BACKGROUND & AIMS: :The oncoprotein LMP1 mimics an activated CD40 receptor, yet it is not known whether constitutive CD40 signaling, like LMP1, is sufficient to transform cells. Here we demonstrate that constitutive activation of the CD40 pathway by a chimeric LMP1CD40 molecule resembles the transforming function of LMP1 in inducing loss of contact inhibition and anchorage independent growth of Rat1 fibroblasts. Rat1 transformation correlates with the expression level of LMP1CD40 and depends on its ability to oligomerize. Our data provide direct evidence for the oncogenic potential of the CD40 signaling pathway, which is also established as a model-mechanism for LMP1-induced transformation.

背景与目标： : 癌蛋白LMP1模仿活化的CD40受体，但尚不清楚组成型CD40信号传导 (如LMP1) 是否足以转化细胞。在这里，我们证明了嵌合LMP1CD40分子对CD40途径的组成型激活类似于LMP1在诱导Rat1成纤维细胞的接触抑制丧失和锚定独立生长方面的转化功能。Rat1转化与LMP1CD40的表达水平相关，并取决于其寡聚能力。我们的数据为CD40信号通路的致癌潜力提供了直接证据，CD40信号通路也被确立为LMP1-induced转化的模型机制。

BACKGROUND & AIMS: BACKGROUND:The combination of inhaled corticosteroids (ICS) and long-acting beta2-agonists (LABA) is recommended by treatment guidelines for the treatment of persistent asthma. Two such combination products, salmeterol/fluticasone propionate (SFC, Seretide GSK, UK) and formoterol/budesonide (FBC, Symbicort, AstraZeneca, UK) are commercially available. OBJECTIVES:The purpose of these studies was to evaluate and compare the duration of bronchodilation of both combination products up to 24 hours after a single dose. METHODS:Two randomised, double blind, placebo-controlled, crossover studies were performed. Study A was conducted in 33 asthmatic adults receiving 400-1200 mcg of budesonide or equivalent. Serial forced expiratory volume in one second (FEV1) was measured over 24 hours to determine the duration of effect of both SFC (50/100 mcg) and FBC (4.5/160 mcg). Study B was conducted in 75 asthmatic adults receiving 800-1200 mcg of budesonide or equivalent and comprised a 4 week run-in of 400 mcg bd Becotide followed by 4 weeks treatment with either SFC 50/100 mcg bd or FBC 4.5/160 mcg bd taken in a cross-over manner. Serial 24-hour FEV1 was measured after the first dose and the last dose after each 4-weeks treatment period to determine the offset of action of each treatment. RESULTS:In study A, a single inhalation of SFC and FBC produced a sustained bronchodilation at 16 hours with an adjusted mean increase in FEV1 from pre-dose of 0.22 L (95% CI 0.19, 0.35 L) for SFC and 0.25 L (95% CI 0.21, 0.37 L) for FBC, which was significantly greater than placebo for both treatments (-0.05 L; p < 0.001). In study B, the slope of decline in FEV1 from 2-24 hours post dose was -16.0 ml/hr for SFC and -14.2 ml/hr for FBC. The weighted mean AUC over 24 hours was 0.21 Lxmin and 0.22 Lxmin and mean change from pre-dose FEV1 at 12 hours was 0.21 L for SFC and 0.20 L for FBC respectively CONCLUSION:Both SFC and FBC produced a similar sustained bronchodilator effect which was prolonged beyond 12 hours post dose and was clearly measurable at 24 h.

