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71.
Mycobacterium tuberculosis (Mtb) is one of the most formidable pathogens causing tuberculosis (TB), a devastating infectious disease responsible for the highest human mortality and morbidity. The emergence of drug-resistant strains of the pathogen has increased the burden of TB tremendously and new therapeutics to overcome the problem of drug resistance are urgently needed. Metabolism of Mtb and its interactions with the host is important for its survival and virulence; this is an important topic of research where there is growing interest in developing new therapies and drugs that target these interactions and metabolism of the pathogen during infection. Mtb adapts its metabolism in its intracellular niche and acquires multiple nutrient sources from the host cell. Carbon metabolic pathways and fluxes of Mtb has been extensively researched for over a decade and is well-defined. Recently, there has been investigations and efforts to measure metabolism of nitrogen, which is another important nutrient for Mtb during infection. This review discusses our current understanding of the central carbon and nitrogen metabolism, and metabolic fluxes that are important for the survival of the TB pathogen. 相似文献
72.
Golgi membranes remain segregated from the endoplasmic reticulum during mitosis in mammalian cells 总被引:8,自引:0,他引:8
What happens to organelles during mitosis, and how they are apportioned to each of the daughter cells, is not completely clear. We have devised a procedure to address whether Golgi membranes fuse with the Endoplasmic Reticulum (ER) during mitosis via the detection of interactions between ER and Golgi proteins. This procedure involves coexpressing an FKBP-tagged Golgi enzyme with an ER-retained protein fused to FRAP in COS cells. Since treatment with rapamycin induces a tight association between FKBP and FRAP, one would expect rapamycin to trap the FKBP-fused Golgi protein in the ER if it ever visits the ER during mitosis. However, after the doubly transfected cells progress through mitosis in the presence of rapamycin, we find the Golgi protein in the newly formed Golgi stacks and not in the ER. Based on these results, we conclude that Golgi membranes remain separate from the ER during mitosis in mammalian cells. 相似文献
73.
Biosensor based on Langmuir–Blodgett films of poly(3-hexyl thiophene) for detection of galactose in human blood 总被引:1,自引:1,他引:0
An amperometric biosensor was developed to estimate galactose in human blood serum. Monolayers of poly(3-hexyl thiophene) were placed on glass plates coated with indium tin oxide formed by dispensing a mixed solution of stearic acid in chloroform on to a water sub-phase. Galactose oxidase was mixed with poly(3-hexyl thiophene)/stearic acid in chloroform and dispensed on to the air-water interface of Langmuir-Blodgett trough. These monolayers were transferred on to glass plates which were used as working electrodes with platinum as a reference electrode. The amperometric galactose biosensor thus fabricated had a linear response from 0.05 to 0.5 g galactose l(-1) in blood serum. The normal level in blood is < 0.05 g galactose l(-1) in adults and 0-0.2 g galactose l(-1) in infants. In case of galactosemia, this increases to above 0.2 g galactose l(-1) in infants. 相似文献
74.
Liu J Masurekar MR Vatner DE Jyothirmayi GN Regan TJ Vatner SF Meggs LG Malhotra A 《American journal of physiology. Heart and circulatory physiology》2003,285(6):H2587-H2591
Aging and diabetes mellitus (DM) both affect the structure and function of the myocardium, resulting in increased collagen in the heart and reduced cardiac function. As part of this process, hyperglycemia is a stimulus for the production of advanced glycation end products (AGEs), which covalently modify proteins and impair cell function. The goals of this study were first to examine the combined effects of aging and DM on hemodynamics and collagen types in the myocardium in 12 dogs, 9-12 yr old, and second to examine the effects of the AGE cross-link breaker phenyl-4,5-dimethylthazolium chloride (ALT-711) on myocardial collagen protein content, aortic stiffness, and left ventricular (LV) function in the aged diabetic heart. The alloxan model of DM was utilized to study the effects of DM on the aging heart. DM induced in the aging heart decreased LV systolic function (LV ejection fraction fell by 25%), increased aortic stiffness, and increased collagen type I and type III protein content. ALT-711 restored LV ejection fraction, reduced aortic stiffness and LV mass with no reduction in blood glucose level (199 +/- 17 mg/dl), and reversed the upregulation of collagen type I and type III. Myocardial LV collagen solubility (%) increased significantly after treatment with ALT-711. These data suggest that an AGE cross-link breaker may have a therapeutic role in aged patients with DM. 相似文献
75.
