Phenotypic and molecular characterization of two novel CTX-M enzymes carried by <Emphasis Type=Italic>Klebsiella pneumoniae</Emphasis>

Two clinical strains (Klebsiella pneumoniae 516 and K. pneumoniae 1335) collected in September 2006 from different hospitals in Anhui Province (China) harboured two novel plasmid-mediated bla _CTX-M genes, designated bla _CTX-M-80 and bla _CTX-M-81, respectively. Both CTX-M-80 with pI of 9.0 and CTX-M-81 with pI of 8.4 were extended-spectrum β-lactamases (ESBLs). The results of susceptibility testing demonstrated two enzymes were highly activity against broad spectrum β-lactams, but the level of resistance was reduced with the addition of β-lactamase inhibitors. The bla _CTX-M-80 gene was detected on a 110-kb plasmid and the bla _CTX-M-81 gene existed on a 120-kb plasmid. The deduced amino acid sequence of CTX-M-80 differed from that of CTX-M-3 by the substitution Ala-27→Val, and CTX-M-81 possessed the Lys→Glu, Lys→Gln, and Asn→His changes at respective position 82, 98, and 132 in compassion with CTX-M-14. The enzymatic properties showed CTX-M-80 and CTX-M-81 had higher affinities for penicillin G (lower Km values) than for cephalosporins. The activities of novel enzymes against ceftazidime were undetectable or limited, as indicated by MICs data, the same response being observed for many other CTX-M enzymes. This report was evidence of the diversity of CTX-M-type ESBLs in China.     

Class 5 transmembrane semaphorins control selective Mammalian retinal lamination and function

In the vertebrate retina, neurites from distinct neuronal cell types are constrained within the plexiform layers, allowing for establishment of retinal lamination. However, the mechanisms by which retinal neurites are segregated within the inner or outer plexiform layers are not known. We find that the transmembrane semaphorins Sema5A and Sema5B constrain neurites from multiple retinal neuron subtypes within the inner plexiform layer (IPL). In Sema5A?/?; Sema5B?/? mice, retinal ganglion cells (RGCs) and amacrine and bipolar cells exhibit severe defects leading to neurite mistargeting into the outer portions of the retina. These targeting abnormalities are more prominent in the outer (OFF) layers of the IPL and result in functional defects in select RGC response properties. Sema5A and Sema5B inhibit retinal neurite outgrowth through PlexinA1 and PlexinA3 receptors both in vitro and in vivo. These findings define a set of ligands and receptors required for the establishment of inner retinal lamination and function.     

βII spectrin (SPTBN1): biological function and clinical potential in cancer and other diseases

βII spectrin, the most common isoform of non-erythrocyte spectrin, is a cytoskeleton protein present in all nucleated cells. Interestingly, βII spectrin is essential for the development of various organs such as nerve, epithelium, inner ear, liver and heart. The functions of βII spectrin include not only establishing and maintaining the cell structure but also regulating a variety of cellular functions, such as cell apoptosis, cell adhesion, cell spreading and cell cycle regulation. Notably, βII spectrin dysfunction is associated with embryonic lethality and the DNA damage response. More recently, the detection of altered βII spectrin expression in tumors indicated that βII spectrin might be involved in the development and progression of cancer. Its mutations and disorders could result in developmental disabilities and various diseases. The versatile roles of βII spectrin in disease have been examined in an increasing number of studies; nonetheless, the exact mechanisms of βII spectrin are still poorly understood. Thus, we summarize the structural features and biological roles of βII spectrin and discuss its molecular mechanisms and functions in development, homeostasis, regeneration and differentiation. This review highlight the potential effects of βII spectrin dysfunction in cancer and other diseases, outstanding questions for the future investigation of therapeutic targets. The investigation of the regulatory mechanism of βII spectrin signal inactivation and recovery may bring hope for future therapy of related diseases.     

Discovery of 1H-benzo[d][1,2,3]triazol-1-yl 3,4,5-trimethoxybenzoate as a potential antiproliferative agent by inhibiting histone deacetylase

Twenty-one benzotriazoles (3-16 and 18-24) were synthesized and half of them (5, 8-16, 20, and 21) were reported for the first time. Their antiproliferative activities against three human cancer cells were assayed. It revealed that 1H-benzo[d][1,2,3]triazol-1-yl 3,4,5-trimethoxybenzoate (9) showed considerable activity against three human cancer cell lines with the half maximal inhibitory concentration (IC(50)) values of 1.2-2.4 nM, which were close to the value of the positive control, doxorubicin. Further investigation indicated compound 9 was a potential histone deacetylase inhibitor (IC(50)=9.4 μM) and its binding mode was simulated using docking method.     

Growth pattern switch of renal cells and expression of cell cycle related proteins at the early stage of diabetic nephropathy

Renal hypertrophy, partly due to cell proliferation and hypertrophy, has been found correlated to renal function deterioration in diabetes mellitus. We screened the up-regulated cell cycle related genes to investigate cell growth and the expression of cell cycle regulating proteins at the early stage of diabetic nephropathy using STZ-induced diabetic rats. Cyclin E, CDK(2) and P(27) were found significantly up-regulated in diabetic kidney. Increased cell proliferation in the kidney was seen at day 3, peaked at day 5, and returned to normal level at day 30. Cyclin E and CDK(2) expression also peeked at day 5 and P(27) activity peaked at day 14. These findings indicate that a hyperplastic growth period of renal cells is followed by a hypertrophic growth period at the early stage of diabetes. The growth pattern switch may be regulated by cell cycle regulating proteins, Cyclin E, CDK(2), and P(27).     

