The heparin binding domain of S-protein/vitronectin binds to complement components C7, C8, and C9 and perforin from cytolytic T-cells and inhibits their lytic activities

S-Protein/vitronectin is a serum glycoprotein that inhibits the lytic activity of the membrane attack complex of complement, i.e., of the complex including the proteins C5b, C6, C7, C8, and C9n. We show that intact S-protein/vitronectin or its cyanogen bromide generated fragments also inhibit the hemolysis mediated by perforin from cytotoxic T-cells at 45 and 11 microM, respectively. The glycosaminoglycan binding site of S-protein/vitronectin is responsible for the inhibition, since a synthetic peptide corresponding to a part of this highly basic domain (amino acid residues 348-360) inhibits complement- as well as perforin-mediated cytolysis. In the case of C9, the synthetic peptide binds to the acidic residues occurring in its N-terminal cysteine-rich domain (residues 101-111). Antibodies raised against this particular segment react 25-fold better with the polymerized form of C9 as compared with its monomeric form, indicating that this site becomes exposed only upon the hydrophilic-amphiphilic transition of C9. Since the cysteine-rich domain of C9 has been shown to be highly conserved in C6, C7, and C8 as well as in perforin, the inhibition of the lytic activities of these molecules by S-protein/vitronectin or by peptides corresponding to its heparin binding site may be explained by a similar mechanism.     

Midsummer heat wave effects on lacustrine plankton: Variation of assemblage structure and fatty acid composition

The effects of the 2003 European heat wave on a freshwater plankton assemblage and its fatty acid (FA) composition were investigated. Composition and FA profiles of four size categories of planktonic organisms collected in 2003 were compared to those of the colder year 2002.     

Climatic forcing and larval dispersal capabilities shape the replenishment of fishes and their habitat‐forming biota on a tropical coral reef

Fluctuations in marine populations often relate to the supply of recruits by oceanic currents. Variation in these currents is typically driven by large‐scale changes in climate, in particular ENSO (El Nino Southern Oscillation). The dependence on large‐scale climatic changes may, however, be modified by early life history traits of marine taxa. Based on eight years of annual surveys, along 150 km of coastline, we examined how ENSO influenced abundance of juvenile fish, coral spat, and canopy‐forming macroalgae. We then investigated what traits make populations of some fish families more reliant on the ENSO relationship than others. Abundance of juvenile fish and coral recruits was generally positively correlated with the Southern Oscillation Index (SOI), higher densities recorded during La Niña years, when the ENSO‐influenced Leeuwin Current is stronger and sea surface temperature higher. The relationship is typically positive and stronger among fish families with shorter pelagic larval durations and stronger swimming abilities. The relationship is also stronger at sites on the coral back reef, although the strongest of all relationships were among the lethrinids (r = .9), siganids (r = .9), and mullids (r = .8), which recruit to macroalgal meadows in the lagoon. ENSO effects on habitat seem to moderate SOI–juvenile abundance relationship. Macroalgal canopies are higher during La Niña years, providing more favorable habitat for juvenile fish and strengthening the SOI effect on juvenile abundance. Conversely, loss of coral following a La Niña‐related heat wave may have compromised postsettlement survival of coral dependent species, weakening the influence of SOI on their abundance. This assessment of ENSO effects on tropical fish and habitat‐forming biota and how it is mediated by functional ecology improves our ability to predict and manage changes in the replenishment of marine populations.     

Developmental study of afferented and deafferented bee antennal lobes.

The role of antennal sensory projections on the ontogeny of the bee antennal lobe was analyzed using both light and transmission electron microscopy. Normal and deafferented developing antennal lobes were examined. The results obtained show that (1) initiation of synaptogenesis in the antennal lobe is independent of the arrival of sensory inputs; (2) sensory inputs are necessary for setting up the glomerular antennal lobe organization; (3) regressive events, such as the reduction of synapse density, occur during the development of the antennal lobe; and (4) glomeruli formation appears as related to glia development.     