背景与目标：

BACKGROUND & AIMS: :Cyclic and congenital neutropenia are caused by mutations in the human neutrophil elastase (HNE) gene (ELA2), leading to an immunodeficiency characterized by decreased or oscillating levels of neutrophils in the blood. The HNE mutations presumably cause loss of enzyme activity, consequently leading to compromised immune system function. To understand the structural basis for the disease, we implemented methods from bioinformatics to analyze all the known HNE missense mutations at both the sequence and structural level. Our results demonstrate that the 32 different mutations have diverse effects on HNE structure and function, affecting structural disorder and aggregation tendencies, stability maintaining contacts, and electrostatic properties. A large proportion of the mutations are located at conserved amino acids, which are usually essential in determining protein structure and function. The majority of the disease-causing HNE missense mutations lead to major structural changes and loss of stability in the protein. A few mutations also affect functional residues, leading into decreased catalytic activity or altered ligand binding. Our analysis reveals the putative effects of all known missense mutations in HNE, thus allowing the structural basis of cyclic and congenital neutropenia to be elucidated. We have employed and analyzed a set of some 30 different methods for predicting the effects of amino acid substitutions. We present results and experience from the analysis of the applicability of these methods in the analysis of numerous genes, proteins, and diseases to reveal protein structure-function relationships and disease genotype-phenotype correlations.

背景与目标： : 周期性和先天性中性粒细胞减少症是由人类中性粒细胞弹性蛋白酶 (HNE) 基因 (ELA2) 突变引起的，导致免疫缺陷，其特征是血液中中性粒细胞水平降低或振荡。HNE突变可能会导致酶活性丧失，从而导致免疫系统功能受损。为了了解疾病的结构基础，我们采用了生物信息学的方法，在序列和结构水平上分析了所有已知的HNE错义突变。我们的结果表明，32种不同的突变对HNE的结构和功能具有不同的影响，影响结构紊乱和聚集趋势，保持接触的稳定性和静电特性。大部分突变位于保守的氨基酸，这通常是确定蛋白质结构和功能的关键。大多数引起疾病的HNE错义突变会导致蛋白质的主要结构变化和稳定性丧失。一些突变也会影响功能残基，导致催化活性降低或配体结合改变。我们的分析揭示了HNE中所有已知的错义突变的推定作用，从而阐明了周期性和先天性中性粒细胞减少症的结构基础。我们已经采用并分析了一组30种不同的方法来预测氨基酸取代的影响。我们介绍了这些方法在众多基因，蛋白质和疾病分析中的适用性分析的结果和经验，以揭示蛋白质结构-功能关系和疾病基因型-表型相关性。

BACKGROUND & AIMS: Low intensity ultrasound signals, similar to that employed in clinical therapy, are found to mediate differential gene transfer and expression of the Green Fluorescence Protein (GFP) reporter in two human prostate cancer cell lines, LnCap and PC-3. Cell suspensions in the presence or in the absence of GFP (44.5nM) were treated at 37 degrees C under a standing wave condition. Cells were exposed to either continuous wave, 932.7kHz ultrasound, or to several independent bursts, each burst comprising a 20% duty cycle (932.7kHz) sine wave. The burst "repetition" frequency was varied from 10Hz to 10kHz in several different experiments and each treatment received a net identical ultrasound energy exposure. Transient GFP expression levels in viable cells were monitored by flow cytometry. The findings revealed a strong ultrasound tone-burst frequency dependence on the transfection efficiencies. Interestingly, the ultrasound signal parameters which are routinely employed in clinical therapy did not yield any statistically significant enhancement in transfection efficiency relative to their sham counterparts.

背景与目标： 发现与临床治疗中使用的低强度超声信号相似，可介导两种人前列腺癌细胞系LnCap和PC-3中的差异基因转移和绿色荧光蛋白 (GFP) 报告基因的表达。在驻波条件下，在37 ℃ 下处理存在或不存在GFP (44.5nm) 的细胞悬浮液。将细胞暴露于连续波、932.7khz超声波或几个独立的突发，每个突发包括20% 占空比 (932.7khz) 正弦波。在几个不同的实验中，突发 “重复” 频率从10Hz到10kHz不等，并且每种处理均获得净相同的超声能量暴露。通过流式细胞术监测活细胞中的瞬时GFP表达水平。研究结果表明，超声音调爆发频率对转染效率有很强的依赖性。有趣的是，与假手术相比，临床治疗中常规使用的超声信号参数在转染效率上没有任何统计学上的显着提高。

