抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Background: Currently, a lack of consensus exists on how best to perform and interpret quantitative real-time PCR (qPCR) experiments. The problem is exacerbated by a lack of sufficient experimental detail in many publications, which impedes a reader’s ability to evaluate critically the quality of the results presented or to repeat the experiments.

Content: The Minimum Information for Publication of Quantitative Real-Time PCR Experiments (MIQE) guidelines target the reliability of results to help ensure the integrity of the scientific literature, promote consistency between laboratories, and increase experimental transparency. MIQE is a set of guidelines that describe the minimum information necessary for evaluating qPCR experiments. Included is a checklist to accompany the initial submission of a manuscript to the publisher. By providing all relevant experimental conditions and assay characteristics, reviewers can assess the validity of the protocols used. Full disclosure of all reagents, sequences, and analysis methods is necessary to enable other investigators to reproduce results. MIQE details should be published either in abbreviated form or as an online supplement.

Summary: Following these guidelines will encourage better experimental practice, allowing more reliable and unequivocal interpretation of qPCR results.

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The MIQE Guidelines: Minimum Information for Publication of Quantitative Real-Time PCR Experiments

World Health Organization Classification of Tumours

Pathology and genetics of tumors of soft tissue and bone

Pathology and genetics of tumours of the urinary system and male genital organs

Human myxoid liposarcomas contain a characteristic chromosomal translocation, t(12;16)(q13;p11), that is associated with a structural rearrangement of the gene encoding CHOP, a growth arrest and DNA-damage inducible member of the C/EBP family of transcription factors residing on 12q13.1. Using a CHOP-specific complementary probe and antiserum we report here the presence of an abnormal CHOP transcript and protein in these tumours. Cloning of the translocation-associated CHOP gene product revealed a fusion between CHOP and a gene provisionally named TLS (translocated in liposarcoma). TLS is a novel nuclear RNA-binding protein with extensive sequence similarity to EWS, the product of a gene commonly translocated in Ewing's sarcoma. In TLS-CHOP the RNA-binding domain of TLS is replaced by the DNA-binding and leucine zipper dimerization domain of CHOP. Targeting of a conserved effector domain of RNA-binding proteins to DNA may play a role in tumour formation.

Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma.

Recent studies of melanin biosynthesis have uncovered an unusual enzymatic activity which converts the non-naturally occurring D-isomer of 2-carboxy-2,3-dihydroindole-5,6-quinone (dopachrome) into 5,6-dihydroxyindole-2-carboxylic acid (DHICA). The aim of the present investigation was to isolate and characterize the enzyme catalyzing this tautomerization reaction. After we performed a tissue survey of D-dopachrome tautomerase activity, 10 bovine lenses were homogenized and used as a source of enzyme. A soluble fraction was obtained by high-speed centrifugation and subjected to successive FPLC chromatography on Phenyl-sepharose, Mono S cation-exchange, and Superdex gel-filtration. The isolated enzyme was electrophoresed, blotted onto PVDF membrane, and the N terminus analyzed by gas phase micro-sequencing. The protein catalyzing the conversion of D-dopachrome to DHICA was purified to homogeneity in 14% yield and showed a molecular weight of 12 kD when analyzed by SDS-PAGE. The first 27 amino acid residues of this protein were sequenced and found to be identical with those of bovine macrophage migration inhibitory factor (MIF). The catalytic activity of native MIF was confirmed by studies of purified recombinant human MIF, which showed the same tautomerase activity. While L-dopachrome was not a substrate for this reaction, the methyl esters of the L- and D-isomers were found to be better substrates for MIF than D-dopachrome. MIF has been described recently to be an anterior pituitary hormone and to be released from immune cells stimulated by low concentrations of glucocorticoids. Once secreted, MIF acts to control, or counter-regulate, the immunosuppressive effects of glucocorticoids on the immune system. Although the tested substrate, D-dopachrome, does not occur naturally, the observation that MIF has tautomerase activity suggests that MIF may mediate its biological effects by an enzymatic reaction. These data also offer a potential approach for the design of small molecule pharmacological inhibitors of MIF that may modulate its potent immunoregulatory effects in vivo.

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The immunoregulatory mediator macrophage migration inhibitory factor (MIF) catalyzes a tautomerization reaction.

