Host response to malaria during pregnancy: placental monocyte recruitment is associated with elevated beta chemokine expression

Malaria during pregnancy is associated with poor birth outcomes, particularly low birth weight. Recently, monocyte infiltration into the placental intervillous space has been identified as a key risk factor for low birth weight. However, the malaria-induced chemokines involved in recruiting and activating placental monocytes have not been identified. In this study, we determined which chemokines are elevated during placental malaria infection and the association between chemokine expression and placental monocyte infiltration. Placental malaria infection was associated with elevations in mRNA expression of three beta chemokines, macrophage-inflammatory protein 1 (MIP-1) alpha (CCL3), monocyte chemoattractant protein 1 (MCP-1; CCL2), and I-309 (CCL1), and one alpha chemokine, IL-8 (CXCL8); all correlated with monocyte density in the placental intervillous space. Placental plasma concentrations of MIP-1 alpha and IL-8 were increased in women with placental malaria and were associated with placental monocyte infiltration. By immunohistochemistry, we localized placental chemokine production in malaria-infected placentas: some but not all hemozoin-laden maternal macrophages produced MIP-1 beta and MCP-1, and fetal stromal cells produced MCP-1. In sum, local placental production of chemokines is increased in malaria, and may be an important trigger for monocyte accumulation in the placenta.     

A multi-scale comparison of trait linkages to environmental and spatial variables in fish communities across a large freshwater lake

Species present in communities are affected by the prevailing environmental conditions, and the traits that these species display may be sensitive indicators of community responses to environmental change. However, interpretation of community responses may be confounded by environmental variation at different spatial scales. Using a hierarchical approach, we assessed the spatial and temporal variation of traits in coastal fish communities in Lake Huron over a 5-year time period (2001–2005) in response to biotic and abiotic environmental factors. The association of environmental and spatial variables with trophic, life-history, and thermal traits at two spatial scales (regional basin-scale, local site-scale) was quantified using multivariate statistics and variation partitioning. We defined these two scales (regional, local) on which to measure variation and then applied this measurement framework identically in all 5 study years. With this framework, we found that there was no change in the spatial scales of fish community traits over the course of the study, although there were small inter-annual shifts in the importance of regional basin- and local site-scale variables in determining community trait composition (e.g., life-history, trophic, and thermal). The overriding effects of regional-scale variables may be related to inter-annual variation in average summer temperature. Additionally, drivers of fish community traits were highly variable among study years, with some years dominated by environmental variation and others dominated by spatially structured variation. The influence of spatial factors on trait composition was dynamic, which suggests that spatial patterns in fish communities over large landscapes are transient. Air temperature and vegetation were significant variables in most years, underscoring the importance of future climate change and shoreline development as drivers of fish community structure. Overall, a trait-based hierarchical framework may be a useful conservation tool, as it highlights the multi-scaled interactive effect of variables over a large landscape.     

How does adaptive consumer movement affect population dynamics in consumer-resource metacommunities with homogeneous patches?

This article uses simple models to explore the impact of adaptive movement by consumers on the population dynamics of a consumer-resource metacommunity consisting of two identical patches. Consumer-resource interactions within a patch are described by the Rosenzweig-MacArthur predator-prey model, and these dynamics are assumed to be cyclic in the absence of movement. The per capita movement rate from one patch to the other is an increasing function of the difference between the per capita birth minus death rate in the destination patch and that in the currently occupied patch. Several variations on this model are considered. Results show that adaptive movement frequently creates anti-phase cycles in the two patches; these suppress the predator-prey cycle and lead to low temporal variation of the total population sizes of both species. Paradoxically, even when movement is very sensitive to the fitness difference between patches, perfect synchrony of patches is often much less likely than in comparable systems with random movement. Under these circumstances adaptive movement of consumers often generates differences in the average properties of the two patches. In addition, mean global densities and responses to global perturbations often differ greatly from similar systems with no movement or random movement.     

