p-Mentha-1,3-dien-9-ol: A novel aggregation-sex pheromone for monitoring longhorn beetles (Cerambycidae) in Eurasia and North America

Longhorn beetles (Cerambycidae) are a diverse family of beetles that can cause considerable damage as forest pests and vectors of pathogens, as well as being important components of forest food webs and ecosystem functionality. In recent years, numerous cerambycid pheromones have been identified, revealing some broad general patterns in functionality in terms of sex or aggregation-sex pheromones in different subfamilies and different types of compounds characterizing the pheromones of various cerambycid taxa. Here, we describe the identification of the aggregation-sex pheromones of the Eurasian longhorn beetle Aromia moschata moschata (L.) (Cerambycinae; tribe Callichromatini) and the North American species Holopleura marginata LeConte (Cerambycinae; Holopleurini), as part of an ongoing effort to extend the taxonomic coverage of identified cerambycid pheromones and to expand the prospects for cerambycid monitoring into the study of biodiversity and ecosystem services. Both species were found to use the novel pheromone compound p-mentha-1,3-dien-9-ol, which also attracted significant numbers of the longhorn beetle Xestoleptura crassipes (LeConte) (Lepturinae; Lepturini) in trials in California. p-Mentha-1,3-dien-9-ol represents a class of pheromone compounds novel to both tribes (Callichromatini and Holopleurini), further increasing the chemical space of identified pheromones within the subfamily Cerambycinae. This compound is also noteworthy because it represents an entirely different chemical class of pheromones than the monoepoxide (E)-2-cis-6,7-epoxynonenal, previously reported as an aggregation-sex pheromone for the invasive Asian congener Aromia bungii (Faldermann)

Determination of the Relative and Absolute Configurations of the Female-produced Sex Pheromone of the Cerambycid Beetle Prionus californicus

We previously identified the basic structure of the female-produced sex attractant pheromone of the cerambycid beetle, Prionus californicus Motschulsky (Cerambycidae: Prioninae), as 3,5-dimethyldodecanoic acid. A synthesized mixture of the four stereoisomers of 3,5-dimethyldodecanoic acid was highly attractive to male beetles. Here, we describe stereoselective syntheses of three of the four possible stereoisomers, and the results of laboratory and field bioassays showing that male beetles are attracted specifically to (3R,5S)-3,5-dimethyldodecanoic acid, but not to its enantiomer, (3S,5R)-3,5-dimethyldodecanoic acid, indicating that the (3R,5S)-enantiomer is the active pheromone component. The diastereomeric (3R,5R)- and (3S,5S)-enantiomers were excluded from consideration because their gas chromatographic retention times were different from that of the insect-produced compound. The mixture of the four stereoisomers of 3,5-dimethyldodecanoic acid was as attractive to male P. californicus as the (3R,5S)-enantiomer, indicating that none of the other three stereoisomers inhibited responses to the active enantiomer. Beetles responded to as little as 10 ng and 10 μg of synthetic 3,5-dimethyldodecanoic acid in laboratory and field studies, respectively. Field studies indicated that capture rate did not increase with dosages of 3,5-dimethyldodecanoic acid greater than 100 μg. In field bioassays, males of a congeneric species, P. lecontei Lameere, were captured in southern California but not in Idaho

Male-Produced Aggregation Pheromones of the Cerambycid Beetles Xylotrechus colonus and Sarosesthes fulminans

Adults of both sexes of the cerambycid beetles Xylotrechus colonus (F.) and Sarosesthes fulminans (F.) were attracted to odors produced by male conspecifics in olfactometer bioassays. Analyses of headspace volatiles from adults revealed that male X. colonus produced a blend of (R)- and (S)-3-hydroxyhexan-2-one and (2 S,3 S)- and (2R,3R)-2,3-hexanediol, whereas male S. fulminans produced (R)-3-hydroxyhexan-2-one and (2 S,3R)-2,3-hexanediol. All of these compounds were absent in the headspace of females. Two field bioassays were conducted to confirm the biological activity of the synthesized pheromones: (1) enantiomerically enriched pheromone components were tested singly and in species-specific blends and (2) four-component mixture of racemic 3-hydroxyhexan-2-one plus racemic 2-hydroxyhexan-3-one and the four-component blend of the stereoisomers of 2,3-hexanediols were tested separately and as a combined eight-component blend. In these experiments, adult male and female X. colonus were captured in greatest numbers in traps baited with the reconstructed blend of components produced by males, although significant numbers were also captured in traps baited with (R)-3-hydroxyhexan-2-one alone or in blends with other compounds. Too few adult S. fulminans were captured for a statistical comparison among treatments, but all were caught in traps baited with lures containing (R)-3-hydroxyhexan-2-one. In addition to these two species, adults of two other species of cerambycid beetles, for which pheromones had previously been identified, were caught: Neoclytus a. acuminatus (F.) and its congener Neoclytus m. mucronatus (F.). Cross-attraction of beetles to pheromone blends of other species, and to individual pheromone components that are shared by two or more sympatric species, may facilitate location of larval hosts by species that compete for the same host species

