C18:1 Methyl Ester Metathesis in [bmim][X] Type Ionic Liquids

The efficacy of [bmim][X] ionic liquids (ILs) (X = PF6−, BF4− and NTf2−) as reaction media for methyl oleate metathesis was compared with that of conventional organic solvents (PhCl, PhMe, DCM and DCE) using the well-defined first and second generation Grubbs precatalysts, RuCl2(PCy3)(L)(=CHPh) (L = PCy3 or H2IMes). Best catalytic performance, with excellent selectivity (>98%) at moderate reaction temperatures, was achieved in [bmim][X] ILs compared to conventional solvents. The effects of anion, reaction temperature, solvent polarity, solvent viscosity, and ligand-anion interaction on the reaction are also addressed

Preventing human immunodeficiency virus infection among sexual assault survivors in Cape Town, South Africa: an observational study.

We describe 131 South African sexual assault survivors offered HIV post-exposure prophylaxis (PEP). While the median days completed was 27 (IQR 27, 28), 34% stopped PEP or missed doses. Controlling for baseline symptoms, PEP was not associated with symptoms (OR = 1.30, 95% CI = 0.66, 2.64). Factors associated with unprotected sex included prior unprotected sex (OR = 6.46, 95% CI = 3.04, 13.74), time since the assault (OR = 1.33, 95% CI = 1.12, 1.57) and age (OR = 1.30, 95% CI = 1.08, 1.57). Trauma counseling was protective (OR = 0.18, 95% CI = 0.05, 0.58). Four instances of seroconversion were observed by 6 months (risk = 3.7%, 95% CI = 1.0, 9.1). Proactive follow-up is necessary to increase the likelihood of PEP completion and address the mental health and HIV risk needs of survivors. Adherence interventions and targeted risk reduction counseling should be provided to minimize HIV acquisition

Presence of extracellular DNA in candida albicans biofilm matrix and its role in biofilm structure and antifungal susceptibility

Biofilms are structurally complex microconsortia of surface adhering cells embedded within an extracellular matrix (ECM) composed of substances produced and secreted by cells or derived from cell lysis. One of the recently discovered bacterial biofilms ECM components is the extracellular DNA (eDNA). Although the investigation on eDNA in fungal biofilms is scarce, preliminary studies suggest that eDNA may play a role in biofilms formed by the opportunistic fungal pathogen Candida albicans. Thus, the present study aimed at determining the eDNA content of C. albicans SC5314 biofilm ECM and the effect of DNase I treatment on biofilm formation and biofilm cells susceptibility to antifungals, as indicators of the role of eDNA in C. albicans biofilms. Results from our experiments showed that the ECM of C. albicans biofilms formed under conditions of flow for 48 h contained 3045.4 ± 227.3 ng eDNA/mg of protein. Additionally, using a microtiter plate model, we observed that different DNase treatments (0.02 - 2 mg/ml) did not affect further biofilm development by C. albicans adherent cells. However, DNase (> 0.03 mg/ml) promoted a general biomass reduction on C. albicans preformed biofilms. Finally, DNase (0.13 mg/ml) did not change C. albicans biofilm cells susceptibility to fluconazole, but increased their susceptibility to amphotericin B and caspofungin, as indicated by the lower SMIC compared to biofilms grown without DNase. This work presents evidence for the role of eDNA in C. albicans biofilm integrity and antifungal resistance consistent with eDNA being a key element of the ECM

