BACKGROUND & AIMS: :The presenilin (PS) proteins are polytopic integral membrane proteins that are critically involved in the development of Alzheimer's disease. The topography of the PS molecule in the endoplasmic reticulum membrane is widely accepted as exhibiting eight-hydrophobic-transmembrane (8-TM) helices. We have previously provided evidence, however, that the intact PS molecule is also present in the cell surface where it exhibits exclusively a 7-TM topography, which differs in significant structural features from the 8-TM model. This evidence, however, has been disparaged and generally rejected by researchers in Alzheimer's disease. The 7-TM model is definitively demonstrated in the present study for PS-1 at the surfaces of PS-1-transfected cells and for endogenous PS-1 at the surfaces of untransfected cells, by immunofluorescence studies using mAbs. These studies force substantial revision of current views of the structural and functional properties of the PS proteins.

背景与目标： : 早老素 (PS) 蛋白是多位整合膜蛋白，与阿尔茨海默氏病的发展密切相关。内质网膜中PS分子的形貌被广泛认为具有八个疏水跨膜 (8-TM) 螺旋。然而，我们以前已经提供了证据，表明完整的PS分子也存在于细胞表面，在那里它仅表现出7-TM形貌，其显着的结构特征与8-TM模型不同。然而，这一证据被阿尔茨海默氏病的研究人员贬低并普遍拒绝。通过使用mab的免疫荧光研究，在本研究中明确证明了在PS-1-transfected细胞表面的PS-1和在未转染细胞表面的内源性PS-1的7-TM模型。这些研究迫使对PS蛋白的结构和功能特性的当前观点进行了实质性修改。

BACKGROUND & AIMS: :MoS2 nanoribbons with armchair-terminated edges are semiconductors suitable for the tuning of electronic and magnetic properties. Our first-principles density function calculations reveal that a variety of transition-metal atomic chains deposited on some of the ribbons is able to transform the semiconductors into half metals, allowing transport of 100% spin-polarized currents. Furthermore, we found that a Si atomic chain is equally capable of achieving half metallicity when adsorbed on the same nanoribbon. These results should be useful for spintronic application.

背景与目标： : 带扶手椅端边的MoS2纳米带是适用于电子和磁性能调谐的半导体。我们的第一原理密度函数计算表明，沉积在某些带上的各种过渡金属原子链能够将半导体转变为半金属，从而允许传输100% 自旋极化电流。此外，我们发现，当吸附在同一纳米带上时，Si原子链同样能够实现半金属性。这些结果对于自旋电子应用应该是有用的。

BACKGROUND & AIMS: :On page 1667 of this issue, Stuart Smith and colleagues [1] demonstrate that the animal fatty acid synthase is a head-to-head dimer rather than the head-to-tail dimer depicted in textbooks. This has important ramifications for the mechanisms of other multifunctional enzymes such as polyketide synthases [2].

背景与目标： : 在本期的第1667页上，Stuart Smith及其同事 [1] 证明了动物脂肪酸合酶是头对头二聚体，而不是教科书中描述的头对尾二聚体。这对其他多功能酶 (例如聚酮化合物合酶) 的机制具有重要影响 [2]。

BACKGROUND & AIMS: :The sepsis syndrome is thought to occur when microbial products activate Toll-like receptors stimulating widespread inflammation, in turn causing organ failure, shock and death. However, recent discoveries reveal that: (i) not only microbial substances but also endogenous molecules can trigger Toll-like receptors; (ii) Toll-like receptor-4, the endotoxin receptor, is constitutively suppressed; and (iii) the first step in sepsis could be the release of Toll-like receptor-4 from suppression. These discoveries suggest that endotoxin might not always initiate the sepsis syndrome and they explain why anti-endotoxin therapies fail. The discoveries also suggest new therapeutic targets - endogenous agonists and Toll-like receptor regulators - for treatment of sepsis.

