The class A macrophage scavenger receptor type I (SR-AI) recognizes complement iC3b and mediates NF-κB activation

The macrophage scavenger receptor SR-AI binds to host tissue debris to perform clearance and it binds to bacteria for phagocytosis. In addition, SR-AI modulates macrophage activation through cell signaling. However, investigation of SR-AI signaling on macrophages is complicated due to its promiscuous ligand specificity that overlaps with other macrophage receptors. Therefore, we expressed SR-AI on HEK 293T cells to investigate its ligand binding and signaling. On 293T cells, SR-AI could respond to E. coli DH5α, leading to NF-κB activation and IL-8 production. However, this requires E. coli DH5α to be sensitized by fresh serum that is treated with heat-inactivation or complement C3 depletion. Anti-C3 antibody inhibits the binding of SR-AI to serum-sensitized DH5α and blocks DH5α stimulation of SR-AI signaling. Further analysis showed that SR-AI can directly bind to purified iC3b but not C3 or C3b. By mutagenesis, The SRCR domain of SR-AI was found to be essential in SR-AI binding to serum-sensitized DH5α. These results revealed a novel property of SR-AI as a complement receptor for iC3b-opsonized bacteria that can elicit cell signaling.     

Mutations in PRDM5 in brittle cornea syndrome identify a pathway regulating extracellular matrix development and maintenance

Extreme corneal fragility and thinning, which have a high risk of catastrophic spontaneous rupture, are the cardinal features of brittle cornea syndrome (BCS), an autosomal-recessive generalized connective tissue disorder. Enucleation is frequently the only management option for this condition, resulting in blindness and psychosocial distress. Even when the cornea remains grossly intact, visual function could also be impaired by a high degree of myopia and keratoconus. Deafness is another common feature and results in combined sensory deprivation. Using autozygosity mapping, we identified mutations in PRDM5 in families with BCS. We demonstrate that regulation of expression of extracellular matrix components, particularly fibrillar collagens, by PRDM5 is a key molecular mechanism that underlies corneal fragility in BCS and controls normal corneal development and maintenance. ZNF469, encoding a zinc finger protein of hitherto undefined function, has been identified as a quantitative trait locus for central corneal thickness, and mutations in this gene have been demonstrated in Tunisian Jewish and Palestinian kindreds with BCS. We show that ZNF469 and PRDM5, two genes that when mutated cause BCS, participate in the same regulatory pathway.     

Identification of a line of sheep carrying a putative autosomal gene increasing ovulation rate in sheep that does not appear to interact with mutations in the transforming growth factor beta superfamily

Sheep lines with mutations in single genes that have major effects on ovulation rate have been very useful in gaining a better understanding of pathways important in controlling follicular development and ovulation rate. To date however, all known mutations are in the transforming growth factor beta (TGFB) superfamily. Ovulation rates were measured in 720 progeny of 20 rams that were descendants of a single prolific ewe. Evaluation of ovulation rates of daughters of closely related sires suggests the presence of a segregating major gene Fecundity Davisdale (FECD) that increases ovulation rate between 0.4 and 0.8 in heterozygous daughters. Key features of mutations in genes of the TGFB superfamily pathway, such as synergistic interactions with other family members, infertility in homozygous carriers, and increased responsiveness to exogenous gonadotropins, were not observed in this line; thus, the mutation does not appear to be acting in the TGFB pathway. Hence, there is likely a novel mutation being carried in this line of sheep that alters ovulation rate. Future identification of the causative mutation may provide new insights into regulation of follicular development and ovulation rate.     

Some inhibitory effects of gentamicin on plant tissue cultures

Summary Tracheary element differentiation in cultured explants of pith parenchyma isolated from heads of romaine lettuce (Lactuca sativa L. var. Romana) was strongly inhibited by concentrations of gentamicin sulfate recommended for tissue culture media (50 to 100 μg/ml). Similar results were obtained with cultured explants of Jerusalem artichoke tuber (Helianthus tuberosus L.). Callus formation was suppressed in the presence of increasing levels of gentamicin sulfate in both tissue systems. Plant tissue culture media employed in studies on cell division and xylem differentiation should be supplemented with this antibiotic in concentrations of 10 μg/ml or less according to these results.     

QTL for live weight traits in Père David's x red deer interspecies hybrids

Interspecies hybrids between Père David's deer (Elaphurus davidianus) and red deer (Cervus elaphus) have proved to be a powerful resource in the search for quantitative trait loci (QTL) in deer. Several regions of the genome with significant effects on live weight and growth rates in backcross hybrids were detected. These include putative QTL for 6-month live weight (LOD 3.90) on linkage group 12, for 14-month live weight (LOD 3.19) on linkage group 1, three putative QTL for growth rate from 3 to 6 months (LOD 4.19 on linkage group 12, LOD 3.92 on linkage group 12, and LOD 3.34 on linkage group 5). In addition, linkage groups 20 and 1 appear to be associated with live weight traits between 9 and 16 months. The variance in traits explained by these QTL ranged between 5.3% and 11.2%. Allele substitution with Père David's alleles at different loci had both positive and negative effects on live weights and growth rates.     