Adaptive foraging by predators as a cause of predator-prey cycles

Summary When foraging has costs, it is generally adaptive for foragers to adjust their foraging effort in response to changes in the population density of their food. If effort decreases in response to increased food density, this can result in a type-2 functional response; intake rate increases in a negatively accelerated manner as prey density increases. Unlike other mechanisms for type-2 responses, adaptive foraging usually involves a timelag, because foraging behaviours do not often change instantaneously with changes in food density or risks. This paper investigates predator-prey models in which there are explicit dynamics for the rate of adaptive change. Models appropriate to both behavioural and evolutionary change are considered. Both types of change can produce cycles under similar circumstances, but under some evolutionary models there is not sufficient genetic variability for evolutionary change to produce cycles. If there is sufficient variability, the remaining conditions required for cycles are surprisingly insensitive to the nature of the adaptive process. A predator population that approaches the optimum foraging strategy very slowly usually produces cycles under similar conditions as does a very rapidly adapting population.     

Irradiation of tumor cells up-regulates Fas and enhances CTL lytic activity and CTL adoptive immunotherapy

CD8(+) CTL play important roles against malignancy in both active and passive immunotherapy. Nonetheless, the success of antitumor CTL responses may be improved by additional therapeutic modalities. Radiotherapy, which has a long-standing use in treating neoplastic disease, has been found to induce unique biologic alterations in cancer cells affecting Fas gene expression, which, consequently, may influence the overall lytic efficiency of CTL. Here, in a mouse adenocarcinoma cell model, we examined whether exposure of these tumor cells to sublethal doses of irradiation 1) enhances Fas expression, leading to more efficient CTL killing via Fas-dependent mechanisms in vitro; and 2) improves antitumor activity in vivo by adoptive transfer of these Ag-specific CTL. Treatment of carcinoembryonic Ag-expressing MC38 adenocarcinoma cells with irradiation (20 Gy) in vitro enhanced Fas expression at molecular, phenotypic, and functional levels. Furthermore, irradiation sensitized these targets to Ag-specific CTL killing via the Fas/Fas ligand pathway. We examined the effect of localized irradiation of s.c. growing tumors on the efficiency of CTL adoptive immunotherapy. Irradiation caused up-regulation of Fas by these tumor cells in situ, based on immunohistochemistry. Moreover, localized irradiation of the tumor significantly potentiated tumor rejection by these carcinoembryonic Ag-specific CTL. Overall, these results showed for the first time that 1) regulation of the Fas pathway in tumor cells by irradiation plays an important role in their sensitization to Ag-specific CTL; and 2) a combination regimen of tumor-targeted irradiation and CTL promotes more effective antitumor responses in vivo, which may have implications for the combination of immunotherapy and radiation therapy.     

Role of the Ring Methyl Groups in Abscisic Acid Activity in Erucic Acid Accumulation in Oilseed Rape (Brassica napus L.)

Modification of the structure of abscisic acid (ABA) has been reported to result in modification of its physiologic activity. In this study we tested the effect of removing methyl groups from the ring and of chirality of ABA on activity in microspore-derived embryos of oilseed rape (Brassica napus L.). The natural (+)-ABA molecule induced growth inhibition and an increase in the amount of erucic acid accumulated in the oil at medium concentrations less than 1 μm. (−)-ABA showed similar effects. Removing the 7′-methyl group resulted in a dramatic decrease in activity: (+)-7′-demethyl-ABA retained some activity as a growth inhibitor; a 10–100 μm concentration of this compound was needed for a response, and (−)-7′-demethyl-ABA was almost completely inactive. Similar effects were observed with regard to elongase activity, which catalyzes erucic acid biosynthesis from oleic acid. Removal of the 8′- and 9′-methyl groups resulted in a more complex response. These compounds all showed intermediate activity; for growth inhibition, the presence of the 9′-methyl was the more important determinant, whereas chirality dominated the response on erucic acid accumulation, with the (+)-enantiomers being more active. Received July 25, 1997; accepted October 31, 1997     

Hydrotris(1-pyrazolyl)borates of chromium(III)

