BACKGROUND & AIMS: :The distributed genome hypothesis (DGH) states that each strain within a bacterial species receives a unique distribution of genes from a population-based supragenome that is many times larger than the genome of any given strain. The observations that natural infecting populations are often polyclonal and that most chronic bacterial pathogens have highly developed mechanisms for horizontal gene transfer suggested the DGH and provided the means and the mechanisms to explain how chronic infections persist in the face of a mammalian host's adaptive defense mechanisms. Having previously established the validity of the DGH for obligate pathogens, we wished to evaluate its applicability to an opportunistic bacterial pathogen. This was accomplished by construction and analysis of a highly redundant pooled genomic library containing approximately 216,000 functional clones that was constructed from 12 low-passage clinical isolates of Pseudomonas aeruginosa, 6 otorrheic isolates and 6 from other body sites. Sequence analysis of 3,214 randomly picked clones (mean insert size, approximately 1.4 kb) from this library demonstrated that 348 (10.8%) of the clones were unique with respect to all genomic sequences of the P. aeruginosa prototype strain, PAO1. Hypothetical translations of the open reading frames within these unique sequences demonstrated protein homologies to a number of bacterial virulence factors and other proteins not previously identified in P. aeruginosa. PCR and reverse transcription-PCR-based assays were performed to analyze the distribution and expression patterns of a 70-open reading frame subset of these sequences among 11 of the clinical strains. These sequences were unevenly distributed among the clinical isolates, with nearly half (34/70) of the novel sequences being present in only one or two of the individual strains. Expression profiling revealed that a vast majority of these sequences are expressed, strongly suggesting they encode functional proteins.

背景与目标： ：分布式基因组假设（DGH）指出，细菌物种中的每个菌株都从基于种群的超基因组中获得独特的基因分布，其比任何给定菌株的基因组都要大很多倍。自然感染人群通常是多克隆的，大多数慢性细菌病原体具有高度发展的水平基因转移机制的观察结果提示了DGH，并提供了解释哺乳动物宿主面对适应性防御机制时慢性感染如何持续存在的手段和机制。先前已确定DGH对专性病原体的有效性，我们希望评估其对机会细菌病原体的适用性。这是通过构建和分析包含约216,000个功能性克隆的高度冗余的集合基因组文库完成的，该文库由铜绿假单胞菌的12种低通道临床分离株，6种耳泻分离株和6个其他身体部位构建而成。对来自该文库的3,214个随机挑选的克隆（平均插入片段大小，约1.4 kb）进行序列分析，结果表明，对于铜绿假单胞菌原型菌株PAO1的所有基因组序列，其中348个（10.8％）克隆是唯一的。在这些独特序列内的开放阅读框的假想翻译证明了与许多细菌毒力因子和以前在铜绿假单胞菌中未鉴定出的其他蛋白质的蛋白质同源性。进行了基于PCR和逆转录PCR的分析，以分析这些序列的70个开放阅读框子集在11种临床菌株中的分布和表达模式。这些序列在临床分离株中分布不均，只有一半或34个新序列出现在一个或两个单独的菌株中。表达谱分析表明这些序列中的绝大多数都被表达，强烈暗示它们编码功能蛋白。

BACKGROUND & AIMS: :The distribution of calcitonin gene-related peptide (CGRP), enkephalin, galanin, neuropeptide Y (NPY), somatostatin, tachykinins and vasoactive intestinal polypeptide (VIP) was compared in cervical, thoracic, lumbar and sacral segmental levels of spinal cord and dorsal root ganglia of horse and pig. In both species, immunoreactivity for the peptides under study was observed at all segmental levels of the spinal cord. Peptide-immunoreactive fibres were generally concentrated in laminae I-III, the region around the central canal, and in the autonomic nuclei. A general increase in the number of immunoreactive nerve fibres was noted in the lumbosacral segments of the spinal cord, which was particularly exaggerated in the case of VIP immunoreactivity. In the horse, some CGRP-, somatostatin- or tachykinin-immunoreactive cell bodies were present in the dorsal horn. In the pig, cells immunoreactive for somatostatin, enkephalin or NPY were noted in a similar location. In the ventral horn most motoneurones were CGRP-immunoreactive in both species. However, in pig many other cell types were CGRP-immunoreactive not only in the ventral horn, but also in laminae V-VI of the dorsal horn. With the exception of enkephalin and NPY immunoreactivity, which was not seen in pig dorsal root ganglia, all peptides studied were localised to neuronal cell bodies and/or fibres in the dorsal root ganglia. In both species, immunolabeled cell bodies were observed in ganglia from cervical, thoracic, lumbar and sacral levels, with the exception of VIP-immunoreactive cells that were detected only in the lumbosacral ganglia. Numerous CGRP- and tachykinin-immunoreactive cell bodies were visualised in both species, while the cells immunolabeled with other peptide antisera were much lower in number. In both species, immunostaining of serial sections revealed that a subset of CGRP-immunoreactive cells co-expressed tachykinin, galanin or somatostatin immunoreactivity. In the horse some enkephalin-immunoreactive cells were also CGRP positive and occasionally combinations of three peptides, e.g. CGRP, tachykinin and galanin or CGRP, tachykinin and enkephalin were identified. The results obtained suggest that the overall pattern of distribution of peptide immunoreactivities is in general agreement with that so far described in other mammals, although some species variations have been observed, particularly regarding the presence of immunoreactive cell bodies in the dorsal horn of the spinal cord.

