Autonomic nervous nonlinear interactions lead to frequency modulation between low- and high-frequency bands of the heart rate variability spectrum

Cardiac sympathetic and parasympathetic neural activities have been found to interact with each other to efficiently regulate the heart rate and maintain homeostasis. Quantitative and noninvasive methods used to detect the presence of interactions have been lacking, however. This may be because interactions among autonomic nervous systems are nonlinear and nonstationary. The goal of this work was to identify nonlinear interactions between the sympathetic and parasympathetic nervous systems in the form of frequency and amplitude modulations in human heart rate data. To this end, wavelet analysis was performed, followed by frequency analysis of the resultant wavelet decomposed signals in several frequency brackets defined as very low frequency (f < 0.04 Hz), low frequency (LF; 0.04-0.15 Hz), and high frequency (HF; 0.15-0.4 Hz). Our analysis suggests that the HF band is significantly modulated by the LF band in the heart rate data obtained in both supine and upright body positions. The strength of modulations is stronger in the upright than supine position, which is consistent with elevated sympathetic nervous activities in the upright position. Furthermore, significantly stronger frequency modulation than in the control condition was also observed with the cold pressor test. The results with the cold pressor test, as well as the body position experiments, further demonstrate that the frequency modulation between LF and HF is most likely due to sympathetic and parasympathetic nervous interactions during sympathetic activations. The modulation phenomenon suggests that the parasympathetic nervous system is frequency modulated by the sympathetic nervous system. In this study, there was no evidence of amplitude modulation among these frequencies.     

Regional pulmonary blood flow in dogs by 4D-X-ray CT.

ECG-triggered computed tomography (CT) was used during passage of iodinated contrast to determine regional pulmonary blood flow (PBF) in anesthetized prone/supine dogs. PBF was evaluated as a function of height within the lung (supine and prone) as a function of various normalization methods: raw unit volume data (PBFraw) or PBF normalized to regional fraction air (PBFair), fractional non-air (PBFgm), or relative number of alveoli (PBFalv). The coefficient of variation of PBFraw, PBFair, PBFalv, and PBFgm ranged between 30 and 50% in both lungs and both body postures. The position of maximal flow along the height of the lung (MFP) was calculated for PBFraw, PBFair, PBFalv, and PBFgm. Only PBFgm showed a significantly different MFP height supine vs. prone (whole lung: 2.60 +/- 1.08 cm supine vs. 5.08 +/- 1.61 cm prone, P < 0.01). Mean slopes (ml/min/gm water content/cm) of PBFgm were steeper supine vs. prone in the right (RL) but not left lung (LL) (RL: -0.65 +/- 0.29 supine vs. -0.26 +/- 0.25 prone, P < 0.02; LL: -0.47 +/- 0.21 supine vs. -0.32 +/- 0.26 prone, P > 0.10). Mean slopes of PBFgm vs. vertical lung height were not different prone vs. supine above this vertical height of MFP (VMFP), but PBFgm slopes were steeper in the supine position below the VMFP in the RL. We conclude that PBFgm distribution was posture dependent in RL but not LL. Support of the heart may play a role. We demonstrate that normalization factors can lead to differing attributions of gravitational effects on PBF heterogeneity.     

Studies of the binding of ethidium bromide to cells before and after enzyme treatment

Summary Binding of ethidium bromide (EB) to cells before and after HCl, pepsin and RNase treatment was investigated by spectrophotometric and fluorimetric methods. Binding isotherms, calculated with the McGheevon Hippel equation, taking EB as a non-interacting ligand, revealed the influence of these treatments on the fluorescence characteristics of the cells which were measured by flow-through cytofluorimetry. Thus pepsin- and RNase-treated cells have a reduced intercalation capacity due to the loss of cytoplasmic RNA and RNA hydrolysis, respectively. HCl alone, or in association with pepsin, increased the equilibrium constant K considerably. Thus at low free EB concentrations the enhanced EB affinity of acid-pretreated cells generates a high fluorescence intensity, by comparison with treatments at neutral pH. This result contradicts the interpretation of high EB binding to acid pretreated cells which is commonly believed to be due to hydrolytic histone removal from potential intercalation sites.With increasing free EB concentrations the fluorescence intensities of RNase- and pepsin-treated cells culminate at the same level due to their almost identical intercalation capacities. Consequently, quantitative DNA analysis of pretreated cell suspensions with EB can only be performed if the alteration, induced by the pretreatment, has previously been studied.     

A proteomic analysis of thioacetamide-induced hepatotoxicity and cirrhosis in rat livers

Thioacetamide (TAA) administration is an established technique for generating rat models of liver fibrosis and cirrhosis. Oxidative stress is believed to be involved as TAA-induced liver fibrosis is initiated by thioacetamide S-oxide, which is derived from the biotransformation of TAA by the microsomal flavine-adenine dinucleotide (FAD)-containing monooxygense (FMO) and cytochrome P450 systems. A two-dimensional gel electrophoresis-mass spectrometry approach was applied to analyze the protein profiles of livers of rats administered with sublethal doses of TAA for 3, 6 and 10 weeks respectively. With this approach, 59 protein spots whose expression levels changed significantly upon TAA administration were identified, including three novel proteins. These proteins were then sorted according to their common biochemical properties and functions, so that pathways involved in the pathogenesis of rat liver fibrosis due to TAA-induced toxicity could be elucidated. As a result, it was found that TAA-administration down-regulated the enzymes of the primary metabolic pathways such as fatty acid beta-oxidation, branched chain amino acids and methionine breakdown. This phenomenon is suggestive of the depletion of succinyl-CoA which affects heme and iron metabolism. Up-regulated proteins, on the other hand, are related to oxidative stress and lipid peroxidation. Finally, these proteomics data and the data obtained from the scientific literature were integrated into an "overview model" for TAA-induced liver cirrhosis. This model could now serve as a useful resource for researchers working in the same area.     

