Encoding social signals in the mouse main olfactory bulb

Mammalian urine releases complex mixtures of volatile compounds that are used in reproduction, territoriality and conspecific recognition. To understand how such complex mixtures are represented in the main olfactory bulb, we analysed the electrophysiological responses of individual mitral cells to volatile compounds in mouse urine. In both males and females, urine volatile compounds evoke robust responses in a small subset of mitral cells. Fractionation of the volatile compounds using gas chromatography showed that out of the hundreds of compounds present, mitral cells are activated by single compounds. One cohort of mitral cells responded exclusively to male urine; these neurons were activated by (methylthio)methanethiol, a potent, previously unknown semiochemical present only in male urine. When added to urine, synthetic (methylthio)methanethiol significantly enhances urine attractiveness to female mice. We conclude that mitral cells represent natural odorant stimuli by acting as selective feature detectors, and that their activation is largely independent of the presence of other components in the olfactory stimulus.     

Structure of the insulin receptor ectodomain reveals a folded-over conformation

The insulin receptor is a phylogenetically ancient tyrosine kinase receptor found in organisms as primitive as cnidarians and insects. In higher organisms it is essential for glucose homeostasis, whereas the closely related insulin-like growth factor receptor (IGF-1R) is involved in normal growth and development. The insulin receptor is expressed in two isoforms, IR-A and IR-B; the former also functions as a high-affinity receptor for IGF-II and is implicated, along with IGF-1R, in malignant transformation. Here we present the crystal structure at 3.8 A resolution of the IR-A ectodomain dimer, complexed with four Fabs from the monoclonal antibodies 83-7 and 83-14 (ref. 4), grown in the presence of a fragment of an insulin mimetic peptide. The structure reveals the domain arrangement in the disulphide-linked ectodomain dimer, showing that the insulin receptor adopts a folded-over conformation that places the ligand-binding regions in juxtaposition. This arrangement is very different from previous models. It shows that the two L1 domains are on opposite sides of the dimer, too far apart to allow insulin to bind both L1 domains simultaneously as previously proposed. Instead, the structure implicates the carboxy-terminal surface of the first fibronectin type III domain as the second binding site involved in high-affinity binding.     

Prevalence of off-target effects in Drosophila RNA interference screens

RNA interference (RNAi) in both plants and animals is mediated by small RNAs of approximately 21-23 nucleotides in length for regulation of target gene expression at multiple levels through partial sequence complementarities. Combined with widespread genome sequencing, experimental use of RNAi has the potential to interrogate systematically all genes in a given organism with respect to a particular function. However, owing to a tolerance for mismatches and gaps in base-pairing with targets, small RNAs could have up to hundreds of potential target sequences in a genome, and some small RNAs in mammalian systems have been shown to affect the levels of many messenger RNAs besides their intended targets. The use of long double-stranded RNAs (dsRNAs) in Drosophila, where Dicer-mediated processing produces small RNAs inside cells, has been thought to reduce the probability of such 'off-target effects' (OTEs). Here we show, however, that OTEs mediated by short homology stretches within long dsRNAs are prevalent in Drosophila. We have performed a genome-wide RNAi screen for novel components of Wingless (Wg) signal transduction in Drosophila S2R + cells, and found few, if any, legitimate candidates. Rather, many of the top candidates exert their effects on Wg response through OTEs on known pathway components or through promiscuous OTEs produced by tandem trinucleotide repeats present in many dsRNAs and genes. Genes containing such repeats are over-represented in candidate lists from published screens, suggesting that they represent a common class of false positives. Our results suggest simple measures to improve the reliability of genome-wide RNAi screens in Drosophila and other organisms.     

求解作业车间调度问题的改进自适应遗传算法

根据当前代种群中的最优个体应该保留,但也要一定交叉与变异概率的思想,提出了改进的自适应遗传算法,开发了工程应用软件包,应用于求解作业车间调度问题,显著提高了收敛速度.特别是在搜索过程中系统能够自动给定交叉概率和变异概率,符合工程实际需要.     

Positional cloning of the combined hyperlipidemia gene Hyplip1.

