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

Central Sensitization: A Generator of Pain Hypersensitivity by Central Neural Plasticity

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 central question in cell biology is how membrane-spanning receptors transmit extracellular signals inside cells to modulate cell adhesion and motility. Focal adhesion kinase (FAK) is a crucial signalling component that is activated by numerous stimuli and functions as a biosensor or integrator to control cell motility. Through multifaceted and diverse molecular connections, FAK can influence the cytoskeleton, structures of cell adhesion sites and membrane protrusions to regulate cell movement.

Focal adhesion kinase: in command and control of cell motility

RNAscope: A Novel in Situ RNA Analysis Platform for Formalin-Fixed, Paraffin-Embedded Tissues

Olfactory information is relayed and processed in the olfactory bulb (OB). Mitral cells, the principal output excitatory neurons of the OB, are controlled by multiple types of interneurons. However, mechanisms that regulate the activity of OB interneurons are not well understood. We provide evidence that the transmembrane tyrosine kinase ErbB4 is selectively expressed in subsets of OB inhibitory neurons in both male and female mice. ErbB4-positive (ErbB4+) neurons are mainly located in the glomerular layer (GL) and granule cell layer (GCL) and do not express previously defined markers. Optogenetic activation of GL-ErbB4+ neurons promotes theta oscillation, whereas activation of those in the GCL generates γ oscillations. Stimulation of OB slices with NRG1, a ligand that activates ErbB4, increases GABA transmission onto mitral cells, suggesting a role of OB NRG1-ErbB4 signaling in olfaction. In accord, ErbB4 mutant mice or acute inhibition of ErbB4 by a chemical genetic approach diminishes GABA transmission, reduces bulbar local field potential power, increases the threshold of olfactory sensitivity, and impairs odor discrimination. Together, these results identified a bulbar inhibitory network of ErbB4+ neurons for olfaction. Considering that both Nrg1 and Erbb4 are susceptibility genes for neuropsychiatric disorders, our study provides insight into pathologic mechanisms of olfactory malfunctions in these disorders. SIGNIFICANCE STATEMENT This study demonstrates that ErbB4+ neurons are a new subset of olfactory bulb inhibitory neurons in the glomerular layer and granule cell layer that innervate mitral cells and ErbB4– cells. They regulate olfaction by controlling local synchrony and distinct oscillations. ErbB4 inhibition diminishes GABA transmission, reduces bulbar local field potential power, increases the threshold of olfactory sensitivity, and impairs odor discrimination. Our results provide insight into pathophysiological mechanism of olfaction deficits in brain disorders associated with Nrg1 or Erbb4 mutations.

An ErbB4-Positive Neuronal Network in the Olfactory Bulb for Olfaction

Excessive mitophagy for anxiety

Erratum: Loss-of-function mutations in HPSE2 cause the autosomal recessive urofacial syndrome (The American Journal of Human Genetics (2010) 86 (957-962))

Author response: Motoneuron Wnts regulate neuromuscular junction development

The precipitate evolution, strength and corrosion resistance of an Al–Zn–Mg–Cu alloy processed by cryorolling, warm rolling and final aging have been investigated. A large number of spherical Zn-rich GP zones formed after warm rolling. In-situ transmission electron microscopy (TEM) observation indicated that the GP zones are stable during aging treatment and can serve as nuclei for subsequent precipitates, leading to homogeneous distribution of precipitates in the matrix after aging. TEM results also showed that ultrafine subgrains were developed in the deformed microstructure during aging. The high density of precipitates and dislocations combined with grain refinement contribute to the higher strength of the thermo-mechanically treated alloy compared with the peak-aged alloy. On the other hand, the η phase with C15 cubic structure having ‧‧‧RR‧‧‧ stacking is found in the thermo-mechanically treated alloy and is different from one with C14 hexagonal structure having ‧‧‧RR−1‧‧‧ stacking that is commonly observed in conventionally aged alloys, where R and R−1 represent rhombic layer and the relatively 180°-rotated rhombic layer, respectively. The transition from ill-defined stacking to C15 stacking and further to C14 stacking is observed in the structure of a η phase. Besides, the combination of warm rolling and aging can avoid the formation of continuous grain boundary precipitates, which is beneficial to the corrosion resistance of the alloy. 

Lin Mei

Papers

An ErbB4-Positive Neuronal Network in the Olfactory Bulb for Olfaction

Excessive mitophagy for anxiety

Erratum: Loss-of-function mutations in HPSE2 cause the autosomal recessive urofacial syndrome (The American Journal of Human Genetics (2010) 86 (957-962))

Author response: Motoneuron Wnts regulate neuromuscular junction development

Precipitate evolution and properties of an Al–Zn–Mg–Cu alloy processed by thermomechanical treatment