Deliberately Losing Control of C−H Activation Processes in the Design of Small-Molecule-Fragment Arrays Targeting Peroxisomal Metabolism

Combined photochemical arylation, “nuisance effect” (S_NAr) reaction sequences have been employed in the design of small arrays for immediate deployment in medium-throughput X-ray protein–ligand structure determination. Reactions were deliberately allowed to run “out of control” in terms of selectivity; for example the ortho-arylation of 2-phenylpyridine gave five products resulting from mono- and bisarylations combined with S_NAr processes. As a result, a number of crystallographic hits against NUDT7, a key peroxisomal CoA ester hydrolase, have been identified.     

Biocatalytic Alkylation Cascades: Recent Advances and Future Opportunities for Late-Stage Functionalization

This Concept article describes the latest developments in the emerging area of late-stage biocatalytic alkylation. Central to these developments is the ability to efficiently prepare S-adenosyl methionine (SAM) cofactor analogues and couple this with enzymatic alkyl transfer. Recent developments in the enzymatic synthesis of SAM cofactor analogues are summarized first, followed by their application as alkyl transfer agents catalyzed by methyltransferases (MTases). Second, innovative methods to regenerate SAM cofactors by enzymatic cascades is reported. Finally, future opportunities towards establishing a generalized platform for late-stage alkylation are described.     

Isoforms p69 and p100 of 2'',5''-oligoadenylate synthetase induced differentially by interferons in vivo and in vitro

There is no better place to test life-saving resuscitation interventions than in the prehospital setting. Patients rarely survive cardiac arrest if resuscitation techniques have failed before leaving the scene. Also, paramedics are usually very experienced in key initial resuscitative techniques, and they routinely operate under strict paramilitary protocol, resulting in better study compliance. In addition, the large study populations that are derived from emergency medical services (EMS) systems lead to faster study completion and statistically stronger data. Most important, by reinforcing standardized care, rigidly scrutinized trials improve patient care, regardless of the effect of the study intervention. The success of productive EMS research centers requires routine communication between hospital and EMS administrators and their medical directors, designation of mutually acceptable data collectors who guarantee confidentiality, reciprocal exchange of study data provided as educational seminars to the hospitals, commitments to support the budget requests of an EMS program and appropriate system modifications, inclusion of EMS personnel in study design from the very beginning, prospective education of the medical community and media before protocol implementation, an authoritative grassroots medical director, and a paramedic supervisor system.     

50-nm Self-Aligned and “Standard” T-gate InP pHEMT Comparison: The Influence of Parasitics on Performance at the 50-nm Node

Continued research into the development of III-V high-electron mobility transistors (HEMTs), specifically the minimization of the device gate length, has yielded the fastest performance reported for any three terminal devices to date. In addition, more recent research has begun to focus on reducing the parasitic device elements such as access resistance and gate fringing capacitance, which become crucial for short gate length device performance maximization. Adopting a self-aligned T-gate architecture is one method used to reduce parasitic device access resistance, but at the cost of increasing parasitic gate fringing capacitances. As the device gate length is then reduced, the benefits of the self-aligned gate process come into question, as at these ultrashort-gate dimensions, the magnitude of the static fringing capacitances will have a greater impact on performance. To better understand the influence of these issues on the dc and RF performance of short gate length InP pHEMTs, the authors present a comparison between In_0.7Ga_0.3As channel 50-nm self-aligned and "standard" T-gate devices. Figures of merit for these devices include transconductance greater than 1.9 S/mm, drive current in the range 1.4 A/mm, and fT up to 490 GHz. Simulation of the parasitic capacitances associated with the self-aligned gate structure then leads a discussion concerning the realistic benefits of incorporating the self-aligned gate process into a sub-50-nm HEMT system     

Sex pheromone of the mullein bug,Campylomma verbasci (Meyer) (Heteroptera: Miridae)

The first known sex pheromone for the family Miridae is reported for the mullein bug,Campylomma verbasci (Meyer) (Heteroptera: Miridae). Extracts of and Porapak Q-trapped volatiles from females were attractive to males in field bioassays. Butyl butyrate and hexyl butyrate were the predominant compounds in the females' volatiles, but these compounds previously had been found to be inactive when released alone or in combination. Butyl butyrate in combination with an isolated trace chemical, (E)-crotyl butyrate (which was inactive alone), rivaled the attraction elicited by five live females. When synthetic butyl butyrate and (E)-crotyl butyrate in a 16: 1 ratio were released at 91 or 183 g/day, they comprised an effective attractant for male bugs.     

