Synthesis and SAR of diazepine and thiazepine TACE and MMP inhibitors

Potent and selective TACE and MMP inhibitors utilizing the diazepine and thiazepine ring systems were synthesized and evaluated for biological activity in in vitro and in vivo models of TNF-alpha release. Oral activity in the mouse LPS model of TNF-alpha release was seen. Efficacy in the mouse collagen induced arthritis model was achieved with diazepine 20.     

Effects of multiple matings on reproductive fitness of male and female Diaeretiella rapae

Mating frequency and the amount of sperm transferred during mating have important consequences on progeny sex ratio and fitness of haplodiploid insects. Production of female offspring may be limited by the availability of sperm for fertilizing eggs. This study examined multiple mating and its effect on fitness of the cabbage aphid parasitoid Diaeretiella rapae McIntosh (Hymenoptera: Aphidiidae). Female D. rapae mated once, whereas males mated with on average more than three females in a single day. The minimum time lag between two consecutive matings by a male was 3 min, and the maximum number of matings a male achieved in a day was eight. Sperm depletion occurred as a consequence of multiple mating in D. rapae. The number of daughters produced by females that mated with multiple‐mated males was negatively correlated with the number of matings achieved by these males. Similarly, the proportion of female progeny decreased in females that mated with males that had already mated three times. Although the proportion of female progeny resulting from multiple mating decreased, the decrease was quicker when the mating occurred on the same day than when the matings occurred once per day over several days. Mating success of males initially increased after the first mating, but then males became ‘exhausted’ in later matings; their mating success decreased with the number of prior matings. The fertility of females was affected by mating with multiple‐mated males. The study suggests that male mating history affects the fitness of male and female D. rapae.     

Body size and fitness relation in male and female Diaeretiella rapae

A strong relationship exists between body size and fitness in parasitoids. However, it is unclear whether the relationship is symmetric or asymmetric in males and females. The present study investigated the body size and fitness relationship in Diaeretiella rapae emerged from small and large nymphs of cabbage aphid Brevicoryne brassicae. A positive relationship existed between the size of the aphid host and growth of parasitoid larva developing in it. The fitness gain in males and females was not proportionate to their body size gain. Females mated with larger males produced 10?% more female offspring than females mated with smaller males. However, females that developed in large hosts produced 62?% more offspring (total male and female) than the females emerged from smaller hosts. The findings suggest that the number of offspring and the progeny sex ratio were affected by the body size of both male and female D. rapae.     

Characteristics associated with Woolly Apple Aphid Eriosoma lanigerum, resistance of three apple rootstocks

The resistance characteristics of the apple resistance genes (Er1, Er2, and Er3) to the woolly apple aphid, Eriosoma lanigerum (Hausmann) (Homoptera: Aphididae) were studied according to the performance measured on apple cultivars containing these resistance genes. The resistance characteristics of Northern Spy (Er1), Robusta 5 (Er2), and Aotea (Er3) were compared to the susceptible cultivar Royal Gala, by measuring the aphid settlement, development, and survival rates correlated with electronically monitored probing behaviour. Er1 and Er2 had a higher level of resistance with a significantly shorter period of phloem feeding, suggesting that the resistance factors were present in the phloem tissue. Phenological measurements indicated that the aphids showed poor settlement, development, and survival on Er2. Er1 also showed low settlement and survival, although not as low as Er2. Aphid performance and feeding on Aotea (Er3) were similar to Royal Gala, suggesting that some woolly apple aphids in New Zealand may have recently overcome Er3 resistance. The differences in resistance mechanisms of Er1, Er2, and Er3 are discussed in relation to the strategy of pyramiding these genes to give a durable resistance to woolly apple aphid.     

Host Location and Ovipositional Behavior of Platygaster demades Walker (Hymenoptera: Platygastridae), an Egg Parasitoid of Apple and Pear Leaf Curling Midges

The foraging responses of 1–2-day-old naïve female Platygaster demades to odors of apple and pear foliage and host insect eggs were measured. The host origin of P. demades had no effect on the parasitoids’ longevity, host preference, or foraging behavior. Four distinct behaviors related to oviposition were identified. In choice experiments, more female parasitoids responded to apple foliage with no midge eggs than to midge eggs alone. In a Y-tube olfactometer, parasitoids preferred the plant cues to clean air, and responded equally to both apple and pear odors. The results indicate that P. demades utilizes plant cues to locate the habitat of its host and then searches for host eggs to parasitize.     

Synthesis and activity of quinolinylmethyl P1′ α-sulfone piperidine hydroxamate inhibitors of TACE

A series of α-sulfone piperidine hydroxamate TACE inhibitors 11a–n bearing a quinolinyl methyl P1′ group was prepared, and their activity was compared to analogous α- and β-sulfone piperidine hydroxamates with a butynyloxy P1′ group. The quinolinyl methyl P1′ group affords increased inhibitory enzyme activity relative to the corresponding butynyloxy P1′ analogs in the α-sulfone piperidine hydroxamate series, and greater selectivity than the corresponding butynyloxy P1′ analogs in the β-sulfone piperidine hydroxamate series.     

Allyl and propargyl substituted penam sulfones as versatile intermediates toward the syntheses of new beta-lactamase inhibitors

Several alkenyl derivatives were prepared using allyl penam sulfone as the key intermediate. Isomers of these derivatives having beta configuration at C-6 showed potent activity against CcrA enzyme. A new method was developed to prepare propargyl penam sulfone. The majority of the triazoles prepared by this route exhibited good activity against all three representative enzymes used for the inhibition assay.     

