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1.
Staphylococci have two mechanisms for resistance to β-lactam antibiotics. One is the production of β-lactamases, enzymes that
hydrolytically destroy β-lactams. The other is the expression of penicillin-binding protein 2a (PBP 2a), which is not susceptible
to inhibition by β-lactam antibiotics. Strains of S. aureus exhibiting either β-lactamase or PBP 2a-directed resistance (or both) have established a considerable ecological niche among
human pathogens. The emergence and subsequent spread of bacterial strains designated as methicillin-resistant S. aureus (MRSA), from the 1960s to the present, has created clinical difficulties for nosocomial treatment on a global scale. The
recent variants of MRSA that are resistant to glycopeptide antibiotics (such as vancomycin) have ushered in a new and disconcerting
chapter in the evolution of this organism.
Received 2 April 2005; received after revision 15 July 2005; accepted 25 July 2005 相似文献
2.
Matin A 《Cellular and molecular life sciences : CMLS》2007,64(11):1317-1322
The 129 mouse strain develops congenital testicular germ cell tumors (TGCTs) at a low frequency. TGCTs in mice resemble the
testicular tumors (teratomas) that occur in human infants. The genes that cause these tumors in 129 have not been identified.
The defect at the Ter locus increases TGCT incidence such that 94% of 129-Ter/Ter males develop TGCTs. The primary effect of the Ter mutation is progressive loss of primordial germ cells (PGCs) during embryonic development. This results in sterility in adult
Ter/Ter mice on all mouse strain backgrounds. However, on the 129 background, Ter causes tumor development in addition to sterility. Therefore, Ter acts as a modifier of 129-derived TGCT susceptibility genes. Ter was identified to be a mutation that inactivates the Dead-end1 (Dnd1) gene. In this perspective, I discuss the possible areas of future investigations to elucidate the mechanism of TGCT development
due to Dnd1 inactivation.
Received 29 September 2006; received after revision 29 January 2007; accepted 19 February 2007 相似文献
3.
Genetic analysis of the nematode Caenorhabditis elegans reveals that all dpy-5 alleles are dominant suppressors of bli-4 blistering. Molecular cloning of dpy-5 establishes that it encodes a cuticle procollagen, defects in which are responsible for the short-body, dumpy phenotype.
The null mutation, e907 removes the entire coding region, whereas the dpy-5 reference allele, e61, contains a nonsense substitution. RT-PCR analysis and a dpy-5::gfp fusion show that dpy-5 is expressed only in hypodermal cells at all post-embryonic life-cycle stages. Variable expression of dpy-5 in V lineage-derived seam cells suggests an alternative regulatory mechanism in these cells. The dpy-5 gene product contains an Arg-X-X-Arg cleavage motif that could be recognized by a proprotein convertase, such as BLI-4. Mutation
of this site cause a dominant dumpy phenotype suggesting Dpy-5 procollagen requires processing for normal cuticle production.
Received 13 January 2006; accepted 23 March 2006 相似文献
4.
Albert-Weissenberger C Cazalet C Buchrieser C 《Cellular and molecular life sciences : CMLS》2007,64(4):432-448
The bacterial pathogen Legionella pneumophila is found ubiquitously in fresh water environments where it replicates within protozoan hosts. When inhaled by humans it can
replicate within alveolar macrophages and cause a severe pneumonia, Legionnaires disease. Yet much needs to be learned regarding
the mechanisms that allow Legionella to modulate host functions to its advantage and the regulatory network governing its intracellular life cycle. The establishment
and publication of the complete genome sequences of three clinical L. pneumophila isolates paved the way for major breakthroughs in understanding the biology of L. pneumophila. Based on sequence analysis many new putative virulence factors have been identified foremost among them eukaryotic-like
proteins that may be implicated in many different steps of the Legionella life cycle. This review summarizes what is currently known about regulation of the Legionella life cycle and gives insight in the Legionella-specific features as deduced from genome analysis.
Received 1 September 2006; received after revision 10 October 2006; accepted 22 November 2006 相似文献
5.