BACKGROUND & AIMS: :Different attempts were made to identify the variables that may be involved in the clinical course of cerebrovascular ischemia. In the case of stroke with mild severity (SMS), the clinical significance of neuroendocrine changes as well as of post-stroke depression (PSD) remains unknown. We therefore evaluated the presence of neuroendocrine changes in the acute and post-acute phase of SMS, and their potential role during convalescence. Serum cortisol, T4, T3, FT4, FT3, TSH and PRL levels were measured in 17 euthyroid patients with stroke on admission (day 1), following morning (day 2), 7 days and 3 months later. TSH and PRL secretion after TRH test were measured. Stroke severity on admission was determined by Scandinavian Stroke Scale (SSS). Montgomery-Asberg Depression Rating Scale (Madrs) was used for assessment of post-stroke depression. On admission, TSH and T3, were within normal limits and were greater compared to values on day 2. Lower basal TSH and decreased TSH response to TRH on day 2, were associated with stroke of greater severity. Delta-PRL after TRH on day 2 was higher in patients who develop PSD. Changes in serum thyroid hormones in SMS, reflects those of non-thyroidal illness. A mild stimulation of hypothalamic-pituitary-adrenal axis was detected. We provide evidence that PRL response to TRH, in the acute phase of stroke may be used as an index for early detection of PSD.

背景与目标： : 进行了不同的尝试来确定可能与脑血管缺血的临床过程有关的变量。对于轻度严重程度 (SMS) 的中风，神经内分泌变化以及卒中后抑郁 (PSD) 的临床意义仍然未知。因此，我们评估了SMS急性期和急性期后神经内分泌变化的存在及其在恢复期中的潜在作用。在入院时 (第1天)，第二天 (第2天)，7天和3个月后的17例甲状腺功能正常的中风患者中测量了血清皮质醇，T4，T3，FT4，FT3，TSH和PRL水平。TRH试验后测量TSH和PRL分泌。入院时卒中严重程度由斯堪的纳维亚卒中量表 (SSS) 确定。Montgomery-Asberg抑郁量表 (Madrs) 用于评估中风后抑郁。入院时，TSH和T3在正常范围内，与第2天的值相比更高。在第2天，较低的基础TSH和对TRH的TSH反应降低与严重程度更高的中风有关。发生PSD的患者在TRH后第2天的Delta-PRL较高。SMS中血清甲状腺激素的变化反映了非甲状腺疾病的变化。检测到下丘脑-垂体-肾上腺轴的轻度刺激。我们提供的证据表明，在中风急性期PRL对TRH的反应可以用作早期发现PSD的指标。

BACKGROUND & AIMS: Development of methodologies for gene transfer into the central nervous system (CNS) is important for fundamental research as well as clinical studies for gene therapy. Cationic liposomes (CL) are attractive vectors because of their safety and ease of use. However, to date only low rates of success have been reported. We succeeded in obtaining high transfection efficiencies into the newborn mouse brain in vivo by CL and a cytoplasmic gene expression system based on T7 RNA polymerase and T7 RNA polymerase- and the luciferase-gene with the T7 promoter sequence. This system showed an efficiency rate 2 orders of magnitude higher than the standard system, which used CL and luciferase genes with a Rous sarcoma virus promoter, pRSVL. In addition, in vitro experiments using LLCMK2 cells showed that cytoplasmic gene expression occurred rapidly (within 6 h) after transfection. In contrast, pRSVL required 24-48 h for induction of luciferase expression. Our results suggest that the cytoplasmic gene expression system is useful for gene delivery into the CNS.

