Configuration of influenza hemagglutinin fusion peptide monomers and oligomers in membranes

AbstractThe 20 N-terminal residues of the HA2 subunit of influenza hemagglutinin (HA), known as the fusion peptide, play a crucial role in membrane fusion. Molecular dynamics simulations with implicit solvation are employed here to study the structure and orientation of the fusion peptide in membranes. As a monomer the α-helical peptide adopts a shallow, slightly tilted orientation along the lipid tail–head group interface. The average angle of the peptide with respect to membrane plane is 12.4 °. We find that the kinked structure proposed on the basis of NMR data is not stable in our model because of the high energy cost related to the membrane insertion of polar groups. Because hemagglutinin-mediated membrane fusion is promoted by low pH, we examined the effect of protonation of the Glu and Asp residues. The configurations of the protonated peptides were slightly deeper in the membrane but at similar angles. Finally, because HA is a trimer, we modeled helical fusion peptide trimers. We find that oligomerization affects the insertion depth of the peptide and its orientation with respect to the membrane: a trimer exhibits equally favorable configurations in which some or all of the helices in the bundle insert obliquely deep into the membrane

Microscopic structure of oxygen defects in gallium arsenide

Accurate total-energy pseudopotential methods are used to study the structures, binding energies, and local vibrational modes of various models for the Ga-O-Ga defect in GaAs. We find that the previously proposed models, OAs (an off-centered substitutional oxygen in arsenic vacancy) and OI (an oxygen atom occupying a tetrahedral interstitial site), are inconsistent with experimental data. We introduce a model, (AsGa)2−OAs (two arsenic antisites and one off-centered substitutional oxygen in arsenic vacancy), the properties of which are in excellent agreement with experimental characterizations.Peer reviewe

Andreev reflection at QGP/CFL interface

In this letter we address the question of the phenomena of Andreev reflection between the cold quark-gluon plasma phase and CFL color superconductor. We show that there are two different types of reflections connected to the structure of the CFL phase. We also calculate the probability current at the interface and we show that it vanishes for energy of scattering quarks below the superconducting gap.Comment: 6 pages, 1 figure. Minor changes in the "Conclusions

The PNPLA3-I148M variant increases polyunsaturated triglycerides in human adipose tissue

Background & Aims The I148M variant in PNPLA3 is the major genetic risk factor for non-alcoholic fatty liver disease (NAFLD). The liver is enriched with polyunsaturated triglycerides (PUFA-TGs) in PNPLA3-I148M carriers. Gene expression data indicate that PNPLA3 is liver-specific in humans, but whether it functions in adipose tissue (AT) is unknown. We investigated whether PNPLA3-I148M modifies AT metabolism in human NAFLD. Methods Profiling of the AT lipidome and fasting serum non-esterified fatty acid (NEFA) composition was conducted in 125 volunteers (PNPLA3(148MM/MI), n = 63; PNPLA3(148II), n = 62). AT fatty acid composition was determined in 50 volunteers homozygous for the variant (PNPLA3(148MM), n = 25) or lacking the variant (PNPLA3(148II), n = 25). Whole-body insulin sensitivity of lipolysis was determined using [H-2(5)]glycerol, and PNPLA3 mRNA and protein levels were measured in subcutaneous AT and liver biopsies in a subset of the volunteers. Results PUFA-TGs were significantly increased in AT in carriers versus non-carriers of PNPLA3-I148M. The variant did not alter the rate of lipolysis or the composition of fasting serum NEFAs. PNPLA3 mRNA was 33-fold higher in the liver than in AT (P <.0001). In contrast, PNPLA3 protein levels per tissue protein were three-fold higher in AT than the liver (P <.0001) and nine-fold higher when related to whole-body AT and liver tissue masses (P <.0001). Conclusions Contrary to previous assumptions, PNPLA3 is highly abundant in AT. PNPLA3-I148M locally remodels AT TGs to become polyunsaturated as it does in the liver, without affecting lipolysis or composition of serum NEFAs. Changes in AT metabolism do not contribute to NAFLD in PNPLA3-I148M carriers.Peer reviewe

Clinical practice selectively follows acute appendicitis guidelines

Peer reviewe

Effect of Topological Defects on Buckling Behavior of Single-walled Carbon Nanotube

