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國立彰化師範大學九十四學年度碩士班招生考試試題 系所:生物技術研究所 科目: 專業英文 ☆☆請在答案紙上作答☆☆ 共 10 頁,第 1 頁 閱讀測驗,單選題,每題 3.3 分。作答時請註明題號。 A. Bird Flu The World Health Organization (WHO) has said it's taking the rapid spread of a deadly new strain of bird flu, H5N1, very seriously. It has warned there's definitely potential for a serious human outbreak. This follows confirmed outbreaks in Thailand, South Korea, Cambodia, Japan and Vietnam. The list of countries known to have the relatively new and deadly strain of bird flu is rapidly growing. The focus now is on Indonesia where tests will soon confirm whether or not the bird flu which killed several million chickens there is the often fatal H5N1, already confirmed in 5 other countries in the region. Reports of an outbreak in Laos are also being investigated. WHO confirmed this fatal virus was clearly spreading and was causing serious concern. As new information was emerging, it was becoming clear that the strain had been around in the region much longer than first thought. That multiplied the risk of human infections, and of the virus mutating, perhaps by attaching itself to human flu, and becoming far more deadly. So far seven people have died, six of them in Vietnam, after being infected with the strain. But so far there's no evidence of direct human to human transmission. Were that to happen, the death rate amongst people could multiply dramatically. This new strain first appeared in Hong Kong in 1997. Scientists then went on to create a prototype vaccine but that's now become redundant because the virus has since mutated. Between 10 and 20 million chickens across the region have died or been killed in an attempt to stop the spread of the virus. 1) The focus of this article is: a) the importance of the WHO in curing the bird flu b) possible explanations for how this bird flu became fatal and spreading c) the new vaccine for the bird flu is affective d) all of the above e) none of the above -1- 國立彰化師範大學九十四學年度碩士班招生考試試題 系所:生物技術研究所 科目: 專業英文 ☆☆請在答案紙上作答☆☆ 共 10 頁,第 2 頁 2) What does “outbreak” means in this essay: a) To bring into existence. b) An end result c) A sudden increase d) emergent 3. Which statement is not true: a) the death rate amongst people is increasing because of the human to human transmission b) H5N1 has been reported in Thailand, South Korea, Cambodia, Japan, Vietnam and Laos c) H5N1 first appeared in Hong Kong in 1997 d) Tests were done in Indonesia and Laos for investigating possible H5N1 infection 4. This fatal bird flu may increase the risk of human infections by: a) the strain had been around in the region much longer than first thought b) the virus is mutating c) human to human transmission d) “a” and “b” e) All of the above 5. What is a “Prototype” vaccine? a) An original type b) a recombinant type c) a fusion protein type d) vaccine with attenuated virus ------------------------------------------------------------------------------------------------------- B. Biallelic Inactivation of BRCA2 in Fanconi Anemia Fanconi anemia (FA) is a rare autosomal recessive cancer susceptibility disorder characterized by cellular hypersensitivity to mitomycin C (MMC). Six FA genes have been cloned, but the gene or genes corresponding to FA subtypes B and D1 remain unidentified. Here we show that cell lines derived from FA-B1 and FA-D1 patients have biallelic mutations in BRCA2 and express truncated BRCA2 proteins. Functional complementation of FA-D1 fibroblasts with -2- 國立彰化師範大學九十四學年度碩士班招生考試試題 系所:生物技術研究所 科目: 專業英文 ☆☆請在答案紙上作答☆☆ 共 10 頁,第 3 頁 wild-type BRCA2 complementary DNA restores MMC resistance. Our results link the six cloned FA genes with BRCA1 and BRCA2 in a common pathway. Germ-line mutation of genes in this pathway may result in cancer risks similar to those observed in families with BRCA1 or BRCA2 mutations. 6. 7. 8. 