Biological-effective versus conventional dose volume histograms correlated with late genitourinary and gastrointestinal toxicity after external beam radiotherapy for prostate cancer: a matched pair analysis

BACKGROUND: To determine whether the dose-volume histograms (DVH's) for the rectum and bladder constructed using biological-effective dose (BED-DVH's) better correlate with late gastrointestinal (GI) and genitourinary (GU) toxicity after treatment with external beam radiotherapy for prostate cancer than conventional DVH's (C-DVH's). METHODS: The charts of 190 patients treated with external beam radiotherapy with a minimum follow-up of 2 years were reviewed. Six patients (3.2%) were found to have RTOG grade 3 GI toxicity, and similarly 6 patients (3.2%) were found to have RTOG grade 3 GU toxicity. Average late C-DVH's and BED-DVH's of the bladder and rectum were computed for these patients as well as for matched-pair control patients. For each matched pair the following measures of normalized difference in the DVH's were computed: (a) δ(AUC )= (Area Under Curve [AUC] in grade 3 patient – AUC in grade 0 patient)/(AUC in grade 0 patient) and (b) δ(V60 )= (Percent volume receiving = 60 Gy [V60] in grade 3 patient – V60 in grade 0 patient)/(V60 in grade 0 patient). RESULTS: As expected, the grade 3 curve is to the right of and above the grade 0 curve for all four sets of average DVH's – suggesting that both the C-DVH and the BED-DVH can be used for predicting late toxicity. δ(AUC )was higher for the BED-DVH's than for the C-DVH's – 0.27 vs 0.23 (p = 0.036) for the rectum and 0.24 vs 0.20 (p = 0.065) for the bladder. δ(V60 )was also higher for the BED-DVH's than for the C-DVH's – 2.73 vs 1.49 for the rectum (p = 0.021) and 1.64 vs 0.71 (p = 0.021) for the bladder. CONCLUSIONS: When considering well-established dosimetric endpoints used in evaluating treatment plans, BED-DVH's for the rectum and bladder correlate better with late toxicity than C-DVH's and should be considered when attempting to minimize late GI and GU toxicity after external beam radiotherapy for prostate cancer

Worldwide tests of generic attractants, a promising tool for early detection of non-native cerambycid species

A large proportion of the insects which have invaded new regions and countries are emerging species, being found for the first time outside their native range. Being able to detect such species upon arrival at ports of entry before they establish in non-native countries is an urgent challenge. The deployment of traps baited with broad-spectrum semiochemical lures at ports-of-entry and other high-risk sites could be one such early detection tool. Rapid progress in the identification of semiochemicals for cerambycid beetles during the last 15 years has revealed that aggregation-sex pheromones and sex pheromones are often conserved at global levels for genera, tribes or subfamilies of the Cerambycidae. This possibly allows the development of generic attractants which attract multiple species simultaneously, especially when such pheromones are combined into blends. Here, we present the results of a worldwide field trial programme conducted during 2018-2021, using traps baited with a standardised 8-pheromone blend, usually com-plemented with plant volatiles. A total of 1308 traps were deployed at 302 sites covering simultaneously or sequentially 13 European countries, 10 Chinese provinces and some regions of the USA, Canada, Australia, Russia (Siberia) and the Caribbean (Martinique). We intended to test the following hypotheses: 1) if a species is regularly trapped in significant numbers by the blend on a continent, it increases the prob-ability that it can be detected when it arrives in other countries/continents and 2) if the blend exerts an effective, generic attraction to multiple species, it is likely that previously unknown and unexpected spe-cies can be captured due to the high degree of conservation of pheromone structures within related taxa. A total of 78,321 longhorned beetles were trapped, representing 376 species from eight subfamilies, with 84 species captured in numbers greater than 50 individuals. Captures comprised 60 tribes, with 10 tribes including more than nine species trapped on different continents. Some invasive species were captured in both the native and invaded continents. This demonstrates the potential of multipheromone lures as ef-fective tools for the detection of 'unexpected' cerambycid invaders, accidentally translocated outside their native ranges. Adding new pheromones with analogous well-conserved motifs is discussed, as well as the limitations of using such blends, especially for some cerambycid taxa which may be more attracted by the trap colour or other characteristics rather than to the chemical blend

