Attachment of a physician's assistant to an English general practice.

A final-year student from the physician''s associate programme at Duke University in North Carolina, USA, worked in an English health centre for eight weeks between May and July. He managed 221 cases under supervision, and they were typical in terms of sex ratio, diagnosis, and the preponderance of children. Current social and economic trends in Britain suggest that selective under-doctoring, especially in inner urban areas, may become acute, and a type of physician''s assistant specially selected and trained for the work in areas with serious and unusual problems should be considered as among the possible, even desirable, solutions.     

Grasping the past. delay can improve visuomotor performance.

"Optic ataxia" is caused by damage to the human posterior parietal cortex (PPC). It disrupts all components of a visually guided prehension movement, not only the transport of the hand toward an object's location, but also the in-flight finger movements pretailored to the metric properties of the object. Like previous cases, our patient (I.G.) was quite unable to open her handgrip appropriately when directly reaching out to pick up objects of different sizes. When first tested, she failed to do this even when she had previewed the target object 5 s earlier. Yet despite this deficit in "real" grasping, we found, counterintuitively, that I.G. showed good grip scaling when "pantomiming" a grasp for an object seen earlier but no longer present. We then found that, after practice, I.G. became able to scale her handgrip when grasping a real target object that she had previewed earlier. By interposing catch trials in which a different object was covertly substituted for the original object during the delay between preview and grasp, we found that I.G. was now using memorized visual information to calibrate her real grasping movements. These results provide new evidence that "off-line" visuomotor guidance can be provided by networks independent of the PPC.     

How a complex life cycle can improve a parasite's sex life

How complex life cycles of parasites are maintained is still a fascinating and unresolved topic. Complex life cycles using three host species, free-living stages, asexual and sexual reproduction are widespread in parasitic helminths. For such life cycles, we propose here that maintaining a second intermediate host in the life cycle can be advantageous for the individual parasite to increase the intermixture of different clones and therefore decrease the risk of matings between genetically identical individuals in the definitive host. Using microsatellite markers, we show that clone mixing occurs from the first to the second intermediate host in natural populations of the eye-fluke Diplostomum pseudospathaceum. Most individuals released by the first intermediate host belonged to one clone. In contrast, the second intermediate host was infected with a diverse array of mostly unique parasite genotypes. The proposed advantage of increased parasite clone intermixture may be a novel selection pressure favouring the maintenance of complex life cycles.     

Flavonoids can replace alpha-tocopherol as an antioxidant

Endogenous antioxidants such as the lipid-soluble vitamin E protect the cell membranes from oxidative damage. Glutathione seems to be able to regenerate alpha-tocopherol via a so-called free radical reductase. The transient protection by reduced glutathione (GSH) against lipid peroxidation in control liver microsomes is not observed in microsomes deficient in alpha-tocopherol. Introduction of antioxidant flavonoids, such as 7-monohydroxyethylrutoside, fisetin or naringenin, into the deficient microsomes restored the GSH-dependent protection, suggesting that flavonoids can take over the role of alpha-tocopherol as a chain-breaking antioxidant in liver microsomal membranes.     

Becoming a face expert.

Young children do not form representations of newly encountered faces as efficiently as do adults. A first step in explaining this difference, like any age-related change, is locating its source. A major source of the improvement is acquisition of knowledge of faces per se, as opposed to age-related changes in general pattern encoding or memorial skills. Two consequences of expertise at individualizing members of classes that share a basic configuration are known: a large inversion effect and a caricature advantage. It is possible that both of these effects reflect increased reliance, with expertise, on configuration distinguishing features. Several phenomena that indicate that inversion interferes with the encoding of configural aspects of faces are reviewed. Finally, developmental data are presented that confirm the suspicion that there are at least two distinct sources of the vulnerability of face encoding to inversion, perhaps reflecting two distinct senses of 'configural encoding' of faces, only one of which is implicated in adult expertise at face encoding.     

Nitric oxide can function as either a killer molecule or an antiapoptotic effector in cardiomyocytes.