Molecular dynamic simulation method has been employed to consider the critical buckling force, pressure, and strain of pristine and defected single-walled carbon nanotube (SWCNT) under axial compression. Effects of length, radius, chirality, Stone–Wales (SW) defect, and single vacancy (SV) defect on buckling behavior of SWCNTs have been studied. Obtained results indicate that axial stability of SWCNT reduces significantly due to topological defects. Critical buckling strain is more susceptible to defects than critical buckling force. Both SW and SV defects decrease the buckling mode of SWCNT. Comparative approach of this study leads to more reliable design of nanostructures

Comparative Proteomic Analysis of Serum from Patients with Systemic Sclerosis and Sclerodermatous GVHD. Evidence of Defective Function of Factor H

BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease characterized by immunological and vascular abnormalities. Until now, the cause of SSc remains unclear. Sclerodermatous graft-versus-host disease (ScGVHD) is one of the most severe complications following bone marrow transplantation (BMT) for haematological disorders. Since the first cases, the similarity of ScGVHD to SSc has been reported. However, both diseases could have different etiopathogeneses. The objective of this study was to identify new serum biomarkers involved in SSc and ScGVHD. METHODOLOGY: Serum was obtained from patients with SSc and ScGVHD, patients without ScGVHD who received BMT for haematological disorders and healthy controls. Bi-dimensional electrophoresis (2D) was carried out to generate maps of serum proteins from patients and controls. The 2D maps underwent image analysis and differently expressed proteins were identified. Immuno-blot analysis and ELISA assay were used to validate the proteomic data. Hemolytic assay with sheep erythrocytes was performed to evaluate the capacity of Factor H (FH) to control complement activation on the cellular surface. FH binding to endothelial cells (ECs) was also analysed in order to assess possible dysfunctions of this protein. PRINCIPAL FINDINGS: Fourteen differentially expressed proteins were identified. We detected pneumococcal antibody cross-reacting with double stranded DNA in serum of all bone marrow transplanted patients with ScGVHD. We documented higher levels of FH in serum of SSc and ScGVHD patients compared healthy controls and increased sheep erythrocytes lysis after incubation with serum of diffuse SSc patients. In addition, we observed that FH binding to ECs was reduced when we used serum from these patients. CONCLUSIONS: The comparative proteomic analysis of serum from SSc and ScGVHD patients highlighted proteins involved in either promoting or maintaining an inflammatory state. We also found a defective function of Factor H, possibly associated with ECs damage

Clinical manifestations and outcome in Staphylococcus aureus endocarditis among injection drug users and nonaddicts: a prospective study of 74 patients

BACKGROUND: Endocarditis is a common complication in Staphylococcus aureus bacteremia (SAB). We compared risk factors, clinical manifestations, and outcome in a large, prospective cohort of patients with S. aureus endocarditis in injection drug users (IDUs) and in nonaddicts. METHODS: Four hundred and thirty consecutive adult patients with SAB were prospectively followed up for 3 months. Definite or possible endocarditis by modified Duke criteria was found in 74 patients: 20 patients were IDUs and 54 nonaddicts. RESULTS: Endocarditis was more common in SAB among drug abusers (46%) than in nonaddicts (14%) (odds ratio [OR], 5.12; 95% confidence interval [CI], 2.65–9.91; P < 0.001). IDUs were significantly younger (27 ± 15 vs 65 ± 15 years, P < 0.001), had less ultimately or rapidly fatal underlying diseases (0% vs 37%, P < 0.001) or predisposing heart diseases (20% vs 50%, P = 0.03), and their SAB was more often community-acquired (95% vs 39%, P < 0.001). Right-sided endocarditis was observed in 60% of IDUs whereas 93% of nonaddicts had left-sided involvement (P < 0.001). An extracardiac deep infection was found in 85% of IDUs and in 89% of nonaddicts (P = 0.70). Arterial thromboembolic events and severe sepsis were also equally common in both groups. There was no difference in mortality between the groups at 7 days, but at 3 months it was lower among IDUs (10%) compared with nonaddicts (39%) (OR, 5.73; 95% CI, 1.20–27.25; P = 0.02). CONCLUSION: S. aureus endocarditis in IDUs was associated with as high complication rates including extracardiac deep infections, thromboembolic events, or severe sepsis as in nonaddicts. Injection drug abuse in accordance with younger age and lack of underlying diseases were associated with lower mortality, but after adjusting by age and underlying diseases injection drug abuse was not significantly associated with mortality