背景与目标： ：比较了降钙素基因相关肽（CGRP），脑啡肽，甘丙肽，神经肽Y（NPY），生长抑素，速激肽和血管活性肠多肽（VIP）在颈，胸，腰和部脊髓和背侧节段水平的分布马和猪的根神经节。在这两个物种中，在脊髓的所有节段水平上都观察到了所研究肽的免疫反应性。肽免疫反应性纤维通常集中在薄层I-III，中央管周围区域和自主神经核中。注意到在脊髓的腰s部中免疫反应性神经纤维的数量普遍增加，在VIP免疫反应性的情况下尤其明显。在马中，背角中存在一些CGRP，生长抑素或速激肽免疫反应性细胞体。在猪中，在相似的位置发现对生长抑素，脑啡肽或NPY具有免疫反应性的细胞。在腹角中，大多数运动神经元在这两个物种中均具有CGRP免疫反应活性。但是，在猪中，许多其他细胞类型不仅在腹角中而且在背角的层状V-VI中均具有CGRP免疫反应性。除了脑啡肽和NPY免疫反应性（在猪背根神经节中未见）外，所有研究的肽均位于背根神经节的神经元细胞体和/或纤维中。在这两个物种中，从颈部，胸部，腰部和部水平观察到的神经节中都有免疫标记的细胞体，只有在腰s神经节中才检测到VIP免疫反应性细胞。在这两个物种中都可以看到大量的CGRP和速激肽免疫反应性细胞体，而用其他肽抗血清进行免疫标记的细胞数量要低得多。在这两个物种中，连续切片的免疫染色显示，CGRP免疫反应性细胞的一部分共表达了速激肽，甘丙肽或生长抑素的免疫反应性。在马匹中，一些脑啡肽免疫反应性细胞也是CGRP阳性的，偶尔会结合三种肽，例如：确定了CGRP，速激肽和甘丙肽或CGRP，速激肽和脑啡肽。获得的结果表明，尽管已经观察到某些物种变异，特别是关于脊髓背角中免疫反应性细胞体的存在，但肽免疫反应性的总体分布模式与到目前为止在其他哺乳动物中描述的总体模式一致。 。

BACKGROUND & AIMS: :Plectin is a widely expressed protein that is very large in size and that has all the attributes of a multifunctional crosslinking and organizing element of the cytoskeleton. It displays a multidomain structure, versatile binding activities, and subcellular localizations that enable it to strengthen cells against mechanical stress forces. Moreover, hereditary gene defects in plectin cause epidermolysis bullosa simplex (EBS)-MD, a severe skin blistering disease with muscular dystrophy. Here we report the analysis of the exonintron organization of the rat plectin gene and the identification of several different isoforms on the transcriptional level. We show that of 35 coding exons identified, 4 serve as alternative first exons splicing into the same successive exon 2, which is the first of 7 exons encoding a highly conserved actin-binding domain. RNase protection mapping of transcripts containing 3 of the identified 4 alternate first exons revealed their coexpression in rat glioma C6 cells and in a series of different rat tissues that we examined. Significant variations in expression levels of first exons indicated the possibility of tissue-specific promoter usage. In addition, plectin splice variants lacking exon 31 (> 3 kb), which encodes the entire rod domain of the molecule, were identified in a variety of rat tissues. This study provides first insights into a complex plectin gene regulatory machinery with similarities to that of dystrophin.

