Biomedical subjects

James R Carey

Publications and source records attributed to James R Carey.

At least 19 recordsLinked to original sources

PubMed2006

Comparative approaches to facilitate the discovery of prolongevity interventions: effects of tocopherols on lifespan of three invertebrate species.

Many compounds hold promise for pharmacologic manipulation of aging. However, such claims are difficult to investigate due to time and budget constraints. Here, we took a comparative approach, using short-lived invertebrate species, to directly test the effects of two tocopherols (Vitamin E) on longevity. gamma-Tocopherol represents the most abundant tocopherol in the Western diet, while alpha-tocopherol is selectively enriched in human plasma. Both isoforms demonstrate antioxidant activity and are proposed to have anti-aging activities. We compared the effects of alpha- and gamma-tocopherol supplementation on lifespan in three invertebrate species. gamma-Tocopherol, but not alpha-tocopherol, slightly extended lifespan in nematodes, but neither significantly affected lifespan in two fly species. This study shows that a comparative approach, utilizing multiple invertebrate species, can increase the robustness of invertebrate-based pilot screens for prolongevity interventions.

Animals↗

PubMed2006

A search for principles of disability using experimental impairment of Drosophila melanogaster.

The results of life table experiments to determine the effects of artificial impairment (leg amputation) in 7500 Drosophila melanogaster adults revealed that the extent to which life expectancy was reduced in impaired individuals was conditional on: (1) leg location and number amputated--front leg had greatest impact and the number of legs amputated directly correlated with mortality impact; (2) age of amputation--the greatest relative reduction in remaining life expectancy occurred when young flies were impaired; (3) vial orientation--mortality in impaired flies was the least when vials held upside-down (most friendly environment) and the greatest when they were right-side up (least friendly environment); and (4) sex--male mortality was increased more than female mortality in nearly all impairment treatments. These results were used to formulate a set of general principles of disability that would apply not only to humans but to all organisms.

Amputation, Surgical↗

PubMed2006

Behavioral trajectories as predictors in event history analysis: male calling behavior forecasts medfly longevity.

A recent study on wild male Mediterranean fruit flies [Papadopoulos, N.T., Katsoyannos, B.I., Kouloussis, N.A., Carey, J.R., Müller, H.-G., Zhang, Y., 2004. High sexual signalling rates of young individuals predict extended life span in male Mediterranean fruit flies. Oecologia 138, 127-134] provided evidence that intense sexual signalling (calling behavior) is associated with longer life span. We demonstrate here an approach based on functional data analysis methodology for predicting individual remaining longevity and the distribution of remaining lifetime from individual behavioral trajectories. A key methodological concept is the time evolution of mean functions and eigenfunctions. This methodology is applied to the event history of calling behavior of male medflies. The results demonstrate complex relationships between male calling behavior and subsequent longevity that complement previous biodemographic analyses of these data. A high level of recent calling activity is found to be associated with increased remaining lifetime for an individual male fly, while calling activity at early ages plays no role for remaining longevity.

Animals↗

PubMed2006

Primary motor area activation during precision-demanding versus simple finger movement.

The authors used functional magnetic resonance imaging to explore whether the primary motor area (M1) serves a processing role in a finger-movement tracking task, emphasizing attention to accuracy, beyond its execution role of simple movements, with no attention to accuracy. Twenty healthy subjects performed alternating conditions: Rest, involving no finger movement; Track, involving careful control of a cursor along a target pathway with finger extension/flexion movements; and Move, involving finger extension/flexion movements without careful control. The authors compared volume of activated voxels in the M1, blood-oxygen-level-dependent (BOLD) signal intensity of activated voxels in the M1, and BOLD signal intensity of all voxels in the M1 between the Track and Move conditions. The results showed greater volume and signal intensity in both the contralateral and ipsilateral M1 during Track than during Move. Overall, the results suggest that the M1 is engaged not only in the execution of movements but also in spatial and temporal processing to produce accurately controlled movements. These findings invite further work exploring whether precision-demanding movements, such as tracking, form a more potent stimulus for promoting helpful brain reorganization in the M1 during the recovery from stroke than simple repetitive movements.

Adult↗

PubMed2006

rTMS combined with motor learning training in healthy subjects.

PURPOSE: This study explored the effects of motor learning training combined with repetitive transcranial magnetic stimulation (rTMS) on motor performance in healthy subjects. METHODS: Twenty-seven right-handed subjects were randomized to three groups: ipsilateral rTMS (IS group), contralateral rTMS (CS group), and sham rTMS (SS group). rTMS was applied for 10 minutes (1 Hz, 90% motor threshold) prior to training. Training involved 10 minutes of finger tracking with the right hand. Tracking performance was tested before, during and after training. RESULTS: Improvement in tracking performance over the posttests was not significantly different between the CS and SS groups, whereas it was significantly lower for the IS group compared to the SS group. No difference was found across groups at retention tests. CONCLUSION: These findings indicate that rTMS interfered with motor performance transiently when applied ipsilateral to the training hand and had no effect when applied contralaterally. These results invite further work to determine whether the disruptive effect of ipsilateral rTMS observed here in healthy subjects, with presumably balanced interhemispheric inhibition, might translate differently to subjects with abnormal interhemispheric inhibition (stroke patients) in a way that disinhibits the ipsilesional hemisphere and improves performance in the paretic hand.

