Crystal structure at 2.4 angstroms resolution of the complex of transducin betagamma and its regulator, phosducin

The crystal structure of transducin's betagamma subunits complexed with phosducin, which regulates Gtbetagamma activity, has been solved to 2.4 angstroms resolution. Phosducin has two domains that wrap around Gtbetagamma to form an extensive interface. The N-terminal domain binds loops on the "top" Gtbeta surface, overlapping the Gtalpha binding surface, explaining how phosducin blocks Gtbetagamma's interaction with Gtalpha. The C-terminal domain shows structural homology to thioredoxin and binds the outer strands of Gtbeta's seventh and first blades in a manner likely to disrupt Gtbetagamma's normal orientation relative to the membrane and receptor. Phosducin's Ser-73, which when phosphorylated inhibits phosducin's function, points away from Gtbetagamma, toward a large flexible loop. Thus phosphorylation is not likely to affect the interface directly, but rather indirectly through an induced conformational change.     

Interleukin-6-type cytokines in vivo: regulated bioavailability

Investigators have traditionally thought of the class of inflammation- and injury-associated cytokines in large part as "free" entities in the peripheral circulation. In the case of interleukin-6 (IL-6), the cytokine can be found in blood in complexes of molecular mass 400-500, 150-200, and 25-35 kDa in association with binding proteins that can include soluble IL-6 receptor (sIL-6R), anti-IL-6, and anti-sIL-6R IgG, and others. Sustained high levels of different particular IL-6 complexes are observed in the human circulation in cancer patients subjected to particular active anticancer immunotherapy regimens. In the "chaperoned" state, circulating IL-6 complexes display differential immunoreactivity in different ELISAs and possess differential biological activity as assayed ex vivo. The discovery of "chaperoned" circulating IL-6 in humans points to a new level of modulation of cytokine function, that of regulated bioavailability of IL-6 in vivo.     

Developmental stability in stocks of White Leghorn chickens

The degree of asymmetry in bilateral morphological characters may reflect genetic and environmental stressors. Shank length and diameter, weight and length of the first primary wing feather, and distance between the junction of upper and lower mandibles and auditory canal (face length) were used to classify bilateral types and measure relative asymmetry (RA) in six genetic stocks. The stocks were the S23 generation of White Leghorn lines selected for high or low antibody response to SRBC, sublines in which selection had been relaxed for eight generations, and reciprocal crosses of the selected lines. Differences were found among all stocks for the traits measured. Rankings among traits for RA in descending order were face length, shank diameter, feather weight, and shank and feather lengths. The RA of shank and feather lengths did not differ from each other. An overall RA composed of mean RA of the five traits showed that the two selected lines exhibited greater RA than the crosses between them. The RA of the two lines where selection had been relaxed was similar to that of selected lines. This research suggests that an overall RA created as a combination of RA of several bilateral traits can be a valid measure of genetic stress in chickens and provides a method of comparing developmental stability among populations.     

Listening to caregiving sons: misunderstood realities

In-depth interviews with 30 sons actively involved in caring for a parent with dementia expand the understanding of sons' caregiving experiences. The within-group analysis revealed common themes that emerged from the narratives--duty, acceptance, taking charge, common emotions, and work flexibility--as well as common issues--loss, sibling relationships, role reversal, coping strategies, and positive outcomes. The interviews also generated a typology of son caregivers that included such types as the dutiful son, the son who goes the extra mile, the strategic planner, and the son who shares the care.     

Absence of normal activation of the left anterior fusiform gyrus during naming in left temporal lobe epilepsy

Patients with left temporal lobe epilepsy (TLE) often have impaired naming. We studied 13 patients with left TLE and 10 healthy control subjects with [(15)O]H2O PET during visual confrontation naming. Statistical mapping detected multiple regions of significant cerebral blood flow increases within individuals. The left fusiform gyrus was activated in nine healthy subjects, but only in two patients with TLE (a significant difference, p < 0.001). Other activation sites were more variable in healthy subjects and those with TLE. Impaired naming ability may be associated with a lack of increased cerebral blood flow in the left fusiform gyrus in TLE.     

Selection and characterization of Toxoplasma gondii mutants resistant to artemisinin

Toxoplasma gondii infection, like malaria, is sensitive to inhibition by artemisinin (ART). Mechanisms of action for ART in malaria treatment have been proposed, but little is known about its effects in T. gondii infection. To better understand its inhibitory effects on T. gondii, mutants resistant to ART were selected by progressive culture in permissive levels of the drug. Five clonal isolates were established and characterized. The isolates were approximately 65-fold less sensitive to ART than is the parental RH and showed cross-resistance to the ART derivatives dihydroartemisinin and artemether. In addition to ART resistance, 1 clone (C9) formed morphologically unusual parasitophorous vacuoles and another (A2) was avirulent for mice and protected mice from challenge with the wild type. These clonal T. gondii mutant isolates will be useful for the study of not only the mechanism of action of ART but also parasite vacuole biology and virulence factors.