BACKGROUND & AIMS: :Many economically important characteristics of agricultural crops are measured as ordinal traits. Statistical analysis of the genetic basis of ordinal traits appears to be quite different from regular quantitative traits. The generalized linear model methodology implemented via the Newton-Raphson algorithm offers improved efficiency in the analysis of such data, but does not take full advantage of the extensive theory developed in the linear model arena. Instead, we develop a multivariate model for ordinal trait analysis and implement an EM algorithm for parameter estimation. We also propose a method for calculating the variance-covariance matrix of the estimated parameters. The EM equations turn out to be extremely similar to formulae seen in standard linear model analysis. Computer simulations are performed to validate the EM algorithm. A real data set is analyzed to demonstrate the application of the method. The advantages of the EM algorithm over other methods are addressed. Application of the method to QTL mapping for ordinal traits is demonstrated using a simulated baclcross (BC) population.

背景与目标： : 农业作物的许多经济上重要的特征被衡量为序数性状。序数性状的遗传基础的统计分析似乎与常规数量性状有很大不同。通过Newton-Raphson算法实现的广义线性模型方法在分析此类数据时提供了更高的效率，但并未充分利用线性模型领域中开发的广泛理论。相反，我们开发了用于顺序特征分析的多变量模型，并实现了用于参数估计的EM算法。我们还提出了一种计算估计参数的方差-协方差矩阵的方法。事实证明，EM方程与标准线性模型分析中的公式极为相似。进行计算机仿真以验证EM算法。分析了实际数据集以证明该方法的应用。讨论了EM算法相对于其他方法的优势。使用模拟的baclcross (BC) 种群证明了该方法在顺序性状的QTL映射中的应用。

BACKGROUND & AIMS: :The vascular endothelial growth factor (VEGF) family of cytokines is involved in the maintenance of existing adult blood vessels as well as in angiogenesis, the sprouting of new vessels. To study the proangiogenic activation of VEGF receptors (VEGFRs) by VEGF family members in skeletal muscle, we develop a computational model of VEGF isoforms (VEGF(121), VEGF(165)), their cell surface receptors, and the extracellular matrix in in vivo tissue. We build upon our validated model of the biochemical interactions between VEGF isoforms and receptor tyrosine kinases (VEGFR-1 and VEGFR-2) and nonsignaling neuropilin-1 coreceptors in vitro. The model is general and could be applied to any tissue; here we apply the model to simulate the transport of VEGF isoforms in human vastus lateralis muscle, which is extensively studied in physiological experiments. The simulations predict the distribution of VEGF isoforms in resting (nonexercising) muscle and the activation of VEGFR signaling. Little of the VEGF protein in muscle is present as free, unbound extracellular cytokine; the majority is bound to the cell surface receptors or to the extracellular matrix. However, interstitial sequestration of VEGF(165) does not affect steady-state receptor binding. In the absence of neuropilin, VEGF(121) and VEGF(165) behave similarly, but neuropilin enhances the binding of VEGF(165) to VEGFR-2. This model is the first to study VEGF tissue distribution and receptor activation in human muscle, and it provides a platform for the design and evaluation of therapeutic approaches.

背景与目标： : 细胞因子的血管内皮生长因子 (VEGF) 家族参与现有成人血管的维持以及血管生成，新血管的萌发。为了研究骨骼肌中VEGF家族成员对VEGF受体 (VEGFRs) 的促血管生成激活，我们建立了VEGF同工型 (VEGF(121)，VEGF(165))，它们的细胞表面受体和细胞外基质的计算模型。体内组织。我们建立在我们验证的VEGF同工型与受体酪氨酸激酶 (VEGFR-1和VEGFR-2) 之间的生化相互作用的模型，以及体外非信号neuropilin-1共受体。该模型是通用的，可以应用于任何组织; 在这里，我们应用该模型来模拟人外侧肌中VEGF同工型的运输，这在生理实验中得到了广泛的研究。模拟预测了静息 (非运动) 肌肉中VEGF亚型的分布以及VEGFR信号传导的激活。肌肉中几乎没有VEGF蛋白以游离的，未结合的细胞外细胞因子的形式存在; 大多数与细胞表面受体或细胞外基质结合。然而，VEGF(165) 的间质隔离不影响稳态受体结合。在不存在神经菌毛蛋白的情况下，VEGF(121) 和VEGF(165) 表现相似，但是神经菌毛蛋白增强VEGF(165) 与VEGFR-2的结合。该模型是第一个研究人肌肉中VEGF组织分布和受体激活的模型，它为治疗方法的设计和评估提供了平台。

