• 【内源性BDNF和NT-3在调节皮质树突生长中的相反作用。】 复制标题 收藏 收藏
    DOI:10.1016/s0896-6273(00)80316-5 复制DOI
    作者列表:McAllister AK,Katz LC,Lo DC
    BACKGROUND & AIMS: :Neurons within each layer of cerebral cortex express multiple members of the neurotrophin family and their corresponding receptors. This multiplicity could provide functional redundancy; alternatively, different neurotrophins may direct distinct aspects of cortical neuronal growth and differentiation. By neutralizing endogenous neurotrophins in organotypic slices of developing cortex with Trk receptor bodies (Trk-IgGs), we found that BDNF and NT-3 oppose one another in regulating the dendritic growth of pyramidal neurons. In layer 4, both endogenous and exogenous NT-3 inhibited the dendritic growth stimulated by BDNF. In contrast, in layer 6 both endogenous and exogenous BDNF inhibited dendritic growth stimulated by NT-3. These antagonistic actions of endogenous BDNF and NT-3 provide a mechanism by which dendritic growth and retraction can be dynamically regulated during cortical development, and suggest that the multiple neurotrophins expressed in developing cortex represent distinct components of an extracellular signaling system for regulating dendritic growth.
    背景与目标: : 大脑皮层各层内的神经元表达神经营养蛋白家族的多个成员及其相应的受体。这种多样性可以提供功能冗余; 或者,不同的神经营养蛋白可能会指导皮质神经元生长和分化的不同方面。通过用Trk受体体 (Trk-igg) 中和发育中的皮层器官型切片中的内源性神经营养蛋白,我们发现BDNF和NT-3在调节锥体神经元的树突状生长方面相互对抗。在第4层中,内源性和外源性NT-3均抑制BDNF刺激的树突状生长。相反,在第6层中,内源性和外源性BDNF均抑制NT-3刺激的树突生长。内源性BDNF和NT-3的这些拮抗作用提供了一种机制,通过该机制可以在皮质发育过程中动态调节树突生长和收缩,并表明在发育中的皮质中表达的多种神经营养蛋白代表了调节树突生长的细胞外信号系统的不同成分。
  • 【烧伤和内脏损伤合并爆炸伤后腹壁全层损失的成功治疗。】 复制标题 收藏 收藏
    DOI:10.1097/01.BCR.0000238090.70355.6D 复制DOI
    作者列表:Başaran O,Karaarslan P,Sakalloğlu AE,Kesik E,Karakayalý H,Haberal M
    BACKGROUND & AIMS: :A 29-year-old man was admitted to our institution 10 days after he had undergone an urgent exploratory laparotomy at a local army hospital after a terrorist bombing attack. On admission, deep second-degree and third-degree burns involving 25% of the upper and lower extremities were present, together with a 25 x 10-cm abdominal full-thickness blast injury defect on the left side, an infected eviscerated midline incision, and a colostomy on the right side of the abdomen. The patient underwent a second laparotomy, at which time the intraabdominal abscess was drained, and the abdominal cavity was irrigated with saline. A jejunal perforation was found and sutured. The abdominal cavity was left open and covered with a Bogota bag for temporary closure. On postburn day 18, the patient underwent débridment and grafting of the third-degree burns to the left and right arm and right lower extremities. After several débridment sessions (postburn days 16, 18, 20, 22, and 24), an abdominal skin release and reapproximation were performed (postburn day 26). On postburn day 36, split-thickness skin grafts were placed directly on the granulated tissue of the intestines and on a defect in the left flank and iliac regions. Postoperatively, the patient did well. He was discharged on postburn day 78 with all wounds well healed. In our opinion, temporary closure followed by direct application of meshed split-thickness skin grafts to exposed abdominal viscera represents a simple method of reconstruction that can be safely performed, with minimal risk, on critically ill patients.