Periplasmic lysozyme inhibitor contributes to lysozyme resistance in <Emphasis Type="Italic">Escherichia coli</Emphasis> 总被引:1,自引:1,他引:0
Deckers D Masschalck B Aertsen A Callewaert L Van Tiggelen CG Atanassova M Michiels CW 《Cellular and molecular life sciences : CMLS》2004,61(10):1229-1237
The product of the Escherichia coli ORFan gene ykfE was recently shown to be a strong inhibitor of C-type lysozyme in vitro. The gene was correspondingly renamed ivy (inhibitor of vertebrate lysozyme), but its biological function in E. coli remains unknown. In this work, we investigated the role of Ivy in the resistance of E. coli to the bactericidal effect of lysozyme in the presence of outer-membrane-permeabilizing treatments. Both in the presence of lactoferrin (3.0 mg/ml) and under high hydrostatic pressure (250 MPa), the lysozyme resistance of E. coli MG1655 was decreased by knock-out of Ivy, and increased by overexpression of Ivy. However, knock-out of Ivy did not increase the lysozyme sensitivity of an E. coli MG1655 mutant previously described to be resistant to lysozyme under high pressure. These results indicate that Ivy is one of several factors that affect lysozyme resistance in E. coli, and suggest a possible function for Ivy as a host interaction factor in commensal and pathogenic E. coli.Received 12 February 2004; received after revision 11 March 2004; accepted 16 March 2004 相似文献
6.
Xue QG Itoh N Schey KL Li YL Cooper RK La Peyre JF 《Cellular and molecular life sciences : CMLS》2007,64(1):82-95
A new lysozyme (cv-lysozyme 2) with a MALDI molecular mass of 12 984.6 Da was purified from crystalline styles and digestive
glands of eastern oysters (Crassostrea virginica) and its cDNA sequenced. Quantitative real time RT-PCR detected cv-lysozyme 2 gene expression primarily in digestive gland
tissues, and in situ hybridization located cv-lysozyme 2 gene expression in basophil cells of digestive tubules. Cv-lysozyme 2 showed high amino
acid sequence similarity to other bivalve mollusk lysozymes, including cv-lysozyme 1, a lysozyme recently purified from C. virginica plasma. Differences between cv-lysozyme 2 and cv-lysozyme 1 molecular characteristics, enzymatic properties, antibacterial
activities, distribution in the oyster body and site of gene expression indicate that the main role of cv-lysozyme 2 is in
digestion. While showing that a bivalve mollusk employs different lysozymes for different functions, findings in this study
suggest adaptive evolution of i type lysozymes for nutrition.
Received 30 August 2006; received after revision 14 October 2006; accepted 6 November 2006 相似文献
7.
Defensive secretions (allomones) from first-instar nymphs of stink bugs in the subfamily Pentatominae contain (E)-4-oxo-2-decenal as a major constituent, whereas this compound is absent from later instars. In contrast, first instars ofEdessa meditabunda (Edessinae) produce allomones like those of later instars. The C6 and C8 (E)-4-oxo-2-alkenals are common, characteristic exocrine compounds of nymphal and adult Heteroptera, but (E)-4-oxo-2-decenal is previously unknown as a major natural product for which a biological role has yet to be established. 相似文献
8.
Hu QD Lu H Huo K Ying K Li J Xie Y Mao Y Li YY 《Cellular and molecular life sciences : CMLS》2003,60(8):1725-1732
The Saccharomyces cerevisiae TPT1 gene plays a role in removing the 2-phosphate from ligated tRNA during the maturation of pre-tRNA. Here we reported the cloning and characterization of the human TRPT1 gene as a homolog of yeast TPT1. The TRPT1 gene is located at human chromosome 11q13 and encodes a polypeptide of 253 amino acids. BLAST searches with its amino acid sequence revealed the ubiquitous occurrence of TRPT1 homologs and their functional relationships with the presence of the DUF60/KptA domain. Northern analysis demonstrated that the gene is primarily expressed in heart and skeletal muscle, with lower or undetectable levels in other tissues studied. A plasmid-shuffling experiment showed that the human TRPT1 gene could complement the tpt1 mutation in S. cerevisiaeReceived 19 March 2003; received after revision 25 April 2003; accepted 22 May 2003 相似文献
9.
