HIV Replication Enhances Production of Free Fatty Acids, Low Density Lipoproteins and Many Key Proteins Involved in Lipid Metabolism: A Proteomics Study

BACKGROUND: HIV-infected patients develop multiple metabolic abnormalities including insulin resistance, lipodystrophy and dyslipidemia. Although progression of these disorders has been associated with the use of various protease inhibitors and other antiretroviral drugs, HIV-infected individuals who have not received these treatments also develop lipid abnormalities albeit to a lesser extent. How HIV alters lipid metabolism in an infected cell and what molecular changes are affected through protein interaction pathways are not well-understood. RESULTS: Since many genetic, epigenetic, dietary and other factors influence lipid metabolism in vivo, we have chosen to study genome-wide changes in the proteomes of a human T-cell line before and after HIV infection in order to circumvent computational problems associated with multiple variables. Four separate experiments were conducted including one that compared 14 different time points over a period of >3 months. By subtractive analyses of protein profiles overtime, several hundred differentially expressed proteins were identified in HIV-infected cells by mass spectrometry and each protein was scrutinized for its biological functions by using various bioinformatics programs. Herein, we report 18 HIV-modulated proteins and their interaction pathways that enhance fatty acid synthesis, increase low density lipoproteins (triglycerides), dysregulate lipid transport, oxidize lipids, and alter cellular lipid metabolism. CONCLUSIONS: We conclude that HIV replication alone (i.e. without any influence of antiviral drugs, or other human genetic factors), can induce novel cellular enzymes and proteins that are significantly associated with biologically relevant processes involved in lipid synthesis, transport and metabolism (p = <0.0002-0.01). Translational and clinical studies on the newly discovered proteins may now shed light on how some of these proteins may be useful for early diagnosis of individuals who might be at high risk for developing lipid-related disorders. The target proteins could then be used for future studies in the development of inhibitors for preventing lipid-metabolic anomalies. This is the first direct evidence that HIV-modulates production of proteins that are significantly involved in disrupting the normal lipid-metabolic pathways

Acoustic emission study on the effect of notch shape and temperature on elastic energy release during impact testing of 17Mn1Si pipe steel

Main fracture mechanisms are determined in 17Mn1Si steel during impact Charpy testing of specimens with three types of notches at different test temperatures covering ductile-to-brittle transition. The influence of the notch shape on the amount of expended mechanical energy (according to the loading diagram) and released elastic energy (according to the recorded acoustic emission signal) is analyzed. A combined application of fracture mechanics and acoustic emission methods is proven effective for better understanding of dynamic fracture and ductile-to-brittle transition from the viewpoint of energy-based approaches to crack initiation and propagation. It is suggested that the link between the AE signal and the ductile-to-brittle transition in dynamic loading can be established to develop a tool for in situ characterization of the fracture process

Influence of energy dissipation at the interphase boundaries on impact fracture behaviour of a plain carbon steel

The paper deals with the impact deformation and fracture behaviour of commercial plain carbon pipe steel 17Mn1Si. The explicit account of the internal grain structure, temperature and geometry of the notch have been made in theoretical physical mesomechanics formulation aiming at in depth understanding of the role of strain energy factors in dynamic fracture. Theoretical method of excitable cellular automata and laboratory impact bending tests followed by fractographic analysis were paired with time–frequency analysis of acoustic emission accompanying local deformation and fracture processes. It was shown that formulation of the crack opening criterion under dynamic loading conditions should explicitly account for rotation energy accumulation and incorporate the microscopic temporal and spatial details of defect generation from internal (grain) boundaries. A fairly good agreement has been found between the strain energy characteristics obtained from mechanical loading data and independently measured acoustic emission signal being distinguished in terms of consumed and released energy. The impact toughness almost linearly decreased with temperature, which was consistent with fractographic observations. At the stage of crack initiation, when the energy dissipation processes at the internal structure elements significantly affect the initiation of dynamic fracture, the acoustic emission energy reduced in proportion to the expended mechanical energy, which considerably decreased with temperature. The vital role of the energy release at interface/grain boundaries and its decreased significance with decreasing temperature was demonstrated both in numeric simulations and in dynamic experiments

The formation of the superheavy hydrogen isotope H-6 in the absorption of stopped pi(-)-mesons by nuclei

An experimental search for the superheavy hydrogen isotope H-6 was conducted through studying the absorption of stopped pi(-)-mesons by Be-9 and B-11 nuclei. A structure in the missing mass spectrum caused by the resonance states of H-6 was observed in three reaction channels, namely, Be-9(pi(-), pd)X, B-11(pi(-), d(3)He)X, and B-11(pi(-), p(4)He)X. The parameters of the lowest state E-r = 6.6 +/- 0.7 MeV and Gamma = 5.5 +/- 2.0 MeV (E-r is the resonance energy with respect to the disintegration into the triton and three neutrons) are evidence that H-6 is a more weakly bound system than H-4 and H-5. Three excited states of H-6 were observed. Their resonance levels (E-1r = 10.7 +/- 0.7 MeV, Gamma(1r) = 4 +/- 2 MeV, E-2r = 15.3 +/- 0.7 MeV, Gamma(2r) = 3 +/- 2 MeV, and E-3r = 21.3 +/- 0.4 MeV, Gamma(3r) = 3.5 +/- 1.0 MeV) are energetically capable of disintegrating into six free nucleons. (C) 2003 MAIK "Nauka / Interperiodica"

The formation of the superheavy hydrogen isotope H-6 in the absorption of stopped pi(-)-mesons by nuclei

An experimental search for the superheavy hydrogen isotope H-6 was conducted through studying the absorption of stopped pi(-)-mesons by Be-9 and B-11 nuclei. A structure in the missing mass spectrum caused by the resonance states of H-6 was observed in three reaction channels, namely, Be-9(pi(-), pd)X, B-11(pi(-), d(3)He)X, and B-11(pi(-), p(4)He)X. The parameters of the lowest state E-r = 6.6 +/- 0.7 MeV and Gamma = 5.5 +/- 2.0 MeV (E-r is the resonance energy with respect to the disintegration into the triton and three neutrons) are evidence that H-6 is a more weakly bound system than H-4 and H-5. Three excited states of H-6 were observed. Their resonance levels (E-1r = 10.7 +/- 0.7 MeV, Gamma(1r) = 4 +/- 2 MeV, E-2r = 15.3 +/- 0.7 MeV, Gamma(2r) = 3 +/- 2 MeV, and E-3r = 21.3 +/- 0.4 MeV, Gamma(3r) = 3.5 +/- 1.0 MeV) are energetically capable of disintegrating into six free nucleons. (C) 2003 MAIK "Nauka / Interperiodica"