Game and player: C. albicans biofilm lifestyle and extracellular DNA

DNA is as a structural component of bacterial biofilms extracellular matrix (ECM). Although evidences have shown that DNA may play a role in C. albicans biofilms, further studies are required to understand the contribution of extracellular DNA (eDNA) in C. albicans biofilm lifestyle. Herein we aimed to determine the eDNA content of C. albicans SC5314 biofilm ECM and the effect of DNase I and exogenous DNA treatments on biofilm formation and biofilm cells susceptibility to antifungals. First, for eDNA estimation in C. albicans biofilm ECM, biofilms were formed under flow conditions for 48 h. ECM was isolated and its DNA and protein contents were determined. Second, DNase (0.02 - 2 mg/ml) and exogenous DNA (10 - 2560 ng/ml) were added at different stages of biofilm development (microtiter plate model under static conditions). The effect of 24 h treatments was evaluated in terms of biofilm biomass by crystal violet assay (A550). Third, for antifungal testing, biofilms (in 96-well plates) were challenged with amphotericin B (0.06 - 16 mg/l), caspofungin (0.008 to 2 mg/l), and fluconazole (4 - 1024 mg/l) alone or in combination with DNase (0.125 mg/ml) or exogenous DNA (320 ng/ml). Sessile minimum inhibitory concentrations (SMIC) were determined at 80 % inhibition compared to drug-free controls using the XTT reduction assay. RPMI medium was used in all the assays. On one hand, C. albicans biofilms ECM contained 3045.4 ± 227.3 ng eDNA/mg of protein. On the other hand, DNase or exogenous DNA treatments did not affect further biofilm development by C. albicans adherent cells. In contrast, DNase (> 0.03 mg/ml) promoted a general biomass reduction on C. albicans preformed biofilms, as indicated by the reduction of A550 compared with the control. Furthermore addition of exogenous DNA (> 160 ng/ml) to preformed biofilms led to an increase in biofilm biomass, similarly assessed by the higher A550 readings compared with control biofilms. Finally, DNase I (0.125 mg/ml) did not change C. albicans biofilm cells susceptibility to fluconazole, but increased their susceptibility to amphotericin B and caspofungin, as indicated by the lower SMIC compared to biofilms grown without DNase. In contrast, exogenous DNA (320 ng/ml) did not affect C. albicans biofilm cells susceptibility against these antifungals

Association of Central Arterial Stiffness and Pressure Pulsatility with Mild Cognitive Impairment and Dementia: The Atherosclerosis Risk in Communities Study-Neurocognitive Study (ARIC-NCS)

The association of central arterial stiffness and pressure pulsatility with mild cognitive impairment and dementia is not well characterized in the population-based setting

Metathesis of Fatty Acid Ester Derivatives in 1,1-Dialkyl and 1,2,3-Trialkyl Imidazolium Type Ionic Liquids

The self-metathesis of methyl oleate and methyl ricinoleate was carried out in the presence of ruthenium alkylidene catalysts 1–4 in [bmim] and [bdmim][X] type ionic liquids (RTILs) (X = PF6−, BF4− and NTf2−) using the gas chromatographic technique. Best catalytic performance was obtained in [bdmim][X] type ionic liquids when compared with [bmim][X] type ionic liquids. Catalyst recycling studies were also carried out in the room temperature ionic liquids (RTILs) with catalysts 1–4 in order to explore their possible industrial application

Dendritic Cell Mediated Delivery of Plasmid DNA Encoding LAMP/HIV-1 Gag Fusion Immunogen Enhances T Cell Epitope Responses in HLA DR4 Transgenic Mice

This report describes the identification and bioinformatics analysis of HLA-DR4-restricted HIV-1 Gag epitope peptides, and the application of dendritic cell mediated immunization of DNA plasmid constructs. BALB/c (H-2d) and HLA-DR4 (DRA1*0101, DRB1*0401) transgenic mice were immunized with immature dendritic cells transfected by a recombinant DNA plasmid encoding the lysosome-associated membrane protein-1/HIV-1 Gag (pLAMP/gag) chimera antigen. Three immunization protocols were compared: 1) primary subcutaneous immunization with 1×105 immature dendritic cells transfected by electroporation with the pLAMP/gag DNA plasmid, and a second subcutaneous immunization with the naked pLAMP/gag DNA plasmid; 2) primary immunization as above, and a second subcutaneous immunization with a pool of overlapping peptides spanning the HIV-1 Gag sequence; and 3) immunization twice by subcutaneous injection of the pLAMP/gag DNA plasmid. Primary immunization with pLAMP/gag-transfected dendritic cells elicited the greatest number of peptide specific T-cell responses, as measured by ex vivo IFN-γ ELISpot assay, both in BALB/c and HLA-DR4 transgenic mice. The pLAMP/gag-transfected dendritic cells prime and naked DNA boost immunization protocol also resulted in an increased apparent avidity of peptide in the ELISpot assay. Strikingly, 20 of 25 peptide-specific T-cell responses in the HLA-DR4 transgenic mice contained sequences that corresponded, entirely or partially to 18 of the 19 human HLA-DR4 epitopes listed in the HIV molecular immunology database. Selection of the most conserved epitope peptides as vaccine targets was facilitated by analysis of their representation and variability in all reported sequences. These data provide a model system that demonstrates a) the superiority of immunization with dendritic cells transfected with LAMP/gag plasmid DNA, as compared to naked DNA, b) the value of HLA transgenic mice as a model system for the identification and evaluation of epitope-based vaccine strategies, and c) the application of variability analysis across reported sequences in public databases for selection of historically conserved HIV epitopes as vaccine targets