背景与目标： : 当微生物产物激活Toll样受体刺激广泛的炎症，进而导致器官衰竭，休克和死亡时，就会发生败血症综合征。然而，最近的发现表明 :( i) 不仅微生物物质，而且内源性分子都可以触发Toll样受体; (ii) Toll样受体-4 (内毒素受体) 被组成性抑制; (iii) 败血症的第一步可能是从抑制中释放Toll样受体4。这些发现表明内毒素可能并不总是引发败血症综合征，它们解释了抗内毒素疗法失败的原因。这些发现还提出了治疗脓毒症的新的治疗靶点-内源性激动剂和Toll样受体调节剂。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: :The chromosome of R6K contains multiple origins of replication. The origin gamma is infrequently used in the original plasmid and remains "silent" in certain miniplasmid derivatives. The inactivation of the origin is caused by a natural origin silencer located adjacent to the minimal ori gamma sequence. The silencer functions in cis and has no trans activity. It has functional polarity and works only in one orientation when present immediately downstream from ori gamma. The silencer apparently initiates an RNA that invades ori gamma and turns it off either by competing with a primer RNA or by disrupting ori gamma structure. As predicted, removal of the silencer blocks the synthesis of silencer RNA and derepresses the origin.

背景与目标： : R6K的染色体包含多个复制起源。原始质粒中很少使用origin γ，在某些小质粒衍生物中保持 “沉默”。原点的失活是由位于最小ori gamma序列附近的自然原点消音器引起的。消音器在顺式中起作用，没有反式活性。它具有功能性极性，并且在ori gamma下游立即存在时仅在一个方向上起作用。消音器显然会启动入侵ori gamma的RNA，并通过与引物RNA竞争或破坏ori gamma结构将其关闭。如预期的那样，去除消音器会阻止消音器RNA的合成并消除原点。

BACKGROUND & AIMS: :To evaluate the effectiveness of a cytological screening to prevent invasive cervical cancer in the province of Trento, a northern Italian area where a population-based cancer registry is active. The history of Pap test was evaluated through a case-control study in 61 population-based invasive cervical cancer patients, incident during 1995-2000, and in 244 age-matched (between 25 and 75 years old) controls. Women who had at least one Pap test had a reduced risk of invasive carcinoma of 80% (odds ratio=0.20; 95% confidence intervals 0.10-0.40). The protection of a previous Pap test for both squamous cell carcinoma (odds ratio=0.23; 95% confidence intervals 0.09-0.58) and adenocarcinoma (odds ratio=0.24; 95% confidence intervals 0.07-0.78) was similar. The overall protective effect of the Pap test was not seen among younger women (<40 years). The protective effect of the Pap test seems to be stronger for shorter intervals. Our study confirms that Pap-test screening, particularly in middle-aged and older women, is an effective public health intervention with encouraging results also for the prevention of cervical adenocarcinoma.

背景与目标： : 评估细胞学筛查在意大利北部特伦托省预防浸润性宫颈癌的有效性，特伦托省是一个基于人群的癌症登记处。通过病例对照研究评估了61例基于人群的浸润性宫颈癌患者的Pap测试史，这些患者在1995-2000期间发生，并且在244年龄匹配 (25至75岁) 的对照中。至少进行了一次巴氏试验的女性患80% 浸润性癌的风险降低 (比值比 = 0.20; 95% 置信区间0.10-0.40)。先前的Pap测试对鳞状细胞癌 (优势比 = 0.23; 95% 置信区间0.09-0.58) 和腺癌 (优势比 = 0.24; 95% 置信区间0.07-0.78) 的保护相似。巴氏试验的总体保护作用在年轻女性 (<40岁) 中未见。对于较短的间隔，巴氏试验的保护作用似乎更强。我们的研究证实，巴氏试验筛查 (尤其是中老年妇女) 是一种有效的公共卫生干预措施，在预防宫颈腺癌方面也取得了令人鼓舞的结果。

BACKGROUND & AIMS: The agouti locus was first identified as a result of its effects on the type and temporal deposition of coat color pigments in mammals. Many mutations at the murine agouti locus have now been found, some of which not only affect coat color, but also interfere with diverse biological processes leading to diabetes, obesity, tumor susceptibility and embryonic lethality. Correlations between the genotype and phenotype of agouti mutants, as well as reasons for the pleiotropy of effects caused by agouti mutations, have begun to unfold with the molecular cloning of the agouti gene and its surrounding genomic region.

