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1.
In an attempt to identify proteins involved in copper transport in the type I methanotroph Methylomicrobium albus BG8, copper-regulated polypeptides were examined. One major copper-repressible membrane polypeptide of approx. 28 500 Da was identified and designated CorA. The gene encoding this polypeptide was isolated and sequenced, and it shared a low identity with a calcium channel protein. An insertion mutation in corA of M. albus BG8 grew very poorly, suggesting that CorA is important for growth of this methanotroph. CorA may be involved in transport of copper and/or other divalent metals ions in M. albus BG8.  相似文献   

2.
ObjectiveTo evaluate the safety, tolerability, and pharmacokinetics of single doses of BG00010 (neublastin, artemin, enovin) in subjects with unilateral sciatica.MethodsThis was a single-center, blinded, placebo-controlled, randomized Phase 1 sequential-cohort, dose-escalation study (ClinicalTrials.gov identifier NCT00961766; funded by Biogen Idec). Adults with unilateral sciatica were enrolled at The Royal Adelaide Hospital, Australia. Four subjects were assigned to each of eleven cohorts (intravenous BG00010 0.3, 1, 3, 10, 25, 50, 100, 200, 400, or 800 μg/kg, or subcutaneous BG00010 50 μg/kg) and were randomized 3:1 to receive a single dose of BG00010 or placebo. The primary safety and tolerability assessments were: adverse events; clinical laboratory parameters and vital signs; pain as measured by a Likert rating scale; intra-epidermal nerve fiber density; and longitudinal assessment of quantitative sensory test parameters. Blood, serum, and plasma samples were collected for pharmacokinetic and pharmacodynamic assessments. Subjects were blinded to treatment assignment throughout the study. The investigator was blinded to treatment assignment until the Data Safety Review Committee review of unblinded data, which occurred after day 28.ResultsBeyond the planned enrollment of 44 subjects, four additional subjects were enrolled into to the intravenous BG00010 200 μg/kg cohort after one original subject experienced mild generalized pruritus. Therefore, a total of 48 subjects were enrolled between August 2009 and December 2011; all were included in the safety analyses. BG00010 was generally well tolerated: in primary analyses, the most common treatment-emergent adverse events were changes in temperature perception, pruritus, rash, or headache; no trends were observed in clinical laboratory parameters, vital signs, intra-epidermal nerve fiber density, or quantitative sensory testing. BG00010 was not associated with any clear, dose-dependent trends in Likert pain scores. BG00010 was rapidly distributed, with a prolonged terminal elimination phase.ConclusionsThese data support the development of BG00010 for the treatment of neuropathic pain.

Trial Registration

ClinicalTrials.gov NCT00961766  相似文献   

3.
Filamentous mutants were induced in a coccoid blue-green alga, Agmenellum quadruplicatum strain BG1, after treatment with N-methyl-N'-nitro-N-nitrosoguanidine (NTG). The mutants fall into two general classes: filaments with cross walls and filaments without cross walls. All mutants of these general types derived from BG1 are stable and have growth rates the same as or very similar to the wild type under a variety of conditions. Detailed examination of one mutant, 53SB2, revealed no difference in deoxyribonucleic acid content nor in base ratios. Mutant 53SB2 did not revert to the normal cell size and shape when grown under different physical conditions nor upon the addition of potential reversing agents to the basal medium. It is our general experience that filamentous mutants such as those described here in BG1 are commonly induced in other coccoid blue-green algae after NTG treatment.  相似文献   