背景与目标： 开发将基因转移到中枢神经系统 (CNS) 的方法对于基因治疗的基础研究和临床研究至关重要。阳离子脂质体 (CL) 是有吸引力的载体，因为它们的安全性和易用性。然而，迄今为止，只有低成功率的报道。我们成功地通过CL和基于T7 RNA聚合酶和T7 RNA聚合酶以及具有T7启动子序列的荧光素酶基因的细胞质基因表达系统在体内获得了高转染效率。该系统的效率比标准系统高2个数量级，标准系统使用具有Rous肉瘤病毒启动子pRSVL的CL和荧光素酶基因。此外，使用LLCMK2细胞的体外实验表明，转染后细胞质基因表达迅速 (在6小时内) 发生。相反，pRSVL需要24-48小时才能诱导荧光素酶表达。我们的结果表明，细胞质基因表达系统可用于将基因传递到CNS中。

BACKGROUND & AIMS: :Polo-like kinases (PLKs) are marked by C-terminal polo box modules with critical protein interaction and subcellular targeting roles. Slevin et al. in this issue of Structure reveal the architecture of a hidden set of polo boxes from the divergent PLK4, a critical player in centrosome duplication, shedding new light on the evolution of PLKs and their functionally related kinase ZYG-1.

背景与目标： : Polo样激酶 (plk) 由C末端polo盒模块标记，具有关键的蛋白质相互作用和亚细胞靶向作用。Slevin等人在本期《结构》中揭示了来自不同PLK4的一组隐藏的polo盒子的架构，PLK4是中心体复制的关键参与者，为plk及其功能相关激酶ZYG-1的演变提供了新的启示。

BACKGROUND & AIMS: :We reviewed six cases of primary sarcomas requiring scapulectomy within the past 13 years in the Surgery Branch of the National Cancer Institute, Bethesda, Md. Five of these patients returned for evaluation of disease status, evaluation of functional defects as determined by muscle group testing, and assessment of daily living skills and limitations. We demonstrated excellent shoulder function with partial scapulectomy and significant impairment with the additional loss of the glenoid fossa. In addition, we developed a thorough method of postoperative evaluation. Involvement of rehabilitation therapists before and after operatively is integral to this process in preparation for surgery and subsequent treatment.

背景与目标： : 在过去的13年中，我们在马里兰州贝塞斯达的国家癌症研究所外科分支机构中回顾了6例需要进行肩胛骨切除术的原发性肉瘤病例。这些患者中有五名返回以评估疾病状况，评估通过肌肉群测试确定的功能缺陷以及评估日常生活技能和局限性。我们通过部分肩胛骨切除术证明了出色的肩部功能，并通过关节盂窝的额外损失而明显受损。此外，我们开发了一种彻底的术后评估方法。在手术和后续治疗的准备过程中，康复治疗师在手术前后的参与是必不可少的。

BACKGROUND & AIMS: :Musical training has emerged as a useful framework for the investigation of training-related plasticity in the human brain. Learning to play an instrument is a highly complex task that involves the interaction of several modalities and higher-order cognitive functions and that results in behavioral, structural, and functional changes on time scales ranging from days to years. While early work focused on comparison of musical experts and novices, more recently an increasing number of controlled training studies provide clear experimental evidence for training effects. Here, we review research investigating brain plasticity induced by musical training, highlight common patterns and possible underlying mechanisms of such plasticity, and integrate these studies with findings and models for mechanisms of plasticity in other domains.