Caspase enzymes are a family of cysteine proteases that play a central role in apoptosis. Recently, it has been demonstrated that caspases can be S-nitrosylated and inhibited by nitric oxide (NO). The present report shows that in chick embryo heart cells (CEHC), NO donor molecules such as S-nitroso-N-acetylpenicillamine (SNAP), S-nitrosoglutathione, spermine-NO or sodium nitroprusside inhibit caspase activity in both basal and staurosporine-treated cells. However, the inhibitory effect of NO donors on caspase activity is accompanied by a parallel cytotoxic effect, that precludes NO to exert its antiapoptotic capability. N-Acetylcysteine (NAC) at a concentration of 10 mM blocks depletion of cellular glutathione and cell death in SNAP-treated CEHC, but it poorly affects the ability of SNAP to inhibit caspase activity. Consequently, in the presence of NAC, SNAP attenuates not only caspase activity but also cell death of staurosporine-treated CEHC. These data show that changes in the redox environment may inhibit NO-mediated toxicity, without affecting the antiapoptotic capability of NO, mediated by inhibition of caspase enzymes. NO may thus be transformed from a killer molecule into an antiapoptotic agent.     

Autophosphorylation within insulin receptor beta-subunits can occur as an intramolecular process.

The insulin receptor is a complex membrane-spanning glycoprotein composed of two alpha-subunits and two beta-subunits connected to form an alpha 2 beta 2 holoreceptor. Insulin binding to the extracellular alpha-subunits activates intracellular beta-subunit autophosphorylation and substrate kinase activity. The current study was designed to differentiate mechanisms of transmembrane signaling by the insulin receptor, specifically whether individual beta-subunits undergo cis- or trans-phosphorylation. We compared relative kinase activities of trypsin-truncated receptors, alpha beta-half receptors, and alpha 2 beta 2 holoreceptors under conditions that allowed us to differentiate intermolecular and intramolecular events. Compared to the insulin-stimulated holoreceptors, the trypsin-truncated receptor undergoes autophosphorylation at similar tyrosine residues and catalyzes substrate phosphorylation in the absence of insulin at a comparable rate. The truncated receptor sediments on a sucrose gradient at a position consistent with a structure comprising a single beta-subunit attached to a fragment of the alpha-subunit and undergoes autophosphorylation in this form in the absence of insulin. Autophosphorylation of the truncated insulin receptor is independent of receptor concentration, and immobilization of the truncated receptor on a matrix composed of an anti-receptor antibody bound to protein A-Sepharose diminishes neither autophosphorylation nor receptor-catalyzed substrate phosphorylation. Therefore, true intramolecular (cis) phosphorylations, which occur within individual beta-subunits derived from trypsin-truncated receptors, lead to kinase activation. However, insulin-stimulated autophosphorylation of insulin receptor alpha beta heterodimers is concentration-dependent, and both autophosphorylation and kinase activity are markedly reduced following immobilization.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mycobacterium tuberculosis can utilize heme as an iron source

Most iron in mammals is found within the heme prosthetic group. Consequently, many bacterial pathogens possess heme acquisition systems to utilize iron from the host. Here, we demonstrate that Mycobacterium tuberculosis can utilize heme as an iron source, suggesting that M. tuberculosis possesses a yet-unknown heme acquisition system.     

Dimethylthetin can substitute for glycine betaine as an osmoprotectant molecule for Escherichia coli.

Glycine betaine is believed to be the most active naturally occurring osmoprotectant molecule for Escherichia coli and other bacteria. It is a dipolar ion possessing a quaternary ammonimum group and a carboxylic acid group. To examine the molecular requirements for osmoprotective activity, dimethylthetin was compared with glycine betaine. Dimethylthetin is identical to glycine betaine except for substitution of dimethyl sulfonium for the quaternary nitrogen group. Dimethylthetin was found to be about equally as effective as glycine betaine in permitting E. coli to grow in hypertonic NaCl, and both compounds were recovered almost completely from bacterial cells grown in the presence of hypertonic NaCl. 3-Dimethylsulfonioproprionate, an analog of dimethylthetin observed in marine algae, and 3-Dimethylsulfonio-2-methylproprionate were found to be less active. Dimethylthetin may prove useful as a molecular probe to study betaine metabolism and as a model for the development of antibacterial agents.