Is there a common pattern of future gas-phase air pollution in Europe under diverse climate change scenarios?

Climate change alone influences future levels of tropospheric ozone and their precursors through modifications of gas-phase chemistry, transport, removal, and natural emissions. The goal of this study is to determine at what extent the modes of variability of gas-phase pollutants respond to different climate change scenarios over Europe. The methodology includes the use of the regional modeling system MM5 (regional climate model version)-CHIMERE for a target domain covering Europe. Two full-transient simulations covering from 1991–2050 under the SRES A2 and B2 scenarios driven by ECHO-G global circulation model have been compared. The results indicate that the spatial patterns of variability for tropospheric ozone are similar for both scenarios, but the magnitude of the change signal significantly differs for A2 and B2. The 1991–2050 simulations share common characteristics for their chemical behavior. As observed from the NO2 and α-pinene modes of variability, our simulations suggest that the enhanced ozone chemical activity is driven by a number of parameters, such as the warming-induced increase in biogenic emissions and, to a lesser extent, by the variation in nitrogen dioxide levels. For gas-phase pollutants, the general increasing trend for ozone found under A2 and B2 forcing is due to a multiplicity of climate factors, such as increased temperature, decreased wet removal associated with an overall decrease of precipitation in southern Europe, increased photolysis of primary and secondary pollutants as a consequence of lower cloudiness and increased biogenic emissions fueled by higher temperatures.

{\it RAS\/} is required for the expression of interleukin-1$\beta$ in two diverse leukemic cell lines

Under normal physiological conditions, cells of the hematopoietic system produce Interleukin-1$\beta$(IL-1$\beta)$ only when a stimulus is present. Leukemic cells, however, can constitutively produce this cytokine without an exogenous source of activation. In addition, IL-1$\beta$ can operate as an autocrine and/or paracrine growth factor for leukemic blasts. In order to study the cellular basis for this aberrant production, we analyzed two leukemic cell lines (B1 and W1) which express high levels of IL-1$\beta$ and use IL-1$\beta$ as an autocrine growth factor. Initial studies demonstrated: (1) lack of rearrangement and/or amplification in the IL-1$\beta$ gene and its promoter; and (2) intact responsiveness to regulators such as cycloheximide and dexamethasone, implying that the molecular defect was upstream. Analysis of the Ras inducible transcription factors by gel shift assay demonstrated constitutive transcription factor binding in the IL-1$\beta$ promoter. Furthermore, RAS mutations were found at codon 12 in the K-RAS and N-RAS genes in the B1 and W1 cells, respectively. To deduce the effects of activated Ras on IL-1$\beta$ expression, two classes of farnesyltransferase inhibitors and an adenoviral vector expressing antisense targeted to K-RAS were utilized. The farnesyltransferase inhibitors perillyl alcohol and B581 were able to reduce IL-1$\beta$ levels by 80% and 50% in the B1 cells, respectively. In W1 cells, IL-1$\beta$ was reduced by 60% with 1mM perillyl alcohol. Antisense RNA targeted to K-RAS confirmed the results demonstrating a 50% reduction in IL-1$\beta$ expression in the B1 cells. In addition, decreased binding at the crucial NF-IL6/CREB binding site correlated with decreased IL-1$\beta$ production and cellular proliferation implying that this site was a downstream effector of Ras signaling. Our data suggest that mutated RAS genes may be responsible for autocrine IL-1$\beta$ production in some leukemias by stimulating signal transduction pathways that activate the IL-1$\beta$ promoter. ^

More efficient aboveground nitrogen use in more diverse Central European forest canopies

We hypothesized that biodiversity improves ecosystem functioning and services such as nutrient cycling because of increased complementarity. We examined N canopy budgets of 27 Central European forests of varying dominant tree species, stand density, and tree and shrub species diversity (Shannon index) in three study regions by quantifying bulk and fine particulate dry deposition and dissolved below canopy N fluxes. Average regional canopy N retention ranged from 16% to 51%, because of differences in the N status of the ecosystems. Canopy N budgets of coniferous forests differed from deciduous forest which we attribute to differences in biogeochemical N cycling, tree functional traits and canopy surface area. The canopy budgets of N were related to the Shannon index which explained 14% of the variance of the canopy budgets of N, suggesting complementary aboveground N use of trees and diverse understorey vegetation. The relationship between plant diversity and canopy N retention varied among regional site conditions and forest types. Our results suggest that the traditional view of belowground complementarity of nutrient uptake by roots in diverse plant communities can be transferred to foliar uptake in forest canopies.

