Deconvolving mutational patterns of poliovirus outbreaks reveals its intrinsic fitness landscape.

Vaccination has essentially eradicated poliovirus. Yet, its mutation rate is higher than that of viruses like HIV, for which no effective vaccine exists. To investigate this, we infer a fitness model for the poliovirus viral protein 1 (vp1), which successfully predicts in vitro fitness measurements. This is achieved by first developing a probabilistic model for the prevalence of vp1 sequences that enables us to isolate and remove data that are subject to strong vaccine-derived biases. The intrinsic fitness constraints derived for vp1, a capsid protein subject to antibody responses, are compared with those of analogous HIV proteins. We find that vp1 evolution is subject to tighter constraints, limiting its ability to evade vaccine-induced immune responses. Our analysis also indicates that circulating poliovirus strains in unimmunized populations serve as a reservoir that can seed outbreaks in spatio-temporally localized sub-optimally immunized populations

Searching for Hyperspectral Optical Proxies to Aid Chesapeake Bay Resource Managers in the Detection of Poor Water Quality

Shellfish aquaculture is a growing industry in the Chesapeake Bay. As population grows near the coast, extreme weather events cause a greater volume of pollutant runoff from impervious surfaces and agricultural lands. Resource managers who monitor shellfish beds need reliable information on a variety of water quality indicators at higher frequency than is possible through field monitoring programs and at a higher level of detail than current satellite products can provide. Although many factors causing degraded water quality that can impact human health are not currently discernable by traditional multispectral techniques, hyperspectral imagery offers a new opportunity to detect phytoplankton communities associated with harmful algal blooms and biotoxin production. Together with resource managers in their routine monitoring of sites around the bay from small boats, we have been exploring remotely sensed optical proxies for the detection of harmful algal blooms and sewage. Early warning by remote sensing could guide sampling and improve the efficiency of shellfish bed closures, ultimately improving health outcomes for humans and animals. An extensive network of routine sampling by Chesapeake Bay Program managers makes this is an ideal location to develop and test future satellite data products to support management decisions. Next generation hyperspectral measurements from the future Plankton Aerosol Cloud ocean Ecosystem (PACE) mission at nearly daily frequency, combined with the potential of higher spatial resolution from the Surface Biology and Geology (SBG) observing system recommended in the recent Decadal Survey, along with high frequency observations from the newly selected Geostationary Littoral Imaging and Monitoring Radiometer (GLIMR) Earth Venture Instrument make this a critical time for defining the needs of the aquaculture and resource management community to save lives, time, and money

Measuring time perspective in adolescents : can you get the right answer by asking the wrong questions?

Time perspective continues to evolve as a psychological construct. The extant literature suggests that higher future orientation and lower present orientation are associated with better developmental outcomes. However, the extant literature also suggests that issues remain with the measurement of the construct. Recently, a 25-item version of the Zimbardo Time Perspective Inventory (ZTPI-25) was suggested for use based on high internal consistency estimates and good discriminant validity of scores in a sample of Italian adolescents. However, the genesis of this scale is uncertain. The present study examined the factorial validity, reliability, and concurrent validity of ZTPI-25 scores in Slovenian, American, and British adolescents. Results revealed satisfactory concurrent validity based on correlations with measures used in the development of the full ZTPI. However, internal consistency and factorial validity of scores were unsatisfactory. The present study questions the use of the ZTPI-25 with adolescents in the context of conceptual and measurement issues more broadly

Infinite coupling duals of N=2 gauge theories and new rank 1 superconformal field theories

We show that a proposed duality [arXiv:0711.0054] between infinitely coupled gauge theories and superconformal field theories (SCFTs) with weakly gauged flavor groups predicts the existence of new rank 1 SCFTs. These superconformal fixed point theories have the same Coulomb branch singularities as the rank 1 E_6, E_7, and E_8 SCFTs, but have smaller flavor symmetry algebras and different central charges. Gauging various subalgebras of the flavor algebras of these rank 1 SCFTs provides many examples of infinite-coupling dualities, satisfying an intricate set of consistency checks. They also provide examples of N=2 conformal theories with marginal couplings but no weak-coupling limits.Comment: 12 page

Pleiotropy of FRIGIDA enhances the potential for multivariate adaptation.

An evolutionary response to selection requires genetic variation; however, even if it exists, then the genetic details of the variation can constrain adaptation. In the simplest case, unlinked loci and uncorrelated phenotypes respond directly to multivariate selection and permit unrestricted paths to adaptive peaks. By contrast, 'antagonistic' pleiotropic loci may constrain adaptation by affecting variation of many traits and limiting the direction of trait correlations to vectors that are not favoured by selection. However, certain pleiotropic configurations may improve the conditions for adaptive evolution. Here, we present evidence that the Arabidopsis thaliana gene FRI (FRIGIDA) exhibits 'adaptive' pleiotropy, producing trait correlations along an axis that results in two adaptive strategies. Derived, low expression FRI alleles confer a 'drought escape' strategy owing to fast growth, low water use efficiency and early flowering. By contrast, a dehydration avoidance strategy is conferred by the ancestral phenotype of late flowering, slow growth and efficient water use during photosynthesis. The dehydration avoidant phenotype was recovered when genotypes with null FRI alleles were transformed with functional alleles. Our findings indicate that the well-documented effects of FRI on phenology result from differences in physiology, not only a simple developmental switch

Activity-based protein profiling of the hepatitis C virus replication in Huh-7 hepatoma cells using a non-directed active site probe

