Dosage-dependent effects of Akt1/protein kinase Balpha (PKBalpha) and Akt3/PKBgamma on thymus, skin, and cardiovascular and nervous system development in mice.

Akt/protein kinase B (PKB) plays a critical role in the regulation of metabolism, transcription, cell migration, cell cycle progression, and cell survival. The existence of viable knockout mice for each of the three isoforms suggests functional redundancy. We generated mice with combined mutant alleles of Akt1 and Akt3 to study their effects on mouse development. Here we show that Akt1-/- Akt3+/- mice display multiple defects in the thymus, heart, and skin and die within several days after birth, while Akt1+/- Akt3-/- mice survive normally. Double knockout (Akt1-/-) Akt3-/-) causes embryonic lethality at around embryonic days 11 and 12, with more severe developmental defects in the cardiovascular and nervous systems. Increased apoptosis was found in the developing brain of double mutant embryos. These data indicate that the Akt1 gene is more essential than Akt3 for embryonic development and survival but that both are required for embryo development. Our results indicate isoform-specific and dosage-dependent effects of Akt on animal survival and development.

A comparative phenotypic and genomic analysis of C57BL/6J and C57BL/6N mouse strains.

BACKGROUND: The mouse inbred line C57BL/6J is widely used in mouse genetics and its genome has been incorporated into many genetic reference populations. More recently large initiatives such as the International Knockout Mouse Consortium (IKMC) are using the C57BL/6N mouse strain to generate null alleles for all mouse genes. Hence both strains are now widely used in mouse genetics studies. Here we perform a comprehensive genomic and phenotypic analysis of the two strains to identify differences that may influence their underlying genetic mechanisms. RESULTS: We undertake genome sequence comparisons of C57BL/6J and C57BL/6N to identify SNPs, indels and structural variants, with a focus on identifying all coding variants. We annotate 34 SNPs and 2 indels that distinguish C57BL/6J and C57BL/6N coding sequences, as well as 15 structural variants that overlap a gene. In parallel we assess the comparative phenotypes of the two inbred lines utilizing the EMPReSSslim phenotyping pipeline, a broad based assessment encompassing diverse biological systems. We perform additional secondary phenotyping assessments to explore other phenotype domains and to elaborate phenotype differences identified in the primary assessment. We uncover significant phenotypic differences between the two lines, replicated across multiple centers, in a number of physiological, biochemical and behavioral systems. CONCLUSIONS: Comparison of C57BL/6J and C57BL/6N demonstrates a range of phenotypic differences that have the potential to impact upon penetrance and expressivity of mutational effects in these strains. Moreover, the sequence variants we identify provide a set of candidate genes for the phenotypic differences observed between the two strains.

ß-Catenin Regulation during the Cell Cycle: Implications in G2/M and Apoptosis

ß-catenin is a multifunctional protein involved in cell-cell adhesion and Wnt signal transduction. ß-Catenin signaling has been proposed to act as inducer of cell proliferation in different tumors. However, in some developmental contexts and cell systems ß-catenin also acts as a positive modulator of apoptosis. To get additional insights into the role of ß-Catenin in the regulation of the cell cycle and apoptosis, we have analyzed the levels and subcellular localization of endogenous ß-catenin and its relation with adenomatous polyposis coli (APC) during the cell cycle in S-phase¿synchronized epithelial cells. ß-Catenin levels increase in S phase, reaching maximum accumulation at late G2/M and then abruptly decreasing as the cells enter into a new G1 phase. In parallel, an increased cytoplasmic and nuclear localization of ß-catenin and APC is observed during S and G2 phases. In addition, strong colocalization of APC with centrosomes, but not ß-catenin, is detected in M phase. Interestingly, overexpression of a stable form of ß-catenin, or inhibition of endogenous ß-catenin degradation, in epidermal keratinocyte cells induces a G2 cell cycle arrest and leads to apoptosis. These results support a role for ß-catenin in the control of cell cycle and apoptosis at G2/M in normal and transformed epidermal keratinocytes.