BACKGROUND & AIMS: :We examined seizure-susceptibility in a Drosophila model of human epilepsy using optogenetic stimulation of ReaChR (red-activatable channelrhodopsin). Photostimulation of the seizure-sensitive mutant parabss1 causes behavioral paralysis that resembles paralysis caused by mechanical stimulation, in many aspects. Electrophysiology shows that photostimulation evokes abnormal seizure-like neuronal firing in parabss1 followed by a quiescent period resembling synaptic failure and apparently responsible for paralysis. The pattern of neuronal activity concludes with seizure-like activity just prior to recovery. We tentatively identify the mushroom body as one apparent locus of optogenetic seizure initiation. The α/β lobes may be primarily responsible for mushroom body seizure induction.

背景与目标： : 我们使用ReaChR (红色激活的通道视紫红质) 的光遗传学刺激检查了果蝇癫痫模型中的癫痫发作敏感性。在许多方面，对癫痫敏感的突变体parabss1的光刺激会导致行为麻痹，类似于机械刺激引起的麻痹。电生理学表明，光刺激会在parabss1中引起异常的癫痫样神经元放电，随后是类似于突触衰竭的静止期，显然是造成瘫痪的原因。神经元活动的模式在恢复之前以癫痫样活动结束。我们初步确定蘑菇体是光遗传发作开始的一个明显基因座。Α/β 裂片可能是引起蘑菇体癫痫发作的主要原因。

BACKGROUND & AIMS: :In this study, several electrocardiogram (ECG)-derived indices corresponding to both ventricular depolarization and repolarization were evaluated during acute myocardial ischemia in an experimental model of myocardial infarction produced by 40 min coronary balloon inflation in 13 pigs. Significant changes were rapidly observed from minute 4 after the start of coronary occlusion, achieving their maximum values between 11 and 22 min for depolarization and between 9 and 12 min for repolarization indices, respectively. Subsequently, these maximum changes started to decrease during the latter part of the occlusion. Depolarization changes associated with the second half of the QRS complex showed a significant but inverse correlation with the myocardium at risk (MaR) estimated by scintigraphic images. The correlation between MaR and changes of the downward slope of the QRS complex, [Formula: see text], evaluated at the two more relevant peaks observed during the occlusion, was r = -0.75, p < 0.01 and r = -0.79, p < 0.01 for the positive and negative deflections observed in [Formula: see text], temporal evolution, respectively. Repolarization changes, analyzed by evaluation of ST segment elevation at the main observed positive peak, also showed negative, however non-significant correlation with MaR: r = -0.34, p = 0.28. Our results suggest that changes evaluated in the latter part of the depolarization, such as those described by [Formula: see text], which are influenced by R-wave amplitude, QRS width and ST level variations simultaneously, correlate better with the amount of ischemia than other indices evaluated in the earlier part of depolarization or during the ST segment.

