BACKGROUND & AIMS: PURPOSE:To determine the effect of latanoprost on the expression of human matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in the trabecular meshwork (TM). METHODS:Total RNA was isolated, and qualitative RT-PCR was performed to detect the mRNA of MMPs and TIMPs in human TM tissue and explant cultures of TM endothelial cells. Cultures of TM cells were treated with vehicle control or latanoprost acid for 24 hours. Real-time RT-PCR of cell cultures from five different donors was performed to determine relative changes in expression. GAPDH served as an endogenous control. RESULTS:The mRNA of MMP-1, -2, -3, -11, -12, -14, -15, -16, -17, -19, and -24 and of TIMP-1 to -4 was present in TM tissue and cultures of TM cells. MMP-9 was not found. In control TM endothelial cells, the relative expression of MMP mRNA were MMP-2 and -14 > MMP-16, -19, and -24 > MMP-15 > MMP-11 and -17 > MMP-1 and -3 > MMP-12. The relative expressions of TIMP mRNA were TIMP-1 > TIMP-2 and -3 > TIMP-4. Latanoprost increased MMP-1 (in four of five cultures), MMP-3 (in four of five cultures), MMP-17 (in three of five cultures), MMP-24 (in all five cultures), TIMP-2, -3, and -4 expression (in three of five cultures); MMP-11 and -15 were downregulated. CONCLUSIONS:Contrary to the expected result, latanoprost seems to have a significant effect on TM cells. The transcription of the genes for MMP-1, -3, -17, and -24 is increased by latanoprost treatment. TIMP-2, -3, and -4 are also upregulated. The upregulation of these TIMPs may compensate for the increase of those MMPs. The absence of MMP-9 and concurrent upregulation of a greater number of TIMPs may explain the limited effect of latanoprost on TM outflow.

背景与目标： 目的：确定拉坦前列素对小梁网（TM）中人基质金属蛋白酶（MMPs）和金属蛋白酶组织抑制剂（TIMPs）表达的影响。
方法：分离总RNA，进行定性RT-PCR检测人TM组织和TM内皮细胞外植体培养物中MMP和TIMP的mRNA。用媒介物对照或拉坦前列素酸处理TM细胞的培养物24小时。对来自五个不同供体的细胞培养物进行了实时RT-PCR，以确定表达的相对变化。 GAPDH用作内源性对照。
结果：MMP-1，-2，-3，-11，-12，-14，-15，-16，-17，-19和-24和TIMP-1至-4的mRNA均存在于TM组织和TM细胞培养物。找不到MMP-9。在对照TM内皮细胞中，MMP mRNA的相对表达为MMP-2和-14> MMP-16，-19和-24> MMP-15> MMP-11和-17> MMP-1和-3> MMP -12。 TIMP mRNA的相对表达为TIMP-1> TIMP-2和-3> TIMP-4。拉坦前列素可提高MMP-1（在五种文化中的四种），MMP-3（在五种文化中的四种），MMP-17（在五种文化中的三种），MMP-24（在五种文化中），TIMP-2，- 3和-4表达（在五种文化中的三种）； MMP-11和-15下调。
结论：与预期结果相反，拉坦前列素似乎对TM细胞有显着影响。拉坦前列素处理可增加MMP-1，-3，-17和-24基因的转录。 TIMP-2，-3和-4也被上调。这些TIMP的上调可以补偿那些MMP的增加。 MMP-9的缺乏和大量TIMP的同时上调可能解释了拉坦前列素对TM外流的作用有限。

BACKGROUND & AIMS: :We examined the effect of exercise on postprandial lipemia (PPL) and insulin resistance in individuals with metabolic syndrome. Subjects were 10 hypertriglyceridemia (HTG) males with insulin resistance [age = 40.1 +/- 2.2 years, body weight = 96.3 +/- 3.3 kg, fasting triglyceride (TG) = 263 +/- 25 mg/dl, VO(2)max = 37 +/- 1.1 ml/kg/min, and Homeostatic Model Assessment (HOMA-IR, an index of insulin resistance) = 3.05 +/- 0.40]. Each subject performed a control trial (Ctr, no exercise), and three exercise trials at 40% (40%T), 60% (60%T), and 70% (70%T) of their VO(2)max. The order of trials was randomized and there were 1-2 weeks wash-out period between the trials. All subjects had a fat-meal in each trial. In the exercise trials, subjects jogged on a treadmill for 1 h at a designated intensity 12 h prior to a fat-meal ingestion. Blood samples were taken at 0 h (before the meal), and 2, 4, 6, and 8 h after the meal. The plasma TG, area score under TG concentration curve for over an 8 h-period (TG AUC) after the meal, and HOMA-IR were analyzed. The TG AUC score in 40%T was 30% lower (P = 0.003), 60%T was 31% lower (P = 0.02), and 70%T was 39% lower (P = 0.02) than Ctr. There were no significant differences in the TG AUC scores among the exercise trials (P > 0.05). The insulin concentrations in both 60 and 70%T were lower than Ctr (P < 0.01) which did not differ from 40%T. HOMA-IR in both 60%T (P = 0.041) and 70%T (P = 0.002) were lower than Ctr, but not different from 40%T (HOMA-IR: Ctr = 3.05 +/- 0.40, 40%T = 2.67 +/- 0.35, 60%T = 2.49 +/- 0.31, 70%T = 2.21 +/- 0.27). The results suggest that for physically inactive individuals with metabolic syndrome, exercising at low to moderate intensity may be sufficient to attenuate PPL and increase insulin sensitivity, whereas higher intensity exercise may be needed to normalize blood glucose.