背景与目标： ：Plectin是一种广泛表达的蛋白质，大小非常大，具有细胞骨架的多功能交联和组织元素的所有属性。它显示了多域结构，多功能的结合活性和亚细胞定位，使其能够增强细胞抵抗机械应力的能力。此外，凝集素中的遗传基因缺陷会导致大疱性表皮松解症（EBS）-MD，这是一种严重的皮肤起泡性疾病，并伴有肌肉营养不良。在这里，我们报告对大鼠plectin基因外显子组织的分析，并在转录水平上鉴定了几种不同的同工型。我们显示，在确定的35个编码外显子中，有4个充当剪接成同一连续外显子2的替代第一个外显子，这是编码高度保守的肌动蛋白结合域的7个外显子中的第一个。包含已鉴定的4个交替的第一个外显子中的3个的转录本的RNase保护图谱揭示了它们在大鼠神经胶质瘤C6细胞和我们检查的一系列不同大鼠组织中的共表达。第一外显子表达水平的显着变化表明使用组织特异性启动子的可能性。另外，在多种大鼠组织中鉴定出缺乏外显子31（> 3 kb）的plectin剪接变体，该外显子编码该分子的整个杆结构域。这项研究提供了与肌营养不良蛋白相似的复杂血凝素基因调控机制的初步见解。

BACKGROUND & AIMS: :An immediately inducible gene by gonadotropin was isolated from rat ovaries primed with pregnant mare serum gonadotropin (PMSG) by using a subtraction cloning procedure. Homology analysis revealed that the gene is a rat homologue of scavenger receptor class B-I, which was recently identified as a specific receptor for high density lipoprotein (HDL). The structure of rat SRBI was determined by nucleotide sequence analysis of full-length cDNAs for SRBI. Northern blot analysis revealed that rat SRBI mRNA levels were rapidly and strongly increased within 3 h by the injection of PMSG. In situ hybridization study revealed that SRBI mRNA was strongly induced in theca interna cells of immature rat ovary stimulated with 30 IU of PMSG for 6 h. SRBI mRNA expression was also observed in corpora lutea of the adult rat ovary. These findings indicate that expression of SRBI mRNA is restricted to and induced in the ovarian steroidogenic cell types where cholesterol is used as a substrate for synthesis of steroid hormones. Our data strongly suggest that SRBI may play a significant role in the ovarian steroidogenesis by mediating selective uptake of cholesterol from HDL to ovarian theca interna cells or to corpus luteum.

背景与目标： ：通过减法克隆程序，从用怀孕母马血清促性腺激素（PMSG）引发的大鼠卵巢中分离出由促性腺激素立即诱导的基因。同源性分析显示该基因是清道夫受体B-I类的大鼠同源物，最近被鉴定为高密度脂蛋白（HDL）的特异性受体。通过SRBI全长cDNA的核苷酸序列分析确定大鼠SRBI的结构。 Northern印迹分析表明，通过注射PMSG，大鼠SRBI mRNA水平在3小时内迅速而强烈地增加。原位杂交研究表明，SRBI mRNA在30 IU PMSG刺激6 h的未成熟大鼠卵巢的内膜细胞中被强烈诱导。在成年大鼠卵巢的黄体中也观察到了SRBI mRNA表达。这些发现表明，SRBI mRNA的表达受限于卵巢类固醇生成细胞类型并在其中被诱导，其中胆固醇被用作类固醇激素合成的底物。我们的数据有力地表明，SRBI可能通过介导HDL对胆固醇和卵巢黄体的选择性摄取来介导胆固醇的选择性摄取，从而在卵巢类固醇生成中发挥重要作用。

BACKGROUND & AIMS: Mayaro virus (alphavirus) infection of Aedes albopictus cells results in inhibition of cell protein synthesis and viral proteins are preferably synthesized. When infected cells are heat shocked, however, there is also an inhibition of viral protein synthesis, and there is preferential synthesis of heat shock proteins. Based on these observations, the distribution of Mayaro viral RNA in polysomes and the association of p34 (capsid protein) with ribosomal fractions of the cells under such conditions have been analyzed. During infection, the viral RNA is mainly observed in light polysomes (60% of total viral RNA in the cell) and also in heavy polysomes (13%). However, when infected cells are heat-shocked, the viral RNA is strongly mobilized from heavy polysomes to the light polysomes fraction and an enrichment in the unbound fraction can be noticed. The amount of p34 associated with the ribosomal fraction was also shown to be decreased in the heat shocked cells. These data lead to the suggestion that two mechanisms could be involved in the inhibition of Mayaro virus protein synthesis in response to heat shock(1) mobilization of Mayaro virus RNA from heavy to light polysomes; (2) a decrease in the amount of the p34 within the ribosomal fraction.