Adolescent↗

PubMed2005

Age-specific and lifetime behavior patterns in Drosophila melanogaster and the Mediterranean fruit fly, Ceratitis capitata.

Patterns of behavior were recorded every 10 min during a 2-h period each day from eclosion to death for individual Drosophila melanogaster (both sexes) and Ceratitis capitata (males-only) including walking, preening, feeding, flying, and resting for the former species, and walking, calling (signaling), supine (upside-down), and resting in the latter. Results reveal that, with the exception of preening in D. melanogaster, behavioral patterns are age-specific and the frequency of several behaviors (e.g. supine in medfly; walking and resting in D. melanogaster) are correlated with time-to-death. This is the first set of studies to report the age patterns over a range of behavioral categories throughout the lives of individuals and thus the first that systematically documents the behavior of individuals at advanced ages. We suggest that the new and unique behaviors (e.g. supine) that emerge from the aging process be referred to as degenerative behaviors, not only to distinguish them from the conventional behavioral classifications (innate, learned), but also to reflect their emergent nature.

Aging↗

PubMed2005

Blue ferrocenium azurin: an organometalloprotein with tunable redox properties.

A ferrocene derivative (2-[(methylsulfonyl)thio]ethylferrocene) (1) has been synthesized and incorporated into apo-azurin from Pseudomonas aeruginosa by covalent attachment to the highly conserved Cys112. The resulting artificial organometalloprotein (a protein containing organometallic compounds in the active site) has been characterized by UV-vis, electrospray mass spectrometry, and cyclic voltammetry (CV). Incorporation of 1 into azurin resulted in a higher solubility of the ferrocene group and improved stability of the ferrocenium species in aqueous solution, as shown by a more intense UV-vis absorption and a more reversible CV of the attached ferrocene group, respectively. The incorporation of 1 also increased the reduction potential of the complex from 402 to 579 mV (vs NHE), consistent with the ferrocene group being encapsulated inside the hydrophobic environment of the protein. Modulation of the reduction potential of ferrocene by residues near the secondary coordination sphere has also been demonstrated. Raising the pH from 4 to 9 resulted in a greater than 80 mV decrease in reduction potential of the protein-bound ferrocene (from 579 to 495 mV), while replacing Met121, an amino acid residue in close proximity to the ferrocene group with a positively charged Arg or negatively charged Glu, resulted in the predicted increase or decrease in reduction potential at all pH values. Similarly, substitution of Met121 with a more hydrophobic Leu raised the reduction potential. The increased solubility, stability, and tune-ability of this organometalloprotein make it an ideal choice for carrying out a number of biological reactions, such as long-range electron transfer or sensing. As an example of such applications, stoichiometric oxidation of ferrocytochrome c by the blue ferrocenium azurin was demonstrated.

Azurin↗

PubMed2005

Biodemography of a long-lived tephritid: reproduction and longevity in a large cohort of female Mexican fruit flies, Anastrepha ludens.

Age of sexual maturity, daily and lifetime reproductive rates, and life span were recorded in a laboratory cohort of Mexican fruit flies consisting of over 1100 females maintained individually. The results revealed that, relative to the medfly, the Mexfly is slower maturing (14 vs 17 days), more fecund (1400 vs 650-1100 eggs/female), and longer lived (50 vs 35 days). The results reinforced the generality of several earlier findings on the medfly including the deceleration of mortality at older ages and the weakness of the correlation between the rate of egg laying at early ages and both subsequent reproduction and remaining longevity. Discussion includes perspectives on the role of artificial selection in shaping the demographic traits of the mass-reared strain of Mexfly used in this study, as well as the overall significance of large scale biodemographic studies in understanding aging and longevity.

Aging↗

PubMed2005

Formation of stable Meisenheimer adduct ion pairs in apolar solvents: implications for stereoselective reactions.