背景与目标： ：我们研究了运动对代谢综合征患者餐后血脂（PPL）和胰岛素抵抗的影响。受试者为10名高甘油三酸酯血症（HTG）男性，胰岛素抵抗[年龄= 40.1 /-2.2岁，体重= 96.3 /-3.3 kg，空腹甘油三酸酯（TG）= 263 /-25 mg / dl，VO（2）max = 37 -/-1.1 ml / kg / min，并且稳态模型评估（HOMA-IR，胰岛素抵抗指数）= 3.05-0.40]。每个受试者进行了一项对照试验（Ctr，无运动），并进行了三项运动试验，试验的最大VO（2）最大为40％（40％T），60％（60％T）和70％（70％T）。试验顺序是随机的，两次试验之间有1-2周的清除期。所有受试者在每次试验中均吃一顿胖饭。在运动试验中，受试者在摄入脂肪餐之前12小时以指定的强度在跑步机上慢跑1小时。在0小时（饭前），饭后2、4、6和8小时采集血样。餐后8 h（TG AUC），血浆TG，TG浓度曲线下的面积得分和HOMA-IR进行了分析。与Ctr相比，在40％T中的TG AUC得分降低了30％（P = 0.003），在60％T中降低了31％（P = 0.02），在70％T中降低了39％（P = 0.02）。在运动试验之间，TG AUC评分无显着差异（P> 0.05）。 60％和70％T中的胰岛素浓度均低于Ctr（P <0.01），与40％T无差异。 60％T（P = 0.041）和70％T（P = 0.002）的HOMA-IR均低于Ctr，但与40％T相同（HOMA-IR：Ctr = 3.05 /-0.40，40％T = 2.67 /-0.35，60％T = 2.49 /-0.31，70％T = 2.21 /-0.27）。结果表明，对于缺乏身体活动能力的代谢综合征患者，低强度至中等强度的运动可能足以减弱PPL和增加胰岛素敏感性，而可能需要更高强度的运动才能使血糖正常化。

BACKGROUND & AIMS: OBJECTIVE:The goal of this study was to develop an improved (62)Zn/(62)Cu generator based on cation exchange resin and remote preparation at high radioactivity scale for clinical use. METHODS:A natural Cu target was irradiated with proton beam in the energy range of 30-->19 MeV at a beam current of 10 muA for 1 h to obtain around 1.7 GBq of (62)Zn. The (62)Zn was isolated from the Cu target on an anion exchange column with more than 97% yield within 2.5 h from the EOB. The (62)Zn/(62)Cu generator was prepared by loading the (62)Zn(2+) on a Sep-Pak plus CM cartridge. RESULTS:The generator showed high elution efficiency ( approximately 96%) using a small volume (ca. 3 ml) of a 200-mM glycine solution with a very low breakthrough of (62)Zn (<0.1%). CONCLUSIONS:This (62)Zn/(62)Cu generator has been proven to be highly useful as a source of (62)Cu for the synthesis of (62)Cu-labeled compounds. The clinical application of [(62)Cu]Cu-ATSM produced with this generator has been already approved by the Institutional Review Board at the National Institute of Radiological Sciences.