FUS, EWS and TAF15 are structurally similar multifunctional proteins that were first discovered upon characterization of fusion oncogenes in human sarcomas and leukemias The proteins belong to the FET (previously TET) family of RNA-binding proteins and are implicated in central cellular processes such as regulation of gene expression, maintenance of genomic integrity and mRNA/microRNA processing In the present study, we investigated the expression and cellular localization of FET proteins in multiple human tissues and cell types FUS, EWS and TAF15 were expressed in both distinct and overlapping patterns in human tissues The three proteins showed almost ubiquitous nuclear expression and FUS and TAF15 were in addition present in the cytoplasm of most cell types Cytoplasmic EWS was more rarely detected and seen mainly in secretory cell types Furthermore, FET expression was downregulated in differentiating human embryonic stem cells, during induced differentiation of neuroblastoma cells and absent in terminally differentiated melanocytes and cardiac muscle cells The FET proteins were targeted to stress granules induced by heat shock and oxidative stress and FUS required its RNA-binding domain for this translocation Furthermore, FUS and TAF15 were detected in spreading initiation centers of adhering cells Our results point to cell-specific expression patterns and functions of the FET proteins rather than the housekeeping roles inferred from earlier studies The localization of FET proteins to stress granules suggests activities in translational regulation during stress conditions Roles in central processes such as stress response, translational control and adhesion may explain the FET proteins frequent involvement in human cancer

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The multifunctional FUS, EWS and TAF15 proto-oncoproteins show cell type-specific expression patterns and involvement in cell spreading and stress response

Most myxoid liposarcomas (MLS) are characterized cytogenetically by a t(12;16)(q13;p11) It is reasonable to assume that this translocation corresponds to the consistent rearrangement of one or two genes in 12q13 and/or 16p11, and that the loci thus affected are important in the normal control of fat cell differentiation and proliferation We have used Southern blot technique to test whether a gene of the CCAAT/enhancer binding protein (C/EBP) family, CHOP, which maps to 12q13 and is assumed to be involved in adipocyte differentiation, could be the 12q gene in question Using a cDNA probe that spans the CHOP coding region, we detected one rearranged and one wild type allele in nine of nine MLS with t(12;16) Using PCR generated, site-specific probes corresponding to the non-coding exons 1 and 2 and intron 2 of CHOP, rearrangements in five of seven tumors mapped to the 24 and 16 kbp PstI fragments that contain the first two exons and introns of the gene and the upstream promoter region In contrast to the findings in MLS, no tumor without a t(12;16) exhibited aberrant CHOP restriction digest patterns These tumors included one highly differentiated liposarcoma with abnormal karyotype but no involvement of 12q13, seven lipomas with various cytogenetic aberrations of 12q13-15, two uterine leiomyomas with t(12;14) (q14-15;q23-24), and one hemangiopericytoma and one chondroma, both of which also had 12q13 changes(ABSTRACT TRUNCATED AT 250 WORDS)

Rearrangement of the transcription factor gene CHOP in myxoid liposarcomas with t(12;16)(q13;p11).

The translocation t(12;16)(q13;p11), which cytogenetically characterizes myxoid liposarcomas (MLS), results in a fusion of the CHOP gene in 12q13 and the FUS gene in 16p11, creating a chimeric FUS/CHOP gene. We have identified two cases of MLS with translocations giving rise to recombination between 12q13 and 22q12. The result was a fusion of the N-terminal part of the EWS gene in 22q12, involved in a number of mesenchymal tumor types, with the CHOP gene and the creation of an EWS/CHOP chimeric gene. The presence of the EWS/CHOP chimeric gene in MLS shows that (i) the N-terminal part of FUS may be replaced by the N-terminal part of EWS in a CHOP fusion oncoprotein (ii) the two N-terminal parts, when fused to certain transcription factors, have a common or very similar oncogenic potential and (iii) the tumorigenic process in MLS and the morphogenetically distinctly different EWS-associated tumor types may be related.

Pierre Åman

Papers

Fusion of CHOP to a novel RNA-binding protein in human myxoid liposarcoma.

The immunoregulatory mediator macrophage migration inhibitory factor (MIF) catalyzes a tautomerization reaction.

The multifunctional FUS, EWS and TAF15 proto-oncoproteins show cell type-specific expression patterns and involvement in cell spreading and stress response

Rearrangement of the transcription factor gene CHOP in myxoid liposarcomas with t(12;16)(q13;p11).

Fusion of the EWS and CHOP genes in myxoid liposarcoma.