背景与目标： 最初是由于其对哺乳动物毛色色素的类型和时间沉积的影响而确定的。现在已经发现了鼠agouti基因座的许多突变，其中一些不仅影响毛色，而且还干扰导致糖尿病，肥胖，肿瘤易感性和胚胎致死率的各种生物学过程。随着agouti基因及其周围基因组区域的分子克隆，agouti突变体的基因型和表型之间的相关性以及由agouti突变引起的多效性影响的原因已开始展开。

BACKGROUND & AIMS: The inflammatory component associated with blackening and subsequent regression of plantar warts has been little appreciated in the literature. Two patients with plantar warts in whom one of the warts showed prominent, clinically evident inflammation were observed. Blackening and subsequent regression of all plantar warts then occurred. In one patient, microscopic examination of biopsy specimens of two lesions that were taken within 24 and 72 hours, respectively, after they had turned black demonstrated the following histologic findingsblood clots and hemorrhage in the stratum corneum, degeneration and necrosis of epidermal cells, eosinophilic cytoplasmic masses within degenerating epidermal cells, thrombosis of superficial and deeper dermal blood vessels, a mononuclear cell infiltrate in and around dermal blood vessels, and a mixed polymorphonuclear and lymphocytic infiltration in the areas of hemorrhage and degenerating epidermis. This constellation of histopathologic changes suggests that involution was in progress long before blackening of the warts occurred.

背景与目标： 与变黑和随后的足底疣消退有关的炎症成分在文献中很少得到重视。观察到两名足底疣患者，其中一个疣表现出明显的临床明显炎症。然后发生所有足底疣的黑化和随后的消退。在一名患者中，分别在变黑后的24和72小时内对两个病变的活检标本进行显微镜检查，结果显示以下组织学发现角质层的血凝块和出血，表皮细胞的变性和坏死，退化的表皮细胞内的嗜酸性细胞质团块，浅表和深层真皮血管的血栓形成，单个核细胞在真皮血管内及其周围浸润，并在出血和表皮退化区域混合多形核和淋巴细胞浸润。这种组织病理学变化的星座表明，在疣变黑之前很久就在进行中。

BACKGROUND & AIMS: BACKGROUND:The optimal surgical strategy for the correction of double outlet right ventricle (DORV, transposition of the great arteries [TGA] type) or TGA with ventricular septal defect (VSD), pulmonary stenosis (PS), and borderline small left ventricle (LV) is still controversial. The half-turned truncal switch operation (HTTSO) introduced by Yamagishi and colleagues is a good option, but it is still challenging in a patient with borderline small LV. We aimed to describe our experience of a case of HTTSO conversion from single ventricle palliation. CASE PRESENTATION:A 5-year-old girl with single ventricle physiology was referred to our hospital from Kazakhstan for a Fontan operation. At the time of birth, she was diagnosed with DORV (TGA type), PS, and situs inversus totalis, with moderate valvar and subvalvar stenosis and a relatively small LV cavity. Her LV volume was not adequate to support the systemic circulation; therefore, doctors in Kazakhstan selected the single ventricle palliation course of treatment for the infant. At 4 months of age, she underwent left-sided modified Blalock-Taussig shunt, patent ductus arteriosus ligation, and atrial septectomy. At 2 years of age, shunt takedown, left bidirectional cavopulmonary shunt, and main pulmonary artery division were performed. Annual echocardiography of the patient showed that the LV size was growing too adequately to persist with the single ventricle palliation course of treatment. Via a multidisciplinary approach, we considered her LV to be suitable for biventricular repair and HTTSO was planned. The operation and postoperative course were uneventful. The patient was discharged on postoperative day 6 and went back to Kazakhstan. CONCLUSIONS:Based on our successful surgical outcome, in patients diagnosed with DORV (TGA type) or TGA with VSD, PS, and borderline LV, HTTSO after achieving adequate LV growth by single ventricle palliation may be considered a good alternative to conventional operations in patients at a high risk for initial biventricular repair.

