New modalities of brain stimulation for stroke rehabilitation.

Stroke is a leading cause of disability, and the number of stroke survivors continues to rise. Traditional neurorehabilitation strategies aimed at restoring function to weakened limbs provide only modest benefit. New brain stimulation techniques designed to augment traditional neurorehabilitation hold promise for reducing the burden of stroke-related disability. Investigators discovered that repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and epidural cortical stimulation (ECS) can enhance neural plasticity in the motor cortex post-stroke. Improved outcomes may be obtained with activity-dependent stimulation, in which brain stimulation is contingent on neural or muscular activity during normal behavior. We review the evidence for improved motor function in stroke patients treated with rTMS, tDCS, and ECS and discuss the mediating physiological mechanisms. We compare these techniques to activity-dependent stimulation, discuss the advantages of this newer strategy for stroke rehabilitation, and suggest future applications for activity-dependent brain stimulation.

Establishment of the Mediterranean fruit fly in California.

Principles of invasion biology are brought to bear on the question of whether the medfly is established in California. Since its first discovery in 1975, the pest has been captured in the Los Angeles Basin in nine separate years including every year from 1986 through 1990. The trend has become distinct--the intervals between captures are decreasing, the numbers captured are increasing, and the area over which they are detected is expanding. In addition, appearances are seasonal and captures in recent years have occurred in many of the same cities and neighborhoods where medflies were found several years before. Evidence suggests that the medfly may be established in the Los Angeles area and that previous eradication programs did not eradicate the medfly from California. It follows that detection, exclusion, and eradication protocols may need to be reexamined.

Induced resistance of cotton seedlings to mites.

Mite populations grew more rapidly on new growth of cotton seedlings that had never been exposed to mites than on new growth of plants whose cotyledons had been previously exposed to them. Experiments in which a second mite introduction on the exposed plants involved a different mite species produced this same result. The substance or substances responsible for the response are transported systemically among leaves of cotton seedlings.

Slowing of mortality rates at older ages in large medfly cohorts.

It is generally assumed for most species that mortality rates increase monotonically at advanced ages. Mortality rates were found to level off and decrease at older ages in a population of 1.2 million medflies maintained in cages of 7,200 and in a group of approximately 48,000 adults maintained in solitary confinement. Thus, life expectancy in older individuals increased rather than decreased with age. These results cast doubt on several central concepts in gerontology and the biology of aging: (i) that senescence can be characterized by an increase in age-specific mortality, (ii) that the basic pattern of mortality in nearly all species follows the same unitary pattern at older ages, and (iii) that species have absolute life-span limits.

Dual modes of aging in Mediterranean fruit fly females.

The life history of medflies is characterized by two physiological modes with different demographic schedules of fertility and survival: a waiting mode in which both mortality and reproduction are low and a reproductive mode in which mortality is very low at the onset of egg laying but accelerates as eggs are laid. Medflies stay in waiting mode when they are fed only sugar. When fed protein, a scarce resource in the wild, medflies switch to reproductive mode. Medflies that switch from waiting to reproductive mode survive longer than medflies kept in either mode exclusively. An understanding of the physiological shift that occurs between the waiting and reproductive modes may yield information about the fundamental processes that determine longevity.

Biodemographic trajectories of longevity.

Old-age survival has increased substantially since 1950. Death rates decelerate with age for insects, worms, and yeast, as well as humans. This evidence of extended postreproductive survival is puzzling. Three biodemographic insights--concerning the correlation of death rates across age, individual differences in survival chances, and induced alterations in age patterns of fertility and mortality--offer clues and suggest research on the failure of complicated systems, on new demographic equations for evolutionary theory, and on fertility-longevity interactions. Nongenetic changes account for increases in human life-spans to date. Explication of these causes and the genetic license for extended survival, as well as discovery of genes and other survival attributes affecting longevity, will lead to even longer lives.

Extraordinary long life spans in fruit-feeding butterflies can provide window on evolution of life span and aging.

