HTLV-I trans-activator protein, tax, is a trans-repressor of the human beta-polymerase gene

Human T cell leukemia virus type I (HTLV-I) is the etiological agent for adult T cell leukemia (ATL). The HTLV-I trans-activator protein Tax can activate the expression of its own long terminal repeat (LTR) and many cellular and viral genes. Tax down-regulated the expression of human beta-polymerase (hu beta-pol), a cellular enzyme involved in host cell DNA repair. This finding suggests a possible correlation between HTLV-I infection and host chromosomal damage, which is often seen in ATL cells.     

Deconstructing myotonic dystrophy

Triplet repeat diseases are disorders in which there is expansion of a repeat sequence of three nucleotides in the affected gene. Although the pathology usually results from production of a defective protein, myotonic dystrophy (DM) has proved to be a puzzle because the expanded repeats appear in a non-coding region of the affected DMPK gene. In a Perspective, Tapscott explains how findings from a new mouse model of DM (Mankodi et al.) could solve this paradox.     

Cladosporium Avr2 inhibits tomato Rcr3 protease required for Cf-2-dependent disease resistance

How plants recognize pathogens and activate defense is still mysterious. Direct interaction between pathogen avirulence (Avr) proteins and plant disease resistance proteins is the exception rather than the rule. During infection, Cladosporium fulvum secretes Avr2 protein into the apoplast of tomato leaves and, in the presence of the extracellular leucine-rich repeat receptor-like Cf-2 protein, triggers a hypersensitive response (HR) that also requires the extracellular tomato cysteine protease Rcr3. We show here that Avr2 binds and inhibits Rcr3 and propose that the Rcr3-Avr2 complex enables the Cf-2 protein to activate an HR.     

Circumsporozoite protein heterogeneity in the human malaria parasite Plasmodium vivax

Phenotypic heterogeneity in the repetitive portion of a human malaria circumsporozoite (CS) protein, a major target of candidate vaccines, has been found. Over 14% of clinical cases of uncomplicated Plasmodium vivax malaria at two sites in western Thailand produced sporozoites immunologically distinct from previously characterized examples of the species. Monoclonal antibodies to the CS protein of other P. vivax isolates and to other species of human and simian malarias did not bind to these nonreactive sporozoites, nor did antibodies from monkeys immunized with a candidate vaccine made from the repeat portion of a New World CS protein. The section of the CS protein gene between the conserved regions I and II of a nonreactive isolate contained a nonapeptide repeat, Ala-Asn-Gly-Ala-Gly-Asn-Gln-Pro-Gly, identical at only three amino acid positions with published nonapeptide sequences. This heterogeneity implies that a P. vivax vaccine based on the CS protein repeat of one isolate will not be universally protective.     

A transgenic mouse model for human neurofibromatosis

Human T-lymphotropic virus type 1 (HTLV-1) has been associated with the neurologic disorder tropical spastic paraparesis and possibly with multiple sclerosis. The tat gene of HTLV-1 under control of its own long terminal repeat is capable of inducing tumors in transgenic mice. The morphologic and biologic properties of these tumors indicate their close resemblance to human neurofibromatosis (von Recklinghausen's disease), the most common single gene disorder to affect the nervous system. The high spontaneous incidence of this disease, together with the diverse clinical and pathologic features associated with it, suggests that environmental factors may account for some of the observed cases. Multiple tumors developed simultaneously in the transgenic tat mice at approximately 3 months of age, and the phenotype was successfully passed through three generations. The tumors arise from the nerve sheaths of peripheral nerves and are composed of perineural cells and fibroblasts. Tumor cells from these mice adapt easily to propagation in culture and continue to express the tat protein in significant amounts. When transplanted into nude mice, these cultured cells efficiently induce tumors. Evidence of HTLV-1 infection in patients with neural and other soft tissue tumors is needed in order to establish a link between infection by this human retrovirus and von Recklinghausen's disease and other nonlymphoid tumors.     