Balancing Detection and Eradication for Control of Epidemics: Sudden Oak Death in Mixed-Species Stands

Culling of infected individuals is a widely used measure for the control of several plant and animal pathogens but culling first requires detection of often cryptically-infected hosts. In this paper, we address the problem of how to allocate resources between detection and culling when the budget for disease management is limited. The results are generic but we motivate the problem for the control of a botanical epidemic in a natural ecosystem: sudden oak death in mixed evergreen forests in coastal California, in which species composition is generally dominated by a spreader species (bay laurel) and a second host species (coast live oak) that is an epidemiological dead-end in that it does not transmit infection but which is frequently a target for preservation. Using a combination of an epidemiological model for two host species with a common pathogen together with optimal control theory we address the problem of how to balance the allocation of resources for detection and epidemic control in order to preserve both host species in the ecosystem. Contrary to simple expectations our results show that an intermediate level of detection is optimal. Low levels of detection, characteristic of low effort expended on searching and detection of diseased trees, and high detection levels, exemplified by the deployment of large amounts of resources to identify diseased trees, fail to bring the epidemic under control. Importantly, we show that a slight change in the balance between the resources allocated to detection and those allocated to control may lead to drastic inefficiencies in control strategies. The results hold when quarantine is introduced to reduce the ingress of infected material into the region of interest.     

Size distribution of luteal cells from pregnant and non-pregnant marmoset monkeys and a comparison of the morphology of marmoset luteal cells with those from the human corpus luteum

The size distribution of marmoset luteal cells was determined on Days 6, 14 and 20 after ovulation in non-pregnant cycles and in early pregnancy. Image analysis was used to estimate the cell diameter of dispersed cells prepared from the marmoset corpus luteum (CL). Steroidogenic cells showed a size distribution consistent with one population of cells. There was a significant increase in mean cell diameter (P less than 0.05) from Day 6 to Day 14 in pregnant and non-pregnant animals with no further increase on Day 20. Micrographs of marmoset luteal tissue showed cells of greater than 10 micron containing the organelles typical of steroid-producing cells, and smaller non-steroidogenic cells surrounding the steroid-producing cells. On the basis of microscopy, there were no areas within the CL where cell composition was noticeably different. In contrast, micrographs of human luteal tissue showed two types of steroidogenic cell; most cells were similar to those in the marmoset CL but a smaller population of smaller cells could be distinguished around the periphery and along vascular septa. It is likely that these smaller and larger types of steroidogenic cells are of theca and granulosa cell origin respectively, the two cell populations differing in the degree of electron density and amount of rough endoplasmic reticulum. A distinguishing feature between marmoset and human luteal cells was the shape of the mitochondrian which were considerably rounder in marmoset luteal cells. The origin of steroidogenic cells in the marmoset CL is unclear, although in marmosets and man the luteal cell types display morphological characteristics distinct from the large and small luteal cells described for CL of the domestic ungulates.     

Perforin is present only in normal activated Lyt2+ T lymphocytes and not in L3T4+ cells, but the serine protease granzyme A is made by both subsets.

We show that among the subsets of peripheral T lymphocytes (Lyt2+ L3T4- and L3T4+ Lyt2- cells) activated in short-term cultures by stimulation with H-2 incompatible leukocytes 97% of the cytolytic activity and all detectable perforin activity resides in the Lyt2+ cells. But both populations contain approximately equal amounts of a serine protease, granzyme A, the expression of which was previously thought to be restricted to cytolytic T lymphocytes.     

Selection of somatic hybrids between diploid clones of potato (Solanum tuberosum L.) transformed by direct gene transfer

Summary Five diploid potato clones have been transformed by electroporation of protoplasts with different selectable markers. The resulting diploid regenerated plants have been used in somatic hybridization. It has been shown that hybrid cell selection on the basis of antibiotic or herbicide resistances brought by the two parents of fusion is an efficient method for the recovery of tetraploid somatic hybrids.     