Information on the life span of organisms in the field is essential for elucidating the evolution of life span and aging. We present mark-recapture data (>30,000 marked individuals, >4000 recaptured at least once) on 47 species of fruit-feeding butterflies in a tropical forest in Uganda. The data reveal adult life spans in the field for several species that are significantly longer than previously recorded in Lepidoptera (butterflies and moths). Longevity records for species of which more than 100 individuals were recaptured ranged from 67 (Bicyclus auricruda) to 293 days (Euphaedra medon). In contrast to the majority of Lepidoptera which are short-lived, these all show exceptionally long life spans, and may thus help to better identify factors that affect aging, particularly when combined with information on temporal patterns in reproduction, strategies to avoid predation, and nutritional ecology. These key traits are readily measurable in butterflies and thus studies on fruit-feeding butterflies have much potential for gaining insight into the evolution of life span and aging, especially given the tradition of field-research on butterflies.

The ecology and biodemography of Caenorhabditis elegans.

The nematode Caenorhabditis elegans is a well-known model organism for research on aging and life span, but very little is known about its ecology and natural history. The strain N2 is the standard wild-type C. elegans and arose from the progeny of a single hermaphrodite. Since N2 has passed through laboratory culture, the influence of inadvertent selection and genetic drift on C. elegans strains kept in culture is unclear. Because it seems that other wild-type strains have also been subject to lengthy laboratory culture, the life span and biodemography of wild-caught C. elegans is of interest. We recovered C. elegans from snails (Helix aspersa) in ca. 50% of the California locations where we made collections. In experiments with one of the wild-caught isolates, it differed in important demographic properties, mortality, fertility, fitness, and activity patterns, from the standard N2 strain, when both strains were evaluated in a common laboratory environment. The differences were not only statistically significant; they were also large enough to be biologically important. The differences are consistent with the hypothesis that N2 has adapted to laboratory conditions.

Muscle fiber orientation in muscles commonly injected with botulinum toxin: an anatomical pilot study.

The endplate zone is assumed to be at about the midpoint of a muscle fiber. This study was designed to locate the middle of the muscle fibers of commonly injected muscles, thus identifying the endplate zone of these muscles. The proximal and distal musculotendinous junctions in muscles of the upper and lower extremities were identified. Orientation of muscle fibers was determined. Measurements using common surface landmarks were used to determine the relationship of these muscles with the landmarks (e.g., biceps muscle bulk extends from the upper fourth to the lower fourth of the humerus). Figures were developed using these measurements so as to be able to extrapolate these measurements to other patients of varying sizes. Illustrations of muscle fiber orientation were done and the assumed location of motor endplate bands marked. Color illustrations will be shown. With the thought that the endplate zone is at the middle of the muscle fiber, this detailed study of muscle fibers helps identify assumed location of motor endplates of specific muscles, thereby improving technique and efficacy of botulinum toxin injections.

Revising the standard wisdom of C. elegans natural history: ecology of longevity.

Here, we consider that most of the research concerning Caenorhabditis elegans has been laboratory focused and that only limited research has directly considered the worm's biology relative to its natural history in the wild. We describe that, although the worm has traditionally been considered a soil nematode, we could not find it in soil but frequently recovered it from snails. Finally, we discuss how a better understanding of the natural history of C. elegans may enhance its usefulness as a model organism for studying aging and other phenomena.

The impact of diet switching on resource allocation to reproduction and longevity in Mediterranean fruitflies.

Understanding the factors that determine the allocation and utilization of organism resources may provide an insight into the mechanisms of adaptation, ageing and reproduction. Resource allocation, which is regarded as a method of adaptation, increases fitness and is genetically controlled. Experiments with variable diet feeding of female Mediterranean fruitflies (Ceratitis capitata) demonstrated that the feeding regime dramatically influences lifespan, mortality and the reproduction of flies. An analysis of experimental data and numerical experiments reveals that resource allocation could explain lifespan increase when females are switched from a sugar-only to a protein-containing diet. The heterogeneity of the initial female cohort in terms of the total amount of resources and its allocation to the processes of maintenance and reproduction plays a significant role in this.

Reproductive potential predicts longevity of female Mediterranean fruitflies.

