Regulation of DNA methylation of Rasgrf1.

In mammals, DNA is methylated at cytosines within CpG dinucleotides. Properly regulated methylation is crucial for normal development. Inappropriate methylation may contribute to tumorigenesis by silencing tumor-suppressor genes or by activating growth-stimulating genes. Although many genes have been identified that acquire methylation and whose expression is methylation-sensitive, little is known about how DNA methylation is controlled. We have identified a DNA sequence that regulates establishment of DNA methylation in the male germ line at Rasgrf1. In mice, the imprinted Rasgrf1 locus is methylated on the paternal allele within a differentially methylated domain (DMD) 30 kbp 5' of the promoter. Expression is exclusively from the paternal allele in neonatal brain. Methylation is regulated by a repeated sequence, consisting of a 41-mer repeated 40 times, found immediately 3' of the DMD. This sequence is present in organisms in which Rasgrf1 is imprinted. In addition, DMD methylation is required for imprinted Rasgrf1 expression. Together the DMD and repeat element constitute a binary switch that regulates imprinting at the locus.     

Single mimivirus particles intercepted and imaged with an X-ray laser

X-ray lasers offer new capabilities in understanding the structure of biological systems, complex materials and matter under extreme conditions. Very short and extremely bright, coherent X-ray pulses can be used to outrun key damage processes and obtain a single diffraction pattern from a large macromolecule, a virus or a cell before the sample explodes and turns into plasma. The continuous diffraction pattern of non-crystalline objects permits oversampling and direct phase retrieval. Here we show that high-quality diffraction data can be obtained with a single X-ray pulse from a non-crystalline biological sample, a single mimivirus particle, which was injected into the pulsed beam of a hard-X-ray free-electron laser, the Linac Coherent Light Source. Calculations indicate that the energy deposited into the virus by the pulse heated the particle to over 100,000?K after the pulse had left the sample. The reconstructed exit wavefront (image) yielded 32-nm full-period resolution in a single exposure and showed no measurable damage. The reconstruction indicates inhomogeneous arrangement of dense material inside the virion. We expect that significantly higher resolutions will be achieved in such experiments with shorter and brighter photon pulses focused to a smaller area. The resolution in such experiments can be further extended for samples available in multiple identical copies.     

Generalized Lévy walks and the role of chemokines in migration of effector CD8+ T cells

Chemokines have a central role in regulating processes essential to the immune function of T cells, such as their migration within lymphoid tissues and targeting of pathogens in sites of inflammation. Here we track T cells using multi-photon microscopy to demonstrate that the chemokine CXCL10 enhances the ability of CD8+ T cells to control the pathogen Toxoplasma gondii in the brains of chronically infected mice. This chemokine boosts T-cell function in two different ways: it maintains the effector T-cell population in the brain and speeds up the average migration speed without changing the nature of the walk statistics. Notably, these statistics are not Brownian; rather, CD8+ T-cell motility in the brain is well described by a generalized Lévy walk. According to our model, this unexpected feature enables T cells to find rare targets with more than an order of magnitude more efficiency than Brownian random walkers. Thus, CD8+ T-cell behaviour is similar to Lévy strategies reported in organisms ranging from mussels to marine predators and monkeys, and CXCL10 aids T cells in shortening the average time taken to find rare targets.     

A simple rule for the evolution of cooperation on graphs and social networks

A fundamental aspect of all biological systems is cooperation. Cooperative interactions are required for many levels of biological organization ranging from single cells to groups of animals. Human society is based to a large extent on mechanisms that promote cooperation. It is well known that in unstructured populations, natural selection favours defectors over cooperators. There is much current interest, however, in studying evolutionary games in structured populations and on graphs. These efforts recognize the fact that who-meets-whom is not random, but determined by spatial relationships or social networks. Here we describe a surprisingly simple rule that is a good approximation for all graphs that we have analysed, including cycles, spatial lattices, random regular graphs, random graphs and scale-free networks: natural selection favours cooperation, if the benefit of the altruistic act, b, divided by the cost, c, exceeds the average number of neighbours, k, which means b/c > k. In this case, cooperation can evolve as a consequence of 'social viscosity' even in the absence of reputation effects or strategic complexity.     

Disruption of CREB function in brain leads to neurodegeneration

Control of cellular survival and proliferation is dependent on extracellular signals and is a prerequisite for ordered tissue development and maintenance. Activation of the cAMP responsive element binding protein (CREB) by phosphorylation has been implicated in the survival of mammalian cells. To define its roles in the mouse central nervous system, we disrupted Creb1 in brain of developing and adult mice using the Cre/loxP system. Mice with a Crem(-/-) background and lacking Creb in the central nervous system during development show extensive apoptosis of postmitotic neurons. By contrast, mice in which both Creb1 and Crem are disrupted in the postnatal forebrain show progressive neurodegeneration in the hippocampus and in the dorsolateral striatum. The striatal phenotype is reminiscent of Huntington disease and is consistent with the postulated role of CREB-mediated signaling in polyglutamine-triggered diseases.     

Realization of the Cirac-Zoller controlled-NOT quantum gate

Quantum computers have the potential to perform certain computational tasks more efficiently than their classical counterparts. The Cirac-Zoller proposal for a scalable quantum computer is based on a string of trapped ions whose electronic states represent the quantum bits of information (or qubits). In this scheme, quantum logical gates involving any subset of ions are realized by coupling the ions through their collective quantized motion. The main experimental step towards realizing the scheme is to implement the controlled-NOT (CNOT) gate operation between two individual ions. The CNOT quantum logical gate corresponds to the XOR gate operation of classical logic that flips the state of a target bit conditioned on the state of a control bit. Here we implement a CNOT quantum gate according to the Cirac-Zoller proposal. In our experiment, two 40Ca+ ions are held in a linear Paul trap and are individually addressed using focused laser beams; the qubits are represented by superpositions of two long-lived electronic states. Our work relies on recently developed precise control of atomic phases and the application of composite pulse sequences adapted from nuclear magnetic resonance techniques.     

Oxidative phosphorylation of guinea-pig aorta

Zusammenfassung Bei der Untersuchung von Aorta-Homogenaten von Meerschweinchen wurde ein hoher P/O Quotient für die oxydative Phosphorylierung gefunden.

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This work was supported by Public Health Service Grand No. HE-00891.