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931.
Land KM Delgadillo-Correa MG Tachezy J Vanacova S Hsieh CL Sutak R Johnson PJ 《Molecular microbiology》2004,51(1):115-122
Ferredoxin, Fd, is often deficient in metronidazole-resistant strains of Trichomonas vaginalis and is thought to be necessary for drug activation. To directly test whether Fd is essential for metronidazole susceptibility, gene replacement technology has been developed for T. vaginalis. The selectable marker gene neomycin phosphotransferase (NEO) flanked by approximately 2.6 and approximately 2.0 kBp of the Fd 5' and 3' flanking regions (pKO-FD-NEO) was introduced into cells on linear DNA and selected for NEO gene expression. Stable transformants were shown to contain the NEO gene in the Fd locus and to have completely lost the Fd gene. Northern and immunoblot analyses confirm the loss of Fd mRNA and protein in pKO-FD-NEO cells. Analyses of the activity of hydrogenosomal proteins in Fd KO cells show a fourfold increase in hydrogenase activity and a 95% decrease in pyruvate/ferredoxin oxidoreductase (PFO) activity. In contrast, PFO and hydrogenase mRNA levels are unchanged. Surprisingly, Fd KO cells are not resistant to metronidazole under aerobic or anaerobic conditions. These cells are capable of producing molecular hydrogen, albeit at 50% the level of the parental strain, demonstrating that the Fd gene product eliminated in KO cells is neither necessary for hydrogen production nor metronidazole activation. Together these data indicate the presence of unidentified Fds or flavodoxins capable of drug activation or an unidentified mechanism that does not require either PFO or Fd for metronidazole activation. 相似文献
932.
Jongbloed JD Grieger U Antelmann H Hecker M Nijland R Bron S van Dijl JM 《Molecular microbiology》2004,54(5):1319-1325
Activity of the Tat machinery for protein transport across the inner membrane of Escherichia coli and the chloroplast thylakoidal membrane requires the presence of three membrane proteins: TatA, TatB and TatC. Here, we show that the Tat machinery of the Gram-positive bacterium Bacillus subtilis is very different because it contains at least two minimal Tat translocases, each composed of one specific TatA and one specific TatC component. A third, TatB-like component is apparently not required. This implies that TatA proteins of B. subtilis perform the functions of both TatA and TatB of E. coli and thylakoids. Notably, the two B. subtilis translocases named TatAdCd and TatAyCy both function as individual, substrate-specific translocases for the twin-arginine preproteins PhoD and YwbN, respectively. Importantly, these minimal TatAC translocases of B. subtilis are representative for the Tat machinery of the vast majority of Gram-positive bacteria, Streptomycetes being the only known exception with TatABC translocases. 相似文献
933.
In eukaryotic cells, all macromolecules that traffic between the nucleus and the cytoplasm cross the double nuclear membrane through nuclear pore complexes (NPCs). NPCs are elaborate gateways that allow efficient, yet selective, translocation of many different macromolecules. Their protein composition has been elucidated, but how exactly these nucleoporins come together to form the pore is largely unknown. Recent data suggest that NPCs are composed of an extremely stable scaffold on which more dynamic, exchangeable parts are assembled. These could be targets for molecular rearrangements that change nuclear pore transport properties and, ultimately, the state of the cell. 相似文献
934.
Mechanism of lipoprotein retention by the extracellular matrix 总被引:2,自引:0,他引:2
PURPOSE OF REVIEW: Considerable evidence suggests that the subendothelial retention of atherogenic lipoproteins is a key early step in atherogenesis. In humans and experimental animals, elevated levels of plasma lipoproteins are associated with increased atherosclerosis, and lipoproteins with higher affinity for arterial proteoglycans are more atherogenic. Here we discuss the molecular mechanisms underlying lipoprotein retention in the arterial wall and how this interaction can be modulated. RECENT FINDINGS: Functional proteoglycan binding sites in lipoproteins containing apolipoprotein B have been identified and shown to have atherogenic potential in vivo. In addition to apolipoprotein B, novel bridging molecules, those that can interact with both proteoglycans and lipoproteins, have been identified that mediate the retention of atherogenic particles in the vessel wall. The interaction between lipoproteins and proteoglycans can be enhanced by the modification of lipoproteins in the circulation and in the arterial wall, by alterations in the subendothelium, and by changes in proteoglycan synthesis that result in a more atherogenic profile. The retention of atherogenic lipoproteins is a potential target for therapies to reverse atherosclerosis, and in-vitro studies have identified compounds that decrease the affinity of proteoglycans for lipoproteins. SUMMARY: Considerable progress has been made in understanding the association between lipoproteins and cardiovascular disease. This review highlights the importance of the interaction between lipoproteins and the arterial matrix. 相似文献
935.
The term microbially influenced corrosion, or biocorrosion, refers to the accelerated deterioration of metals owing to the presence of biofilms on their surfaces. The detailed mechanisms of biocorrosion are still poorly understood. Recent investigations into biocorrosion have focused on the influence of biomineralization processes taking place on metallic surfaces and the impact of extracellular enzymes, active within the biofilm matrix, on electrochemical reactions at the biofilm-metal interface. 相似文献
936.
Dendrites show remarkable diversity in morphology and function, but the mechanisms that produce the characteristic forms is poorly understood. Insect systems offer a unique opportunity to manipulate and study identified neurons in otherwise undisturbed environments. Recent studies in Drosophila show that dendritic targeting, branching patterns, territories, and metamorphic remodeling are controlled in specific ways, by intrinsic genetic programs and extrinsic cues, with important implications for function. Here, we review some recent advances in our understanding of dendritic development in insects, focusing primarily on insights that have been gained from studies of Drosophila. 相似文献
937.
