BACKGROUND & AIMS: Bi-hemispheric cerebral blood flow (CBF) measurements during rest and hyperventilation, with intra-arterial 133Xe injection method, were investigated in 19 cases, angiographically diagnosed as unilateral internal carotid artery (ICA) occlusion, including 8 cases with TIAs and 11 cases with completed strokes as the onset. Indices of cerebral vascular resistance and CO2 reactivity with decreasing arterial PCO2 were also investigated. A significant decrease (P less than 0.05) of hemispheric mean CBF was noted in the ischemic hemisphere, but normal flow values in the unaffected hemisphere and preserved CO2 responsiveness during hyperventilation were observed in both the affected and unaffected hemispheres in patients with TIAs. Moreover, a direct relationship between CBF and blood pressure, observed in 11 cases with completed strokes, was not recognized in 8 cases with TIAs. A degree of the abnormalities of the affected hemisphere in cerebral circulation was suggested to be somewhat different between TIAs and completed strokes in ICA occlusions, and bi-hemispheric CBF measurements would be an useful method for evaluating the various indices of the CBF in ICA occlusions.

背景与目标： 在19例经血管造影诊断为单侧颈内动脉（ICA）阻塞的病例中，调查了19例经静息和过度通气期间双半球脑血流量（CBF）的测量，包括8例TIA和11例完成中风为发作。还研究了脑血管阻力和CO2反应性随动脉PCO2降低的指标。在缺血半球中，半球平均CBF显着降低（P小于0.05），但是在TIA患者的受影响和未受影响的半球中，未受影响的半球中的正常血流值和过度换气过程中观察到的CO2响应保持不变。此外，在11例完成卒中的患者中，未发现CBF与血压之间的直接关系，在8例TIA患者中未发现。提示TIA与ICA闭塞中的完整卒中在大脑循环中受影响的半球的异常程度有所不同，双半球CBF测量将是评估ICA闭塞中CBF各项指标的有用方法。

BACKGROUND & AIMS: The response of the regional cerebral blood flow (rCBF) to brain topical superfusion of 20 mM K+ was characterized in a closed cranial window preparation in barbiturate anesthetized and ventilated ratsIncreasing K+ in the artificial cerebrospinal fluid (ACSF) induced a rCBF elevation (measured by laser-Doppler flowmetry) of +85 +/- 37% above baseline (n = 19). This elevation was stable for > 3 h with continuous superfusion of increased K+ (n = 5) and partially reversible to a level of +18 +/- 19% above baseline when returning to a physiological K+ concentration. Nitric oxide synthase (NOS) inhibition by brain topical superfusion with N omega-nitro-L-arginine (L-NA) revealed (a) Addition of L-NA to high-potassium ACSF reduced the rCBF increase from +94 +/- 36% to +21 +/- 18% (p < or = 0.01, n = 7). (b) When L-NA was superfused for 60 min before increasing K+, rCBF decreased to -17 +/- 7% below baseline. Subsequent coapplication of L-NA and increased K+ induced only an elevation of +7 +/- 4% above baseline (n = 4). (c) When the NO donor S-nitroso-N-acetylpenicillamine (SNAP) was added during NOS inhibition to restore basal tissue NO levels, the resultant level of rCBF was +28 +/- 54% above baseline. Subsequent increase of K+ in the presence of NOS inhibition and SNAP elevated rCBF to +137 +/- 89% above baseline (n = 4).

背景与目标： 在巴比妥酸盐麻醉和通气大鼠的闭合颅窗准备中，表征了局部脑血流（rCBF）对20 mM K的脑局部灌注的反应。在人工脑脊液（ACSF）中增加K导致rCBF升高（通过激光测量） -多普勒流量计）比基线高85％-37％（n = 19）。该升高在大于3 h的时间内保持稳定，并且持续不断地增加了K（n = 5），并且当恢复到生理K浓度时，可部分逆转至基线以上18 /-19％的水平。通过脑局部灌注N-ω-硝基-L-精氨酸（L-NA）对一氧化氮合酶（NOS）的抑制作用表明（a）在高钾ACSF中添加L-NA可使rCBF从94 /-36％降低至21 /-18％（p <或= 0.01，n = 7）。 （b）当L-NA在增加K之前融合60分钟时，rCBF降低至基线以下-17 /-7％。随后共施用L-NA和增加的K只会使基线升高7％-4％（n = 4）。 （c）当在NOS抑制期间添加NO供体S-亚硝基-N-乙酰青霉胺（SNAP）以恢复基础组织NO水平时，所得rCBF水平比基线高28 /-54％。随后在存在NOS抑制和SNAP的情况下K升高，使rCBF升高至基线以上137 /-89％（n = 4）。