4.
5.
A device providing frequent, automatic, and non-invasive glucose measurements for persons with diabetes has been developed: the GlucoWatch® biographer. This device extracts glucose through intact skin via reverse iontophoresis where it is detected by an amperometric biosensor. The biographer can provide glucose readings every 20 min for 12 h. The performance of this device was evaluated in two large clinical studies in a controlled clinical environment (n=231), and the home environment (n=124). Accuracy of the biographer was evaluated by comparing the automatic biographer readings to serial finger-stick blood glucose (BG) measurements. Biographer performance was comparable in both environments. Mean difference between biographer and finger-stick measurements was −0.01 and 0.26 mmol l−1 for the clinical and home environments, respectively. The mean absolute value of the relative difference was 1.06 and 1.18 mmol l−1 for the same studies. Correlation coefficient (r) between biographer and finger-stick measurements was 0.85 and 0.80 for the two studies. In both studies, over 94% of the biographer readings were in the clinically acceptable A+B region of the Clarke Error Grid. A slight positive bias is observed for the biographer readings at low BG levels. Biographer accuracy is relatively constant over all rates of BG changes, except when BG decreases more than 10 mmol l−1 h−1, which occurred for only 0.2% of points in the home environment study. Biographer precision, as measured by CV%, is approx. 10%. Skin irritation, characterized by erythema and edema, was either non-existent or mild in >90% of subjects and resolved in virtually all subjects without treatment in several days.  相似文献   

6.

Background

Hyperglycemia is common after stroke, and it is well known to worsen its outcome. However, it is important to consider that blood glucose (BG) levels can undergo dynamic changes during the acute stage of ischemic stroke. We sought to investigate the clinical significance of various glucose parameters within first 24 hours in acute ischemic stroke (AIS). The study focused on hyperacute stage patients who underwent IVT and investigated which parameters of glucose demonstrated to be helpful for predicting outcome.

Methods

This was a retrospective study of consecutive patients with AIS at a single stroke center. Patients were consecutively enrolled if they were treated with IV-tPA within 3 hours of symptom onset. BG was measured immediately upon arrival in ER, after IVT and every 6–8 hours during the first 24 hours after IVT. The various parameters of BG were the following: BG before IVT, BG after IVT, mean BG (mBG), maximal BG (max BG), standard deviation of BG (sdBG), and standard deviation of mean BG (sdmBG).

Results

207 patients (127 men and 80 women) were included in this study. Seventy seven of 207 patients had favorable outcomes at 3 months. High BG after IVT, mBG and max BG were independently associated with mRS>2 at 3 months (adjusted by age, NIHSS, and atrial fibrillation). Several parameters of BG were also independently associated with early mortality within 3 months (BG after IVT, mBG, and max BG). BG after IVT and mBG over 180 mg/dL were independently associated with early mortality within 3 months.

Conclusion

Serial measurements of BG might be a better predictor of clinical outcome in patients with AIS treated with IVT than single BG measurements before IVT. Therefore, these results suggest that variable parameters of BG could be important for the prediction of clinical outcome in AIS treated with IVT.  相似文献   

7.
We developed a model system to study the signal transduction pathways leading to the activation of Arabidopsis thaliana genes involved in the defense against pathogen attack. Here we describe the identification and characterization of virulent and avirulent Pseudomonas syringae strains that elicit disease or resistance symptoms when infiltrated into Arabidopsis leaves. The virulent and avirulent strains were characterized by determining growth of the pathogen in Arabidopsis leaves and by measuring accumulation of mRNA corresponding to Arabidopsis phenylalanine ammonia-lyase (PAL), beta-1,3-glucanase (BG), and chalcone synthase (CHS) genes in infected leaves. The virulent strain, P. syringae pv maculicola ES4326, multiplied 10(5)-fold in Arabidopsis leaves and strongly elicited BG1, BG2, and BG3 mRNA accumulation but had only a modest effect on PAL mRNA accumulation. In contrast, the avirulent strain, P. syringae pv tomato MM1065, multiplied less than 10-fold in leaves and had only a minimal effect on BG1, BG2, and BG3 mRNA accumulation, but it induced PAL mRNA accumulation. No accumulation of CHS mRNA was found with either ES4326 or MM1065. We also describe the cloning of a putative avirulence (avr) gene from the avirulent strain MM1065 that caused the virulent strain ES4326 to grow less well in leaves and to strongly elicit PAL but not BG1 and BG3 mRNA accumulation. These results suggest that the Arabidopsis PAL and BG genes may be activated by distinct signal transduction pathways and show that differences in plant gene induction by virulent and avirulent strains can be attributed to a cloned presumptive avr gene.  相似文献   