Growth and Persistence of Diverse Intertidal Crusts: Survival of the Slow in a Fast-Paced World

Encrusting algae are conspicuous components of hard-substratum benthic communities in the photic zone despite being poor competitors and slow growers. Little is known about their growth rates or about mechanisms controlling key processes such as wound healing and surviving overgrowth. We manipulated 12 crustose species (including red and brown algae and a lichen) from the intertidal zone of Washington, USA, studying their varying responses to identical experimental conditions. Three of 8 crust species tested showed increased growth rates with size. Species healed from standardized wounds at different rates and using different mechanisms (e.g. lateral vs vertical regeneration) as seen in cross-sections. Three species showed altered growth rates at unwounded margins of wounded crusts, suggesting intrathallus communication. Year-long experiments involving simulated overgrowth showed that some species can maintain healthy tissue in a covered area, and one (the coralline Lithothamnion phymatodeum) even grew new tissue there. Other species gradually lost color, thickness, and area in covered areas. Hildenbrandia occidentalis survived remarkably well when covered, possibly due to its very slow growth and low metabolic demand. One suggested mechanism underlying the high variation in responses among crusts is the degree to which their thalli may be anatomically integrated by features such as cell fusions; physiological work testing translocation via these features is needed. Other mechanisms allowing persistence include rapid wound healing and frequent recruitment.

SNPs for parentage testing and traceability in globally diverse breeds of sheep

DNA-based parentage determination accelerates genetic improvement in sheep by increasing pedigree accuracy. Single nucleotide polymorphism (SNP) markers can be used for determining parentage and to provide unique molecular identifiers for tracing sheep products to their source. However, the utility of a particular "parentage SNP" varies by breed depending on its minor allele frequency (MAF) and its sequence context. Our aims were to identify parentage SNPs with exceptional qualities for use in globally diverse breeds and to develop a subset for use in North American sheep. Starting with genotypes from 2,915 sheep and 74 breed groups provided by the International Sheep Genomics Consortium (ISGC), we analyzed 47,693 autosomal SNPs by multiple criteria and selected 163 with desirable properties for parentage testing. On average, each of the 163 SNPs was highly informative (MAF≥0.3) in 48±5 breed groups. Nearby polymorphisms that could otherwise confound genetic testing were identified by whole genome and Sanger sequencing of 166 sheep from 54 breed groups. A genetic test with 109 of the 163 parentage SNPs was developed for matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry. The scoring rates and accuracies for these 109 SNPs were greater than 99% in a panel of North American sheep. In a blinded set of 96 families (sire, dam, and non-identical twin lambs), each parent of every lamb was identified without using the other parent's genotype. In 74 ISGC breed groups, the median estimates for probability of a coincidental match between two animals (PI), and the fraction of potential adults excluded from parentage (PE) were 1.1×10(-39) and 0.999987, respectively, for the 109 SNPs combined. The availability of a well-characterized set of 163 parentage SNPs facilitates the development of high-throughput genetic technologies for implementing accurate and economical parentage testing and traceability in many of the world's sheep breeds.

Parameterization of temperature sensitivity of spring phenology and its application in explaining diverse phenological responses to temperature change

Existing evidence of plant phenological change to temperature increase demonstrates that the phenological responsiveness is greater at warmer locations and in early-season plant species. Explanations of these findings are scarce and not settled. Some studies suggest considering phenology as one functional trait within a plant's life history strategy. In this study, we adapt an existing phenological model to derive a generalized sensitivity in space (SpaceSens) model for calculating temperature sensitivity of spring plant phenophases across species and locations. The SpaceSens model have three parameters, including the temperature at the onset date of phenophases (Tp), base temperature threshold (Tb) and the length of period (L) used to calculate the mean temperature when performing regression analysis between phenology and temperature. A case study on first leaf date of 20 plant species from eastern China shows that the change of Tp and Tb among different species accounts for interspecific difference in temperature sensitivity. Moreover, lower Tp at lower latitude is the main reason why spring phenological responsiveness is greater there. These results suggest that spring phenophases of more responsive, early-season plants (especially in low latitude) will probably continue to diverge from the other late-season plants with temperatures warming in the future.

