Van Fraassen meets Popper: Logical relations and cognitive abilities

Van Fraassen, like Popper before him, assumes that confirmation and disconfirmation relations are logical relations and thus hold only among abstract items. This raises a problem about how experience, for Popper, and observables, for van Fraassen, enter into epistemic evaluations. Each philosopher offers a drastic proposal: Popper holds that basic statements are accepted by convention; van Fraassen introduces his “pragmatic tautology.” Another alternative is to reject the claim that all evaluative relations are logical relations. Ayer proposed this option in responding to Popper, as did Sosa in a different context. I argue that this option should be pursued and propose a line of research that the option suggests.     

Peptide bond formation destabilizes Shine-Dalgarno interaction on the ribosome

The ribosome is a molecular machine that translates the genetic code contained in the messenger RNA into an amino acid sequence through repetitive cycles of transfer RNA selection, peptide bond formation and translocation. Here we demonstrate an optical tweezer assay to measure the rupture force between a single ribosome complex and mRNA. The rupture force was compared between ribosome complexes assembled on an mRNA with and without a strong Shine-Dalgarno (SD) sequence-a sequence found just upstream of the coding region of bacterial mRNAs, involved in translation initiation. The removal of the SD sequence significantly reduced the rupture force in complexes carrying an aminoacyl tRNA, Phe-tRNA(Phe), in the A site, indicating that the SD interactions contribute significantly to the stability of the ribosomal complex on the mRNA before peptide bond formation. In contrast, the presence of a peptidyl tRNA analogue, N-acetyl-Phe-tRNA(Phe), in the A site, which mimicked the post-peptidyl transfer state, weakened the rupture force as compared to the complex with Phe-tRNA(Phe), and the resultant force was the same for both the SD-containing and SD-deficient mRNAs. These results suggest that formation of the first peptide bond destabilizes the SD interaction, resulting in the weakening of the force with which the ribosome grips an mRNA. This might be an important requirement to facilitate movement of the ribosome along mRNA during the first translocation step.     

Basis for a ubiquitin-like protein thioester switch toggling E1-E2 affinity

Ubiquitin-like proteins (UBLs) are conjugated by dynamic E1-E2-E3 enzyme cascades. E1 enzymes activate UBLs by catalysing UBL carboxy-terminal adenylation, forming a covalent E1 throught UBL thioester intermediate, and generating a thioester-linked E2 throught UBL product, which must be released for subsequent reactions. Here we report the structural analysis of a trapped UBL activation complex for the human NEDD8 pathway, containing NEDD8's heterodimeric E1 (APPBP1-UBA3), two NEDD8s (one thioester-linked to E1, one noncovalently associated for adenylation), a catalytically inactive E2 (Ubc12), and MgATP. The results suggest that a thioester switch toggles E1-E2 affinities. Two E2 binding sites depend on NEDD8 being thioester-linked to E1. One is unmasked by a striking E1 conformational change. The other comes directly from the thioester-bound NEDD8. After NEDD8 transfer to E2, reversion to an alternate E1 conformation would facilitate release of the E2 throught NEDD8 thioester product. Thus, transferring the UBL's thioester linkage between successive conjugation enzymes can induce conformational changes and alter interaction networks to drive consecutive steps in UBL cascades.     

The ectodomain of Toll-like receptor 9 is cleaved to generate a functional receptor

Mammalian Toll-like receptors (TLRs) 3, 7, 8 and 9 initiate immune responses to infection by recognizing microbial nucleic acids; however, these responses come at the cost of potential autoimmunity owing to inappropriate recognition of self nucleic acids. The localization of TLR9 and TLR7 to intracellular compartments seems to have a role in facilitating responses to viral nucleic acids while maintaining tolerance to self nucleic acids, yet the cell biology regulating the transport and localization of these receptors remains poorly understood. Here we define the route by which TLR9 and TLR7 exit the endoplasmic reticulum and travel to endolysosomes in mouse macrophages and dendritic cells. The ectodomains of TLR9 and TLR7 are cleaved in the endolysosome, such that no full-length protein is detectable in the compartment where ligand is recognized. Notably, although both the full-length and cleaved forms of TLR9 are capable of binding ligand, only the processed form recruits MyD88 on activation, indicating that this truncated receptor, rather than the full-length form, is functional. Furthermore, conditions that prevent receptor proteolysis, including forced TLR9 surface localization, render the receptor non-functional. We propose that ectodomain cleavage represents a strategy to restrict receptor activation to endolysosomal compartments and prevent TLRs from responding to self nucleic acids.     

Esox lucius (Esocidae) and Stizostedion vitreum (Percidae) in the Green River basin, Colorado and Utah

Northern pike, Esox lucius , stocked in the Yampa River in 1977, invaded the mainstream Green River by 1981 and subsequently increased in range and abundance. The speed of this invasion is indicated by two recaptured pike that moved 78 and 110 km, respectively, downstream in about one year. Pike stomachs (n = 123) were usually empty (54.5%), but some contained fish (43%) and nonfish items (2.4%). Red shiner, Notropis lutrensis , and fathead minnow, Pimephales promelas , predominated among the 12 fish species eaten. Walleye, Stizostedion vitreum , presumably introduced to the Green River drainage in the 1960s, was widely distributed but low in abundance. Most of 61 adult walleye stomachs contained food (60.7%) ; of 6 fish species eaten, channel catfish, lctalurus punctatus , and fathead minnow were most frequently consumed. Northern pike and walleye were captured in habitats occupied by endangered Colorado River fishes, particularly Colorado squawfish, Ptychocheilus lucius . Predation on endangered fishes was not detected, but northern pike and walleye consumed at least three other native fishes. The northern pike may pose a threat to endangered fishes due to its population expansion, piscivory, and resource sharing. Diets of northern pike and walleye species should be further evaluated if their abundance increases.     

Migrating Mormon Crickets, Anabrus simplex (Orthoptera: Tettigoniidae), as food for stream fishes

Migrating bands Mormon crickets ( Ananbrus simplex ) were observed crossing the Green and Yampa rivers in Dinosaur National Monument, Colorado and Utah, in 1986 and 1987. Swimming crickets were swept downstream and eaten by four- endemic and seven introduced fish species. Included were two endangered fishes, Colorado squawfish ( Ptychocheilus lucius ) and humpback chub ( Gila cypha ). Direct and indirect effects to aquatic food webs associated with application of pesticides for Mormon cricket control may pose a threat to these fishes and to man.