EPG technique as a tool to reveal host plant acceptance by xylem sap‐feeding insects

The discovery of a new exotic insect herbivore triggers responses from biosecurity agencies, one of which is the decision of whether or not to attempt eradication. Rapid determination of the host range of the new invader is necessary, but when sap‐sucking insects are first collected from plants, the lack of visible signs of feeding damage makes it difficult to determine their host status. We investigated the Electrical Penetration Graph (EPG‐DC) technique as tool to assess host range of a xylem sap‐feeding invader, using Carystoterpa fingens (Hemiptera: Aphrophoridae), a New Zealand endemic xylem feeder, as a model insect. Real‐time probing and feeding events over a 12‐h recording period were compared for adult C. fingens on 18 plant species. Hebe azure, a known host, was designated the ‘reference plant species’ against which events on all other plants were statistically compared. EPG waveforms were categorized on their amplitude, frequency, voltage and electrical origin, and six parameters (time taken to first probe, time to first xylem ingestion from first probe, total probing time, number of xylem‐ingesting events, duration of the longest xylem‐ingesting event and total xylem ingestion time) were measured. The total xylem ingestion period (i.e. the actual feeding period) on each plant species expressed as a percentage of total probing time was considered the best parameter for comparing the host status of plants with H. azure. Although the EPG data overestimated the actual host range of C. fingens, we consider that they provided a reasonable first guide to the potential host status of the unknown plants, and so might usefully be used to rapidly assess whether a plant from which a new invader was collected was a host, or whether the association was merely incidental.     

Stylet penetration activities linked to the acquisition and inoculation of Candidatus Liberibacter solanacearum by its vector tomato potato psyllid

The tomato potato psyllid (TPP), Bactericera cockerelli (Sulc) (Hemiptera: Triozidae), is the main vector of the bacterium Candidatus Liberibacter solanacearum (Lso), a major disease of solanaceous crops. Feeding of TPP is associated with Lso transmission. However, very little is known about the stylet penetration activities linked to acquisition and inoculation of Lso. The electrical penetration graph (EPG)‐DC system was used to monitor stylet penetration activities during acquisition and inoculation of Lso by individual TPP on tomato [Solanum lycopersicum L. (Solanaceae)]. Female TPP from Lso‐free and Lso‐infected colonies were used in acquisition and inoculation tests, respectively. In the acquisition tests, TPP were tested for Lso after EPG recording of their stylet penetration activities on Lso‐infected tomato shoots. In the inoculation tests, samples from the tomato plants on which the stylet penetration of Lso‐infected TPP had been recorded were tested for Lso infection. The relationships between qPCR results and the EPG waveforms (C, G, D, E1, and E2) representing the main stylet penetration activities performed by individual insects in inoculation and acquisition tests were investigated. Results confirmed that a single adult TPP is capable of infecting a plant with Lso. Our data suggest that acquisition of the bacteria occurs during phloem ingestion (E2), and inoculation is likely associated with salivation into the phloem sieve elements (E1). The durations of EPG parameters were not significantly different between Lso‐infected and Lso‐free TPP (later shown by qPCR) in acquisition tests. In inoculation tests, the durations of E1 or E2 recorded from TPP on Lso‐infected and Lso‐free plants that were later shown by qPCR were not significantly different. However, C was shorter on Lso‐infected plants than on Lso‐free plants, where TPP performed phloem activities. The minimum plant access period required for Lso transmission by a single TPP was estimated to be ca. 2 h, with an acquisition threshold of about 36 min.     

Oviposition preferences of the Hessian fly and their consequences for the survival and reproductive potential of offspring

1. The relationship between oviposition preference and offspring performance was investigated experimentally for the Hessian fly Mayetiola destructor (Say) using 10 grass genotypes that represented five different genera and six different species. Oviposition preferences were quantified in a choice test using arrays of 200–400 plants. Offspring performance was estimated by recording survival during three phases of the insect–plant association and by measuring wing length, a correlate of adult reproductive potential. Density effects were examined for all offspring variables, and were taken into account when offspring performance was compared across the 10 grasses. 2. Egg counts from the oviposition choice test revealed a consistent ranking of plants: 18ITSN triticale > Otane bread wheat = Caldwell bread wheat = Stacy bread wheat > 3424 bread wheat = PND durum wheat = Fleet barley = Valetta barley = Matua brome grass > Awapuni oat. 3. Survival and adult wing length varied significantly on the 10 plant types. Survival was ranked: Otane bread wheat > 3424 bread wheat = Fleet barley = Matua brome grass > Caldwell bread wheat = Valetta barley > 18ITSN triticale = PND durum wheat = Stacy bread wheat > Awapuni oat. Adult male and female wing lengths were greatest on Otane, the bread wheat that also provided the best survival. 4. For Hessian flies on each of the 10 plant types, data on survival, wing length, and wing length–fecundity relationships were combined into a single fitness measure. When these fitness measures were compared with egg counts, no overall pattern emerged. On seven of the 10 plant types, there was a positive linear relationship between egg counts and offspring fitness. On the other three plant types, egg counts were high while fitness was low. Possible reasons why Hessian fly females lay eggs on plants that are poor hosts for their offspring are discussed.