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1.
Identification of P‐glycoprotein co‐fractionating proteins and specific binding partners in rat brain microvessels 下载免费PDF全文
Margaret E. Tome Charles P. Schaefer Leigh M. Jacobs Yifeng Zhang Joseph M. Herndon Fabian O. Matty Thomas P. Davis 《Journal of neurochemistry》2015,134(2):200-210
Drug delivery to the brain for the treatment of pathologies with a CNS component is a significant clinical challenge. P‐glycoprotein (PgP), a drug efflux pump in the endothelial cell membrane, is a major factor in preventing therapeutics from crossing the blood‐brain barrier (BBB). Identifying PgP regulatory mechanisms is key to developing agents to modulate PgP activity. Previously, we found that PgP trafficking was altered concomitant with increased PgP activity and disassembly of high molecular weight PgP‐containing complexes during acute peripheral inflammatory pain. These data suggest that PgP activity is post‐translationally regulated at the BBB. The goal of the current study was to identify proteins that co‐localize with PgP in rat brain microvessel endothelial cell membrane microdomains and use the data to suggest potential regulatory mechanisms. Using new density gradients of microvessel homogenates, we identified two unique pools (1,2) of PgP in membrane fractions. Caveolar constituents, caveolin1, cavin1, and cavin2, co‐localized with PgP in these fractions indicating the two pools contained caveolae. A chaperone (Hsc71), protein disulfide isomerase and endosomal/lysosomal sorting proteins (Rab5, Rab11a) also co‐fractionated with PgP in the gradients. These data suggest signaling pathways with a potential role in post‐translational regulation of PgP activity at the BBB.
2.
Speciation in a keystone plant genus is driven by elevation: a case study in New Guinean Ficus 下载免费PDF全文
S. T. Segar J. Zima Jnr B. Isua M. Sisol L. Sam K. Sam D. Souto‐Vilarós V. Novotny 《Journal of evolutionary biology》2017,30(3):512-523
Much of the world's insect and plant biodiversity is found in tropical and subtropical ‘hotspots’, which often include long elevational gradients. These gradients may function as ‘diversity pumps’ and contribute to both regional and local species richness. Climactic conditions on such gradients often change rapidly along short vertical distances and may result in local adaptation and high levels of population genetic structure in plants and insects. We investigated the population genetic structure of two species of Ficus (Moraceae) along a continuously forested elevational gradient in Papua New Guinea. This speciose plant genus is pollinated by tiny, species‐specific and highly coevolved chalcid wasps (Agaonidae) and represented by at least 73 species at our study gradient. We present results from two species of Ficus sampled from six elevations between 200 m and 2700 m a.s.l. (almost the entire elevational range of the genus) and 10 polymorphic microsatellite loci. These results show that strong barriers to gene flow exist between 1200 m and 1700 m a.s.l. Whereas lowland populations are panmictic across distances over 70 km, montane populations can be disjunct over 4 km, despite continuous forest cover. We suggest that the limited gene flow between populations of these two species of montane Ficus may be driven by environmental limitations on pollinator or seed dispersal in combination with local adaptation of Ficus populations. Such a mechanism may have wider implications for plant and pollinator speciation across long and continuously forested elevational gradients if generalist insect pollinators and vertebrate seed dispersers also form populations based on elevation. 相似文献
3.
Hongxu Wu Shifang Yang Xiaojie Wu Junling Zhao Jianping Zhao Qin Ning Yongjian Xu Jungang Xie 《Biochemical and biophysical research communications》2014
Interleukin-33 is a newly described member of the interleukin-1 family. Recent research suggests that IL-33 is increased in lungs and plays a critical role in chronic airway inflammation in cigarette smoke-induced chronic obstructive pulmonary disease (COPD) mice. To determine the role of IL-33 in systemic inflammation, we induced COPD mice models by passive cigarette smoking and identified the IL-33 expression in bronchial endothelial cells and peripheral blood mononuclear cells (PBMCs) of them. After isolation, PBMCs were cultured and stimulated in vitro. We measured expressions of interleukin-6 and interleukin-8 in PBMCs in different groups. The expression of IL-33 in bronchial endothelial cells and PBMCs of COPD mice were highly expressed. Stimulated by cigarette smoke extract (CSE), the expression of IL-6 and IL-8 were induced and enhanced by IL-33. PBMCs of COPD mice produced more IL-6 and IL-8 stimulated by CSE and IL-33. Expression of IL-6 and IL-8 were decreased when stimulated by IL-33 together with soluble ST2. The mRNA production of ST2 in IL-33 stimulated PBMCs was increased. Being pretreated with several kinds of MAPK inhibitors, the secretions of IL-6 and IL-8 in PBMCs did not decrease except for the p38 MAPK inhibitor. We found that IL-33 could induce and enhance the expression of IL-6 and IL-8 in PBMCs of COPD mice via p38 MAPK pathway, and it is a promoter of the IL-6 and IL-8 production in systemic inflammation in COPD mice. 相似文献
4.
Tomoaki Kudo Tohru Hosoyama Makoto Samura Shunsaku Katsura Arata Nishimoto Naruji Kugimiya Yasuhiko Fujii Tao-Sheng Li Kimikazu Hamano 《Biochemical and biophysical research communications》2014
Peripheral blood mononuclear cell (PBMNC) is one of powerful tools for therapeutic angiogenesis in hindlimb ischemia. However, traditional approaches with transplanted PBMNCs show poor therapeutic effects in severe ischemia patients. In this study, we used autograft models to determine whether hypoxic pretreatment effectively enhances the cellular functions of PBMNCs and improves hindlimb ischemia. Rabbit PBMNCs were cultured in the hypoxic condition. After pretreatment, cell adhesion, stress resistance, and expression of angiogenic factor were evaluated in vitro. To examine in vivo effects, we autografted preconditioned PBMNCs into a rabbit hindlimb ischemia model on postoperative day (POD) 7. Preconditioned PBMNCs displayed significantly enhanced functional capacities in resistance to oxidative stress, cell viability, and production of vascular endothelial growth factor. In addition, autologous transplantation of preconditioned PBMNCs significantly induced new vessels and improved limb blood flow. Importantly, preconditioned PBMNCs can accelerate vessel formation despite transplantation on POD 7, whereas untreated PBMNCs showed poor vascularization. Our study demonstrated that hypoxic preconditioning of PBMNCs is a feasible approach for increasing the retention of transplanted cells and enhancing therapeutic angiogenesis in ischemic tissue. 相似文献
5.