Changes in the size and docosahexaenoic acid content of adipocytes during chick embryo development

The development of adipose tissue in the chick embryo was investigated using two groups of fertile eggs which differed by 1.7-fold in their initial yolk lipid levels. The triacylglycerol content of the subcutaneous adipose depot in both groups increased dramatically from day 12 of the 21-day embryonic period, attaining a maximal value just prior to hatching. During this period, the amount of triacylglycerol deposited in the adipose tissue was very highly correlated with the amount of lipid transferred from the yolk. The triacylglycerol content of the depot was also dependent on the initial yolk lipid content. During the hatching period, the amount of adipose triacylglycerol remained approximately constant in the group with the higher initial yolk lipid content but, in the case of the group with the lower initial yolk lipid levels, decreased by approximately 25%. The size distribution of adipocytes isolated from the tissue was determined by computerized image analysis microscopy. The mean adipocyte diameter increased from approximately 6 to 35 μm between days 12 and 19, irrespective of the initial yolk content, although development within the eggs with the lower initial yolk content resulted in a decrease in cell size over the hatching period. Both the triacylglycerol and phospholipid fractions of the isolated adipocytes contained substantial proportions (approximately 6%, w/w) of docosahexaenoic acid (DHA) at days 12 and 14, and lower levels of this fatty acid at the later stages. The amount (mg/depot) of DHA in adipose triacylglycerol decreased dramatically over the hatching period. The amount (mg/brain) of DHA in brain phospholipid increased by more than 5-fold between day 12 of development and hatching. A possible explanation for the data may be that DHA is preferentially mobilized from adipose tissue in order to deliver the fatty acid to the developing neural tissues in a form suitable for uptake.     

Disruption of Secondary Attraction of the Spruce Beetle, Dendroctonus rufipennis, by Pheromones of Two Sympatric Species

Capture of spruce beetles, Dendroctonus rufipennis, in multiple-funnel traps baited with frontalin and -pinene was reduced by up to 42% in the presence of synthetic (+)-exo- and (+)-endo-brevicomin, aggregation pheromones of the sympatric species Dryocoeles affaber. (±)-endo-Brevicomin was inhibitory to spruce beetles in two experiments and (±)-exo-brevicomin was inhibitory in one experiment, reducing spruce beetle trap catches by up to 87% and 75%, respectively. Spruce beetle trap catches were also reduced by 85% by (±)- or (+)-ipsdienol, but not by (–)-ipsdienol. Ips tridens, a second sympatric species, produces both enantiomers of ipsdienol in its pheromone blend. Responses by D. affaber to its own pheromone were significantly enhanced by addition of the spruce beetle lure. Enantiospecific pheromones of secondary competing species, or less costly racemic substitutes, may be useful for managing spruce beetles using competitive displacement or exclusion. Baiting susceptible hosts with pheromones of secondary species may enhance attack by secondary species, while partially repelling spruce beetles.     

Photoisomerization of antiaggregation pheromone verbenone: Biological and practical implications with respect to the mountain pine beetle,Dendroctonus ponderosae Hopkins (Coleoptera: Scolytidae)

Release of the antiaggregation pheromone, verbenone, at 3.8 mg/ day from a concentrated source within a multiple-funnel trap completely inhibited response by the mountain pine beetle (MPB),Dendroctonus ponderosae Hopkins, to attractive semiochemical lures. When aerial applications were simulated and verbenone was released at the same rate from beads lying in a 2×2-m area on the forest floor 15–35 cm below a trap, the response of the MPB was inhibited by only 50%. This reduced inhibition may be explained in part by the photoisomerism of verbenone. When exposed to full sunlight on two occasions, the times required for 50% of verbenone vapors to be converted to chrysanthenone were 75 and 100 min, respectively. Trap and tree-baiting experiments indicated no biological activity of chrysanthenone. Rapid photoisomerization could reduce the concentration of verbenone below biologically active levels and would allow the MPB to colonize trees close to already occupied hosts, contributing to the characteristic clumped distribution of MPB attack. The rate of verbenone photoisomerization may vary according to geographic location, stand elevation and density, and should be considered before verbenone is applied to control the MPB and other bark beetles.     

β-Phellandrene: kairomone for pine engraver,Ips pini (Say) (Coleoptera: Scolytidae)

The responses ofIps pini (Scolytidae) to multiple-funnel traps baited with the pheromone, ipsdienol, and various monoterpenes were determined in stands of lodgepole pine in southern and central British Columbia.Ips pini was attracted to both ipsdienol and -phellandrene, demonstrating that -phellandrene is a kairomone for this species.Lasconotus complex (Colydiidae) and aCorticeus sp. (Tenebrionidae) were attracted to both ipsdienol and -phellandrene. TheCorticeus sp. exhibited a synergistic response to the combination of ipsdienol and -phellandrene; the responses of the other two species to the combination were additive. The predators,Thanasimus undatulus, Enoclerus sphegeus, andE. lecontei (Cleridae), were attracted to ipsdienol-baited traps, whileMonochamus clamator (Cerambycidae) andDendroctonus ponderosae (Scolytidae) were attracted to -phellandrene. Attraction of all eight species increased with increasing release rates of ipsdienol and/or -phellandrene.