In this article, we consider whether studies in rats can provide useful information regarding the debate about the functions of the primate prefrontal cortex. At a superficial level, comparison of regional specializations within the prefrontal cortices of different species suggests functional correspondence. Unfortunately, the nature of functional specialization in primate prefrontal cortex is controversial, and data supporting the idea of homology between specific areas of rat and primate prefrontal cortex are weak. Nevertheless, we argue here that studies of the computational functions within the relatively undifferentiated prefrontal cortex of rats can shed light on processing in primate prefrontal cortex.
A novel domain (the BRICHOS domain) of ∼100 amino acids has been identified in several previously unrelated proteins that are linked to major diseases. These include BRI , which is related to familial British and Danish dementia (FBD and FDD); Chondromodulin-I (ChM-I), related to chondrosarcoma; CA11, related to stomach cancer; and surfactant protein C (SP-C), related to respiratory distress syndrome (RDS). In several of these, the conserved BRICHOS domain is located in the propeptide region that is removed after proteolytic processing. Experímental data suggest that the role of this domain could be related to the complex post-translational processing of these proteins.
Transport of cystine across the cell membrane is essential for synthesis of the major cellular antioxidant glutathione. Cystine uptake in the brain occurs by both the Na -independent x cystine-glutamate exchanger and the X family of high-affinity, Na -dependent glutamate transporters. New evidence concerning the role of cystine transport in the defence against oxidative stress is described.
Family 3 G-protein-coupled receptors (GPCRs) comprise the metabotropic glutamate (mglu) receptors, GABA receptors, Ca -sensing receptors and some taste and putative pheromone receptors. All are composed of two domains, an extracellular ligand-binding domain and a transmembrane heptahelical domain that activates G proteins. Here we propose a model for the function of family 3 GPCRs that takes into account their structure. This model fits with specific pharmacological features of some family 3 GPCRs, such as modulation by positive and negative allosteric regulators. The model also reveals differences between GABA receptors and Group I mglu receptors: in the former there is 'tight' functional coupling between the two domains of the receptor whereas the 'loose' coupling in the latter gives these receptors specific features not shared by many other GPCRs.
Exploration of the potential of site-specific and target-oriented drug delivery systems has gained interest recently. Indeed, the efficient cellular mechanism of transferrin uptake has been exploited for the delivery not only of anticancer drugs and proteins, but also of therapeutic genes into proliferating malignant cells that overexpress transferrin receptors. In particular, the transferrin receptor offers great promise in the delivery of therapeutic agents across the blood-brain barrier to the brain.
The term 'apoptosis' describes an active process of cellular deconstruction originally contrasted morphologically with necrosis. The mistaken equivalence of the terms apoptosis and 'programmed cell death' has caused confusion and implied that apoptosis is an identifiable therapeutic target rather than a name of a type of cell death. The roots of confusion are suggested to lie not in superficial disagreements about the morphology and biochemistry of cell death, but in the lamentable disconnection of modern science from its philosophical foundations (i.e. Socratic definition, nominalism versus realism, and William of Ockham's advocacy of Aristotelian metaphysics over Plato's Theory of Forms). Renewed awareness of these issues might be the key to understanding that apoptosis is a created concept, not a real entity, and that the use of terms that defy definition has become an obstacle to clear thinking about preventable cell death.
The Mononegavirales virus group comprises several major human pathogens, including measles, rabies and Ebola viruses. This article reports a computational analysis of the C-terminal region of RNA-dependent RNA-polymerases from Mononegavirales. Using a combination of sequence similarity and threading analysis, a 2′-O-ribose methyltransferase domain was identified that is involved in the capping of viral mRNAs.
The ribosome is a molecular machine that converts genetic information in the form of RNA, into protein. Recent structural studies reveal a complex set of interactions between the ribosome and its ligands, mRNA and tRNA, that indicate ways in which the ribosome could avoid costly translational errors. Ribosomes must decode each successive codon accurately, and structural data provide a clear indication of how ribosomes limit recruitment of the wrong tRNA (sense errors). In a triplet-based genetic code there are three potential forward reading frames, only one of which encodes the correct protein. Errors in which the ribosome reads a codon out of the normal reading frame (frameshift errors) occur less frequently than sense errors, although it is not clear from structural data how these errors are avoided. Some mRNA sequences, termed programmed-frameshift sites, cause the ribosome to change reading frame. Based on recent work on these sites, this article proposes that the ribosome uses the structure of the codon-anticodon complex formed by the peptidyl-tRNA, especially its wobble interaction, to constrain the incoming aminoacyl-tRNA to the correct reading frame.
The study of the covalent modifications of the N-terminal tails of histones and their effects on chromatin structure and function, known as 'the histone code', is proceeding at a rapid pace. Recent work by several groups suggests that coactivators, such as p300/CBP, are also controlled by an array of various covalent modifications. This suggests the existence of a 'coactivator code' for p300/CBP and other seemingly promiscuous coregulators. Such a code could have wide-reaching implications for conferring specificity to general, ubiquitous transcriptional regulatory factors.
Prospecting the full biodiversity of nature to find leads for new drugs is not necessary. Because finding leads is aimed at identifying biological activity, structure is of secondary importance. Furthermore, although natural chemical diversity might be unrivalled, functional diversity is bound to be considerably less. It is likely that many millions of chemically distinct molecules exist in nature but it is inconceivable that the number of different biological functions is near this number. This is corroborated by knowledge obtained from the genome sequences of an increasing number of species. It is unlikely that ligands for specific molecular targets are restricted to one species and even individual compounds are often found in more than one species. Important molecular mechanisms are likely to be ubiquitous and there are no a priori reasons to assume that some are restricted to, for example, tropical rainforests. Thus, there are no obvious advantages of 'biodiversity prospecting', which will, possibly, endanger fragile ecosystems in the search for rare species.