<p>Abstract</p> <p>Background</p> <p>Hepatitis C virus (HCV) poses a growing threat to global health as it often leads to serious liver diseases and is one of the primary causes for liver transplantation. Currently, no vaccines are available to prevent HCV infection and clinical treatments have limited success. Since HCV has a small proteome, it relies on many host cell proteins to complete its life cycle. In this study, we used a non-directed phenyl sulfonate ester probe (PS4≡) to selectively target a broad range of enzyme families that show differential activity during HCV replication in Huh-7 cells.</p> <p>Results</p> <p>The PS4≡ probe successfully targeted 19 active proteins in nine distinct protein families, some that were predominantly labeled <it>in situ </it>compared to the <it>in vitro </it>labeled cell homogenate. Nine proteins revealed altered activity levels during HCV replication. Some candidates identified, such as heat shock 70 kDa protein 8 (or HSP70 cognate), have been shown to influence viral release and abundance of cellular lipid droplets. Other differentially active PS4≡ targets, such as electron transfer flavoprotein alpha, protein disulfide isomerase A5, and nuclear distribution gene C homolog, constitute novel proteins that potentially mediate HCV propagation.</p> <p>Conclusions</p> <p>These findings demonstrate the practicality and versatility of non-directed activity-based protein profiling (ABPP) to complement directed methods and accelerate the discovery of altered protein activities associated with pathological states such as HCV replication. Collectively, these results highlight the ability of <it>in situ </it>ABPP approaches to facilitate the identification of enzymes that are either predominantly or exclusively labeled in living cells. Several of these differentially active enzymes represent possible HCV-host interactions that could be targeted for diagnostic or therapeutic purposes.</p

Natural variation in abiotic stress responsive gene expression and local adaptation to climate in Arabidopsis thaliana.

Gene expression varies widely in natural populations, yet the proximate and ultimate causes of this variation are poorly known. Understanding how variation in gene expression affects abiotic stress tolerance, fitness, and adaptation is central to the field of evolutionary genetics. We tested the hypothesis that genes with natural genetic variation in their expression responses to abiotic stress are likely to be involved in local adaptation to climate in Arabidopsis thaliana. Specifically, we compared genes with consistent expression responses to environmental stress (expression stress responsive, "eSR") to genes with genetically variable responses to abiotic stress (expression genotype-by-environment interaction, "eGEI"). We found that on average genes that exhibited eGEI in response to drought or cold had greater polymorphism in promoter regions and stronger associations with climate than those of eSR genes or genomic controls. We also found that transcription factor binding sites known to respond to environmental stressors, especially abscisic acid responsive elements, showed significantly higher polymorphism in drought eGEI genes in comparison to eSR genes. By contrast, eSR genes tended to exhibit relatively greater pairwise haplotype sharing, lower promoter diversity, and fewer nonsynonymous polymorphisms, suggesting purifying selection or selective sweeps. Our results indicate that cis-regulatory evolution and genetic variation in stress responsive gene expression may be important mechanisms of local adaptation to climatic selective gradients

Conference 2008 - Integrating Science and Mathematics Education Research into Teaching IV: Resources and Tool for Improved Learning

The Center for Science and Mathematics Education at the University of Maine continues its series of national conferences on providing professional development and resources for integrating mathematics and science education research into teaching. The first part of the conference consists of three days of parallel presentations and discussions by nationally recognized experts along with short workshops. The workshops provide first hand experience with either research-based STEM curricula or cutting edge STEM research projects that can serve as a basis for classroom instruction. The purposes of the conference include bringing together 150 participants in all aspects of STEM education (researchers, teachers, administrators, and preservice students) to exchange ideas about research, curriculum and assessment, to help teachers integrate research based instructional strategies in their teaching, and to build sustainable collaborations between participants. The second part of the conference is a two day summer academy in which about 60 participants have the option of (1) working on implementing a module of technology-rich curriculum in their classroom; (2) developing plans, curricular materials and assessments for involving teachers and students in a STEM research project; or (3) adapting and implementing a research-supported curriculum in their teaching. The academy continues throughput the year. A focus on research-based strategies that advance the successful participation of underrepresented groups is embedded in all activities

Progressive Bidirectional Age-Related Changes in Default Mode Network Effective Connectivity across Six Decades

The default mode network (DMN) is a set of regions that is tonically engaged during the resting state and exhibits task-related deactivation that is readily reproducible across a wide range of paradigms and modalities. The DMN has been implicated in numerous disorders of cognition and, in particular, in disorders exhibiting age-related cognitive decline. Despite these observations, investigations of the DMN in normal aging are scant. Here, we used blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) acquired during rest to investigate age-related changes in functional connectivity of the DMN in 120 healthy normal volunteers comprising six, 20-subject, decade cohorts (from 20–29 to 70–79). Structural equation modeling (SEM) was used to assess age-related changes in inter-regional connectivity within the DMN. SEM was applied both using a previously published, meta-analytically derived, node-and-edge model, and using exploratory modeling searching for connections that optimized model fit improvement. Although the two models were highly similar (only 3 of 13 paths differed), the sample demonstrated significantly better fit with the exploratory model. For this reason, the exploratory model was used to assess age-related changes across the decade cohorts. Progressive, highly significant changes in path weights were found in 8 (of 13) paths: four rising, and four falling (most changes were significant by the third or fourth decade). In all cases, rising paths and falling paths projected in pairs onto the same nodes, suggesting compensatory increases associated with age-related decreases. This study demonstrates that age-related changes in DMN physiology (inter-regional connectivity) are bidirectional, progressive, of early onset and part of normal aging