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81.
82.
It has been suggested that recombination may be mutagenic, which, if true, would inflate intraspecies diversity and interspecies silent divergence in regions of high recombination. Here, we test this hypothesis comparing human/orangutan genome-wide non-coding divergence (K) to that in the pseudoautosomal genes which were reported to recombine much more frequently than the rest of the genome. We demonstrate that, compared to the average human/orangutan non-coding divergence (K=3%), the substitution rate is significantly elevated in the introns of SHOX (K=5.7%), PPP2R3L (K=8.7%) and ASMT (K=6.5%) genes located in the human and orangutan Xp/Yp pseudoautosomal region (p-PAR), where recombination is over 20-fold higher than the genomic average. On the other hand, human/orangutan non-coding divergence at the Xp/Yp pseudoautosomal boundary (K=3.5%) and in the SYBL1 gene (K=2.7%), located in the human Xq/Yq pseudoautosomal region (q-PAR), where recombination is known to be less frequent than in p-PAR, was not significantly higher than the genome average. The data are consistent with the hypothesis that recombination may be mutagenic. 相似文献
83.
Mast cells: an unexpected finding in the modulation of cutaneous wound repair by charged beads 总被引:2,自引:0,他引:2
Sasaki A Mueller RV Xi G Sipe R Buck D Hollinger J 《Plastic and reconstructive surgery》2003,111(4):1446-1453
Increased numbers of mast cells are affiliated with a broad spectrum of pathologic skin conditions, including ulcers, atopic dermatitis, neurofibromatosis, hemangiomas, keloids, and hypertrophic scars. It has been proposed that mast cells play a primary pathophysiologic role in these disorders and that their presence represents not merely a secondary event. While investigating their recent hypothesis that positively charged cross-linked diethylaminoethyl dextran (CLDD) beads potentiate cutaneous wound healing, the authors serendipitously observed increased numbers of mast cells in the deep dermis of wounds treated with CLDD beads. The authors propose that mast cells may play an important role in the modulation of healing seen with CLDD beads. Incisional wounds were studied in 30 Sprague-Dawley rats partitioned into two groups that were killed 7 or 14 days after wounding. The wounds were treated with positively, negatively, or neutrally charged CLDD beads. Physiologic saline served as a control. At the designated times after incisional wounding, biopsy specimens were tested for wound breaking strength or processed for histologic testing, fixed in 4% paraformaldehyde, and stained with Giemsa and Goldner-Masson trichrome. Mast cells were counted under light microscopy in a blinded fashion and were expressed as the number of cells per millimeter squared. Significant increases in the number of mast cells were observed in the deep dermis of incisional wounds after implantation with positively or negatively charged CLDD beads. In contrast, neutrally charged beads had no effect on mast cell numbers. At 7 days, the incisions treated with positively charged beads averaged 2.1 times more mast cells compared with those treated with physiologic saline or neutrally charged beads, whereas the incisions treated with negatively charged beads displayed 3.2 times more mast cells. By day 14, the incisions treated with positively charged beads averaged 2.5 times more mast cells than those wounds treated with saline or neutrally charged beads; the incisions treated with negatively charged CLDD beads had 3.4 times more mast cells. The 7-day tensiometric data indicated that wounds treated with negatively charged CLDD beads had increased breaking strength compared with wounds treated with neutrally charged beads or saline (1.8 and 1.7 times, respectively; p = 0.01 and p = 0.02). Wounds treated with positively charged beads also showed increased breaking strength compared with wounds treated with neutrally charged beads or saline (1.5 and 1.4 times greater); however, this did not reach statistical significance. There was no apparent difference in breaking strength when neutrally charged beads were compared with those treated with saline. At 14 days, there was no statistically significant difference in wound breaking strength between different treatments. These findings are clinically germane to the assessment of proposed therapeutic applications of CLDD beads for a variety of impaired wound-healing states. Furthermore, if increased mast cell populations are intimately linked to hypertrophic scar and keloid formation, the results of the authors' study suggest that CLDD bead therapy of cutaneous wounds may lead to pathologic wound healing in humans. 相似文献
84.