背景与目标： : 在这项研究中，在13头猪的40分钟冠状动脉球囊充气产生的心肌梗死实验模型中，评估了急性心肌缺血期间对应于心室去极化和复极化的几种心电图 (ECG) 衍生指标。从冠状动脉闭塞开始后的第4分钟开始迅速观察到显着变化，分别在去极化11至22分钟和复极化指数9至12分钟之间达到最大值。随后，在闭塞的后期，这些最大变化开始减少。与QRS复合物的后半部分相关的去极化变化与闪烁显像估计的危险心肌 (MaR) 呈显着但呈负相关。在闭塞期间观察到的两个更相关的峰处评估的MaR与QRS复合体向下斜率的变化之间的相关性为r = -0.75，p <0.01和r = -0.79，对于在 [公式: 参见文本] 中观察到的正偏转和负偏转，分别为p <0.01。通过评估主要观察到的正峰处的ST段抬高来分析复极化变化，也显示出负的，但与MaR无关: r = -0.34，p = 0.28。我们的结果表明，在去极化的后半部分评估的变化，例如 [公式: 参见文本] 所描述的变化，同时受到R波振幅，QRS宽度和ST电平变化的影响，与在去极化早期或ST段期间评估的其他指标相比，与缺血量的相关性更好。

BACKGROUND & AIMS: OBJECTIVE:Incontinentia pigmenti (IP) is a genetic disease leading to severe neurological symptoms, such as epileptic seizures, but no specific treatment is available. IP is caused by pathogenic variants that inactivate the Nemo gene. Replacing Nemo through gene therapy might provide therapeutic benefits. METHODS:In a mouse model of IP, we administered a single intravenous dose of the adeno-associated virus (AAV) vector, AAV-BR1-CAG-NEMO, delivering the Nemo gene to the brain endothelium. Spontaneous epileptic seizures and the integrity of the blood-brain barrier (BBB) were monitored. RESULTS:The endothelium-targeted gene therapy improved the integrity of the BBB. In parallel, it reduced the incidence of seizures and delayed their occurrence. Neonate mice intravenously injected with the AAV-BR1-CAG-NEMO vector developed no hepatocellular carcinoma or other major adverse effects 11 months after vector injection, demonstrating that the vector has a favorable safety profile. INTERPRETATION:The data show that the BBB is a target of antiepileptic treatment and, more specifically, provide evidence for the therapeutic benefit of a brain endothelial-targeted gene therapy in IP. Ann Neurol 2017;82:93-104.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Persons with a negative result on screening colonoscopy are recommended to repeat the procedure in 10 years. OBJECTIVE:To assess the effectiveness and costs of colonoscopy versus other rescreening strategies after an initial negative colonoscopy result. DESIGN:Microsimulation model. DATA SOURCES:Literature and data from the Surveillance, Epidemiology, and End Results program. TARGET POPULATION:Persons aged 50 years who had no adenomas or cancer detected on screening colonoscopy. TIME HORIZON:Lifetime. PERSPECTIVE:Societal. INTERVENTION:No further screening or rescreening starting at age 60 years with colonoscopy every 10 years, annual highly sensitive guaiac fecal occult blood testing (HSFOBT), annual fecal immunochemical testing (FIT), or computed tomographic colonography (CTC) every 5 years. OUTCOME MEASURES:Lifetime cases of colorectal cancer, life expectancy, and lifetime costs per 1000 persons, assuming either perfect or imperfect adherence. RESULTS OF BASE-CASE ANALYSIS:Rescreening with any method substantially reduced the risk for colorectal cancer compared with no further screening (range, 7.7 to 12.6 lifetime cases per 1000 persons [perfect adherence] and 17.7 to 20.9 lifetime cases per 1000 persons [imperfect adherence] vs. 31.3 lifetime cases per 1000 persons with no further screening). In both adherence scenarios, the differences in life-years across rescreening strategies were small (range, 30 893 to 30 902 life-years per 1000 persons [perfect adherence] vs. 30 865 to 30 869 life-years per 1000 persons [imperfect adherence]). Rescreening with HSFOBT, FIT, or CTC had fewer complications and was less costly than continuing colonoscopy. RESULTS OF SENSITIVITY ANALYSIS:Results were sensitive to test-specific adherence rates. LIMITATION:Data on adherence to rescreening were limited. CONCLUSION:Compared with the currently recommended strategy of continuing colonoscopy every 10 years after an initial negative examination, rescreening at age 60 years with annual HSFOBT, annual FIT, or CTC every 5 years provides approximately the same benefit in life-years with fewer complications at a lower cost. Therefore, it is reasonable to use other methods to rescreen persons with negative colonoscopy results. PRIMARY FUNDING SOURCE:National Cancer Institute.

