Fundulus as the premier teleost model in environmental biology: opportunities for new insights using genomics

A strong foundation of basic and applied research documents that the estuarine fish Fundulus heteroclitus and related species are unique laboratory and field models for understanding how individuals and populations interact with their environment. In this paper we summarize an extensive body of work examining the adaptive responses of Fundulus species to environmental conditions, and describe how this research has contributed importantly to our understanding of physiology, gene regulation, toxicology, and ecological and evolutionary genetics of teleosts and other vertebrates. These explorations have reached a critical juncture at which advancement is hindered by the lack of genomic resources for these species. We suggest that a more complete genomics toolbox for F. heteroclitus and related species will permit researchers to exploit the power of this model organism to rapidly advance our understanding of fundamental biological and pathological mechanisms among vertebrates, as well as ecological strategies and evolutionary processes common to all living organisms.     

Determination of the processes driving the acquisition of immunity to malaria using a mathematical transmission model

Acquisition of partially protective immunity is a dominant feature of the epidemiology of malaria among exposed individuals. The processes that determine the acquisition of immunity to clinical disease and to asymptomatic carriage of malaria parasites are poorly understood, in part because of a lack of validated immunological markers of protection. Using mathematical models, we seek to better understand the processes that determine observed epidemiological patterns. We have developed an age-structured mathematical model of malaria transmission in which acquired immunity can act in three ways (“immunity functions”): reducing the probability of clinical disease, speeding the clearance of parasites, and increasing tolerance to subpatent infections. Each immunity function was allowed to vary in efficacy depending on both age and malaria transmission intensity. The results were compared to age patterns of parasite prevalence and clinical disease in endemic settings in northeastern Tanzania and The Gambia. Two types of immune function were required to reproduce the epidemiological age-prevalence curves seen in the empirical data; a form of clinical immunity that reduces susceptibility to clinical disease and develops with age and exposure (with half-life of the order of five years or more) and a form of anti-parasite immunity which results in more rapid clearance of parasitaemia, is acquired later in life and is longer lasting (half-life of >20 y). The development of anti-parasite immunity better reproduced observed epidemiological patterns if it was dominated by age-dependent physiological processes rather than by the magnitude of exposure (provided some exposure occurs). Tolerance to subpatent infections was not required to explain the empirical data. The model comprising immunity to clinical disease which develops early in life and is exposure-dependent, and anti-parasite immunity which develops later in life and is not dependent on the magnitude of exposure, appears to best reproduce the pattern of parasite prevalence and clinical disease by age in different malaria transmission settings. Understanding the effector mechanisms underlying these two immune functions will assist in the design of transmission-reducing interventions against malaria.     

Sarcopenic obesity and inflammation in the InCHIANTI study.

The aging process is often paralleled by decreases in muscle and increases in fat mass. At the extreme these two processes lead to a condition known as "sarcopenic obesity" (Roubenoff R. Ann NY Acad Sci 904: 553-557, 2000). Research suggests that inflammatory cytokines produced by adipose tissue, especially visceral fat, accelerate muscle catabolism and thus contribute to the vicious cycle that initiates and sustains sarcopenic obesity. We tested the hypothesis that obesity and poor muscle strength, hallmarks of sarcopenic obesity, are associated with high circulating levels of proinflammatory cytokines in a random sample of the residents of two municipalities in the Chianti geographic area (Tuscany, Italy). The study sample consisted of 378 men and 493 women 65 yr and older with complete data on anthropometrics, handgrip strength, and inflammatory markers. Participants were cross-classified according to sex-specific tertiles of waist circumference and grip strength and according to a cut point for obesity of body mass index > or =30 kg/m(2). After adjusting for age, sex, education, smoking history, physical activity, and history of comorbid diseases, components of sarcopenic obesity were associated with elevated levels of IL-6, C-reactive protein, IL-1 receptor antagonist, and soluble IL-6 receptor (P < 0.05). Our findings suggest that global obesity and, to a greater extent, central obesity directly affect inflammation, which in turn negatively affects muscle strength, contributing to the development and progression of sarcopenic obesity. These results suggest that proinflammatory cytokines may be critical in both the development and progression of sarcopenic obesity.     

