A prevalent POLG CAG microsatellite length allele in humans and African great apes

The human nuclear gene for the catalytic subunit of mitochondrial DNA polymerase (POLG) contains within its coding region a CAG microsatellite encoding a polyglutamine repeat. Previous studies demonstrated an association between length variation at this repeat and male infertility, suggesting a mechanism whereby the prevalent (CAG)₁₀ allele, which occurs at a frequency of >80% in different populations, could be maintained by selection. Sequence analysis of the POLG CAG microsatellite region of more than 1000 human chromosomes reveals that virtually all allelic variation at the locus is accounted for by length variation of the CAG repeat. Analysis of POLG from African great apes shows that a prevalent length allele is present in each species, although its exact length is species-specific. In common chimpanzee (Pan troglodytes) a number of different sequence variants contribute to the prevalent length allele, strongly supporting the idea that the length of the POLG microsatellite region, rather than its exact nucleotide or amino acid sequence, is what is maintained. Analysis of POLG in other primates indicates that the repeat has expanded from a shorter, glutamine-rich sequence, present in the common ancestor of Old and New World monkeys.     

Independent regulation of synaptic size and activity by the anaphase-promoting complex

Neuronal plasticity relies on tightly regulated control of protein levels at synapses. One mechanism to control protein abundance is the ubiquitin-proteasome degradation system. Recent studies have implicated ubiquitin-mediated protein degradation in synaptic development, function, and plasticity, but little is known about the regulatory mechanisms controlling ubiquitylation in neurons. In contrast, ubiquitylation has long been studied as a central regulator of the eukaryotic cell cycle. A critical mediator of cell-cycle transitions, the anaphase-promoting complex/cyclosome (APC/C), is an E3 ubiquitin ligase. Although the APC/C has been detected in several differentiated cell types, a functional role for the complex in postmitotic cells has been elusive. We describe a novel postmitotic role for the APC/C at Drosophila neuromuscular synapses: independent regulation of synaptic growth and synaptic transmission. In neurons, the APC/C controls synaptic size via a downstream effector Liprin-alpha; in muscles, the APC/C regulates synaptic transmission, controlling the concentration of a postsynaptic glutamate receptor.     

Benzimidazolone p38 inhibitors

The synthesis and in vitro p38 alpha activity of a novel series of benzimidazolone inhibitors is described. The p38 alpha SAR is consistent with a mode of binding wherein the benzimidazolone carbonyl serves as the H-bond acceptor to Met109 of p38 alpha in a manner analogous to the pyridine nitrogen of prototypical pyridylimidazole p38 inhibitors. Potent p38 alpha activity comparable to that of several previously reported p38 inhibitors is observed for this novel chemotype.     

Allometric scaling of kidney function in green iguanas

Numerous physiological parameters, such as metabolic rate and glomerular filtration rate (GFR), are allometrically related to body mass. Whereas the interspecific relationships between metabolic rate and body mass have been extensively studied in vertebrates, intraspecific studies of renal function have been limited. Therefore, kidney function was studied in 16 green iguanas, (Iguana iguana; 322-4764 g), by using nuclear scintigraphy to measure the renal uptake of 99mTc-diethylenetriamine pentaacetic acid (99mTc-DTPA), following either intravenous or intraosseous administration. Route of 99mTc-DTPA administration did not affect the percentage of the dose that accumulated in the kidney (P > 0.05). Renal uptake of 99mTc-DTPA was related to body mass (W, g) as: %Dose Kidney (min-1) = 11.09W(-0.235). Although not directly measured, the apparent renal clearance of 99mTc-DTPA could be described as: Renal CL 99mTc-DTPA (ml.min-1) = 0.005W(0.759), and the mass exponent did not differ from either the 2/3 or 3/4 values (P > 0.05). The similarity of the mass exponents relating both renal function and metabolic rate to body mass suggests a common mechanism underlying these allometric relationships. As this study also demonstrated that renal scintigraphy can be used to quantify kidney function in iguanas, this technique may be a useful research and diagnostic tool.     