    背景与目标: : 一名29岁的男子在恐怖爆炸袭击后在当地一家军队医院接受紧急剖腹探查术10天后被送入我们的机构。入院时,出现了涉及上下肢25% 的深二度和三度烧伤,左侧有25x10 cm的腹部全层爆炸伤缺损,感染的内脏中线切口,以及腹部右侧的结肠造口术。患者接受了第二次剖腹手术,此时引流了腹腔内脓肿,并用盐水冲洗了腹腔。发现空肠穿孔并缝合。腹腔保持开放状态,并用波哥大袋覆盖,以暂时关闭。在烧伤后第18天,患者接受了三度烧伤的移植,并将其移植到左,右臂和右下肢。经过几次缓解 (烧伤后第16、18、20、22和24天) 后,进行了腹部皮肤释放和重新逼近 (烧伤后第26天)。在烧伤后的第36天,将厚度分开的皮肤移植物直接放置在肠的颗粒状组织以及左侧和ili区的缺损处。术后,患者表现良好。他在烧伤后第78天出院,所有伤口均愈合良好。在我们看来,暂时封闭,然后直接将网状厚度的皮肤移植物应用到暴露的腹部内脏上,代表了一种简单的重建方法,可以对危重病人安全地进行,风险最小。
  • 【EMX2的潜在靶基因包括Odz/Ten-M和其他对皮质模式有影响的基因家族。】 复制标题 收藏 收藏
    DOI:10.1016/j.mcn.2006.06.012 复制DOI
    作者列表:Li H,Bishop KM,O'Leary DD
    BACKGROUND & AIMS: :EMX2 and PAX6 are expressed by cortical progenitors and specify area patterning. We used representational difference analysis (RDA) to compare expressed RNAs from wild type and Emx2-/- cortex and identified 41 unique clones. Using secondary screening by in situ hybridization, we selected five genes for further analysis, Cdk4, Cofilin1, Crmp1, ME2, and Odz4, involved in neuronal proliferation, differentiation, migration, and axon guidance. Each exhibits differential expression in wild type cortex. Odz4 is one of four members of a vertebrate gene family homologous to the Drosophila pair-rule patterning gene, Odd Oz (Odz), a transmembrane receptor. We show that Odz genes are expressed in complementary patterns in cortex, as well as in nuclei-specific patterns in thalamus that relates to their area-unique cortical expression. In addition, each of the genes analyzed shows different expression patterns in wild type cortex, Emx2, and Pax6 mutant cortex, consistent with potential roles in area patterning. These findings identify potential targets of EMX2 that might account for its function and the defects in Emx2-/- cortex, and suggest that the Odz family of transmembrane proteins influences cortical area patterning downstream to EMX2 and PAX6.
    背景与目标: : EMX2和PAX6由皮质祖细胞表示并指定区域图案。我们使用代表性差异分析 (RDA) 来比较野生型和Emx2-/-皮质的表达rna,并鉴定出41个独特的克隆。使用原位杂交的二次筛选,我们选择了五个基因进行进一步分析,Cdk4,Cofilin1,Crmp1,ME2和Odz4,涉及神经元增殖,分化,迁移和轴突指导。每个在野生型皮层中表现出不同的表达。Odz4是与果蝇对规则模式基因Odd Oz (Odz) (跨膜受体) 同源的脊椎动物基因家族的四个成员之一。我们显示Odz基因在皮层的互补模式中表达,以及在丘脑的核特异性模式中表达,这与其区域独特的皮层表达有关。此外,所分析的每个基因在野生型皮层,Emx2和Pax6突变皮层中显示出不同的表达模式,与区域模式中的潜在作用一致。这些发现确定了可能解释其功能和EMX2-/-皮质缺陷的Emx2的潜在靶标,并表明跨膜蛋白的Odz家族会影响EMX2和pax6下游的皮质区域模式。
  • 【健康人皮质兴奋性和连通性的年龄相关变化: 通过tms-eeg对感觉运动网络进行非侵入性评估。】 复制标题 收藏 收藏
    DOI:10.1016/j.neuroscience.2017.06.014 复制DOI
    作者列表:Ferreri F,Guerra A,Vollero L,Ponzo D,Maatta S,Mervaala E,Iannello G,Di Lazzaro V
    BACKGROUND & AIMS: :The sensorimotor cortical system undergoes structural and functional changes across its lifespan. Some of these changes are physiological and parallel the normal aging process, while others might represent pathophysiological mechanisms underlying neurodegenerative disorders. In the last years, the study of possible age-related modifications in brain sensorimotor functional characteristics has been the focus of several research projects. Here we have used the transcranial magnetic stimulation (TMS)-electroencephalography (EEG) navigated co-registration to investigate the influence of physiological aging on the excitability and connectivity of the human sensorimotor cortical system. To this end, we compared the TMS-evoked EEG potentials (TEPs) collected after stimulating the dominant primary motor cortex (M1) in healthy young subjects (mean age 24.5years) with those collected in healthy older adults (mean age 67.6years). We have shown that, after stimulation of the left motor cortex, TEPs are significantly affected by physiological aging. This phenomenon has a clear spatio-temporal specificity and we speculate that normal aging per se leads to some changes in the excitability of specific cortical neural assemblies whereas other alterations could reflect compensatory mechanisms to such changes.