Stirnimann CU Grütter MG Glockshuber R Capitani G 《Cellular and molecular life sciences : CMLS》2006,63(14):1642-1648
DsbD is a redox-active protein of the inner Escherichia coli membrane possessing an N-terminal (nDsbD) and a C-terminal (cDsbD) periplasmic domain. nDsbD interacts with four different
redox proteins involved in the periplasmic disulfide isomerization and in the cytochrome c maturation systems. We review here the studies that led to the structural characterization of all soluble DsbD domains involved
and, most importantly, of trapped disulfide intermediate complexes of nDsbD with three of its four redox partners. These results
revealed the structural features enabling nDsbD, a ‘redox hub’ with an immunoglobulin-like fold, to interact efficiently with
its different thioredoxin-like partners.
Received 3 February 2006; received after revision 1 March 2006; accepted 5 April 2006 相似文献
10.
Multiple roles of the DSCR1 (Adapt78 or RCAN1) gene and its protein product Calcipressin 1 (or RCAN1) in disease 总被引:5,自引:0,他引:5
The DSCR1 (Adapt78) gene1 is transiently induced by stresses to temporarily protect cells against further potentially lethal challenges. However, chronic
expression of the DSCR1 (Adapt78) gene has now been implicated in several pathological conditions including Alzheimer’s disease, Down syndrome and cardiac
hypertrophy. Calcipressin 1 has been shown to function through direct binding and inhibition of the serine threonine protein
phosphatase Calcineurin. Pharmacological inhibition of calcineurin, by the immunosuppressive drugs cyclosporin A and FK506,
affects a wide variety of diseases. It is, therefore, likely that this endogenous calcineurin inhibitor, calcipressin 1, may
also play a role in a variety of human diseases.
1Please note that the mammalian DSCR1 gene is also called Adapt78 or RCAN1, and its protein products have been named Calcipressin1, MCIP1 and RCAN1. A proposal to adopt a single gene name of RCAN1 and a protein name RCAN1 (for Regulator of Calcineurin) has been endorsed by the HUGO Gene Nomenclature Committee, but final
approval must await agreement from a majority of researchers in the field.
Received 2 March 2005; received after revision 27 May 2005; accepted 19 July 2005 相似文献
11.
X. M. Jia Y. Wang Y. Jia P. H. Gao Y. G. Xu L. Wang Y. Y. Cao Y. B. Cao L. X. Zhang Y. Y. Jiang 《Cellular and molecular life sciences : CMLS》2009,66(1):122-134
The calcineurin pathway has been reported to be essential for the development of azole resistance in Candida albicans. The depletion or ectopic over-expression of RTA2 increased or decreased susceptibility of C. albicans to azoles, respectively. CaCl2- induced activation of the calcineurin pathway in wildtype C. albicans promoted resistance to azoles, while the Ca
2+ chelator (EGTA), calcineurin inhibitors (FK506 and cyclosporin A) and the deletion of RTA2 blocked the resistance-promoting effects of CaCl2. Furthermore, we found that RTA2 was up-regulated in a calcineurin-dependent manner. The depletion of RTA2 also made the cell membrane of C. albicans liable to be destroyed by azoles and RTA2 over-expression attenuated the destroying effects. Finally, the disruption of RTA2 caused an increased accumulation of dihydrosphingosine (DHS), one of the two sphingolipid long-chain bases, by decreasing
release of DHS. In conclusion, our findings suggest that RTA2 is involved in calcineurin-mediated azole resistance and sphingoid long-chain base release in C. albicans.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
Received 14 July 2008; received after revision 29 August 2008; accepted 16 September 2008 相似文献
12.
Biomedicine and diseases: the Klippel-Trenaunay syndrome, vascular anomalies and vascular morphogenesis 总被引:2,自引:0,他引:2
Vascular morphogenesis is a vital process for embryonic development, normal physiologic conditions (e.g. wound healing) and pathological processes (e.g. atherosclerosis, cancer). Genetic studies of vascular anomalies have led to identification of critical genes involved in vascular morphogenesis. A susceptibility gene, VG5Q (formally named AGGF1), was cloned for Klippel-Trenaunay syndrome (KTS). AGGF1 encodes a potent angiogenic factor, and KTS-associated mutations enhance angiogenic activity of AGGF1, defining ‘increased angiogenesis’ as one molecular mechanism for the pathogenesis of KTS. Similar studies have identified other genes involved in vascular anomalies as important genes for vascular morphogenesis, including TIE2, VEGFR-3, RASA1, KRIT1, MGC4607, PDCD10, glomulin, FOXC2, NEMO, SOX18, ENG, ACVRLK1, MADH4, NDP, TIMP3, Notch3, COL3A1 and PTEN. Future studies of vascular anomaly genes will provide insights into the molecular mechanisms for vascular morphogenesis, and may lead to the development of therapeutic strategies for treating these and other angiogenesis-related diseases, including coronary artery disease and cancer.Received 24 November 2004; received after revision 21 January 2005; accepted 2 March 2005 相似文献
13.