Supplement Information to the August 2008 Infrastructure and Transportation Task Force Report, August 2008

The Rebuild Iowa Infrastructure and Transportation Task Force is acutely aware of the critical role infrastructure plays in Iowa’s communities, the lives of the residents, and the economic well-being of the state. With encouragement to the Rebuild Iowa Advisory Commission (RIAC) for its consideration of great need for infrastructure and transportation repairs, the Task Force provides its assessment and recommendations. As the RIAC fulfills its obligations to guide the recovery and reconstruction in Iowa, infrastructure and transportation must be recognized for its impact on all Iowans. The tornadoes, storms, and floods were devastating to infrastructure and transportation systems across the state. The damage did not distinguish between privately-owned and public assets. The significance of the damage emerges further with the magnitude of the damage estimates. Infrastructure includes components that some might initially overlook, such as communication systems, landfills, and water treatment. The miles of damaged roads and bridges are more evident to many Iowans. Given the reliance on infrastructure systems, many repairs are already underway, though gaps have emerged in the funding for repairs to certain infrastructure systems. Supplement Information to the August 2008

The amphioxus genome illuminates vertebrate origins and cephalochordate biology.

Cephalochordates, urochordates, and vertebrates evolved from a common ancestor over 520 million years ago. To improve our understanding of chordate evolution and the origin of vertebrates, we intensively searched for particular genes, gene families, and conserved noncoding elements in the sequenced genome of the cephalochordate Branchiostoma floridae, commonly called amphioxus or lancelets. Special attention was given to homeobox genes, opsin genes, genes involved in neural crest development, nuclear receptor genes, genes encoding components of the endocrine and immune systems, and conserved cis-regulatory enhancers. The amphioxus genome contains a basic set of chordate genes involved in development and cell signaling, including a fifteenth Hox gene. This set includes many genes that were co-opted in vertebrates for new roles in neural crest development and adaptive immunity. However, where amphioxus has a single gene, vertebrates often have two, three, or four paralogs derived from two whole-genome duplication events. In addition, several transcriptional enhancers are conserved between amphioxus and vertebrates--a very wide phylogenetic distance. In contrast, urochordate genomes have lost many genes, including a diversity of homeobox families and genes involved in steroid hormone function. The amphioxus genome also exhibits derived features, including duplications of opsins and genes proposed to function in innate immunity and endocrine systems. Our results indicate that the amphioxus genome is elemental to an understanding of the biology and evolution of nonchordate deuterostomes, invertebrate chordates, and vertebrates.

Surface collective oscillations of metal clusters and spheres: Random-phase-approximation sum-rules approach

Using the once and thrice energy-weighted moments of the random-phase-approximation strength function, we have derived compact expressions for the average energy of surface collective oscillations of clusters and spheres of metal atoms. The L=0 volume mode has also been studied. We have carried out quantal and semiclassical calculations for Na and Ag systems in the spherical-jellium approximation. We present a rather thorough discussion of surface diffuseness and quantal size effects on the resonance energies.

E-learning initiatives in forensic interpretation: report on experiences from current projects and outlook

