BACKGROUND & AIMS: :This minireview considers the possibility that there is a correlation between the slow rate of morphological change and speciation events that has been occurred within the lungfish lineage since the Permian period, and the apparent slow rate of divergence in the amino acid sequences of lungfish opioid precursor sequences. The status of lungfish as "living fossils" is considered.

背景与目标： : 这篇小型评论认为，自二叠纪以来，肺鱼谱系内发生的形态变化和物种形成事件的缓慢速率与肺鱼阿片类药物前体序列的氨基酸序列的明显差异速率之间存在相关性。考虑了肺鱼作为 “活化石” 的地位。

BACKGROUND & AIMS: :We report a patient with a unique combination of features, including microcephaly; mental retardation; poorly developed frontal lobes; hypoplastic pituitary gland; hypothyroidism; alopecia universalis; single maxillary central incisor; taurodontism; median palatal ridge; longitudinally grooved nails; and scoliosis. His unbalanced karyotype was found to be 45,XY,der(15;18)(q10;q10). The constellation of anomalies appears to represent a contiguous gene syndrome caused, at least in part, by deletion of TGIF and the gene responsible for hereditary hypotrichosis simplex. The phenotype of our patient differs other reported patients with del(18p). Possible explanations include (1) the effects of a different deleted region, (2) a positional effect caused by a gene close by, or (3) by interruption of a different gene resulting from chromosomal translocation.

背景与目标： : 我们报告了一名具有独特特征组合的患者，包括小头畸形; 智力低下; 额叶发育不良; 垂体发育不良; 甲状腺功能减退; 普遍脱发; 单个上颌中切牙; 牛角牙症; 正中腭嵴; 纵向开槽的指甲; 和脊柱侧弯。发现他的不平衡核型为45，XY，der(15;18)(q10;q10)。异常星座似乎代表了一个连续的基因综合征，至少部分是由TGIF和负责遗传性低毛丝菌病的基因缺失引起的。我们患者的表型不同于其他报告的del患者 (18p)。可能的解释包括 (1) 不同缺失区域的影响，(2) 由接近的基因引起的位置效应，或 (3) 由染色体易位引起的不同基因的中断。

BACKGROUND & AIMS: We report on an association study between a tetranucleotide repeat polymorphism in the GABR beta1 gene and manic-depressive illness in a Spanish population. This gene may be an important candidate for bipolar affective disorders since severe GABergic alterations have been described in patients. Although our results do not reveal a clear evidence for association between manic-depressive illness and GABR beta1, we have found significant differences between patients and controls in the female subpopulation.

背景与目标： 我们报告了一项西班牙人群中GABR beta1基因的四核苷酸重复多态性与躁狂抑郁症之间的关联研究。该基因可能是双相情感障碍的重要候选者，因为已经在患者中描述了严重的GABergic改变。尽管我们的结果并未揭示出躁狂抑郁症与GABR beta1之间存在关联的明确证据，但我们发现女性亚群的患者与对照组之间存在显着差异。

BACKGROUND & AIMS: :Rhodopseudomonas palustris is a purple, facultatively phototrophic bacterium that uses hydrogen gas as an electron donor for carbon dioxide fixation during photoautotrophic growth or for ammonia synthesis during nitrogen fixation. It also uses hydrogen as an electron supplement to enable the complete assimilation of oxidized carbon compounds, such as malate, into cell material during photoheterotrophic growth. The R. palustris genome predicts a membrane-bound nickel-iron uptake hydrogenase and several regulatory proteins to control hydrogenase synthesis. There is also a novel sensor kinase gene (RPA0981) directly adjacent to the hydrogenase gene cluster. Here we show that the R. palustris regulatory sensor hydrogenase HupUV acts in conjunction with the sensor kinase-response regulator protein pair HoxJ-HoxA to activate hydrogenase expression in response to hydrogen gas. Transcriptome analysis indicated that the HupUV-HoxJA regulatory system also controls the expression of genes encoding a predicted dicarboxylic acid transport system, a putative formate transporter, and a glutamine synthetase. RPA0981 had a small effect in repressing hydrogenase synthesis. We also determined that the two-component system RegS-RegR repressed expression of the uptake hydrogenase, probably in response to changes in intracellular redox status. Transcriptome analysis indicated that about 30 genes were differentially expressed in R. palustris cells that utilized hydrogen when growing photoheterotrophically on malate under nitrogen-fixing conditions compared to a mutant strain that lacked uptake hydrogenase. From this it appears that the recycling of reductant in the form of hydrogen does not have extensive nonspecific effects on gene expression in R. palustris.

