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Biomedical subjects

John Hunt

Publications and source records attributed to John Hunt.

At least 19 recordsLinked to original sources
PubMed2007

No intra-locus sexual conflict over reproductive fitness or ageing in field crickets.

Differences in the ways in which males and females maximize evolutionary fitness can lead to intra-locus sexual conflict in which genes delivering fitness benefits to one sex are costly when expressed in the other. Trade-offs between current reproductive effort and future reproduction and survival are fundamental to the evolutionary biology of ageing. This leads to the prediction that sex differences in the optimization of age-dependent reproductive effort may generate intra-locus sexual conflict over ageing rates. Here we test for intra-locus sexual conflict over age-dependent reproductive effort and longevity in the black field cricket, Teleogryllus commodus. Using a half-sib breeding design, we show that the most important components of male and female reproductive effort (male calling effort and the number of eggs laid by females) were positively genetically correlated, especially in early adulthood. However, the genetic relationships between longevity and reproductive effort were different for males and females, leading to low genetic covariation between male and female longevity. The apparent absence of intra-locus sexual conflict over ageing suggests that male and female longevity can evolve largely independently of one another.

Aging↗
PubMed2007

Effect of titanium carbide coating on the osseointegration response in vitro and in vivo.

Titanium has limitations in its clinical performance in dental and orthopaedic applications. This study describes a coating process using pulsed laser deposition (PLD) technology to produce surfaces of titanium carbide (TiC) on titanium substrates and evaluates the biological response both in vitro and in vivo. X-ray photoelectron spectroscopy (XPS) analysis revealed the presence of 18.6-21.5% TiC in the surface layer, accompanied by oxides of titanium 78.5-81.4% in the following concentrations: 11.1-13.0% Ti(2)O(3), 50.8-55.8% TiO(2), 14.5-14.7% TiO. Expression of genes central to osteoblast differentiation (alkaline phosphatase, A2 pro-collagen type 1, osteocalcin, BMP-4, TGFbeta and Cbfa-1) were up-regulated in all cell lines (primary human osteoblasts, hFOB1.19 and ROS.MER#14) grown on TiC compared with uncoated titanium when measured by semiquantitative PCR and real time-PCR, whilst genes involved in modulation of osteoclastogenesis and osteoclast activity (IL-6 and M-CSF) were unchanged. Bone density was shown to be greater around TiC-coated implants after 2 and 4 weeks in sheep and both 4 and 8 weeks in rabbits compared to uncoated titanium. Rapid bone deposition was demonstrated after only 2 weeks in the rabbit model when visualized with intravital staining. It is concluded that coating with TiC will, in comparison to uncoated titanium, improve implant hardness, biocompatibility through surface stability and osseointegration through improved bone growth.

Animals↗
PubMed2006

Where do all the maternal effects go? Variation in offspring body size through ontogeny in the live-bearing fish Poecilia parae.

Maternal effects are an important source of adaptive variation, but little is known about how they vary throughout ontogeny. We estimate the contribution of maternal effects, sire genetic and environmental variation to offspring body size from birth until 1 year of age in the live-bearing fish Poecilia parae. In both the sexes, maternal effects on body size were initially high in juveniles, and then declined to zero at sexual maturity. In sons, this was accompanied by a sharp rise in sire genetic variance, consistent with the expression of Y-linked loci affecting male size. In daughters, all variance components decreased with time, consistent with compensatory growth. There were significant negative among-dam correlations between early body size and the timing of sexual maturity in both sons and daughters. However, there was no relationship between early life maternal effects and adult longevity, suggesting that maternal effects, although important early in life, may not always influence late life-history traits.

Age Factors↗
PubMed2006

S100A12 provokes mast cell activation: a potential amplification pathway in asthma and innate immunity.

BACKGROUND: The calcium-binding protein S100A12 might provoke inflammation and monocyte recruitment through the receptor for advanced glycation end products. OBJECTIVE: Because inflammation elicited by S100A12 in vivo had characteristics of mast cell (MC) activation, we aimed to define the mechanism. METHODS: Various MC populations were used to test S100A12 activation assessed on the basis of morphology, histamine release, leukotriene production, and cytokine induction. MC dependence of S100A12-provoked inflammation was tested in mice and on the rat microcirculation by means of intravital microscopy. Immunohistochemistry localized S100A12 in the asthmatic lung, and levels in sputum from asthmatic patients were quantitated by means of ELISA. Expression of the receptor for advanced glycation end products was evaluated by means of RT-PCR and Western blotting. RESULTS: S100A12 provoked degranulation of mucosal and tissue MCs in vitro and in vivo and amplified IgE-mediated responses. It induced a cytokine profile indicating a role in innate/T(H)1-mediated responses. S100A12-induced edema and leukocyte rolling, adhesion, and transmigration in the microcirculation were MC dependent. Eosinophils in airway tissue from asthmatic patients were S100A12 positive, and levels were increased in sputum. S100A12 responses were partially blocked by an antagonist to the receptor for advanced glycation end products, but MCs did not express mRNA or protein, suggesting an alternate receptor. CONCLUSION: This novel pathway highlights the potential importance of S100A12 in allergic responses and in infectious and chronic inflammatory diseases. CLINICAL IMPLICATIONS: MC activation by S100A12 might exacerbate allergic inflammation and asthma. S100A12 might provide a novel marker for eosinophilic asthma.