Modeling seizures in the Human Phenotype Ontology according to contemporary ILAE concepts makes big phenotypic data tractable.

OBJECTIVE: The clinical features of epilepsy determine how it is defined, which in turn guides management. Therefore, consideration of the fundamental clinical entities that comprise an epilepsy is essential in the study of causes, trajectories, and treatment responses. The Human Phenotype Ontology (HPO) is used widely in clinical and research genetics for concise communication and modeling of clinical features, allowing extracted data to be harmonized using logical inference. We sought to redesign the HPO seizure subontology to improve its consistency with current epileptological concepts, supporting the use of large clinical data sets in high-throughput clinical and research genomics. METHODS: We created a new HPO seizure subontology based on the 2017 International League Against Epilepsy (ILAE) Operational Classification of Seizure Types, and integrated concepts of status epilepticus, febrile, reflex, and neonatal seizures at different levels of detail. We compared the HPO seizure subontology prior to, and following, our revision, according to the information that could be inferred about the seizures of 791 individuals from three independent cohorts: 2 previously published and 150 newly recruited individuals. Each cohort\u27s data were provided in a different format and harmonized using the two versions of the HPO. RESULTS: The new seizure subontology increased the number of descriptive concepts for seizures 5-fold. The number of seizure descriptors that could be annotated to the cohort increased by 40% and the total amount of information about individuals\u27 seizures increased by 38%. The most important qualitative difference was the relationship of focal to bilateral tonic-clonic seizure to generalized-onset and focal-onset seizures. SIGNIFICANCE: We have generated a detailed contemporary conceptual map for harmonization of clinical seizure data, implemented in the official 2020-12-07 HPO release and freely available at hpo.jax.org. This will help to overcome the phenotypic bottleneck in genomics, facilitate reuse of valuable data, and ultimately improve diagnostics and precision treatment of the epilepsies

学会抄録

<p><b>Pod-IVR Pharmacokinetics in macaques</b> (A) <i>In vivo</i> release of TDF and FTC from each pod-IVR (N = 6/time point) over the course of the efficacy study determined by residual drug measurements from the pod-IVRs that were in place for 19 weeks with IVRs exchanged for new devices every 2 weeks. The top and bottom of the boxes show the 75th and 25th percentiles, respectively, and the line in the middle of the box is the median value. The dotted lines show the mean (N = 6) <i>in vivo</i> release from identical pod-IVRs obtained during the PK study preceding this efficacy study [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0157061#pone.0157061.ref026" target="_blank">26</a>]. (B) <i>In vivo</i> release profile for individual macaques (T1-T6) shows variability between animals. (C) TDF, TFV, TDF+TFV, and FTC levels in vaginal fluids collected at each ring exchange. Vaginal fluids were collected with Weck-Cel sponges proximal and distal to the pod-IVR placement. The dotted horizontal lines correspond to the medians from our previous PK study [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0157061#pone.0157061.ref026" target="_blank">26</a>]. Left panels-proximal; Right panels-distal; Dots-median.</p