背景与目标：

BACKGROUND & AIMS: :Purpose. To evaluate whether 3T clinical MRI with a small-animal coil and gradient-echo (GE) sequence could be used to characterize long-term left ventricular remodelling (LVR) following nonreperfused myocardial infarction (MI) using semi-automatic segmentation software (SASS) in a rat model. Materials and Methods. 5 healthy rats were used to validate left ventricular mass (LVM) measured by MRI with postmortem values. 5 sham and 7 infarcted rats were scanned at 2 and 4 weeks after surgery to allow for functional and structural analysis of the heart. Measurements included ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV), and LVM. Changes in different regions of the heart were quantified using wall thickness analyses. Results. LVM validation in healthy rats demonstrated high correlation between MR and postmortem values. Functional assessment at 4 weeks after MI revealed considerable reduction in EF, increases in ESV, EDV, and LVM, and contractile dysfunction in infarcted and noninfarcted regions. Conclusion. Clinical 3T MRI with a small animal coil and GE sequence generated images in a rat heart with adequate signal-to-noise ratio (SNR) for successful semiautomatic segmentation to accurately and rapidly evaluate long-term LVR after MI.

背景与目标： : 目的。评估是否可以使用半自动分割软件 (SASS) 在大鼠模型中使用带有小动物线圈和梯度回波 (GE) 序列的3t临床MRI来表征非再灌注心肌梗死 (MI) 后的长期左心室重塑 (LVR)。材料和方法。5只健康大鼠用于验证MRI测量的左心室质量 (LVM) 和死后值。在手术后2周和4周对5只假手术大鼠和7只梗死大鼠进行扫描，以进行心脏的功能和结构分析。测量包括射血分数 (EF)，舒张末期容积 (EDV)，收缩末期容积 (ESV) 和LVM。使用壁厚分析来量化心脏不同区域的变化。结果。健康大鼠的LVM验证表明MR与死后值之间存在高度相关性。MI后4周的功能评估显示EF显着降低，ESV，EDV和LVM增加以及梗塞和非梗塞区域的收缩功能障碍。结论。具有小动物线圈和GE序列的临床3T MRI在大鼠心脏中生成的图像具有足够的信噪比 (SNR)，可成功进行半自动分割，以准确，快速地评估MI后的长期LVR。

BACKGROUND & AIMS: :Lung cancer is the leading cause of cancer-related mortality in both men and women throughout the world. This disease is strongly associated with tobacco smoking. The aim of this manuscript was to establish an in vitro model that mimics the chronic exposures of alveolar epithelial type II cells to the tobacco-specific nitrosamine carcinogen, NNK. Immortalized non-neoplastic alveolar epithelial cells type II, (E10 cells), from BALB/c mice were exposed to low concentration of NNK (100 pM) during 5, 10, 15, and 20 cycles of 48 h. NNK-transformed cells showed an increase of proliferation rate and motility. Moreover, these cells underwent epithelial-to-mesenchymal transition (EMT). Increased migratory capacity and EMT were correlated to the time of exposure to NNK. NNK-transformed cells were tested for their growth and metastatic capacity in vivo. Subcutaneous injection of cells exposed to NNK for 20 cycles (E10-NNK20 clone) into BALB/c mice led to the formation of subcutaneous tumors that arose after 40 ± 17 d in all animals, which died 95 ± 18 d after cell inoculation, with lymph nodes and lung metastasis. The morphological characteristics of tumors were compatible with metastatic undifferentiated carcinoma. Cells exposed to NNK for 5-10 cycles did not display metastatic capacity, while those exposed for 15 cycles displayed low capacity. Our results show that prolonged exposures to NNK led the cells to increasingly acquire malignant properties. The cellular model presented in this study is suitable for studying the molecular events involved in the different stages of malignant transformation.