    背景与目标: : 感觉运动皮层系统在其整个生命周期内经历结构和功能变化。其中一些变化是生理性的,与正常的衰老过程平行,而另一些变化可能代表神经退行性疾病的病理生理机制。在过去的几年中,对大脑感觉运动功能特征中可能与年龄相关的修饰的研究一直是一些研究项目的重点。在这里,我们使用经颅磁刺激 (TMS)-脑电图 (EEG) 导航的共同配准来研究生理衰老对人感觉运动皮层系统的兴奋性和连通性的影响。为此,我们比较了在健康的年轻受试者 (平均年龄24.5岁) 中刺激显性初级运动皮层 (M1) 后收集的TMS诱发EEG电位 (TEPs) 与在健康的老年人 (平均年龄67.6岁) 中收集的TMS诱发EEG电位 (TEPs)。我们已经表明,在刺激左运动皮层后,tep受到生理衰老的显着影响。这种现象具有明显的时空特异性,我们推测正常衰老本身会导致特定皮质神经组件的兴奋性发生某些变化,而其他变化可能反映出这种变化的补偿机制。
  • 【低强度rTMS对穿透性皮质刺伤后神经胶质的局部反应具有性别依赖性作用。】 复制标题 收藏 收藏
    DOI:10.1016/j.expneurol.2017.06.019 复制DOI
    作者列表:Clarke D,Penrose MA,Harvey AR,Rodger J,Bates KA
    BACKGROUND & AIMS: :Repetitive transcranial magnetic stimulation (rTMS), a non-invasive form of brain stimulation, has shown experimental and clinical efficacy in a range of neuromodulatory models, even when delivered at low intensity (i.e. subthreshold for action potential generation). After central nervous system (CNS) injury, studies suggest that reactive astrocytes and microglia can have detrimental but also beneficial effects; thus modulating glial activity, for example through application of rTMS, could potentially be a useful therapeutic tool following neurotrauma. Immunohistochemistry was used to measure the effect of low intensity rTMS (LI-rTMS) on GFAP (astrocyte), IBA1 (microglial), and CS56 (proteoglycan) expression in a unilateral penetrating cortical stab injury model of glial scarring in young adult and aged male and female C57BL6/J mice. Mice received contralateral low frequency, ipsilateral low frequency, ipsilateral high frequency or sham LI-rTMS (4-5mT intensity), for two weeks following injury. There was no significant difference in the overall volume of tissue containing GFAP positive (+) astrocytes, IBA1+ microglia, or proteoglycan expression, between sham and LI-rTMS-treated mice of all ages and sex. Importantly however, the density of GFAP+ astrocytes and IBA1+ microglia immediately adjacent to the injury was significantly reduced following ipsilateral low and high frequency stimulation in adult and aged females (p≤0.05), but was significantly increased in adult and aged males (p≤0.05). LI-rTMS effects were generally of greater magnitude in aged mice compared to young adult mice. These results suggest that sex differences need to be factored into therapeutic rTMS protocols. In particular, more work analyzing frequency and intensity specific effects, especially in relation to age and sex, is required to determine how rTMS can best be used to modify glial reactivity and phenotype following neurotrauma.
    背景与目标: 重复经颅磁刺激 (rTMS) 是一种非侵入性的脑刺激形式,即使在低强度 (即动作电位产生的亚阈值) 下,也已在一系列神经调节模型中显示出实验和临床功效。中枢神经系统 (CNS) 损伤后,研究表明反应性星形胶质细胞和小胶质细胞可能具有有害但有益的作用; 因此,例如通过应用rTMS调节神经胶质活性,可能是神经创伤后有用的治疗工具。免疫组织化学用于测量低强度rTMS (LI-rTMS) 对年轻成年和老年C57BL6/J小鼠单侧穿透性皮质瘢痕损伤模型中GFAP (星形胶质细胞),IBA1 (小胶质细胞) 和CS56 (蛋白聚糖) 表达的影响。损伤后两周,小鼠接受对侧低频,同侧低频,同侧高频或假LI-rTMS (4-5mT强度)。在所有年龄和性别的sham和LI-rTMS治疗的小鼠之间,含有GFAP阳性 () 星形胶质细胞,IBA1小胶质细胞或蛋白聚糖表达的组织的总体积均无显着差异。然而,重要的是,在同侧低频和高频刺激后,与损伤紧邻的GFAP + 星形胶质细胞和IBA1 + 小胶质细胞的密度在成年和老年女性中显著降低 (p ≤ 0.05),但在成年和老年男性中显著增加 (p ≤ 0.05)。与年轻的成年小鼠相比,老年小鼠的LI-rTMS效应通常更大。这些结果表明,需要将性别差异纳入治疗性rTMS方案。特别是,需要更多的工作来分析频率和强度的特定影响,尤其是与年龄和性别有关的影响,以确定rTMS如何最好地用于改变神经创伤后的神经胶质反应性和表型。
  • 【色带厚度影响干法制粒过程中的精细生成。】 复制标题 收藏 收藏
    DOI:10.1016/j.ijpharm.2017.06.038 复制DOI
    作者列表:Sun WJ,Sun CC
    BACKGROUND & AIMS: :Uncontrolled fine generation during the milling process is a challenge for dry granulation by roller compaction. Here, we report the observation that ribbon thickness can significantly influence percentage of fines. Thus, among other parameters, ribbon thickness needs to be controlled for the development of a robust roller compaction process and ensure successful scale up.
