The genome versus experience dichotomy has dominated understanding of behavioral individuality. By contrast, the role of nonheritable noise during brain development in behavioral variation is understudied. Using Drosophila melanogaster, we demonstrate a link between stochastic variation in brain wiring and behavioral individuality. A visual system circuit called the dorsal cluster neurons (DCN) shows nonheritable, interindividual variation in right/left wiring asymmetry and controls object orientation in freely walking flies. We show that DCN wiring asymmetry instructs an individual’s object responses: The greater the asymmetry, the better the individual orients toward a visual object. Silencing DCNs abolishes correlations between anatomy and behavior, whereas inducing DCN asymmetry suffices to improve object responses.

Detecting pathogens and mounting immune responses upon infection is crucial for animal health. However, these responses come at a high metabolic price (McKean and Lazzaro, 2011, Kominsky et al., 2010), and avoiding pathogens before infection may be advantageous. The bacterial endotoxins lipopolysaccharides (LPS) are important immune system infection cues (Abbas et al., 2014), but it remains unknown whether animals possess sensory mechanisms to detect them prior to infection. Here we show that Drosophila melanogaster display strong aversive responses to LPS and that gustatory neurons expressing Gr66a bitter receptors mediate avoidance of LPS in feeding and egg laying assays. We found the expression of the chemosensory cation channel dTRPA1 in these cells to be necessary and sufficient for LPS avoidance. Furthermore, LPS stimulates Drosophila neurons in a TRPA1-dependent manner and activates exogenous dTRPA1 channels in human cells. Our findings demonstrate that flies detect bacterial endotoxins via a gustatory pathway through TRPA1 activation as conserved molecular mechanism.DOI: http://dx.doi.org/10.7554/eLife.13133.001

Dietary supplements that prevent bone loss at the hip and that can be applied safely in the elderly are likely to reduce hip fractures. A daily dietary supplement of 750 mg calcium or 15 microg 25OH vitamin D3 on bone loss at the hip and other sites, bone turnover and calcium-regulating hormones were studied over 4 yr in elderly volunteers using a randomized, double-blind, placebo-controlled trial. Bone mineral density (BMD) was measured by dual x-ray absorptiometry and bone structure by radiographs. Calcium biochemistry and bone turnover markers were measured in blood and urine. The 316 women entering the trial had a mean age of 73.7 yr and the 122 men of 75.9 yr. Baseline median calcium intake was 546 mg/day, and median serum 25OH vitamin D3 was 59 nmol/L. On placebo, loss of BMD at total hip was 2% and femoral medulla expansion was 3% over 4 yr. Calcium reduced bone loss, secondary hyperparathyroidism, and bone turnover. 25OH vitamin D3 was intermediate between placebo and calcium. Fracture rates and drop-out rates were similar among groups, and there were no serious adverse events with either supplement. A calcium supplement of 750 mg/day prevents loss of BMD, reduces femoral medullary expansion, secondary hyperparathyroidism, and high bone turnover. A supplement of 15 microg/day 25OH vitamin D3 is less effective, and because its effects are seen only at low calcium intakes, suggests that its beneficial effect is to reverse calcium insufficiency.

The aim of this study was to assess the usefulness of the inbred rat model for studies of genetic influences on skeletal fragility. We characterized bone mass, geometry, and skeletal biomechanics in 11 inbred strains of rats. This study showed that considerable variation exists in bone structure, areal bone mineral density (aBMD), and fragility phenotypes among inbred strains of rats. Interestingly, the variability in skeletal phenotypes in rats was site specific, suggesting that no single gene regulates skeletal fragility at all sites. For instance, the Copenhagen 2331 (COP) strain had the greatest biomechanical properties in the femoral neck but only modest bone strength at the femoral midshaft, compared with other strains. Consequently, COP rats appear to have alleles that specifically enhance femoral neck biomechanical properties and may serve as a model for studying genetic influences on hip strength. The Brown Norway (BN) and Fischer 344 (F344) strains may provide models for vertebral fragility because each has relatively fragile lumbar vertebrae. The F344 rats also had the most fragile femora and, thus, appear to carry alleles that cause overall skeletal fragility. We identified two inbred rat crosses that will facilitate the study of genetic influences on skeletal fragility at clinically relevant skeletal sites: Lewis (LEW) with F344 (primarily for vertebral fragility) and COP with DA (primarily for femoral neck fragility). The results strongly suggest that selected crosses of inbred strains of rats will provide useful models for studying genetic influences on bone strength and structure.