Adult↗
PubMed2006

Genetic association between male attractiveness and female differential allocation.

Differential allocation of reproductive effort towards offspring of attractive mates is a form of post-copulatory mate choice. Although differential allocation has been demonstrated in many taxa, its evolutionary implications have received little attention. Theory predicts that mate choice will lead to a positive genetic correlation between female preference and male attractiveness. This prediction has been upheld for pre-copulatory mate choice, but whether such a relationship between male attractiveness and female differential allocation exists has never been tested. Here, we show that both female pre-copulatory mate choice and post-copulatory differential allocation are genetically associated with male attractiveness in house crickets, Acheta domesticus. Daughters of attractive males mated sooner and laid more eggs when paired with larger males. These forms of mate choice are strongest in large females, suggesting that costs decrease with increasing female size. The genetic association between attractiveness and differential allocation suggests potential for differential allocation to become exaggerated by coevolutionary runaway processes in an analogous manner to pre-copulatory choice. Sexual selection is thus likely to be stronger than predicted by pre-copulatory choice alone.

Animals↗
PubMed2006

Patterns and trends in sediment toxicity in the San Francisco Estuary.

Widespread sediment toxicity has been documented throughout the San Francisco Estuary since the mid-1980s. Studies conducted in the early 1990s as part of the Bay Protection and Toxic Cleanup Program (BPTCP), and more recently as part of the Regional Monitoring Program (RMP) have continued to find sediment toxicity in the Estuary. Results of these studies have shown a number of sediment toxic hotspots located at selected sites in the margins of the Estuary. Recent RMP monitoring has indicated that the magnitude and frequency of sediment toxicity is greater in the winter wet season than in the summer dry season, which suggests stormwater inputs are associated with sediment toxicity. Additionally, spatial trends in sediment toxicity data indicate that toxic sediments are associated with inputs from urban creeks surrounding the Estuary, and from Central Valley rivers entering the northern Estuary via the Delta. Sediment toxicity has been correlated with a number of contaminants, including selected metals, PAHs and organochlorine pesticides. While toxicity identification evaluations (TIEs) suggest that metals are the primary cause of sediment toxicity to bivalve embryos; TIEs conducted with amphipods have been inconclusive.

Amphipoda↗
PubMed2006

Automated streak-seeding with micromachined silicon tools.

This report presents a new approach to streak-seeding based on custom-designed silicon microtools. Experimental data show that the microtools produce similar results to the commonly used boar bristles. One advantage to using silicon is that it is rigid and can easily serve as an accurately calibrated end-effector on a micro-robotic system. Additionally, the fabrication technology allows the production of microtools of various shapes and sizes. A working prototype of an automatic streak-seeding system based on these microtools was built and successfully applied for protein crystallization.

Automation↗
PubMed2006

Artificial selection on male longevity influences age-dependent reproductive effort in the black field cricket Teleogryllus commodus.

Although the trade-off between reproductive effort and longevity is central to both sexual selection and evolutionary theories of aging, there has been little synthesis between these fields. Here, we selected directly on adult longevity of male field crickets Teleogryllus commodus and measured the correlated responses of age-dependent male reproductive effort, female lifetime fecundity, and several other life-history traits. Male longevity responded significantly to five generations of divergent selection. Males from downward-selected lines commenced calling sooner and reached their peak calling effort at a younger age. They called more per night and, despite living less than half as long, called more overall than males selected for increased longevity. Females from the downward-selected lines lived significantly shorter lives than females from the upward-selected lines but still produced the same number of offspring. Nymph survival, development time, and body size and weight at eclosion did not show significant correlated response to selection on male longevity, despite evidence for substantial genetic variation in each of these traits. Collectively, our findings directly support the antagonistic pleiotropy model of aging and suggest an important role for sexual selection in the aging process.