[reaction: see text] A detailed study concerning the formation of Meisenheimer adducts in biphasic solvent systems is described. The process relies on utilizing a significantly lipophilic quaternary ammonium salt to transfer a nucleophile (e.g., hydroxide ion) between an aqueous and organic layer containing the electron-deficient aromatic substrate. Provided that the organic layer is sufficiently apolar, the resultant Meisenheimer adduct is considerably stable, likely the result of a strong ion-pairing interaction between the large polarizable anionic complex and the diffusively charged tetraalkylammonium cation. Using the diethylamide of 3,5-dinitrobenzoic acid as a model compound, the influence of ion-pairing reagents and solvents on adduct formation was investigated. Dramatically increased equilibrium formation of the Meisenheimer adduct is observed in the biphasic medium (e.g., benzene/2 M NaOH) relative to the same adduct generated in single-phase systems. Spectroscopic studies on this adduct are consistent with those conducted in single-phase polar or dipolar aprotic solvents. The methodology is extended to performing highly enantioselective biphasic kinetic resolutions of several racemic electron-deficient amides.

Journal Article↗

PubMed2005

Trends in lipid and protein contents during medfly aging: an harmonic path to death.

Survival and egg-laying trends were investigated in Mediterranean fruit flies (Ceratitis capitata) adults maintained on a sucrose-only diet, or on a full diet that consisted of a 3:1 sucrose and yeast hydrolizate mixture. In addition, we followed the total individual lipid and protein contents of aging flies in a cohort. Survival trends and life expectancy parameters at eclosion for males and females on full diet and for males on sucrose only were very similar. In contrast, the mortality of females on sucrose only was high early in life, but then slowed down. Egg-laying was ten times greater in female flies on full diet than in flies on sucrose only. Lipid contents in males and females on both types of diets were very similar, and harmonically oscillated with an amplitude of approximately 10 days. Successive crests of lipids tended to be smaller with the ageing of the cohort, and lipids contents significantly dropped at very advanced ages and close to the maximal age of the whole cohort. Protein contents of flies maintained on a full diet were high and stayed at a constant level throughout the entire life of the cohort. Protein levels in males and females on sucrose only dropped drastically during the first days of adult life, but then stayed stable at a low level until advanced ages. We propose that the synchronous rhythmic oscillation in lipid contents of male and female flies seems to be independently set by an internal clock. Protein reserves are allocated according to the access to protein food sources and these levels of protein are closely associated to egg production and mortality. Our results are discussed in view of resource allocation during reproduction and senescence.

Age Factors↗

PubMed2005

The symmetry of longevity.

We tested the hypothesis that relatively symmetrical flies live longer. Vein measurements on the left and right wings from the same individual were used to characterize bilateral symmetry in relationship to age-specific survival in defined cohorts. A longitudinal cohort study supported the hypothesis of a correlation between bilateral symmetry and longevity. For another type of experiment, wings were removed from females and males at approximately the beginning of adult life. Thus, there would be no effect of wings per se on adult survival. These wings were measured to characterize bilateral asymmetry, and the day of death of each dewinged individual was determined. Wing symmetry of females and males proved to be a statistically significant predictor of life span, especially for males.

Animals↗

PubMed2005

Individual fecundity and senescence in Drosophila and medfly.

Evolutionary theory postulates that there should be a robust relationship between fecundity and longevity. Prior work has generally supported this concept, but has not shed much light on the mechanisms at play. In preceding work, we have developed and verified a mathematical model of Drosophila melanogaster female fecundity based on the analysis of empirical studies independently done by several different laboratories. Then we applied this technique to Mediterranean fruit fly (medfly) populations. In this article we analyze associations between individual longevity and the parameters of individual fecundity pattern in Drosophila and medfly. We cluster both Drosophila and medfly individuals by life span and discuss the differences. It allows us to demonstrate that only one fecundity-related parameter is associated with longevity in Drosophila, whereas two such parameters can be found in medflies. This difference demonstrates different ways of aging in various Diptera species. Finally, we discuss the possible implications of this finding.

Aging↗

PubMed2005

Stochastic dietary restriction using a Markov-chain feeding protocol elicits complex, life history response in medflies.

Lifespan in individually housed medflies (virgins of both sexes) and daily reproduction for females were studied following one of 12 dietary restriction (DR) treatments in which the availability of high-quality food (yeast-sugar mixture) for each fly was based on a Markov chain feeding scheme--a stochastic dietary regime which specifies that the future dietary state depends only on the present dietary state and not on the path by which the present state was achieved. The stochastic treatments consisted of a combination of one of four values of a 'discovery' parameter and one of three values of a 'persistence' parameter. The results supported the hypotheses that: (i) longevity is extended in most medfly cohorts subject to stochastic DR; and (ii) longevity is more affected by the patch discovery than the patch persistence parameter. One of the main conclusions of the study is that, in combination with the results of earlier dietary restriction studies on the medfly, the results reinforce the concept that the details of the dietary restriction protocols have a profound impact on the sign and magnitude of the longevity extension relative to ad libitum cohorts and that a deeper understanding of the effect of food restriction on longevity is not possible without an understanding of its effect on reproduction.

Age Factors↗

PubMed2005

Neuroplasticity promoted by task complexity.