背景与目标： : 肺癌是全世界男性和女性癌症相关死亡率的主要原因。这种疾病与吸烟密切相关。本手稿的目的是建立一个体外模型，该模型模拟肺泡上皮II型细胞对烟草特异性亚硝胺致癌物NNK的慢性暴露。来自BALB/c小鼠的永生化的非肿瘤性II型肺泡上皮细胞 (E10细胞) 在48  h的5、10、15和20个周期中暴露于低浓度的NNK (100  pM)。NNK转化的细胞显示出增殖速率和运动能力的增加。此外，这些细胞经历了上皮-间质转化 (EMT)。迁移能力和EMT的增加与NNK暴露时间相关。测试NNK转化的细胞在体内的生长和转移能力。在BALB/c小鼠中皮下注射暴露于NNK 20个周期的细胞 (E10-NNK20克隆) 导致所有动物皮下肿瘤的形成，该肿瘤在40  ±   17 d后出现，在细胞接种后95  ±   18 d死亡，并伴有淋巴结和肺转移。肿瘤的形态特征与转移性未分化癌相容。暴露于NNK 5-10个周期的细胞未显示转移能力，而暴露于15个周期的细胞显示低容量。我们的结果表明，长时间暴露于NNK导致细胞越来越多地获得恶性特性。本研究中提出的细胞模型适用于研究恶性转化不同阶段涉及的分子事件。

BACKGROUND & AIMS: OBJECTIVE:Acute stress reactions (ASR) and postpartum depressive symptoms (PDS) are frequent after childbirth. The present study addresses the change and overlap of ASR and PDS from the 1- to 3-week postpartum and examines the interplay of caregiver support and subjective birth experience with regard to the development of ASR/PDS within a longitudinal path model. METHOD:A total of 219 mothers completed questionnaires about caregiver support and subjective birth experience (Salmon's Item List) at 48-6-h postpartum. ASR and PDS were measured for 1- and 3-week postpartum. The Impact of Event Scale (IES) was used to assess ASR, and the Edinburgh Postnatal Depression Scale (EPDS) was used to assess PDS. RESULTS:ASR was frequent 1-week postpartum (44.7%) and declined till week 3 (24.8%, p <.001), while the prevalence of PDS was continuous (14.2% week 1; 12.6% week 3; p = .380). Favorable reports of caregiver support were related to better subjective childbirth experience, which was related to lower ASR and PDS (controlled for age, mode of delivery, parity, EDA and duration of childbirth). CONCLUSION:High quality of intrapartum care and positive birth experiences facilitate psychological adjustment in the first 3-week postpartum.

背景与目标：

BACKGROUND & AIMS: :The need to find effective treatments for patients with Anorexia or Bulimia nervosa has led to the professionals who care for them to develop new forms of treatment that take into account the variables that cause resistance to change. Patients in this study (2006-2009) have the following characteristics: 340 patients who have 7 or more years of evolution and/or have tried numerous previous treatments without having succeeded in starting and / or maintaining the desired changes, that allowed them to recover steadily. As the proposed treatment, the patient-treatment team is based on the principles of the training model. It considers the patient holistically, it informs and provides him with resources to increase its commitment to change. Teaches the patient to take care physically and mentally as a way to regain their health and leave the disorder in a stable way. Includes family members as essential support in the recovery of their closest. Therapists require extensive experience in the treatment of ED, flexibility, ability to integrate with other team members even if they use different theoretical models, skills for group sessions, ability to handle negative emotions and frustration tolerance. Finally, the model presented below has been implemented, recovered patients whose stay in the disorder exceeded 15 years of development and led to permanent occupational disability.

