Postmortem levels of native neopterin (D-erythro-neopterin) were measured in cerebral cortical samples from 44 human immunodeficiency virus type 1-infected and eight uninfected, nonneurological control patients. Cerebral cortical gray and white matter neopterin levels for the controls ranged from 0.5 to 7.2 pmol/mg of protein in contrast to neopterin levels in brains of the virus-infected patients, which frequently were more than threefold and occasionally more than 30-fold higher than mean control levels. Cortical neopterin levels did not correlate with severity of the acquired immunodeficiency syndrome dementia complex, but subcortical levels correlated with the presence of active human immunodeficiency virus type 1 infection, as reflected by pathological evidence of multinucleated giant cell encephalitis. Evidence of opportunistic cytomegalovirus infections in approximately 25% of the human immunodeficiency virus type 1-infected patients was associated with enhanced levels of neopterin in frontal cortex. 相似文献
DNA fork displacement rates were measured in three lines of Bloom's syndrome cells and in a normal diploid fibroblast line. Fork displacement rates in Bloom's cells were approx. 55–65% of the rate in normal fibroblasts. 相似文献
Decreasing the dietary intake of methionine exerts robust anti‐adiposity effects in rodents but modest effects in humans. Since cysteine can be synthesized from methionine, animal diets are formulated by decreasing methionine and eliminating cysteine. Such diets exert both methionine restriction (MR) and cysteine restriction (CR), that is, sulfur amino acid restriction (SAAR). Contrarily, SAAR diets formulated for human consumption included cysteine, and thus might have exerted only MR. Epidemiological studies positively correlate body adiposity with plasma cysteine but not methionine, suggesting that CR, but not MR, is responsible for the anti‐adiposity effects of SAAR. Whether this is true, and, if so, the underlying mechanisms are unknown. Using methionine‐ and cysteine‐titrated diets, we demonstrate that the anti‐adiposity effects of SAAR are due to CR. Data indicate that CR increases serinogenesis (serine biosynthesis from non‐glucose substrates) by diverting substrates from glyceroneogenesis, which is essential for fatty acid reesterification and triglyceride synthesis. Molecular data suggest that CR depletes hepatic glutathione and induces Nrf2 and its downstream targets Phgdh (the serine biosynthetic enzyme) and Pepck‐M. In mice, the magnitude of SAAR‐induced changes in molecular markers depended on dietary fat concentration (60% fat >10% fat), sex (males > females), and age‐at‐onset (young > adult). Our findings are translationally relevant as we found negative and positive correlations of plasma serine and cysteine, respectively, with triglycerides and metabolic syndrome criteria in a cross‐sectional epidemiological study. Controlled feeding of low‐SAA, high‐polyunsaturated fatty acid diets increased plasma serine in humans. Serinogenesis might be a target for treating hypertriglyceridemia. 相似文献
ObjectiveInfluenza A virus belongs to the most studied virus and its mutant initiates epidemic and pandemics outbreaks. Inoculation is the significant foundation to diminish the risk of infection. To prevent an incidence of influenza from the transmission, various practical approaches require more advancement and progress. More efforts and research must take in front to enhance vaccine efficacy.MethodsThe present research emphasizes the development and expansion of a universal vaccine for the influenza virus. Research focuses on vaccine design with high efficacy. In this study, numerous computational approaches were used, covering a wide range of elements and ideas in bioinformatics methodology. Various B and T-cell epitopic peptides derived from the Neuraminidase protein N1 are recognized by these approaches. With the implementation of numerous obtained databases and bioinformatics tools, the different immune framework methods of the conserved sequences of N1 neuraminidase were analyzed. NCBI databases were employed to retrieve amino acid sequences. The antigenic nature of the neuraminidase sequence was achieved by the VaxiJen server and Kolaskar and Tongaonkar method. After screening of various B and T cell epitopes, one efficient peptide each from B cell epitope and T cell epitopes was assessed for their antigenic determinant vaccine efficacy. Identical two B cell epitopes were recognized from the N1 protein when analyzed using B-cell epitope prediction servers. The detailed examination of amino acid sequences