One condition that appears to have a strong impact on the neuroplastic changes presumed to subserve skillful motor performance is the complexity of tasks during motor training. This paper reviews some of the morphological, physiological, and behavioral effects associated with training on difficult tasks involving in-depth information processing, compared to simpler tasks, requiring lesser processing.

Animals↗

PubMed2004

A site-selective dual anchoring strategy for artificial metalloprotein design.

Introducing nonnative metal ions or metal-containing prosthetic groups into a protein can dramatically expand the repertoire of its functionalities and thus its range of applications. Particularly challenging is the control of substrate-binding and thus reaction selectivity such as enantioselectivity. To meet this challenge, both non-covalent and single-point attachments of metal complexes have been demonstrated previously. Since the protein template did not evolve to bind artificial metal complexes tightly in a single conformation, efforts to restrict conformational freedom by modifying the metal complexes and/or the protein are required to achieve high enantioselectivity using the above two strategies. Here we report a novel site-selective dual anchoring (two-point covalent attachment) strategy to introduce an achiral manganese salen complex (Mn(salen)), into apo sperm whale myoglobin (Mb) with bioconjugation yield close to 100%. The enantioselective excess increases from 0.3% for non-covalent, to 12.3% for single point, and to 51.3% for dual anchoring attachments. The dual anchoring method has the advantage of restricting the conformational freedom of the metal complex in the protein and can be generally applied to protein incorporation of other metal complexes with minimal structural modification to either the metal complex or the protein.

Animals↗

PubMed2004

From genes to societies.

Research on model organisms has substantially advanced our understanding of aging. However, these studies collectively lack any examination of the element of sociality, an important feature of human biology. Social insects present a number of unique possibilities for investigating social influences on aging and potentially detecting new mechanisms for extremely prolonged, healthy life spans that have evolved naturally. Social evolution has led to life spans in reproductive females that are much longer (up to over 100-fold) than those of males or of nonreproductive worker castes. These differences are particularly dramatic because they are due to environmental influences, as all individuals develop from the same genomes. Social insect colonies consist of semi-autonomous individuals, and the relationship between the colony and the individual creates many interesting predictions in the light of the common theories of aging. Furthermore, the variety of lifestyles of social insects creates the potential for crucial comparative analyses across distinct social systems.

Animals↗

PubMed2004

Demographic window to aging in the wild: constructing life tables and estimating survival functions from marked individuals of unknown age.

Summary We address the problem of establishing a survival schedule for wild populations. A demographic key identity is established, leading to a method whereby age-specific survival and mortality can be deduced from a marked cohort life table established for individuals that are randomly sampled at unknown age and marked, with subsequent recording of time-to-death. This identity permits the construction of life tables from data where the birth date of subjects is unknown. An analogous key identity is established for the continuous case in which the survival schedule of the wild population is related to the density of the survival distribution in the marked cohort. These identities are explored for both life tables and continuous lifetime data. For the continuous case, they are implemented with statistical methods using non-parametric density estimation methods to obtain flexible estimates for the unknown survival distribution of the wild population. The analytical model provided here serves as a starting point to develop more complex models for residual demography, i.e. models for estimating survival of wild populations in which age-at-entry is unknown and using remaining information in randomly encountered individuals. This is a first step towards a broad new concept of 'expressed demographic information content of marked or captured individuals'.

Age Factors↗

PubMed2003

Electrical stimulation driving functional improvements and cortical changes in subjects with stroke.

It has been proposed that somatosensory stimulation in the form of electromyographically triggered neuromuscular electrical stimulation (NMES) to the peripheral nerve can influence functional measures of motor performance in subjects with stroke and can additionally produce changes in cortical excitability. Using a controlled, double-blind design, we studied the effects of intensive (60 h/3 weeks) treatment at home with NMES compared with a sham treatment, applied to the extensor muscles of the hemiplegic forearm to facilitate hand opening in 16 chronic stroke subjects. We investigated improvement in functional use of the hand and change in cortical activation as measured by functional magnetic resonance imaging (fMRI). Following treatment, subjects improved on measures of grasp and release of objects (Box and Block Test and Jebsen Taylor Hand Function Test [JTHFT]: small objects, stacking, heavy cans), isometric finger extension strength, and self-rated Motor Activity Log (MAL): Amount of Use and How Well score. The sham subjects did not improve on any grasp and release measure or self-rated scale, but did improve on isometric finger extension strength. Importantly, however, following crossover, these subjects improved further in the measure of strength, grasp and release (Box and Block [JTHFT]: page turning), and self-rated MAL: Amount of Use score and How Well score. Using fMRI and a finger-tracking task, an index of cortical intensity in the ipsilateral somatosensory cortex increased significantly from pre-test to post-test following treatment. Cortical activation, as measured by voxel count, did not change. These findings suggest that NMES may have an important role in stimulating cortical sensory areas allowing for improved motor function.

Adult↗