Sequence and Structure Signatures of Cancer Mutation Hotspots in Protein Kinases

Protein kinases are the most common protein domains implicated in cancer, where somatically acquired mutations are known to be functionally linked to a variety of cancers. Resequencing studies of protein kinase coding regions have emphasized the importance of sequence and structure determinants of cancer-causing kinase mutations in understanding of the mutation-dependent activation process. We have developed an integrated bioinformatics resource, which consolidated and mapped all currently available information on genetic modifications in protein kinase genes with sequence, structure and functional data. The integration of diverse data types provided a convenient framework for kinome-wide study of sequence-based and structure-based signatures of cancer mutations. The database-driven analysis has revealed a differential enrichment of SNPs categories in functional regions of the kinase domain, demonstrating that a significant number of cancer mutations could fall at structurally equivalent positions (mutational hotspots) within the catalytic core. We have also found that structurally conserved mutational hotspots can be shared by multiple kinase genes and are often enriched by cancer driver mutations with high oncogenic activity. Structural modeling and energetic analysis of the mutational hotspots have suggested a common molecular mechanism of kinase activation by cancer mutations, and have allowed to reconcile the experimental data. According to a proposed mechanism, structural effect of kinase mutations with a high oncogenic potential may manifest in a significant destabilization of the autoinhibited kinase form, which is likely to drive tumorigenesis at some level. Structure-based functional annotation and prediction of cancer mutation effects in protein kinases can facilitate an understanding of the mutation-dependent activation process and inform experimental studies exploring molecular pathology of tumorigenesis

Search for Eccentric Black Hole Coalescences during the Third Observing Run of LIGO and Virgo

Despite the growing number of confident binary black hole coalescences observed through gravitational waves so far, the astrophysical origin of these binaries remains uncertain. Orbital eccentricity is one of the clearest tracers of binary formation channels. Identifying binary eccentricity, however, remains challenging due to the limited availability of gravitational waveforms that include effects of eccentricity. Here, we present observational results for a waveform-independent search sensitive to eccentric black hole coalescences, covering the third observing run (O3) of the LIGO and Virgo detectors. We identified no new high-significance candidates beyond those that were already identified with searches focusing on quasi-circular binaries. We determine the sensitivity of our search to high-mass (total mass $M>70$ $M_\odot$) binaries covering eccentricities up to 0.3 at 15 Hz orbital frequency, and use this to compare model predictions to search results. Assuming all detections are indeed quasi-circular, for our fiducial population model, we place an upper limit for the merger rate density of high-mass binaries with eccentricities $0 < e \leq 0.3$ at $0.33$ Gpc$^{-3}$ yr$^{-1}$ at 90\% confidence level.Comment: 24 pages, 5 figure

Open data from the third observing run of LIGO, Virgo, KAGRA and GEO

The global network of gravitational-wave observatories now includes five detectors, namely LIGO Hanford, LIGO Livingston, Virgo, KAGRA, and GEO 600. These detectors collected data during their third observing run, O3, composed of three phases: O3a starting in April of 2019 and lasting six months, O3b starting in November of 2019 and lasting five months, and O3GK starting in April of 2020 and lasting 2 weeks. In this paper we describe these data and various other science products that can be freely accessed through the Gravitational Wave Open Science Center at https://gwosc.org. The main dataset, consisting of the gravitational-wave strain time series that contains the astrophysical signals, is released together with supporting data useful for their analysis and documentation, tutorials, as well as analysis software packages.Comment: 27 pages, 3 figure