Isolation profoundly influences social behavior in all animals. In humans, isolation has serious effects on health. Drosophila melanogaster is a powerful model to study small-scale, temporally-transient social behavior. However, longer-term analysis of large groups of flies is hampered by the lack of effective and reliable tools. We built a new imaging arena and improved the existing tracking algorithm to reliably follow a large number of flies simultaneously. Next, based on the automatic classification of touch and graph-based social network analysis, we designed an algorithm to quantify changes in the social network in response to prior social isolation. We observed that isolation significantly and swiftly enhanced individual and local social network parameters depicting near-neighbor relationships. We explored the genome-wide molecular correlates of these behavioral changes and found that whereas behavior changed throughout the six days of isolation, gene expression alterations occurred largely on day one. These changes occurred mostly in metabolic genes, and we verified the metabolic changes by showing an increase of lipid content in isolated flies. In summary, we describe a highly reliable tracking and analysis pipeline for large groups of flies that we use to unravel the behavioral, molecular and physiological impact of isolation on social network dynamics in Drosophila.

In metastasis, the cancer cells that travel through the body are capable of establishing new tumors in locations remote from the site of the original disease. To metastasize, a cancer cell must break away from its tumor and invade either the circulatory or lymphatic system, which will carry it to a new location, and establish itself in the new site. Once in the blood stream, the cancer cells now have access to every portion of the body. Here, we have used the ''in vivo flow cytometer'' to study if there is any relationship between metastatic potential and depletion kinetics of circulating tumor cells. The in vivo flow cytometer has the capability to detect and quantify continuously the number and flow characteristics of fluorescently labelled cells in vivo. We have improved the counting algorithm and measured the depletion kinetics of cancer cells with different metastatic potential. Interestingly, more invasive PC-3 prostate cancer cells are depleted faster from the circulation than LNCaP cells. In addition, we have measured the depletion kinetics of two related human hepatocellular carcinoma (liver cancer) cell lines, high-metastatic HCCLM3 cells, and low-metastatic HepG2 cells. More than 60% HCCLM3 cells are depleted within the first hour. Interestingly, the low-metastatic HepG2 cells possess noticeably slower depletion kinetics. In comparison, \40% HepG2 cells are depleted within the first hour. The differences in depletion kinetics might provide insights into early metastasis processes. ' 2011 International Society for Advancement of Cytometry Key terms in vivo flow cytometer; cancer metastasis; circulating tumor cells; prostate cancer; hepatocellular carcinoma; in vivo confocal imaging METASTASIS is a complicated process that has yet to be completely understood. In metastasis, the cancer cells that travel through the body are capable of establishing new tumors in locations remote from the site of the original disease. To metastasize, a cancer cell must break away from its tumor and invade either the circulatory or lymph system (1-3). Once in the blood stream, the cancer cells now have access to every portion of the body. The cancer cells in the bloodstream must fight the body's defense system and try to reattach itself in a new location. Fewer than 1 in 10,000 cancer cells survive circulation to create a new tumor. The circulation of the blood plays an important role in determining where cancer cells travel. The cancer cells usually are trapped in the first set of capillaries that they encounter downstream from their point of entry. These capillaries are often in the lung, since returning deoxygenated venous blood leaving many organs is returned to the lung for reoxygenation. From the intestines, the blood go to the liver first, thus cancer cells leaving the intestines will go there. Therefore, the lung and the liver are the two most common sites for metastasis in the human body. Many circulating cancer cells cannot finish the entire process of metastasis (4).

No abstract

An electro-hydraulic shaking table is a useful experimental apparatus to real-time replicate the desired acceleration signal for evaluating the performance of the tested structural systems. The article proposes a combined control strategy to improve the tracking accuracy of the electro-hydraulic shaking table. First, the combined control strategy utilizes an adaptive inverse control as a feedforward controller for extending the acceleration frequency bandwidth of the electro-hydraulic shaking table when the estimated plant model may be a nonminimum phase system and its inverse model is an unstable system. The adaptive inverse control feedforward compensator guarantees the stability of the estimated inverse transfer function. Then, the combined control strategy employs an improved internal model control for obtaining high fidelity tracking accuracy after the modeling error between the estimated inverse transfer function using adaptive inverse control and the electro-hydraulic shaking table actual inverse system is improved by the improved internal model control. So, the proposed control strategy combines the merits of adaptive inverse control feedforward compensator and improved internal model control. The combined strategy is programmed in MATLAB/Simulink, and then is compiled to a real-time PC system with xPC target technology for implementation. The experimental results demonstrate that a better tracking performance with the proposed combined control strategy is achieved in an electro-hydraulic shaking table than with a conventional controller.