CXCR4 utilization is sufficient to trigger CD4+ T cell depletion in HIV-1-infected human lymphoid tissue

The human chemokine receptors CCR5 and CXCR4 have emerged as the predominant cofactors, along with CD4, for cellular entry of HIV-1 in vivo whereas the contribution of other chemokine receptors to HIV disease has not been yet determined. CCR5-specific (R5) viruses predominate during primary HIV-1 infection whereas viruses with specificity for CXCR4 (R5/X4 or X4 viruses) often emerge in late stages of HIV disease. The evolution of X4 viruses is associated with a rapid decline in CD4+ T cells, although a causative relationship between viral tropism and CD4+ T cell depletion has not yet been proven. To rigorously test this relationship, we assessed CD4+ T cell depletion in suspensions of human peripheral blood mononuclear cells and in explants of human lymphoid tissue on exposure to paired viruses that are genetically identical (isogenic) except for select envelope determinants specifying reciprocal tropism for CXCR4 or CCR5. In both systems, X4 HIV-1 massively depleted CD4+ lymphocytes whereas matched R5 viruses depleted such cells only mildly despite comparable viral replication kinetics. These findings demonstrate that the coreceptor specificities of HIV-1 are a causal factor in CD4+ T cell depletion ex vivo and strongly support the hypothesis that the evolution of viral envelope leading to usage of CXCR4 in vivo accelerates loss of CD4+ T cells, causing immunodeficiency.     

Nutritional Approaches as a Treatment for Impaired Bone Growth and Quality Following the Consumption of Ultra-Processed Food

The severe impairment of bone development and quality was recently described as a new target for unbalanced ultra-processed food (UPF). Here, we describe nutritional approaches to repair this skeletal impairment in rats: supplementation with micro-nutrients and a rescue approach and switching the UPF to balanced nutrition during the growth period. The positive effect of supplementation with multi-vitamins and minerals on bone growth and quality was followed by the formation of mineral deposits on the rats’ kidneys and modifications in the expression of genes involved in inflammation and vitamin-D metabolism, demonstrating the cost of supplementation. Short and prolonged rescue improved trabecular parameters but incompletely improved the cortical parameters and the mechanical performance of the femur. Cortical porosity and cartilaginous lesions in the growth-plate were still detected one week after rescue and were reduced to normal levels 3 weeks after rescue. These findings highlight bone as a target for the effect of UPF and emphasize the importance of a balanced diet, especially during growth.     

Layered Al2O3-TiO2 compositedielectric resonators

Aluminium oxide displays a very low tanδ at microwave frequencies. It also possesses a remarkably high thermal conductivity, ideal for heat dissipation in high power satellite filters. However, its temperature coefficient of the resonant frequency (τ_f) is approximately 60 ppm/K. It is shown that the application of a film of titanium oxide which has a T_f of opposite sign (45O ppm/K) produces a composite in which the τ_f can be tuned to be zero over a wide temperature range. The tanδ of the composite at zero T_f is 3.3×10⁵ (Q=30000) at room temperature and at 10 GHz     

Effects of monovalent cations on the competitive adsorption of perfluoroalkyl acids by kaolinite: experimental studies and modeling

Our hypothesis that longer-chained perfluoroalkyl acids (PFAAs) outcompete shorter-chained PFAAs during adsorption was tested in this study, wherein the adsorption interactions of six frequently detected PFAAs with kaolinite clay were modeled and examined experimentally using various suspension compositions. Competitive adsorption of PFAAs on the kaolinite surface was observed for the first time, and longer-chained PFAAs outcompeted those with a shorter chain. The electrostatic repulsion between adsorbed PFAA molecules is a primary inhibitory factor in PFAA adsorption. An increase in aqueous sodium or hydrogen ion concentration weakened electrostatic repulsions and changed the adsorption free energy. Therefore, the adsorption of a shorter-chained PFAA with weaker hydrophobicity could occur at high sodium or hydrogen ion concentrations. The experimental and modeling data suggest that the adsorption of shorter-chained PFAAs (≤4 perfluorinated carbons) in freshwater with a typical ionic strength of 10(-2.5) is not thermodynamically favorable. Furthermore, by measuring the electrokinetic potential of kaolinite suspension in the presence of PFAAs, we found that the kaolinite surface became more negatively charged because of the adsorption of PFAAs. This observation indicates that the adsorbed PFAA molecules were within the electrical double layer of the kaolinite surface and that they contributed to the potential at the slipping plane. The possible alignments of adsorbed PFAA molecules on the kaolinite surface were then proposed.     