This paper reports on the purpose, design, methodology and target audience of E-learning courses in forensic interpretation offered by the authors since 2010, including practical experiences made throughout the implementation period of this project. This initiative was motivated by the fact that reporting results of forensic examinations in a logically correct and scientifically rigorous way is a daily challenge for any forensic practitioner. Indeed, interpretation of raw data and communication of findings in both written and oral statements are topics where knowledge and applied skills are needed. Although most forensic scientists hold educational records in traditional sciences, only few actually followed full courses that focussed on interpretation issues. Such courses should include foundational principles and methodology - including elements of forensic statistics - for the evaluation of forensic data in a way that is tailored to meet the needs of the criminal justice system. In order to help bridge this gap, the authors' initiative seeks to offer educational opportunities that allow practitioners to acquire knowledge and competence in the current approaches to the evaluation and interpretation of forensic findings. These cover, among other aspects, probabilistic reasoning (including Bayesian networks and other methods of forensic statistics, tools and software), case pre-assessment, skills in the oral and written communication of uncertainty, and the development of independence and self-confidence to solve practical inference problems. E-learning was chosen as a general format because it helps to form a trans-institutional online-community of practitioners from varying forensic disciplines and workfield experience such as reporting officers, (chief) scientists, forensic coordinators, but also lawyers who all can interact directly from their personal workplaces without consideration of distances, travel expenses or time schedules. In the authors' experience, the proposed learning initiative supports participants in developing their expertise and skills in forensic interpretation, but also offers an opportunity for the associated institutions and the forensic community to reinforce the development of a harmonized view with regard to interpretation across forensic disciplines, laboratories and judicial systems.

Cycling of nutrients and silicon in pigeonpea and pearl millet monoculture and intercropping

In a no-tillage system, cover crops must be used that combine shoot dry matter production and nutrient recycling. The aim of this study was to evaluate shoot dry matter production, decomposition rate and macronutrient and silicon release from pigeonpea and pearl millet in monoculture and intercropping systems. A randomized block design was used with a 3 x 6 factorial arrangement, with four replications. The first factor consisted of three cover crops (pigeonpea, pearl millet and intercropping of these cover crops) and the second consisted of six sampling times [0, 18, 32, 46, 74 and 91 days after desiccation (DAD)]. Pearl millet produced greater amounts of shoot dry matter and content of N, P, K, Ca, Mg, S, C and Si and had a higher decomposition rate and macronutrient and Si release than the other cover crops. The rates of decomposition and daily nutrient release from shoot dry matter were highest in the first period of evaluation (0-18 DAD). Over time, the C/N, C/P and C/S ratios increased, while C/Si and the decomposition rate decreased. Potassium was the nutrient most quickly released to the soil, especially from pearl millet residue. Silicon had the lowest release rate, with 62, 82 and 74 % of the total content in the shoot dry matter remaining in the last evaluation of pearl millet, pigeonpea and in the intercrop system, respectively. The shoot dry matter from the intercrop system had a different decomposition rate than that from the pearl millet monoculture and pigeonpea. Plants with greater shoot dry matter production and lower C/Si ratio are more effective in a no-tillage system for providing a more complete and persistent soil cover.

SOIL FUNGISTASIS AGAINST FUSARIUM GRAMINEARUM UNDER DIFFERENT CROP MANAGEMENT SYSTEMS

Soil management, in terms of tillage and cropping systems, strongly influences the biological properties of soil involved in the suppression of plant diseases. Fungistasis mediated by soil microbiota is an important component of disease-suppressive soils. We evaluated the influence of different management systems on fungistasis against Fusarium graminearum, the relationship of fungistasis to the bacterial profile of the soil, and the possible mechanisms involved in this process. Samples were taken from a long-term experiment set up in a Paleudult soil under conventional tillage or no-tillage management and three cropping systems: black oat (Avena strigose L.) + vetch (Vicia sativa L.)/maize (Zea mays L.) + cowpea (Vigna sinensis L.), black oat/maize, and vetch/maize. Soil fungistasis was evaluated in terms of reduction of radial growth of F. graminearum, and bacterial diversity was assessed using ribosomal intergenic spacer analysis (RISA). A total of 120 bacterial isolates were obtained and evaluated for antibiosis, and production of volatile compounds and siderophores. No-tillage soil samples showed the highest level of F. graminearum fungistasis by sharply reducing the development of this pathogen. Of the cropping systems tested, the vetch + black oat/maize + cowpea system showed the highest fungistasis and the oat/maize system showed the lowest. The management system also affected the genetic profile of the bacteria isolated, with the systems from fungistatic soils showing greater similarity. Although there was no clear relationship between soil management and the characteristics of the bacterial isolates, we may conclude that antibiosis and the production of siderophores were the main mechanisms accounting for fungistasis.