M. Mathy-Hartert G. Deby-Dupont P. Melin M. Lamy C. Deby 《Cellular and molecular life sciences : CMLS》1996,52(2):167-174
Myeloperoxidase (MPO) is an enzyme located within polymorphonuclear neutrophils capable of producting cytotoxic oxidant species that are particularly active against bacteria with polysaccharide capsules.Pseudomonas aeruginosa (106 bacteria per 1 ml) are killed within 1 h in vitro by a MPO/H2O2/Cl– system (48 mU=132 ng of MPO). The question arose as to whether human macrophages would acquire cytotoxic activity when loaded with this enzyme. Monocytes were therefore isolated from human blood and cultured for up to ten days to induce maturation to macrophages. These cells lost endogenous MPO within five days while H2O2 production in response to stimulation by phorbol myristate acetate (10–6M) decreased to 23% within ten days. On the other hand, their capacity to take up exogenous MPO increased fourfold from day three to day ten. Human macrophages cultured from eight days (when both H2O2 production and MPO uptake were sufficient) were therefore used to study the effects of MPO uptake on cytocidal activity againstPseudomonas aeruginosa. After a 1 h MPO loading period, macrophages (5×105 cells per ml) were incubated in the presence of bacteria (0.5 to 2×106 bacteria per ml) for 2 h at 37°C. At a bacteria/macrophage ratio of 1, only 34.8±7.0% of bacteria survived (compared to killing by non-loaded macrophages), while 74.4±9.3% survived at a ratio of 4. From these results, we conclude that loading macrophages with exogenous MPO could enhance their microbicidal activity, suggesting a potentially useful therapeutic application. 相似文献
14.
Unique evolution of Bivalvia arginine kinases 总被引:1,自引:0,他引:1
Takeuchi M Mizuta C Uda K Fujimoto N Okamoto M Suzuki T 《Cellular and molecular life sciences : CMLS》2004,61(1):110-117
The clams Pseudocardium, Solen, Corbicula and Ensis possess a unique form of arginine kinase (AK) with a molecular mass of 80 kDa and an unusual two-domain structure, a result of gene duplication and subsequent fusion. These AKs also lack two functionally important amino acid residues, Asp62 and Arg193, which are strictly conserved in other 40-kDa AKs and are assumed to be key residues for stabilizing the substrate-bound structure. However, these AKs show higher enzyme activity. The cDNA-derived amino acid sequences of 40-kDa AKs from the blood clam Scapharca broughtonii and the oyster Crassostrea gigas were determined. While Asp62 and Arg193 are conserved in Scapharca AK, these two key residues are replaced by Asn and Lys, respectively, in Crassostrea AK. The native enzyme from Crassostrea and both of the recombinant enzymes show an enzyme activity similar to that of two-domain clam AKs and at least twofold higher than that of other molluskan AKs. Although the replacement of Asp62 or Arg193 by Gly in normal AK causes a considerable decrease in Vmax (6–15% of wild-type enzyme) and a two- to threefold increase in Km for arginine, the same replacement in Scapharca AK had no pronounced effect on enzyme activity. Together with the observation that bivalve AKs are phylogenetically distinct from other molluskan AKs, these results suggest that bivalve AKs have undergone a unique molecular evolution; the characteristic stabilizing function of residues 62 and 193 has been lost and, consequently, the enzyme shows higher activity than normal.Received 14 October 2003; accepted 1 November 2003 相似文献
15.
The proton-dependent synthesis of ATP was demonstrated in representative members of the generaHalobacterium, Haloarcula, andHaloferax. In all cases, synthesis was not inhibited by nitrate or N-ethylmaleimide, inhibitors of the vacuolar-like ATPase found in Archaea, but was affected by azide, an inhibitor of F0F1-ATP syntheses. These observations extend the earlier observations withHalobacterium saccharovorum and suggest that ATP synthesis in these organisms is brought about by an F0F1-APT synthase. 相似文献
16.