Pharmacology of L-660,711 (MK-571): a novel potent and selective leukotriene D4 receptor antagonist

L-660,711 (3-(3-(2-(7-chloro-2-quinolinyl)ethenyl)phenyl) ((3-dimethyl amino-3-oxo propyl)thio)methyl)thio)propanoic acid is a potent and selective competitive inhibitor of [3H]leukotriene D4 binding in guinea pig (Ki value, 0.22 nM) and human (Ki value, 2.1 nM) lung membranes but is essentially inactive versus [3H]leukotriene C4 binding (IC50 value in guinea pig lung, 23 microM). Functionally it competitively antagonized contractions of guinea pig trachea and ileum induced by leukotriene (LT) D4 (respective pA2 values, 9.4 and 10.5) and LTE4 (respective pA2 values, 9.1 and 10.4) and contractions of human trachea induced by LTD4 (pA2 value, 8.5). L-660,711 (5.8 x 10(-8)M) antagonized contractions of guinea pig trachea induced by LTC4 in the absence (dose ratio = 28) but not in the presence of 45 mM L-serine borate (dose ratio less than 2). L-660,711 (1.9 x 10(-5)M) did not block contractions of guinea pig trachea induced by histamine, acetylcholine, 5-hydroxytryptamine, PGF2 alpha, U-44069, or PGD2. In the presence of atropine, mepyramine, and indomethacin, L-660,711 (1.9 x 10(-5)M) inhibited a small component of the response to antigen on guinea pig trachea but completely blocked anti-IgE-induced contractions of human trachea. L-660,711 (i.v.) antagonized bronchoconstriction induced in anesthetized guinea pigs by i.v. LTC4, LTD4, and LTE4 but did not block bronchoconstriction to arachidonic acid, U-44069, 5-hydroxytryptamine, histamine, or acetylcholine. Intraduodenal L-660,711 antagonized LTD4 (0.2-12.8 micrograms/kg)-induced bronchoconstriction in guinea pigs, and p.o. L-660,711 blocked LTD4- and Ascaris-induced bronchoconstriction in conscious squirrel monkeys and ovalbumin-induced bronchoconstriction in conscious sensitized rats treated with methysergide (3 micrograms/kg). The pharmacological profile of L-660,711 indicates that it is a potent, selective, orally active leukotriene receptor antagonist which is well suited to determine the role played by LTD4 and LTE4 in asthma and other pathophysiologic conditions.     

The pharmacology of L-670,596, a potent and selective thromboxane/prostaglandin endoperoxide receptor antagonist

L-670,596 ((-)6,8-difluoro-9-rho-methylsulfonyl benzyl-1,2,3,4- tetrahydrocarbazol-1-yl-acetic acid) has been shown to be a potent receptor antagonist as evidenced by the inhibition of the binding of 125I-labeled PTA-OH to human platelets (IC50, 5.5 x 10(-9) M), inhibition of U-44069 induced aggregation of human platelet rich plasma (IC50, 1.1 x 10(-7) M), and competitive inhibition of contractions of the guinea pig tracheal chain induced by U-44069 (pA2,9.0). The compound was also active in vivo as shown by inhibition of arachidonic acid and U-44069 induced bronchoconstriction in the guinea pig (ED50 values, 0.04 and 0.03 mg/kg i.v., respectively), U44069 induced renal vasoconstriction in the pig (ED50, 0.02 mg/kg i.v.), and inhibition of ex vivo aggregation of rhesus monkey platelets to U-44069 (active 1-5 mg/kg p.o.). The selectivity of the compound was indicated by the failure to inhibit, first, ADP-induced human or primate platelet aggregation and, second, bronchoconstriction in the guinea pig in vivo and contraction of the guinea pig tracheal chain in vitro to a variety of agonists. It is concluded that L-670,596 is a potent, selective, orally active thromboxane A2/prostaglandin endoperoxide receptor antagonist.