Inter- and Intra-Subject Variability of Neuromagnetic Resting State Networks

Functional connectivity studies conducted at the group level using magnetoencephalography (MEG) suggest that resting state networks (RSNs) emerge from the large-scale envelope correlation structure within spontaneous oscillatory brain activity. However, little is known about the consistency of MEG RSNs at the individual level. This paper investigates the inter- and intra-subject variability of three MEG RSNs (sensorimotor, auditory and visual) using seed-based source space envelope correlation analysis applied to 5 min of resting state MEG data acquired from a 306-channel whole-scalp neuromagnetometer (Elekta Oy, Helsinki, Finland) and source projected with minimum norm estimation. The main finding is that these three MEG RSNs exhibit substantial variability at the single-subject level across and within individuals, which depends on the RSN type, but can be reduced after averaging over subjects or sessions. Over- and under-estimations of true RSNs variability are respectively obtained using template seeds, which are potentially mislocated due to inter-subject variations, and a seed optimization method minimizing variability. In particular, bounds on the minimal number of subjects or sessions required to obtain highly consistent between- or within-subject averages of MEG RSNs are derived. Furthermore, MEG RSN topography positively correlates with their mean connectivity at the inter-subject level. These results indicate that MEG RSNs associated with primary cortices can be robustly extracted from seed-based envelope correlation and adequate averaging. MEG thus appears to be a valid technique to compare RSNs across subjects or conditions, at least when using the current methods.     

釉基质蛋白对人牙髓细胞成牙本质分化的影响

目的 探讨釉基质蛋白对人牙髓细胞(human dental pulp cells,HDPC)成牙本质分化的影响,为牙本质的组织工程学研究提供有效的生物活性物质.方法 将HDPC接种于6孔板(2×105个/孔)后分为5组,分别加入含1、10、100 mg/L釉基质蛋白(enamel matrix proteins,EMP)(分别为EMP 1、10、100 mg/L组)、10-8 mol/L地塞米松及100 mg/L抗坏血酸(dexamethasone and ascorbic acid,Dex-AA组)、单纯基础培养液(对照组).于培养1、5、10 d分别用碱性磷酸酶(alkaline phosphatase,ALP)试剂盒检测ALP活性,实时荧光定量反转录聚合酶链反应技术检测成牙本质相关基因牙本质基质蛋白1(dentine matrix protein-1,DMP-1)及牙本质涎磷蛋白(dentine sialophosphoprotein,DSPP)的表达,应用2-△△CT方法得出具体数值并进行单因素方差分析与Post Hoe 检验,用茜素红染色检测并定量分析矿化情况.结果 各组ALP水平呈时间依赖性上调,培养1d后各组ALP活性与对照组相比差异均无统计学意义;5 d后EMP 10、100 mg/L组及Dex-AA组ALP活性显著增高,分别达到7.573±0.267、6.119±0.502、5.846±0.096,与对照组相比差异均有统计学意义(P＜0.05);10 d后10 mg/L EMP组及Dex-AA组ALP活性增高更显著,分别达21.035±0.149、13.223±0.797,与对照组(5.825±0.404)相比差异均有统计学意义(P＜0.01).培养1d后各组DMP-1及DSPP mRNA水平均较对照组显著升高,差异均有统计学意义(P＜0.01);培养10 d后10 mg/L EMP组DMP-1和DSPP表达水平均显著增高,分别达到14.791±0.164、12.238±0.421.培养10 d后各组均有矿化,10 mg/L EMP组钙离子浓度[(191.8±2.0) μmol/L]显著高于对照组[(81.1±8.1)μmol/L],差异有统计学意义(P＜0.01).结论 适当浓度的EMP对HDPC的成牙本质分化有一定的促进作用.     

Evaluation of fluorescent plasma markers for in vivo microscopy of the microcirculation

This study evaluated four fluorescent-protein conjugates to monitor microcirculatory variables using the murine cremaster muscle and determined acute and long-term responses to repeated administration of FITC-BSA [conjugated at the University of Sheffield (UoS)] within a dorsal microcirculatory chamber (DMC) in rats. For analysis of the cremaster muscle, male C3H/HeN mice were anaesthetized, the cremaster muscle was exteriorized, then TRITC-BSA, TRITC-dextran, FITC-BSA, FITC-BSA (UoS) or FITC-dextran (0.25 ml/100 g) were administered systemically. The microcirculation was viewed with epi-illumination every 10 min for 120 min. For analysis of the DMC, male Wistar rats were implanted with the chamber. Three weeks later, FITC-BSA (UoS) was administered systemically, and the microcirculation response was monitored using three different protocols. In addition, in vitro stability of fluorescent conjugates was measured over 8 h. With regard to the cremaster muscle, initially no differences in interstitial fluorescence or vessel diameter were observed between the four fluorescent conjugates. By the end of the study, interstitial fluorescence from TRITC-dextran, FITC-dextran and FITC-BSA (Sigma) was significantly (p < 0.05) increased compared to FITC-BSA (UoS). With regard to the DMC, there was no interstitial fluorescence leakage after 180 min or 5 weeks despite repeated administration, but a significant (p < 0.05) leak was detected between 4 and 24 h. FITC-BSA (UoS) was the most stable fluorescent conjugate both in vitro and in vivo and was comparable with other conjugates for evaluating skeletal muscle microcirculation using fluorescent in vivo microscopy.     

Pharmacological modulation of cardiac function and blood vessel calibre

Sympathomimetics such as noradrenaline, adrenaline and dopamine all have a positive inotropic effect and may be useful in treating different aspects of cardiovascular collapse. Digoxin, which inhibits the cardiac Na⁺/K⁺ adenosine triphosphatase pump and the phosphodiesterase III inhibitors milrinone and amironone, which both increase in cyclic adenosine monophosphate may also be useful for treatment of angina and heart failure respectively. The cardiac effects of β-blockers, L-type Ca²⁺ channel antagonists, K⁺ channel openers, I(f) inhibitors and nitrovasodilators and their role in angina are described in this article. The list of pharmacological control mechanisms that regulate the calibre of blood vessels is ever expanding and, for ease of understanding, they have been divided into neural, humoral and local mechanisms capable of inducing either vasodilation or vasoconstriction. Moment-to-moment sympathetic nerves and α₁ adrenoceptors maintain vascular tone but, locally, L-type Ca²⁺ channels (LTCC) also have an important function. LTCC antagonists inhibit influx at three sites on the α-subunit of the channel (dihydropyridine, phenylalkylamines and benzothiazepines) to alleviate hypertension. Inhibiting circulating hormones or the receptor targets for hormones, such as angiotensin-II or vasopressin may also be useful for the treatment of hypertension or shock. Nitric oxide (NO) is also one of the most important vasodilator local-control mechanisms, via stimulation of guanylyl cyclase and increased cyclic guanosine monophosphate, and this is counteracted by endothelin-1, one of the most potent vasoconstrictors, which, like NO, also has an important role in diseases such as sepsis.