9. The focus of this article is: a) BRCA2 causes breast cancer b) FA-D1 has biallelic mutations in MMC c) Two defective copies of the BRCA2 can lead to FA d) MMC gene is inactivated in FA patients What does “complementation ” means in this abstract: a) Interaction between two genetic units b) Make up for the genetic defect c) Having come to an end d) To create by putting two genes together Which statement is not true for FA: a) FA may lead to cancer development b) Cell lines derived from FA-B1 and FA-D1 patients have similar genotype c) FA is sensitive to MMC d) Truncated BRCA2 proteins were found in all FA patients e) “b” and “d” f) ”a” and ”d” Which statement is true: a) FA patient with BRCA2 gene mutation have the same cancer risk as those with BRCA2 and BRCA1 mutation b) FA is an inherited genetics disorder caused by BRCA2 gene solely c) FA-B1 and FA-D1 cell lines are from patients’ leukocytes d) Inactivation of BRCA2 is due to hypermethylation 10. What is “Germ-line mutation”? a) a somatic mutation b) a mutation in gametes c) a rare mutation -3- 國立彰化師範大學九十四學年度碩士班招生考試試題 系所:生物技術研究所 科目: 專業英文 ☆☆請在答案紙上作答☆☆ 共 10 頁,第 4 頁 d) a polymorphism ----------------------------------------------------------------------------------------------------- C. Cell Polarity in Bacteria The bacterium Caulobacter crescentus is particularly well suited to studies of cell polarity because of its inherently asymmetric life cycle that yields, at each cell division, progeny that have different polar morphologies and cell fates. The larger ‘‘stalked’’ cell progeny has a cytoplasmic extension known as a stalk at one pole, and the smaller ‘‘swarmer’’ cell progeny has a flagellum and pili at one pole. Immediately after cell division, the stalked cell initiates DNA replication, grows, and synthesizes a flagellum and a pilus secretion apparatus at the pole opposite the stalk before dividing asymmetrically. After emerging from a brief G1 arrest, the swarmer cell sheds its flagellum and pili, develops a stalk at that same pole, and initiates DNA replication. This new stalked cell then proceeds through the same asymmetric life cycle as other stalked cells. The stalk is clearly identifiable by light microscopy, making it easy to monitor Caulobacter polarity throughout the cell cycle. In addition, several structural and regulatory proteins as well as the origin of replication have been shown to dynamically localize to the stalked pole, the swarmer pole, or both poles during the cell cycle. These proteins and chromosomal regions serve as molecular markers of cell polarity. Subcellularly localized molecules are not unique to Caulobacter. For example, chemoreceptors, histidine kinases, response regulators, and several chromosomal loci have specific addresses in a wide variety of bacteria, including those without obvious morphological asymmetry. In addition, virtually every eukaryotic cell has subcellularly localized proteins, such as secretory molecules localized to the bud tip in yeast and neurotransmitter receptors localized to neuronal synapses. 11. Which of the following objects is most similar in shape to a “stalked cell”? a) a champagne bottle b) a beaker c) a graduated cylinder d) a Petri dish 12. Which of the following adjectives best describes the life cycle of C. crescentus? a) monotonous -4- 國立彰化師範大學九十四學年度碩士班招生考試試題 系所:生物技術研究所 科目: 專業英文 ☆☆請在答案紙上作答☆☆ 共 10 頁,第 5 頁 b) biphasic c) localized d) asymmetric. 13. Which of the following statements concerning cell polarity is not true? a) The idea of cell polarity does not apply to cells with symmetrical shapes. b) C. crescentus is a good model organism for studying cell polarity. c) Yeast cells are polarized during cell division. d) Cell polarity determines the subcellular location of DNA replication in some organisms. 14. The flagellum of C. crescentus a) grows on the tip of a stalk b) is replaced by a stalk after each cell division c) is the origin of replication for chromosome d) does not appear on a stalked cell 15. According the above passage , neurotransmitter receptors share which of the following properties with flagella of C. crescentus? a) b) c) d) being synthesized only after the G1 phase being made up of multiple subunits appearing on specific locations on the cell surface playing critical roles in signal transduction and cell motility ------------------------------------------------------------------------------------------------------- D. Substrates and Physiological Roles of the E. coli GroE Chaperone The GroES and GroEL proteins comprise one of the major molecular chaperone systems of the E. coli cell. The two genes are highly conserved in all bacteria. The GroE chaperone system has been postulated to have several functions in the cell, but most study to date has focused on its role in protein folding. In vitro, GroES and GroEL can mediate the folding of many proteins which would otherwise become aggregated or misfolded when refolding from the denatured state. This reaction generally requires the binding and often the hydrolysis of ATP. The mechanism involves