背景与目标： : 音乐训练已成为研究人脑中与训练相关的可塑性的有用框架。学习演奏乐器是一项高度复杂的任务，涉及几种模态和高阶认知功能的相互作用，并导致行为，结构和功能在从数天到数年内的时间范围内发生变化。虽然早期的工作侧重于音乐专家和新手的比较，但最近越来越多的受控训练研究为训练效果提供了明确的实验证据。在这里，我们回顾了研究由音乐训练引起的大脑可塑性的研究，强调了这种可塑性的常见模式和可能的潜在机制，并将这些研究与其他领域的可塑性机制的发现和模型相结合。

BACKGROUND & AIMS: :Flavohemoglobins (FHbs) are members of the globin superfamily, widely distributed among prokaryotes and eukaryotes that have been shown to carry out nitric oxide dioxygenase (NOD) activity. In prokaryotes, such as Escherichia coli, NOD activity is a defence mechanism against the NO release by the macrophages of the hosts' immune system during infection. Because of that, FHbs have been studied thoroughly and several drugs have been developed in an effort to fight infectious processes. Nevertheless, the protein's structural determinants involved in the NOD activity are still poorly understood. In this context, the aim of the present work is to unravel the molecular basis of FHbs structural dynamics-to-function relationship using state of the art computer simulation tools. In an effort to fulfill this goal, we studied three key processes that determine NOD activity, namely i) ligand migration into the active site ii) stabilization of the coordinated oxygen and iii) intra-protein electron transfer (ET). Our results allowed us to determine key factors related to all three processes like the presence of a long hydrophobic tunnel for ligand migration, the presence of a water mediated hydrogen bond to stabilize the coordinated oxygen and therefore achieve a high affinity, and the best possible ET paths between the FAD and the heme, where water molecules play an important role. Taken together the presented results close an important gap in our understanding of the wide and diverse globin structural-functional relationships.

背景与目标： : 黄素血红蛋白 (FHbs) 是球蛋白超家族的成员，广泛分布在原核生物和真核生物中，已证明具有一氧化氮双加氧酶 (NOD) 活性。在原核生物 (例如大肠杆菌) 中，NOD活性是抵抗宿主免疫系统巨噬细胞在感染过程中释放NO的防御机制。因此，已经对FHbs进行了彻底的研究，并开发了几种药物来对抗传染过程。尽管如此，与NOD活性有关的蛋白质的结构决定因素仍然知之甚少。在这种情况下，本工作的目的是使用最先进的计算机模拟工具来阐明FHbs结构动力学与功能关系的分子基础。为了实现这一目标，我们研究了确定NOD活性的三个关键过程，即i) 配体迁移到活性位点ii) 配位氧的稳定和iii) 蛋白质内电子转移 (ET)。我们的结果使我们能够确定与所有三个过程相关的关键因素，例如配体迁移的长疏水隧道的存在，水介导的氢键的存在以稳定配位氧并因此实现高亲和力，以及FAD和血红素之间的最佳ET路径，水分子起着重要作用。综合起来，提出的结果缩小了我们对广泛而多样的珠蛋白结构-功能关系的理解中的重要差距。

BACKGROUND & AIMS: BACKGROUND:Choline is essential for fetal brain development, and it is not known whether a typical American diet contains enough choline to ensure optimal brain development. OBJECTIVE:The study was undertaken to determine whether supplementing pregnant women with phosphatidylcholine (the main dietary source of choline) improves the cognitive abilities of their offspring. DESIGN:In a double-blind, randomized controlled trial, 140 pregnant women were randomly assigned to receive supplemental phosphatidylcholine (750 mg) or a placebo (corn oil) from 18 wk gestation through 90 d postpartum. Their infants (n = 99) were tested for short-term visuospatial memory, long-term episodic memory, language development, and global development at 10 and 12 mo of age. RESULTS:The women studied ate diets that delivered ∼360 mg choline/d in foods (∼80% of the recommended intake for pregnant women, 65% of the recommended intake for lactating women). The phosphatidylcholine supplements were well tolerated. Groups did not differ significantly in global development, language development, short-term visuospatial memory, or long-term episodic memory. CONCLUSIONS:Phosphatidylcholine supplementation of pregnant women eating diets containing moderate amounts of choline did not enhance their infants' brain function. It is possible that a longer follow-up period would reveal late-emerging effects. Moreover, future studies should determine whether supplementing mothers eating diets much lower in choline content, such as those consumed in several low-income countries, would enhance infant brain development.