Cao J McNevin J Malhotra U McElrath MJ 《Journal of immunology (Baltimore, Md. : 1950)》2003,171(7):3837-3846
Induction of HIV-1-specific CD8(+) T cells during acute infection is associated with a decline in viremia. The role CD8(+) effectors play in subsequently establishing viral set point remains unclear. To address this, we focused on two acutely infected patients with the same initial Tat-specific CD8(+) response, analyzing their CD8(+) T cell responses longitudinally in conjunction with viral load and sequence evolution. In one patient initiating treatment during acute infection, the frequencies of Tat-specific CD8(+) T cells gradually diminished but persisted, and the Tat epitope sequence was unaltered. By contrast, in the second patient who declined treatment, the Tat-specific CD8(+) T cells disappeared below detection, in conjunction with Gag-specific CD4(+) T cell loss, as plasma viremia reached a set point. This coincided with the emergence of an escape variant within the Tat epitope and an additional Vpr epitope. New CD8(+) T cell responses emerged but with no further associated decline in viremia. These findings indicate that, in the absence of treatment, the initial CD8(+) T cell responses have the greatest impact on reducing viremia, and that later, continuously evolving responses are less efficient in further reducing viral load. The results also suggest that T cell help may contribute to the antiviral efficiency of the acute CD8(+) T cell response. 相似文献
76.
77.
In order to assess the utility of nested clade analysis, both standard phylogenetic algorithms and nested clade analysis were performed on a geographically widespread survey of mitochondrial DNA haplotypes of the bamboo viper, Trimeresurus stejnegeri, within Taiwan. Gross tree topologies were congruent for all analyses and indicated the presence of two geographically overlapping clades within Taiwan. The smaller lineage was restricted to the north and east coasts, whereas the larger lineage occupied all but the northern range of the species within Taiwan including the Pacific offshore populations of Green and Orchid Islands. The phylogeographical pattern supports the existence of at least one colonization event from the continent since the initial isolation of Taiwan from the mainland in the Pliocene. However, determining the exact number of colonization events was not possible due to the simultaneous vicariant forces of hypothesized continental landbridge connections and the occurrence of dramatic in situ orogenesis throughout the Pleistocene. Nested clade analysis provided multiple temporal and spatial population historical inferences that are not possible with standard analyses and therefore should become widely applied to future phylogeographical studies. 相似文献
78.
There are a huge number of phylogenetic studies based on mitochondrial DNA (mtDNA); however, these may represent gene trees that may not be congruent with the species tree. A solution to this problem is to include additional, independent, loci from the nuclear genome. At fine taxonomic levels, i.e. between populations and closely related species, previously suggested nuclear markers such as intron sequence data may not be appropriate. In this study we investigate the use of amplified fragment length polymorphisms (AFLP) to aid determination of the species tree for 24 specimens of a medically important snake, Trimeresurus albolabris. This is of particular importance for many venomous snakes as venom often varies intraspecifically. Five different primer combinations produced 434 bands and were analysed by constructing a phylogenetic tree using neighbour joining and principal component analysis. Results were similar across all methods and found distinct groupings. The results were compared with mtDNA data and a reconciled tree was constructed in order to determine the species tree for T. albolabris. We found that T. albolabris (sensu lato) is not monophyletic. Specimens from the Indonesian islands (except West Java) form a distinct clade and we propose elevation to species level. A specimen from Nepal is also distinct and suggests that this population also deserves specific status. We suggest that AFLPs may prove a valuable aid in determining species trees as opposed to gene trees at fine taxonomic levels and this should facilitate the incorporation of molecular data into such activities as antivenom production and conservation management. 相似文献
79.