Familial combined hyperlipidemia (FCHL, MIM-144250) is a common, multifactorial and heterogeneous dyslipidemia predisposing to premature coronary artery disease and characterized by elevated plasma triglycerides, cholesterol, or both. We identified a mutant mouse strain, HcB-19/Dem (HcB-19), that shares features with FCHL, including hypertriglyceridemia, hypercholesterolemia, elevated plasma apolipoprotein B and increased secretion of triglyceride-rich lipoproteins. The hyperlipidemia results from spontaneous mutation at a locus, Hyplip1, on distal mouse chromosome 3 in a region syntenic with a 1q21-q23 FCHL locus identified in Finnish, German, Chinese and US families. We fine-mapped Hyplip1 to roughly 160 kb, constructed a BAC contig and sequenced overlapping BACs to identify 13 candidate genes. We found substantially decreased mRNA expression for thioredoxin interacting protein (Txnip). Sequencing of the critical region revealed a Txnip nonsense mutation in HcB-19 that is absent in its normolipidemic parental strains. Txnip encodes a cytoplasmic protein that binds and inhibits thioredoxin, a major regulator of cellular redox state. The mutant mice have decreased CO2 production but increased ketone body synthesis, suggesting that altered redox status down-regulates the citric-acid cycle, sparing fatty acids for triglyceride and ketone body production. These results reveal a new pathway of potential clinical significance that contributes to plasma lipid metabolism.     

Using sampling and inverse distance weighted modeling for mapping invasive plants

Accurate time- and cost-efficient mapping is central to successful rangeland invasive plant management. In this study sampling together with Inverse Distance Weighted (IDW) interpolation modeling was tested as a mapping alternative to expensive full-coverage delineation survey mapping methods. Our objective was to examine accuracies of presence/absence maps generated from 18 sampling strategies (3 sampling methods × 6 sample densities) using IDW. Invasive plant field survey maps with known accuracies were used to generate samples and to test interpolation results at 2 sites. Site 1 was approximately 6.0 km 2 , dominated by Russian knapweed ( Acroptilon repens L.). Site 2, an upland area of approximately 13.5 km 2 , was dominated by spotted knapweed ( Centaurea maculosa Lam). Sampling method × sample density combinations were gathered from field survey infestation maps using repeated computer-based sampling methods. IDW modeling was applied to each of the sample data sets. Accuracies of the IDW interpolation results were calculated by re-referencing field survey maps. We determined that sampling at density of 0.25% (about 1 point per ha) using a systematic sampling method was the preferred sampling strategy for both sites. This combination of sampling density and method yielded 85% accurate presence/absence maps. We conclude that sampling combined with IDW interpolation modeling can generate accurate invasive plant maps and is a potential alternative to current delineation survey methods.     

Fertile island development around perennial shrubs across a Mojave Desert chronosequence

Spatial heterogeneity has been examined only recently as a factor in studies of ecosystem processes. The effect of this factor on desert organisms is exemplified in the ""fertile island"" a concentration of essential soil nutrients under perennial shrubs. In this study we examined fertile island patterns in undisturbed desert areas and on abandoned roadways to see at what rate and magnitude these fertile patches reappeared after disturbance. Small-scale examination of patterns of soil P, organic matter, moisture, and bulk density showed that soils beneath Larrea tridentata (DC.) Cov. shrubs on the roads lacked the tight circular gradient in these variables that was characteristic of soils beneath control shrubs, even 88 years after road abandonment. The nature of the initial soil disturbance altered both spatial patterns of soil N and temporal patterns of fertile island development. Fertile island patterns for total soil N, available P, and organic matter were more circular than patterns for bulk density, texture, or pH. We suggest that patterns of soil heterogeneity may develop first for elements that may be limiting to desert shrub growth (N, P, organic matter), followed by spatial development in other less limiting soil factors (bulk density, texture, pH).     

Summer food habits of coyotes in Idaho's River of No Return Wilderness Area

Summer food habits of coyotes ( Canis latrans )in the River of No Return Wilderness Area, Idaho, were determined. Analysis of 51 scats (fecal samples) revealed that Columbian ground squirrels ( Spermophilus columbianus ), mule deer ( Odocoileus hemionus ), and deer mice ( Peromyscus manniculatus ) exhibited the greatest frequency of occurrence for identified food items, being detected in 57%, 27%, and 16%, respectively, of scats examined.