背景与目标：

BACKGROUND & AIMS: :The solution of the forward problem in fluorescence molecular imaging strongly influences the successful convergence of the fluorophore reconstruction. The most common approach to meeting this problem has been to apply the diffusion approximation. However, this model is a first-order angular approximation of the radiative transfer equation, and thus is subject to some well-known limitations. This manuscript proposes a methodology that confronts these limitations by applying the radiative transfer equation in spatial regions in which the diffusion approximation gives decreased accuracy. The explicit integro differential equations that formulate this model were solved by applying the Galerkin finite element approximation. The required spatial discretization of the investigated domain was implemented through the Delaunay triangulation, while the azimuthal discretization scheme was used for the angular space. This model has been evaluated on two simulation geometries and the results were compared with results from an independent Monte Carlo method and the radiative transfer equation by calculating the absolute values of the relative errors between these models. The results show that the proposed forward solver can approximate the radiative transfer equation and the Monte Carlo method with better than 95% accuracy, while the accuracy of the diffusion approximation is approximately 10% lower.

背景与目标： : 荧光分子成像中正向问题的解决方案强烈影响荧光团重建的成功收敛。解决此问题的最常见方法是应用扩散近似。但是，该模型是辐射传递方程的一阶角近似，因此受到一些众所周知的限制。该手稿提出了一种方法，该方法通过在空间区域中应用辐射传递方程来应对这些限制，在空间区域中，扩散近似值降低了精度。通过应用Galerkin有限元近似求解了建立该模型的显式积分微分方程。通过Delaunay三角剖分实现了所研究域所需的空间离散化，而角度空间则使用了方位角离散化方案。该模型已在两个模拟几何上进行了评估，并通过计算这些模型之间相对误差的绝对值，将结果与独立的蒙特卡洛方法和辐射传递方程的结果进行了比较。结果表明，提出的前向求解器能够较好地逼近辐射传递方程和蒙特卡罗方法，精度优于95%，而扩散逼近的精度约为10%。

BACKGROUND & AIMS: :Spermatogenesis is a dynamic process that is regulated by adhesive interactions between germ and Sertoli cells. Germ cells express the Junctional Adhesion Molecule-C (JAM-C, encoded by Jam3), which localizes to germ/Sertoli cell contacts. JAM-C is involved in germ cell polarity and acrosome formation. Using a proteomic approach, we demonstrated that JAM-C interacted with the Golgi reassembly stacking protein of 55 kDa (GRASP55, encoded by Gorasp2) in developing germ cells. Generation and study of Gorasp2-/- mice revealed that knock-out mice suffered from spermatogenesis defects. Acrosome formation and polarized localization of JAM-C in spermatids were altered in Gorasp2-/- mice. In addition, Golgi morphology of spermatocytes was disturbed in Gorasp2-/- mice. Crystal structures of GRASP55 in complex with JAM-C or JAM-B revealed that GRASP55 interacted via PDZ-mediated interactions with JAMs and induced a conformational change in GRASP55 with respect of its free conformation. An in silico pharmacophore approach identified a chemical compound called Graspin that inhibited PDZ-mediated interactions of GRASP55 with JAMs. Treatment of mice with Graspin hampered the polarized localization of JAM-C in spermatids, induced the premature release of spermatids and affected the Golgi morphology of meiotic spermatocytes.