干旱条件下冷季型草光合蒸腾特性的研究

对9种冷季型草在春夏季干旱条件下的光合、蒸腾等生理特性进行测定.结果表明:春季冷季型草净光合速率在6:00较低,8:00~12:00后出现最大值后逐渐下降,呈曲线变化.不同种类的日平均净光合速率,以虉草和看麦娘最高,达11μmol?m-2?s-1,匍匐剪股颖不到5μmol?m-2?s-1,其它草种居中,为6~10μmol?m-2?s-1.夏季测定时,大部分冷季型草在6:00净光合速率为全天最大值,8:00后光合速率下降,至16:00光合速率最低,几乎呈直线下降的变化.不同种类的日平均净光合速率,紫羊茅最高,为16.5μmol?m-2?s-1,鸭茅和虉草仅6~7μmol?m-2?s-1,其它草种居中.春季蒸腾速率早晨6:00~8:00最低,随后逐步升高至最高峰后又逐渐回落.不同种类的日平均蒸腾速率,看麦娘、高羊茅、虉草、草地早熟禾较高,为2 mmol?m-2?s-1左右,最低为匍匐剪股颖0.8 mmol?m-2?s-1,其它草种为1.3~1.8 mmol?m-2?s-1.夏季大部分植物在6:00蒸腾速率较高,至8:00开始回落,10:00后上升,到最高点后回降,呈多峰变化的曲线.不同种类的日平均蒸腾速率,紫羊茅最高为3.5 mmol?m-2?s-1,最低为无芒雀麦、鸭茅、虉草,为1.4~1.7 mmol?m-2?s-1,其它草种为2.1~2.8 mmol?m-2?s-1.     

Phylogenetic relationships and biogeographic history of the unique Saxifraga sect. Irregulares (Saxifragaceae) from eastern Asia

Saxifraga L. is the largest genus in Saxifragaceae and a characteristic component of the herbaceous flora of the temperate and alpine mountains in the Northern Hemisphere. Section Irregulares is a small group of 15–20 species, representing one of the early‐diverged lineages in the genus characterized with unique zygomorphic flowers. We used both nuclear internal transcribed spacer and chloroplast DNA regions (psbA‐trnH, trnL‐F, and matK) to reconstruct its species relationships, estimate divergence times, and infer its historical biogeography. Our phylogenetic results corroborate the monophyly of sect. Irregulares and its sister relationship to sect. Heterisia from North America. The section was well resolved into two lineages corresponding to their morphological features and biogeographic distributions. One represents ser. Stoloniferae including S. stolonifera Curtis and S. nipponica Makino with long‐creeping stolons/rhizomes and small petals with spots and the other comprises the remaining taxa (ser. Rufescentes) which lack long‐creeping rhizomes. Spots on leaves (abaxially spotted vs. abaxially without spots) and spots on petals (without spots vs. with spots) are inferred to be phylogenetically informative within ser. Rufescentes. Divergence time estimates and ancestral area analysis suggested a western North American origin of sect. Irregulares with migration into East Asia by way of the Bering land bridge in the Middle Oligocene. The development of drying and desertification belt in the late Miocene could have played an important role in the subsequent restriction and separation of the north and south lineages within eastern Asia.     

Development of a triclosan scaffold which allows for adaptations on both the A- and B-ring for transport peptides

The enoyl acyl-carrier protein reductase (ENR) enzyme is harbored within the apicoplast of apicomplexan parasites providing a significant challenge for drug delivery, which may be overcome through the addition of transductive peptides, which facilitates crossing the apicoplast membranes. The binding site of triclosan, a potent ENR inhibitor, is occluded from the solvent making the attachment of these linkers challenging. Herein, we have produced 3 new triclosan analogs with bulky A- and B-ring motifs, which protrude into the solvent allowing for the future attachment of molecular transporters for delivery.     

毛竹的花药发育研究

竹类植物因有着较长的开花周期,其生殖生物学研究的报道相对较少。该研究采用石蜡切片与野外观察的方法,对毛竹花药的发育以及花药发育与花序的关系进行了研究。结果表明:毛竹的花药壁结构包括4层细胞:表皮细胞、药室内壁细胞、中层细胞和绒毡层细胞。药室内壁和中层都只有一层细胞,而且细胞形状较扁,花药发育后期药室内壁会逐渐降解,而中层则会完全解体消失。花药壁的发育为单子叶型,绒毡层为腺质型,而且只有一层,细胞径向较长,最后也会消失。小孢子母细胞减数分裂时,胞质分裂方式为连续型。形成的小孢子经一次有丝分裂后逐渐形成成熟花粉粒,大多为二细胞型,很少产生三细胞型。此外,还发现毛竹花药的发育与花序形态变化存在着相对应的关系。野外连续观察和切片发现,随着花序形态的不断发育变化,首先花药开始形成并不断分化,药壁备层也逐渐形成;接着小孢子逐渐成熟,备层也慢慢随之解体、消失;最后花药逐渐开裂并开始散粉。该研究结果不仅丰富了毛竹和竹类生殖生物学的研究内容,而且对毛竹种质的研究也具有重要意义。     

Shared as well as distinct roles of EHD proteins revealed by biochemical and functional comparisons in mammalian cells and <Emphasis Type="Italic">C. elegans</Emphasis>

Background  

The four highly homologous human EHD proteins (EHD1-4) form a distinct subfamily of the Eps15 homology domain-containing protein family and are thought to regulate endocytic recycling. Certain members of this family have been studied in different cellular contexts; however, a lack of concurrent analyses of all four proteins has impeded an appreciation of their redundant versus distinct functions.