背景与目标： 白纹伊蚊细胞的Mayaro病毒（alphavirus）感染导致细胞蛋白合成受到抑制，并且优选合成病毒蛋白。然而，当热激感染的细胞时，也抑制了病毒蛋白的合成，并且优先合成了热激蛋白。基于这些观察，已经分析了在这种情况下Mayaro病毒RNA在多核糖体中的分布以及p34（衣壳蛋白）与细胞核糖体级分的关系。在感染过程中，病毒RNA主要在轻多核小体（细胞中总病毒RNA的60％）和重多核小体（13％）中观察到。然而，当受热细胞受到热激时，病毒RNA从重多囊泡强烈地转移到轻多囊泡部分，未结合的部分富集。在热激细胞中，与核糖体级分相关的p34的量也显示减少。这些数据表明，响应热休克反应，Mayaro病毒蛋白合成的抑制可能涉及两种机制（1）Mayaro病毒RNA从重链体到轻链体的动员； （2）核糖体组分中p34的含量减少。

BACKGROUND & AIMS: Although asthmatic patients are known to have increased levels of IgG antibody against house dust mite (HDM), it is not clear whether or not the presence of HDM-specific IgG antibody is associated with the etiological mechanism of asthma. To address this problem, we evaluated the relationship between HDM-specific IgG antibody levels and incidence of asthma in a general pediatric population. IgE and IgG antibody levels against Dermatophagoides farinae (Df) were examined by RAST and ELISA in a total of 722 randomly selected schoolchildren including 26 subjects with asthma, and the relative prevalence rates of asthma in this population were evaluated in relation to both Df-specific IgE and IgG levels. The incidence of asthma correlated not only with levels of Df-specific IgE, but also with those of Df-specific IgG. There was a significant correlation between Df-specific IgE and IgG levels both in the total population and in the asthmatic children. Because IgG and IgE responses occurred in parallel in this population, the clinical significance of HDM-specific IgG anti-body remains unclear. However, our findings have suggested that clinical expression of asthma in children is primarily dependent on their capacity to mount a immune response to HDM, which includes both IgE and IgG responses.

背景与目标： 尽管已知哮喘患者的抗屋尘螨（HDM）IgG抗体水平升高，但尚不清楚HDM特异性IgG抗体的存在是否与哮喘的病因机制有关。为了解决这个问题，我们评估了一般儿科人群中HDM特异性IgG抗体水平与哮喘发生率之间的关系。通过RAST和ELISA检查了722名随机选择的学龄儿童的IgE和IgG抗体水平，其中包括26名哮喘患者，评估了该人群中相对于Df特异性的哮喘相对患病率IgE和IgG水平。哮喘的发病率不仅与Df特异性IgE水平相关，而且与Df特异性IgG水平相关。在总人群和哮喘儿童中，Df特异性IgE和IgG水平之间存在显着相关性。由于IgG和IgE反应在该人群中同时发生，因此HDM特异性IgG抗体的临床意义尚不清楚。但是，我们的发现表明，儿童哮喘的临床表达主要取决于其对HDM产生免疫应答的能力，其中包括IgE和IgG应答。

BACKGROUND & AIMS: BACKGROUND:Trabecular bone strength diminishes as a result of osteoporosis and altered biomechanical loading at the vertebral and spinal levels. The spine consists of the anterior, middle and posterior columns and the load supported by the anterior and middle columns will differ across different regions of the spine. Stress shielding of the anterior column can contribute to bone loss and increase the risk of wedge fracture. There is a lack of quantitative data related to regional spinal bone mineral density distribution over time. We hypothesize that there is an increase in the posterior-to-anterior vertebral body bone mineral density ratio and a decrease in whole-body bone mineral density over time. METHODS:Bone mineral density was measured in 33 subjects using quantitative computed tomography scans for L1-L3 vertebrae, region (anterior and posterior vertebral body), and time (baseline and 6 years after). FINDINGS:Lumbar bone mineral density decreased significantly (Δ: ~15%) from baseline to the 6th year visit. Individual vertebra differences over time (L1: ~14%, L2: ~14%, L3: ~17%) showed statistical significance. Anterior bone mineral density change was significantly greater than in the posterior vertebral body region (Δ anterior: ~18%; Δ posterior: ~13%). Posterior-to-anterior bone mineral density ratio was significantly greater in the 6th year compared to baseline values (mean (SD), 1.33 (0.2) vs. 1.23 (0.1)). INTERPRETATION:This study provides longitudinal quantitative measurement of bone mineral density in vertebrae as well as regional changes in the anterior and posterior regions. Understanding bone mineral density distribution over time may help to decrease the risk of wedge fractures if interventions can be developed to bring spine loading to its normal state.