BACKGROUND & AIMS: :The Arabidopsis CBF cold response pathway has a central role in cold acclimation, the process whereby plants increase in freezing tolerance in response to low nonfreezing temperatures. Here we examined the changes that occur in the Arabidopsis metabolome in response to low temperature and assessed the role of the CBF cold response pathway in bringing about these modifications. Of 434 metabolites monitored by GC-time-of-flight MS, 325 (75%) were found to increase in Arabidopsis Wassilewskija-2 (Ws-2) plants in response to low temperature. Of these 325 metabolites, 256 (79%) also increased in nonacclimated Ws-2 plants in response to overexpression of C-repeat/dehydration responsive element-binding factor (CBF)3. Extensive cold-induced changes also occurred in the metabolome of Arabidopsis Cape Verde Islands-1 (Cvi-1) plants, which were found to be less freezing tolerant than Ws-2 plants. However, low-temperature-induced expression of CBF1, CBF2, CBF3, and CBF-targeted genes was much lower in Cvi-1 than in Ws-2 plants, and the low-temperature metabolome of Cvi-1 plants was depleted in metabolites affected by CBF3 overexpression. Taken together, the results indicate that the metabolome of Arabidopsis is extensively reconfigured in response to low temperature, and that the CBF cold response pathway has a prominent role in this process.

背景与目标： 拟南芥CBF的冷响应途径在冷驯化中起着核心作用，在该过程中，植物对低非冻结温度的响应提高了其耐寒性。在这里，我们检查了响应低温的拟南芥代谢组中发生的变化，并评估了CBF冷响应途径在实现这些修饰中的作用。 GC飞行时间质谱仪监测的434种代谢产物中，发现325种（75％）的拟南芥Wassilewskija-2（Ws-2）植物响应低温而增加。在这325种代谢产物中，响应于C重复/脱水反应性元素结合因子（CBF）3的过表达，在未适应的Ws-2植物中也增加了256种（79％）。拟南芥佛得角群岛-1（Cvi-1）植物的代谢组中也发生了广泛的冷诱导变化，发现该植物的耐寒性低于Ws-2植物。但是，低温诱导的CBF1，CBF2，CBF3和CBF靶向基因的表达在Cvi-1中比在Ws-2植物中低得多，并且Cvi-1植物的低温代谢组在受影响的代谢物中被消耗掉了由CBF3过度表达。两者合计，结果表明拟南芥的代谢组被广泛地配置以响应低温，并且CBF冷响应途径在这一过程中具有重要作用。

BACKGROUND & AIMS: :The cold acclimation process in plants is primarily regulated through the signal transduction pathways that lead to the induction and enhancement of expression of different sets of Cor/Lea genes. Winter wheat 'Mironovskaya 808' (M808) exhibited a much higher level of freezing tolerance than spring wheat 'Chinese Spring' (CS), and the difference became clearer after the long-term cold acclimation. To understand the molecular basis of this cultivar difference, we isolated two CBF/DREB1 homologs, Wcbf2, which are the candidate gene for a transcription factor of the Cor/Lea genes. Expression of the Wcbf2 gene was induced rapidly by low temperature (LT) and drought but not by abscisic acid (ABA). The gene expression was temporal and at least twice up-regulated by LT. The first up-regulation occurred within 1-4 h, which might correspond to the rapid response to LT, while the second up-regulation occurred during 2-3 weeks of cold acclimation. After the second up-regulation, the amount of Wcbf2 transcript greatly decreased in CS, while it increased again in M808 after 4 weeks until 9 weeks (end of the test period). The maintenance of this high level of the Wcbf2 transcript might represent the long-term effect of cold acclimation. The activation of Cor/Lea genes followed the accumulation of Wcbf2 transcript suggested direct involvement of the Wcbf2 gene in the induction and enhancement of the Cor/Lea gene expression. The cultivar difference in freezing tolerance developed during different stages of cold acclimation can be at least partly explained by the differential and coordinated regulation of the predicted Cor/Lea gene signal transduction pathway that is mediated by the CBF/DREB1 transcription factors in common wheat.