背景与目标： : 红假单胞菌 (Rhodopseudomonas palustris) 是一种紫色的兼性光养细菌，在光自养生长过程中使用氢气作为电子供体进行二氧化碳固定或在固氮过程中进行氨合成。它还使用氢作为电子补充剂，以使氧化的碳化合物 (例如苹果酸盐) 在光异养生长过程中完全同化为细胞材料。R. palustris基因组预测了膜结合的镍铁吸收氢化酶和几种控制氢化酶合成的调节蛋白。还有一个新的传感器激酶基因 (RPA0981) 直接与氢化酶基因簇相邻。在这里，我们显示了R. palustris调节传感器氢化酶HupUV与传感器激酶响应调节蛋白对HoxJ-HoxA共同作用，以响应氢气激活氢化酶表达。转录组分析表明，HupUV-HoxJA调节系统还控制编码预测的二羧酸转运系统，推定的甲酸转运蛋白和谷氨酰胺合成酶的基因的表达。RPA0981在抑制氢化酶合成方面的作用很小。我们还确定，两组分系统RegS-RegR抑制了摄取氢化酶的表达，可能是对细胞内氧化还原状态变化的响应。转录组分析表明，与缺乏摄取氢化酶的突变菌株相比，在固氮条件下在苹果酸上光异养生长时利用氢的R. palustris细胞中约30个基因差异表达。由此看来，以氢形式回收还原剂对R. palustris的基因表达没有广泛的非特异性影响。

BACKGROUND & AIMS: BACKGROUND:We examined loss of heterozygosity (LOH) of the P53 gene in bladder cancer, and investigated the role of the P53 gene on malignant progression of papillary tumors. In addition, the clonality of recurrent bladder cancer was examined. METHODS:LOH of the P53 gene was analyzed in 67 bladder cancers from 47 patients. DNA was extracted from formalin-fixed, paraffin-embedded tissues, amplified by the polymerase chain reaction (PCR) at 3 polymorphic loci in the P53 gene, and analyzed with nonradioisotopic single-strand conformation polymorphism (Non-RI SSCP) analysis. RESULTS:Out of 40 informative samples, LOH was detected in 13 samples, containing 4 of 7 in grade 3 (57%), 9 of 23 in grade 2 (39%), and none of 10 in grade 1 (10%). Statistical significance was observed between the LOH in grades 1 and 2, and in grades 1 and 3. An analysis of 5 cases showing malignant progression revealed that 3 (60%) showed an LOH in the primary tumor, and 2 showed LOH in recurrent tumors, in contrast to LOH found in 3 cases of 19 (16%) not showing malignant progression. Four cases with metachronous recurrence exhibited LOH; 2 at recurrent tumors, 1 only at the initial tumor, and 1 at both tumors. CONCLUSIONS:The alterations of the P53 gene were considered to correlate with tumor grade, and contribute to the malignant progression of bladder cancer. LOH in the P53 gene may serve as a clinical indicator for prognosis in superficial bladder cancer.

背景与目标：

BACKGROUND & AIMS: :In a previous large scale screen for differentially expressed genes in pancreatic cancer, we identified a gene highly overexpressed in cancer encoding a novel protein with four K-homologous (KH) domains. KH-domains are found in a subset of RNA-binding proteins, including pre-mRNA-binding (hnRNP) K protein and the fragile X mental retardation gene product (FMR1). By fluorescence in situ hybridization (FISH) the identified gene named koc (KH domain containing protein overexpressed in cancer) was assigned to chromosome 7p11.5. Two pseudogenes were localised on chromosome 6 and 11. The cloned koc cDNA has a 250 bp 5'-UTR, a 1740 bp ORF and a 2168 bp 3'-UTR. The AU-rich 3'-untranslated region of koc contains eight AUUUA and four AUUUUUA reiterated motifs. The deduced koc protein with 580 amino-acids has a relative molecular mass (Mr) of approximately 65,000 (65 K). The koc transcript is highly overexpressed in pancreatic cancer cell lines and in pancreatic cancer tissue as compared to both, normal pancreas and chronic pancreatitis tissue. High levels of expression were as well found in tissue samples of other human tumours. As the KH domain has been shown to be involved in the regulation of RNA synthesis and metabolism, we speculate that koc may assume a role in the regulation of tumour cell proliferation by interfering with transcriptional and or posttranscriptional processes. However, the precise role of koc in human tumour cells is unknown and remains to be elucidated.