8.
《Journal of Physiology》2013,107(3):219-229
Dysfunction of the dopaminergic system leads to motor, cognitive, and motivational symptoms in brain disorders such as Parkinson’s disease. The basal ganglia (BG) are involved in sensorimotor learning and receive a strong dopaminergic signal, shown to play an important role in social interactions. The function of the dopaminergic input to the BG in the integration of social cues during sensorimotor learning remains however largely unexplored. Songbirds use learned vocalizations to communicate during courtship and aggressive behaviors. Like language learning in humans, song learning strongly depends on social interactions. In songbirds, a specialized BG–thalamo-cortical loop devoted to song is particularly tractable for elucidating the signals carried by dopamine in the BG, and the function of dopamine signaling in mediating social cues during skill learning and execution. Here, I review experimental findings uncovering the physiological effects and function of the dopaminergic signal in the songbird BG, in light of our knowledge of the BG–dopamine interactions in mammals. Interestingly, the compact nature of the striato-pallidal circuits in birds led to new insight on the physiological effects of the dopaminergic input on the BG network as a whole. In singing birds, D1-like receptor agonist and antagonist can modulate the spectral variability of syllables bi-directionally, suggesting that social context-dependent changes in spectral variability are triggered by dopaminergic input through D1-like receptors. As variability is crucial for exploration during motor learning, but must be reduced after learning to optimize performance, I propose that, the dopaminergic input to the BG could be responsible for the social-dependent regulation of the exploration/exploitation balance in birdsong, and possibly in learned skills in other vertebrates.  相似文献   

9.
Streptozotocin-induced diabetes mellitus (STZ-DM) in rats is a model of type 1 diabetes, which is commonly used to study diabetes, but differs from human diabetic pathophysiology in its insulin resistance. An STZ-DM rat can be administered five times the dose of insulin compared to that of a diabetic patient. Thus, attaining normoglycaemia in STZ-DM rats with insulin injections is complicated, and it involves an obvious risk of overdosing before getting a response. This study was designed to investigate whether suboptimal treatment with long-acting insulin restores insulin sensitivity in the STZ-DM rat, and thus an approach to more closely mimic the human condition. Male Sprague-Dawley rats were made diabetic by means of a single intravenous injection of STZ (55 mg/kg body weight (BW)), resulting in an increase in blood glucose (BG) from 6.5 ± 0.2 to 22.5 ± 1.0 mmol/l (P 0.05) within 24 h. After treating the STZ-DM rats with vehicle for 14 days, BG was 26.1 ± 1.1 mmol/l, and the response to a single injection of fast-acting insulin (Humalog, 5 IE/kg BW) was a 23% reduction in BG. Thereafter, the rats were treated daily with a suboptimal dose of long-acting insulin for a total of 7 days (Insulatard, 5 IE/kg per day), which resulted in a BG level of 19.4 ± 2.7. The response to fast-acting insulin after the suboptimal treatment was a 61% reduction in BG. Thereafter, the animals were vehicle-treated for another 7 days, which resulted in a response to fast-acting insulin similar to the initial values (-34%). Furthermore, the group treated with suboptimal doses of long-acting insulin had a longer duration of the reduction in BG (150 min, as opposed to 90 min in the vehicle-treated groups). We conclude that the development of a decreased insulin response occurs rapidly within the first 2 weeks after the onset of diabetes in STZ-DM rats. This leads to a brief and significantly reduced decrease in BG when fast-acting insulin is administered. The insulin response is increased by treatment with suboptimal doses of long-acting insulin, but rapidly decreases again when treatment is withdrawn. Regular administration of suboptimal insulin doses may provide an approach to eliminate the effects of a lowered insulin response.  相似文献   