The preparation and characterization of dichloro- (hydrotris(1-pyrazolyl)borato)pyridinechromium(III), CrCl₂(HB(PYZ)₃)Py, (Py = pyridine and HB(PYZ)₃^-1 is the hydrotris(1-pyrazolyl)borato anion) is described. The structure of the compound was determined by single crystal X-ray diffraction. Crystals were monoclinic, P2₁/c, a = 11.603(2), b = 9.845(1), c = 16.095(2) Å, β = 96.04(1)° with four formula units in the unit cell. Intensities were measured on a Nicolet P3 diffractometer with use of Mokα radiation. The structure was solved by standard methods and refined to R₁ = 0.0601, R₂ = 0.0397 based on 3142 independent reflections. Bond lengths and angles are normal. The pyridine molecule is oriented such that the plane bisects the angle between the two cis pyrazole rings. The synthesis and preparation of the related Cr(III) species CrCl₂(HB(PYZ)₃)pyrazole, Ph₄As[CrCl₃HB(PYZ)₃] and [Cr(HB(PYZ)₃)₂]PF₆ are described and the evaluation of the CrCl₂(HB(PYZ)3)L (L = pyridine or pyrazole) species for genotoxicity is discussed.     

Affinity labeling of 3 alpha-hydroxysteroid dehydrogenase with 3 alpha-bromoacetoxyandrosterone and 11 alpha-bromoacetoxyprogesterone. Isolation and sequence of active site peptides containing reactive cysteines; sequence confirmation using nucleotide sequence from a cDNA clone

Homogeneous 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD, EC 1.1.1.50) of rat liver cytosol is potently inhibited at its active site by nonsteroidal anti-inflammatory drugs (NSAIDs). Using 3 alpha-bromoacetoxy-5 alpha-androstan-17-one (BrAnd, a substrate analog) and 11 alpha-bromoacetoxyprogesterone (Br11P, a glucocorticoid analog) as affinity-labeling agents, kinetic evidence was obtained that these agents alkylate this site. Inactivation of 3 alpha-HSD with either [14C]BrAnd or [14C] Br11P led to the incorporation of 1 mol of affinity-labeling agent per enzyme monomer. Complete acid hydrolysis of 3 alpha-HSD radiolabeled with either agent followed by amino acid analysis led to the identification of [14C]carboxymethylcysteine indicating that [14C]BrAnd and [14C]Br11P covalently tag discrete reactive cysteine(s) at the enzyme active site. Trypsin digestion of [14C]BrAnd-inactivated 3 alpha-HSD followed by peptide mapping led to the purification of a single radiolabeled peptide (3A1) which gave the following sequence: H2N-Ser-Ile-Gly-Val-Ser-Asn-Phe-Asn-X-Arg-CO2H. Identical experiments on [14C] Br11P-inactivated 3 alpha-HSD led to the purification of three radiolabeled peptides (11P1-11P3). The major radiolabeled peptide (11P1) had an identical sequence to 3A1 which was tagged with [14C]BrAnd. The minor radiolabeled peptides had the following sequences: H2N-Ser-Lys-Asp-Ile-Ile-Leu-Val-Ser-Tyr-X-Thr-Leu-Gly-Ser-Ser-Arg-CO2H (11P2) and H2N-Ser-Pro-Val-Leu-Leu-Asp-Asp-Pro-Val-Leu-X-Ala-Ile-Ala-Lys-CO2H (11P3). In each peptide group X was identified as carboxymethylcysteine. Alignment of the peptide sequences with the primary structure of 3 alpha-HSD, deduced from its cDNA clone, assigned peptide 11P1 to residues 162-171, peptide 11P2 to residues 208-223, and peptide 11P3 to residues 232-246 of the amino acid sequence. The reactive cysteines correspond to Cys170, Cys217, and Cys242. We propose that Cys170 labeled by BrAnd may lie within the catalytic pocket of the enzyme. By contrast the 11 alpha-bromoacetoxy group in Br11P labeled several reactive cysteines which may be involved in the binding of glucocorticoids and NSAIDs.