Progress in biomimetic carbohydrate recognition

The importance of carbohydrate recognition in biology, and the unusual challenges involved, have lead to great interest in mimicking saccharide-binding proteins such as lectins. In this review, we discuss the design of artificial carbohydrate receptors, focusing on those which work under natural (i.e. aqueous) conditions. The problem is intrinsically difficult because of the similarity between substrate (carbohydrate) and solvent (water) and, accordingly, progress has been slow. However, recent developments suggest that solutions can be found. In particular, the “temple” family of carbohydrate receptors show good affinities and excellent selectivities for certain all-equatorial substrates. One example is selective for O-linked β-N-acetylglucosamine (GlcNAc, as in the O-GlcNAc protein modification), while another is specific for β-cellobiosyl and closely related disaccharides. Both show roughly millimolar affinities, matching the strength of some lectin–carbohydrate interactions.     

TRPV3 is a temperature-sensitive vanilloid receptor-like protein

Vanilloid receptor-1 (VR1, also known as TRPV1) is a thermosensitive, nonselective cation channel that is expressed by capsaicin-sensitive sensory afferents and is activated by noxious heat, acidic pH and the alkaloid irritant capsaicin. Although VR1 gene disruption results in a loss of capsaicin responses, it has minimal effects on thermal nociception. This and other experiments--such as those showing the existence of capsaicin-insensitive heat sensors in sensory neurons--suggest the existence of thermosensitive receptors distinct from VR1. Here we identify a member of the vanilloid receptor/TRP gene family, vanilloid receptor-like protein 3 (VRL3, also known as TRPV3), which is heat-sensitive but capsaicin-insensitive. VRL3 is coded for by a 2,370-base-pair open reading frame, transcribed from a gene adjacent to VR1, and is structurally homologous to VR1. VRL3 responds to noxious heat with a threshold of about 39 degrees C and is co-expressed in dorsal root ganglion neurons with VR1. Furthermore, when heterologously expressed, VRL3 is able to associate with VR1 and may modulate its responses. Hence, not only is VRL3 a thermosensitive ion channel but it may represent an additional vanilloid receptor subunit involved in the formation of heteromeric vanilloid receptor channels.     

Functional profiling of the Saccharomyces cerevisiae genome

Determining the effect of gene deletion is a fundamental approach to understanding gene function. Conventional genetic screens exhibit biases, and genes contributing to a phenotype are often missed. We systematically constructed a nearly complete collection of gene-deletion mutants (96% of annotated open reading frames, or ORFs) of the yeast Saccharomyces cerevisiae. DNA sequences dubbed 'molecular bar codes' uniquely identify each strain, enabling their growth to be analysed in parallel and the fitness contribution of each gene to be quantitatively assessed by hybridization to high-density oligonucleotide arrays. We show that previously known and new genes are necessary for optimal growth under six well-studied conditions: high salt, sorbitol, galactose, pH 8, minimal medium and nystatin treatment. Less than 7% of genes that exhibit a significant increase in messenger RNA expression are also required for optimal growth in four of the tested conditions. Our results validate the yeast gene-deletion collection as a valuable resource for functional genomics.     

The genome sequence of Schizosaccharomyces pombe

We have sequenced and annotated the genome of fission yeast (Schizosaccharomyces pombe), which contains the smallest number of protein-coding genes yet recorded for a eukaryote: 4,824. The centromeres are between 35 and 110 kilobases (kb) and contain related repeats including a highly conserved 1.8-kb element. Regions upstream of genes are longer than in budding yeast (Saccharomyces cerevisiae), possibly reflecting more-extended control regions. Some 43% of the genes contain introns, of which there are 4,730. Fifty genes have significant similarity with human disease genes; half of these are cancer related. We identify highly conserved genes important for eukaryotic cell organization including those required for the cytoskeleton, compartmentation, cell-cycle control, proteolysis, protein phosphorylation and RNA splicing. These genes may have originated with the appearance of eukaryotic life. Few similarly conserved genes that are important for multicellular organization were identified, suggesting that the transition from prokaryotes to eukaryotes required more new genes than did the transition from unicellular to multicellular organization.     

Cadmium - a complex environmental problem. Part II. Cadmium in sludges used as fertilizer

In intensively populated countries efficient sewage treatment is essential to protect river quality. An inevitable by-product is sewage sludge which has to be disposed of safely and economically. Utilisation of sludge as a fertilizer of agricultural land is the most economic disposal route for inland sewage-treatment works and also benefits farmers by providing a cheap manure. Much of the cadmium in wastewater is concentrated into sludge which consequently contains higher concentrations of cadmium than soil does. It is impracticable to reduce cadmium concentrations in sludge below certain levels. When sludge is used on farmland rates of application must be controlled so that cadmium concentrations in soil never reach levels that could significantly contaminate food crops. Cadmium is a principal factor limiting the use of sludge on land. Nevertheless, it is a local problem since agricultural land in general receives more cadmium from aerial deposition and phosphatic fertilizers. The significance of accumulations of cadmium in soil depends mainly on its availability for crop uptake. Investigations are described which have attempted to identify and to determine the availability of forms of cadmium in soil. There is considerable research interest in cadmium in soil solution which is likely to be directly available for crop uptake. Another area of interest is the apparent disappearance of cadmium from sludge-treated soil. Soil analysis often cannot fully account for the cadmium added in sludge. Apart from the effect of soil conditions, especially pH value, crop uptake varies according to the particular crop examined. Highest concentrations of cadmium occur in tobacco, lettuce, spinach and other leafy vegetables. Using crop uptake data from field trials it is possible to relate potential human dietary intake of cadmium, on which hazard depends, to soil concentrations of cadmium, which can be controlled by regulating applications of sludge. This provides an objective basis for limits for cadmium concentrations in soils receiving sludge. Transfer of cadmium via farm animals to meat and dairy products for human consumption is thought to be minimal, even allowing for some direct ingestion of sludge-treated soil by the animals. Evidence from these and other investigations suggests that a loading rate limit of 5 kg Cd/ha (equivalent to a soil concentration of about 3.5 mg Cd/kg) affords adequate protection to the foodchain where sludge is used on agricultural land. More research work is needed to provide a basis for predicting the long-term availability of cadmium introduced to the soil in sludge.     

Saliva is viscoelastic

Zusammenfassung Untersuchungen mit dem Weissenberg-Rheogoniometer zeigen, dass Speichel viskoelastisch ist und dass dessen dynamische Viskosität sich über einen Frequenzbereich von 2.5×10^–3 bis 10 Hz und von 400 bis 0.1 Poise bewegt.     

Day-night periodicity in pentobarbital response of mice and the influence of socio-psychological conditions

Résumé L'étude de la réaction de la souris à des doses anesthésiques de pentobarbital montre une périodicité nycthémérale. La réaction est forte pendant le jour, faible pendant la nuit. Chez les souris soumises à des conditions qui empêchent l'hypothermie ordinaire de se produire pendant l'anesthésie, l'amplitude de périodicité diminue. La périodicité disparaît le plus souvent lorsqu'on éclaire les souris sans interruption. L'amplitude de la périodicité diminue lorsque les souris sont parquées individuellement plutôt qu'en groupes. Les mécanismes physiologiques répondant à ces observations sont suggérés.

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This work was initiated with the aid of a grant from the University of Oklahoma Faculty Research Committee and was later supported by grant B-2250, National Institutes of Health, U.S. Public Health Service.