Dave KR Syal AR Katyare SS 《Zeitschrift für Naturforschung. C, Journal of biosciences》2000,55(1-2):100-108
The substrate saturation and temperature-dependent kinetic properties of soluble and membrane-bound forms of acetylcholinestarase (AChE) from brain and butyrylcholinesterase (BChE) from heart and liver were examined. In simultaneous studies these parameters were also measured for AChE in erythrocyte membranes and for BChE in the serum from rat and humans. For both soluble and membrane-bound forms of the enzyme from the three tissues, two components were discernible. In the brain, Km of component I (high affinity) and component II (low affinity) was somewhat higher in membrane-bound form than that of the soluble form components, while the Vmax values were significantly higher by about five fold. In the heart, Km of component II was lower in membrane-bound form than in the soluble form, while Vmax for both the components was about four to six fold higher in the membrane-bound form. In the liver, Vmax was marginally higher for the two components of the membrane-bound enzyme; the Km only of component I was higher by a factor of 2. In the rat erythrocyte membranes three components of AChE were present showing increasing values of Km and Vmax. In contrast, in the human erythrocyte membranes only two components could be detected; the one corresponding to component II of rat erythrocyte membranes was absent. In the rat serum two components of BChE were present while the human serum was found to possess three components. Component I of the human serum was missing in the rat serum. Temperature kinetics studies revealed that the Arrhenius plots were biphasic for most of the systems except for human serum. Membrane binding of the enzyme resulted in decreased energy of activation with shift in phase transition temperature (Tt) to near physiological temperature. 相似文献
85.
The 3' hydroxylation of kaempferol forms quercetin with an orthodihydroxy structure having two neighboring hydroxyl groups that could theoretically chelate with metal ions and mediate oxidative phenomena. Colorless flavonoids were purified by high pressure liquid chromatography (HPLC) and screened by diode array analysis. The accumulation of quercetin derivatives in Arabidopsis was coordinately regulated with flavonoid biosynthesis in a chalcone isomerase mutant having reduced flux through the biosynthetic pathway, but not within differing wild-type tissues, where seedling, floral, and leaf tissue have a reduced ratio of quercetin to kaempferol derivatives, respectively. The accumulation of lipid peroxidation products in kaempferol proficient mutant seedlings was indistinguishable from that in quercetin proficient wild-type seedlings, leaving no evidence for the role of quercetin antioxidants. However, laser scanning confocal microscopy revealed quercetin derivatives lining the tonoplast of diphenylboric acid 2-aminoethyl ester-stained Arabidopsis seedling tissue and floral papillae, and Norfluorazon induced oxidative stress decreased the most lipophilic of HPLC purified quercetin derivatives. Its potential involvement with lipophyllic oxidative phenomena may warrant further study. 相似文献
86.
John Ambler Emma Baker Lyndon Brown Paul Butler Dave Farr Karen Dunnet Darren Le Grand Diana Janus Darryl Jones Keith Menear Mark Mercer Garrick Smith Mark Talbot Morris Tweed 《Bioorganic & medicinal chemistry letters》1998,8(24):189-3588
The chemical optimisation of CGH1668 1 is described employing an in vivo model of absorption to determine the influence on bioavailability of single point modifications to five key molecular templates. The discovery of an orally bioavailable and selective thrombin inhibitor, 24, highlights the utility of this approach. 相似文献
87.
Charles H. Cohan Jake T. Neumann Kunjan R. Dave Aleksey Alekseyenko Marc Binkert Kenneth Stransky Hung Wen Lin Carol A. Barnes Clinton B. Wright Miguel A. Perez-Pinzon 《PloS one》2015,10(5)
Cardiopulmonary arrest is a leading cause of death and disability in the United States that usually occurs in the aged population. Cardiac arrest (CA) induces global ischemia, disrupting global cerebral circulation that results in ischemic brain injury and leads to cognitive impairments in survivors. Ischemia-induced neuronal damage in the hippocampus following CA can result in the impairment of cognitive function including spatial memory. In the present study, we used a model of asphyxial CA (ACA) in nine month old male Fischer 344 rats to investigate cognitive and synaptic deficits following mild global cerebral ischemia. These experiments were performed with the goals of 1) establishing a model of CA in nine month old middle-aged rats; and 2) to test the hypothesis that learning and memory deficits develop following mild global cerebral ischemia in middle-aged rats. To test this hypothesis, spatial memory assays (Barnes circular platform maze and contextual fear conditioning) and field recordings (long-term potentiation and paired-pulse facilitation) were performed. We show that following ACA in nine month old middle-aged rats, there is significant impairment in spatial memory formation, paired-pulse facilitation n dysfunction, and a reduction in the number of non-compromised hippocampal Cornu Ammonis 1 and subiculum neurons. In conclusion, nine month old animals undergoing cardiac arrest have impaired survival, deficits in spatial memory formation, and synaptic dysfunction. 相似文献
88.
