot syndrome virus (WSSV) was cloned into expression vector pET-30a and transformed into the Escherichia coli strain BL21.After induction,the recombinant VP28 (rVP28) protein was purified and then used to immunize Balb/c mice for monoclonal antibody (MAb) production.It was observed by immuno-electron microscopy the MAbs specific to rVP28 could recognize native VP28 target epitopes of WSSV and dot-blot analysis was used to detect natural WSSV infection.Competitive PCR showed that the viral level was approximately 104 copies/mg tissue in the dilution of gill homogenate of WSSV-infected crayfish at the detection limit of dot-blot assay.Our results suggest that dot-blot analysis with anti-rVP28 MAb could rapidly and sensitively detect WSSV at the early stages of WSSV infection.

In vivo effects of 17-β-estradiol on plasma immunoglobulin levels and leukocyte density in zebrafish Danio rerio

Estradiol, or 17-β-estradiol （E2）, the most potent naturally occurring estrogen, is involved in the hormone-immune system interaction in both mammals and fish. However, in vivo studies are largely limited, and little is known about whether E2 exerts similar effects on both female and male zebrafish （Danio rerio）. Here, we show exposure of both sexes ofD. rerio to 20 nmol/L E2 resulted in a significant increase in Vgl expression, but caused little damage to the hepatocytes, suggesting that this is the optimum E2 concentration. Also, exposure to 20 nmol/L E2 for 20 days caused a marked increase in plasma IgM levels, but had little influence on the peripheral leukocyte density, providing the first evidence of a hormone-immune system interaction in this species.

Optimum Fish for Fish Glue Processing for Fish Skin Value Added and the Glue Character

Fish glue is the collagen from scale skin and bone of fish. It is known for value added product from fish processing and the adhesive agent for wood paper book binding etc. This work was aimed with the method to produce fish glue from fish skin through representing optimum fish type and its glue character by study on standard method for fish glue processing （using Oreochromis niloticus skin as the model）, optimum fish type and characterization of the glue from optimum fish skin. Soaking fish skin in 0.1 N NaOH for 6 h and changed it every 3 h for pretreatment before acid extraction with 0.5 M acetic acid was the optimum condition for the standard processing. Among 20 types （O. niloticus, Oreochromis sp., Nemipterus sp., Psettodes erumei, Epiephelus malabaricus, Sphyraena obstsata, Channa striata, Xenentodon cancila, Barbonymus gonionotus, Liza vaigiensis, Anabas testudineus, Chanos chanos, Micronema bleekeri, Thunnus tonggol, Rastrelliger brachysom, Epinephelus lanceolatus, Lutjanus lineolatus, Pomadasys hasta, Selar crumenophthalmus and Sardaorentalis sp.）, Chanos chanos was an appropriate type for glue production. Fat, protein, carbohydrate, moisture, pH and viscosity of Chanos chanos glue were 0.32%, 4.23%, 83.8%, 11.56%, 3.35, 4,978.33-8,180 cp, respectively. The glue was collagen type I which was composed ofal （148 kDa） and a2 （129 kDa） chain and could bind paper, wood and foam sheet.

A COMPLEX OF INTERMEDIATE FILAMENT PROTEIN－DNA：A TARGET FOR AUTOANTIBODIES IN SYSTEMIC LUPUS ERYTHEMATOSUS？

Autoantibodies in systemic lupus erythematosus which cross-react with double stranded DNA and intermediate filament proteins are frequently reported. However, little is Known about the origin and the target of these antibodies. In this paper, a polyspecific monoclonal antibody, XY12, produced by the immunization of genetically non-autoimmune mice with a DNA-protein complex is detailed. Its antigen binding patterns are very similar to the autoantibodies. The data suggest that these autoantibedies may be triggered by a circulating nucleoprotein.

