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High resolution three‐dimensional reconstruction of fibrotic skeletal muscle extracellular matrix 纤维化骨骼肌细胞外基质的高分辨率三维重建
Pub Date : 2017-02-15 DOI: 10.1113/JP273376
Allison R Gillies, Mark A. Chapman, E. Bushong, T. Deerinck, Mark Ellisman, R. Lieber
Fibrosis occurs secondary to many skeletal muscle diseases and injuries, and can alter muscle function. It is unknown how collagen, the most abundant extracellular structural protein, alters its organization during fibrosis. Quantitative and qualitative high‐magnification electron microscopy shows that collagen is organized into perimysial cables which increase in number in a model of fibrosis, and cables have unique interactions with collagen‐producing cells. Fibrotic muscles are stiffer and have a higher concentration of collagen‐producing cells. These results improve our understanding of the organization of fibrotic skeletal muscle extracellular matrix and identify novel structures that might be targeted by antifibrotic therapy.
纤维化继发于许多骨骼肌疾病和损伤,可改变肌肉功能。胶原蛋白是最丰富的细胞外结构蛋白,在纤维化过程中如何改变其组织结构尚不清楚。定量和定性高倍率电子显微镜显示,在纤维化模型中,胶原蛋白被组织成膜周索,其数量增加,并且索与胶原蛋白产生细胞有独特的相互作用。纤维化肌肉更硬,产生胶原蛋白的细胞浓度更高。这些结果提高了我们对纤维化骨骼肌细胞外基质组织的理解,并确定了可能被抗纤维化治疗靶向的新结构。
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引用次数: 45
Effects of postural change from supine to head‐up tilt on the skin sympathetic nerve activity component synchronised with the cardiac cycle in warmed men 在温暖的男性中,从仰卧到头朝上的体位变化对与心脏周期同步的皮肤交感神经活动成分的影响
Pub Date : 2017-02-15 DOI: 10.1113/JP273281
Yu Ogawa, Y. Kamijo, S. Ikegawa, S. Masuki, H. Nose
Humans are unique in controlling body temperature in a hot environment by a large amount of skin blood flow; however, the decrease in total peripheral resistance due to systemic cutaneous vasodilatation and the reduction of venous return to the heart due to blood pooling in the cutaneous vein threatens blood pressure maintenance in the upright position, and occasionally causes heat syncope. Against this condition, cutaneous vasodilatation is reportedly suppressed to maintain arterial pressure; however, the nerve activity responsible for this phenomenon has not been identified. In the present study, we found that the skin sympathetic nerve activity component that was synchronised with the cardiac cycle increased in hyperthermia, but the increase was suppressed when the posture was changed from supine to head‐up tilt. The profile of the component agreed with that of cutaneous vasodilatation. Thus, the component might contribute to the prevention of heat syncope in humans.
在炎热的环境中,人类通过大量的皮肤血液流动来控制体温,这是独一无二的;然而,全身皮肤血管扩张导致的总外周阻力降低,以及皮静脉淤积导致的静脉回流心脏减少,会威胁直立体位血压的维持,偶尔还会引起热晕厥。在这种情况下,皮肤血管舒张被抑制以维持动脉压;然而,导致这种现象的神经活动尚未被确定。在本研究中,我们发现与心脏周期同步的皮肤交感神经活动成分在高温下增加,但当姿势从仰卧变为头向上倾斜时,这种增加被抑制。该成分的特征与皮肤血管扩张的特征一致。因此,该成分可能有助于预防人类热晕厥。
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引用次数: 6
Effect of maternal position on fetal behavioural state and heart rate variability in healthy late gestation pregnancy 健康孕晚期孕妇体位对胎儿行为状态和心率变异性的影响
Pub Date : 2017-02-15 DOI: 10.1113/JP273201
P. Stone, Wendy Burgess, Jordan P R McIntyre, A. Gunn, Christopher A. Lear, L. Bennet, E. Mitchell, J. Thompson
Fetal behavioural state in healthy late gestation pregnancy is affected by maternal position. Fetal state 1F is more likely to occur in maternal supine or right lateral positions. Fetal state 4F is less likely to occur when the woman lies supine or semi‐recumbent. Fetal state change is more likely when the woman is supine or semi‐recumbent. Fetal heart rate variability is affected by maternal position with variability reduced in supine and semi‐recumbent positions.