背景与目标： : 精子发生是一个动态过程，由生殖细胞和支持细胞之间的粘附相互作用调节。生殖细胞表达连接粘附分子-C (JAM-C，由Jam3编码)，其定位于生殖/支持细胞接触。JAM-C参与生殖细胞极性和胚体形成。使用蛋白质组学方法，我们证明了JAM-C在发育中的生殖细胞中与55 kDa的高尔基重组堆积蛋白 (GRASP55，由Gorasp2编码) 相互作用。Gorasp2-/-小鼠的产生和研究表明，敲除小鼠患有精子发生缺陷。在Gorasp2-/-小鼠中，精子细胞中JAM-C的顶体形成和极化定位发生了改变。此外，Gorasp2-/-小鼠的精母细胞高尔基体形态受到干扰。GRASP55与JAM-C或JAM-B配合物的晶体结构表明，GRASP55通过PDZ介导的与JAMs的相互作用，并在其自由构象方面引起GRASP55的构象变化。计算机药效团方法确定了一种称为Graspin的化合物，该化合物抑制了PDZ介导的GRASP55与果酱的相互作用。用Graspin处理小鼠会阻碍JAM-C在精子中的极化定位，诱导精子的过早释放并影响减数分裂精母细胞的高尔基体形态。

BACKGROUND & AIMS: :T cell regulation of the generation of thyroglobulin plaque-forming cells (Tg PFC) and protein A plaque-forming cells (Prot A PFC) was investigated using lymphocytes from patients with autoimmune thyroid disease. T and B cell mixed cultures (T-B MC) were carried out without mitogenic or antigenic stimulation to identify physiological T cell effects in the system. Tg PFC were found in 8 (44%) of 18 patients who had high titers of thyroglobulin antibody in their sera. Tg-specific and nonspecific immunoregulation by T cells from patients and normal subjects was studied using B cells from these eight patients in the T-B MC system. Remarkably lower values of Tg PFC induction compared to Prot A PFC induction were found after T cell addition. Normal T cells inhibited Tg PFC induction, but patient T cells did not, while the same extent of helper effects were found on Prot A PFC induction by the addition of patient and normal T cells. Irradiation (1500 rads) of T cells from patients and normal subjects significantly enhanced both TgPFC and Prot A PFC induction. Thus, Tg-specific suppressor T cells are present in all normal subjects as part of the radiosensitive suppressor T cell subset. The increase in Tg-PFC caused by irradiation-induced inhibition of Tg-specific suppressor T cell function was significantly greater in normal subjects than in patients. Histamine type 2 receptor-bearing T cells inhibited Prot A PFC induction, but not Tg PFC induction, in the autologous T-B MC system. No Tg PFC were induced from normal B cells in any combination with untreated T cells, irradiated T cells, or histamine type 2 receptor-negative T cells from patients or normal subjects. These data indicate that in vitro Tg-specific T cell regulation can be studied in the T-B MC system by using B cells from patients with autoimmune thyroid disease with high Tg antibody titers in their sera. Tg-specific suppressor T cells appear to be present in all individuals and to be involved in the regulation of Tg antibody production. The lower activity of Tg-specific suppressor T cells in patients compared to that in normal subjects may be related to Tg antibody production in vivo. This abnormality, however, is heterogeneous and is not a complete but, rather, is a relative defect of Tg-specific suppressor T cells.

