Determination of dependence of binding parameters on receptor occupancy

Measurements of the binding of ligand to receptors that are macromolecules, either free or components of biomembranes, often show deviation from what is expected of a simple reaction described by an association and a dissociation rate constant. A more versatile model and more discriminating experiments are required for a satisfactory explanation. This paper is based on a general model of the binding reaction in which the rate constants and equilibrium constant are dependent upon occupancy of receptors. The analysis of the model leads to three kinds of experiments: (1) equilibrium measurements which permit quantitative determination of a dissociation equilibrium parameter as a function of receptor occupancy; (2) measurements prior to equilibrium which yield the same information; and (3) measurements prior to equilibrium which reveal quantitatively the dependence of both association and dissociation rate parameters separately, on occupancy.     

AVPR1b variation and the emergence of adaptive phenotypes in Platyrrhini primates

Platyrrhini (New World monkeys, NWm) are a group of primates characterized by behavioral and reproductive traits that are otherwise uncommon among primates, including social monogamy, direct paternal care, and twin births. As a consequence, the study of Platyrrhine primates is an invaluable tool for the discovery of the genetic repertoire underlying these taxon‐specific traits. Recently, high conservation of vasopressin (AVP) sequence, in contrast with high variability of oxytocin (OXT), has been described in NWm. AVP and OXT functions are possible due to interaction with their receptors: AVPR1a, AVPR1b, AVPR2, and OXTR; and the variability in this system is associated with the traits mentioned above. Understanding the variability in the receptors is thus fundamental to understand the function and evolution of the system as a whole. Here we describe the variability of AVPR1b coding region in 20 NWm species, which is well‐known to influence behavioral traits such as aggression, anxiety, and stress control in placental mammals. Our results indicate that 4% of AVPR1b sites may be under positive selection and a significant number of sites under relaxed selective constraint. Considering the known role of AVPR1b, we suggest that some of the changes described here for the Platyrrhini may be a part of the genetic repertoire connected with the complex network of neuroendocrine mechanisms of AVP–OXT system in the modulation of the HPA axis. Thus, these changes may have promoted the emergence of social behaviors such as direct paternal care in socially monogamous species that are also characterized by small body size and twin births.     

Rinvenimenti Floristici Marchigiani

Summary

The author communicates the list of taxa not commonly occurring in the “Marche”, which he has collected in localities not yet mentioned in the bibliography of that area. The list includes also several species more or less widely cultivated in that zone.     

A Cholesterol Recognition Amino Acid Consensus Domain in GP64 Fusion Protein Facilitates Anchoring of Baculovirus to Mammalian Cells

Baculoviridae is a large family of double-stranded DNA viruses that selectively infect insects. Autographa californica multiple nucleopolyhedrovirus (AcMNPV) is the best-studied baculovirus from the family. Many studies over the last several years have shown that AcMNPV can enter a wide variety of mammalian cells and deliver genetic material for foreign gene expression. While most animal viruses studied so far have developed sophisticated mechanisms to selectively infect specific cells and tissues in an organism, AcMNPV can penetrate and deliver foreign genes into most cells studied to this date. The details about the mechanisms of internalization have been partially described. In the present study, we have identified a cholesterol recognition amino acid consensus (CRAC) domain present in the AcMNPV envelope fusion protein GP64. We demonstrated the association of a CRAC domain with cholesterol, which is important to facilitate the anchoring of the virus at the mammalian cell membrane. Furthermore, this initial anchoring favors AcMNPV endocytosis via a dynamin- and clathrin-dependent mechanism. Under these conditions, efficient baculovirus-driven gene expression is obtained. In contrast, when cholesterol is reduced from the plasma membrane, AcMNPV enters the cell via a dynamin- and clathrin-independent mechanism. The result of using this alternative internalization pathway is a reduced level of baculovirus-driven gene expression. This study is the first to document the importance of a novel CRAC domain in GP64 and its role in modulating gene delivery in AcMNPV.     

Immune surveillance and neoplasia—II A two-stage mathematical model

In a previous paper (DeLisi and Rescigno, 1977) a model for the interaction of tumor cells and killer lymphocytes was presented. Although that model was highly simplified, the qualitative behavior was in accord with intuitive expectations and a wide range of data. It could not however account forde novo tumor development. In this paper a slightly more realistic model is presented by introducing a delay in the formation of killer lymphocytes. This is done by requiring two stages in the production of a killer. We show that introduction of this second stage allows tumor development from even a single cell, thus removing an important limitation of two variable systems.