背景与目标： 背景：由于骨质疏松症以及椎体和脊柱水平的生物力学负荷改变，小梁的骨强度降低。脊柱由前，中和后柱组成，由前柱和中柱支撑的载荷在脊柱的不同区域会有所不同。前柱的应力屏蔽可能会导致骨质流失并增加楔形骨折的风险。缺乏与区域脊柱骨矿物质密度随时间分布有关的定量数据。我们假设随着时间的推移，椎体前后骨矿物质密度比增加，而全身骨矿物质密度降低。
方法：采用定量计算机断层扫描技术对33名受试者的L1-L3椎骨，区域（椎体的前后）和时间（基线及术后6年）进行了骨矿物质密度测量。
结果：从基线到第6年随访，腰椎骨矿物质密度显着降低（Δ：〜15％）。随时间变化的各个椎骨差异（L1：〜14％，L2：〜14％，L3：〜17％）显示出统计学意义。前骨矿物质密度变化显着大于后椎体区域（Δ前：〜18％；Δ后：〜13％）。与基线值相比，第6年的前后骨矿物质密度比显着更高（平均值（SD）为1.33（0.2）对1.23（0.1））。
解释：这项研究提供了纵向定量测量椎骨中骨矿物质密度以及前后区域的变化的信息。如果可以采取干预措施使脊柱负荷恢复到正常状态，那么了解随着时间推移的骨矿物质密度分布可能有助于降低楔形骨折的风险。

BACKGROUND & AIMS: The hypothesis that only melanosomal catecholic amino acids contribute to melanin formation was tested by studying adult bovine eyes in which pigment synthesis is considered to be low or absent. Dopa and 5-S-cysteinyldopa were investigated in different cell fractions of the choroid and retinal pigment epithelium of cattle. Most of the dopa and 5-S-cysteinyldopa was found in the cytoplasm and very little in the large granule fraction. The presence of cysteinyldopa in the adult eye is evidence of tyrosinase activity, but the catechol amino acids in the cytoplasm probably do not give rise to melanin formation. It is assumed that they instead are excreted from the cells.

背景与目标： 通过研究成年牛眼中只有黑色素体的儿茶酚氨基酸有助于黑色素形成的假说，在该成年牛眼中色素合成被认为很少或不存在。在牛的脉络膜和视网膜色素上皮的不同细胞部分中研究了多巴和5-S-半胱氨酰多巴。多巴和5-S-半胱氨酰多巴大部分在细胞质中发现，而在大颗粒部分中则很少。成年眼中半胱氨酰多巴的存在是酪氨酸酶活性的证据，但是细胞质中的儿茶酚氨基酸可能不会引起黑色素的形成。假定它们是从细胞中排出的。

BACKGROUND & AIMS: :Plasminogen activator inhibitor-1 (PAI-1) is an inhibitor of fibrinolysis. Increased plasma PAI-1 levels play an essential role in the pathogenesis of cardiovascular risk and other diseases associated with thrombosis. The 4G/5G polymorphism of the PAI-1 promoter region has been extensively studied in different populations. We studied 160 healthy unrelated Lebanese individuals using a reverse hybridization PCR assay to detect the 5G/5G, 4G/5G and, 4G/4G genotypes of the PAI-1 gene and the frequencies of the 4G and 5G alleles. We found that 4G/5G genotype was the most prevalent (45.6%) followed by 5G/5G (36.9%) and 4G/4G (17.5%). The frequencies of the 4G and 5G alleles were calculated to be 0.403 and 0.597, respectively. Compared to other ethnic communities, the Lebanese population was found to harbour a relatively high prevalence of the rare 4G allele. This, in turn, may predispose this population to develop cardiovascular diseases and other thrombotic clinical conditions. This study aids to enhance our understanding of the genetic features of the Lebanese population.

背景与目标： ：Plasminogen activator inhibitor-1（PAI-1）是纤维蛋白溶解抑制剂。血浆PAI-1水平升高在心血管风险和其他与血栓形成有关的疾病的发病机理中起着至关重要的作用。 PAI-1启动子区域的4G / 5G多态性已在不同人群中进行了广泛研究。我们使用反向杂交PCR方法研究了160名健康的黎巴嫩无关个体，以检测PAI-1基因的5G / 5G，4G / 5G和4G / 4G基因型以及4G和5G等位基因的频率。我们发现4G / 5G基因型是最普遍的（45.6％），其次是5G / 5G（36.9％）和4G / 4G（17.5％）。计算得出4G和5G等位基因的频率分别为0.403和0.597。与其他种族社区相比，发现黎巴嫩人口中稀有4G等位基因的患病率较高。反过来，这可能使该人群容易患上心血管疾病和其他血栓形成性临床状况。这项研究有助于增进我们对黎巴嫩人口遗传特征的了解。