背景与目标： 目的：本研究的目的是开发一种改进的（62）Zn /（62）Cu生成器，该生成器基于阳离子交换树脂和高放射性规模的远程制备方法，可用于临床。
方法：在能量范围为30-> 19 MeV的质子束中，以10μA的束流对天然Cu靶辐照1 h，以获得约1.7 GBq的（62）Zn。从EOB到2.5 h内，从阴离子交换柱上的Cu靶中分离出（62）Zn。通过将（62）Zn（2）加载到Sep-Pak plus CM滤芯上来制备（62）Zn /（62）Cu发生器。
结果：使用少量（约3 ml）的200 mM甘氨酸溶液，生成器显示出较高的洗脱效率（约96％），其中（62）Zn的穿透率极低（<0.1％）。
结论：该（62）Zn /（62）Cu生成物已被证明可高度有效地用作（62）Cu的来源，用于合成（62）Cu标记的化合物。用这种发生器产生的[（62）Cu] Cu-ATSM的临床应用已经由美国放射科学学会的机构审查委员会批准。

BACKGROUND & AIMS: :Consonant identification was measured for a stationary and amplitude-modulated noise masker in four listeners with flat cochlear hearing loss, and four age-matched normal-hearing listeners. The masker modulation rate was systematically varied between 2 and 128 Hz. Masking release (MR), that is better identification performance in fluctuating, than in stationary noise, was highest in a masker fluctuating at 8-16 Hz in all normal-hearing listeners. In comparison, MR was only observed in two out of the four impaired listeners. In these listeners, MR was poorer than normal, and peaked at lower rates, that is 2 or 8 Hz. MR corresponded to increased reception of information for voicing, place, and manner between 2 and 64 Hz in all normal-hearing listeners. In impaired listeners, increased reception of information was mainly observed for manner, and mainly reduced for place, but these differences were not significant. For all phonetic features, MR was observed at lower masker fluctuation rates (< or =32 Hz) than in normal-hearing listeners. This study therefore shows that cochlear damage affects MR, both quantitatively and qualitatively.

背景与目标： ：在四个平直的人工耳聋听力下降的听众和四个年龄相匹配的正常听力的听众中，对平稳和调幅的噪声掩蔽器的辅音识别进行了测量。掩蔽调制率在2到128 Hz之间系统地变化。在所有正常听力的听众中，以8-16 Hz波动的掩蔽器中，掩蔽释放（MR）的波动性要好于平稳噪声，这在静态噪声中表现得更好。相比之下，只有四个受损听者中有两个观察到了MR。在这些听众中，MR比正常人差，并且以较低的频率（即2或8 Hz）达到峰值。 MR对应于在所有正常听力的收听者中2至64 Hz之间的声音，位置和方式信息接收的增加。在听力受损的听众中，主要是通过方式观察到了信息接收的增加，而对于场所则主要是观察到的减少，但是这些差异并不明显。对于所有的语音特征，与正常听力的听众相比，在较低的掩蔽者波动率（<或= 32 Hz）下观察到了MR。因此，这项研究表明，耳蜗损害在数量和质量上都影响MR。

BACKGROUND & AIMS: Shunting inhibition, a conductance increase with a reversal potential close to the resting potential of the cell, has been shown to have a divisive effect on subthreshold excitatory postsynaptic potential amplitudes. It has therefore been assumed to have the same divisive effect on firing rates. We show that shunting inhibition actually has a subtractive effect on the firing rate in most circumstances. Averaged over several interspike intervals, the spiking mechanism effectively clamps the somatic membrane potential to a value significantly above the resting potential, so that the current through the shunting conductance is approximately independent of the firing rate. This leads to a subtractive rather than a divisive effect. In addition, at distal synapses, shunting inhibition will also have an approximately subtractive effect if the excitatory conductance is not small compared to the inhibitory conductance. Therefore regulating a cell's passive membrane conductance-for instance, via massive feedback-is not an adequate mechanism for normalizing or scaling its output.

背景与目标： 分流抑制（电导增加，其反向电位接近细胞的静息电位）已显示对阈下兴奋性突触后电位幅度有分裂作用。因此，已假定它对点火速率具有相同的分裂作用。我们表明，在大多数情况下，分流抑制实际上对点火速率具有减法作用。平均在几个尖峰间隔之间，尖峰机制有效地将体膜电位钳制到显着高于静息电位的值，从而使通过分流电导的电流大致与发射速率无关。这导致相减而不是相除作用。另外，在远端突触处，如果兴奋性电导与抑制性电导相比很小，则分流抑制也将具有近似的减法作用。因此，例如通过大量反馈来调节细胞的被动膜电导率，不是一种用于标准化或缩放其输出的适当机制。

