Subharmonic microbubble emissions for noninvasively tracking right ventricular pressures

Right heart catheterization is often required to monitor intra-cardiac pressures in a number of disease states. Ultrasound contrast agents can produce pressure modulated subharmonic emissions that may be used to estimate right ventricular (RV) pressures. A technique based on subharmonic acoustic emissions from ultrasound contrast agents to track RV pressures noninvasively has been developed and its clinical potential evaluated. The subharmonic signals were obtained from the aorta, RV, and right atrium (RA) of five anesthetized closed-chest mongrel dogs using a SonixRP ultrasound scanner and PA4-2 phased array. Simultaneous pressure measurements were obtained using a 5-French solid state micromanometer tipped catheter. Initially, aortic subharmonic signals and systemic blood pressures were used to obtain a calibration factor in units of millimeters of mercury per decibel. This factor was combined with RA pressures (that can be obtained noninvasively) and the acoustic data from the RV to obtain RV pressure values. The individual calibration factors ranged from -2.0 to -4.0 mmHg/dB. The subharmonic signals tracked transient changes in the RV pressures within an error of 0.6 mmHg. Relative to the catheter pressures, the mean errors in estimating RV peak systolic and minimum diastolic pressures, and RV relaxation [isovolumic negative derivative of change in pressure over time (-dP/dt)] by use of the subharmonic signals, were -2.3 mmHg, -0.8 mmHg, and 2.9 mmHg/s, respectively. Overall, acoustic estimates of RV peak systolic and minimum diastolic pressures and RV relaxation were within 3.4 mmHg, 1.8 mmHg, and 5.9 mmHg/s, respectively, of the measured pressures. This pilot study demonstrates that subharmonic emissions from ultrasound contrast agents have the potential to noninvasively track in vivo RV pressures with errors below 3.5 mmHg.     

Life history variation within a parthenogenetic population of Daphnia parvula (Crustacea: Cladocera)

Summary Evidence for genetically determined life history variability within a population or a species is rare. In this three year experimental examination of a parthenogenetically reproducing population of the planktonic crustacean Daphnia parvula, we found evidence for a succession of clones or groups of clones that exhibited distinctive body size and reproductive differences that were maintained after numerous generations under standardized conditions in the laboratory. The D. parvula population reached maximum density in the fall and maintained relatively high densities through the winter and spring. Isolates from this fall-winter-spring period all had a larger body size at death and higher fecundity when compared with summer isolates under natural food and temperature conditions. These differences could not be accounted for by differences in temperature and food abundance among the seasons. An additional difference in these experiments was a shift in reproductive effort by the summer isolate which produced a higher proportion of its offspring in the first two broods. The shift in life history characteristics and a summer decline of the Daphnia parvula population was correlated with both an increase in inedible and perhaps toxic blue-green algae and an increase in a dipteran predator Chaoborus. Comparison of the survivorship curves for all of the seasonal life history experiments indicated that D. parvula survivorship was not lower during the summer discounting a toxic effect from blue-green algae. Positive population growth on natural food in the laboratory at this time indicated food was not limiting and that predation was the probable cause of the population decline.Laboratory life history experiments under standardized food and temperature conditions were run with D. parvula isolates from the spring and summer plankton. Genetically based differences as determined in these experiments were smaller body size, lower fecundity, smaller brood size, and shorter life span for the summer animals relative to spring animals. Thirty seven percent of the summer animals also reproduced at an earlier age under standardized conditions. The shift in reproductive effort to earlier broods by summer animals rnder natural conditions appeared to be a phenotypic response as the summer isolate did not produce a higher proportion of its offspring in early broods under standardized conditions.When estimates of predatory mortality were added to the life tables of the standardized experiments, the earlier reproduction of some of the summer animals allowed a population increase under a regime of intense predation. Life tables for the spring animals predicted a population decline under these circumstances. Predictable seasonal changes in biotic factors such as predation suggest a mechanism whereby diverse life history patterns with corresponding differences in r may be maintained within a population.     