The preconcentration of analytes improves sensing using probe tips. In this work, we report a method based on creating a squeeze flow between a cylinder and circular coverslip to preconcentrate material at the liquid–gas interface while allowing a probe tip to be readily inserted there. In verification tests using enhanced green fluorescent protein, this capacity is proven. We estimated a 9.7 times increase in probability for fluorophores to be picked up at the tip using inference from fluorescence intensity distributions found. The method is expeditious, simple, and inexpensive, and it does not require any electrical energy source to operate. 相似文献
6.
7.
在高中生物教学中,血糖平衡的调节一直是重要的教学内容。以往的教学设计思路主要是依靠教师讲述,学生被动接受,因此学生在学习上缺乏主动性。且由于内容比较抽象,学生很难真正理解。教师如何依据现代教育理论,通过组织和引导学生模拟血糖的调节机制,建构和不断修正动态的物理模型,再建构抽象的血糖调节的图解式概念模型,从而使学生深入理解血糖调节的机制,更好地理解体内激素对生命活动进行的调节,不仅是突破教学难点有效途径,对学生建立科学思维方式也具有重要的意义。结合课堂教学实际,介绍“建立血糖调节模型”的教学设计和“概念模型”的教学组织策略两个方面研究成果。 相似文献
8.
Brain energy disorders and oxidative stress due to chronic hypoperfusion were considered to be the major risk factors in the pathogenesis of dementia. In previous studies, we have demonstrated that acupuncture treatment improved cognitive function of VaD patients and multi-infarct dementia (MID) rats. Acupuncture therapy also increased the activities of glycometabolic enzymes in the brain. But it is not clear whether acupuncture treatment compensates neuronal energy deficit after cerebral ischemic through enhancing the activities of glucose metabolic enzymes and preserving mitochondrial function, and whether acupuncture neuroprotective effect is associated with activations of mitochondrial antioxidative defense system. So, the effect of acupuncture therapy on cognitive function, cerebral blood flow (CBF), mitochondrial respiratory function and oxidative stress in the brain of MID rats was investigated in this study. The results showed that acupuncture treatment significantly improved cognitive abilities and increased regional CBF of MID rats. Acupuncture elevated the activities of total SOD, CuZnSOD and MnSOD, decreased the level of malondialdehyde (MDA) and superoxide anion, regulated the ratio of reduced glutathione (GSH) and oxidized glutathione (GSSG) in mitochondria, and raised the level of the respiratory control index (RCI) and P/O ratio and the activities of mitochondrial respiratory enzymes of MID rats. These results indicated that acupuncture treatment improved cognitive function of MID rats; and this improvement might be due to increased CBF, which ameliorated mitochondrial dysfunction induced by ischemia and endogenous oxidative stress system of brain. 相似文献
9.
Ann-Charlotte E. Granholm Michelle L. Price Michael D. Owen 《Cell and tissue research》1995,280(1):49-57
We have investigated the distribution of tyrosine-hydroxylase-like immunoreactivity in the cerebral ganglia of the American cockroach, Periplaneta americana. Groups of tyrosine-hydroxylase-immunoreactive cell bodies occur in various parts of the three regions of the cerebral ganglia. In the protocerebrum, single large neurons or small groups of neurons are located in the lateral neuropil, adjacent to the calyces, and in the dorsal portion of the pars intercerebralis. Small scattered cell bodies are found in the outer layers of the optic lobe, and clusters of larger cell bodies can be found in the deutocerebrum, medial and lateral to the antennal glomeruli. Thick bundles of tyrosine-hydroxylase-positive nerve fibers traverse the neuropil in the proto- and deutocerebrum and innervate the glomerular and the nonglomerular neuropil with fine varicose terminals. Dense terminal patterns are present in the medulla and lobula of the optic lobe, the pars intercerebralis, the medial tritocerebrum, and the area surrounding the antennal glomeruli, the central body and the mushroom bodies. The pattern of tyrosine-hydroxylase-like immunoreactivity is similar to that previously described for catecholaminergic neurons, but it is distinctly different from the distribution of histaminergic and serotonergic neurons. 相似文献
10.
Scott L. Nyberg Russell A. Shatford William D. Payne Wei-Shou Hu Frank B. Cerra 《Biotechnic & histochemistry》1993,68(1):56-63
To establish the importance of fluorescein diacetate (FDA) as a viability stain for cultured hepatocytes. we hypothesized that FDA staining would correlate positively with hepatocyte viability and function. Mixtures of live and dead cells were stained with FDA and scanned by flow cytometry. A close correlation was observed between the live cell fraction and percent viability as determined by FDA staining (R2 = 0.962). Hepatocytes were also sorted into low fluorescence and high fluorescence groups. Both albumin production and lidocaine metabolism (P-450 activity) were significantly increased in the high fluorescence group compared to the low fluorescence group. An automated, fluorescence-activated assay was useful for rapid assessment of hepatocyte viability. In addition. the intensity of green fluorescence following staining with FDA correlated well with two specific measures of hepatocyte function. 相似文献