背景与目标： ：植物的冷驯化过程主要通过信号转导途径来调节，该信号转导途径导致不同Cor / Lea基因集的表达的诱导和增强。冬小麦“ Mironovskaya 808”（M808）的耐寒性要比春小麦“中国春”（CS）高得多，经过长期的冷驯化，差异变得更加明显。为了了解此品种差异的分子基础，我们分离了两个CBF / DREB1同源物Wcbf2，它们是Cor / Lea基因转录因子的候选基因。 Wcbf2基因的表达是由低温（LT）和干旱迅速诱导的，而不是由脱落酸（ABA）诱导的。基因表达是暂时的，并且至少两次被LT上调。第一次上调发生在1-4小时内，这可能与对LT的快速反应相对应，而第二次上调发生在冷适应的2-3周内。第二次上调后，CS中的Wcbf2转录物数量大大减少，而在4周后直到9周（测试期结束），其在M808中再次增加。保持这种高水平的Wcbf2转录本可能代表冷驯化的长期影响。 Wcbf2转录物的积累跟随着Cor / Lea基因的激活，表明Wcbf2基因直接参与了Cor / Lea基因表达的诱导和增强。在冷驯化的不同阶段中形成的耐寒性品种差异至少可以部分通过普通小麦的CBF / DREB1转录因子介导的预测Cor / Lea基因信号转导途径的差异和协调调节来解释。

BACKGROUND & AIMS: A simple, noninvasive method of measuring CBF that uses single photon emission computed tomography (SPECT) of 99mTc-hexamethylpropyleneamine oxime (99mTc-HMPAO) and whole-brain CBF obtained by 133Xe clearance technique was developed. SPECT data were normalized to the count density of HMPAO uptake in the whole brain and then converted to the absolute units of CBF by multiplying average CBF in the whole brain obtained by 133Xe. Mean CBF values in healthy volunteers (n = 12) were 49 +/- 7 and 30 +/- 5 ml 100 g-1 min-1 for gray matter and white matter, respectively, with a global flow value of 45 +/- 5 ml 100 g-1 min-1. The mean flow value was 19 +/- 7 ml 100 g-1 min-1 for the core of the infarct and 31 +/- 5 ml 100 g-1 min-1 for the contralateral region (n = 13). CBF values were reproducible for all brain regions. The method was convenient to use and suitable for the routine measurement of regional CBF in normal and pathologic states.

背景与目标： 开发了一种简单，无创的测量CBF的方法，该方法使用99mTc-六甲基丙胺肟（99mTc-HMPAO）的单光子发射计算机断层扫描（SPECT）和通过133Xe清除技术获得的全脑CBF。将SPECT数据标准化为整个大脑中HMPAO摄取的计数密度，然后通过乘以133Xe获得的整个大脑中的平均CBF，将其转换为CBF的绝对单位。健康志愿者（n = 12）的平均CBF值分别为灰质和白质分别为49 /-7和30 /-5 ml 100 g-1 min-1，全局流量值为45 /-5 ml 100 g-1分钟-1。对于梗塞的核心，平均血流值为19/7 ml 100 g-1 min-1，对侧区域的平均血流值为31 /-5 ml 100 g-1 min-1（n = 13）。所有脑区的CBF值均可重现。该方法使用方便，适用于正常和病理状态下区域脑血流的常规测量。

BACKGROUND & AIMS: :Heterogeneous ribonucleoproteins (hnRNPs) have key roles in RNA biogenesis, including pre-mRNP assembly, transport and cytoplasmic localization. Here we show by biochemical fractionation of nuclear extracts and protein-protein interaction assays that the A/B-type hnRNP CBF-A is in a multiprotein complex with hnRNP A2 and A3 and hnRNP U. Using RNA affinity chromatography and gel retardation assays, CBF-A was found to bind directly to RNA trafficking sequences in the 3'-UTR of the myelin basic protein (MBP) mRNA. In primary oligodendrocytes, astrocytes, neurons, and mouse forebrain sections, CBF-A revealed a characteristic granular cytoplasmic distribution. In mouse forebrain CBF-A-positive granules were preferentially found in regions with loosely bundled myelin fibers. In cultured oligodendrocytes, CBF-A was found to be specifically associated with endogenous MBP mRNA and CBF-A gene silencing resulted in the retention of MBP granules in the cell body. Finally, immunoelectron microscopy in differentiating oligodendrocytes showed that CBF-A is located in cytoplasmic granules that are often associated with the cytoskeleton. The results suggest that CBF-A is a novel transacting factor required for cytoplasmic mRNA transport and localization.