10.
A polymer-producing strain of unicellular cyanobacteria, Synechococcus sp., was isolated from a coastal lagoon in Florida. This strain, designated BG0011, excreted a highly viscous polysaccharide. Maximum observed growth rates for BG0011 were 2.5 div. day-2. BG0011 also exhibited nitrogen fixation (nitrogenase) activity under aerobic conditions and grew at near maximum rates in medium lacking reduced nitrogen. Growth and carbohydrate production were enhanced by carbon dioxide enrichment. Rheological study of the extracellular polysaccharide revealed a viscosity versus shear rate curve similar in shape to that of xanthan gum. Maximum observed rate of carbohydrate production was 1 g dry weight liter-1 month-1.  相似文献   

11.
Alterations in mitochondrial structure and function are a hallmark of cancer cells compared to normal cells and thus targeting mitochondria has emerged as an novel approach to cancer therapy. The mitochondrial thioredoxin 2 (Trx2) system is critical for cell viability, but its role in cancer biology is not well understood. Recently some cationic triphenylmethanes such as brilliant green (BG) and gentian violet were shown to have antitumor and antiangiogenic activity with unknown mechanisms. Here we demonstrate that BG killed cells at nanomolar concentrations and targeted mitochondrial Trx2, which was oxidized and degraded. HeLa cells were more sensitive to BG than fibroblasts. In HeLa cells, Trx2 down-regulation by siRNA resulted in increased sensitivity to BG, whereas for fibroblasts, the same treatments had no effect. BG was observed to accumulate in mitochondria and cause a rapid and dramatic decrease in mitochondrial Trx2 protein. With a redox Western blot method, we found that treatment with BG caused oxidation of both Trx1 and Trx2, followed by release of cytochrome c and apoptosis-inducing factor from the mitochondria into the cytosol. Moreover, this treatment resulted in an elevation of the mRNA level of Lon protease, a protein quality control enzyme in the mitochondrial matrix, suggesting that the oxidized Trx2 may be degraded by Lon protease.  相似文献   

12.
Early vascularization is a prerequisite for successful bone healing and endothelial progenitor cells (EPC), seeded on appropriate biomaterials, can improve vascularization. The type of biomaterial influences EPC function with bioglass evoking a vascularizing response. In this study the influence of a composite biomaterial based on polylactic acid (PLA) and either 20 or 40% bioglass, BG20 and BG40, respectively, on the differentiation and survival of EPCs in vitro was investigated. Subsequently, the effect of the composite material on early vascularization in a rat calvarial critical size defect model with or without EPCs was evaluated. Human EPCs were cultured with β-TCP, PLA, BG20 or BG40, and seeding efficacy, cell viability, cell morphology and apoptosis were analysed in vitro. BG40 released the most calcium, and improved endothelial differentiation and vitality best. This effect was mimicked by adding an equivalent amount of calcium to the medium and was diminished in the presence of the calcium chelator, EGTA. To analyze the effect of BG40 and EPCs in vivo, a 6-mm diameter critical size calvarial defect was created in rats (n = 12). Controls (n = 6) received BG40 and the treatment group (n = 6) received BG40 seeded with 5×105 rat EPCs. Vascularization after 1 week was significantly improved when EPCs were seeded onto BG40, compared to implanting BG40 alone. This indicates that Ca2+ release improves EPC differentiation and is useful for enhanced early vascularization in critical size bone defects.  相似文献   

13.
细菌菌影(bacterial ghost,BG)是革兰阴性菌在噬菌体PhiX174的裂解基因E的作用下形成不含核酸、核糖体等胞质内容物的细菌空壳。这种细菌空壳保留了与天然细菌一样的完整外膜结构,且不具有活菌样的致病作用,可作为疫苗无需佐剂就能诱导机体产生体液免疫应答和细胞免疫应答。菌影内部及外膜上可装载DNA、抗原和药物等异源物质,易被机体免疫细胞识别捕获,使其成为一种新型的生物递送载体。另外,菌影具有制备简单,易于保存等优点。细菌菌影在疾病预防和治疗方面具有广阔的应用前景。  相似文献   