Feasibility of Partial Replacement of Fishmeal with Proteins from Different Sources in Diets of Korean Rockfish(Sebastes schlegeli)

An 8-week feeding experiment was conducted in an indoor recirculation seawater system to investigate the effects of partial replacement of dietary fishmeal with proteins from five sources on the growth performance and feed utilization of Sebastes schlegeli. Six isonitrogenous and isoenergetic diets were formulated using fishmeal(FM, the control) as sole protein source, or proteins from five sources including poultry by-product meal(PBM), meat and bone meal(MBM), soybean meal(SBM), cottonseed meal(CSM) and canola meal(CNM). Fifteen percent of the crude protein provided by fish meal was replaced, respectively. The results showed that the differences in specific growth rate(SGR) and survival rate(SR) among fish fed PBM, MBM, SBM, CSM and whole FM diets were not significant. However, SGR and SR of fish fed CNM diet was significantly lower than that of other treatments. Feeding rate, feed conversion, nutrient retention showed similar patterns to that of growth. Fish fed CSM and CNM showed significantly lower apparent digestibility coefficient(ADC) of dry matter and gross energy than those fed others while fish fed CNM showed lower ADC of crude protein than those fed others(P<0.05). These results suggested that it was feasible to substitute 15% dietary protein provided by fishmeal with PBM, MBM, SBM and CSM, respectively, but not with CNM as the replacement with CNM reduced fish growth and feed utilization.

Expression, Characterization and Antimicrobial Ability of a Variant T4 Lysozyme in Pichia pastoris

T4 lysozyme was engineered with disulfide bonds and expressed in Pichia pastoris. The secreted proteins were purified and made into powder by lyophiliza-tion. Recombinant protein purity was more than 70% measured by HPLC. The lytic activity of variant T4-lysozyme was measured by the lysis of the cel wal of Xan-thomonas oryzae pv. oryzae, X. oryzae pv. oryzicola, Ralstonia solanacearum comb. nov, Clavibacter michiganensis subsp. michiganensis, X. campestris pv. mal-vacearum, Fusarium oxysporium sp. vasinfectum, Verticil ium dahliae kleb. Inhibition zone assay showed that variant T4 lysozyme significantly inhibited X. o. oryzicola and X. c. malvacearum. The antifungal activities of this protein against F. o. vasin-fectum and V. d. kleb were also analyzed.

Cutting-Edge FAK-targeting PROTACs:design,synthesis,and biological evaluation

Focal adhesion kinase(FAK)is an intracellular tyrosine kinase that plays a critical role in the occurrence,development,and metastasis of cancer through both its kinase-dependent catalytic functions and kinase-independent scaffolding functions.Current kinase inhibitors target only its catalytic activity,leaving the scaffolding functions unaffected.However,proteolysis targeting chimeras(PROTACs)offers a promising approach by degrading the entire FAK protein,thereby inhibiting both functions simultaneously.In this study,we designed and synthesized novel PROTAC degraders,utilizing a defactinib derivative(compound 12)as the FAK ligand and a lenalidomide analog as the E3 ligase ligand.The structures of these compounds were confirmed through^(1)H NMR,^(13)C NMR,and high-resolution mass spectrometry(HRMS).Among the synthesized compounds,the optimized compound 16b exhibited potent degradation activity against FAK protein in A549 cells,with a DC_(50)of 6.16±1.13 n M,significantly inhibiting the proliferation and colony formation of these cells.Compared to defactinib,16b showed enhanced inhibition of A549 cell migration and invasion.Furthermore,our research demonstrated that the rapid and effective FAK degradation induced by 16b was mediated by a CRBN-dependent proteasome mechanism.

全球医药快讯

脑中淀粉样蛋白斑成像药物Amyvid 近日,美国FDA批准Florbetapir F18注射剂（Amyvid）作为脑中淀粉样蛋白斑成像药物,用于疑似阿尔兹海默病（AD）或其他原因引起的认知功能衰退成年患者的大脑PET扫描。认知功能衰退是指个人无法正常思考、形成清晰理性的思维以及决定能力受到限制的情况。它会使患者失去与现实、自身、他人、外部事件以及环境的接触能力,