背景与目标： : 在先前对胰腺癌中差异表达基因的大规模筛选中，我们鉴定了一个在癌症中高度过表达的基因，该基因编码具有四个K同源 (KH) 域的新型蛋白质。KH结构域存在于RNA结合蛋白的子集中，包括前mRNA结合 (hnRNP) K蛋白和脆弱的X智力低下基因产物 (FMR1)。通过荧光原位杂交 (FISH)，将鉴定出的名为koc (含KH结构域的蛋白质在癌症中过表达) 的基因分配到7p11.5号染色体上。两个假基因位于6号和11号染色体上。克隆的koc cDNA具有250 bp 5 '-UTR、1740 bp ORF和2168 bp 3'-UTR。科威特石油公司富含非盟的3 '-非翻译区包含八个AUUUA和四个auuuuuua重申的图案。推导的具有580个氨基酸的koc蛋白具有约65,000 (65 K) 的相对分子质量 (Mr)。与正常胰腺和慢性胰腺炎组织相比，koc转录本在胰腺癌细胞系和胰腺癌组织中高度过表达。在其他人类肿瘤的组织样本中也发现了高水平的表达。由于KH结构域已被证明参与RNA合成和代谢的调节，因此我们推测koc可能通过干扰转录和或转录后过程而在肿瘤细胞增殖的调节中发挥作用。然而，koc在人类肿瘤细胞中的确切作用尚不清楚，尚待阐明。

BACKGROUND & AIMS: :Oral cancer is a neoplasm with some known causes. Proliferation genes are significant among its few pathogenetic and prognostic factors. Calcyclin is a cell-cycle-related gene, the function of which is still unclear. Its expression and that of Haras and histone-H3 have been investigated in an assessment of their pathogenetic role in squamous cell carcinoma. RNA extracted from the pathological and normal mucosa of patients with squamous cell carcinoma (SCC) and benign lesions was reverse transcribed and amplified by the polymerase chain reaction (PCR). The expression of all three genes in the pathological mucosa was enhanced in SCC only. This suggests that they may be involved in its pathogenesis and provides another parameter for the differentiation of malignant and benign lesions.

背景与目标： 口腔癌是一种已知病因的肿瘤。增殖基因在其少数致病和预后因素中具有重要意义。钙周期蛋白是一个与细胞周期相关的基因，其功能尚不清楚。在评估其在鳞状细胞癌中的致病作用时，已研究了其表达以及Haras和histone-H3的表达。从鳞状细胞癌 (SCC) 和良性病变患者的病理和正常粘膜中提取的RNA被逆转录并通过聚合酶链反应 (PCR) 扩增。仅在SCC中，病理粘膜中所有三个基因的表达均增强。这表明它们可能参与其发病机理，并为恶性和良性病变的鉴别提供了另一个参数。

BACKGROUND & AIMS: :We have constructed a physical map of a > 2-Mb region on mouse chromosome 6 that contains the natural killer gene complex (NKC). The map comprises a contig of 14 overlapping yeast artificial chromosomes onto which we positioned 25 NKC markers. NKC genetically linked genes encode > 17 proteins that directly control innate NK cell-mediated tumor lysis and disease resistance. Herein we show that Nkrp1 genes are clustered in a region flanked by A2m and Cd69 genes and that most Ly49 genes are clustered in a distal region -1 Mb distant. Importantly, syntenic intervals of mouse chromosome 6 and human chromosome 12p that include the NKC are conserved. NKC species conservation suggests that the human NKC may contain orthologues for the mouse viral disease resistance genes, Cmv1 and Rmp1. The high-resolution NKC map will facilitate investigation of NKC gene regulation and identification of phenotypically defined gene products that confer NK cell defense against viral pathogens.