BACKGROUND & AIMS: :An alteration in cell/matrix interactions is one of the suggested mechanisms leading to cyst formation in polycystic kidney diseases. Most of these interactions are mediated by beta 1-integrins, a subfamily of integrin receptors, formed by the association of the beta 1-chain with different alpha-subunits. To date, no study on alpha-integrin subunit distribution during the early stages of cyst development has been reported. Using immunofluorescence, we analyzed the distribution of alpha-integrin subunits (alpha 1, alpha 2, alpha 3, alpha 5, and alpha 6) and basement membrane proteins in kidneys of fetuses with autosomal dominant (ADPKD) or autosomal recessive polycystic kidney disease (ARPKD). The distribution was compared with that observed in normal fetal and post-natal kidneys, and in fetal cystic dysplasia and Meckel syndrome. Marked increase in alpha 1-integrin staining was observed in normal and cystic collecting duct cells of both polycystic diseases (PKD), compared with normal and cystic controls. The distribution of integrin subunits alpha 2, alpha 3, and alpha 6 was irregular in cyst epithelial cells of PKD and cystic controls. The increased expression of the alpha 1-subunit specifically observed in PKD collecting duct cells may be an early consequence of the genetic defect in ARPKD. In ADPKD it parallels the reported expression of polycystin, the protein product of PKD1. The irregular expression of alpha 2, alpha 3, and alpha 6 integrin subunits observed in all types of cysts suggests that cell/matrix interactions are altered early and may participate in the development of cysts, perhaps by contributing to the deregulation of cell survival in cystic diseases.

背景与目标： ：细胞/基质相互作用的改变是导致多囊性肾脏疾病中形成囊肿的机制之一。这些相互作用中的大多数是由β1整联蛋白（β1整联蛋白）介导的，它是β1链与不同的α亚基缔合而形成的整联蛋白受体的一个亚家族。迄今为止，尚无关于囊肿发展早期α-整联蛋白亚基分布的研究的报道。我们使用免疫荧光分析了常染色体显性遗传（ADPKD）或常染色体隐性隐性多囊性肾脏疾病（ADPKD）胎儿肾脏中α-整联蛋白亚基（α1，α2，α3，α5和α6）和基底膜蛋白的分布（ ARPKD）。将该分布与在正常胎儿和出生后肾脏以及胎儿囊性异型增生和Meckel综合征中观察到的分布进行了比较。与正常和囊性对照相比，在两种多囊性疾病（PKD）的正常和囊性收集导管细胞中均观察到了α1-整合素染色的显着增加。在PKD的囊肿上皮细胞和囊性对照中，整联蛋白亚基α2，α3和α6的分布是不规则的。在PKD收集导管细胞中特异性观察到的α1-亚基表达增加可能是ARPKD遗传缺陷的早期结果。在ADPKD中，它与报道的PKD1蛋白产物多囊蛋白的表达平行。在所有类型的囊肿中观察到的α2，α3和α6整联蛋白亚基的不规则表达表明，细胞/基质相互作用早期发生改变，并可能参与了囊肿的发展，也许是通过促进囊性细胞存活的失调而引起的。疾病。

BACKGROUND & AIMS: :Seventeen consecutive patients with dystrophic amyloidosis are reported here (eight Chinese, three Indian, three Iban, two Malay and one Caucasian). Ten were females and seven males, with ages ranging from 12 to 80 years (mean of 48 years). Five instances of dystrophic amyloidosis occurred in areas of tissue damage in the cardiovascular system, including fibrotic cardiac valves and an atheromatous plaque. Three occurred in osteoarthritic joint tissue. Of note were three occurrences in endometriotic cyst walls, four in the fibrotic walls of epidermal cysts, one in a hernial sac and one at the edge of a skin ulcer. All deposits were congophilic and exhibited green-birefringence and permanganate-resistance. Immunohistochemistry did not reveal reactivity for AA protein or immunoglobulin lambda or kappa light-chains. AP protein was detected in 35% of cases. Our results show that, besides the usual sites of osteoarthritic joints and damaged heart valves, dystrophic amyloidosis can complicate other areas of chronic tissue damage and fibrosis such as walls of cysts and ulcers. While the pathogenesis and biochemical nature remain unresolved, immunohistochemistry indicates that neither AA nor AL proteins are present in the deposits, and suggests that a different amyloid protein is involved.