Aging↗
PubMed2006

Identification of acid reflux cough using serial assays of exhaled breath condensate pH.

BACKGROUND: Chronic cough is a common problem, frequently caused or exacerbated by acid reflux. Diagnosis of acid reflux cough is haphazard currently, often relying on long therapeutic trials of expensive medications. We tested the hypothesis that the most relevant mechanistic component of acid reflux in chronic cough is when it rises to the level of the airway where acid can potentially be aspirated. We further wished to determine if multi-sample exhaled breath condensate (EBC) pH profiles can identify chronic cough patients likely to respond to proton pump inhibitor therapy. METHODS: 59 subjects were recruited for this study. Initially we examined EBC pH (gas-standardized with Argon) in the setting of 15 experimental pharyngeal acid challenges to determine duration of EBC acidification. Subsequently, we enrolled 22 healthy subjects to determine a normal multi-sample exhaled breath condensate pH profile over 1-3 days. We additionally obtained multi-sample EBC pH profiles in 22 patients with chronic cough. These samples were timed to occur after coughing episodes. Exhaled breath condensate pH was measured after gas standardization. RESULTS: We found that exhaled breath condensate pH is substantially reduced for approximately 15 minutes after pharyngeal acid load. Healthy subjects rarely have any low EBC pH values (defined as < 7.4 based on a normative reference range from 404 healthy subjects). Patients with chronic cough who subsequently responded well to proton pump inhibition (n = 8) invariably had one or more cough episodes associated with EBC acidification. No patient who had normal EBC pH with each of their cough episodes reported a clinically relevant response to proton-pump inhibition. CONCLUSION: Patients whose cough responds to proton pump inhibition have transient exhaled breath condensate acidification with coughing episodes, supporting the role of airway acidification in reflux-triggered cough. Multi-sample EBC pH profiles, involving samples collected immediately subsequent to a coughing episode, may be useful appropriately to direct therapy to those patients with cough who have relevant acid reflux.

Journal Article↗
PubMed2006

Complex multivariate sexual selection on male acoustic signaling in a wild population of Teleogryllus commodus.

Mate choice may impose both linear (i.e., directional) and nonlinear (i.e., quadratic and correlational) sexual selection on advertisement traits. Traditionally, mate recognition and sensory tuning have been thought to impose stabilizing (i.e., negative quadratic) sexual selection, whereas adaptive mate choice effects directional selection. It has been suggested that adaptive choice may exert positive quadratic and/or correlational sexual selection. Earlier, we showed that five structural components of the advertisement call of male field crickets (Teleogryllus commodus) were under multivariate stabilizing selection under laboratory conditions. Here we experimentally estimate selection on these five traits plus a measure of calling activity (the number of repeats in a looped bout of calling) in the field. There was general support for multivariate stabilizing selection on call structure, and calling activity was under strong positive directional selection, as predicted for a signal of genetic quality. There was, however, also appreciable correlational selection, suggesting an interaction between male call structure and calling effort. Interestingly, selection for short interbout durations of silence favored longer intercall durations in the field, in contrast to results from continuous looped call playback in the laboratory. We discuss the general importance of nonlinear selection in the honest signaling of genetic quality.

Acoustic Stimulation↗
PubMed2006

Airway acidification: interactions with nitrogen oxides and airway inflammation.

Airway acidification is increasingly appreciated to occur in inflammatory obstructive airway diseases, resulting from acid reflux and aspiration and from direct acid formation in the airways. Acidity activates oxidants and nitrogen oxides to create a potent antimicrobial environment. Neurogenic inflammation is triggered by airway or esophageal acidification, innate immune cells are affected by acidity, and there are pathways by which the acquired immune system also can be activated by the chemistry of an acidic airway. Measuring airway acidity is now readily achievable with noninvasive breath assays, a procedure that has opened a window on the need to understand airway pH homeostasis in health and pH dysregulation in disease.

Acids↗
PubMed2006

pH increase observed in exhaled breath condensate from welding fume exposure.

