Chromosome translocations are a hallmark of cancer cells. We have developed an experimental system to visualize the formation of translocations in living cells and apply it to characterize the spatial and dynamic properties of translocation formation. We demonstrate that translocations form within hours of the occurrence of double-strand breaks (DSBs) and that their formation is cell cycle-independent. Translocations form preferentially between prepositioned genome elements, and perturbation of key factors of the DNA repair machinery uncouples DSB pairing from translocation formation. These observations generate a spatiotemporal framework for the formation of translocations in living cells.
A blood clot needs to have the right degree of stiffness and plasticity to stem the flow of blood and yet be digestable by lytic enzymes so as not to form a thrombus, causing heart attacks, strokes, or pulmonary emboli, but the origin of these mechanical properties is unknown. Clots are made up of a three-dimensional network of fibrin fibers stabilized through ligation with a transglutaminase, factor XIIIa. We developed methods to measure the elastic moduli of individual fibrin fibers in fibrin clots with or without ligation, using optical tweezers for trapping beads attached to the fibers that functioned as handles to flex or stretch a fiber. Here, we report direct measurements of the microscopic mechanical properties of such a polymer. Fibers were much stiffer for stretching than for flexion, as expected from their diameter and length. Elastic moduli for individual fibers in plasma clots were 1.7 ؎ 1.3 and 14.5 ؎ 3.5 MPa for unligated and ligated fibers, respectively. Similar values were obtained by other independent methods, including analysis of measurements of fluctuations in bead force as a result of Brownian motion. These results provide a basis for understanding the origin of clot elasticity.fibrinogen ͉ optical trap ͉ viscoelasticity ͉ microrheology ͉ cardiovascular B lood clots play an essential role by stopping bleeding, but they can also cause heart attacks and strokes. Clots are formed when the enzyme thrombin cleaves fibrinogen to generate fibrin monomers, which polymerize to produce a threedimensional network of fibers (1-8). Fibrin is stabilized by ligation, ¶ the formation of intermolecular covalent bonds at specific sites with a transglutaminase, factor XIIIa, rendering the whole clot stiffer and resistant to fibrinolytic dissolution (9, 10). The viscoelastic properties of clots and their major constituent fibrin are normally finely tuned to optimize how they stop bleeding while also minimizing their effect in cardiovascular disease, because bleeding occurs if clot stiffness is too low; a decreased rate of fibrinolysis and increased thrombosis and thromboembolism are generally associated with stiff and friable clots, although such relationships are complex (10 -14). Although much is known of fibrin assembly mechanisms (1)(2)(3)(4)(5)(6)(7)(8)(15)(16)(17)(18), the origin of clot viscoelasticity remains to be established.The elasticity of a fibrin clot, like that of rubber-like polymers, is characterized by very large deformability with essentially complete recovery (19). However, the elasticity of the fibrin clot cannot be rubber-like, because it is not a random-coil network made up of thin, highly flexible strands; instead, it is a network made up of thick branching fibers. As an example of how unrealistic such rubber-like models are, it can be calculated from clot stiffness that there would be an average of only one fibrin molecule per branch point for a rubber-like model (20), yet electron micrographs show that the clots used for these experiments commonly have Ϸ1 million fibrin molecules bet...
The United State generates the most waste among OECD countries, and there are adverse effects of the waste generation. One of the most serious adverse effects is greenhouse gas, especially CH4, which causes global warming. However, the amount of waste generation is not decreasing, and the United State recycling rate, which could reduce waste generation, is only 26%, which is lower than other OECD countries. Thus, waste generation and greenhouse gas emission should decrease, and in order for that to happen, identifying the causes should be made a priority. The research objective is to verify whether the Environmental Kuznets Curve relationship is supported for waste generation and GDP across the U.S. Moreover, it also confirmed that total waste generation and recycling waste influences carbon dioxide emissions from the waste sector. The annual-based U.S. data from 1990 to 2012 were used. The data were collected from various data sources, and the Granger causality test was applied for identifying the causal relationships. The results showed that there is no causality between GDP and waste generation, but total waste and recycling generation significantly cause positive and negative greenhouse gas emissions from the waste sector, respectively. This implies that the waste generation will not decrease even if GDP increases. And, if waste generation decreases or recycling rate increases, the greenhouse gas emission will decrease. Based on these results, it is expected that the waste generation and carbon dioxide emission from the waste sector can decrease more efficiently.
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