Specific binding of antigenic peptides to cell-associated MHC class I molecules

T lymphocytes recognize antigen in the form of peptides that associate with specific alleles of class I or class II major histocompatibility (MHC) molecules. By contrast with the clear MHC allele-specific binding of peptides to purified class II molecules purified solubilized class I molecules either bind relatively poorly or show degenerate specificity. Using photo-affinity labelling, we demonstrate here the specific interaction of peptides with cell-associated MHC class I molecules and show that this involves metabolically active processes.     

Can the behavioral sciences self-correct? A social epistemic study

Advocates of the self-corrective thesis argue that scientific method will refute false theories and find closer approximations to the truth in the long run. I discuss a contemporary interpretation of this thesis in terms of frequentist statistics in the context of the behavioral sciences. First, I identify experimental replications and systematic aggregation of evidence (meta-analysis) as the self-corrective mechanism. Then, I present a computer simulation study of scientific communities that implement this mechanism to argue that frequentist statistics may converge upon a correct estimate or not depending on the social structure of the community that uses it. Based on this study, I argue that methodological explanations of the “replicability crisis” in psychology are limited and propose an alternative explanation in terms of biases. Finally, I conclude suggesting that scientific self-correction should be understood as an interaction effect between inference methods and social structures.     

Molecular basis of parathyroid hormone receptor signaling and trafficking: a family B GPCR paradigm

The parathyroid hormone (PTH) receptor type 1 (PTHR), a G protein-coupled receptor (GPCR), transmits signals to two hormone systems—PTH, endocrine and homeostatic, and PTH-related peptide (PTHrP), paracrine—to regulate different biological processes. PTHR responds to these hormonal stimuli by activating heterotrimeric G proteins, such as G_S that stimulates cAMP production. It was thought that the PTHR, as for all other GPCRs, is only active and signals through G proteins on the cell membrane, and internalizes into a cell to be desensitized and eventually degraded or recycled. Recent studies with cultured cell and animal models reveal a new pathway that involves sustained cAMP signaling from intracellular domains. Not only do these studies challenge the paradigm that cAMP production triggered by activated GPCRs originates exclusively at the cell membrane but they also advance a comprehensive model to account for the functional differences between PTH and PTHrP acting through the same receptor.     

Rediscovered population of Mexican Plateau spotted whiptail lizard, Aspidoscelis septemvittata , from México, D.F.

Multiple surveys carried out by herpetologists in México, D.F., during the 1980s failed to find specimens of Aspidoscelis septemvitatta (Squamata: Teiidae). However, 10 specimens were recently collected to the east of México, D.F., inside a protected area, Sierra de Santa Catarina. The Sierra de Santa Catarina has been heavily modified by human activity and habitation. Morphological and natural history information about the specimens are presented, as well as notes on locality.     

Steady-state kinetic studies with the polysulfonate U-9843, an HIV reverse transcriptase inhibitor

The tetramer of ethylenesulfonic acid (U-9843) is a potent inhibitor of HIV-1 RT^* and possesses excellent antiviral activity at nontoxic doses in HIV-1 infected lymphocytes grown in tissue culture. Kinetic studies of the HIV-1 RT-catalyzed RNA-directed DNA polymerase activity were carried out in order to determine if the inhibitor interacts with the template: primer or the deoxyribonucleotide triphosphate (dNTP) binding sites of the polymerase. Michaelis-Menten kinetics, which are based on the establishment of a rapid equilibrium between the enzyme and its substrates, proved inadequate for the analysis of the experimental data. The data were thus analyzed using steady-state Briggs-Haldane kinetics assuming that the template:primer binds to the enzyme first, followed by the binding of the dNTP and that the polymerase is a processive enzyme. Based on these assumptions, a velocity equation was derived which allows the calculation of all the specific forward and backward rate constants for the reactions occurring between the enzyme, its substrates and the inhibitor. The calculated rate constants are in agreement with this model and the results indicated that U-9843 acts as a noncompetitive inhibitor with respect to both the template:primer and dNTP binding sites. Hence, U-9843 exhibits the same binding affinity for the free enzyme as for the enzyme-substrate complexes and must inhibit the RT polymerase by interacting with a site distinct from the substrate binding sites. Thus, U-9843 appears to impair an event occurring after the formation of the enzyme-substrate complexes, which involves either an event leading up to the formation of the phosphoester bond, the formation of the ester bond itself or translocation of the enzyme relative to its template:primer following the formation of the ester bond.     

On the question of American eels,Anguilla rostrata versus European eels,Anguilla anguilla

Zusammenfassung Der amerikanische AalAnguilla rostrata (2n=38; 20M+18A) gehört einer anderen Spezies an als der europäischeAnguilla anguilla (2n=38; 32M+6A).

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This work was supported in part by a grant No. CA 05138 from the National Cancer Institute, U.S. Public Health Service.     

Rewarding effects of opiates are absent in mice lacking the receptor for substance P

Modulation of substance P activity offers a radical new approach to the management of depression, anxiety and stress. The substance P receptor is highly expressed in areas of the brain that are implicated in these behaviours, but also in other areas such as the nucleus accumbens which mediate the motivational properties of both natural rewards such as food and of drugs of abuse such as opiates. Here we show a loss of the rewarding properties of morphine in mice with a genetic disruption of the substance P receptor. The loss was specific to morphine, as both groups of mice responded when cocaine or food were used as rewards. The physical response to opiate withdrawal was also reduced in substance P receptor knockout mice. We conclude that substance P has an important and specific role in mediating the motivational aspects of opiates and may represent a new pharmacological route for the control of drug abuse.     

Sufficient Reason and Reason Enough

I offer an analysis of the Principle of Sufficient Reason and its relevancy for the scientific endeavour. I submit that the world is not, and cannot be, rational—only some brained beings are. The Principle of Sufficient Reason is not a necessary truth nor a physical law. It is just a guiding metanomological hypothesis justified a posteriori by its success in helping us to unveil the mechanisms that operate in Nature.     

New occurrences and host records for two species of parasitic isopods (Isopoda,Cymothoida, Bopyridae) associated with caridean shrimps (Decapoda,Caridea) from Brazil

ABSTRACT

Two species of bopyrid isopods of the Bopyrinae subfamily are recorded from new localities and hosts in northeastern Brazil. Parabopyrella lata (Nierstrasz and Brender à Brandis, 1929) was recorded from the state of Ceará, found for the first time parasitising the caridean shrimp Alpheus packardii Kingsley, 1880. In addition, Probopyrus cf. pandalicola (Packard, 1879) is recorded from the state of Bahia, parasitising the palaemonid shrimp Palaemon northropi (Rankin, 1898). Taxonomic comments are provided for each species.