    背景与目标: : 碾磨过程中不受控制的精细产生是通过辊压进行干法造粒的挑战。在这里,我们报告了色带厚度会显着影响细粉百分比的观察结果。因此,除其他参数外,还需要控制色带厚度,以开发坚固的压辊压实工艺并确保成功扩大规模。
  • 【精神分裂症患者的错配负性与皮质厚度之间是否存在关联?】 复制标题 收藏 收藏
    DOI:10.1177/1550059417714705 复制DOI
    作者列表:Seol JJ,Kim M,Lee KH,Hur JW,Cho KIK,Lee TY,Chung CK,Kwon JS
    BACKGROUND & AIMS: INTRODUCTION:Mismatch negativity (MMN) is thought to reflect preattentive, automatic auditory processing. Reduced MMN amplitude is among the most robust findings in schizophrenia research. MMN generators have been shown to be located in the temporal and frontal cortices, which are key areas in the pathophysiology of schizophrenia. This study investigated whether frontotemporal cortical thickness was associated with reduced MMN current source density (CSD) strength in patients with schizophrenia. METHODS:Sixteen schizophrenia patients and 18 healthy controls (HCs) were examined using magnetoencephalography while they performed a passive auditory oddball paradigm. All participants underwent a T1 structural magnetic resonance imaging scan in a separate session. We evaluated MMN CSD and cortical thickness, and their associations, in the superior and transverse temporal gyri, as well as in the inferior and middle frontal gyri. RESULTS:Patients exhibited significantly reduced CSD strength in all temporal and frontal areas of interest relative to HCs. There was a positive correlation between CSD strength and cortical thickness in both temporal and frontal areas in HCs. However, schizophrenia patients showed negative correlations between CSD strength and cortical thickness in the bilateral inferior frontal gyri. Additionally, we found positive correlations between frontal cortical thickness and negative and total scores on the Positive and Negative Syndrome Scale (PANSS). CONCLUSIONS:Our findings provide evidence for deficient temporal and frontal MMN generators and a disruption of normal structure-function relationship in patients with schizophrenia.
    背景与目标:
  • 【Kronos早期雌激素预防研究中与女性颈动脉内膜中层厚度和冠状动脉钙化相关的遗传多态性。】 复制标题 收藏 收藏
    DOI:10.1152/physiolgenomics.00114.2012 复制DOI
    作者列表:Miller VM,Petterson TM,Jeavons EN,Lnu AS,Rider DN,Heit JA,Cunningham JM,Huggins GS,Hodis HN,Budoff MJ,Santoro N,Hopkins PN,Lobo RA,Manson JE,Naftolin F,Taylor HS,Harman SM,de Andrade M
    BACKGROUND & AIMS: :Menopausal hormone treatment (MHT) may limit progression of cardiovascular disease (CVD) but poses a thrombosis risk. To test targeted candidate gene variation for association with subclinical CVD defined by carotid artery intima-media thickness (CIMT) and coronary artery calcification (CAC), 610 women participating in the Kronos Early Estrogen Prevention Study (KEEPS), a clinical trial of MHT to prevent progression of CVD, were genotyped for 13,229 single nucleotide polymorphisms (SNPs) within 764 genes from anticoagulant, procoagulant, fibrinolytic, or innate immunity pathways. According to linear regression, proportion of European ancestry correlated negatively, but age at enrollment and pulse pressure correlated positively with CIMT. Adjusting for these variables, two SNPs, one on chromosome 2 for MAP4K4 gene (rs2236935, β = 0.037, P value = 2.36 × 10(-06)) and one on chromosome 5 for IL5 gene (rs739318, β = 0.051, P value = 5.02 × 10(-05)), associated positively with CIMT; two SNPs on chromosome 17 for CCL5 (rs4796119, β = -0.043, P value = 3.59 × 10(-05); rs2291299, β = -0.032, P value = 5.59 × 10(-05)) correlated negatively with CIMT; only rs2236935 remained significant after correcting for multiple testing. Using logistic regression, when we adjusted for waist circumference, two SNPs (rs11465886, IRAK2, chromosome 3, OR = 3.91, P value = 1.10 × 10(-04); and rs17751769, SERPINA1, chromosome 14, OR = 1.96, P value = 2.42 × 10(-04)) associated positively with a CAC score of >0 Agatston unit; one SNP (rs630014, ABO, OR = 0.51, P value = 2.51 × 10(-04)) associated negatively; none remained significant after correcting for multiple testing. Whether these SNPs associate with CIMT and CAC in women randomized to MHT remains to be determined.
