Utilization of Iron Sources and Its Possible Roles in the Pathogenesis of Vibrio parahaemolyticus

Vibrio parahaemolyticus is an important enteropathogen in Japan, Taiwan and other coastal regions. The influence of the regulation of iron on the pathogenesis of this pathogen has not been well characterized. The growth of pathogenic and non-pathogenic strains of V. parahaemolyticus on iron-limited agar plates was stimulated by ferritin, lactoferrin and transferrin at 30 μM , and also by hemin, hemoglobin and ferric ammonium citrate at 100 μM . Spontaneous iron-utilizing mutant strains (mutants) were derived from a clinical strain, ST550. Compared with the parent strain, lowered virulence was demonstrated for these mutants, as assayed by adult mouse and suckling mouse models. The in vivo growth and enterotoxigenicity of these mutants were also lower in the suckling mice. Adherence of the mutants to excised mouse intestine was lower as demonstrated by scanning electron microscopy. The iron-regulated outer membrane protein profile also changed in selected mutants. These results indicate that iron-regulated outer membrane proteins and other unknown factors associated with iron utilization may have profound influences, besides iron acquisition, on the pathogenesis of V. parahaemolyticus.     

Adherence Patterns and DNA Probe Types of Escherichia coli Isolated from Diarrheal Patients in China

One hundred and seventy-two strains of Escherichia coli isolated from diarrheal patients in Beijing, P. R. China, were analyzed for plasmid DNA profile, HEp-2 cell adherence ability and reactivity to 10 previously described DNA probes. They had not been recognized as pathogenic E. coli in China. Of the 110 strains tested, 76 (69%) contained one or multiple large plasmids. Of the 71 strains with the large plasmids 64 could adhere to HEp-2 cells. Of the 172 strains, 102 (59.3%) were hybridized with at least one of the 10 probes. Of those, seven strains hybridized with enteroaggregative E. coli (EAggEC) probe. Their serotypes were O128 (two strains), O6 (one strain), and O111 (one strain). Three strains were untypable. Six and three strains were hybridized with enteropathogenic E. coli (EPEC) attaching and effacing genes (eae) or EPEC adherence factor (EAF) probe, respectively. Two non-O157: H7 strains hybridized with enterohemorrhagic E. coli (EHEC) probe. Seventy-two strains (41.9%) hybridized with shiga-like toxin 2 or 1 (SLT2 or SLT1) probes. Among the SLT1 or SLT2 probe-positive strains, 54 hybridized with invasive (INV) plasmid probe developed for identification of enteroinvasive E. coli (EIEC) and Shigella species. The INV and SLT probe-positive strains might represent a new variety of verotoxin-producing E. coli (VTEC).     

丹参酮Ⅱ－A磺酸钠对鼠肝线粒体功能的影响

利用大鼠肝脏线粒体为材料,以琥珀酸为底物,研究了不同浓度的丹参酮Ⅱ－Ａ磺酸钠对线粒体态４、态３呼吸及呼吸控制率,线粒体跨膜电位,线粒体呼吸链复合体（Ⅱ＋Ⅲ）电子传递及质子转移活性的影响。结果证明丹参酮ⅡＡ－磺酸钠是线粒体呼吸链复合体（Ⅱ＋Ⅲ）的有效抑制剂。文中对丹参酮ⅡＡ－磺酸钠在心肌缺血再灌注过程中的保护作用的分子机理进行了讨论。     

汉防己甲素及克矽平对矽肺大鼠Ⅰ型和Ⅲ型胶原mRNA的影响

汉防己甲素（汉甲）及克矽平（Ｐｏｌｙｖｉｎｙｌｐｙｒｉｄｉｎｅ－Ｎ－Ｏｘｉｄｅ,ＰＶＮＯ）是目前较为有效的抑制矽肺纤维化的药物。本文研究了其对胶原ｍＲＮＡ水平的影响．斑点杂交实验表明大鼠接尘６０天和１２０天后α１（Ⅰ）及α１（Ⅲ）ｍＲＮＡ水平明显上升,经汉甲或克矽平治疗１个月或３个月后,胶原ｍＲＮＡ水平明显下降。原位杂交结果表明胶原ｍＲ－ＮＡ银颗粒与细胞性结节和增厚的肺泡壁的成纤维细胞分布重合。汉甲或克矽平治疗后银颗粒数下降。提示汉甲及克矽平对矽肺进程中的胶原基因表达增强有抑制作用。     