BACKGROUND & AIMS: :Few details are known about how the human immunodeficiency virus type 1 (HIV-1) genomic RNA is trafficked in the cytoplasm. Part of this process is controlled by the activity of heterogeneous nuclear ribonucleoprotein A2 (hnRNP A2). The role of hnRNP A2 during the expression of a bona fide provirus in HeLa cells is investigated in this study. Using immunofluorescence and fluorescence in situ hybridization techniques, we show that knockdown of hnRNP A2 expression in HIV-1-expressing cells results in the rapid accumulation of HIV-1 genomic RNA in a distinct, cytoplasmic space that corresponds to the microtubule-organizing center (MTOC). The RNA exits in the nucleus and accumulates at the MTOC region as a result of hnRNP A2 knockdown even during the expression of a provirus harboring mutations in the hnRNP A2-response element (A2RE), the expression of which results in nuclear retention of genomic RNA. We also demonstrate that hnRNP A2 expression is required for downstream trafficking of genomic RNA from the MTOC in the cytoplasm. Genomic RNA localization at the MTOC that was both the result of hnRNP A2 knockdown and the overexpression of Rab7-interacting lysosomal protein had little effect on pr55Gag synthesis but negatively influenced virus production and infectivity. These data indicate that altered HIV-1 genomic RNA localization modulates viral assembly and that the MTOC serves as a central site to which HIV-1 genomic RNA converges following its exit from the nucleus, with the host protein, hnRNP A2, playing a central role in taking it to and from this site in the cell.

背景与目标： 关于人类免疫缺陷病毒1型（HIV-1）基因组RNA如何在细胞质中运输的信息鲜为人知。该过程的一部分由异质核糖核蛋白A2（hnRNP A2）的活性控制。这项研究调查了hnRNP A2在HeLa细胞中表达真正的原病毒的过程中的作用。使用免疫荧光和荧光原位杂交技术，我们显示敲低表达HIV-1的细胞中hnRNP A2表达的表达导致HIV-1基因组RNA在与微管组织中心相对应的独特细胞质空间中的快速积累（ MTOC）。即使hnRNP A2反应元件（A2RE）中携带有突变的原病毒表达，RNA仍会通过hnRNP A2敲除而留在细胞核中并在MTOC区域积聚，其表达会导致基因组RNA的核保留。我们还证明hnRNP A2表达是从细胞质MTOC下游运输基因组RNA所必需的。基因组RNA在MTOC处的定位既是hnRNP A2敲除的结果，又是与Rab7相互作用的溶酶体蛋白的过表达，对pr55Gag的合成影响很小，但对病毒的产生和感染性产生负面影响。这些数据表明，改变的HIV-1基因组RNA定位可调节病毒装配，MTOC充当HIV-1基因组RNA从细胞核退出后向其汇聚的中心位点，宿主蛋白hnRNP A2发挥着核心作用。将其带入和移出该单元格中的此站点。

BACKGROUND & AIMS: :The membrane potential (DeltaPsim) dependence of the generation of reactive oxygen species (ROS) in isolated guinea-pig brain mitochondria respiring on NADH-linked substrates (glutamate plus malate) was addressed. Depolarization by FCCP was without effect on H(2)O(2) formation in the absence of bovine serum albumin (BSA). Addition of BSA (0.025%) to the assay medium hyperpolarized mitochondria by 6.1 +/- 0.9 mV (from 169 +/- 3 to 175.1 +/- 2.1 mV) and increased the rate of H(2)O(2) formation from 207 +/- 4.5 to 312 +/- 12 pmol/min/mg protein. Depolarization by FCCP (5-250 nM) in the presence of BSA decreased H(2)O(2) formation but only to the level observed in the absence of BSA. Rotenone stimulated the formation of H(2)O(2) both in the absence and presence of BSA. It is suggested that H(2)O(2) formation in mitochondria supported by NADH-linked substrates is sensitive to changes in DeltaPsim only when mitochondria are highly polarized and even then, 60% of ROS generation is independent of DeltaPsim. This is in contrast to earlier reports on the highly DeltaPsim sensitive ROS formation related to reverse electron flow observed in well-coupled succinate-supported mitochondria.

背景与目标： ：解决了在NADH连接的底物（谷氨酸加苹果酸）上呼吸的分离的豚鼠脑线粒体中活性氧物质（ROS）生成的膜电位（DeltaPsim）依赖性。在没有牛血清白蛋白（BSA）的情况下，通过FCCP去极化对H（2）O（2）的形成没有影响。将BSA（0.025％）添加到测定介质超极化线粒体的6.1 /-0.9 mV（从169 /-3到175.1 /-2.1 mV），并将H（2）O（2）的形成速率从207 /-增加4.5至312 /-12 pmol / min / mg蛋白质。由存在于BSA的FCCP（5-250 nM）进行的去极化降低了H（2）O（2）的形成，但仅达到了在没有BSA的情况下所观察到的水平。鱼藤酮在没有和存在BSA的情况下刺激H（2）O（2）的形成。建议仅在线粒体高度极化并且即使那时，60％的ROS生成独立于DeltaPsim时，NADH链接的底物支持的线粒体中的H（2）O（2）形成对DeltaPsim的变化敏感。这与早先报道的关于高度DeltaPsim敏感的ROS形成相反，后者在良好耦合的琥珀酸负载的线粒体中观察到与反向电子流有关。