背景与目标： : 需要为厌食症或神经性贪食症患者找到有效的治疗方法，这导致了照顾他们的专业人员开发新的治疗方法，其中考虑了导致耐药性变化的变量。该研究中的患者 (2006-2009) 具有以下特征: 340具有7年或更长时间的进化和/或尝试了许多先前治疗而没有成功开始和/或维持期望的变化的患者，这使他们能够稳定地恢复。作为建议的治疗方法，患者治疗团队基于培训模型的原理。它从整体上考虑患者，告知并为他提供资源，以增加其对变革的承诺。教导患者在身体和精神上保持谨慎，以恢复健康并以稳定的方式离开疾病。包括家庭成员作为他们最亲近的恢复的基本支持。治疗师需要在治疗ED方面的丰富经验，灵活性，与其他团队成员整合的能力，即使他们使用不同的理论模型，小组会议的技能，处理负面情绪和挫折承受能力。最后，下面介绍的模型已经实施，康复的患者在疾病中的停留时间超过15年，并导致永久性职业残疾。

BACKGROUND & AIMS: INTRODUCTION:Management of traumatic brain injury (TBI) is focused on minimizing or preventing secondary brain injury. Remote ischemic conditioning (RIC) is an established treatment modality that has been shown to improve patient outcomes in different clinical settings by influencing inflammatory insults. In a clinical trial, RIC showed amelioration of SB100 and neuron-specific enolase. The aim of our study was to further elucidate the mechanisms and outcome when applying RIC in a mouse model of traumatic brain injury. METHODS:We subjected 100 male C57BL mice to a closed-skull cortical-controlled impact injury. Two hours after the TBI, the animals were allocated to either the RIC group (n = 50) or the sham group (n = 50). By clamping the exposed femoral artery, we induced RIC by six 4-minute cycles of ischemia and reperfusion. Circulating levels of S100-B, neuron-specific enolase, and glial fibrillary acidic protein were measured at multiple time points. Animals were additionally observed daily for cognition and motor coordination via novel object recognition and rotarod. Brain sections were stained and evaluated for neuronal injury at post-TBI Day 5. RESULTS:The RIC animals had a significantly higher recognition index than did sham at 24, 48, and 72 hours after intervention. Rotarod latency was higher in the RIC animals compared to the sham animals at all-time points, and statistically significant at 120 hours after intervention. The RIC group demonstrated preserved cognitive function and motor coordination compared to the sham. On hematoxylin and eosin and immunohistochemical staining of brain sections, there was less area of neuronal degeneration and astrocytosis, respectively, in the RIC group compared to the sham group. There was no significant difference in systemic neuronal markers between the RIC and sham animals. CONCLUSION:Remote ischemic conditioning 2 hours after injury preserved cognitive functions and motor coordination in a mouse model of TBI. Remote ischemic conditioning can preserve viability of neurons and astrocytes after TBI and has potential as a clinically noninvasive and relatively easy method to improve outcome after TBI. LEVEL OF EVIDENCE:Therapeutic studies, randomized controlled trial, level I.

背景与目标：

BACKGROUND & AIMS: :Selected plants documented as medicinal in an ethnobotanical study with the Nahua of the Sierra de Zongolica (Veracruz, Mexico) were evaluated for anti-inflammatory and antibacterial activity. One of the potential sides of action of anti-inflammatory drugs is the transcription factor NF-κB. This factor is essential for the immune, inflammatory, and acute phase responses. We therefore tested extracts from a total of 28 plants used by the Nahua Indians for their potential effect on the activation of the transcription factor NF-κB. The leaves of Tithonia diversifolia (Hemsl.) A. Gray (Asteraceae) was the only extract which showed inhibitory activity. Nonspecific DNA binding activities were not noticably influenced. Phytochemical studies to isolate the active principle and further biochemical studies in order to better understand the mode of action of this NF-κB inhibitor have been initiated. Five plants showed noteworthy antibacterial activity against some pathogenic (Staphylococcus aureus ATCC 25933 and Yersinia enterocolitica 03) and nonpathogenic (E. coli DSM 1077, Micrococcus luteus DSM 348) microorganism: Acacia cornigera, Cuscuta tinctoria, Ludwigia octovalvis, Lysiloma divaricata, and Tithonia diversifolia.