Landscape fragmentation affects responses of avian communities to climate change

Forecasting the consequences of climate change is contingent upon our understanding of the relationship between biodiversity patterns and climatic variability. While the impacts of climate change on individual species have been well‐documented, there is a paucity of studies on climate‐mediated changes in community dynamics. Our objectives were to investigate the relationship between temporal turnover in avian biodiversity and changes in climatic conditions and to assess the role of landscape fragmentation in affecting this relationship. We hypothesized that community turnover would be highest in regions experiencing the most pronounced changes in climate and that these patterns would be reduced in human‐dominated landscapes. To test this hypothesis, we quantified temporal turnover in avian communities over a 20‐year period using data from the New York State Breeding Atlases collected during 1980–1985 and 2000–2005. We applied Bayesian spatially varying intercept models to evaluate the relationship between temporal turnover and temporal trends in climatic conditions and landscape fragmentation. We found that models including interaction terms between climate change and landscape fragmentation were superior to models without the interaction terms, suggesting that the relationship between avian community turnover and changes in climatic conditions was affected by the level of landscape fragmentation. Specifically, we found weaker associations between temporal turnover and climatic change in regions with prevalent habitat fragmentation. We suggest that avian communities in fragmented landscapes are more robust to climate change than communities found in contiguous habitats because they are comprised of species with wider thermal niches and thus are less susceptible to shifts in climatic variability. We conclude that highly fragmented regions are likely to undergo less pronounced changes in composition and structure of faunal communities as a result of climate change, whereas those changes are likely to be greater in contiguous and unfragmented habitats.     

Head-to-Head Comparison of Soluble vs. Qβ VLP Circumsporozoite Protein Vaccines Reveals Selective Enhancement of NANP Repeat Responses

Circumsporozoite protein (CSP) of Plasmodium falciparum is a promising malaria vaccine target. RTS,S, the most advanced malaria vaccine candidate consists of the central NANP repeat and carboxy-terminal region of CSP displayed on a hepatitis B virus-like particle (VLP). To build upon the success of RTS,S, we produced a near full-length Plasmodium falciparum CSP that also includes the conserved amino-terminal region of CSP. We recently showed that this soluble CSP, combined with a synthetic Toll-like-receptor-4 (TLR4) agonist in stable oil-in-water emulsion (GLA/SE), induces a potent and protective immune response in mice against transgenic parasite challenge. Here we have investigated whether the immunogenicity of soluble CSP could be further augmented by presentation on a VLP. Bacteriophage Qβ VLPs can be readily produced in E.coli, they have a diameter of 25 nm and contain packaged E. coli RNA which serves as a built in adjuvant through the activation of TLR7/8. CSP was chemically conjugated to Qβ and the CSP-Qβ vaccine immunogenicity and efficacy were compared to adjuvanted soluble CSP in the C57Bl/6 mouse model. When formulated with adjuvants lacking a TLR4 agonist (Alum, SE and Montanide) the Qβ-CSP induced higher anti-NANP repeat titers, higher levels of cytophilic IgG2b/c antibodies and a trend towards higher protection against transgenic parasite challenge as compared to soluble CSP formulated in the same adjuvant. The VLP and soluble CSP immunogenicity difference was most pronounced at low antigen dose, and within the CSP molecule, the titers against the NANP repeats were preferentially enhanced by Qβ presentation. While a TLR4 agonist enhanced the immunogenicity of soluble CSP to levels comparable to the VLP vaccine, the TLR4 agonist did not further improve the immunogenicity of the Qβ-CSP vaccine. The data presented here pave the way for further improvement in the Qβ conjugation chemistry and evaluation of both the Qβ-CSP and soluble CSP vaccines in the non-human primate model.     

