Temporal precision in the neural code and the timescales of natural vision

The timing of action potentials relative to sensory stimuli can be precise down to milliseconds in the visual system, even though the relevant timescales of natural vision are much slower. The existence of such precision contributes to a fundamental debate over the basis of the neural code and, specifically, what timescales are important for neural computation. Using recordings in the lateral geniculate nucleus, here we demonstrate that the relevant timescale of neuronal spike trains depends on the frequency content of the visual stimulus, and that 'relative', not absolute, precision is maintained both during spatially uniform white-noise visual stimuli and naturalistic movies. Using information-theoretic techniques, we demonstrate a clear role of relative precision, and show that the experimentally observed temporal structure in the neuronal response is necessary to represent accurately the more slowly changing visual world. By establishing a functional role of precision, we link visual neuron function on slow timescales to temporal structure in the response at faster timescales, and uncover a straightforward purpose of fine-timescale features of neuronal spike trains.     

Developmental reprogramming after chromosome transfer into mitotic mouse zygotes

Until now, animal cloning and the production of embryonic stem cell lines by somatic cell nuclear transfer have relied on introducing nuclei into meiotic oocytes. In contrast, attempts at somatic cell nuclear transfer into fertilized interphase zygotes have failed. As a result, it has generally been assumed that unfertilized human oocytes will be required for the generation of tailored human embryonic stem cell lines from patients by somatic cell nuclear transfer. Here we report, however, that, unlike interphase zygotes, mouse zygotes temporarily arrested in mitosis can support somatic cell reprogramming, the production of embryonic stem cell lines and the full-term development of cloned animals. Thus, human zygotes and perhaps human embryonic blastomeres may be useful supplements to human oocytes for the creation of patient-derived human embryonic stem cells.     

A binding site for the T-cell co-receptor CD8 on the alpha 3 domain of HLA-A2

Adhesion measurements between CD8 and 48 point mutants of HLA-A2.1 show that the CD8 alpha-chain binds to the alpha 3 domain of HLA-A2.1. Three clusters of alpha 3 residues contribute to the binding, with an exposed, negatively charged loop (residues 223-229) playing a dominant role. CD8 binding correlates with cytotoxic T-cell recognition and sensitivity to inhibition by anti-CD8 antibodies. Impaired alloreactive T-cell recognition of an HLA-A2.1 mutant with reduced affinity for CD8 is not restored by functional CD8 binding sites on an antigenically irrelevant class I molecule. Therefore, complexes of CD8 and the T-cell receptor bound to the same class I major histocompatibility complex molecule seem to be necessary for T-cell activation.     

Atomic structure of a fragment of human CD4 containing two immunoglobulin-like domains.

The structure of an N-terminal fragment of CD4 has been determined to 2.4 A resolution. It has two tightly abutting domains connected by a continuous beta strand. Both have the immunoglobulin fold, but domain 2 has a truncated beta barrel and a non-standard disulphide bond. The binding sites for monoclonal antibodies, class II major histocompatibility complex molecules, and human immunodeficiency virus gp120 can be mapped on the molecular surface.     

Binding of iron by rat placental tissues

Zusammenfassung Nachweis, dass das Eisenbindungsvermögen der Dottersackplacenta bedeutend grösser ist als bei der chorioallantoiden Placenta und dass diese auch unter der Einwirkung von den Stoffwechsel beeinflussenden Stoffen ein verschiedenes Verhalten zeigt.

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This work was supported by U.S. Public Health Service Grant No. HD05016 and Predoctoral Fellowship Grant No. FO1-DE41063 to R.J.B.G.     

Bcr encodes a GTPase-activating protein for p21rac

More than thirty small guanine nucleotide-binding proteins related to the ras-encoded oncoprotein, termed Ras or p21ras, are known. They regulate many fundamental processes in all eukaryotic cells, such as growth, vesicle traffic and cytoskeletal organization. GTPase-activating proteins (GAPs) accelerate the intrinsic rate of GTP hydrolysis of Ras-related proteins, leading to down-regulation of the active GTP-bound form. For p21ras, two GAP proteins are known, rasGAP and the neurofibromatosis (NF1) gene product. There is evidence that rasGAP may also be a target protein for regulation by Ras and be involved in downstream signalling. We have purified a GAP protein for p21rho, which is involved in the regulation of the actin cytoskeleton. Partial sequencing of rhoGAP reveals significant homology with the product of the bcr (breakpoint cluster region) gene, the translocation breakpoint in Philadelphia chromosome-positive chronic myeloid leukaemias. We show here that the carboxy-terminal domains of the bcr-encoded protein (Bcr) and of a Bcr-related protein, n-chimaerin, are both GAP proteins for the Ras-related GTP-binding protein, p21rac. This result suggest that Bcr could be a target for regulation by Rac and has important new implications for the role of bcr translocations in leukaemia.