Generation of a cell culture-adapted hepatitis C virus with longer half life at physiological temperature

Background

We previously reported infectious HCV clones that contain the convenient reporters, green fluorescent protein (GFP) and Renilla luciferase (Rluc), in the NS5a-coding sequence. Although these viruses were useful in monitoring viral proliferation and screening of anti-HCV drugs, the infectivity and yield of the viruses were low.

Methodology/Principal Findings

In order to obtain a highly efficient HCV cultivation system, we transfected Huh7.5.1 cells [1] with JFH 5a-GFP RNA and then cultivated cells for 20 days. We found a highly infectious HCV clone containing two cell culture-adapted mutations. Two cell culture-adapted mutations which were responsible for the increased viral infectivity were located in E2 and p7 protein coding regions. The viral titer of the variant was ∼100-fold higher than that of the parental virus. The mutation in the E2 protein increased the viability of virus at 37°C by acquiring prolonged interaction capability with a HCV receptor CD81. The wild-type and p7-mutated virus had a half-life of ∼2.5 to 3 hours at 37°C. In contrast, the half-life of viruses, which contained E2 mutation singly and combination with the p7 mutation, was 5 to 6 hours at 37°C. The mutation in the p7 protein, either singly or in combination with the E2 mutation, enhanced infectious virus production about 10–50-fold by facilitating an early step of virion production.

Conclusion/Significance

The mutation in the E2 protein generated by the culture system increases virion viability at 37°C. The adaptive mutation in the p7 protein facilitates an earlier stage of virus production, such as virus assembly and/or morphogenesis. These reporter-containing HCV viruses harboring adaptive mutations are useful in investigations of the viral life cycle and for developing anti-viral agents against HCV.     

Adeno-associated virus Rep78 binds to E2-responsive element 1 of bovine papillomavirus type 1

Adeno-associated virus type-2 (AAV-2) is a helper-dependent parvovirus that has been implicated in the inhibition of replication and oncogenic transformation of bovine papillomavirus type-1 (BPV-1) and other transforming DNA viruses. Previous studies have suggested that the Rep78 protein of AAV-2 is a key player mediating this effect. In this report we have analyzed the effect of AAV-2 Rep78 protein on the regulation of gene expression of a reporter gene under the control of the long control region (LCR) of BPV-1. Our results show that Rep78 is capable of down-regulating the promoter activity of the LCR in vivo in tissue culture cells. Inhibition of LCR activity in vivo suggested the need for Rep78 to bind to a region of the LCR promoter spanning the E2-responsive elements of BPV-1. This observation was further confirmed in vitro with gel shift assays showing specific binding of Rep78 to DNA oligonucleotides containing E2-responsive element 1 (E2RE1) sequences of BPV-1 LCR. Our results expand the understanding of the mechanism of trans-regulation mediated by Rep78 and involving this protein and DNA sequences with complex secondary structure.     

Effect of low-xenon and krypton supplementation on signal/noise of regional CT-based ventilation measurements.

Xenon computed tomography (Xe-CT) is used to estimate regional ventilation by measuring regional attenuation changes over multiple breaths while rebreathing a constant Xe concentration ([Xe]). Xe-CT has potential human applications, although anesthetic properties limit [Xe] to 相似文献   

Construction of CoP/NiCoP Nanotadpoles Heterojunction Interface for Wide pH Hydrogen Evolution Electrocatalysis and Supercapacitor

Constructing well defined nanostructures is promising but still challenging for high‐efficiency catalysts for hydrogen evolution reaction (HER) and energy storage. Herein, utilizing the differences in surface energies between (111) facets of CoP and NiCoP, a novel CoP/NiCoP heterojunction is designed and synthesized with a nanotadpoles (NTs)‐like morphology via a solid‐state phase transformation strategy. By effective interface construction, the disorder in terms of electronic structure and coordination environment at the interface in CoP/NiCoP NTs is created, which leads to dramatically elevated HER performance within a wide pH range. Theoretical calculations prove that an optimized proton chemisorption and H₂O dissociation are achieved by an optimized phosphide polymorph at the interface, accelerating the HER reaction. The CoP/NiCoP NTs are also proved to be excellent candidates for use in supercapacitors (SCs) with a high specific capacitance (1106.2 F g^?1 at 1 A g^?1) and good cycling stability (nearly 100% initial capacity retention after 1000 cycles). An asymmetric supercapacitor shows a high energy density (145 F g^?1 at 1 A g^?1) and good cycling stability (capacitance retention is 95% after 3200 cycles). This work provides new insights into the catalyst design for electrocatalytic and energy storage applications.