Fungal chitin from asthma-associated home environments induces eosinophilic lung infiltration

Development of asthma and allergic inflammation involves innate immunity, but the environmental contributions remain incompletely defined. Analysis of dust collected from the homes of asthmatic individuals revealed that the polysaccharide chitin is environmentally widespread and associated with β-glucans, possibly from ubiquitous fungi. Cell wall preparations of Aspergillus isolated from house dust induced robust recruitment of eosinophils into mouse lung, an effect that was attenuated by enzymatic degradation of cell wall chitin and β-glucans. Mice expressing constitutively active acidic mammalian chitinase in the lungs demonstrated a significant reduction in eosinophil infiltration after fungal challenge. Conversely, chitinase inhibition prolonged the duration of tissue eosinophilia. Thus, fungal chitin derived from home environments associated with asthma induces eosinophilic allergic inflammation in the lung, and mammalian chitinases, including acidic mammalian chitinase, limit this process.     

Effects of 28Si Ions, 56Fe Ions,and Protons on the Induction of Murine Acute Myeloid Leukemia and Hepatocellular Carcinoma

Estimates of cancer risks posed to space-flight crews by exposure to high atomic number, high-energy (HZE) ions are subject to considerable uncertainty because epidemiological data do not exist for human populations exposed to similar radiation qualities. We assessed the carcinogenic effects of 300 MeV/n ²⁸Si or 600 MeV/n ⁵⁶Fe ions in a mouse model for radiation-induced acute myeloid leukemia and hepatocellular carcinoma. C3H/HeNCrl mice were irradiated with 0.1, 0.2, 0.4, or 1 Gy of 300 MeV/n ²⁸Si ions, 600 MeV/n ⁵⁶Fe ions or 1 or 2 Gy of protons simulating the 1972 solar particle event (1972SPE) at the NASA Space Radiation Laboratory. Additional mice were irradiated with ¹³⁷Cs gamma rays at doses of 1, 2, or 3 Gy. All groups were followed until they were moribund or reached 800 days of age. We found that ²⁸Si or ⁵⁶Fe ions do not appear to be substantially more effective than gamma rays for the induction of acute myeloid leukemia. However, ²⁸Si or ⁵⁶Fe ion irradiated mice had a much higher incidence of hepatocellular carcinoma than gamma ray irradiated or proton irradiated mice. These data demonstrate a clear difference in the effects of these HZE ions on the induction of leukemia compared to solid tumors, suggesting potentially different mechanisms of tumorigenesis. Also seen in this study was an increase in metastatic hepatocellular carcinoma in the ²⁸Si and ⁵⁶Fe ion irradiated mice compared with those exposed to gamma rays or 1972SPE protons, a finding with important implications for setting radiation exposure limits for space-flight crew members.     

One Solution for Two Challenges: The Lizard Microlophus atacamensis Avoids Overheating by Foraging in Intertidal Shores

In lizards, one of the most important behavioral mechanisms to cope with spatial and temporal variations in thermal resources observed is activity time. The longer a lizard can maintain activity, the more time it has to forage and reach larger adult body size. We studied the behavioral adjustments to different climatic regimens on daily and seasonal scales in three natural populations of the lizard Microlophus atacamensis along a latitudinal temperature and rainfall gradient. We also used Niche Mapper to determinate the amount of thermally suitable time for activity for this species. Abundance and daily activity patterns varied greatly over the year for the three populations. In summer and spring, the daily activity times were greater, and were reduced in fall and winter seasons. In summer, when stressful heat loads should prohibit activity over a midday gap, lizards did not show bimodal patterns of activity. Instead, they move to the cooler intertidal habitat. Abundance and thermal quality in the southernmost coolest site was lower, and the potential annual activity time decreases with latitude. Contrary to expectations, lizards from this locality showed the largest body sizes possibly due to diet and/or time to sexual maturation. Our results indicate that the intertidal habitat is a key factor that influences daily and seasonal activity of M. atacamensis lizards. While this habitat is not climatically optimal for lizards, it allows them to behaviorally extend their activity window and gain access to food in the intertidal areas.