    背景与目标: : 更年期激素治疗 (MHT) 可能会限制心血管疾病 (CVD) 的进展,但会带来血栓形成的风险。为了测试与颈动脉内膜中层厚度 (CIMT) 和冠状动脉钙化 (CAC) 定义的亚临床CVD相关的靶向候选基因变异,610参加Kronos早期雌激素预防研究 (KEEPS) 的妇女,MHT预防CVD进展的临床试验,在抗凝剂,促凝剂,纤溶或先天免疫途径的764基因内对13,229单核苷酸多态性 (snp) 进行基因分型。根据线性回归,欧洲血统的比例呈负相关,但入学年龄和脉压与CIMT呈正相关。调整这些变量,两个snp,一个在2号染色体上的MAP4K4基因 (rs2236935,β = 0.037,p值 = 2.36 × 10(-06)),一个在5号染色体上的IL5基因 (rs739318,β = 0.051,p值 = 5.02 × 10(-05)),与CIMT呈正相关; CCL5 17号染色体上的两个snp (rs4796119,β = -0.043,p值 = 3.59 × 10(-05); rs2291299,β = -0.032,p值 = 5.59 × 10(-05)) 与CIMT呈负相关; 校正多重测试后,只有rs2236935仍然显著。使用逻辑回归,当我们调整腰围时,两个snp (rs11465886,IRAK2,3号染色体,OR = 3.91,p值 = 1.10 × 10(-04); 和rs17751769,SERPINA1,14号染色体,OR = 1.96,p值 = 2.42 × 10(-04)) 与> 0 Agatston单位的CAC评分呈正相关; 1个SNP (rs630014,ABO,OR = 0.51,p值 = 2.51 × 10(-04)) 呈负相关; 校正多重测试后无显著。这些snp是否与CIMT和CAC相关,在随机分配到MHT的女性中仍有待确定。
  • 【皮质神经元中的Na ()-Ca2交换电流: 伴随的正向和反向操作以及谷氨酸的作用。】 复制标题 收藏 收藏
    DOI:10.1111/j.1460-9568.1997.tb01482.x 复制DOI
    作者列表:Yu SP,Choi DW
    BACKGROUND & AIMS: Na(+)-Ca2+ exchanger-associated membrane currents were studied in cultured murine neocortical neurons, using whole-cell recording combined with intracellular perfusion. A net inward current specifically associated with forward (Na+(o)-Ca2+(i)) exchange was evoked at -40 mV by switching external 140 mM Li+ to 140 mM Na+. The voltage dependence of this current was consistent with that predicted for 3Na+1Ca2+ exchange. As expected, the current depended on internal Ca2+, and could be blocked by intracellular application of the exchanger inhibitory peptide, XIP. Raising internal Na+ from 3 to 20 mM or switching the external solution from 140 mM Li+ to 30 mM Na+ activated outward currents, consistent with reverse (Na+(i)-Ca2+(o)) exchange. An external Ca2(+)-sensitive current was also identified as associated with reverse Na(+)-Ca2+ exchange based on its internal Na+ dependence and sensitivity to XIP. Combined application of external Na+ and Ca2+ in the absence of internal Na+ triggered a 3.3-fold larger inward current than the current activated in the presence of 3 mM internal Na+, raising the intriguing possibility that Na(+)-Ca2+ exchangers might concurrently operate in both the forward and the reverse direction, perhaps in different subcellular locations. With this idea in mind, we examined the effect of excitotoxic glutamate receptor activation on exchanger operation. After 3-5 min of exposure to 100-200 microM glutamate, the forward exchanger current was significantly increased even when external Na+ was reduced to 100 mM, and the external Ca2(+)-activated reverse exchanger current was eliminated.