repeated rounds of binding and release of unfolded or partially folded substrate protein to the GroEL, and the eventual release of protein in a form which is competent to fold without aggregation. The precise role of the GroES and GroEL proteins in the bacterial -5- 國立彰化師範大學九十四學年度碩士班招生考試試題 系所:生物技術研究所 科目: 專業英文 ☆☆請在答案紙上作答☆☆ 共 10 頁,第 6 頁 cell remains to be fully defined. Both are strongly induced by heat shock, and are essential at all temperatures. Experiments with groEL ts mutants show that at the non-permissive temperature, several model substrate proteins fail to fold correctly and the general protein profile of proteins in the cell is substantially altered. Lowering the levels of GroEL in the cell causes induction of the stress response, although cells are quite tolerant, at normal growth temperatures, to significant decreases in GroEL levels. Although in vitro experiments show that approximately 50% of E. coli proteins can bind to GroEL, the actual in vivo substrates are not known. Some studies have suggested that GroEL may have other roles in the cell, including an involvement with protein transport across the inner membrane, and an effect on mRNA stability 16. According to the above passage, GroEL is a) present in all bacterial cells b) nonfunctional at high temperatures c) the key component of the only chaperone in E. coli d) not needed for cell survival at normal growth temperatures. 17. Which of the followings is not a natural substrate for GroE? a) misfolded protein b) unfolded protein c) correctly folded protein d) partially folded protein. 18. The term “ general protein profile” refers to a) the amount of model substrate proteins in the cytoplasm b) the entire complement of cytoplasmic proteins c) the variety of denatured proteins in the cytoplasm d) the ensemble of chaperone systems in the cytoplasm. 19. The statement “Although in vitro experiments show that approximately 50% of E. coli proteins can bind to GroEL, the actual in vivo substrates are not known.” implies that a) we need to know about the other 50% of E. coli proteins in order to determine the real substrates for GroEL b) the results of in vitro experiments are useless for identifying the in vivo substrates of GroEL c) GroEL must first bind with its substrate in order to function as a chaperone -6- 國立彰化師範大學九十四學年度碩士班招生考試試題 系所:生物技術研究所 科目: 專業英文 ☆☆請在答案紙上作答☆☆ 共 10 頁,第 7 頁 d) in E. coli cells half of the GroEL molecules are associated with irrelevant proteins 20. According to this passage, protein released from GroE chaperone is a) folded properly b) ready to fold c) aggregated with each other d) misfolded. ------------------------------------------------------------------------------------------------- E. Enhancement of Cardiac Function and Suppression of Heart Failure Progression By Inhibition of Protein Phosphatase 1 Abnormal calcium cycling, characteristic of experimental and human heart failure, is associated with impaired sarcoplasmic reticulum calcium uptake activity. This reflects decreases in the cAMP-pathway signaling and increases in type 1 phosphatase activity. The increased protein phosphatase 1 activity is partially due to dephosphorylation and inactivation of its inhibitor-1, promoting dephosphorylation of phospholamban and inhibition of the sarcoplasmic reticulum calcium-pump. Indeed, cardiac-specific expression of a constitutively active inhibitor-1 results in selective enhancement of phospholamban phosphorylation and augmented cardiac contractility at the cellular and intact animal levels. Furthermore, the -adrenergic response is enhanced in the transgenic hearts compared with wild types. On aortic constriction, the hypercontractile cardiac function is maintained, hypertrophy is attenuated and there is no decompensation in the transgenics compared with wild-type controls. Notably, acute adenoviral gene delivery of the active inhibitor-1, completely restores function and partially reverses remodeling, including normalization of the hyperactivated p38, in the setting of pre-existing heart failure. Thus, the inhibitor 1 of the type 1 phosphatase may represent an attractive new therapeutic target. 