背景与目标： ：异质核糖核蛋白（hnRNPs）在RNA生物发生中具有关键作用，包括mRNP的前装配，转运和细胞质定位。在这里，我们通过核提取物的生化分级分离和蛋白质-蛋白质相互作用分析表明，A / B型hnRNP CBF-A与hnRNP A2和A3和hnRNP U处于多蛋白复合物中。使用RNA亲和色谱和凝胶阻滞分析，CBF发现-A直接与髓鞘碱性蛋白（MBP）mRNA的3'-UTR中的RNA运输序列结合。在原发性少突胶质细胞，星形胶质细胞，神经元和小鼠前脑切片中，CBF-A显示出特征性颗粒状胞质分布。在小鼠前脑中，优先发现髓磷脂纤维束松散的区域的CBF-A阳性颗粒。在培养的少突胶质细胞中，发现CBF-A与内源MBP mRNA特异性相关，而CBF-A基因沉默导致MBP颗粒保留在细胞体内。最后，在分化少突胶质细胞中的免疫电子显微镜显示，CBF-A位于通常与细胞骨架相关的细胞质颗粒中。结果表明，CBF-A是细胞质mRNA转运和定位所需的新型交易因子。

BACKGROUND & AIMS: OBJECTIVE:The multicenter prospective cohort study (Japan Cooperative SPECT Study on Assessment of Mild Impairment of Cognitive Function: J-COSMIC) aimed to examine the value of (123)I-N-isopropyl-4-iodoamphetamine cerebral blood flow (IMP-CBF) SPECT in regards to early diagnosis of Alzheimer's disease (AD) in patients with mild cognitive impairment (MCI). METHODS:Three hundred and nineteen patients with amnestic MCI at 41 participating institutions each underwent clinical and neuropsychological examinations and (123)I-IMP-CBF SPECT at baseline. Subjects were followed up periodically for 3 years, and progression to dementia was evaluated. SPECT images were classified as AD/DLB (dementia with Lewy bodies) pattern and non-AD/DLB pattern by central image interpretation and automated region of interest (ROI) analysis, respectively. Logistic regression analyses were used to assess whether baseline (123)I-IMP-CBF SPECT was predictive of longitudinal clinical outcome. RESULTS:Ninety-nine of 216 amnestic MCI patients (excluding 3 cases with epilepsy (n = 2) or hydrocephalus (n = 1) and 100 cases with incomplete follow-up) converted to AD within the observation period. Central image interpretation and automated ROI analysis predicted conversion to AD with 56 and 58 % overall diagnostic accuracy (sensitivity, 76 and 81 %; specificity, 39 and 37 %), respectively. Multivariate logistic regression analysis identified SPECT as a predictor, which distinguished AD converters from non-converters. The odds ratio for a positive SPECT to predict conversion to AD with automated ROI analysis was 2.5 and combining SPECT data with gender and mini-mental state examination (MMSE) further improved classification (joint odds ratio 20.08). CONCLUSIONS:(123)I-IMP-CBF SPECT with both automated ROI analysis and central image interpretation was sensitive but relatively nonspecific for prediction of clinical outcome during the 3-year follow-up in individual amnestic MCI patients. A combination of statistically significant predictors, both SPECT with automated ROI analysis and neuropsychological evaluation, may increase predictive utility.