The components of individual Dufours glands excised fromAnoplolepis custodiens workers were analysed by GC-MS. In addition to then-alkanes andn-alkenes previously reported2 in these glands, primary alcohols (C19-C22), secondary alcohols (C20-C23), 2-ketones (C20-C23) and possibly carboxylate ethyl esters (C19 and C21) were identified as components of these glands. It seems possible that these high-boiling compounds are used by the workers in laying trails on the hot sandy surfaces of their characteristic habitat and in lining of the inner walls of nests, but no standard compounds have been available to us for any behavioral studies. 相似文献
17.
N. Ishii 《Cellular and molecular life sciences : CMLS》1986,42(7):810-812
Summary The maximal unloaded shortening velocity (Vmax) of smooth muscle cells isolated from the pedal retractor muscle ofMytilus was more than twice as large as that of the whole muscle, suggesting the presence of extracellular components which resist the contraction of the whole muscle. The Vmax of the isolated cells was almost constant at cell lengths ranging between 0.5 and 0.8310 (10, optimal length for tension generation) indicating that the intracellular resistance to contraction is negligible within this range of lengths. 相似文献
18.
Heras SR Thomas MC García-Canadas M de Felipe P García-Pérez JL Ryan MD López MC 《Cellular and molecular life sciences : CMLS》2006,63(12):1449-1460
A comparative analysis of 40 Trypanosoma cruzi L1Tc elements showed that the 2A self-cleaving sequence described in viruses is present in them. Of these elements, 72% maintain
the canonical 2A motif (DxExNPGP). A high percentage has a conserved point mutation within the motif that has not been previously
described. In vitro and in vivo expression of reporter polyproteins showed that the L1Tc2A sequence is functional. Mutations within certain L1Tc2A sequences
affect the efficiency of the cleavage. The data indicate that the L1Tc2A sequence may be influencing the L1Tc enzymatic machinery
determining the composition and level of the translated products. The residues located immediately upstream of the 2A consensus
sequence increase the cleaving efficiency and appear to stabilize the relative amount of translated products.
These authors contributed equally to this work.
Received 26 January 2006; received after revision 11 April 2006; accepted 21 April 2006 相似文献
19.
dng1 is a Dictyostelium homologue of the mammalian tumor suppressor ING gene. DNG1 protein localizes in the nucleus, and has a highly conserved PHD finger domain found in chromatin-remodeling proteins. Both dng1 disruption and overexpression impaired cell proliferation. In dng1-null cells, the progression of differentiation was delayed in a cell-density-dependent manner, and many tiny aggregates were formed. Exogenously applied cAMP pulses reversed the inhibitory effect caused by dng1 disruption on the aggregation during early development, but formation of tiny aggregates was not restored. dng1-overexpressing cells acquired the ability to undergo chemotaxis to cAMP earlier and exhibited enhanced differentiation. These phenotypes were found to be coupled with altered expressions of early genes such as cAMP receptor 1 (car1) and contact site A (csA). Furthermore, disordered histone modifications were demonstrated in dng1-null cells. These results suggest a regulatory role of dng1 in the transition of cells from growth to differentiation.Received 29 December 2004; received after revision 24 May 2005; accepted 26 May 2005 相似文献
20.
Protein-O-mannosyltransferases (Pmt proteins) catalyse the addition of mannose to serine or threonine residues of secretory proteins.
This modification was described first for yeast and later for other fungi, mammals, insects and recently also for bacteria.
O-mannosylation depends on specific isoforms of the three Pmt1, 2 and 4 subfamilies. In fungi, O-mannosylation determines the structure and integrity of cell walls, as well as cellular differentiation and virulence. O-mannosylation of specific secretory proteins of the human fungal pathogen Candida albicans and of the bacterial pathogen Mycobacterium tuberculosis contributes significantly to virulence. In mammals and insects, Pmt proteins are essential for cellular differentiation and
development, while lack of Pmt activity causes Walker-Warburg syndrome (muscular dystrophy) in humans. The susceptibility
of human cells to certain viruses may also depend on O-mannosyl chains. This review focuses on the various roles of Pmt proteins in cellular differentiation, development and virulence.
Received 6 September 2007; received after revision 3 October 2007; accepted 5 October 2007 相似文献