背景与目标： : 在一项民族植物学研究中与Sierra de Zongolica (墨西哥韦拉克鲁斯) 的Nahua进行了记录为药用植物的抗炎和抗菌活性评估。抗炎药物的潜在作用方面之一是转录因子NF-κ b。该因素对于免疫，炎症和急性期反应至关重要。因此，我们测试了纳华印第安人使用的总共28种植物的提取物对转录因子NF-κ b激活的潜在影响。Tithonia diversifolia (Hemsl.) A.Gray (菊科) 是唯一具有抑制活性的提取物。非特异性DNA结合活性没有受到明显影响。分离活性原理的植物化学研究和进一步的生化研究已经开始，以便更好地了解这种NF-κ b抑制剂的作用方式。五种植物对某些致病性 (金黄色葡萄球菌ATCC 25933和小肠结肠炎耶尔森氏菌03) 和非致病性 (大肠杆菌DSM 1077，微球菌DSM 348) 微生物具有显着的抗菌活性: 金相相思，刺槐，octovalvis，Lysiloma divaricata和Tithonia diversifolia。

BACKGROUND & AIMS: :After nerve injury, Schwann cells proliferate and revert to a phenotype that supports nerve regeneration. This phenotype-changing process can be viewed as Schwann cell dedifferentiation. Here, we investigated the role of extracellular ATP in Schwann cell dedifferentiation and proliferation during Wallerian degeneration. Using several markers of Schwann cell dedifferentiation and proliferation in sciatic explants, we found that extracellular ATP inhibits Schwann cell dedifferentiation and proliferation during Wallerian degeneration. Furthermore, the blockage of lysosomal exocytosis in ATP-treated sciatic explants is sufficient to induce Schwann cell dedifferentiation. Together, these findings suggest that ATP-induced lysosomal exocytosis may be involved in Schwann cell dedifferentiation.

背景与目标： : 神经损伤后，雪旺氏细胞增殖并恢复为支持神经再生的表型。这种表型变化过程可以看作是雪旺细胞去分化。在这里，我们研究了细胞外ATP在华勒变性过程中雪旺细胞去分化和增殖中的作用。使用坐骨外植体中雪旺细胞去分化和增殖的几种标记，我们发现细胞外ATP在华勒变性过程中抑制雪旺细胞去分化和增殖。此外，ATP处理的坐骨外植体中溶酶体胞吐作用的阻断足以诱导雪旺氏细胞去分化。总之，这些发现表明ATP诱导的溶酶体胞吐作用可能与雪旺氏细胞去分化有关。