Targeting membrane-bound viral RNA synthesis reveals potent inhibition of diverse coronaviruses including the middle East respiratory syndrome virus.

Coronaviruses raise serious concerns as emerging zoonotic viruses without specific antiviral drugs available. Here we screened a collection of 16671 diverse compounds for anti-human coronavirus 229E activity and identified an inhibitor, designated K22, that specifically targets membrane-bound coronaviral RNA synthesis. K22 exerts most potent antiviral activity after virus entry during an early step of the viral life cycle. Specifically, the formation of double membrane vesicles (DMVs), a hallmark of coronavirus replication, was greatly impaired upon K22 treatment accompanied by near-complete inhibition of viral RNA synthesis. K22-resistant viruses contained substitutions in non-structural protein 6 (nsp6), a membrane-spanning integral component of the viral replication complex implicated in DMV formation, corroborating that K22 targets membrane bound viral RNA synthesis. Besides K22 resistance, the nsp6 mutants induced a reduced number of DMVs, displayed decreased specific infectivity, while RNA synthesis was not affected. Importantly, K22 inhibits a broad range of coronaviruses, including Middle East respiratory syndrome coronavirus (MERS-CoV), and efficient inhibition was achieved in primary human epithelia cultures representing the entry port of human coronavirus infection. Collectively, this study proposes an evolutionary conserved step in the life cycle of positive-stranded RNA viruses, the recruitment of cellular membranes for viral replication, as vulnerable and, most importantly, druggable target for antiviral intervention. We expect this mode of action to serve as a paradigm for the development of potent antiviral drugs to combat many animal and human virus infections.

Constraining age distributions of groundwater from public supply wells in diverse hydrogeological settings in Scania, Sweden

Twenty-five public supply wells throughout the hydrogeologically diverse region of Scania, southern Sweden are subjected to environmental tracer analysis (³H–³He,⁴He, CFCs, SF₆ and for one well only also ⁸⁵Kr and ³⁹Ar) to study well and aquifer vulnerability and evaluate possibilities of groundwater age distribution assessment. We find CFC and SF₆ concentrations well above solubility equilibrium with modern atmosphere, indicating local contamination, as well as indications of CFC degradation. The tracer-specific complications considerably constrain possibilities for sound quantitative regional ground- water age distribution assessment and demonstrate the importance of initial qualitative assessment of tracer-specific reliability, as well a need for additional, complementary tracers (e.g. ⁸⁵Kr,³⁹Ar and potentially also ¹⁴C). Lumped parameter modelling yields credible age distribution assessments for representative wells in four type aquifers. Pollution vulnerability of the aquifer types was based on the selected LPM models and qualitative age characterisation. Most vulnerable are unconfined dual porosity and fractured bedrock aquifers, due to a large component of very young groundwater. Unconfined sedimentary aquifers are vulnerable due to young groundwater and a small pre-modern component. Less vulnerable are semi-confined sedimentary or dual-porosity aquifers, due to older age of the modern component and a larger pre-modern component. Confined aquifers appear least vulnerable, due an entirely pre-modern groundwater age distribution (recharged before 1963). Tracer complications aside, environmental tracer analyses and lumped parameter modelling aid in vulnerability assessment and protection of regional groundwater resources.

Distance from Sub-Saharan Africa Predicts Mutational Load in Diverse Human Genomes

The Out-of-Africa (OOA) dispersal ∼50,000 y ago is characterized by a series of founder events as modern humans expanded into multiple continents. Population genetics theory predicts an increase of mutational load in populations undergoing serial founder effects during range expansions. To test this hypothesis, we have sequenced full genomes and high-coverage exomes from seven geographically divergent human populations from Namibia, Congo, Algeria, Pakistan, Cambodia, Siberia, and Mexico. We find that individual genomes vary modestly in the overall number of predicted deleterious alleles. We show via spatially explicit simulations that the observed distribution of deleterious allele frequencies is consistent with the OOA dispersal, particularly under a model where deleterious mutations are recessive. We conclude that there is a strong signal of purifying selection at conserved genomic positions within Africa, but that many predicted deleterious mutations have evolved as if they were neutral during the expansion out of Africa. Under a model where selection is inversely related to dominance, we show that OOA populations are likely to have a higher mutation load due to increased allele frequencies of nearly neutral variants that are recessive or partially recessive.