Colon-specific drug delivery systems (CDDS) are desirable for the treatment of a range of local diseases such as ulcerative colitis, Crohn’s disease, irritable bowel syndrome, chronic pancreatitis, and colonic cancer. In addition, the colon can be a potential site for the systemic absorption of several drugs to treat non-colonic conditions. Drugs such as proteins and peptides that are known to degrade in the extreme gastric pH, if delivered to the colon intact, can be systemically absorbed by colonic mucosa. In order to achieve effective therapeutic outcomes, it is imperative that the designed delivery system specifically targets the drugs into the colon. Several formulation approaches have been explored in the development colon-targeted drug delivery systems. These approaches involve the use of formulation components that interact with one or more aspects of gastrointestinal (GI) physiology, such as the difference in the pH along the GI tract, the presence of colonic microflora, and enzymes, to achieve colon targeting. This article highlights the factors influencing colon-specific drug delivery and colonic bioavailability, and the limitations associated with CDDS. Further, the review provides a systematic discussion of various conventional, as well as relatively newer formulation approaches/technologies currently being utilized for the development of CDDS.KEY WORDS: colon targeting, factors affecting colon delivery, future trends, novel approaches, traditional approaches 相似文献
89.
Areti Gkourtsa Janny van den Burg Karin Strijbis Teja Avula Sietske Bijvoets Dave Timm Frans Hochstenbach Ben Distel 《Eukaryotic cell》2015,14(2):182-193
Membrane reshaping resides at the core of many important cellular processes, and among its mediators are the BAR (Bin, Amphiphysin, Rvs) domain-containing proteins. We have explored the diversity and function of the Rvs BAR proteins in Candida albicans and identified a novel family member, Rvs167-3 (orf19.1861). We show that Rvs167-3 specifically interacts with Rvs162 to form a stable BAR heterodimer able to bind liposomes in vitro. A second, distinct heterodimer is formed by the canonical BAR proteins Rvs161 and Rvs167. Purified Rvs161/Rvs167 complex also binds liposomes, indicating that C. albicans expresses two functional BAR heterodimers. We used live-cell imaging to localize green fluorescent protein (GFP)-tagged Rvs167-3 and Rvs167 and show that both proteins concentrate in small cortical spots. However, while Rvs167 strictly colocalizes with the endocytic marker protein Abp1, we do not observe any colocalization of Rvs167-3 with sites of endocytosis marked by Abp1. Furthermore, the rvs167-3Δ/Δ mutant is not defective in endocytosis and strains lacking Rvs167-3 or its partner Rvs162 do not display increased sensitivity to high salt concentrations or decreased cell wall integrity, phenotypes which have been observed for rvs167Δ/Δ and rvs161Δ/Δ strains and which are linked to endocytosis defects. Taken together, our results indicate different roles for the two BAR heterodimers in C. albicans: the canonical Rvs161/Rvs167 heterodimer functions in endocytosis, whereas the novel Rvs162/Rvs167-3 heterodimer seems not to be involved in this process. Nevertheless, despite their different roles, our phenotypic analysis revealed a genetic interaction between the two BAR heterodimers, suggesting that they may have related but distinct membrane-associated functions. 相似文献
90.
Melissa L. Potestio Jamie M. Boyd Sean M. Bagshaw Daren Heyland Peter Oxland Christopher J. Doig Dave Zygun Henry T. Stelfox 《PloS one》2015,10(11)