抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Molecular approaches to understanding the functional circuitry of the nervous system promise new insights into the relationship between genes, brain and behaviour. The cellular diversity of the brain necessitates a cellular resolution approach towards understanding the functional genomics of the nervous system. We describe here an anatomically comprehensive digital atlas containing the expression patterns of approximately 20,000 genes in the adult mouse brain. Data were generated using automated high-throughput procedures for in situ hybridization and data acquisition, and are publicly accessible online. Newly developed image-based informatics tools allow global genome-scale structural analysis and cross-correlation, as well as identification of regionally enriched genes. Unbiased fine-resolution analysis has identified highly specific cellular markers as well as extensive evidence of cellular heterogeneity not evident in classical neuroanatomical atlases. This highly standardized atlas provides an open, primary data resource for a wide variety of further studies concerning brain organization and function.

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Genome-wide atlas of gene expression in the adult mouse brain

With few exceptions biological tissues strongly scatter light, making high-resolution deep imaging impossible for traditional⎯including confocal⎯fluorescence microscopy. Nonlinear optical microscopy, in particular two photon–excited fluorescence microscopy, has overcome this limitation, providing large depth penetration mainly because even multiply scattered signal photons can be assigned to their origin as the result of localized nonlinear signal generation. Two-photon microscopy thus allows cellular imaging several hundred microns deep in various organs of living animals. Here we review fundamental concepts of nonlinear microscopy and discuss conditions relevant for achieving large imaging depths in intact tissue.

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Deep tissue two-photon microscopy

This paper gives the 2010 self-consistent set of values of the basic constants and conversion factors of physics and chemistry recommended by the Committee on Data for Science and Technology (CODATA) for international use. The 2010 adjustment takes into account the data considered in the 2006 adjustment as well as the data that became available from 1 January 2007, after the closing date of that adjustment, until 31 December 2010, the closing date of the new adjustment. Further, it describes in detail the adjustment of the values of the constants, including the selection of the final set of input data based on the results of least-squares analyses. The 2010 set replaces the previously recommended 2006 CODATA set and may also be found on the World Wide Web at physics.nist.gov/constants.

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CODATA Recommended Values of the Fundamental Physical Constants: 2006

中枢神経系疾患の治療は正常細胞（ニューロン）の機能維持を目的とするが，脳血管障害のように機能障害の原因が細胞の死滅に基づくことは多い．一方，脳腫瘍の治療においては薬物療法や放射線療法といった腫瘍細胞の死滅を目標とするものが大きな位置を占める．いずれの場合にも，細胞死の機序を理解することは各種病態や治療法の理解のうえで重要である．現在のところ最も研究の進んでいる細胞死の型はアポトーシスである．そのなかで重要な位置を占めるミトコンドリアにおける反応および抗アポトーシス因子について概要を紹介する．

Neuroscience 細胞死：最近の知見

A system monitors or images a portion of a sample. The system includes an optical interferometer with a measurement arm, a reference arm, and an optical splitter. The arms are coupled to receive light from the optical splitter. One of the arms includes an acousto-optical modulator. The interferometer is configured to interfere light output from the two arms. The system also includes a detector that receives the interfered light and uses the received light to determine a depth-dependent quantity characterizing a portion of the interior of the sample.

Acousto-optic monitoring and imaging in a depth sensitive manner

Active stabilization of electrodes for intracellular recording in awake behaving animals.