OBJECTIVES: We sought to investigate changes in exhaled breath condensate (EBC) pH in healthy workers exposed to welding fumes. METHODS: Fourteen exposed participants (median age 39 years, 5 smokers) and 8 nonexposed controls (median age 44 years, 1 smoker) were monitored at an apprentice welding school. Exposure to fine particulate matter less than 2.5 microm (PM2.5) was assessed using cyclone samplers. EBC samples were collected at baseline and at the end of the work shift. EBC samples were deaerated using argon and pH values were measured using standard pH microelectrodes. RESULTS: Mean +/- SEM PM2.5 levels were 1.17 +/- 0.18 mg/m for exposed subjects and 0.03 +/- 0.01 mg/m for controls. Baseline median (range) EBC pH values for the control and exposed group were similar (P = 0.86), 7.21 (4.91 to 8.26), and 7.39 (4.85 to 7.79), respectively. The exposed subjects had a small-but-marginally significant (P = 0.07) pre- to post-work shift increase in pH of 0.28, whereas the control group showed a minimal increase of only 0.03 (P = 0.56). Compared with the control group, the exposed group had a median cross-shift pH increase of 0.25 (P = 0.49). CONCLUSIONS: The aerosolized fine particulate matter contained in metal fumes may be associated with an acute increase in EBC pH values. Further study is necessary to investigate the acute rise in EBC pH after acute exposure to welding fume.

Adult↗
PubMed2006

Sexual conflict and cryptic female choice in the black field cricket, Teleogryllus commodus.

The prevalence and evolutionary consequences of cryptic female choice (CFC) remain highly controversial, not least because the processes underlying its expression are often concealed within the female reproductive tract. However, even when female discrimination is relatively easy to observe, as in numerous insect species with externally attached spermatophores, it is often difficult to demonstrate directional CFC for certain male phenotypes over others. Using a biological assay to separate male crickets into attractive or unattractive categories, we demonstrate that females strongly discriminate against unattractive males by removing their spermatophores before insemination can be completed. This results in significantly more sperm being transferred by attractive males than unattractive males. Males respond to CFC by mate guarding females after copulation, which increases the spermatophore retention of both attractive and unattractive males. Interestingly, unattractive males who suffered earlier interruption of sperm transfer benefited more from mate guarding, and they guarded females more vigilantly than attractive males. Our results suggest that postcopulatory mate guarding has evolved via sexual conflict over insemination times rather than through genetic benefits of biasing paternity toward vigorous males, as has been previously suggested.

Animals↗
PubMed2005

Comparisons of NMR spectral quality and success in crystallization demonstrate that NMR and X-ray crystallography are complementary methods for small protein structure determination.

X-ray crystallography and NMR spectroscopy provide the only sources of experimental data from which protein structures can be analyzed at high or even atomic resolution. The degree to which these methods complement each other as sources of structural knowledge is a matter of debate; it is often proposed that small proteins yielding high quality, readily analyzed NMR spectra are a subset of those that readily yield strongly diffracting crystals. We have examined the correlation between NMR spectral quality and success in structure determination by X-ray crystallography for 159 prokaryotic and eukaryotic proteins, prescreened to avoid proteins providing polydisperse and/or aggregated samples. This study demonstrates that, across this protein sample set, the quality of a protein's [15N-1H]-heteronuclear correlation (HSQC) spectrum recorded under conditions generally suitable for 3D structure determination by NMR, a key predictor of the ability to determine a structure by NMR, is not correlated with successful crystallization and structure determination by X-ray crystallography. These results, together with similar results of an independent study presented in the accompanying paper (Yee, et al., J. Am. Chem. Soc., accompanying paper), demonstrate that X-ray crystallography and NMR often provide complementary sources of structural data and that both methods are required in order to optimize success for as many targets as possible in large-scale structural proteomics efforts.

Animals↗
PubMed2005

Assaying all of the nitrogen oxides in breath modifies the interpretation of exhaled nitric oxide.

Exhaled nitric oxide (NO) assays measure the quantity of NO that emanates from the airway, not the amount of NO that is formed. Consumptive processes-including oxidation reactions-decrease the amount of gas phase NO available for exhalation. Higher oxides of nitrogen (HiNO(x)) are resulting reaction products, and are easily measured in exhaled breath condensate (EBC). We performed concurrent sampling of exhaled breath for gas phase NO and EBC HiNO(x) in controls and stable asthmatics. We identified that, mole for mole, asthma patients hourly exhale more HiNO(x) than they do NO, with a HiNO(x)/NO ratio of 1.21 (0.54-3.4). This is the reverse of the ratio found in controls, in whom the HiNO(x)/NO ratio was 0.75 (0.44-0.93), p=0.04. The sum of the hourly molar exhalation of NO and HiNO(x) was significantly higher in asthmatics (333 nmol/h (221-543) than controls (179 (138-231), p<0.001). We conclude that exhaled oxides of nitrogen are more informative when measured together as opposed to in isolation. We suggest that inflammation can be better evaluated with HiNO(x) and NO measured concurrently, and that the level of oxidation in the lung can be evaluated by comparing the easily measured ratios of HiNO(x) to NO in the exhaled breath.

Adolescent↗