背景与目标： 目的：进行多中心前瞻性队列研究（日本合作社SPECT评估轻度认知功能障碍研究：J-COSMIC），旨在研究（123）IN-异丙基-4-碘苯丙胺脑血流（IMP-CBF）SPECT的价值关于轻度认知障碍（MCI）患者的阿尔茨海默氏病（AD）的早期诊断。
方法：41个参与机构的319例记忆删除型MCI患者均接受了临床和神经心理学检查，并且在基线时接受了（123）I-IMP-CBF SPECT。定期对受试者进行3年的随访，并评估其进展为痴呆的程度。通过中央图像解释和自动关注区域（ROI）分析，将SPECT图像分别分类为AD / DLB（路易氏体痴呆）模式和非AD / DLB模式。使用逻辑回归分析评估基线（123）I-IMP-CBF SPECT是否可预测纵向临床结果。
结果：216例记忆消除型MCI患者中有99例（不包括3例癫痫（n = 2）或脑积水（n = 1）和100例随访不完全的患者）在观察期内转变为AD。中央图像解释和自动ROI分析预测以总诊断准确率56％和58％（敏感性分别为76％和81％;特异性39％和37％）转换为AD。多元逻辑回归分析确定SPECT为预测变量，从而将AD转换程序与非转换程序区分开。阳性SPECT通过自动ROI分析预测为AD的阳性几率是2.5，将SPECT数据与性别和小心理状态检查（MMSE）相结合，可以进一步改善分类效果（联合赔率比20.08）。
结论：（123）I-IMP-CBF SPECT具有自动ROI分析和中央图像解释功能，对个体记忆删除MCI患者的3年随访期间的临床结果预测较敏感，但相对非特异性。 SPECT与自动ROI分析和神经心理学评估相结合，具有统计学意义的预测指标可以提高预测效用。

BACKGROUND & AIMS: :The induction of C-repeat binding factors (CBFs) is crucial for plant survival at low temperatures. Therefore, understanding the mechanisms that regulate CBF transcription is vital for the future development of crops with increased cold tolerance. Here, we provide evidence for the existence of a LONG HYPOCOTYL 5 (HY5)-MYB15-CBFs transcriptional cascade that plays a crucial role in the cold response in tomato. The exposure of tomato plants to cold (4°C) increased the levels of HY5, MYB15 and CBFs transcripts. Moreover, mutations in HY5 or MYB15 decreased the levels of CBF transcripts. In contrast, overexpression of HY5 or MYB15 increased CBF transcript abundance. Crucially, the HY5 transcription factor activated the expression of MYB15 by directly binding to the promoter region, while both HY5 and MYB15 activated the expression of CBF1, CBF2 and CBF3. Taken together, these data show that HY5 can directly regulate CBF transcript levels, and also influence CBF expression indirectly via MYB15. The coordinated action of HY5 and MYB15 allows precise regulation of CBF expression and subsequent cold tolerance. These findings provide an improved understanding of the molecular mechanisms affording transcriptional regulation of CBFs, which can be exploited in the future to enhance cold tolerance in crops.

背景与目标： ：C-重复结合因子（CBF）的诱导对于低温下植物的存活至关重要。因此，了解调节CBF转录的机制对于提高耐寒性的作物的未来发展至关重要。在这里，我们提供的证据表明存在长的hypocotyyl 5（HY5）-MYB15-CBFs转录级联反应，在番茄的冷反应中起着至关重要的作用。番茄植物暴露于冷（4°C）下会增加HY5，MYB15和CBFs转录本的水平。此外，HY5或MYB15中的突变降低了CBF转录本的水平。相反，HY5或MYB15的过表达增加了CBF转录本的丰度。至关重要的是，HY5转录因子通过直接结合启动子区域激活了MYB15的表达，而HY5和MYB15都激活了CBF1，CBF2和CBF3的表达。综上所述，这些数据表明，HY5可以直接调节CBF转录水平，也可以通过MYB15间接影响CBF的表达。 HY5和MYB15的协同作用可以精确调节CBF表达和随后的耐寒性。这些发现提供了对提供CBFs转录调控的分子机制的更好的理解，可以在将来被利用来增强农作物的耐寒性。

BACKGROUND & AIMS: :The mts1/S100A4 gene encodes a small acidic calcium-binding protein that is expressed in a cell-specific manner in development, tumorigenesis and certain tissues of adult mice. A composite enhancer that is active in murine mammary adenocarcinoma cells was previously identified in the first intron of the mts1/S100A4 gene. Here we present a detailed analysis of the structure and function of this enhancer in the Mts1/S100A4-expressing CSML100 and non-expressing CSML0 mouse adenocarcinoma cell lines. In CSML100 cells the enhancer activity is composed of at least six cis-elements interacting with Sp1 and AP-1 family members and CBF/AML/PEBP2 and KRC transcription factors. In addition, a minisatellite-like DNA sequence significantly contributes to the enhancer activity via interaction with abundant proteins, which likely have been described previously under the name minisatellite-binding proteins. Extensive mutational analysis of the mts1/S100A4 enhancer revealed a cooperative function of KRC and the factors binding minisatellite DNA. This is the first example of an enhancer where two nuclear factors earlier implicated in different recombination processes cooperate to activate transcription. In Mts1/S100A4-negative CSML0 cells the strength of the enhancer was 7- to 12.5-fold lower compared to that in CSML100 cells, when referred to the activities of three viral promoters. In CSML0 cells the enhancer could be activated by exogenous AP-1 and CBF transcription factors.