    背景与目标: 使用全细胞记录结合细胞内灌注,在培养的鼠新皮层神经元中研究了Na ()-Ca2交换剂相关的膜电流。通过将外部140 mM Li切换到140 mM Na,在40 mV时诱发了与正向 (Na (o)-Ca2 (i)) 交换特别相关的净向内电流。该电流的电压依赖性与3Na 1Ca2交换的预测一致。如预期的那样,电流取决于内部Ca2,并且可以通过在细胞内应用交换抑制肽XIP来阻断电流。将内部Na + 从3升高到20 mm或将外部溶液从140 mM Li + 切换到30mm Na + 激活的外向电流,与反向 (Na +(i)-Ca2 +(o)) 交换一致。根据其内部Na依赖性和对XIP的敏感性,还确定了对外部Ca2 () 敏感的电流与反向Na ()-Ca2交换有关。在不存在内部Na的情况下组合施加外部Na和Ca2触发的内向电流比在3毫米内部Na存在下激活的电流大3.3倍,提出了Na ()-Ca2交换剂可能同时在正向和反向同时运行的有趣可能性,也许在不同的亚细胞位置。考虑到这一想法,我们研究了兴奋性谷氨酸受体激活对交换器操作的影响。暴露于100-200 microM谷氨酸3-5分钟后,即使外部Na降低到100 mM,正向交换电流也显着增加,并且消除了外部Ca2 () 激活的反向交换电流。
  • 【酵母皮质标签蛋白Bud8p和Bud9p的不同结构域具有极性定位和功能。】 复制标题 收藏 收藏
    DOI:10.1091/mbc.e06-10-0899 复制DOI
    作者列表:Krappmann AB,Taheri N,Heinrich M,Mösch HU
    BACKGROUND & AIMS: :In Saccharomyces cerevisiae, diploid yeast cells follow a bipolar budding program, which depends on the two transmembrane glycoproteins Bud8p and Bud9p that potentially act as cortical tags to mark the cell poles. Here, we have performed systematic structure-function analyses of Bud8p and Bud9p to identify functional domains. We find that polar transport of Bud8p and Bud9p does not depend on N-terminal sequences but instead on sequences in the median part of the proteins and on the C-terminal parts that contain the transmembrane domains. We show that the guanosine diphosphate (GDP)/guanosine triphosphate (GTP) exchange factor Bud5p, which is essential for bud site selection and physically interacts with Bud8p, also interacts with Bud9p. Regions of Bud8p and Bud9p predicted to reside in the extracellular space are likely to confer interaction with the N-terminal region of Bud5p, implicating indirect interactions between the cortical tags and the GDP/GTP exchange factor. Finally, we have identified regions of Bud8p and Bud9p that are required for interaction with the cortical tag protein Rax1p. In summary, our study suggests that Bud8p and Bud9p carry distinct domains for delivery of the proteins to the cell poles, for interaction with the general budding machinery and for association with other cortical tag proteins.
    背景与目标: : 在酿酒酵母中,二倍体酵母细胞遵循双极出芽程序,该程序取决于两种跨膜糖蛋白Bud8p和Bud9p,它们可能充当皮质标签来标记细胞极。在这里,我们对Bud8p和Bud9p进行了系统的结构功能分析,以识别功能域。我们发现Bud8p和Bud9p的极性转运不依赖于N端序列,而是依赖于蛋白质中值部分和包含跨膜结构域的C端部分的序列。我们表明,鸟苷二磷酸 (GDP)/鸟苷三磷酸 (GTP) 交换因子Bud5p对于芽位点选择至关重要,并且与Bud8p物理相互作用,也与Bud9p相互作用。预测驻留在细胞外空间中的Bud8p和Bud9p区域可能会与Bud5p的N端区域产生相互作用,从而暗示皮质标签与GDP/GTP交换因子之间的间接相互作用。最后,我们确定了与皮质标签蛋白Rax1p相互作用所需的Bud8p和Bud9p区域。总而言之,我们的研究表明Bud8p和Bud9p具有不同的结构域,用于将蛋白质传递到细胞极,与一般的出芽机制相互作用以及与其他皮质标签蛋白结合。
  • 【唇腭裂中独特的皮质关节表现: 一项初步的功能磁共振成像研究。】 复制标题 收藏 收藏
    DOI:10.1597/05-027 复制DOI
    作者列表:Shinagawa H,Ono T,Honda E,Kurabayashi T,Iriki A,Ohyama K
    BACKGROUND & AIMS: OBJECTIVE:To investigate cortical representation of articulation of the bilabial plosive in patients with cleft lip and palate. DESIGN:We examined cortical representation for /pa/-articulation in cleft lip and palate patients using blood oxygenation level-dependent functional magnetic resonance imaging. SUBJECTS:Data from four postsurgical adult cleft lip and palate patients were compared with those from six healthy volunteers. RESULTS:Activation foci were found in the bilateral primary sensorimotor cortex in all cleft lip and palate patients, as in the controls. The sensorimotor cortex ipsilateral to the side of cleft lip and palate showed greater activation in unilateral cleft lip and palate patients, whereas the sensorimotor cortex contralateral to the side on which cheiloplasty had been performed earlier showed greater activation in a bilateral cleft lip and palate patient. CONCLUSIONS:The results suggest that there may be an ipsilateral dominance in cortical representation during bilabial articulation to the side of the cleft in the upper lip.
