Intermediate expression of CCRL1 reveals novel subpopulations of medullary thymic epithelial cells that emerge in the postnatal thymus

Cortical and medullary thymic epithelial cells (cTECs and mTECs, respectively) provide inductive microenvironments for T‐cell development and selection. The differentiation pathway of cTEC/mTEC lineages downstream of common bipotent progenitors at discrete stages of development remains unresolved. Using IL‐7/CCRL1 dual reporter mice that identify specialized TEC subsets, we show that the stepwise acquisition of chemokine (C–C motif) receptor‐like 1 (CCRL1) is a late determinant of cTEC differentiation. Although cTECs expressing high CCRL1 levels (CCRL1^hi) develop normally in immunocompetent and Rag2^?/?thymi, their differentiation is partially blocked in Rag2^?/?Il2rg^?/? counterparts. These results unravel a novel checkpoint in cTEC maturation that is regulated by the cross‐talk between TECs and immature thymocytes. Additionally, we identify new Ulex europaeus agglutinin 1 (UEA)⁺ mTEC subtypes expressing intermediate CCRL1 levels (CCRL1^int) that conspicuously emerge in the postnatal thymus and differentially express Tnfrsf11a, Ccl21, and Aire. While rare in fetal and in Rag2^?/? thymi, CCRL1^int mTECs are restored in Rag2^?/?Marilyn TCR‐Tg mice, indicating that the appearance of postnatal‐restricted mTECs is closely linked with T‐cell selection. Our findings suggest that alternative temporally restricted routes of new mTEC differentiation contribute to the establishment of the medullary niche in the postnatal thymus.     

CCRL1 marks heterogeneity in cortical and medullary thymic epithelial cells

Cortical thymic epithelial cells (cTECs) and medullary thymic epithelial cells (mTECs), which play essential roles in the establishment of a functionally competent and self‐tolerant repertoire of T cells, are derived from common thymic epithelial progenitor cells (pTECs). Recent findings indicate that mTECs are derived from cells that express molecules that are abundant in cTECs rather than mTECs, and provide fresh insight into the characteristics of pTECs and their diversification pathways into TEC subpopulations. In this issue of the European Journal of Immunology, Ribeiro et al. [Eur. J. Immunol. 2014. 44: 2918–2924] focus on CCRL1, an atypical chemokine receptor that is highly expressed by cTECs rather than mTECs, and show that CCRL1‐expressing embryonic TECs can give rise to mTECs. Interestingly, Ribeiro et al. further report that a fraction of postnatal mTECs express CCRL1 at a low level, suggesting novel complexity in mTECs.     

Analysis on Bilateral Hindlimb Mapping in Motor Cortex of the Rat by an Intracortical Microstimulation Method

Intracortical microstimulation (ICMS) is a technique that was developed to derive movement representation of the motor cortex. Although rats are now commonly used in motor mapping studies, the precise characteristics of rat motor map, including symmetry and consistency across animals, and the possibility of repeated stimulation have not yet been established. We performed bilateral hindlimb mapping of motor cortex in six Sprague-Dawley rats using ICMS. ICMS was applied to the left and the right cerebral hemisphere at 0.3 mm intervals vertically and horizontally from the bregma, and any movement of the hindlimbs was noted. The majority (80%±11%) of responses were not restricted to a single joint, which occurred simultaneously at two or three hindlimb joints. The size and shape of hindlimb motor cortex was variable among rats, but existed on the convex side of the cerebral hemisphere in all rats. The results did not show symmetry according to specific joints in each rats. Conclusively, the hindlimb representation in the rat motor cortex was conveniently mapped using ICMS, but the characteristics and inter-individual variability suggest that precise individual mapping is needed to clarify motor distribution in rats.

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Local and distant cortical responses to single pulse intracranial stimulation in the human brain are differentially modulated by specific stimulation parameters

BackgroundElectrical neuromodulation via direct electrical stimulation (DES) is an increasingly common therapy for a wide variety of neuropsychiatric diseases. Unfortunately, therapeutic efficacy is inconsistent, likely due to our limited understanding of the relationship between the massive stimulation parameter space and brain tissue responses.ObjectiveTo better understand how different parameters induce varied neural responses, we systematically examined single pulse-induced cortico-cortico evoked potentials (CCEP) as a function of stimulation amplitude, duration, brain region, and whether grey or white matter was stimulated.MethodsWe measured voltage peak amplitudes and area under the curve (AUC) of intracranially recorded stimulation responses as a function of distance from the stimulation site, pulse width, current injected, location relative to grey and white matter, and brain region stimulated (N = 52, n = 719 stimulation sites).ResultsIncreasing stimulation pulse width increased responses near the stimulation location. Increasing stimulation amplitude (current) increased both evoked amplitudes and AUC nonlinearly. Locally (<15 mm), stimulation at the boundary between grey and white matter induced larger responses. In contrast, for distant sites (>15 mm), white matter stimulation consistently produced larger responses than stimulation in or near grey matter. The stimulation location-response curves followed different trends for cingulate, lateral frontal, and lateral temporal cortical stimulation.ConclusionThese results demonstrate that a stronger local response may require stimulation in the grey-white boundary while stimulation in the white matter could be needed for network activation. Thus, stimulation parameters tailored for a specific anatomical-functional outcome may be key to advancing neuromodulatory therapy.     

三种中草药制剂对肠道致病菌体外抗菌作用的分析

目的：探讨分析三种中草药制剂对肠道致病菌体外抗菌作用。方法以连续稀释法检测三种中草药制剂（黄柏、黄连、黄芩）的最低抑菌浓度。结果三种中草药制剂对大肠杆菌的最低抑菌浓度：黄柏为6.3 g/L,黄连为1.6 g/L,黄芩为6.3 g/L;对金黄色葡萄球菌的最低抑菌浓度：黄柏为3.2 g/L,黄连为0.8 g/L,黄芩为1.6 g/L;对副溶血性弧菌的最低抑菌浓度：黄柏为0.8 g/L,黄连为0.8 g/L,黄芩为1.6 g/L;对沙门菌的最低抑菌浓度：黄柏为3.2 g/L,黄连为3.2 g/L,黄芩为12.5 g/L;对志贺菌的最低抑菌浓度：均为3.2 g/L。结论三种中草药制剂（黄柏、黄连、黄芩）对肠道致病菌体外抗菌作用较强。     

Dynamic of neurochemical alterations in striatum,hippocampus and cortex after the 6-OHDA mesostriatal lesion

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