for interpretation of B and T cell epitopes was achieved with the help of the ABCPred and Immune Epitope Database.ResultsComputational immunology via immunoinformatic study exhibited RPNDKTG as having its high conservancy efficiency and demonstrated as a good antigenic, accessible surface hydrophilic B-cell epitope. Among T cell epitope analysis, YVNISNTNF was selected for being a conserved epitope. T cell epitope was also analyzed for its allergenicity and cytotoxicity evaluation. YVNISNTNF epitope was found to be a non-allergen and not toxic for cells as well. This T-cell epitope with maximum world populace coverages was scrutinized for its association with the HLA-DRB1*0401 molecule. Results from docking simulation analyses showed YVNISNTNF having lower binding energy, the radius of gyration (Rg), RMSD values, and RMSE values which make the protein structure more stable and increase its ability to become an epitopic peptide for influenza virus vaccination.ConclusionsWe propose that this epitope analysis may be successfully used as a measurement tool for the robustness of an antigen–antibody reaction between mutant strains in the annual design of the influenza vaccine. 相似文献
Verotoxin (VT) production was investigated in 11 human isolates of Escherichia coli O113:H21. Only 6 strains were found to produce VT and none produced classic heat-labile (LT) and/or heat-stable (ST) enterotoxins. Neutralization studies demonstrated antigenic heterogeneity of VT produced by these strains of E. coli O113. 相似文献
1. The relationship between plant morphology and the senses used by dispersal agents to find fruit was examined. 'Flagellichory' (fruit borne on pendulous structures), a costly morphology associated with dispersal by bats, is focused on. 2. Using Gurania spinulosa , a flagellichorous vine, and its major dispersal agent, Phyllostomus hastatus , the hypothesis was tested that flagellichory increases the conspicuousness of fruit to bats that use echolocation to find fruit. 3. The responses of wild-caught P. hastatus to various fruiting branch morphologies and fruit odour were recorded. Phyllostomus hastatus used echolocation rather than olfaction to detect fruit, and consistently chose fruit displayed on pendulous leafless branches, ignoring fruit held among leaves on horizontal branches. 4. By comparing echolocation signals with the distance between fruiting branches of G. spinulosa and surrounding vegetation, it was shown that pendulous fruiting branches present clear, clutter-free targets that can be detected by echolocating bats. This is the first demonstration of neotropical frugivorous bats using echolocation to find fruit. 相似文献
Most textbook knowledge on ventricular repolarization is based on animal data rather than on data from the in vivo human heart. Yet, these data have been extrapolated to the human heart, often without an appropriate caveat. Here, we review multiple aspects of repolarization, from basic membrane currents to cellular aspects including extrinsic factors such as the effects of the sympathetic nervous system. We critically discuss some mechanistic aspects of the genesis of the T-wave of the ECG in the human heart.
Obviously, the T-wave results from the summation of repolarization all over the heart. The T-wave in a local electrogram ideally reflects local repolarization. The repolarization moment is composed of the moment of local activation plus local action potential duration (APD) at 90% repolarization (APD90). The duration of the latter largely depends on the balance between L-type Ca2+ current and the delayed rectifier currents. Generally speaking, there is an inverse relationship between local activation time and local APD90, leading to less dispersion in repolarization moments than in activation moments or in APD90. In transmural direction, the time needed for activation from endocardium toward epicardium has been considered to be overcompensated by shorter APD90 at the epicardium, leading to the earliest repolarization at the subepicardium. In addition, mid-myocardial cells would display the latest repolarization moments. The sparse human data available, however, do not show any transmural dispersion in repolarization moment. Also, the effect of adrenergic stimulation on APD90 has been studied mainly in animals. Again, sparse human data suggest that the effect of adrenergic stimulation is different in the human heart compared to many other mammalian hearts. Finally, aspects of the long QT syndrome are discussed, because this intrinsic genetic disease results from repolarization disorders with extrinsic aspects. 相似文献