Expanded repeat in canine epilepsy

Epilepsy afflicts 1% of humans and 5% of dogs. We report a canine epilepsy mutation and evidence for the existence of repeat-expansion disease outside humans. A canid-specific unstable dodecamer repeat in the Epm2b (Nhlrc1) gene recurrently expands, causing a fatal epilepsy and contributing to the high incidence of canine epilepsy. Tracing the repeat origins revealed two successive events, starting 50 million years ago, unique to canid evolution. A genetic test, presented here, will allow carrier and presymptomatic diagnosis and disease eradication. Clinicopathologic characterization establishes affected animals as a model for Lafora disease, the most severe teenage-onset human epilepsy.     

Exercise and genetic rescue of SCA1 via the transcriptional repressor Capicua

Spinocerebellar ataxia type 1 (SCA1) is a fatal neurodegenerative disease caused by expansion of a translated CAG repeat in Ataxin-1 (ATXN1). To determine the long-term effects of exercise, we implemented a mild exercise regimen in a mouse model of SCA1 and found a considerable improvement in survival accompanied by up-regulation of epidermal growth factor and consequential down-regulation of Capicua, which is an ATXN1 interactor. Offspring of Capicua mutant mice bred to SCA1 mice showed significant improvement of all disease phenotypes. Although polyglutamine-expanded Atxn1 caused some loss of Capicua function, further reduction of Capicua levels--either genetically or by exercise--mitigated the disease phenotypes by dampening the toxic gain of function. Thus, exercise might have long-term beneficial effects in other ataxias and neurodegenerative diseases.     

The Structure and Sequence Analysis of TLR4 Gene in Cattle

Toll-like receptor 4 （TLR4） is essential for initiating the innate response to lipopolysaccharide （LPS） from Gram-negative bacteria by acting as a signal transducting receptor. In order to help in investigating TLR4 as a candidate disease-resistance gene in cows, we isolated the cDNA （GenBank accession no. DQ839566） by RT-PCR and rapid amplification of cDNA ends （RACE） experiments and analyzed the sequence characters by bioinformatics. The results showed that cattle TLR4 gene about 3 739 bp contains an open reading frame of 2 526 bp encoded 841 amino acids （aa）, 470 bp 5′ untranslated region （UTR）, and 743 bp 3′ UTR. Tissue expression profile by RT-PCR indicated that TLR4 gene expresses in mammary glands, liver, muscle, duodenum, fats, uterus, kidneys, hearts, lungs, pancreas, and ovary. TLR4 protein domain predicted by bioinformatics consists of signal peptide, transmembrane helices domain, 3 sorts of leucine-rich repeat domains （LRR, LRR-TYP, and LRRCT）, and a toll-interleukinl-resistance domain （TIR）. Leucine-rich repeat domains were related with recognizing a broad of pathogen-associated molecular patterns （PAMP） from pathogen, and TIR domain for downstream signaling transduction was most conservative （98% identify） than other domains after alignment of protein from ovine, porcine, human, and mouse. In addition, a 470 bp 5′-flanking region sequence was amplified by PCR, and 15 putative DNA binding sites were predicted, but this sequence lacks TATA box, CCAAT character, and GC-rich regions.     

erbB-2 is a potent oncogene when overexpressed in NIH/3T3 cells

A wide variety of human tumors contain an amplified or overexpressed erbB-2 gene, which encodes a growth factor receptor-like protein. When erbB-2 complementary DNA was expressed in NIH/3T3 cells under the control of the SV40 promoter, the gene lacked transforming activity despite expression of detectable levels of the erbB-2 protein. A further five- to tenfold increase in its expression under influence of the long terminal repeat of Moloney murine leukemia virus was associated with activation of erbB-2 as a potent oncogene. The high levels of the erbB-2 product associated with malignant transformation of NIH/3T3 cells were observed in human mammary tumor cells that overexpressed this gene. These findings demonstrate a new mechanism for acquisition of oncogenic properties by genes encoding growth factor receptor-like proteins and provide a functional basis for the role of their overexpression in the development of human malignancies.     