背景与目标： : 我们已经在小鼠6号染色体上构建了一个> 2-Mb区域的物理图，其中包含自然杀伤基因复合物 (NKC)。该图谱包含14个重叠的酵母人工染色体的重叠群，我们在其上定位了25个NKC标记。NKC基因连接的基因编码> 17种直接控制先天NK细胞介导的肿瘤溶解和抗病的蛋白质。在本文中，我们显示Nkrp1基因聚集在A2m和Cd69基因两侧的区域中，并且大多数Ly49基因聚集在远端区域-1 Mb远处。重要的是，包含NKC的小鼠6号染色体和人类12p染色体的同义间隔是保守的。NKC物种保护表明，人类NKC可能包含小鼠病毒抗病基因Cmv1和rmp1的直系同源物。高分辨率NKC图谱将有助于NKC基因调控的研究和表型定义的基因产物的鉴定，这些基因产物赋予NK细胞针对病毒病原体的防御能力。

BACKGROUND & AIMS: :By screening a pigeon genomic DNA library, we isolated a recombinant phage clone containing the alpha(A)-globin gene. The DNA sequence of the approximately 6kbp-long insert fragment of the phage clone was determined. The sequence suggested the existence of pigeon alpha(D)-globin gene located 3.1 kbp upstream from the alpha(A)-globin gene. The expression of the alpha(D)-globin in late embryo was also shown by the N-terminal amino-acid sequence of the intact globin chain. These results show that two adult alpha-globin genes, alpha(A) and alpha(D), exist in the pigeon genome, and the alpha(D)-globin is expressed at the late embryo stage. The stage-specific expression suggests the existence of regulatory elements and factors interacting to inhibit transcription at the adult stage.

背景与目标： : 通过筛选鸽子基因组DNA文库，我们分离出含有 α (a)-珠蛋白基因的重组噬菌体克隆。确定了噬菌体克隆的约6kbp长的插入片段的DNA序列。该序列表明存在位于 α (A)-珠蛋白基因上游3.1 kbp的鸽子 α (D)-珠蛋白基因。完整珠蛋白链的N端氨基酸序列也显示了 α (D)-珠蛋白在晚期胚胎中的表达。这些结果表明，鸽子基因组中存在两个成年的 α-珠蛋白基因 α (A) 和 α (D)，并且 α (D)-珠蛋白在胚胎晚期表达。阶段特异性表达表明存在调节元件和因子相互作用以抑制成年阶段的转录。

BACKGROUND & AIMS: :Phosphorus MRS was evaluated as a monitor of tumour therapeutic response to the herpes simplex virus thymidine kinase suicide gene therapy paradigm. In vivo 31P spectra were obtained from subcutaneous rat C6 gliomas constitutively expressing the HSVtk gene post treatment with ganciclovir (GCV, 15 mg/kg i.p., twice-daily). Significant regression (p < 0.1) of tumour volume was observed 10 days after beginning GCV administration. However, no changes in tumour pH or energy metabolites from pre-treatment values were observed. High-resolution 31P spectra of tumour extracts revealed a statistically significant reduction in the phosphocholine to phosphoethanolamine ratio six days post-GCV administration. These results indicate that the HSVtk/GCV-induced killing of tumours is not associated with corresponding changes in 31P MRS-observable energy metabolites and pH. The observed reduction in the PE/PC ratio may provide a non-invasive in vivo indicator of therapeutic efficacy.

背景与目标： : 磷MRS被评估为对单纯疱疹病毒胸苷激酶自杀基因治疗范例的肿瘤治疗反应的监测仪。体内31p光谱是从用更昔洛韦治疗后组成性表达HSVtk基因的皮下大鼠C6神经胶质瘤获得的 (GCV，15 mg/kg i.P.，每天两次)。在开始GCV给药10天后观察到肿瘤体积的显著回归 (p <0.1)。然而，未观察到肿瘤pH或能量代谢物与治疗前值的变化。肿瘤提取物的高分辨率31p光谱显示，GCV给药六天后，磷酸胆碱与磷酸乙醇胺的比率在统计学上显着降低。这些结果表明，HSVtk/GCV诱导的肿瘤杀伤与31P MRS可观察到的能量代谢产物和pH的相应变化无关。观察到的PE/PC比率的降低可能提供治疗功效的非侵入性体内指标。