背景与目标： : 使用自身免疫性甲状腺疾病患者的淋巴细胞研究了甲状腺球蛋白斑块形成细胞 (Tg PFC) 和蛋白A斑块形成细胞 (Prot A PFC) 生成的T细胞调节。在没有促有丝分裂或抗原刺激的情况下进行T细胞和b细胞混合培养 (t-b MC)，以鉴定系统中的生理T细胞作用。在18例血清中甲状腺球蛋白抗体滴度较高的患者中，有8例 (44% 例) 发现了Tg PFC。在t-b MC系统中，使用这八名患者的b细胞研究了患者和正常受试者的T细胞对Tg的特异性和非特异性免疫调节。添加T细胞后，与Prot A PFC诱导相比，Tg PFC诱导值明显降低。正常T细胞抑制Tg PFC诱导，但患者T细胞不抑制，而通过添加患者和正常T细胞对Prot A PFC诱导发现了相同程度的辅助作用。来自患者和正常受试者的T细胞的照射 (1500 rads) 显着增强了TgPFC和Prot A PFC的诱导。因此，Tg特异性抑制T细胞作为放射敏感性抑制T细胞亚群的一部分存在于所有正常受试者中。在正常受试者中，由辐射诱导的Tg特异性抑制T细胞功能抑制引起的tg-pfc的增加明显大于患者。在自体t-b MC系统中，带有组胺2型受体的T细胞抑制Prot A PFC诱导，但不抑制Tg PFC诱导。正常b细胞与未经治疗的T细胞，辐照的T细胞或来自患者或正常受试者的组胺2型受体阴性T细胞的任何组合均未诱导Tg PFC。这些数据表明，可以使用来自血清中Tg抗体滴度较高的自身免疫性甲状腺疾病患者的b细胞，在t-b MC系统中研究体外Tg特异性T细胞调控。Tg特异性抑制T细胞似乎存在于所有个体中，并参与Tg抗体产生的调节。与正常受试者相比，患者中Tg特异性抑制T细胞的活性较低可能与体内Tg抗体的产生有关。然而，这种异常是异质的，不是完整的，而是Tg特异性抑制T细胞的相对缺陷。

BACKGROUND & AIMS: :Among the three major food crops (rice, wheat and maize), wheat is unique in accumulating gluten proteins in its grains. Of these proteins, the high and low molecular weight glutenin subunits (HMW-GSs and LMW-GSs) form glutenin macropolymers that are vital for the diverse end-uses of wheat grains. In this work, we developed a new series of deletion mutants lacking one or two of the three Glu-1 loci (Glu-A1, -B1 and -D1) specifying HMW-GSs. Comparative analysis of single and double deletion mutants reinforced the suggestion that Glu-D1 (encoding the HMW-GSs 1Dx2 and 1Dy12) has the largest effects on the parameters related to gluten and dough functionalities and breadmaking quality. Consistent with this suggestion, the deletion mutants lacking Glu-D1 or its combination with Glu-A1 or Glu-B1 generally exhibited strong decreases in functional glutenin macropolymers (FGMPs) and in the incorporation of HMW-GSs and LMW-GSs into FGMPs. Further examination of two knockout mutants missing 1Dx2 or 1Dy12 showed that 1Dx2 was clearly more effective than 1Dy12 in promoting FGMPs by enabling the incorporation of more HMW-GSs and LMW-GSs into FGMPs. The new insight obtained and the mutants developed by us may aid further research on the control of wheat end-use quality by glutenin proteins.

背景与目标： : 在三大粮食作物 (水稻、小麦和玉米) 中，小麦在谷物中积累麸质蛋白是独一无二的。在这些蛋白质中，高分子量和低分子量谷蛋白亚基 (hmw-gss和lmw-gss) 形成谷蛋白大聚合物，对于小麦籽粒的多种最终用途至关重要。在这项工作中，我们开发了一系列新的缺失突变体，缺少指定hmw-gss的三个Glu-1基因座 (Glu-A1，-B1和-D1) 中的一个或两个。单缺失突变体和双缺失突变体的比较分析强化了Glu-D1 (编码hmw-gss 1Dx2和1Dy12) 对与面筋和面团功能以及面包制作质量有关的参数影响最大的建议。与该建议一致，缺乏Glu-D1的缺失突变体或其与Glu-A1或Glu-B1的组合通常表现出功能性谷蛋白大聚合物 (fgmp) 和hmw-gss和lmw-gss掺入fgmp中的强烈降低。对两个缺失1Dx2或1Dy12的敲除突变体的进一步检查表明，通过将更多的hmw-gss和lmw-gss掺入fgmp中，1Dx2在促进fgmp方面明显比1Dy12更有效。我们获得的新见解和开发的突变体可能有助于通过谷蛋白控制小麦最终用途品质的进一步研究。