人鼻咽癌细胞基因组中瘤基因Ha－ras－1的Dnase Ⅰ超敏感位点的初步研究

ＤＮａｓｅⅠ超敏感位点的研究能够发现潜在的调控基因转录活化的位点,比较正常人外周血有核细胞,淋巴瘤细胞株Ｐ３ＨＲ１和人鼻咽癌低分化磷癌细胞株ＨＯｎＥ１和ＨＮＥ２中Ｈａ－ｒａｓ－１瘤基因的ＤＮａｓｅⅠ超敏感位点发现,只有ＨＯＮＥ１和ＨＮＥ２细胞基因组中存在一个ＤＮａｓｅⅠ超敏感位点,位于第一个外显子上游０．３７ｋｂ处,上述结果提示正常白细胞和Ｐ３ＨＲ１细胞中Ｈａ－ｒａｓ－１基因处于失活状态,而在鼻咽癌细胞基因组中则处于活化状态,它的活化可能与０．３７ｋｂ处的ＤＮＡ序列有密切的关系。     

Development of the respiratory swimbladder of Pangasius sutchi

The swimbladder of Pangusius sutchi first appears on the dorsal surface of the oesophagus at about 5 days after hatching. The swimbladder has double chambers when it is separated by a medial septum at 8–10 days. Alveoli start to develop and function in air-breathing at 12–14 days. Their number is increased by subdivision, and the respiratory portion grows towards the centre. Morphometric analysis shows that the swimbladder increases in respiratory surface, volume and surface area: volume ratio during development. On a histological basis, the development of the swimbladder is divided into three distinct periods: a blind tube, a double chamber and an alveolus period. It is characteristic that the flat epithelial cell arises from a primordial cuboidal cell and that a double capillary system is arranged in the interalveolar septa. Multilamellar bodies appear and a blood-air barrier is established when the swimbladder becomes functional.     

Proteomics and Phosphoproteomic Analysis to Identify Spleen of Takifugu rubripes Infected Cryptocaryon irritans

Marine Biotechnology - Takifugu rubripes is important commercially fish species in China and it is under serious threat from white spot disease (cyptocaryoniasis), which leads to heavy economic...     

Higher-order interactions of Bcr-Abl can broaden chronic myeloid leukemia (CML) drug repertoire

Bcr-Abl, a nonreceptor tyrosine kinase, is associated with leukemias, especially chronic myeloid leukemia (CML). Deletion of Abl's N-terminal region, to which myristoyl is linked, renders the Bcr-Abl fusion oncoprotein constitutively active. The substitution of Abl's N-terminal region by Bcr enables Bcr-Abl oligomerization. Oligomerization is critical: it promotes clustering on the membrane, which is essential for potent MAPK signaling and cell proliferation. Here we decipher the Bcr-Abl specific, step-by-step oligomerization process, identify a specific packing surface, determine exactly how the process is structured and identify its key elements. Bcr's coiled coil (CC) domain at the N-terminal controls Bcr-Abl oligomerization. Crystallography validated oligomerization via Bcr-Abl dimerization between two Bcr CC domains, with tetramerization via tight packing between two binary assemblies. However, the structural principles guiding Bcr CC domain oligomerization are unknown, hindering mechanistic understanding and drugs exploiting it. Using molecular dynamics (MD) simulations, we determine that the binary complex of the Bcr CC domain serves as a basic unit in the quaternary complex providing a specific surface for dimer–dimer packing and higher-order oligomerization. We discover that the small α1-helix is the key. In the binary assembly, the helix forms interchain aromatic dimeric packing, and in the quaternary assembly, it contributes to the specific dimer–dimer packing. Our mechanism is supported by the experimental literature. It offers the key elements controlling this process which can expand the drug discovery strategy, including by Bcr CC-derived peptides, and candidate residues for small covalent drugs, toward quenching oligomerization, supplementing competitive and allosteric tyrosine kinase inhibitors.