    背景与目标:
  • 【NMDA受体介导皮质损伤后fos和fos相关抗原的皮质诱导。】 复制标题 收藏 收藏
    DOI:10.1016/s0014-4886(05)80023-8 复制DOI
    作者列表:Sharp JW,Sagar SM,Hisanaga K,Jasper P,Sharp FR
    BACKGROUND & AIMS: :Cortical cavity lesions and lateral ventricular injections of quinolinic acid, a NMDA receptor agonist, induce Fos and Fos-related antigens (FRAs) throughout ipsilateral adult rat brain cortex in similar patterns. c-fos mRNA, assessed using in situ hybridization, was induced by 1 h and disappeared between 3 and 8 h following cortical lesions. Fos proteins, detected using a specific monoclonal antibody, were induced by 1 h and disappeared by 4 h after cortical lesions. FRA proteins, detected using polyclonal antibodies, were induced between 1 and 4 h and persisted for at least 72 h following focal cortical injury. Intraventricular injections of CPP, a competitive NMDA receptor antagonist, completely blocked the induction of these nuclear proteins in cortex ipsilateral to the focal cortical lesions--except around the injury site itself. Intraventricular injections of quisqualate, a non-NMDA glutamate analogue, induced Fos in hippocampus but not in cortex. These data show that NMDA receptors mediate the induction of Fos and FRAs following cortical injury. It is proposed that local cortical injury releases excitatory amino acids that act at NMDA receptors to initiate spreading depression and that the resultant depolarization induces Fos in neurons throughout the cortex. Since Fos and FRAs are proteins that regulate the expression of target genes, they could mediate long-term biochemical adaptations in neurons following cortical injury.
    背景与目标: : 皮质腔病变和侧脑室注射喹啉酸 (一种NMDA受体激动剂) 以相似的方式在同侧成年大鼠大脑皮层中诱导Fos和Fos相关抗原 (fra)。使用原位杂交评估的c-fos mRNA在1小时内被诱导,并在皮质病变后3至8小时内消失。使用特异性单克隆抗体检测到的Fos蛋白在1小时内被诱导,并在皮质病变后4小时消失。使用多克隆抗体检测到的FRA蛋白在1至4小时之间被诱导,并在局灶性皮质损伤后持续至少72小时。脑室内注射CPP (一种竞争性NMDA受体拮抗剂) 完全阻断了局灶性皮质病变同侧皮质中这些核蛋白的诱导-除了损伤部位本身周围。脑室内注射非NMDA谷氨酸类似物quisqualate会在海马中诱导Fos,但在皮质中不诱导Fos。这些数据表明,NMDA受体介导皮质损伤后Fos和fra的诱导。有人提出,局部皮层损伤会释放起NMDA受体作用的兴奋性氨基酸,从而引发扩散抑制,并且由此产生的去极化会在整个皮层的神经元中诱导Fos。由于Fos和fra是调节靶基因表达的蛋白质,因此它们可以介导皮层损伤后神经元的长期生化适应。
  • 【使用光学相干断层扫描,视网膜厚度分析和地形血管造影对年龄相关性黄斑变性中色素上皮脱离的三维成像。】 复制标题 收藏 收藏
    DOI:10.1007/s00417-006-0418-z 复制DOI
    作者列表:Ahlers C,Michels S,Beckendorf A,Birngruber R,Schmidt-Erfurth U
    BACKGROUND & AIMS: INTRODUCTION:New diagnostic tools such as the retinal thickness analyzer (RTA), optical coherence tomography (OCT), and topographic angiography (TAG) were introduced into clinical ophthalmology during the last years giving the examiner new insights into anatomical and functional aspects of macular disease. In this study, advantages and disadvantages of the new imaging methods have been evaluated in patients with serous (sPED) and fibrovascular pigment epithelial detachments (fPED) secondary to age-related macular degeneration (AMD). METHODS:TAG, using fluorescein angiography (FA), provides a three-dimensional profile of the fluorescein pattern based on the analysis of a set of 32 confocal images over a depth of 4 mm. RTA and OCT provide cross-sectional images of the neurosensory retina and the retinal pigment epithelium-choriocapillary complex as well as retinal thickness data encoded in a false color map. We compared and evaluated these modalities in 15 patients with fPED and 15 patients with sPED secondary to AMD. RESULTS:In patients with classic fPED, TAG detected neovascular structures and delineated their configuration. In sPEDs, pooling of extravascular fluid was detected in a dome-shaped configuration. OCT provided detailed information on the neurosensory retina's structures but failed to detect the neovascular membrane in fPED. Mapping the retinal thickness, RTA and OCT both failed to detect the PED and showed typical algorithm error-based patterns. CONCLUSION:TAG OCT and RTA are useful imaging modalities in the evaluation of AMD cases. TAG visualizes the vascular configuration, dynamic perfusion, and leakage changes. OCT and RTA are able to complementarily document intra-, subretinal, and sub-RPE fluid accumulation secondary to CNV. However, OCT seems to be more efficient in imaging AMD-related pathologies than RTA, as this modality is often compromised by intra- or subretinal structural abnormalities. Nevertheless, all modalities may provide further valuable insight into AMD pathogenesis, enhance diagnostic quality, and improve the assessment of therapeutic effects.
