Cuticular aphrodisiacs fromD. melanogaster females were further characterized and the male response specificity towards such natural and synthetic unsaturated hydrocarbons was investigated. The behavioral activity seems to be correlated with some chain-length requirement and double-bond position; at least one double bond in position 7 seems necessary. This position is more abundant among natural monoenes, and among dienes which also bear a second double bond in position 11, whatever the chain length. Bioassays of the synthetic (Z,Z)-7,11-heptacosadiene yielded a dose-response curve close to that of the natural mixture of heptacosadienes in which the 7-11 isomer is predominant. This female specific 7,11 heptacosadiene appears to be the most potent aphrodisiac for males of the species. Its threshold is lower than that of both 7,11-nonacosadiene and 7-pentacosene which might also play a role in sex and species recognition.

No abstract

A sex pheromone isolated from the cuticle and feces of the female house fly attracts the male fly; it has been identified as ( Z )-9-tricosene. Chemical and biological comparisons of the natural and synthesized compounds show that they are identical.

Various combinations of six candidate attractants--butanone, carbon dioxide (CO2), honey, octenol, lactic acid and mixed phenols--were tested against natural populations of mosquitoes in Everglades National Park, Florida, U.S.A., using unlighted CDC-baited traps. With few exceptions, the attractancy of these candidate compounds to mosquitoes, when used alone, was less than that of CO2 alone. The exceptions were that octenol and honey extract alone attracted larger numbers of Coquillettidia perturbans (Walker). Addition of lactic acid and/or octenol to CO2 increased trap collections of Aedes taeniorhynchus (Wiedemann), Anopheles atropos D. & K., and An. crucians Wiedemann by 1.4-13.8 times. Culex nigripalpus Theobald collections were increased 2.7 times by the addition of lactic acid, while the addition of octenol produced mixed results. Whereas the addition of lactic acid reduced collections of Cx (Melanoconion) spp., the addition of octenol generally increased collections. The opposite happened for Wyeomyia mitchellii (Theobald). For the biting midge, Culicoides furens (poey), octenol (1.6-23.4 x ) and phenol (2.7 x ) alone attracted larger numbers, and lactic acid alone attracted approximately the same numbers as CO2 alone. The combinations octenol + phenol and octenol + 200 ml/min CO2 increased C. furens collections c. 100 times over CO2 alone. The combination of octenol + CO2 increased (1.6 x ) collections of the tabanid Diachlorus ferrugatus (Fabricius). Butanone appeared to decrease the trap collections of all species when combined with CO2 or octenol + CO2.

Natural and synthetic long-chain alkenes, alkadienes, and alkatrienes (C25-C37) were readily derlvatlzed to stable adducts with dimethyl disulfide (DMDS). This technique was extended to mixtures of unseparated alkanes, alkenes, alkadienes, and alkatrienes, but limited here to the types found In two-winged Insects Including African honey bees, fruit flies, and stable flies, which included several unreported compounds. Capillary column gas chromatography/electron Ionization mass spectrometry (GC/EI-MS) of stable DMDS adducts allowed location of both Internal and terminal unsaturated sites. Derivatization of the total hydrocarbon fraction gave excellent results after only 4 h of reaction time. Alkanes eluted first, followed by the alkene adducts, then the dladducts of dienes, with each group well separated from the others. Molecular ions of diand trladducts were observed, together with Ions showing losses of 48, 94, 141, and 188; cleavage at carbons bearing SCH3, then losses of 48 and 94 located both double bonds. The Cto and C37 dladducts were well separated during GC/MS or GC, with no thermal cleavage observed. Homologous C^, C24, and C2S trlene dladducts and the C2S trlene triadduct survived GC/MS and displayed characteristic cleavage patterns. Major differences were found in proportions of honey bee alkenes that differentiated European and African races, as the C31, C33, and C& alkenes, mentioned as diagnostic for the races, were present In the diagnostic proportion when viewed as adducts. Also, a 9-Isomer in the C31 homologue Indicated the presence of African genetic material In worker bees and wax. The variety of dienes giving linear adducts was limited In that the double bonds were separated by four or more methylenes; otherwise cyclic derivatives of up to 29 carbons were observed.

Summary Tumor necrosis factor α (TNFα) has both positive and negative roles in human disease. In certain cancers, TNFα is infused locally to promote tumor regression, but dose-limiting inflammatory effects limit broader utility. In autoimmune disease, anti-TNFα antibodies control inflammation in most patients, but these benefits are offset during chronic treatment. TAK1 acts as a key mediator between survival and cell death in TNFα-mediated signaling. Here, we describe Takinib, a potent and selective TAK1 inhibitor that induces apoptosis following TNFα stimulation in cell models of rheumatoid arthritis and metastatic breast cancer. We demonstrate that Takinib is an inhibitor of autophosphorylated TAK1 that binds within the ATP binding pocket, yet is non-competitive, and inhibits by slowing down the rate-limiting step of TAK1 activation. Overall, Takinib is an attractive starting point for the development of inhibitors that sensitize cells to TNFα-induced cell death, with general implications for cancer and autoimmune disease treatment.

Many tumors are dependent on de novo fatty acid synthesis to maintain cell growth. Fatty acid synthase (FASN) catalyzes the final synthetic step of this pathway, and its upregulation is correlated with tumor aggressiveness. The consequences and adaptive responses of acute or chronic inhibition of essential enzymes such as FASN are not fully understood. Herein we identify Fasnall, a thiophenopyrimidine selectively targeting FASN through its co-factor binding sites. Global lipidomics studies with Fasnall showed profound changes in cellular lipid profiles, sharply increasing ceramides, diacylglycerols, and unsaturated fatty acids as well as increasing exogenous palmitate uptake that is deviated more into neutral lipid formation rather than phospholipids. We also showed that the increase in ceramide levels contributes to some extent in the mediation of apoptosis. Consistent with this mechanism of action, Fasnall showed potent anti-tumor activity in the MMTV-Neu model of HER2(+) breast cancer, particularly when combined with carboplatin.

A successful interpretation of the complex manner by which the GC retention indexes of methylalkanes produced by insects are related to chemical structure was achieved using the quantitative structure-property relationship (QSPR) method. A general QSPR model including mainly topological descriptors was obtained for 178 data points. The error of the model is similar to the experimental error. The model was supported by (i) leave-one-out cross validation and (ii) division into three sets and prediction of each set from the other two. As a further test of the utility of the model, retention indexes were successfully predicted for an external set of 30 methyl-branched hydrocarbons not involved in the deduction of the correction equation from the main data set. General trends of the structural variation of compounds in any given range of retention index are discussed. The average error was 4.6 overall and 4.3 for the 165 compounds remaining after leaving out small monomethyl alkanes.