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Examples of selectivity of mRNA export Evidence is accumulating that mRNA export in mam mals can be selective, although it remains possible that a large proportion of mRNAs are exported by bulk export pathways. Diverse biological processes, including throu DNA repair, maintenance of pluripotency, gene expres- and ion, stress responses, cell proliferation, cell survival and haematopoiesis 4-22 can be regulated by selective mRNA export and, in most of these cases, although not all, selectivity is mediated by components of the TREx and TREX-2 complexes.



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    Nuclear export of mRNAs is a crucial step in the regulation of gene expression, linking transcription in the nucleus to translation in the cytoplasm. Although important components of the mRNA export machinery are well characterized, such as transcription-export complexes TREX and TREX-2, recent work has shown that, in some instances, mammalian mRNA export can be selective and can regulate crucial biological processes such as DNA repair, gene expression, maintenance of pluripotency, haematopoiesis, proliferation and cell survival. Such findings show that mRNA export is an unexpected, yet potentially important, mechanism for the control of gene expression and of the mammalian transcriptome.

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    1. although the transcripts that it exports are unknown. 2. suggesting that competition with the bulk mRNA export pathway for specific class of mRNA may be one mechanism by which cells can respond efficiently to extracellular stimuli.

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    although most mRNAs use TREX, TREX-2 and NXF1 receptors to transit through NPCs, a subset of mRNAs use CRM1, the major protein-export receptor.

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    1. this raises the possibility that GANP (and hence TREX-2) mediates a priority fast-track export route for transcripts that control cell behavior, presumably facilitating rapid adaptation to changing cellular environment.

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    Each ten years, the government conducts a national census, which is authorized by the Constitution. Most of us do not object to answering the questions that the census poses, but what if you should decide to refuse to answer the questions? Could you do so on the basis that they represent an invasion of your privacy? This has been answered by the courts, which hold that it is a proper government function and a necessary one to gather reliable statistics that have a bearing on governmental functions, and that intelligent legislation can only be formulated if the government has the facts. It is probable that people answer the census questions because they believe their answers will be kept confidential and that the information will not be used to hurt them. Census answers cannot be utilized by parties in a lawsuit and used without the consent of the party giving the answers. However, general statistics can be used, and the statistics gathered in the census have been used, for the good of all.

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    POINT LATTICES AND THE UNIT CELL Let’s consider the three-dimensional arrangement of points in Fig.15.This arrangement is called a point lattice. If we take any point in the point lattice it has exactly the same number and arrangement of neighbors(i.e.,identical surroundings) as any other point in the lattice. This condition should be fairly obvious considering our description of long-range order in Sec. 2.1 We can also see from Fig. 15 that it is possible to divide the point lattice into much smaller untils such that when these units are stacked in three dimensions they reproduce the point lattice. This small repeating unit is known as the unit cell of the lattice and is shown in Fig.16 A unit cell may be described by the interrelationship between the lengths(a,b,c) of its sides and the interaxial angles (α,β,γ)between them. (α is the angle between the b and c, axes,β is the angle between the a and c axes, and γ is the angle between the a and b axes.)The actual values of a,b,and c, and α,β and γ are not important, but their interrelation is. The lengths are measured from one corner of the cell, which is taken as the origin. These lengths and angles are called the lattice parameters of the unit cell, or sometimes the lattice constants of the cell. But the latter term is not really appropriate because they are not necessarily constants; for example, they can vary with changes in temperature and pressure and with alloying. [Note: We use a,b and c to indicate the axes of the unit cell; a,b and c for the lattice parameters, and a,b and c for the vectors lying along the unit-cell axes.]

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    The body is protected against attack from bacteria and viruses by the immune system.White blood cells, especially those known as T-cells, play a central role in this fight against harmful invaders. In rare cases, however, the natural action of the immune system can cause problems. One such case is organ transplantation, in which the immune system attacks the new organ and causes the body to reject it. In order to suppress this rejection, several types of immunosuppressant drugs have been used. However, the discovery of cyclosporine in 1976 has been unparalleled by any other breakthrough in the long history of tissuen and organ transplantation. This medication has had a revolutionary impact, enabling the graft survival rate of renal transplants to increase from 40 to 90 percent. It is safe to say that the drug has moved transplantation from the realm of miracle into routine therapy. Cyclosporine prevents organ rejection by blocking certain immune pathways that are activated when the body detects foreign cells. At the same time, however, this medication indiscriminately blocks other cellular signal pathways, causing serious side effects such as high blood pressure and high cholesterol. These conditions can cause cardiovascular disease and kidney toxicity that may ultimately lead to organ failures. In addition, long-term cyclosporine use damages the body's immune system itself, preventing it from fighting off infections following transplant. Now, research is being done to develop drugs that can prevent rejection as effectively as cyclosporine, while avoiding its harmful side effects. One such drug is belatacept. This promising new immunosuppressant prevents T-cell activation by selectively blocking one of the two signals T-cells need in order to become fully activated and to initiate an immune response against a transplanted organ. By selectively blocking this co-stimulatory signal, the drug allows the body to continue fighting infections, while preventing organ rejection. Though further study and testing must be done before the drug can be recommended as a routine replacement for cyclosporine, belatacept could brighten the futures of many who suffer from chronic renal disease and other types of organ failure.

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    The diffculties and disputes which attended the first revival of science have recurred in the present century in consequence of the growth of geology. It is in truth only the old question over again-precisely the same point of theology which is involved, although the difficulties which present themselves are fresh. The school books of the present day, while they teach the child that the earth moves, yet [they] assure him that it is a little less than six thousand years old and that it was made in six days. On the other hand, geologists of all religious creeds are agreed that the earth has existed for an immense series of years-to be [to be=it should be] counted by millions rather than by thousands:and that indubitably more than six days elapsed from its first creation to the appearance of man upon its surface. By this broad discrepancy between old and doctrine is the modern mind startled, as were the men of the sixteenth century [startled] when [they were] told that the earth moved.

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    1. mRNPs diffuse throughout interchromatin space or zones of heterochromatin exclusionin the nucleoplasm to reach NPCs 2. targeting of TREX-2 components to NPCs requires TPR, suggesting that it may be advantageous for TREX-2-associated mRNPs to interact with TPR-mediated scaffolds, as this could potentially increase the efficiency of their diffusion to NPCs.

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    和訳お願いします。 また訳せないところがでてきてしまいました。文が途中で切れてしまっているところもありますが、よろしくお願いします。 The technical risk(established by site service and regulatory /agency personnel) The percieved risk(outrage)by the public; and The regulatory risk relative to past, current, and future standards and position. Exhibit 12 presents a suite of issues and concerns that that could fall within the perceived risk assessment. However, each site is unique and its perceived risk will reflect its unique conditions. Perceived risk is perhaps the most difficult of all risks to anticipate and deal with efficiently. For example, it can be manipulated by activist groups interested in controlling or defeating the site restoration project.