Dimethylsphingosine evokes diverse cellular death modes in HL60

Among the barriers to successful cancer treatment is the acquired resistance that tumors undergo due to clonal evolution. Non-cross resistant drugs could add to the current options of chemotherapeutic drugs. In order to improve tumor response, investigators have been identifying defective death pathways acquired by specific cancer types, so to target directly those pathways. Sphingolipids have emerged as potential drugs for tumor-targeted therapy, and among them, Dimethylsphingosine (DMS), known to be a competitive inhibitor of Sphingosine Kinase (SK). DMS actions have been documented by several investigators, but the mechanisms by which DMS exerts cytotoxicity have not been fully investigated. We evaluated the cytotoxicity of DMS against human leukemia cell lines and against blasts isolated from leukemia patients. Cell line viability decreased proportionally to DMS concentration and treatment time. Resistant and MDR positive cell lines were the most sensitive, indicating DMS efficacy against human leukemia MDR. Importantly, leukemia samples showed a similar sensitivity to DMS, the first demonstration of DMS activity against fresh human leukemia specimens. Mechanistically we have demonstrated that DMS efficacy is due to its ability to induce cytotoxicity by inducing necrosis, apoptosis or both concomitantly, revealing a mixed-feature cell death mode never described before for DMS. Further, we have shown evidence suggesting pathways cross-talk, since apoptosis inhibition led to accelerated rate of necrosis. DMS diverse killing mechanisms and the high expression of SK in leukemias could explain DMS potent cytotoxicity. DMS-based regimens may increase response rates and therefore, improve leukemia treatment. ^

Preservice Teacher Preparation in Meeting the Needs of Gifted and Other Academically Diverse Students

The issue of how to respond to the diverse academic needs of students is one of the central challenges of teaching. This project studied how preservice teachers develop an awareness of the needs of academically diverse learners and how they intend to implement and/or modify instruction to meet those needs. Participants all came from one university. As part of the design of the study, the participants were surveyed to investigate (a) their attitudes and beliefs towards academically diverse learners; (b) the teaching practices they would utilize in response to academic diversity in their classrooms; and (c) the confidence they have in their abilities to identify and address these various needs in their classrooms. Several strategies including activities to enhance creativity, cooperative learning, individual instruction, problem-solving activities, and projects were considered noteworthy for the ratings by the preservice teachers as appropriate for all students. Small differences were found based on the preservice teachers' year of placement in the School of Education, indicating that as students progress through this program, they may learn more about different techniques and when and for whom they are appropriate; however, differences across groups were not statistically significant. Results also indicated that across the different years in the program, preservice teachers did not have very high or very low confidence in addressing these issues in their own classrooms. Each grouping fell around the middle level of confidence.

The Dental School Applicant Pool and the Oral Healthcare Workforce

One of the major challenges faced by the dental profession today is the recruitment of the most qualified dental school applicants who are capable of serving the nation’s future oral healthcare needs. The Association of Schools of Public Health (ASPH) also recognizes this challenge, describing one of the three core functions of public health as “assuring that all populations have access to appropriate and cost effective care, including health promotion and disease prevention services.” To achieve this core function, the ASPH cites “a competent public health and personal healthcare workforce” as one of the ten essential public health services. Unfortunately, the goals of both quality and equality in terms of the dental workforce and access to oral healthcare have yet to be realized. When considering access to oral health services on a national or state level, a thoughtful and thorough consideration of the dental school applicant pool is essential. According to a recent study published in the Journal of the American Dental Association, the annual number of retiring dentists will exceed the number of newly licensed dental practitioners in 2009, a trend which is projected to continue throughout the next decade. The approximately 4,400 dentists produced each year from the nation’s 57 accredited dental education programs are charged with the responsibility of meeting the oral healthcare needs of the population at large.