Reproduction exacts a price in terms of decreased survival. Our analysis of the interplay between age patterns of fecundity and mortality for individual female medflies (Ceratitis capitata) revealed that individual mortality is associated with the time-dynamics of the egg-laying trajectory. In a sample of 531 medflies, we found that each individual has a characteristic rate of decline in egg laying with age. This defines an individual's rate of reproductive exhaustion. This rate was shown to predict subsequent mortality The larger the remaining reproductive potential, the lower the subsequent mortality An increased mortality risk was seen in flies for which egg production declined rapidly early on, irrespective of the level of egg production. Thus, reproductive potential and lifetime are coupled in such a way that those flies which are able to profit most from an extended life span in terms of increased egg output are indeed likely to live longer.

Demographic mechanisms for the evolution of long life in social insects.

One of the most remarkable life history traits of many species of eusocial insects is the extraordinary longevity of their queens, with the recorded life span of some individuals exceeding 30 years. Surprisingly, little research has been conducted on either the proximate or ultimate questions concerning what factors favor the evolution of the long life spans in social insects. The broad objective of this paper is to address four sets of questions: (1) What are the similarities and differences in the longevity patterns among species in the four main groups of social insects - bees, wasps, ants and termites? (2) What is the evolutionary association of longevity and sociality in insects? (3) Are there biodemographic principles that can be derived from studies on longevity in social insects? and (4) What are the general implications for longevity in vertebrates, including humans?

Sex-specific life table aging rates in large medfly cohorts.

Life table aging rate (LAR) is defined as the age-specific rate of mortality change with age and corresponds to the first derivative or slope of the mortality schedule at each age. We computed the sex-specific LARs for 167 Medfly cohorts, containing a total of approximately 600,000 individuals of each sex. We found that: (a) the LAR is not constant for either sex; at the youngest ages, mortality changes by approximately 1.4-fold daily, whereas at the older ages (>30 days), mortality levels off and decreases; (b) female LAR is higher than male LAR from 0 to 12 days, at which time the rates cross over and male LAR is higher than female LAR; however, at about 30 days, both male and female LARs are less than or equal to unity; (c) mortality in each of the 167 cohorts leveled off for both sexes. The average age for this leveling off was around 23 days for females and 31 days for males; and (d) the mortality rate at the age of leveling off was approximately 1.4-fold higher in males than in females--0.13/day for females and 0.19/day for males. Implications of these findings are briefly discusses, including the use of summary measures of senescence, the arbitrariness of selecting the age of senescence onset, and test of hypotheses concerned with explanations of mortality patterns such as leveling off at older ages.

Comparative demography of isogenic populations of Caenorhabditis elegans.

Demographic characteristics of the bacterial-feeding nematode Caenorhabditis elegans were determined in two long-lived mutant strains, TJ1052 (age-1), CB4876 (clk-1), and a wild-type strain, N2. Within each strain, there was little correlation between longevity and reproduction for individuals that lived longer than 10days. Long-lived mutant strains produced fewer eggs than the wild type. Mean total life spans were 13.2days for the wild type, 21.9days for age-1, and 15.8days for clk-1; maximum life spans were 24days for the wild type, 47days for age-1, and 32days for clk-1. Differences in total life span resulted primarily from longer post-reproductive survival. The mean post-reproductive life spans were longer than the wild type by 183% in age-1 and 60% in clk-1. We conclude that (i) post-reproductive survival is not correlated with egg production within isogenic populations of C. elegans, and (ii) the relationship between reproduction and longevity differs among isogenic populations with specific longevity genes.

Mortality dynamics of density in the Mediterranean fruit fly.

The effects on medfly age-specific mortality of three types of densities--initial, current, and cumulative--were examined using sex-specific data from two sets of studies: (1) previous research on mortality patterns in 1.2 million individuals maintained in 167 different cages (1992 Science 258, 457) and ii) density experiments using a total of 210,000 individuals contained in 49 cages and maintained at one of three initial densities--2500, 5000 and 10,000 flies/cage. A central death rate was computed for each of the 216 cages at specified numerical levels (e.g., 5000, 4000, 1000, 500, 100, and so forth), which was distributed over a range of ages. This yielded a series of mortality schedules at "equivalent current densities." Two main results are reported. First, the leveling off and decline in mortality at the most advanced ages as observed in the original study of 1.2 million medflies cannot be explained as an artifact of declining current densities at older ages. Second, increased initial density heightened the mortality level at each age but had essentially no effect on mortality pattern. The overall methodology and many of the results are believed to be general and thus both logistical and conceptual implications for gerontology and population biology are discussed.

