Bilayer-mediated assembly of cationic nanoparticles adsorbed to lipid bilayers: Insights from molecular simulations

Understanding interactions between functionalized gold nanoparticles (NPs) and lipid bilayers is essential for biomedical applications. Experiments have shown that NPs that are stable in solution can assemble into clusters when adsorbed to a lipid bilayer, suggesting that bilayer-mediated interactions facilitate assembly. In this work, we use coarse-grained molecular dynamics simulations to study bilayer-mediated interactions between NPs adsorbed to single- and multicomponent lipid bilayers. We perform unbiased simulations and umbrella sampling calculations using an implicit solvent force field to determine the thermodynamic contributions to assembly. We show that bilayer-mediated interactions drive the assembly of NPs into linear aggregates on liquid-disordered bilayers, which we attribute to a reduction in bilayer curvature. Similar bilayer-mediated interactions induce the alignment of NP clusters with phase boundaries in phase-separated bilayers. Together, these simulation results provide new physical insight into the balance of forces that dictate the assembly of charged NPs at multicomponent lipid bilayer interfaces.     

Cadaver lungs for transplantation. Effect of ventilation with alveolar gas

In an effort to increase the donor pool for lung transplantation (LTX), we have demonstrated the feasibility of LTX from circulation-arrested cadavers in a canine LTX model. We hypothesized that ventilation of the cadaver lung with alveolar gas (20% O2, 5% CO2, balance N2) (AG) would be superior to ventilation with 100% oxygen (O2) after circulatory arrest of the donor. Twelve mongrel dogs were intubated, heparinized and euthanized by pentothal injection and ventilated with AG (n=6) or O2 (n=6). Four hours later, donor animals underwent sternotomy, and the lungs were flushed with cold modified Euro-Collins solution, harvested, and stored inflated in ice slush. Left lung allotransplantation was performed, and recipients were made dependent o n the transplanted lung by occlusion of the contralateral bronchus and pulmonary artery. Recipient animals were ventilated with an FiO2 of 0.4 and followed for 8 hr. Total ischemic time was 7.9 hr for both groups. Pulmonary edema developed in all recipients of AG lungs; one recipient survived the 8-hr observation period with poor oxygenation. In contrast, three of six recipients of O2-ventilated lungs survived for 8-hr with excellent gas exchange. Specimens of donor lungs before and after transplant were evaluated histologically utilizing trypan blue exclusion as an indicator of cell viability. At the time of organ retrieval 4 hr after death, 6% of cells were nonviable in the O2-ventilated cadaver lungs. Circulation-arrested cadaver lungs ventilated with 100% O2 prior to organ retrieval have superior pulmonary function after transplant compared with lungs ventilated with AG. Ventilation of cadaver lungs with AG induces pulmonary injury in this model. retrieval of donor lungs from circulation-arrested cadavers has potential for increasing the pulmonary donor pool.     

Absence of detectable human herpesvirus 8 in the semen of human immunodeficiency virus-infected men without Kaposi's sarcoma

The prevalence of human herpesvirus 8 (HHV-8)/Kaposi's sarcoma (KS)-associated herpesvirus was investigated in the semen of 99 human immunodeficiency virus (HIV)-infected men (median CD4 cell count, 357/mm3) by use of a polymerase chain reaction (PCR) assay capable of detecting <10 copies of HHV-8 DNA. Of the subjects, 95 (96%) self-identified as men who have sex with men (MSM), and 3 had a history of clinical KS. Seminal cell specimens were negative for HHV-8 in 98 subjects. None of the 26 without KS (27.1% of 96 tested) who were seropositive for HHV-8 by IFA for latency-associated nuclear antigens had HHV-8 detected in their semen. The only subject with any evidence for seminal HHV-8 DNA was seropositive for HHV-8 and had active KS. HHV-8 was detected in 10 (10.4%) of 96 peripheral blood mononuclear cell specimens. The prevalence of HHV-8 DNA by PCR in semen of HIV-infected MSM without KS is low.     

Characterization and modeling of a noncollinearly phase-matchedfemtosecond optical parametric oscillator based on KTA and operating tobeyond 4 μm

We describe the design and operation of a critically phase-matched femtosecond optical parametric oscillator based on KTA. By employing a small pump-signal noncollinear angle, tuning of the idler to beyond 4 μm is achieved using a Ti:sapphire pump laser. A Gaussian-beam model is described which can be used to identify the optimal noncollinear phase-matching geometry. Idler and signal pulses are characterized fully both temporally and spectrally and interferometric autocorrelation data at 3.5 μm showing idler pulses of only eight optical cycles duration are presented     

