Parasite infections are a product of both ecological processes affecting host-parasite encounter rates and evolutionary dynamics affecting host susceptibility. However, few studies examine natural infection variation from both ecological and evolutionary perspectives. Here, we describe the ecological and evolutionary factors generating variation in infection rates by a tapeworm (Schistocephalus solidus) in a vertebrate host, the threespine stickleback (Gasterosteus aculeatus). To explore ecological aspects of infection, we measured tapeworm prevalence in Canadian stickleback inhabiting two distinct environments: marine and freshwater. Consistent with ecological control of infection, the tapeworm is very rare in marine environments, even though marine fish are highly susceptible. Conversely, commonly infected freshwater stickleback exhibit substantial resistance in controlled laboratory trials, suggesting that high exposure risk overwhelms their recently evolved resistance. We also tested for parasite adaptation to its host by performing transcontinental reciprocal infections, using stickleback and tapeworm populations from Europe and western Canada. More infections occurred in same-continent host-parasite combinations, indicating parasite "local" adaptation, at least on the scale of continents. However, the recently evolved immunity of freshwater hosts applies to both local and foreign parasites. The pattern of adaptation described here is not wholly compatible with either of the common models of host-parasite coevolution (i.e., matching infection or targeted recognition). Instead, we propose a hybrid, eco-evolutionary model to explain the remarkable pattern of global host resistance and local parasite infectivity.
Highly sensitive multiplex biomarker detection is critical for the early diagnosis of liver cancer. Here, a surface-enhanced Raman scattering (SERS) frequency-shift immunoassay is developed for detection of liver cancer biomarkers α-fetoprotein and Glypican-3 down to subpicomolar concentrations in saline solution. A high temperature modification of the Tollen's method affords silver nanoparticle films with excellent SERS response upon which ordered domains of Raman reporters are chemisorbed by microcontact printing. Shifts in the reporters SERS spectrum in response to a bound antibody's biomarker recognition constitutes the frequency shift assay, exhibiting here exceptional sensitivity and specificity and shown to function in fetal calf serum and in the serum of a patient with hepatocellular carcinoma.
The Ca 2+ /calmodulin-dependent protein phosphatase calcineurin (CN), a heterodimer composed of a catalytic subunit A and an essential regulatory subunit B, plays critical functions in various cellular processes such as cardiac hypertrophy and T cell activation. It is the target of the most widely used immunosuppressants for transplantation, tacrolimus (FK506) and cyclosporin A. However, the structure of a large part of the CNA regulatory region remains to be determined, and there has been considerable debate concerning the regulation of CN activity. Here, we report the crystal structure of full-length CN (β isoform), which revealed a novel autoinhibitory segment (AIS) in addition to the well-known autoinhibitory domain (AID). The AIS nestles in a hydrophobic intersubunit groove, which overlaps the recognition site for substrates and immunosuppressant-immunophilin complexes. Indeed, disruption of this AIS interaction results in partial stimulation of CN activity. More importantly, our biochemical studies demonstrate that calmodulin does not remove AID from the active site, but only regulates the orientation of AID with respect to the catalytic core, causing incomplete activation of CN. Our findings challenge the current model for CN activation, and provide a better understanding of molecular mechanisms of CN activity regulation.
The soybean seed chemical quality traits (including protein content, oil content, fatty acid composition, isoflavone content, and protein subunits), soymilk chemical character (soluble solid), and soymilk sensory attributes were evaluated among 70 genotypes to determine the correlation between seed chemical quality traits and soymilk sensory attributes. Six sensory parameters (i.e., soymilk aroma, smoothness in the mouth, thickness in the mouth, sweetness, colour and appearance, and overall acceptability) and a seven-point hedonic scale for each parameter were developed. Significant positive correlations were observed between overall acceptability and the other five evaluation parameters, suggesting that overall acceptability is an ideal parameter for evaluating soymilk flavour. The soymilk sensory attributes were significantly positively correlated with the characteristics of the glycinin (11S)/beta-conglycinin (7S) protein ratio, soluble solid, and oil content but negatively correlated with glycitein and protein content. Our results indicated that soymilk sensory attributes could be improved by selecting the desirable seed chemical quality traits in practical soybean breeding programs.
Vertebrates’ gut microbial communities can be altered by the hosts’ parasites. Helminths inhabiting the gut lumen can interact directly with their host’s microbiota via physical contact, chemical products, or competition for nutrients. Indirect interactions can also occur, for instance when helminths induce or suppress host immunity in ways that have collateral effects on the microbiota. If there is genetic variation in host immune responses to parasites, we would expect such indirect effects to be conditional on host genotype. To test for such genotype by infection interactions, we experimentally exposed Gasterosteus aculeatus to their naturally co-evolved parasite, Schistocephalus solidus. The host microbiota differed in response to parasite exposure, and between infected and uninfected fish. The magnitude and direction of microbial responses to infection differed between host sexes, and also differed between variants at autosomal quantitative trait loci. These results indicate that host genotype and sex regulate the effect of helminth infection on a vertebrate gut microbiota. If this result holds in other taxa, especially humans, then helminth-based therapeutics for dysbiosis might need to be tailored to host genotype and sex.
A new molecular model for quinolone haptens was developed based on molecular field-overlapping. The quanlitive modeling of 3-D conformations showed that the conformation difference among quinolones is caused mainly by the different substitutes at the 1 and 7 positions. The 8-substitute also showed some effect by its inter-reaction with the 1-substitute. The conformational similarity of 27 quinolones to each other was for the first time calculated and exploited for a selection of haptens according to desired broad specificity of corresponding antibodies. The developed model was preliminarily validated with antibodies against different quinolones. A significant positive correlation (R = 0.7793) was observed between calculated overlapping coefficients of haptens and the cross-reactivity of corresponding polyclonal antibodies (Pabs), which confirmed the overall accuracy of the developed model and its application in quantitative structure-activity relationship analysis. On the basis of molecular modeling results, the strategy for the production of broad specific antibodies against quinolones was suggested and the potentiality of several candidates was predicted.
In recent years, an increasing number of biological experiments and clinical reports have shown that lncRNA is closely related to the development of various complex human diseases.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.