HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design

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Residues of brodifacoum and other anticoagulant pesticides in target and non‐target species,Nelson Lakes National Park,New Zealand

Abstract

Cereal‐based bait containing 20 ppm brodifacoum was used in bait stations continuously from December 1997 to August 2000 in the Rotoiti Nature Recovery Project area, for controlling brushtail possum (Trichosurus vulpecula), ship rat (Rattus rattus), and house mouse (Mus musculus) populations. Concurrently (and before and after), baits containing brodifacoum, bromadiolone, flocoumafen, coumatetralyl, or warfarin were also used in St Arnaud village and on farms immediately adjacent to the project area. Brodifacoum residues were detected in the livers of 234 mammals from eight species, and two birds from two species captured alive, and a further seven birds from five species found dead in the project area (cause of death unknown). The highest concentration of brodifacoum residues in mammalian livers was recorded during the period brodifacoum was used in the project area. However, residues were present in the livers of some individuals at least 24 months after brodifacoum use in the project area stopped. These residues may have persisted in animals surviving brodifacoum use in the project area, and/or been transported into the area by animals moving to and from the adjacent village and farms, where brodifacoum use continued. Residues of flocoumafen, coumatetralyl, or warfarin, used only in the village and on farms, were also detected in the livers of animals captured up to at least 8 km from the nearest source. The results concur with other studies cautioning against indiscriminate or prolonged use of persistent anticoagulants for vertebrate pest control. However, the risks from such pesticides must be balanced against the demonstrable benefits of reducing pest abundance.     

Sesquiterpene lactones of Montanoa guatemalensis and Montanoa tomentosa subsp. Xanthiifolia

New 4,5-epoxygermacra-12,6β-olides from Montanoa guatemalensis and a Guatemalan disjunct collection of M. tomentosa subsp. xanthiifolia are reported. These compounds were unlike those from the 10 other Mexican collections of M. tomentosa previous investigated.     

Inhibition of humoral immunity in vivo by monoclonal antibody to L3T4: studies with soluble antigens in intact mice

Monoclonal antibody (MAb) to the mouse "helper" T cell antigen L3T4 inhibits the T cell response to class II major histocompatibility antigens on antigen-presenting cells in vitro and in thymectomized mice. To examine the effect of MAb to L3T4 on humoral immunity in euthymic mice, we treated BALB/c mice with 1 mg of anti-L3T4 i.p. at the time of immunization with either bovine serum albumin (BSA) or chicken egg ovalbumin (OA) in complete Freund's adjuvant. Administration of MAb to L3T4 selectively depleted greater than 90% of L3T4+ cells from the blood, spleen, and lymph nodes, but it had little effect on thymocytes. Mice treated with anti-L3T4 were unable to generate an IgG response to either BSA or OA. Treatment with anti-L3T4 also prevented the antigen-specific IgM response to these antigens, although it did not prevent nonspecific stimulation of IgM anti-BSA and anti-OA antibodies induced by adjuvant in the absence of antigen. Humoral immunity was inhibited even when treatment was delayed until 48 hr after immunization. These findings indicate that T cell help for humoral immunity can be abrogated in intact mice by MAb to L3T4.     

Lake bathymetry and species occurrence predict the distribution of a lacustrine apex predator

This study examined the abiotic and biotic characteristics of ecosystems that allow expression of a life history called ferox trout, the colloquial name given to brown trout Salmo trutta adopting a piscivorous life history strategy, an apex predator in post‐glacial lakes in northern Europe. One hundred and ninety‐two lakes in Scotland show evidence of currently, or historically, supporting ferox S. trutta; their presence was predicted in logistic models by larger and deeper lakes with a large catchment that also support populations of Arctic charr Salvelinus alpinus.     

Blood modeling using polystyrene microspheres

The steady flow viscosity at shear rates 0 to 120 sec-1 and dynamic viscoelasticity at frequencies 0.02 to 0.8 Hz were determined for aqueous suspensions of uniform polystyrene microspheres of 1.0 micron diameter. Rheological properties of the microsphere suspensions were Newtonian for particle concentrations up to 32%. By introducing dextran and calcium chloride into the particle suspensions, non-Newtonian behavior was produced similar to that observed for human blood. The cooperative effects of dextran and calcium ions promoted aggregation of particles at a concentration as low as 12%. Thus, a suspension of uniform sized spherical polystyrene particles in aqueous solution of dextran may be made to mimic blood by controlling the surface charge on the polystyrene spheres using addition of calcium ions to the medium.     

Induction of immune tolerance by administration of monoclonal antibody to L3T4

Immune responses can be profoundly altered in mice by treatment with monoclonal antibodies (MAb) to L3T4, the mouse homologue for the CD4 antigen in humans. Treatment of mice with anti-L3T4 blocks both primary and secondary immune responses, delays allograft rejection, and retards autoimmunity. To determine whether anti-L3T4 could also be used to induce tolerance, we investigated the effect of treatment with rat MAb to L3T4 on the immune response to two other rat MAb: MAb to chicken egg ovalbumin (OVA) and MAb to T200, an antigen expressed on all mouse mononuclear blood cells. Treatment with anti-L3T4 prevented the primary humoral response to both of these MAb. Moreover, the anti-L3T4 MAb induced tolerance to itself, and it induced tolerance to the anti-OVA MAb when the two MAb were given concurrently. However, anti-L3T4 did not induce tolerance to the anti-T200 MAb when these MAb were given concurrently. These findings indicate that treatment with MAb to L3T4 may provide a new method for inducing tolerance to some, but not all, antigens. Because L3T4 in mice is homologous to CD4 in humans, our findings suggest that it may be possible to use anti-CD4 to induce tolerance to specific xenogeneic MAb, thereby facilitating their use as therapeutic agents in people.     

Temperature acclimation in crucian carp, Carassius carassius L., morphometric analyses of muscle fibre ultrastructure

Carp show a partial compensation in metabolic rate and activity following temperature acclimation. In the present study crucian carp, Carassius carassius , were acclimated for eight weeks to either 2deg; C or 28deg; C. The effects of temperature acclimation on muscle fibre ultrastructure has been investigated. The fractional volume (%) of each fibre type occupied by mitochondria and myofibrils was determined using a point counting morphometric method. Mitochondrial density was found to be higher in the muscles of cold (red fibres 25%; pink fibres 20% and white fibres 4%) than in those of warm acclimated fish (red fibres 14%, pink fibres 11%, white fibres 1%). The proportion of subsarcolemmal to intra-myofibrillar mitochondria was significantly lower in the red fibres of cold acclimated fish. Metabolic compensation to low temperatures are therefore associated with an increase in the number of mitochondria per cell. In contrast, the fractional volume occupied by myofibrils actually decreased following cold acclimation. Evidence is reviewed that temperature compensation of contractile activity results from qualitative rather than quantitative changes in myofibrillar proteins.