14.
Many genes important in immunity are found as multigene families. The butyrophilin genes are members of the B7 family, playing diverse roles in co-regulation and perhaps in antigen presentation. In humans, a fixed number of butyrophilin genes are found in and around the major histocompatibility complex (MHC), and show striking association with particular autoimmune diseases. In chickens, BG genes encode homologues with somewhat different domain organisation. Only a few BG genes have been characterised, one involved in actin-myosin interaction in the intestinal brush border, and another implicated in resistance to viral diseases. We characterise all BG genes in B12 chickens, finding a multigene family organised as tandem repeats in the BG region outside the MHC, a single gene in the MHC (the BF-BL region), and another single gene on a different chromosome. There is a precise cell and tissue expression for each gene, but overall there are two kinds, those expressed by haemopoietic cells and those expressed in tissues (presumably non-haemopoietic cells), correlating with two different kinds of promoters and 5′ untranslated regions (5′UTR). However, the multigene family in the BG region contains many hybrid genes, suggesting recombination and/or deletion as major evolutionary forces. We identify BG genes in the chicken whole genome shotgun sequence, as well as by comparison to other haplotypes by fibre fluorescence in situ hybridisation, confirming dynamic expansion and contraction within the BG region. Thus, the BG genes in chickens are undergoing much more rapid evolution compared to their homologues in mammals, for reasons yet to be understood.  相似文献   

15.
Our studies suggest a tripartite structure for the 60-kDa allergen of Bermuda grass pollen (BG60) including a short N-terminal segment, a FAD-binding domain, and a C-terminal domain. The lower molecular weight isoallergens lack the N-terminal segment. The higher protease susceptibility and the lower melting temperature of approximately 20 degrees C of the lower molecular weight isoforms suggest that the N-terminal segment is essential for a compact structure. Database screening reveals that the protease-digested peptide sequences (approximately 180 residues in total) share 40% identity with the plant berberine bridge enzymes. In particular, a 24-residue peptide sequence displays high similarity to a conserved FAD-binding motif. The spectroscopic and SDS-PAGE analyses suggest that the cofactor FAD is covalently linked to the central domain. Therefore, we conclude that BG60 is identified as the first flavinylated allergen.  相似文献   

16.
Although its usefulness and possibility of the well-known definition of the basic reproduction number R0 for structured populations by Diekmann, Heesterbeek and Metz (J Math Biol 28:365-382, 1990) (the DHM definition) have been widely recognized mainly in the context of epidemic models, originally it deals with population dynamics in a constant environment, so it cannot be applied to formulate the threshold principle for population growth in time-heterogeneous environments. Since the mid-1990s, several authors proposed some ideas to extend the definition of R0 to the case of a periodic environment. In particular, the definition of R0 in a periodic environment by Baca?r and Guernaoui (J Math Biol 53:421-436, 2006) (the BG definition) is most important, because their definition of periodic R0 can be interpreted as the asymptotic per generation growth rate, which is an essential feature of the DHM definition. In this paper, we introduce a new definition of R0 based on the generation evolution operator (GEO), which has intuitively clear biological meaning and can be applied to structured populations in any heterogeneous environment. Using the generation evolution operator, we show that the DHM definition and the BG definition completely allow the generational interpretation and, in those two cases, the spectral radius of GEO equals the spectral radius of the next generation operator, so it gives the basic reproduction number. Hence the new definition is an extension of the DHM definition and the BG definition. Finally we prove a weak sign relation that if the average Malthusian parameter exists, it is nonnegative when R0>1 and it is nonpositive when R0<1.  相似文献   

17.
Mucopolysaccharidosis type VII is a lysosomal storage disease resulting from a deficiency of beta-glucuronidase (BG) activity. To facilitate the investigation of mutation in the disease and provide molecular diagnostic tools for affected families, we have isolated human BG cDNA clones. The SV40-transformed human fibroblast cDNA library of Okayama and Berg [Mol. Cell. Biol. 3 (1982) 280-289] was screened with a fragment of a murine BG cDNA clone (pGUS-1). The 17 human cDNA clones (pHUG) isolated were identical by restriction mapping, varying only in length. The pHUG clones show 80% DNA sequence homology with pGUS-1 in a 198-bp PvuII-SstI restriction fragment. Both pGUS-1 and the pHUG clones contained an open reading frame (ORF) throughout the sequenced region with a predicted amino acid sequence homology of 73%. Expression in Escherichia coli of a 1150-bp fragment of pHUG-1 subcloned in pUC9 resulted in an isopropyl-thio-beta-galactoside (IPTG)-inducible 35-kDal fusion protein which was specifically immunoprecipitated by goat anti-human BG immunoglobulin G (IgG). This evidence provides direct confirmation that the pHUG cDNA clones correspond to human BG.  相似文献   

18.