背景与目标： ：mts1 / S100A4基因编码一种小的酸性钙结合蛋白，该蛋白在成年小鼠的发育，肿瘤发生和某些组织中以细胞特异性方式表达。先前在mts1 / S100A4基因的第一个内含子中鉴定出了一种在鼠乳腺腺癌细胞中有活性的复合增强子。在这里，我们目前在表达Mts1 / S100A4的CSML100和非表达CSML0小鼠腺癌细胞系中对该增强子的结构和功能进行详细分析。在CSML100细胞中，增强子活性由至少六个与Sp1和AP-1家族成员以及CBF / AML / PEBP2和KRC转录因子相互作用的顺式元件组成。另外，类似小卫星的DNA序列通过与丰富的蛋白质相互作用而显着地促进了增强子的活性，这可能先前已经以小卫星结合蛋白的名称进行了描述。对mts1 / S100A4增强子的广泛突变分析揭示了KRC和结合小卫星DNA的因子的协同功能。这是增强子的第一个例子，其中先前涉及不同重组过程的两个核因子协同激活转录。在Mts1 / S100A4阴性CSML0细胞中，与三种病毒启动子的活性相比，增强子的强度比CSML100细胞低7到12.5倍。在CSML0细胞中，增强子可以被外源AP-1和CBF转录因子激活。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: The chromosomal inversion 16(p13;q22) associated with human acute myeloid leukemia generates the chimeric PEBP2 beta/CBF beta-SMMHC gene. The PEBP2 beta/CBF beta portion of the chimeric polypeptide harbors most of the amino acid sequence of the PEBP2 beta/CBF beta protein, the non-DNA binding subunit of the heterodimeric transcription factor, PEBP2/CBF, whereas the SMMHC portion of the chimera consists of the rod domain of the smooth muscle myosin heavy chain molecule. In this study we examined the subcellular localization of the chimeric protein and its effect both on stress fibers and transcriptional activation by transfecting cDNA into tissue culture cells. The localization of the chimera was investigated by immunocytochemical staining of cells and was found to be both cytoplasmic and nuclear. One aspect of the effect of expression of the chimera was a drastic alteration of cell morphology. The cells appeared elongated and possessed long cytoplasmic processes. Double fluorescent labeling revealed disorganization of the stress fibers and an altered F-actin staining pattern in the transfected cells. Studies using a deletion mutant showed that both the PEBP2 beta/CBF beta and SMMHC domains are necessary for the induction of the morphological alteration. A significant proportion of the chimeric protein was retained in the cytoskeleton after detergent extraction of the cells and could be recuperated as a membrane fraction, suggesting that this is one of the probable sites of action of the PEBP2 beta/CBF beta-SMMHC protein. Another effect of the chimeric protein was inhibition of transcriptional activation dependent on the PEBP2/CBF binding DNA sequence. However, deregulation of PEBP2/CBF site dependent transcription by itself was not sufficient to induce cell morphological changes. Taken together, these results indicate that the PEBP2 beta/CBF beta-SMMHC chimeric protein acts at two levels, at the level of stress fiber organization and at the level of transcriptional activation. We suggest that the action of PEBP2 beta/CBF beta-SMMHC depends to a great extent on whether it is located in the cytoplasm or in the nucleus.