BACKGROUND & AIMS: :Activating mutations in the tyrosine kinase domain of the HER2 gene have recently been reported in lung adenocarcinomas, mainly in East Asian patients. Our study was devised to evaluate the prevalence and nature of HER2 mutations in lung adenocarcinomas from Caucasian patients. The mutational status of the HER2 gene was evaluated in 403 lung adenocarcinomas by PCR-single strand conformation polymorphism analysis and direct sequencing of Exons 19 and 20. We found HER2 mutations in 9 (2.2%) cases. Seven (78%) of the mutations were in frame duplications/insertions at codons 776-779 (YVMA), the other 2 were base substitutions resulting in aminoacid changes. The hotspot mutation at bases 776-779 was previously found to be the most frequent HER2 mutation in Asiatic patients. The distribution of mutations was significantly different between conventional lung adenocarcinomas (CLAs) and lung adenocarcinomas with bronchioloalveolar features (ABAFs). Seven (6.2%) of 113 ABAFs and 2 (0.7%) of 290 CLA were mutated (p = 0.0025). In addition, the frequency of HER2 mutations was slightly higher in females (4.1%) than in males (1.8%) and in never smokers (3.1%) than in smokers (1.9%), but differences were not statistically significant. This series of tumors was also investigated for EGFR and K-ras mutations. EGFR mutations were observed in 43 (10.7%) cases, and K-ras mutations in 110 (27.3%) cases. EGFR, HER2 and K-ras mutations were found to be mutually exclusive events. The presence of HER2 mutations in a subset of patients with lung adenocarcinoma raise hope to treat these patients with HER2 specific kinase inhibitors.

背景与目标： : 最近在肺腺癌 (主要是东亚患者) 中报道了HER2基因酪氨酸激酶结构域的激活突变。我们的研究旨在评估白种人肺腺癌中HER2突变的患病率和性质。通过PCR-单链构象多态性分析和外显子19和20的直接测序，评估了403例肺腺癌中HER2基因的突变状态。我们在9 (2.2%) 例病例中发现HER2突变。7 (78%) 个突变在密码子776-779 (YVMA) 的帧重复/插入中，另外2个是导致氨基酸变化的碱基取代。先前发现776-779碱基的热点突变是亚洲患者中最常见的HER2突变。在常规肺腺癌 (cras) 和具有细支气管肺泡特征的肺腺癌 (ABAFs) 之间，突变的分布显着不同。113 ABAFs中的7个 (6.2%) 和290 CLA中的2个 (0.7%) 发生突变 (p = 0.0025)。此外，女性 (4.1%) 的HER2突变频率略高于男性 (1.8%)，从不吸烟者 (3.1%) 高于吸烟者 (1.9%)，但差异无统计学意义。还研究了这一系列肿瘤的EGFR和K-ras突变。在43 (10.7%) 例中观察到EGFR突变，在110 (27.3%) 例中观察到K-ras突变。发现EGFR，HER2和K-ras突变是相互排斥的事件。在一部分肺腺癌患者中存在HER2突变，这使人们希望用HER2特异性激酶抑制剂治疗这些患者。

BACKGROUND & AIMS: :A retroviral vector was constructed with an autoregulatory cassette to allow expression of the gene of interest in response to oral administration of doxycycline (Dox) in vivo. The cassette contains all the components of the reverse tetracycline-regulated (rtTA) system, a drug selectable marker with the internal ribosome entry site and the gene of interest (GFP). FACS analyses showed an induction of GFP-fluorescence of two orders of magnitude in retrovirus-infected 208F cells dependent on the amount of Dox in the medium. Furthermore, oral administration of Dox resulted in GFP expression in transplanted 208F cells in the peritoneal cavity of nude mice. Thus this reverse tetracycline-regulated retroviral vector (RTRV) system simplifies the delivery of controllable genes to cultured and implanted cells. It is hoped that this approach may pave the way to controlled gene expression during a particular window of time in gene therapy applications.