Renal length in sickle cell disease: observations from a cohort study

Renal length has been measured by ultrasound in 237 subjects with homozygous sickle cell (SS) disease, 147 with sickle cell-hemoglobin C (SC) disease, and in 78 age-matched controls with a normal hemoglobin (AA) genotype. As expected, renal length increased with age in all genotypes but mean length was significantly greater in SS disease compared with SC disease (mean difference 4.3 mm after adjustment for height) and significantly greater in both genotypes than in AA controls (SS/AA difference 9.2 mm, SC/AA difference 5.0 mm after adjustment for height). Examination of relationships between renal length and some hematological indices (hemoglobin, fetal hemoglobin, reticulocyte counts, alpha thalassemia status) in SS or SC disease showed only a significant negative correlation with hemoglobin and positive correlation with reticulocyte count in SS disease. Further analysis suggested that the stronger relationship was between renal length and high reticulocyte count. The mechanism of renal enlargement is unknown although glomerular hypertrophy and increased renal blood volume are likely contributors.     

The region Ser333-Arg356 of the alpha-chain of human C4b-binding protein is involved in the binding of complement C4b

Human C4b-binding protein (C4BP) functions as a cofactor to factor I in the degradation of C4b and accelerates the decay rate of the C4b2a complex. In this study we describe a monoclonal antibody directed against the alpha-chain of C4BP that inhibits the binding of C4b to C4BP. In order to identify the structural domain of the alpha-chain of C4BP that interacts with C4b, tryptic fragments of C4BP were generated. Amino acid sequence analysis of the fragments revealed that the residues Ser333-Arg356 of the alpha-chain of C4BP contain the epitope of this antibody, and as a consequence, that this part of the alpha-chain of C4BP is likely to be involved in the interaction with C4b.     

The Tenckhoff catheter in acute renal failure

The results of a retrospective study of routine measurement of haemoglobin at the examination of one-year-old children at Gr?land mother and child clinic during 1989-91 showed that 37% of the children had anaemia. There was no difference between immigrants and the European population. There was no correlation between anaemia and sex in either of the population groups. This may imply that routine haemoglobin measurement should be generally introduced as part of the regular control of one-year-old children.     

Determinants of genital human papillomavirus infection among cytologically normal women attending the University of New Mexico student health center

OBJECTIVES: To confirm the risk factors for genital human papillomavirus (HPV) infection. GOAL OF THIS STUDY: To investigate risk factors for HPV detection apart from the correlated risk factors for cervical neoplasia. STUDY DESIGN: Cervical human papillomavirus (HPV) DNA was assessed in 357 cytologically normal women attending the University of New Mexico student health center. Cervical swab samples were obtained for HPV DNA detection and typing using a PCR-based DNA amplification system. Possible determinants of cervical HPV were examined including age, ethnicity, history of sexually transmitted disease, oral contraceptive use, smoking, age at first intercourse, lifetime number of sex partners, marital status, and history of pregnancy. RESULTS: A 44.3% overall prevalence of cervical HPV was observed. On univariate analysis, factors associated with increasing HPV prevalence included higher lifetime number of sex partners and single marital status. After adjustment for potential confounding variables, we found that HPV prevalence increased with higher lifetime number of sexual partners. CONCLUSION: These findings, along with those from the companion reports in this issue of the journal, support the sexual route of transmission of the virus.     

Effects of chronic U50,488H treatment on binding and mechanical responses of the rat hearts

The effects of chronic injection of U50,488H (trans-3,4-dichloro-N-[2-(1-pyrrolidinyl)cyclohexyl]benzeacetamidel++ +), a selective kappa opioid agonist, on the properties of the binding sites of tritiated U69593 [(5 alpha,7 alpha,8 beta)-(-)-N-methyl-N-(7-(1-pyrrolidinyl)-1-oxaspiro (4,5)dec-8-yl)benzeneacetamide], another selective kappa opioid agonist, and mechanical responses to U50,488H of the heart were studied. Rats received injection twice a day with U50,488H for 4 days. Binding studies on the crude membrane homogenates revealed that there was no change in maximum binding, but a significant increase in Kd after the treatment, indicating that the number of kappa binding sites remained unchanged whereas the affinity of the binding sites to kappa-agonist decreased. The study on the mechanical responses to U50,488H in the isolated perfused heart preparation showed that although the agonist at 10(-6) M caused MR2266 reversible reductions in heart rate and force of contraction as well as ventricular ectopic beat in the heart of rats in the control group, its effects were absent in the U50,488H-treated group, indicating the development of tolerance to the mechanical effects of U50,488H on the heart. The results indicate that the development of tolerance to the mechanical effects of a kappa-agonist after chronic treatment with the agonist was not accompanied by down-regulation, but only a slight and significant reduction in affinity of kappa binding sites in the rat heart.