健康孕晚期胎儿行为状态受母体体位的影响。胎儿状态1F更可能发生在母亲仰卧位或右侧卧位。当妇女仰卧或半平卧时,胎儿状态4F不太可能发生。当孕妇仰卧或半平卧时,胎儿状态改变的可能性更大。胎儿心率变异性受母亲体位的影响,在仰卧位和半卧位时变异性降低。
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引用次数: 46
Impact of vesicular glutamate leakage on synaptic transmission at the calyx of Held 谷氨酸囊泡渗漏对花萼突触传递的影响
Pub Date : 2017-02-15 DOI: 10.1113/JP273467
Chihiro Takami, Kohgaku Eguchi, T. Hori, Tomoyuki Takahashi
It is controversial whether glutamate can leak out of vesicles in the nerve terminal. To address this issue, we abolished vesicular glutamate uptake by washing out presynaptic cytosolic glutamate or by blocking vacuolar ATPase activity using bafilomycin A1. In the absence of vesicular glutamate uptake, both spontaneous and nerve‐evoked EPSCs underwent a rundown, suggesting that vesicular glutamate can leak out of vesicles. However, the rundown of evoked EPSCs was caused mainly by accumulation of unfilled vesicles after exocytic release of glutamate, suggesting a minor influence of glutamate leakage on synaptic transmission.
谷氨酸是否会从神经末梢的囊泡中渗出,目前还存在争议。为了解决这个问题,我们通过洗去突触前胞质谷氨酸或使用巴霉素A1阻断空泡atp酶活性来消除囊泡谷氨酸摄取。在没有水疱性谷氨酸摄取的情况下,自发的和神经诱发的EPSCs都经历了衰竭,这表明水疱性谷氨酸可以从水疱中泄漏出来。然而,被诱发的EPSCs的损耗主要是由于谷氨酸分泌后未填充囊泡的积累引起的,这表明谷氨酸泄漏对突触传递的影响很小。
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引用次数: 12
Cerebral haemodynamic response to somatosensory stimulation in near‐term fetal sheep 胎儿羊对体感刺激的脑血流动力学反应
Pub Date : 2017-02-15 DOI: 10.1113/JP273163
S. Nakamura, D. Walker, F. Wong
Cerebral haemodynamic response to neural stimulation has been extensively investigated in animal and clinical studies, in both adult and paediatric populations, but little is known about cerebral haemodynamic functional response in the fetal brain. The present study describes the cerebral haemodynamic response measured by near‐infrared spectroscopy to somatosensory stimulation in fetal sheep. The cerebral haemodynamic response in the fetal sheep brain changes from a positive (increase in oxyhaemoglobin (oxyHb)) response pattern to a negative or biphasic response pattern when the duration of somatosensory stimulation is increased, probably due to cerebral vasoconstriction with prolonged stimulations. In contrast to adult studies, we have found that changes in fetal cerebral blood flow and oxyHb are positively increased in response to somatosensory stimulation during hypercapnia. We propose this is related to reduced vascular resistance and recruitment of cerebral vasculature in the fetal brain during hypercapnia.
脑血流动力学对神经刺激的反应已经在动物和临床研究中进行了广泛的研究,包括成人和儿科人群,但对胎儿脑的脑血流动力学功能反应知之甚少。本研究描述了用近红外光谱测量胎儿羊对体感刺激的脑血流动力学反应。当体感刺激持续时间增加时,可能是由于长时间刺激导致脑血管收缩,胎羊脑血流动力学反应从阳性(氧合血红蛋白(oxyHb)增加)反应模式转变为阴性或双相反应模式。与成人研究相反,我们发现胎儿脑血流量和氧血红蛋白的变化在高碳酸血症期间响应体感觉刺激而正增加。我们认为这与高碳酸血症期间胎儿大脑血管阻力降低和脑血管系统募集有关。
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引用次数: 14
FoxO‐dependent atrogenes vary among catabolic conditions and play a key role in muscle atrophy induced by hindlimb suspension FoxO依赖性萎缩基因因分解代谢条件而异,在后肢悬吊引起的肌肉萎缩中起关键作用
Pub Date : 2017-02-15 DOI: 10.1113/JP273097
L. Brocca, L. Toniolo, C. Reggiani, R. Bottinelli, M. Sandri, M. Pellegrino
Muscle atrophy is a debilitating condition that affects a high percentage of the population with a negative impact on quality of life. Dissecting the molecular level of the atrophy process, and the similarities/dissimilarities among different catabolic conditions, is a necessary step for designing specific countermeasures to attenuate/prevent muscle loss. The FoxO family transcription factors represent one of the most important regulators of atrophy programme stimulating the expression of many atrophy‐related genes. The findings of the present study clearly indicate that the signalling network controlling the atrophy programme is specific for each catabolic condition.