21. The action of active (phosphorylated) inhibitor-1 leads to a) inactivation of cAMP-dependent protein kinase b) increased protein phosphatase 1 activity c) dephosphorylation of phospholamban d) activation of calcium uptake activity -7- 國立彰化師範大學九十四學年度碩士班招生考試試題 系所:生物技術研究所 科目: 專業英文 ☆☆請在答案紙上作答☆☆ 共 10 頁,第 8 頁 e) heart failure 22. A drug that directly increases sarcoplasmic reticulum calcium-pump activity would mostly likely a) causes heart failure b) enhances cardiac contractility c) inhibits inhibitor-1 activity d) decreases protein phosphatase 1 activity e) increases phosphorylation of phospholamban 23. When compared to a wild type heart, a transgenic heart a) is less hypertrophic b) has a lower calcium uptake activity c) exhibits a lower cardiac contractility d) has a lower response to stimulation of b-adrenergic receptor e) is more decompensated 24. Which of the following molecules is an ideal site of action for a drug intended for preventing heart failure a) inhibitor-1 b) protein phosphatase 1 c) phospholamban d) sarcoplasmic reticulum calcium-pump e) cAMP-dependent protein kinase 25. The abnormal calcium cycling mentioned above is mostly due to a) an elevated calcium channel function b) a decreased calcium channel function c) an elevated calcium pump function d) a decreased calcium pump function e) none of the above -------------------------------------------------------------------------------------------------- F. Cytokines differentially regulate the synthesis of prostanoid and nitric oxide mediators in tumorigenic vs. non-tumorigenic mouse lung epithelial cell lines -8- 國立彰化師範大學九十四學年度碩士班招生考試試題 系所:生物技術研究所 科目: 專業英文 ☆☆請在答案紙上作答☆☆ 共 10 頁,第 9 頁 Studies using transgenic and knockout mice have demonstrated that particular cytokines influence lung tumor growth and identified prostaglandin E2 (PGE2), prostacyclin (PGI2), and nitric oxide (NO) as critical mediators of this process. PGE2 and NO were pro-tumorigenic while PGI2 was anti-tumorigenic. We describe herein an in vitro experimental approach to examine interactions among cytokines, prostaglandins (PGs), and NO. PGE2, PGI2, and NO levels were assayed in culture media from non-tumorigenic mouse lung epithelial cell lines, their spontaneous transformants, and mouse lung tumor-derived cell lines, before or after exposure to the cytokines TNF, IFN, and IL1, alone and in combination. More PGE2 than PGI2 was produced by neoplastic cells, while the opposite was observed in non-tumorigenic lines. Cytokine exposure magnified the extent of these differential concentrations. The PGE2/PGI2 ratio was also greater in chemically-induced mouse lung tumors than in adjacent tissue or control lungs, supporting the physiological relevance of this in vitro model. Expression of PG biosynthetic enzymes in these cell lines correlated with production of the corresponding prostaglandins. Cytokine treatment enhanced NO production by inducing the inflammation-associated biosynthetic enzyme, inducible NO synthase (iNOS), but this did not correlate with the neoplastic status of cells. Inhibition of iNOS or cyclooxygenase 2 (COX-2) activity using aminoguanidine or NS-398 respectively, demonstrated that NO did not affect PG production nor did PGs influence NO production. Since lack of iNOS inhibits mouse lung tumor formation, we propose that this is independent of any modulation of PG synthesis in epithelial cells. The similar normal/neoplastic trends in PGE2/PGI2 ratios in vitro and in vivo, together with an amplification of this difference upon cytokine exposure, are consistent with the hypothesis that cytokines released during inflammation exacerbate differences in the behavior of neoplastic and normal lung cells. 26. Which of the following molecules is a cytokine a) PGE2 b) aminoguanidine c) IFN d) COX-2 e) NS-398 27. The PGE2/PGI2 ratio is -9- 國立彰化師範大學九十四學年度碩士班招生考試試題 系所:生物技術研究所 科目: 專業英文 ☆☆請在答案紙上作答☆☆ a) b) c) d) 共 10 頁,第 10 頁 lower in non-tumorigenic cells than in neoplastic cells higher in non-tumorigenic cells than in neoplastic cells increased by cytokine treatment in non-tumorigenic cells decreased by NO treatment 28. Cytokine treatment a) has no effect on the PGE2/PGI2 ratio in neoplastic cells b) increases the PGE2/PGI2 ratio in neoplastic cells c) depresses iNOS expression d) decreases NO production 29. The observation that the PGE2/PGI2 ratio is correlated with the neoplastic status of cells was demonstrated a) both in vitro and in vivo b) only in vitro c) only in vivo d) neither in vitro nor in vivo 30. Which of the following statements is true a) iNOS is the enzyme that catalyzes formation of prostaglandins (PGs) b) overexpression of iNOS is pro-tumorigenic c) NO increases PG production in epithelial cells d) PG decreases NO production in epithelial cells -10-