The incidence of dengue fever epidemics has increased dramatically over the last few decades. However, no vaccine or antiviral therapies are available. Therefore, the need for safe and effective antiviral drugs has become imperative. The entry of dengue virus into a host cell is mediated by its major envelope (E) protein. The crystal structure of the E protein reveals a hydrophobic pocket that is presumably important for low-pHmediated membrane fusion. High-throughput docking with this hydrophobic pocket was performed, and hits were evaluated in cell-based assays. Compound 6 was identified as one of the inhibitors and had an average 50% effective concentration of 119 nM against dengue virus serotype 2 in a human cell line. Mechanism-ofaction studies demonstrated that compound 6 acts at an early stage during dengue virus infection. It arrests dengue virus in vesicles that colocalize with endocytosed dextran and inhibits NS3 expression. The inhibitors described in this report can serve as molecular probes for the study of the entry of flavivirus into host cells.

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Background Bone bruising is commonly observed on magnetic resonance imaging (MRI) after non-contact anterior cruciate ligament (ACL) injury. Objectives The primary objective of this study was to determine if the location and prevalence of tibial and femoral bone bruises after ACL injury can be explained by specific injury mechanism(s). The secondary objective was to determine whether the bone bruise literature supports sex-specific injury mechanism(s). We hypothesized that most studies would report bone bruising in the lateral femoral condyle (LFC) and on the posterior lateral tibial plateau (LTP). Methods MEDLINE, PubMed, and SCOPUS were searched for studies that reported bone bruise prevalence and location in ACL-injured subjects. Sex differences in bone bruise patterns were assessed. Time from injury to imaging was assessed to account for confounding effects on bone bruise size and location. Results Thirty-eight studies met the inclusion/exclusion criteria. Anterior-posterior location of bone bruises within the tibiofemoral compartment was assessed in eleven studies. Only five of these studies reported bone bruise locations on both the tibia and the femur. The most common bone bruise combination in all five studies was on the LFC and the posterior LTP. Sex differences were only assessed in three studies, and only one reported significantly greater prevalence of LTP bruising in females. Conclusion Bone bruise patterns in the current literature support a valgus-driven ACL injury mechanism. However, more studies should report the specific locations of tibial and femoral bone bruises. There is insufficient evidence in the literature to determine whether there are sex-specific bone bruise patterns in ACL-injured subjects.

Wax esters are major constituents of the surface lipids in many terrestrial arthropods, but their study is complicated by their diversity. We developed a procedure for quantifying isomers in mixtures of straight-chain saturated and unsaturated wax esters having the same molecular weights, using single-ion monitoring of the total ion current data from gas chromatography-mass spectrometry. We examined the biological consequences of structural differences by measuring the melting temperatures, Tm, of >60 synthetic wax esters, containing 26–48 carbon atoms. Compounds containing saturated alcohol and acid moieties melted at 38–73°C. The main factor affecting Tm was the total chain length of the wax ester, but the placement of the ester bond also affected Tm. Insertion of a double bond into either the alcohol or acid moiety decreased Tm by ∼30°C. Simple mixtures of wax esters with n-alkanes melted several °C lower than predicted from the melting points of the component lipids. Our results indicate that the wax esters of primary alcohols that are most typically found on the cuticle of terrestrial arthropods occur in a solid state under physiological conditions, thereby conferring greater waterproofing. Wax esters of secondary alcohols, which occur on melanopline grasshoppers, melted >60°C below primary esters of the same molecular weight and reduced Tm of the total surface lipids to environmental values.