Mapping and characterization of the functional epitopes of tissue inhibitor of metalloproteinases (TIMP)-3 using TIMP-1 as the scaffold: a new frontier in TIMP engineering

Tumor necrosis factor-alpha (TNF-alpha) converting enzyme (TACE/ADAM-17) is responsible for the release of TNF-alpha, a potent proinflammatory cytokine associated with many chronic debilitating diseases such as rheumatoid arthritis. Among the four variants of mammalian tissue inhibitor of metalloproteinases (TIMP-1 to -4), TACE is specifically inhibited by TIMP-3. We set out to delineate the basis for this specificity by examining the solvent accessibility of every epitope on the surface of a model of the truncated N-terminal domain form of TIMP-3 (N-TIMP-3) in a hypothetical complex with the crystal structure of TACE. The epitopes suspected of interacting with TACE were systematically transplanted onto N-TIMP-1. We succeeded in transforming N-TIMP-1 into an active inhibitor for TACE (K(i)(app) 15 nM) with the incorporation of Ser4, Leu67, Arg84, and the TIMP-3 AB-loop. The combined effects of these epitopes are additive. Unexpectedly, introduction of "super-N-TIMP-3" epitopes, defined in our previous work, only impaired the affinity of N-TIMP-1 for TACE. Our mutagenesis results indicate that TIMP-3-TACE interaction is a delicate process that requires highly refined surface topography and flexibility from both parties. Most importantly, our findings confirm that the individual characteristics of TIMP could be transplanted from one variant to another.     

THE ROLE OF PERIPHYTON IN PHOSPHORUS RETENTION IN SHALLOW FRESHWATER AQUATIC SYSTEMS

Eutrophication caused by phosphorus (P) leads to water quality problems in aquatic systems, particularly freshwaters, worldwide. Processing of nutrients in shallow habitats removes P from water naturally and periphyton influences P removal from the water column in flowing waters and wetlands. Periphyton plays several roles in removing P from the water column, including P uptake and deposition, filtering particulate P from the water, and attenuating flow, which decreases advective transport of particulate and dissolved P from sediments. Furthermore, periphyton photosynthesis locally increases pH by up to 1 unit, which can lead to increased precipitation of calcium phosphate, concurrent deposition of carbonate-phosphate complexes, and long-term burial of P. Actively photosynthesizing periphyton can cause super-saturated O₂ concentrations near the sediment surface encouraging deposition of metal phosphates. However, anoxia associated with periphyton respiration at night may offset this effect. Linking the small-scale functional role of periphyton to ecosystem-level P retention will require more detailed studies in a variety of ecosystems or large mesocosms. A case study from the Everglades illustrates the importance of considering the role of periphyton in P removal from wetlands. In general, periphyton tends to increase P retention and deposition. In pilot-scale constructed periphyton-dominated wetlands in South Florida, about half of the inflowing total P was removed.     

Mesocosm studies on the influence of phosphate enrichment on ammonium and nitrate flux in an oligotrophic lake

The fate of ¹⁵NH _inf4 ^sup+ and ¹⁵NOinf3⁻ was followed in control and PO _inf4 ^sup3− enriched 1570 l mesocosms filled with epilimnetic water from an oligotrophic Rocky Mountain lake. Volumetric incorporation of ¹⁵NH _inf4 ^sup+ and ¹⁵NO _inf3 ^sup− into phytoplankton and bacterioplankton (particulates between 280 and 0.7 μm), and crustacean zooplankton > 80 μm was enhanced by PO _inf4 ^sup3− , but no increase in biomass specific rates of uptake by phytoplankton and bacteria occurred for either form of ¹⁵N. Dilution of both ¹⁵NH _inf4 ^sup+ and ¹⁵NO _inf3 ^sup− by ¹⁴NH _inf4 ^sup+ and ¹⁴NO _inf3 ^sup− , respectively, was evident indicating regeneration of these nutrients, but regeneration rates were not effected by PO _inf4 ^sup3− enrichment. The results illustrate the strong trophic coupling between N dynamics and PO _inf4 ^sup3− enrichment in this system.     

Considering species richness and rarity when selecting optimal survey traps: comparisons of semiochemical baited flight intercept traps for Cerambycidae in eastern North America

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