    背景与目标:
  • 【视觉皮层区域MT的早期成熟取决于下牙髓的视网膜内侧部分的输入。】 复制标题 收藏 收藏
    DOI:10.1523/JNEUROSCI.3269-12.2012 复制DOI
    作者列表:Warner CE,Kwan WC,Bourne JA
    BACKGROUND & AIMS: :The hierarchical development of the primate visual cortex and associated streams remains somewhat of a mystery. While anatomical, physiological, and psychological studies have demonstrated the early maturation of the dorsal "where"/"how" or motion cortical stream, little is known about the circuitry responsible. The influence of the retinogeniculostriate pathway has been investigated, but little attention has been paid to the role of two more recently described disynaptic retinothalamic projections to the middle temporal (MT) area, an early maturing dorsal stream cortical field, and which bypass the primary visual cortex (V1). These pathways are via the koniocellular layers of the lateral geniculate nucleus (LGN) and the medial portion of the inferior pulvinar (PIm). Both have been demonstrated in the adult nonhuman primate, but their influence during the maturation of the visual cortex is unknown. We used a combination of neural tracing and immunohistochemistry to follow the development of LGN and PIm inputs to area MT in the marmoset monkey. Our results revealed that the early maturation of area MT is likely due to the disynaptic retinopulvinar input and not the retinogeniculate input or the direct projection from V1. Furthermore, from soon after birth to adulthood, there was a dynamic shift in the ratio of input from these three structures to area MT, with an increasing dominance of the direct V1 afference.
    背景与目标: : 灵长类视觉皮层和相关流的分层发展仍然是一个谜。尽管解剖学,生理学和心理学研究表明背侧 “where”/“how” 或运动皮质流的早期成熟,但对负责的电路知之甚少。已经研究了视网膜原肌纹状体途径的影响,但很少关注两个最近描述的双突触视网膜丘脑投射对中颞 (MT) 区域的作用,即早熟的背流皮层场,并且绕过了初级视觉皮层 (V1)。这些途径是通过外侧膝状核 (LGN) 和下牙髓 (PIm) 的内侧部分的细胞层。两者都已在成年非人类灵长类动物中得到证实,但它们在视觉皮层成熟过程中的影响尚不清楚。我们使用神经追踪和免疫组织化学的组合来跟踪LGN和PIm输入到mar猴中MT区域的发育。我们的结果表明,区域MT的早期成熟可能是由于非突触视网膜的输入,而不是视网膜的输入或来自v1的直接投影。此外,从出生后不久到成年,这三个结构的输入与区域MT的比率发生了动态变化,直接V1传入的优势越来越大。
  • 【在皮质失步过程中,通过感觉刺激引起的顺序神经活动模式的形成和混响得到增强。】 复制标题 收藏 收藏
    DOI:10.1016/j.neuron.2013.06.013 复制DOI
    作者列表:Bermudez Contreras EJ,Schjetnan AG,Muhammad A,Bartho P,McNaughton BL,Kolb B,Gruber AJ,Luczak A
    BACKGROUND & AIMS: :Memory formation is hypothesized to involve the generation of event-specific neural activity patterns during learning and the subsequent spontaneous reactivation of these patterns. Here, we present evidence that these processes can also be observed in urethane-anesthetized rats and are enhanced by desynchronized brain state evoked by tail pinch, subcortical carbachol infusion, or systemic amphetamine administration. During desynchronization, we found that repeated tactile or auditory stimulation evoked unique sequential patterns of neural firing in somatosensory and auditory cortex and that these patterns then reoccurred during subsequent spontaneous activity, similar to what we have observed in awake animals. Furthermore, the formation of these patterns was blocked by an NMDA receptor antagonist, suggesting that the phenomenon depends on synaptic plasticity. These results suggest that anesthetized animals with a desynchronized brain state could serve as a convenient model for studying stimulus-induced plasticity to improve our understanding of memory formation and replay in the brain.
    背景与目标: : 假设记忆形成涉及学习过程中事件特定的神经活动模式的产生以及这些模式随后的自发重新激活。在这里,我们提供的证据表明,这些过程也可以在氨基甲酸酯麻醉的大鼠中观察到,并且通过尾巴捏合,皮质下卡巴胆碱输注或全身苯丙胺给药引起的不同步的大脑状态而增强。在去同步化过程中,我们发现反复的触觉或听觉刺激诱发了体感和听觉皮层中神经放电的独特顺序模式,并且这些模式随后在随后的自发活动中再次发生,类似于我们在清醒动物中观察到的情况。此外,这些模式的形成被NMDA受体拮抗剂阻断,表明该现象取决于突触可塑性。这些结果表明,大脑状态不同步的麻醉动物可以作为研究刺激诱导的可塑性的方便模型,以提高我们对大脑中记忆形成和重放的理解。

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