Oligopeptide Signaling through TbGPR89 Drives Trypanosome Quorum Sensing

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Radial arm maze performance of rats following repeated low level microwave radiation exposure

We examined the possibility of changes in "working" memory of rats following whole body exposure to microwave (MW) radiation. During each of 10 days, we exposed rats within circularly polarized waveguides for 45 min to 2450 MHz fields at whole body SARs of 0.6 W/kg (2 micros pulses, 500 pps), followed by testing in a 12 arm, radial arm maze (RAM). Rats received a preexposure injection of one of three psychoactive compounds or saline, to determine whether a compound would interact with MW exposure to affect performance in the maze. Error rate, i.e., reentry into arms already visited, and time to criterion data for 10 consecutive days of testing were analyzed by a three way analysis of variance (ANOVA) using main effects of "exposure" and "drug" and a repeated factor of "test day." Our alpha limit for significance was P <.05. Analyzes of error rates revealed no significant exposure effect, no significant drug effect and no significant interaction between the two main factors. There was a significant difference in test days, as expected, with repeated test-trial days, which indicates that learning was accomplished. There was no significant interaction of test day and the other two factors. The results of our analyzes of time to criterion data included no significant exposure effect, a significant drug effect, a significant test day effect, and a significant interaction between drug and test day factors. Post hoc analyzes of the drug factor revealed that rats treated with either physostigmine or nalrexone hydrochloride, took significantly longer to complete the maze task than rats pretreated with saline or with naloxone methodide. We conclude that there is no evidence from the current study that exposure to of MW radiation under parameters examined caused decrements in the ability of rats to learn the spatial memory task.     

Racial and ethnic variations in knowledge and attitudes about genetic testing

This study was designed to shed light on whether differences in utilization of genetic testing by African-Americans, Latinos, and non-Hispanic Whites are due primarily to different preferences, or whether they instead reflect other values and beliefs or differential access. It explores the values, attitudes, and beliefs of African-Americans, Latinos, and non-Hispanic Whites with respect to genetic testing by means of a telephone survey of representative samples of these three groups. The study finds clear evidence that Latinos and African-Americans are, if anything, more likely to express preferences for both prenatal and adult genetic testing than White respondents. At the same time, they hold other beliefs and attitudes that may conflict with, and override, these preferences in specific situations. African-Americans and Latinos are also less knowledgeable about genetic testing than non-Hispanic Whites, and they are less likely to have the financial resources or insurance coverage that would facilitate access to testing.     

Nitric oxide protects cardiac sarcolemmal membrane enzyme function and ion active transport against ischemia-induced inactivation

Nitric oxide (NO.) generated from nitric oxide synthase (NOS) isoforms bound to cellular membranes may serve to modulate oxidative stresses in cardiac muscle and thereby regulate the function of key membrane-associated enzymes. Ischemia is known to inhibit the function of sarcolemmal enzymes, including the (Na+ + K+)-ATPase, but it is unknown whether concomitant injury to sarcolemma (SL)-associated NOS isoforms may contribute to this process by reducing the availability of locally generated NO. Here we report that nNOS, as well as eNOS (SL NOSs), are tightly associated with cardiac SL membranes in several different species. In isolated perfused rat hearts, global ischemia caused a time-dependent irreversible injury to cardiac SL NOSs and a disruption of SL NO. generation. Pretreatment with low concentrations of the NO. donor 1-hydroxy-2-oxo-3-(N-3-methyl-aminopropyl)-3-methyl-1-triazene (NOC-7) markedly protected both SL NOS and (Na+ + K+)-ATPase functions against ischemia-induced inactivation. Moreover, ischemia impaired SL Na+/K+ binding, and NOC-7 significantly prevented ischemic injury to the ion binding sites on (Na+ + K+)-ATPase. These novel findings indicate that NO. can protect cardiac SL NOSs and (Na+ + K+)-ATPase against ischemia-induced inactivation and suggest that locally generated NO. may serve to regulate SL Na+/K+ ion active transport in the heart.