BACKGROUND & AIMS: :Neural transplantation of GABA-producing cells into key structures within seizure-suppressing circuits holds promise for medication-resistant epilepsy patients not eligible for resection of the epileptic focus. The substantia nigra pars reticulata (SNr), a basal ganglia output structure, is well known to modulate different seizure types. A recent microinjection study by our group indicated that the subthalamic nucleus (STN), which critically regulates nigral activity, might be a more promising target for focal therapy in epilepsies than the SNr. As a proof of principle, we therefore assessed the anticonvulsant efficacy of bilateral and unilateral allografting of GABA-producing cell lines into the STN using the timed intravenous pentylenetetrazole seizure threshold test, which allows repeated seizure threshold determinations in individual rats. We observed (a) that grafted cells survived up to the end of the experiments, (b) that anticonvulsant effects can be induced by bilateral transplantation into the STN using immortalized GABAergic cells derived from the rat embryonic striatum and cells additionally transfected to obtain higher GABA synthesis than the parent cell line, and (c) that anticonvulsant effects were observed even after unilateral transplantation into the STN. Neither grafting of control cells nor transplantation outside the STN induced anticonvulsant effects, emphasizing the site and cell specificity of the observed anticonvulsant effects. To our knowledge, the present study is the first showing anticonvulsant effects by grafting of GABA-producing cells into the STN. The STN can be considered a highly promising target region for modulation of seizure circuits and, moreover, has the advantage of being clinically established for functional neurosurgery.

背景与目标： : 将产生GABA的细胞神经移植到癫痫发作抑制回路中的关键结构中，对于不符合切除癫痫灶的药物耐药性癫痫患者有望实现。众所周知，黑质网状组织 (SNr) 是基底神经节的输出结构，可以调节不同的癫痫发作类型。我们小组最近的一次显微注射研究表明，严格调节黑质活性的丘脑底核 (STN) 可能比SNr更有希望成为癫痫局灶性治疗的靶标。作为原理证明，因此，我们使用定时静脉内戊四唑癫痫发作阈值测试评估了将产生GABA的细胞系双侧和单侧同种异体移植到STN中的抗惊厥功效，该测试可在单个大鼠中反复确定癫痫发作阈值。我们观察到 (a) 移植的细胞存活到实验结束，(b) 使用源自大鼠胚胎纹状体的永生化GABA能细胞和另外转染的细胞通过双侧移植到STN中可以诱导抗惊厥作用，从而获得比亲本细胞系更高的GABA合成，(c) 即使单侧移植到STN中，也观察到抗惊厥作用。对照细胞的移植或STN外的移植均未引起抗惊厥作用，强调了观察到的抗惊厥作用的部位和细胞特异性。据我们所知，本研究是第一个通过将产生GABA的细胞移植到STN中而显示出抗惊厥作用的研究。STN可以被认为是调节癫痫发作回路的非常有前途的靶区，而且具有在临床上为功能性神经外科手术建立的优势。

BACKGROUND & AIMS: The human immunodeficiency virus (HIV) is neuroinvasive and can be neurovirulent. Indeed, 20-30% of individuals with the acquired immune deficiency syndrome (AIDS) develop cognitive and motor dysfunction (termed the AIDS dementia complex or HIV dementia) coincident with advanced immunosuppression. Despite massive research efforts to discern viral neuropathogenic mechanisms, much remains incompletely understood. Recently, we and others developed animal model systems to elucidate how HIV infection within the brain can lead to impairment of central nervous system function. In this report, we evaluate each of the published animal models for their ability to mirror HIV dementia. Ease of handling and expense were also under consideration. Ultimately, studies in animal systems should permit a better understanding of the nature of HIV-1-induced neurological injury and aid in the development of effective treatments for this dreaded complication of HIV infection.

背景与目标： 人类免疫缺陷病毒 (HIV) 具有神经侵袭性，可能具有神经毒性。事实上，20-30% 的获得性免疫缺陷综合征 (AIDS) 个体出现认知和运动功能障碍 (称为AIDS痴呆复合体或HIV痴呆) 与晚期免疫抑制同时发生。尽管进行了大量研究以识别病毒的神经致病机制，但仍有许多不完全了解的地方。最近，我们和其他人开发了动物模型系统，以阐明大脑中的HIV感染如何导致中枢神经系统功能受损。在本报告中，我们评估了每个已发表的动物模型对HIV痴呆的反映能力。易于处理和费用也在考虑之中。最终，对动物系统的研究应该可以更好地了解HIV-1-induced神经损伤的性质，并有助于为这种可怕的HIV感染并发症开发有效的治疗方法。