肌肉萎缩是一种使人衰弱的疾病,影响了很大一部分人口,对生活质量产生了负面影响。剖析萎缩过程的分子水平,以及不同分解代谢条件之间的异同,是设计减轻/预防肌肉损失的具体对策的必要步骤。FoxO家族转录因子是刺激许多萎缩相关基因表达的萎缩程序中最重要的调节因子之一。本研究的结果清楚地表明,控制萎缩程序的信号网络对每种分解代谢条件都是特异性的。
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引用次数: 58
Cholinergic modulation of the parafacial respiratory group 面旁呼吸群的胆碱能调节
Pub Date : 2017-02-15 DOI: 10.1113/JP273012
Rozlyn C. T. Boutin, Zaki Alsahafi, S. Pagliardini
This study investigates the effects of cholinergic transmission on the expiratory oscillator, the parafacial respiratory group (pFRG) in urethane anaesthetized adult rats. Local inhibition of the acetyl cholinesterase enzyme induced activation of expiratory abdominal muscles and active expiration. Local application of the cholinomimetic carbachol elicited recruitment of late expiratory neurons, expiratory abdominal muscle activity and active expiration. This effect was antagonized by local application of the muscarinic antagonists scopolamine, J104129 and 4DAMP. We observed distinct physiological responses between the more medial chemosensitive region of the retrotrapezoid nucleus and the more lateral region of pFRG. These results support the hypothesis that pFRG is under cholinergic neuromodulation and the region surrounding the facial nucleus contains a group of neurons with distinct physiological roles.
本研究探讨了胆碱能传递对氨基甲酸乙酯麻醉成年大鼠呼气振子、面旁呼吸组(pFRG)的影响。乙酰胆碱酯酶的局部抑制诱导了呼气腹肌的激活和主动呼气。局部应用拟胆碱乙醇可引起呼气晚神经元的募集、呼气腹肌活动和主动呼气。局部应用毒蕈碱拮抗剂东莨菪碱、J104129和4DAMP可拮抗这种作用。我们观察到在梯形后核更内侧的化学敏感区和pFRG更外侧的区域之间有明显的生理反应。这些结果支持了pFRG受胆碱能神经调节的假设,并且面核周围区域包含一组具有不同生理作用的神经元。
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引用次数: 39
Non‐uniform phase sensitivity in spatial frequency maps of the human visual cortex 人类视觉皮层空间频率图中的非均匀相位灵敏度
Pub Date : 2017-02-15 DOI: 10.1113/JP273206
R. Farivar, S. Clavagnier, Bruce C. Hansen, Ben Thompson, R. Hess
Just as a portrait painting can come from a collection of coarse and fine details, natural vision can be decomposed into coarse and fine components. Previous studies have shown that the early visual areas in the brain represent these components in a map‐like fashion. Other studies have shown that these same visual areas can be sensitive to how coarse and fine features line up in space. We found that the brain actually jointly represents both the scale of the feature (fine, medium, or coarse) and the alignment of these features in space. The results suggest that the visual cortex has an optimized representation particularly for the alignment of fine details, which are crucial in understanding the visual scene.