背景与目标： ：这里报道了连续17例营养不良性淀粉样变性患者（八名中国人，三名印度人，三名伊班人，两名马来人和一名高加索人）。十名女性和七名男性，年龄在12至80岁之间（平均48岁）。营养不良性淀粉样变性的五种情况发生在心血管系统的组织损伤区域，包括纤维化心脏瓣膜和动脉粥样斑块。三例发生在骨关节炎关节组织中。值得注意的是，在子宫内膜异位囊肿壁中出现了三处，在表皮囊肿的纤维化壁中发生了四处，在疝囊中发生了一次，在皮肤溃疡边缘处发生了一次。所有沉积物都是嗜酸性的，并且表现出绿色双折射和高锰酸盐抗性。免疫组织化学未显示对AA蛋白或免疫球蛋白λ或κ轻链的反应性。在35％的病例中检测到AP蛋白。我们的结果表明，除了骨关节炎关节和受损的心脏瓣膜的常见部位外，营养不良性淀粉样变性病还可以使其他慢性组织损伤和纤维化区域复杂化，例如囊肿和溃疡壁。虽然发病机理和生化性质尚未解决，但免疫组织化学表明沉积物中既不存在AA蛋白质也不存在AL蛋白，并且暗示了涉及的淀粉样蛋白也不同。

BACKGROUND & AIMS: :Sound streams were generated by randomly choosing the levels of tone pips from two different distributions, A and B. Of the 18 tone pips, the first nine were drawn from distribution A and the second nine from distribution B, or the opposite. The listeners' task was to indicate order, A-B or B-A. In two conditions the A and B distributions differed in mean (condition 1) or variance (condition 2). In contrast to an ideal observer, listeners' strategies were consistent across the two conditions. Analyses suggest that listeners relied primarily on the more intense tone pips in making their decisions.

背景与目标： ：通过从两个不同的分布A和B中随机选择音调点的级别来生成声音流。在这18个音调点中，前9个是从分布A提取的，后两个是从分布B提取的，或者相反。收听者的任务是指示顺序，A-B或B-A。在两个条件下，A和B分布的均值（条件1）或方差（条件2）不同。与理想的观察者相反，在这两种情况下，听众的策略是一致的。分析表明，听众在做出决定时主要依靠更强烈的语调点。

BACKGROUND & AIMS: :Former long-term mining and smelting of pollymetallic ores in the Middle Spiš area caused a serious contamination problem of the environment with heavy metals and metalloids, especially mercury (Hg). Several studies have reported concentration of Hg in the area but this paper provides first detailed characterization of Hg contamination of different environmental components in agricultural, forest, grassland and urban ecosystems. The ecosystems are in different distances from emission sources - former mercury and copper smelting plants in NE Slovakia. Total Hg content was studied in soil/substrate samples (n = 234) and characteristic biological samples (Athyrium filix-femina (L.) Roth, Macrolepiota procera (Scop.) Singer, Boletus edulis Bull., Cyanoboletus pulverulentus (Opat.) Gelardi, Vizzini & Simonini, Triticum aestivum (L.), Poa pratensis (L.)) (n = 234) collected in the above-mentioned ecosystems. The level of contamination and environmental risks were assessed by contamination factor (Cf), index of geoaccumulation (Igeo) and potential environmental risk index (PER). To determine the level of transition of Hg from abiotic to biotic environment, bioconcentration factor (BCF) was used. To determine a health risk resulting from regular and long-term consumption of the locally available species, the results of the Hg content were compared with the Provisional Tolerable Weekly Intake (PTWI) for Hg defined by World Health Organization. The results suggest that almost 63% of the area belong to the very high risk category and 80% of the sampling sites shown very high contamination factor. Geoaccumulation index showed that almost 30% of the area is very strongly contaminated and only 8% is not contaminated with Hg. Spearman's correlation relationship confirmed that the values of PER, BCF, Cf and Igeo decreased with an increasing distance from the pollution source. The percentage of contribution to PTWI ranged between 5.76-69.0% for adults and 11.5-138% for children. Mushroom M. procera showed the highest %PTWI among the tested biological samples. Studied ecotoxicological parameters showed high level of health risk for population living in the area. Consumption of the crops grown in the area and mainly edible wild mushrooms might negatively affect the health of the consumers in the long-term.