背景与目标：

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: :Proteins of the fast component of axonal transport were analyzed by one- and two-dimensional polyacrylamide gel electrophoresis in the guinea pig spiral ganglion, which has its cell bodies in the cochlea and its axons in the eighth cranial nerve projecting to the ipsilateral cochlear nucleus. We found that we could easily identify the proteins of the fast component even though these axons are only about 3 mm long because the cochlea minimized diffusion of labeled precursor into the cochlear nucleus. The composition of the fast component of the spiral ganglion cells was similar, but not identical, to the fast component of guinea pig retinal ganglion cells. One difference was the predominance in the spiral ganglion cell fast component of a rapidly turned-over glycoprotein (RTGP) with a molecular weight of 110,000-140,000 and an isoelectric point of 5.0 RTGP accumulated in the cochlear nucleus for just the first 3 hr after the application of the labeled precursor and then rapidly disappeared, whereas the other major fast component polypeptides continued to accumulate for 12-24 hr. RTGP was also tentatively identified in the fast component of retinal ganglion cells, but was not as prominently labeled relative to the other fast-component proteins in those cells. The rapid disappearance of RTGP from spiral ganglion cell terminals in the cochlear nucleus may be a result of secretion, perhaps as part of a synaptic vesicle, or retrograde transport as a feedback signal. The difference in the relative amounts of RTGP found in spiral ganglion and retinal ganglion cell terminals may reflect differences in the fundamental properties of the two groups of neurons.

背景与目标： : 通过一维和二维聚丙烯酰胺凝胶电泳在豚鼠螺旋神经节中分析了轴突转运快速成分的蛋白质，该神经节的细胞体在耳蜗中，其在第八颅神经中的轴突投射到同侧耳蜗核。我们发现，即使这些轴突仅约3毫米长，我们也可以轻松识别快速成分的蛋白质，因为耳蜗使标记的前体扩散到耳蜗核中最小化。螺旋神经节细胞的快速成分的组成与豚鼠视网膜神经节细胞的快速成分相似，但不完全相同。一个区别是快速翻转糖蛋白 (RTGP) 的螺旋神经节细胞快速成分的优势，其分子量为110,000-140,000，等电点为5.0 RTGP，仅在耳蜗核中积累了最初的3小时后，标记的前体，然后迅速消失，而其他主要的快速成分多肽继续积累12-24小时。RTGP也在视网膜神经节细胞的快速成分中初步鉴定，但相对于这些细胞中的其他快速成分蛋白而言，标记不明显。RTGP从耳蜗核的螺旋神经节细胞末端迅速消失可能是分泌的结果，可能是突触小泡的一部分，或者是作为反馈信号的逆行运输。在螺旋神经节和视网膜神经节细胞末端中发现的RTGP相对量的差异可能反映了两组神经元基本特性的差异。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: :Classically, monocular deprivation leaves all layers of visual cortex dominated by the non-deprived eye. Unexpectedly, the changes first appear in the outer layers, not the central input layer. Do thalamocortical and corticocortical synapses differ in their plasticity and could the outer layers drive input plasticity?

背景与目标： : 经典的是，单眼剥夺留下了由非剥夺眼主导的所有视觉皮层层。出乎意料的是，变化首先出现在外层，而不是中心输入层。丘脑皮质和皮质皮质突触的可塑性是否不同，外层是否可以驱动输入可塑性？

BACKGROUND & AIMS: :The nematode Caenorhabditis elegans is emerging as a facile and economical model host for the study of evolutionarily conserved mechanisms of microbial pathogenesis and innate immunity. A rapidly growing number of human and animal microbial pathogens have been shown to injure and kill nematodes. In many cases, microbial genes known to be important for full virulence in mammalian models have been shown to be similarly required for maximum pathogenicity in nematodes. C. elegans has been used in mutation-based screening systems to identify novel virulence-related microbial genes and immune-related host genes, many of which have been validated in mammalian models of disease. C. elegans-based pathogenesis systems hold the potential to simultaneously explore the molecular genetic determinants of both pathogen virulence and host defense.

背景与目标： : 线虫秀丽隐杆线虫正在成为研究微生物发病机理和先天免疫的进化保守机制的简便而经济的模型宿主。越来越多的人类和动物微生物病原体已被证明会伤害和杀死线虫。在许多情况下，已知对哺乳动物模型中的完全毒力很重要的微生物基因已被证明是线虫最大致病性所必需的。秀丽隐杆线虫已被用于基于突变的筛选系统，以鉴定新的毒力相关微生物基因和免疫相关宿主基因，其中许多已在哺乳动物疾病模型中得到验证。基于秀丽隐杆线虫的发病机制系统具有同时探索病原体毒力和宿主防御的分子遗传决定因素的潜力。