背景与目标： : 用自动调节盒构建逆转录病毒载体，以响应体内口服强力霉素 (Dox) 的目的基因表达。该盒包含反向四环素调节 (rtTA) 系统的所有成分，该系统是具有内部核糖体进入位点和目标基因 (GFP) 的药物选择标记。FACS分析显示，在逆转录病毒感染的208F细胞中，取决于培养基中Dox的量，诱导了两个数量级的GFP荧光。此外，口服Dox导致裸鼠腹膜腔中移植的208F细胞中GFP表达。因此，这种反向四环素调节的逆转录病毒载体 (RTRV) 系统简化了可控基因向培养和植入细胞的传递。希望这种方法可以为在基因治疗应用中的特定时间窗口内控制基因表达铺平道路。

BACKGROUND & AIMS: :EMX2 and PAX6 are expressed by cortical progenitors and specify area patterning. We used representational difference analysis (RDA) to compare expressed RNAs from wild type and Emx2-/- cortex and identified 41 unique clones. Using secondary screening by in situ hybridization, we selected five genes for further analysis, Cdk4, Cofilin1, Crmp1, ME2, and Odz4, involved in neuronal proliferation, differentiation, migration, and axon guidance. Each exhibits differential expression in wild type cortex. Odz4 is one of four members of a vertebrate gene family homologous to the Drosophila pair-rule patterning gene, Odd Oz (Odz), a transmembrane receptor. We show that Odz genes are expressed in complementary patterns in cortex, as well as in nuclei-specific patterns in thalamus that relates to their area-unique cortical expression. In addition, each of the genes analyzed shows different expression patterns in wild type cortex, Emx2, and Pax6 mutant cortex, consistent with potential roles in area patterning. These findings identify potential targets of EMX2 that might account for its function and the defects in Emx2-/- cortex, and suggest that the Odz family of transmembrane proteins influences cortical area patterning downstream to EMX2 and PAX6.

背景与目标： : EMX2和PAX6由皮质祖细胞表示并指定区域图案。我们使用代表性差异分析 (RDA) 来比较野生型和Emx2-/-皮质的表达rna，并鉴定出41个独特的克隆。使用原位杂交的二次筛选，我们选择了五个基因进行进一步分析，Cdk4，Cofilin1，Crmp1，ME2和Odz4，涉及神经元增殖，分化，迁移和轴突指导。每个在野生型皮层中表现出不同的表达。Odz4是与果蝇对规则模式基因Odd Oz (Odz) (跨膜受体) 同源的脊椎动物基因家族的四个成员之一。我们显示Odz基因在皮层的互补模式中表达，以及在丘脑的核特异性模式中表达，这与其区域独特的皮层表达有关。此外，所分析的每个基因在野生型皮层，Emx2和Pax6突变皮层中显示出不同的表达模式，与区域模式中的潜在作用一致。这些发现确定了可能解释其功能和EMX2-/-皮质缺陷的Emx2的潜在靶标，并表明跨膜蛋白的Odz家族会影响EMX2和pax6下游的皮质区域模式。

BACKGROUND & AIMS: Expression of genes coding for ubiquitin and heatshock protein (hsp) 70 were examined by in situ hybridization using a rat model with permanent occlusion of the distal middle cerebral artery (MCA). Only polyubiquitin (UbC) mRNA increased markedly following ischaemia in the central zone of the MCA territory of the neocortex. UbC gene expression reached the maximum level 4 h post-occlusion and remained elevated at 24 h. UbC expression was retarded slightly compared with that of the hsp70 gene. UbB and Ub-S30 were expressed at almost similar levels in both the ischaemic and non-ischaemic hemispheres. These results indicated that UbC probably has the most stress-inducible characteristics among the three ubiquitin genes.

