A dioestrous increase in thymocyte proliferation during the oestrous cycle

Coitus, which precedes internal fertilisation, is a unique physiological event which allows motile allogeneic spermatozoa to enter the female host and invade her tissues. The cyclic cellular proliferation observed in the thymus of the female rat may be an important preparation of her immune system for this event.     

Bovine papillomavirus E5 oncoprotein binds to the 16K component of vacuolar H(+)-ATPases.

The major transforming protein of bovine papillomavirus type 1, E5, is mainly associated with endomembranes, specifically binding to a cellular protein of relative molecular mass 16,000 (16K). At the same time as transformation, E5 causes the phosphorylation of tyrosine residues in epidermal and platelet-derived growth factor receptors. We show here that the 16K protein associated with E5 is the 16K component of vacuolar ATPases. This protein is known to be an integral membrane protein in endosomes, bovine chromaffin granules, synaptic vesicles, fungal and plant vacuoles and clathrin-coated vesicles, as well as a component of gap-junction-like membrane complexes. Because proton pumps are critical for the function of cellular compartments that process growth-factor receptors, the interaction of E5 with the 16K protein could explain the pleiomorphic features of cells transformed by E5.     

Human-specific loss of regulatory DNA and the evolution of human-specific traits

Humans differ from other animals in many aspects of anatomy, physiology, and behaviour; however, the genotypic basis of most human-specific traits remains unknown. Recent whole-genome comparisons have made it possible to identify genes with elevated rates of amino acid change or divergent expression in humans, and non-coding sequences with accelerated base pair changes. Regulatory alterations may be particularly likely to produce phenotypic effects while preserving viability, and are known to underlie interesting evolutionary differences in other species. Here we identify molecular events particularly likely to produce significant regulatory changes in humans: complete deletion of sequences otherwise highly conserved between chimpanzees and other mammals. We confirm 510 such deletions in humans, which fall almost exclusively in non-coding regions and are enriched near genes involved in steroid hormone signalling and neural function. One deletion removes a sensory vibrissae and penile spine enhancer from the human androgen receptor (AR) gene, a molecular change correlated with anatomical loss of androgen-dependent sensory vibrissae and penile spines in the human lineage. Another deletion removes a forebrain subventricular zone enhancer near the tumour suppressor gene growth arrest and DNA-damage-inducible, gamma (GADD45G), a loss correlated with expansion of specific brain regions in humans. Deletions of tissue-specific enhancers may thus accompany both loss and gain traits in the human lineage, and provide specific examples of the kinds of regulatory alterations and inactivation events long proposed to have an important role in human evolutionary divergence.     

Lifespan of human lymphocyte subsets defined by CD45 isoforms.

The lifespan of thymic-derived or T lymphocytes is of particular interest because of their central role in immunological memory. Is the recall of a vaccination or early infection, which may be demonstrated clinically up to 50 years after antigen exposure, retained by a long-lived cell, or by its progeny? Using the observation that T lymphocyte expression of isoforms of CD45 corresponds with their ability to respond to recall antigens, we have investigated the lifespan of both CD45R0 (the subset containing responders, or 'memory' cells) and CD45RA (the unresponsive, or 'naive' subset) lymphocytes in a group of patients after radiotherapy. Here we report rapid loss of unstable chromosomes from the CD45R0 but not the CD45RA pool. Immunological memory therefore apparently resides in a population with a more rapid rate of division. Differing survival curves for the two subsets are best described by a model in which there is also reversion in vivo from the CD45R0 to the CD45RA phenotype. Expression of CD45R0 in T cells may therefore be reversible.     

A topographic map of recruitment in spinal cord

Animals move over a range of speeds by using rhythmic networks of neurons located in the spinal cord. Here we use electrophysiology and in vivo imaging in larval zebrafish (Danio rerio) to reveal a systematic relationship between the location of a spinal neuron and the minimal swimming frequency at which the neuron is active. Ventral motor neurons and excitatory interneurons are rhythmically active at the lowest swimming frequencies, with increasingly more dorsal excitatory neurons engaged as swimming frequency rises. Inhibitory interneurons follow the opposite pattern. These inverted patterns of recruitment are independent of cell soma size among interneurons, but may be partly explained by concomitant dorso-ventral gradients in input resistance. Laser ablations of ventral, but not dorsal, excitatory interneurons perturb slow movements, supporting a behavioural role for the topography. Our results reveal an unexpected pattern of organization within zebrafish spinal cord that underlies the production of movements of varying speeds.     

The complete nucleotide sequence of chromosome 3 of Plasmodium falciparum.

Analysis of Plasmodium falciparum chromosome 3, and comparison with chromosome 2, highlights novel features of chromosome organization and gene structure. The sub-telomeric regions of chromosome 3 show a conserved order of features, including repetitive DNA sequences, members of multigene families involved in pathogenesis and antigenic variation, a number of conserved pseudogenes, and several genes of unknown function. A putative centromere has been identified that has a core region of about 2 kilobases with an extremely high (adenine + thymidine) composition and arrays of tandem repeats. We have predicted 215 protein-coding genes and two transfer RNA genes in the 1,060,106-base-pair chromosome sequence. The predicted protein-coding genes can be divided into three main classes: 52.6% are not spliced, 45.1% have a large exon with short additional 5' or 3' exons, and 2.3% have a multiple exon structure more typical of higher eukaryotes.     

cDNA sequence of human apolipoprotein(a) is homologous to plasminogen

Lipoprotein(a) is an LDL-like lipoprotein whose concentration in plasma is correlated with atherosclerosis. The characteristic protein component of lipoprotein(a) is apolipoprotein(a) which is disulphide-linked to apolipoprotein B-100. Sequencing of cloned human apolipoprotein(a) complementary DNA shows that it is very similar to human plasminogen. It contains a serine protease domain and two types of plasminogen-like kringle domains, one of which is present in 37 copies.     

A novel antihypertensive agent: 1,2,3,5-tetrahydroimidazo[2,1-b]quinazoline

Zusammenfassung 1,2,3,5-Tetrahydroimidazo(2,1-b)chinazolin wurde als neuer Typ eines bei Tieren gut wirksamen Hypotensivums erkannt. Bei -blockierender Komponente wurde keine orthostatische Hypotonie festgestellt.