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During meiosis, cohesins--protein complexes that hold sister chromatids together--are lost from chromosomes in a step-wise manner. Loss of cohesins from chromosome arms is necessary for homologous chromosomes to segregate during meiosis I. Retention of cohesins around centromeres until meiosis II is required for the accurate segregation of sister chromatids. Here we show that phosphorylation of the cohesin subunit Rec8 contributes to step-wise cohesin removal. Our data further implicate two other key regulators of meiotic chromosome segregation, the cohesin protector Sgo1 and meiotic recombination in bringing about the step-wise loss of cohesins and thus the establishment of the meiotic chromosome segregation pattern. Understanding the interplay between these processes should provide insight into the events underlying meiotic chromosome mis-segregation, the leading cause of miscarriages and mental retardation in humans. 相似文献
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Matsushita H Vesely MD Koboldt DC Rickert CG Uppaluri R Magrini VJ Arthur CD White JM Chen YS Shea LK Hundal J Wendl MC Demeter R Wylie T Allison JP Smyth MJ Old LJ Mardis ER Schreiber RD 《Nature》2012,482(7385):400-404
Cancer immunoediting, the process by which the immune system controls tumour outgrowth and shapes tumour immunogenicity, is comprised of three phases: elimination, equilibrium and escape. Although many immune components that participate in this process are known, its underlying mechanisms remain poorly defined. A central tenet of cancer immunoediting is that T-cell recognition of tumour antigens drives the immunological destruction or sculpting of a developing cancer. However, our current understanding of tumour antigens comes largely from analyses of cancers that develop in immunocompetent hosts and thus may have already been edited. Little is known about the antigens expressed in nascent tumour cells, whether they are sufficient to induce protective antitumour immune responses or whether their expression is modulated by the immune system. Here, using massively parallel sequencing, we characterize expressed mutations in highly immunogenic methylcholanthrene-induced sarcomas derived from immunodeficient Rag2(-/-) mice that phenotypically resemble nascent primary tumour cells. Using class I prediction algorithms, we identify mutant spectrin-β2 as a potential rejection antigen of the d42m1 sarcoma and validate this prediction by conventional antigen expression cloning and detection. We also demonstrate that cancer immunoediting of d42m1 occurs via a T-cell-dependent immunoselection process that promotes outgrowth of pre-existing tumour cell clones lacking highly antigenic mutant spectrin-β2 and other potential strong antigens. These results demonstrate that the strong immunogenicity of an unedited tumour can be ascribed to expression of highly antigenic mutant proteins and show that outgrowth of tumour cells that lack these strong antigens via a T-cell-dependent immunoselection process represents one mechanism of cancer immunoediting. 相似文献
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Manske M Miotto O Campino S Auburn S Almagro-Garcia J Maslen G O'Brien J Djimde A Doumbo O Zongo I Ouedraogo JB Michon P Mueller I Siba P Nzila A Borrmann S Kiara SM Marsh K Jiang H Su XZ Amaratunga C Fairhurst R Socheat D Nosten F Imwong M White NJ Sanders M Anastasi E Alcock D Drury E Oyola S Quail MA Turner DJ Ruano-Rubio V Jyothi D Amenga-Etego L Hubbart C Jeffreys A Rowlands K Sutherland C Roper C Mangano V Modiano D Tan JC Ferdig MT Amambua-Ngwa A Conway DJ Takala-Harrison S Plowe CV 《Nature》2012,487(7407):375-379
Malaria elimination strategies require surveillance of the parasite population for genetic changes that demand a public health response, such as new forms of drug resistance. Here we describe methods for the large-scale analysis of genetic variation in Plasmodium falciparum by deep sequencing of parasite DNA obtained from the blood of patients with malaria, either directly or after short-term culture. Analysis of 86,158 exonic single nucleotide polymorphisms that passed genotyping quality control in 227 samples from Africa, Asia and Oceania provides genome-wide estimates of allele frequency distribution, population structure and linkage disequilibrium. By comparing the genetic diversity of individual infections with that of the local parasite population, we derive a metric of within-host diversity that is related to the level of inbreeding in the population. An open-access web application has been established for the exploration of regional differences in allele frequency and of highly differentiated loci in the P.?falciparum genome. 相似文献
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利用美国A632,B37,B73,B68,C103,Va26等30个Ht单基因鉴别寄主, 按美国伊利诺伊大学的大田接种方案与鉴定方法, 建立了适合中国的监测玉米
大斑病菌生理小种鉴定的21个Ht单基因系. 从吉林省15个地区的不同玉米品种中采集玉米大斑病样本, 采用单孢分离获得了32个玉米大斑病菌菌株, 利用已建立的上述21个Ht单基因鉴别寄主, 通过美国的大田鉴定方案进行生理小种鉴定. 结果表明, 这32个菌株均为0号小种, 并未出现生理小种分化现象. 相似文献
大斑病菌生理小种鉴定的21个Ht单基因系. 从吉林省15个地区的不同玉米品种中采集玉米大斑病样本, 采用单孢分离获得了32个玉米大斑病菌菌株, 利用已建立的上述21个Ht单基因鉴别寄主, 通过美国的大田鉴定方案进行生理小种鉴定. 结果表明, 这32个菌株均为0号小种, 并未出现生理小种分化现象. 相似文献
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INTRODUCTIONDuring the past few years, the use of recycled fiber has increased dramatically due to the shortage of fiber resources and restrictive environmental regulations on paper landfills. Since the successful application of flotation in the paper recycling industry from the minerals industry in 1980s, flotation deinking has become a necessary process for ink removal from wastepaper in many paper recycling mills. The deinking chemistry and the physicochemical interactions among air bub… 相似文献
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