背景与目标： 使用具有远端大脑中动脉 (MCA) 永久闭塞的大鼠模型，通过原位杂交检查了编码泛素和热休克蛋白 (hsp) 70的基因的表达。在新大脑皮层MCA区域的中央区域发生缺血后，只有聚泛素 (UbC) mRNA显着增加。UbC基因表达在闭塞后4小时达到最大水平，并在24小时保持升高。与hsp70基因相比，UbC表达略有延迟。在缺血性和非缺血性半球中，UbB和Ub-S30的表达水平几乎相似。这些结果表明，在三个泛素基因中，UbC可能具有最易受胁迫诱导的特征。

BACKGROUND & AIMS: :A novel procaryotic transcriptional regulatory element, AlgP, with a histone H1-like carboxy-terminal domain was identified in Pseudomonas aeruginosa. AlgP is required for transcription of the key biosynthetic gene algD, which is necessary for production of the exopolysaccharide alginate causing mucoidy in P. aeruginosa. Mucoidy is a critical virulence determinant of P. aeruginosa invariably associated with the respiratory infections causing high mortality in cystic fibrosis. Here we show that AlgP and histones H1 both have repeated units of the Lys-Pro-Ala-Ala motif (KPAA) and its variations within their long (over 100 amino acids) carboxy-terminal domains. This region of histone H1 tails has been shown to bind to the linker DNA in eucaryotic chromatin fibers. A synthetic 50-mer peptide consisting of repeats from the AlgP carboxy-terminal domain was found to bind DNA in a mobility shift DNA-binding assay. AlgP is encoded by a gene that contains multiple direct repeats organized as tandem, head-to-tail, 12-base-pair (bp) units overlapping with six highly conserved 75-bp units. The repetitive structure of the algP gene appears to participate in the processes underlying the metastable character of mucoidy in P. aeruginosa. Relatively large DNA rearrangements spanning the region with tandem direct repeats encoding the carboxy-terminal histone H1-like structure of AlgP were detected in several strains upon conversion from the mucoid to the nonmucoid phenotype. The frequency of the detectable algP rearrangements associated with the transition into the nonmucoid state varied from strain to strain and ranged from 0 to 50%. The nonmucoid derivatives with the clearly rearranged chromosomal copy of algP were complemented to mucoidy with plasmids containing algP from P. aeruginosa PAO. When a random collection of mucoid strains, isolated from different cystic fibrosis patients, was analyzed by using polymerase chain reaction, an additional level of strain-dependent sequence variation in algP was observed. Variations in the number of the 12-bp repeats were found; however, they did not appear to influence the mucoid status of the strains examined. Thus, the repeated region of algP appears to be a hot spot for DNA rearrangements and strain-dependent variability.

背景与目标： : 在铜绿假单胞菌中鉴定了一种新型的原核转录调节元件AlgP，其具有组蛋白H1-like羧基末端结构域。AlgP是关键生物合成基因algD转录所必需的，这对于产生引起铜绿假单胞菌粘液的胞外多糖藻酸盐是必需的。粘液症是铜绿假单胞菌的关键毒力决定因素，总是与导致囊性纤维化高死亡率的呼吸道感染相关。在这里，我们显示了AlgP和组蛋白H1都具有Lys-Pro-Ala基序 (KPAA) 的重复单元及其在其长 (超过100个氨基酸) 羧基末端结构域中的变化。已显示组蛋白H1尾巴的该区域与真核染色质纤维中的接头DNA结合。在迁移率转移DNA结合试验中，发现由来自AlgP羧基末端结构域的重复序列组成的合成50聚体肽结合DNA。AlgP由一个基因编码，该基因包含多个直接重复序列，组织为串联，头对尾，12碱基对 (bp) 单元，与六个高度保守的75 bp单元重叠。algP基因的重复结构似乎参与了铜绿假单胞菌黏液的亚稳态特征的潜在过程。从粘液样转化为非粘液样表型后，在几个菌株中检测到跨越编码AlgP羧基末端组蛋白H1-like结构的串联直接重复序列的区域的相对较大的DNA重排。与过渡到非粘液状态相关的可检测的algP重排的频率因菌株而异，范围为0至50%。具有明显重排的algP染色体拷贝的非粘液衍生物与含有铜绿假单胞菌PAO的algP的质粒互补为粘液。当使用聚合酶链反应分析从不同的囊性纤维化患者中分离出的粘液样菌株的随机集合时，观察到algP中菌株依赖性序列变异的额外水平。发现12 bp重复序列的数量有所变化; 但是，它们似乎并未影响所检查菌株的粘液状态。因此，algP的重复区域似乎是DNA重排和应变依赖性变异性的热点。