How an individual fecundity pattern looks in Drosophila and medflies.

Reproduction usually is characterized by a mean-population fecundity pattern. Such a pattern has a maximum at earlier ages and a subsequent gradual decline in egg production. It is shown that individual fecundity trajectories do not follow such a pattern. In particular, the regular individual fecundity pattern has no maximum so that experimentally observed maximums are average-related artifacts. The three-stage description of individual fecundity, which includes maturation, maturity, and reproductive senescence, is more appropriate. Data are presented for Drosophila and Mediterranean fruitfly females that clearly confirm this hypothesis. A systematic error between egg-laying scores and the regular individual pattern allows for evaluation of how close the random scores are to the pattern. The first finding of the analysis of the systematic errors is that they are consistent with the three-stage hypothesis and do not contradict the absence of the maximum in the regular individual pattern. The other finding is the existence of obvious dynamic properties of the systematic error. The slow decrease in egg-laying at the maturity stage might be the result of a cost of mating. It can also be a consequence of "structural" senescence, that is, a slow rate accumulation of oxidative damage in the gonads.

Postreproductive life predicted by primate patterns.

Regression analyses of primate life spans on recently revised female body and brain masses of Old World primates predict a human life span of between 72 years and 91 years-estimates that exceed the age of human menopause (and prior estimates) by well over 20 years. The life spans predicted from body and brain sizes in the early Homo suggest that postreproductive life spans predate Homo sapiens Among anthropoid primates, residual longevity after body and brain effects are controlled is greatest for Homo and for the New World monkeys of the genus Cebus. Body and brain masses predict a 25-year life span for Cebus, although recorded life spans exceed 50 years. Cebus are geographically widespread, have a female-bonded social organization convergent with Old World monkeys, and are primarily frugivorous, though the diet is heavily supplemented with vertebrate prey. Regressions of phylogenetically independent contrasts indicate that body mass and brain mass relationships to longevity remain significant when phylogeny is controlled and that brain mass is a more robust predictor than body mass. These data are new in terms of the completeness of species representation, more reliable body masses, presentation of various comparison group regressions, and control for phylogenetic independence.

Relationship of age patterns of fecundity to mortality, longevity, and lifetime reproduction in a large cohort of Mediterranean fruit fly females.

Daily reproduction was monitored throughout the lives of 1000 individual female Mediterranean fruit flies (Ceratitis capitata). Inasmuch as the average female medfly lived 35.6 days and laid 740 eggs in her lifetime, the overall data set consisted of information on around 740,000 eggs distributed over 35,600 fly-days. Results described include the frequency distributions of eggs/day at young (< or =30 days), middle (31-60 days), and older (61-90 days) ages, the relationship between individual life span and lifetime reproduction, the distribution of deaths for non-egg layers versus egg layers, and density plots for daily egg production relative to both lifetime reproduction and life span. One of the more surprising results was the lack of correlation of the total number of eggs laid by females at younger ages (all ages under 30) and subsequent reproduction and life span. Technical and conceptual implications for analyses of reproductive data on other species and groups are briefly discussed.

Mortality oscillations induced by periodic starvation alter sex-mortality differentials in Mediterranean fruit flies.

Sex-specific mortality rates of medflies were monitored in cages containing individuals of both sexes and with food (either sugar-only or full diet) removed every 2nd, 3rd, or 4th day (plus ad libitum controls). The general finding is that periodic starvation led to marked oscillations in raw mortality rates. The specific findings are as follows: (i) female medflies live longer than male medflies when they are subjected to periodic starvation; (ii) male medflies maintained on a full diet experience a catastrophic increase in mortality (40%) on the first day food is removed. This mortality surge was not observed for females on either diet or for males maintained on a sugar-only diet; (ii) life expectancy is inversely related to the amplitude of mortality oscillations caused by food deprivation; and (iv) the large perturbations in mortality at younger ages caused by periodic starvation has little effect on the amplitude of mortality at older ages. In general, our data shed new light on the complexity of the mortality response of medflies to both the type and availability of food and thus provide a complimentary perspective to findings from dietary restriction studies on both vertebrate and invertebrate systems.