Background  

Brewer's spent grain (BG), a by-product of the brewing process, is attracting increasing scientific interest as a low-cost feedstock for many biotechnological applications. BG in the present study is evaluated as a substrate for lignocellulolytic enzyme production and for the production of ethanol by the mesophilic fungus Fusarium oxysporum under submerged conditions, implementing a consolidated bioconversion process. Fermentation experiments were performed with sugar mixtures simulating the carbohydrate content of BG in order to determine the utilization pattern that could be expected during the fermentation of the cellulose and hemicellulose hydrolysate of BG. The sugar mixture fermentation study focused on the effect of the initial total sugar concentration and on the effect of the aeration rate on fermenting performance of F. oxysporum. The alkali pretreatment of BG and different aeration levels during the ethanol production stage were studied for the optimization of the ethanol production by F. oxysporum.  相似文献   

19.
Fish arylsulfatases (arylsulfate sulfohydrolase; EC 3.1.6.1) were resolved into cationic arylsulfatase A-like (ARSA) and anionic arylsulfatase B-like (ARSB) fractions by DEAE-Sephacel chromatography. Green sunfish (GSF) hepatic ARSA was more acidic and more thermostable than bluegill (BG) ARSA. GSF × BG interspecific hybrids preferentially expressed GSF ARSA, while BG × GSF hybrids appeared to produce a dimeric enzyme consisting of both GSF and BG ARSA polypeptides. GSF hepatic betaglucuronidase (GUS) also proved to be more thermostable than BG GUS. Thermostabilities of GUS produced by reciprocal interspecific hybrids were very similar to that of GSF GUS. Either GSF GUS is preferentially expressed in both interspecific hybrids or both the GSF and BG GUS polypeptides are synthesized in comparable amounts, and the GSF GUS polypeptide sufficiently stabilizes the heterotetramers produced by the hybrids to produce denaturation profiles closely approximating that of the GSF enzyme.  相似文献   

20.
Plants of the seagrass Zostera noltii were cultured in the laboratory (mesocosms) for two weeks to assess the effect of above:below-ground (AG/BG) biomass ratios and light on growth, photosynthesis and chemical composition. Experimental plant units (EPUs) with different proportions between AG and BG biomass were obtained from plants of the same size (containing 6 shoots and 5 internodes) by excising 0-5 shoots. The EPUs maintained the proportions in AG/BG biomass ratios during the experiment. While growth rate was unaffected by biomass partitioning at high light, maximum growth at low light was recorded in plants with low AG/BG ratios. The production of shoots and rhizomes showed a compensatory morphological response depending on the initial AG/BG proportions regardless of the light level. While shoot production, estimated as shoot appearance rate, was high at low AG/BG ratios and minimal under high AG/BG values, rhizome production, estimated as internode appearance rate and internode elongation rate, was maximal under high AG/BG proportions and decreased towards lower AG/BG ratios. This rhizomatic response was observed for secondary rhizomes and not for primary ones. In contrast to morphological response, no significant differences were detected in maximum electron transport rates (ETRm) among the different shoots in the plant. However, mean values of ETRm in plants were affected by biomass partitioning and light. EPUs grown in low light increased the sucrose stored in shoots as the AG/BG biomass ratios decreased; however, EPUs grown at high light showed no effect of biomass partitioning on sucrose levels. In conclusion, shoots excision by experimental manipulation caused a compensatory morphological response in plants while photosynthetic performance remained almost unaffected.  相似文献   

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