Positronium is the quasistable bound system consisting of an electron and its antiparticle, the positron. Its energy levels can be explained to a high degree of accuracy by the electromagnetic interaction, affording an ideal test of the quantum electrodynamic (QED) theory of bound systems. We have measured the 1 $^{3}$${\mathit{S}}_{1}$--2 $^{3}$${\mathit{S}}_{1}$ interval in positronium by Doppler-free two-photon spectroscopy to be 1 233 607 216.4\ifmmode\pm\else\textpm\fi{}3.2 MHz. We employ continous-wave (cw) excitation to eliminate the problems inherent with pulsed laser measurements of nonlinear transitions. Positronium (Ps) atoms generated in vacuum are excited to the 2S state using cw laser light built up to 2.5 kW circulating power in a resonant Fabry-P\'erot cavity. The excited-state atoms are photoionized using a pulsed laser at 532 nm, and the liberated positrons counted as the cw laser is tuned relative to a reference line in tellurium (${\mathrm{Te}}_{2}$) molecular vapor. The fit of a detailed theoretical model to the measured line shape determines the Ps resonance frequency relative to the ${\mathrm{Te}}_{2}$ reference line. The Monte Carlo model includes details of the excitation and detection geometry, the Ps velocity distribution, and the dynamic Stark shift, and gives excellent agreement with the measured line shapes. The quoted 2.6 parts per billion (ppb) uncertainty is dominated by the measurement of the Ps line center relative to the ${\mathrm{Te}}_{2}$ reference line, with a 1.0-ppb contribution from a recent calibration of our ${\mathrm{Te}}_{2}$ cell relative to the hydrogen 1S-2S transition frequency. The measurement is in excellent agreement with theory and sufficiently accurate to provide a test of the as-yet-uncalculated ${\mathrm{\ensuremath{\alpha}}}^{4}$${\mathit{R}}_{\mathrm{\ensuremath{\infty}}}$ QED correction. Our measurement tests the ${\mathrm{\ensuremath{\alpha}}}^{2}$${\mathit{R}}_{\mathrm{\ensuremath{\infty}}}$ QED contributions to the energy of the 1 $^{3}$${\mathit{S}}_{1}$ and 2 $^{3}$${\mathit{S}}_{1}$ states to 3.5 parts in ${10}^{5}$.

/pdf/measurement-of-the-positronium-1-3s1-2-3s1-interval-by-6zhyh6vxgi.pdf

Measurement of the positronium 1 3S1–2 3S1 interval by continuous-wave two-photon excitation

Sparse neural codes have been widely observed in cortical sensory and motor areas. A striking example of sparse temporal coding is in the song-related premotor area high vocal center (HVC) of songbirds: The motor neurons innervating avian vocal muscles are driven by premotor nucleus robustus archistriatalis (RA), which is in turn driven by nucleus HVC. Recent experiments reveal that RA-projecting HVC neurons fire just one burst per song motif. However, the function of this remarkable temporal sparseness has remained unclear. Because birdsong is a clear example of a learned complex motor behavior, we explore in a neural network model with the help of numerical and analytical techniques the possible role of sparse premotor neural codes in song-related motor learning. In numerical simulations with nonlinear neurons, as HVC activity is made progressively less sparse, the minimum learning time increases significantly. Heuristically, this slowdown arises from increasing interference in the weight updates for different synapses. If activity in HVC is sparse, synaptic interference is reduced, and is minimized if each synapse from HVC to RA is used only once in the motif, which is the situation observed experimentally. Our numerical results are corroborated by a theoretical analysis of learning in linear networks, for which we derive a relationship between sparse activity, synaptic interference, and learning time. If songbirds acquire their songs under significant pressure to learn quickly, this study predicts that HVC activity, currently measured only in adults, should also be sparse during the sensorimotor phase in the juvenile bird. We discuss the relevance of these results, linking sparse codes and learning speed, to other multilayered sensory and motor systems.

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Temporal sparseness of the premotor drive is important for rapid learning in a neural network model of birdsong

The pallido-recipient thalamus transmits information from the basal ganglia to the cortex and is critical for motor initiation and learning. Thalamic activity is strongly inhibited by pallidal inputs from the basal ganglia, but the role of nonpallidal inputs, such as excitatory inputs from cortex, remains unclear. We simultaneously recorded from presynaptic pallidal axon terminals and postsynaptic thalamocortical neurons in a basal ganglia-recipient thalamic nucleus that is necessary for vocal variability and learning in zebra finches. We found that song-locked rate modulations in the thalamus could not be explained by pallidal inputs alone and persisted following pallidal lesion. Instead, thalamic activity was likely driven by inputs from a motor cortical nucleus that is also necessary for singing. These findings suggest a role for cortical inputs to the pallido-recipient thalamus in driving premotor signals that are important for exploratory behavior and learning.

Michale S. Fee

Papers

Acousto-optic monitoring and imaging in a depth sensitive manner

Active stabilization of electrodes for intracellular recording in awake behaving animals.

Measurement of the positronium 1 3S1–2 3S1 interval by continuous-wave two-photon excitation

Temporal sparseness of the premotor drive is important for rapid learning in a neural network model of birdsong

A cortical motor nucleus drives the basal ganglia-recipient thalamus in singing birds.