背景与目标： 与人类急性髓细胞白血病相关的染色体倒置16（p13; q22）产生嵌合的PEBP2 beta / CBF beta-SMMHC基因。嵌合多肽的PEBP2 beta / CBF beta部分包含PEBP2 beta / CBF beta蛋白的大部分氨基酸序列，即异二聚体转录因子PEBP2 / CBF的非DNA结合亚基，而嵌合体的SMMHC部分由平滑肌肌球蛋白重链分子的杆结构域组成。在这项研究中，我们通过将cDNA转染到组织培养细胞中，研究了嵌合蛋白的亚细胞定位及其对应激纤维和转录激活的影响。通过细胞的免疫细胞化学染色研究了嵌合体的定位，发现它既是细胞质的又是核的。嵌合体表达效果的一方面是细胞形态的急剧改变。细胞出现拉长并具有长的细胞质过程。双重荧光标记揭示了转染细胞中应力纤维的混乱和F-肌动蛋白染色模式的改变。使用缺失突变体的研究表明，PEBP2 beta / CBF beta和SMMHC结构域对于诱导形态学改变都是必需的。在去污剂提取细胞后，大部分嵌合蛋白保留在细胞骨架中，并且可以作为膜级分回收，这表明这是PEBP2 beta / CBF beta-SMMHC蛋白的可能作用位点之一。嵌合蛋白的另一个作用是抑制转录激活，依赖于PEBP2 / CBF结合DNA序列。然而，PEBP2 / CBF位点依赖转录的失调本身不足以诱导细胞形态变化。综上所述，这些结果表明，PEBP2 beta / CBF beta-SMMHC嵌合蛋白在两个水平上起作用，分别在应激纤维组织水平和转录激活水平上。我们建议，PEBP2 beta / CBF beta-SMMHC的作用在很大程度上取决于它是位于细胞质中还是位于细胞核中。

BACKGROUND & AIMS: Spatial specificities of the calcium-dependent synaptic activity, hemodynamic-based blood oxygenation level-dependent (BOLD) and cerebral blood flow (CBF) fMRI were quantitatively compared in the same animals. Calcium-dependent synaptic activity was imaged by exploiting the manganese ion (Mn++) as a calcium analog and an MRI contrast agent at 9.4 T. Following forepaw stimulation in alpha-chloralose anesthetized rat, water T1 of the contralateral forepaw somatosensory cortex (SI) was focally and markedly reduced from 1.99 +/- 0.03 sec to 1.30 +/- 0.18 sec (mean +/- SD, N = 7), resulting from the preferential intracellular Mn++ accumulation. Based on an in vitro calibration, the estimated contralateral somatosensory cortex [Mn++] was approximately 100M, which was 2-5-fold higher than the neighboring tissue and the ipsilateral SI. Regions with the highest calcium activities were localized around cortical layer IV. Stimulus-induced BOLD and CBF changes were 3.4 +/- 1.6% and 98 +/- 33%, respectively. The T1 synaptic activity maps extended along the cortex, whereas the hemodynamic-based activation maps extended radially along the vessels. Spatial overlaps among the synaptic activity, BOLD, and CBF activation maps showed excellent co-registrations. The center-of-mass offsets between any two activation maps were less than 200 microm, suggesting that hemodynamic-based fMRI techniques (at least at high field) can be used to accurately map the spatial loci of synaptic activity.

背景与目标： 在同一动物中定量比较了钙依赖性突触活性，血流动力学基于血氧水平（BOLD）和脑血流量（CBF）fMRI的空间特异性。通过在9.4 T下利用锰离子（Mn）作为钙类似物和MRI造影剂对钙依赖的突触活性进行成像。在α-氯醛糖麻醉的大鼠中用前爪刺激后，对侧前爪体感皮层（SI）的水T1为由于优先的细胞内Mn积累，焦距从1.99 /-0.03秒显着降低到1.30 /-0.18秒（平均SD，N = 7）。根据体外校准，估计对侧体感皮层[Mn]约为100M，比邻近组织和同侧SI高2-5倍。钙活度最高的区域位于IV皮质层附近。刺激引起的BOLD和CBF变化分别为3.4 /-1.6％和98 /-33％。 T1突触活动图沿皮质延伸，而基于血流动力学的激活图沿血管径向延伸。突触活动，BOLD和CBF激活图之间的空间重叠显示出极好的共配准。任何两个激活图之间的质心偏移都小于200微米，这表明基于血液动力学的fMRI技术（至少在高视野下）可用于精确映射突触活动的空间位点。

BACKGROUND & AIMS: :A technique has been developed and tested that provides an automated method of temporally aligning the PET tissue activity curve with the arterial activity curve for quantification of cerebral blood flow using the H(2)(15)O autoradiographic model. This technique not only determines the relative time delay between the two curves, but also provides the start time of integration. Variability in computing global cerebral blood flow using this technique is shown to be less than that obtained by trained observers manually selecting parameters and at least as good as that obtained by using another automated alignment technique.