就像一幅肖像画可以由粗细的细节组成一样,自然视觉也可以分解成粗细的成分。先前的研究表明,大脑的早期视觉区域以类似地图的方式代表这些成分。其他研究表明,这些相同的视觉区域对粗糙和精细的特征在空间中的排列很敏感。我们发现,大脑实际上同时代表了特征的尺度(精细、中等或粗糙)和这些特征在空间中的对齐。结果表明,视觉皮层具有优化的表征,特别是对精细细节的对齐,这对理解视觉场景至关重要。
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引用次数: 4
Tonotopic action potential tuning of maturing auditory neurons through endogenous ATP 内源性ATP调控成熟听觉神经元的张力异位动作电位
Pub Date : 2017-02-15 DOI: 10.1113/JP273272
Saša Virijević Jovanović, T. Radulovic, C. Coddou, Beatrice Dietz, Jana Nerlich, S. Stojilkovic, R. Rübsamen, I. Milenkovic
Following the genetically controlled formation of neuronal circuits, early firing activity guides the development of sensory maps in the auditory, visual and somatosensory system. However, it is not clear whether the activity of central auditory neurons is specifically regulated depending on the position within the sensory map. In the ventral cochlear nucleus, the first central station along the auditory pathway, we describe a mechanism through which paracrine ATP signalling enhances firing in a cell‐specific and tonotopically‐determined manner. Developmental down‐regulation of P2X2/3R currents along the tonotopic axis occurs simultaneously with an increase in AMPA receptor currents, suggesting a high‐to‐low frequency maturation pattern. Facilitated action potential (AP) generation, measured as higher firing rate, shorter EPSP‐AP delay in vivo and shorter AP latency in slice experiments, is consistent with increased synaptic efficacy caused by ATP. The long lasting change in intrinsic neuronal excitability is mediated by the heteromeric P2X2/3 receptors.
在基因控制的神经元回路形成之后,早期的放电活动指导了听觉、视觉和体感系统中感觉地图的发展。然而,目前尚不清楚中央听觉神经元的活动是否根据感觉地图中的位置被特异性调节。在耳蜗腹侧核,听觉通路上的第一个中枢,我们描述了旁分泌ATP信号以细胞特异性和tonotopically决定的方式增强放电的机制。P2X2/3R电流沿张力轴的发育下调与AMPA受体电流的增加同时发生,表明一个高-低频率的成熟模式。促进动作电位(AP)的产生,通过更高的放电率、更短的体内EPSP - AP延迟和更短的切片实验AP潜伏期来测量,与ATP引起的突触效能增加一致。内禀神经元兴奋性的长期变化是由异质P2X2/3受体介导的。
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引用次数: 12
Minimum number of myosin motors accounting for shortening velocity under zero load in skeletal muscle 在骨骼肌中,在零负荷下,肌凝蛋白马达的最小数量可以缩短速度
Pub Date : 2017-02-15 DOI: 10.1113/JP273299
L. Fusi, Valentina Percario, E. Brunello, M. Caremani, P. Bianco, J. Powers, M. Reconditi, V. Lombardi, G. Piazzesi
Myosin filament mechanosensing determines the efficiency of the contraction by adapting the number of switched ON motors to the load. Accordingly, the unloaded shortening velocity (V0) is already set at the end of latency relaxation (LR), ∼10 ms after the start of stimulation, when the myosin filament is still in the OFF state. Here the number of actin‐attached motors per half‐myosin filament (n) during V0 shortening imposed either at the end of LR or at the plateau of the isometric contraction is estimated from the relation between half‐sarcomere compliance and force during the force redevelopment after shortening. The value of n decreases progressively with shortening and, during V0 shortening starting at the end of LR, is 1–4. Reduction of n is accounted for by a constant duty ratio of 0.05 and a parallel switching OFF of motors, explaining the very low rate of ATP utilization found during unloaded shortening.
肌凝蛋白丝机械传感通过调整开关上电机的数量来确定收缩的效率。因此,卸载缩短速度(V0)已经设定在潜伏期松弛(LR)结束时,刺激开始后约10 ms,此时肌球蛋白丝仍处于OFF状态。在这里,在V0缩短期间,无论是在LR结束还是在等距收缩平台,每半肌球蛋白丝(n)的肌动蛋白附着电机的数量都是根据缩短后力重建过程中半肌节顺应性与力之间的关系来估计的。随着缩短,n的值逐渐减小,从LR结束开始的V0缩短期间,n的值为1-4。n的减少是通过恒定的占空比0.05和电机并联关闭来解释的,这解释了在空载缩短期间发现的非常低的ATP利用率。
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引用次数: 31
期刊
The Japanese journal of physiology
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