Recent segmental duplications in the human genome

Primate-specific segmental duplications are considered important in human disease and evolution. The inability to distinguish between allelic and duplication sequence overlap has hampered their characterization as well as assembly and annotation of our genome. We developed a method whereby each public sequence is analyzed at the clone level for overrepresentation within a whole-genome shotgun sequence. This test has the ability to detect duplications larger than 15 kilobases irrespective of copy number, location, or high sequence similarity. We mapped 169 large regions flanked by highly similar duplications. Twenty-four of these hot spots of genomic instability have been associated with genetic disease. Our analysis indicates a highly nonrandom chromosomal and genic distribution of recent segmental duplications, with a likely role in expanding protein diversity.     

GBP5 promotes NLRP3 inflammasome assembly and immunity in mammals

Inflammasomes are sensory complexes that alert the immune system to the presence of infection or tissue damage. These complexes assemble NLR (nucleotide binding and oligomerization, leucine-rich repeat) or ALR (absent in melanoma 2-like receptor) proteins to activate caspase-1 cleavage and interleukin (IL)-1β/IL-18 secretion. Here, we identified a non-NLR/ALR human protein that stimulates inflammasome assembly: guanylate binding protein 5 (GBP5). GBP5 promoted selective NLRP3 inflammasome responses to pathogenic bacteria and soluble but not crystalline inflammasome priming agents. Generation of Gbp5(-/-) mice revealed pronounced caspase-1 and IL-1β/IL-18 cleavage defects in vitro and impaired host defense and Nlrp3-dependent inflammatory responses in vivo. Thus, GBP5 serves as a unique rheostat for NLRP3 inflammasome activation and extends our understanding of the inflammasome complex beyond its core machinery.     

非小细胞肺癌中MAGE-3蛋白的Western Blot分析

目的：观察黑素瘤抗原-3(MAGE-3)蛋白在非小细胞肺癌(NSCLC)中的表达。方法：用Western blot方法对3种人肺癌细胞系和56例NSCLC标本及相邻正常肺组织标本MAGE-3蛋白的表达情况进行研究。结果：3种人肺癌细胞系均表达MAGE-3蛋白;56例NSCLC标本中,28你表达MAGE-3蛋白,而相邻正常肺组织均不表达MAGE-3蛋白。结论：MAGE-3蛋白在NSCLC中有较高比率的表达．有望以该抗原作为适宜靶点对NSCLC患者进行免疫治疗。     

Aneuploidy drives genomic instability in yeast

Aneuploidy decreases cellular fitness, yet it is also associated with cancer, a disease of enhanced proliferative capacity. To investigate one mechanism by which aneuploidy could contribute to tumorigenesis, we examined the effects of aneuploidy on genomic stability. We analyzed 13 budding yeast strains that carry extra copies of single chromosomes and found that all aneuploid strains exhibited one or more forms of genomic instability. Most strains displayed increased chromosome loss and mitotic recombination, as well as defective DNA damage repair. Aneuploid fission yeast strains also exhibited defects in mitotic recombination. Aneuploidy-induced genomic instability could facilitate the development of genetic alterations that drive malignant growth in cancer.     

参与植物防御反应的LRR型蛋白结构与功能

植物含有多种富含亮氨酸重复（LRRs）结构的蛋白质,它们在植物生长、发育和抗病反应等方面发挥着重要作用。综述了这类具有LRRs结构蛋白质家族的结构特征及其参与植物防御反应的功能。参与植物防御反应LRR型蛋白质家族包括：抗病基因编码蛋白质、类受体蛋白激酶、多聚半乳糖醛酸酶抑制蛋白和伸展蛋白家族。这四大蛋白质家族成员主要通过LRRs结构识别并结合病原物蛋白质,参与抗病信号传递,诱导植物防卫基因的表达,使植物获得系统抗性。其中LRRs序列中氨基酸的不同和单位重复数目的差异决定了蛋白识别的特异性和结合能力。