背景与目标： ：已开发并测试了一种技术，该技术提供了一种自动方法，可以使用H（2）（15）O放射自显影模型在时间上将PET组织活性曲线与动脉活性曲线进行比对，以定量脑血流量。该技术不仅确定两条曲线之间的相对时间延迟，而且还提供了积分的开始时间。结果表明，使用该技术计算整体脑血流量的变异性小于训练有素的观察者手动选择参数所获得的变异性，至少与使用另一种自动对齐技术获得的变异性一样好。

BACKGROUND & AIMS: The CCAAT motif is one of the common promoter elements present in the proximal promoter of numerous mammalian genes transcribed by RNA polymerase II. CBF (also called NF-Y and CP1) consists of three different subunits and interacts specifically with the CCAAT motif. In each CBF subunit, the segment needed for formation of the CBF-DNA complex is conserved from yeast to human and, interestingly, the conserved segment of two CBF subunits, CBF-A and CBF-C, are homologous to the histone-fold motif of eukaryotic histones and archaebacterial histone-like protein HMf-2. The histone fold motifs of CBF-A and CBF-C interact with each other to form a heterodimer that associates with CBF-B to form a heterotrimeric CBF molecule, which then binds to DNA.

背景与目标： CCAAT基序是存在于RNA聚合酶II转录的众多哺乳动物基因的近端启动子中的常见启动子元件之一。 CBF（也称为NF-Y和CP1）由三个不同的亚基组成，并与CCAAT基序特异性相互作用。在每个CBF亚基中，形成CBF-DNA复合物所需的片段从酵母到人都是保守的，有趣的是，两个CBF亚基的保守片段CBF-A和CBF-C与组蛋白折叠基序同源真核组蛋白和古细菌组蛋白样蛋白HMf-2的鉴定CBF-A和CBF-C的组蛋白折叠基序彼此相互作用形成异二聚体，该异二聚体与CBF-B结合形成异三聚体CBF分子，然后与DNA结合。

BACKGROUND & AIMS: :To investigate whether Hyperbaric Oxygen Therapy (HBO2) could improve neurologic deficits and regional cerebral blood flow (rCBF) in chronic traumatic brain injuries (TBI), the authors employed a nonrandomized control pilot trial. Five subjects, at least three years post head injury, received HBO2. Five head injured controls (HIC) were matched for age, sex, and type of injury. Five healthy subjects served as normal controls. Sixty-eight normal volunteers comprised a reference data bank against which to compare SPECT brain scans. HBO2 subjects received 120 HBO2 in blocks of 80 and 40 treatments with an interval five-month break. Normal controls underwent a single SPECT brain scan, HBO2, and repeat SPECT battery. TBI subjects were evaluated by neurologic, neuropsychometric, exercise testing, and pre and post study MRIs, or CT scans if MRI was contraindicated. Statistical Parametric Mapping was applied to SPECT scans for rCBF analysis. There were no significant objective changes in neurologic, neuropsychometric, exercise testing, MRIs, or rCBF. In this small pilot study, HBO2 did not effect clinical or regional cerebral blood flow improvement in TBI subjects.

背景与目标： ：为了研究高压氧疗法（HBO2）是否可以改善慢性创伤性脑损伤（TBI）中的神经功能缺损和局部脑血流量（rCBF），作者采用了非随机对照试验。五名受试者，至少在头部受伤后三年，接受了HBO2治疗。根据年龄，性别和伤害类型对五个头部受伤的对照（HIC）进行匹配。五名健康​​受试者作为正常对照。 68名正常志愿者组成了一个参考数据库，可以将其与SPECT脑部扫描进行比较。 HBO2受试者接受80次和40次治疗，每5个月休息一次，共接受120次HBO2。正常对照进行一次SPECT脑部扫描，HBO2，并重复SPECT电池。通过神经系统，神经心理测量，运动测试以及研究前和研究后MRI或CT扫描（如果MRI禁忌）对TBI受试者进行评估。将统计参数映射应用于SPECT扫描以进行rCBF分析。神经学，神经心理学，运动测试，MRI或rCBF没有明显的客观变化。在这项小型先导研究中，HBO2并未影响TBI受试者的临床或局部脑血流量改善。