Analysis of Volatile Organic Compounds in Human Saliva by a Static Sorptive Extraction Method and Gas Chromatography-Mass Spectrometry

Human saliva not only helps control oral health (with anti-microbial proteins), but it may also play a role in chemical communication. As is the case with other mammalian species, human saliva contains peptides, proteins, and numerous volatile organic compounds (VOCs). A high-throughput analytical method is described for profiling a large number of saliva samples to screen the profiles of VOCs. Saliva samples were collected in a non-stimulated fashion. The method utilized static stir bar extraction followed by gas chromatography-mass spectrometry (GC-MS). The method provided excellent reproducibility for a wide range of salivary compounds, including alcohols, aldehydes, ketones, carboxylic acids, esters, amines, amides, lactones, and hydrocarbons. Furthermore, substantial overlap of salivary VOCs and the previously reported skin VOCs in the same subject group was found in this study by using pattern recognition analyses. Sensitivity, precision, and reproducibility of the method suggest that this technique has potential in physiological, metabolomic, pharmacokinetic, forensic, and toxicological studies of small organic compounds where a large number of human saliva samples are involved.     

Single injection thermodilution. A flow-corrected method

BACKGROUND: Application of the Stewart-Hamilton equation in the thermodilution technique requires flow to be constant. In patients in whom ventilation of the lungs is controlled, flow modulations may occur leading to large errors in the estimation of mean cardiac output. METHODS: To eliminate these errors, a modified equation was developed. The resulting flow-corrected equation needs an additional measure of the relative changes of blood flow during the period of the dilution curve. Relative flow was computed from the pulmonary artery pressure with use of the pulse contour method. Measurements were obtained in 16 patients undergoing elective coronary artery bypass surgery. In 11 patients (group A), pulmonary artery pressure was measured with a catheter tip transducer, in a partially overlapping group of 11 patients (group B), it was measured with a fluid-filled system. For reference cardiac output we used the proven method of four uncorrected thermodilution estimates equally spread over the ventilatory cycle. RESULTS: A total of 208 cardiac output estimates was obtained in group A, and 228 in group B. In group B, 48 estimates could not be corrected because of insufficient pulmonary artery pressure waveform quality from the fluid-filled system. Individual uncorrected Stewart-Hamilton estimates showed a large variability with respect to their mean. In group A, mean cardiac output was 5.01 l/min with a standard deviation of 0.53 l/min, or 10.6%. After flow correction, this scatter decreased to 5.0% (P < 0.0001). With no bias, the corresponding limits of agreement decreased from +/- 1.06 to +/- 0.5 l/min after flow correction. In group B, the scatter decreased similarly and the limits of agreement also became +/- 0.5 l/min after flow correction. CONCLUSION: It was concluded that a single thermodilution cardiac output estimate using the flow-corrected equation is clinically feasible. This is obtained at the cost of a more complex computation and an extra pressure measurement, which often is already available. With this technique it is possible to reduce the fluid load to the patient considerably.     

Comparison of ribotyping and arbitrarily primed PCR for molecular typing of Salmonella enterica and relationships between strains on the basis of these molecular markers

Arbitrarily primed PCR (AP-PCR) using a discriminatory 10-mer primer and an automated EcoRI ribotyping technique (Riboprinter) were compared for their ability to discriminate between 100 serovars of Salmonella, including multiple isolates representing Salm. Enteritidis PT4 and Salm. Typhimurium DT104. Profiles generated by each method were subjected to numerical analysis using GelCompar software, resulting in the construction of phylogenetic trees and calculation of Simpson's numerical index of diversity (DI). Both methods were highly discriminatory for isolates of Salmonella (Ribotype DI = 0.990, AP-PCR DI = 0.997) with EcoRI ribotyping proving more discriminatory than AP-PCR for isolates of Typhimurium DT104. The population structure was found to be clonal by numerical analysis of markers generated by both methods with serovars being polyphyletic in some cases and grouped in a single cluster in others. No absolute correlation was observed in the relationships between strains formed on the basis of ribo- and AP-PCR markers and serological characteristics.