背景与目标： ：斯皮什中部地区过去长期开采和冶炼金属金属矿石，严重污染了环境中的重金属和准金属，特别是汞（Hg）。几项研究报告了该地区汞的浓度，但是本文首先详细介绍了农业，森林，草原和城市生态系统中不同环境成分的汞污染特征。生态系统与排放源的距离不同-斯洛伐克东北部以前的汞和铜冶炼厂。在土壤/底物样品（n = 234）和特征性生物样品（Athyrium filix-femina（L.）Roth，Macrolepiota procera（Scop。）歌手，Boletus edulis Bull。，Cyanoboletus pulverulentus（Opat。）Gelardi中研究了总汞含量，维齐尼和西蒙尼尼，普通小麦（L.），波阿普拉（L.））（n = 234）收集在上述生态系统中。通过污染因子（Cf），地质累积指数（Igeo）和潜在环境风险指数（PER）评估污染水平和环境风险。为了确定汞从非生物环境向生物环境的过渡水平，使用了生物浓缩因子（BCF）。为了确定长期和长期食用当地可用物种而引起的健康风险，将汞含量的结果与世界卫生组织确定的汞的暂定每周耐受摄入量（PTWI）进行了比较。结果表明，几乎63％的区域属于极高风险类别，而80％的采样点显示极高的污染因子。地质累积指数表明，该地区近30％的区域受到非常严重的污染，只有8％的区域未被Hg污染。 Spearman的相关关系证实，PER，BCF，Cf和Igeo的值随着距污染源距离的增加而降低。成人对PTWI的贡献百分比在5.76-69.0％之间，儿童为11.5-138％。在所测试的生物样品中，蘑菇proc。procera显示出最高的％PTWI。研究的生态毒理学参数显示出该地区居民的健康风险较高。从长远来看，该地区种植的农作物和主要是食用野生蘑菇的消费可能会对消费者的健康产生负面影响。

BACKGROUND & AIMS: :In this paper, four pairs of insoles with different comfort characteristics were used to investigate the relationship between the pressure distribution under the foot and running shoe comfort. Fourteen male subjects were tested in four insole conditions by walking and running on a treadmill. The pressure at the plantar surface of the foot was measured by using an EMED pressure-measuring insole. For walking there were significantly higher pressures and forces in the midfoot area and significantly lower pressures in the medial forefoot and hallux area by wearing the most comfortable insole compared with wearing the least comfortable insole. The shift of the pressure from forefoot to midfoot for the most comfortable insole provided an even distribution of the pressure at the plantar surface of the foot. The results also demonstrated that the path of centre of force at the plantar surface of the foot moved to the lateral aspect of the foot for the most comfortable insole. For running, only the pressure in the medial forefoot area was found significantly lower for the most comfortable insole than for the least comfortable insole. The results of this study indicated that the pressure distribution between the plantar surface of the foot and the shoe could detect the change of shoe comfort. Thus it is a suggestion that pressure measurement may be related to understand factors important for shoe comfort. Comfort of sport shoes is important for the appropriate execution of sport activities. Additionally, comfort may influence fatigue and possibly the development of injuries. The quantification of comfort of sport shoes and the understanding of mechanical and/or biological functions related to it may be enhanced with the use of pressure measurements between the plantar surface of the foot and the shoe sole.

背景与目标： ：本文采用四对具有不同舒适特性的鞋垫来研究脚底压力分布与跑鞋舒适性之间的关系。通过在跑步机上行走和跑步，在四种鞋垫条件下测试了十四名男性受试者。脚的足底表面的压力通过使用EMED压力测量鞋垫进行测量。对于步行而言，与穿着最不舒适的鞋垫相比，穿着最舒适的鞋垫在中脚区域的压力和力量明显较高，而在前脚内侧和拇趾区域的压力则明显较低。压力从前脚到中脚的变化为最舒适的鞋垫提供了在足底表面上压力的均匀分布。结果还表明，脚底面的力中心路径移到了脚的侧面，从而获得了最舒适的鞋垫。对于跑步而言，发现最舒适的鞋垫只比前脚掌内侧的前足区域的压力低得多。研究结果表明，足底和鞋子之间的压力分布可以检测出鞋子舒适度的变化。因此，建议压力测量可能与了解对鞋子舒适性重要的因素有关。运动鞋的舒适性对于正确执行运动活动很重要。此外，舒适度可能会影响疲劳并可能导致受伤。通过使用脚的足底表面和鞋底之间的压力测量，可以增强运动鞋的舒适度的量化以及与之相关的机械和/或生物学功能的理解。

BACKGROUND & AIMS: :The case of a 57-year-old white female who was found deceased at home by her husband is presented. A suicide note was found at the scene. No remarkable findings were observed at autopsy. Comprehensive toxicological analysis of the heart blood identified ethanol (0.16 g/dL), diazepam (1.1 mg/L), and tizanidine (2.3 mg/L). Blood concentrations of tizanidine following therapeutic use do not exceed 0.025 mg/L. The medical examiner ruled that the cause of death was combined ethanol and multiple drug intoxication, and the manner of death was suicide.

背景与目标： ：介绍了一位57岁的白人女性，她的丈夫在家里发现死者的案例。现场发现一名自杀遗书。尸检未观察到明显的发现。心脏血液的全面毒理学分析确定了乙醇（0.16 g / dL），地西epa（1.1 mg / L）和替扎尼定（2.3 mg / L）。治疗后的替扎尼定血药浓度不超过0.025 mg / L。体检医师裁定死亡原因为乙醇和多种药物中毒的结合，死亡方式为自杀。