Two-dimensional gel electrophoresis database of murine R1 embryonic stem cells

Embryonic stem (ES) cell lines represent a population of undifferentiated pluripotent cells capable of multilineage differentiation in vitro. Although very useful for studying developmental processes, human ES cell lines have also been suggested as a potential and unlimited source for cellular transplantation and the treatment of human disease. The proteomic basis of embryonic stemness (pluripotentiality and multilineage differentiation) and the transitions that lead to specific cell lineages however, remain to be defined. As an important first step in defining these processes, we have performed a proteomic analysis of undifferentiated mouse R1 ES cell lines using pH 3-10, 4-7 and 6-11 two-dimensional electrophoresis gels, matrix-assisted laser desorption/ionization and tandem mass spectrometry. Of the 700 gel spots analyzed, 241 distinct protein species were identified corresponding to 218 unique proteins, with a significant proportion functionally related to protein expression.     

Constructing an organ: the Drosophila salivary gland as a model for tube formation

Tubes are required in metazoans to transport the liquids and gases that sustain life. The conservation of molecules and mechanisms involved in tube formation suggests that what we learn by studying simple systems will apply to related processes in higher animals. Studies over the past 10 years have revealed the molecules that specify cell fate in Drosophila salivary gland and the cellular events that mediate tube morphogenesis. Here, we discuss how anterior-posterior and dorsal-ventral patterning information specifies both the position of salivary-gland primordia and how many cells they contain. We examine the transformation of a polarized epithelial sheet into an elongated, unbranched tube, and the intrinsic and extrinsic factors that influence the final position of the salivary gland.     

Fixed precision sequential sampling plans for the greenbug and bird cherry-oat aphid (Homoptera: Aphididae) in winter wheat

The numbers of greenbugs, Schizaphis graminum (Rondani), and bird cherry-oat aphids, Rhopalosiphum padi L., per wheat tiller (stem) were estimated in 189 production winter wheat (Triticum aestivum L.) fields located throughout Oklahoma. Taylor's power law regressions were calculated from these data and used to construct fixed precision sequential sampling schemes for each species. An evaluation data set was constructed from 240 samples taken during three growing seasons from winter wheat fields at four locations in Oklahoma. Wheat cultivar and growth stage were recorded for each field on the day of sampling. Taylor's power law parameters for evaluation fields differed significantly for both species among growing seasons, locations, and plant growth stages. Median precision achieved using the fixed precision sequential sampling schemes for each species departed <20% from expected precision over the range population intensity in the evaluation data. For the 10% of samples with greatest deviation between observed and expected precision, observed precision was 13.8-81.8% greater than that expected precision depending on aphid species and population intensity. For the greenbug, the distribution of the percentage deviation between observed and expected precision was positively skewed, so that the sampling scheme tended to over-predict precision. For the bird cherry-oat aphid, the distribution was more symmetric. Even though precision observed using the sampling schemes frequently varied from expected precision, because of the inevitable consequence of sampling error and environmental variation, the sampling schemes yielded median observed precision levels close to expected precision levels over a broad range of population intensity.     

The genetics of mating recognition between Drosophila simulans and D. sechellia

During courtship, visual and chemical signals are often exchanged between the sexes. The proper exchange of such signals ensures intraspecific recognition. We have examined the genetic basis of interspecific differences in male mating behaviour and pheromone concentration between Drosophila simulans and D. sechellia by using Drosophila simulans/D. sechellia introgression lines. Our results show a majority of quantitative trait loci (QTLs) explaining variation in both male mating behaviour and pheromone concentration to be located on the third chromosome. One QTL found on the third chromosome explains variation in time needed to start courtship and copulation as well as time spent courting. The position of such QTL (approximately 84A-88B) with effects on courtship and copulation aspects of mating includes the candidate sex determination gene doublesex (84E5-6) and Voila (86E1-2), a gene that affects male courtship in D. melanogaster. One additional third chromosome QTL explained variation in 7-tricosene pheromone concentrations among males. The interval mapping position of this QTL (approximately 68E-76E) did not overlap with the position detected for differences in mating behaviour and the intervals did not include candidate genes previously identified as having an effect on D. melanogaster cuticular hydrocarbon production. We did not detect any directionality of the effect of Drosophila sechellia allele introgressions in male mating recognition.