Neuroproteomics: Expression Profiling of the Brain's Proteomes in Health and Disease 总被引:6,自引:0,他引:6
Kim SI Voshol H van Oostrum J Hastings TG Cascio M Glucksman MJ 《Neurochemical research》2004,29(6):1317-1331
The term "proteome" describes the protein complement of a genome. Proteomes of cells are dynamic and are directly affected by environmental factors, such as stress and/or drug treatment, or as a result of aging and disease. One of the distinct advantages of proteomic analysis, not attainable with RNA expression data, is the ability to fractionate the cell's proteins into various subpopulations. In neuroscience, "neuromics" (proteomics in the central nervous system) is in its infancy, with a paucity of studies in the context of the brain. One of the objectives of this review is to illustrate the potential of neuromics to profile differences in the distribution of thousands of proteins as a function of disease markers. We have previously used this approach to determine the effects of varied postmortem interval in examining human brain tissue and to identify biomarkers. Here we review proteomic studies of schizophrenia, Alzheimer's disease, and Parkinson's disease. Experimental results regarding Parkinson's disease are presented to illustrate the potential of neuromics to identify pathways of pathogenesis and novel therapeutic targets. 相似文献
938.
A thrombin inhibitor from the ixodid tick, Amblyomma hebraeum 总被引:2,自引:0,他引:2
A novel thrombin inhibitor named Amblin was identified from the haemolymph of the ixodid (hard) tick, Amblyomma hebraeum, and the coding cDNA was isolated from a tick cDNA library. This cDNA codes for a preprotein of 166 amino acids, including a predicted signal peptide composed of 15 amino acids N-terminal to the mature Amblin. The 151-amino-acid mature Amblin contains 14 cysteines and two Kunitz-like domains. It displays high sequence similarity with a tissue factor pathway inhibitor (TFPI), Ixolaris, from the ixodid tick, Ixodes scapularis, which has 10 cysteines, and a thrombin inhibitor, Boophilin, from the ixodid tick, Boophilus microplus, which has 12 cysteines. Recombinant Amblin specifically inhibited thrombin as efficiently as native Amblin did. This is the first report of a thrombin inhibitor from tick haemolymph. 相似文献
939.
Reconstruction of large composite oromandibulomaxillary defects with free vertical rectus abdominis myocutaneous flaps 总被引:2,自引:0,他引:2
Large composite oromandibulomaxillary defects resulting from oncologic resection can be challenging to reconstruct with a single flap, and functional outcomes remain anecdotal. The purpose of this study was to evaluate the authors' surgical experience and scientifically analyze and describe the functional outcomes associated with the use of the vertical rectus abdominis myocutaneous flap for reconstruction of these defects. The records of seven patients (mean age, 62 years) who underwent composite resection including hemimandibulectomy, partial maxillectomy, partial pharyngectomy, and floor-of-mouth resection followed by immediate free vertical rectus abdominis myocutaneous flap reconstruction at The University of Texas M. D. Anderson Cancer Center (1998 to 2002) were retrospectively reviewed. The tumor type was squamous cell carcinoma in all seven cases; four patients had T4 primary lesions and three had local recurrences. Radiotherapy was used preoperatively in each of the three recurrent cases (mean dose, 70.6 Gy) and postoperatively in three of the four patients with primary tumors (mean dose, 63.0 Gy). The mean length of hospitalization was 8.7 days. There were no major flap complications, fistulas, or donor-site complications. Partial flap necrosis (4 percent of flap area) occurred in one patient and dehiscence of the neck incision occurred in another. Both cases were managed with surgical débridement and closure. A third patient developed a 0.75-cm superficial suture line abscess that healed with dressing changes. The mean postoperative follow-up was 15 months. Six of the seven patients remained tube dependent for their nutrition despite some swallowing improvement; one patient returned to full oral intake. The most common swallowing deficit was impaired laryngeal excursion, which occurred in all six patients evaluated with videofluoroscopic examination and resulted in risk for aspiration in patients and frank aspiration in 83 percent. Speech was intelligible on routine follow-up visits in all patients except one. Four patients died as a result of their cancer, one was alive with metastatic disease, and two were alive with no evidence of disease at last follow-up. The goal for patients undergoing extensive composite oromandibulomaxillary resection for advanced cancer is to restore structure, minimize postoperative morbidity, and optimize the quality of remaining life. Reconstruction with the free vertical rectus abdominis myocutaneous flap achieves early wound healing, allows timely delivery of adjuvant therapy, and can be accomplished with predictable success and minimal morbidity. To our knowledge, this study represents the first to scientifically analyze and quantify swallowing function following free vertical rectus abdominis myocutaneous flap reconstruction for large oromandibulomaxillary defects. Understanding of the specific physiologic swallowing deficits that typically occur after such reconstructions will provide clinicians with important surgical and reconstructive information to enable future improvements in functional success in a population for whom the prognosis is poor and treatment options are limited. 相似文献
940.
We link deterministic integrodifference equations to stochastic, individual-based simulations by means of branching random walks. Using standard methods, we determine speeds of invasion for both average densities and furthest-forward individuals. For density-independent branching random walks, demographic stochasticity can produce extinction. Demographic stochasticity does not, however, reduce the overall asymptotic speed of invasion or preclude continually accelerating invasions. 相似文献