Zager JS Delman KA Malhotra S Ebright MI Bennett JJ Kates T Halterman M Federoff H Fong Y 《Molecular medicine (Cambridge, Mass.)》2001,7(8):561-568
BACKGROUND: Herpes simplex type I (HSV)-based vectors have been used experimentally for suicide gene therapy, immunomodulatory gene delivery, and direct oncolytic therapy. The current study utilizes the novel concept of regional delivery of an oncolytic virus in combination with or serving as the helper virus for packaging herpes-based amplicon vectors carrying a cytokine transgene, with the goal of identifying if this combination is more efficacious than either modality alone. MATERIALS AND METHODS: A replication competent oncolytic HSV (G207) and a replication incompetent HSV amplicon carrying the gene for the immunomodulatory cytokine IL-2 (HSV-IL2) were tested in murine syngeneic colorectal carcinoma and in rat hepatocellular carcinoma models. Liver tumors were treated with vascular delivery of (1) phosphate-buffered saline (PBS), (2) G207, (3) HSV-IL2, (4) G207 and HSV-IL2 mixed in combination (mG207/HSV- IL2), and (5) G207 as the helper virus for packaging the construct HSV-IL2 (pG207/HSV-IL2). RESULTS: Tumor burden was significantly reduced in all treatment groups in both rats and mice treated with high-dose G207, HSV-IL2, or both (p < 0.02). When a low dose of virus was used in mice, anti-tumor efficacy was improved by use of G207 and HSV-IL2 in combination or with HSV-IL2 packaged by G207 (p < 0.001). This improvement was abolished when CD4(+) and CD8(+) lymphocytes were depleted, implying that the enhanced anti-tumor response to low-dose combined therapy is immune mediated. CONCLUSIONS: Vascular regional delivery of oncolytic and amplicon HSV vectors can be used to induce improved anti-tumor efficacy by combining oncolytic and immunostimulatory strategies. 相似文献
80.
Optimal conditions for bio-oxidation of ferrous ions to ferric ions using Thiobacillus ferrooxidans 总被引:7,自引:0,他引:7
A chemo-biochemical process using Thiobacillus ferrooxidans for desulphurization of gaseous fuels and emissions containing hydrogen sulphide (H2S) has been developed. In the first stage, H2S present in fuel gas and emissions is selectively oxidized to elemental sulphur using ferric sulphate. The ferrous sulphate produced in the first stage of the process is oxidized to ferric sulphate using Thiobacillus ferrooxidans for recycle and reuse in the process. The effects of process variables, temperature, pH, total dissolved solids (TDS), elemental sulphur, ferric and magnesium ions on bio-oxidation of ferrous ions to ferric ions were investigated using flask culture experiments. The bio-oxidation of ferrous ions to ferric ions could be achieved efficiently in the temperature range of 20(+/-1)-44(+/-1) degrees C. A pH range of 1.8(+/-0.02)-2.2(+/-0.02) was optimum for the growth of culture and effective bio-oxidation of ferrous ions to ferric ions. The effect of TDS on bio-oxidation of ferrous ions indicated that a preacclimatized culture in a growth medium containing high dissolved solid was required to achieve effective bio-oxidation of ferrous ions. Elemental sulphur ranging from 1000 to 100,000 mg/l did not have any effect on efficiency of ferrous ion oxidation. The efficiency of bio-oxidation of ferrous ions to ferric ions was not affected in the presence of ferric ions up to a concentration of 500 mg/l while 3 mg/l of magnesium ion was optimal for achieving effective bio-oxidation. 相似文献