Strategic Enterprise Architecture Management - Challenges, Best Practices, and Future Developments

The discipline of Enterprise Architecture Management (EAM) deals with the alignment of business and information systems architectures. While EAM has long been regarded as a discipline for IT managers this book takes a different stance: It explains how top executives can use EAM for leveraging their strategic planning and controlling processes and how EAM can contribute to sustainable competitive advantage. Based on the analysis of best practices from eight leading European companies from various industries the book presents crucial elements of successful EAM. It outlines what executives need to do in terms of governance, processes, methodologies and culture in order to bring their management to the next level. Beyond this, the book points how EAM might develop in the next decade allowing today's managers to prepare for the future of architecture management.

Schizotypy as an organizing framework for social and affective sciences

Schizotypy, defined in terms of commonly occurring personality traits related to the schizophrenia spectrum, has been an important construct for understanding the neurodevelopment and stress-diathesis of schizophrenia. However, as schizotypy nears its sixth decade of application, it is important to acknowledge its impressively rich literature accumulating outside of schizophrenia research. In this article, we make the case that schizotypy has considerable potential as a conceptual framework for understanding individual differences in affective and social functions beyond those directly involved in schizophrenia spectrum pathology. This case is predicated on (a) a burgeoning literature noting anomalies in a wide range of social functioning, affiliative, positive and negative emotional, expressive, and social cognitive systems, (b) practical and methodological features associated with schizotypy research that help facilitate empirical investigation, and (c) close ties to theoretical constructs of central importance to affective and social science (eg, stress diathesis, neural compensation). We highlight recent schizotypy research, ie providing insight into the nature of affective and social systems more generally. This includes current efforts to clarify the neurodevelopmental, neurobiological, and psychological underpinnings of affiliative drives, hedonic capacity, social cognition, and stress responsivity systems. Additionally, we discuss neural compensatory and resilience factors that may mitigate the expression of stress-diathesis and functional outcome, and highlight schizotypy's potential role for understanding cultural determinants of social and affective functions.

IL-17F co-expression improves cell growth characteristics and enhances recombinant protein production during CHO cell line engineering.

The generation of a high productivity cell line is a critical step in the production of a therapeutic protein. Many innovative engineering strategies have been devised in order to maximize the expression rate of production cells for increased process efficiency. Less effort has focused on improvements to the cell line generation process, which is typically long and laborious when using mammalian cells. Based on unexpected findings when generating stable CHO cell lines expressing human IL-17F, we studied the benefit of expressing this protein during the establishment of production cell lines. We demonstrate that IL-17F expression enhances the rate of selection and overall number of selected cell lines as well as their transgene expression levels. We also show that this benefit is observed with different parental CHO cell lines and selection systems. Furthermore, IL-17F expression improves the efficiency of cell line subcloning processes. IL-17F can therefore be exploited in a standard manufacturing process to obtain higher productivity clones in a reduced time frame.

Correlation between microtensile bond strength data and clinical outcome of Class V restorations.

OBJECTIVE: To determine if the results of resin-dentin microtensile bond strength (µTBS) is correlated with the outcome parameters of clinical studies on non-retentive Class V restorations. METHODS: Resin-dentin µTBS data were obtained from one test center; the in vitro tests were all performed by the same operator. The µTBS testing was performed 8h after bonding and after 6 months of storing the specimens in water. Pre-test failures (PTFs) of specimens were included in the analysis, attributing them a value of 1MPa. Prospective clinical studies on cervical restorations (Class V) with an observation period of at least 18 months were searched in the literature. The clinical outcome variables were retention loss, marginal discoloration and marginal integrity. Furthermore, an index was formulated to be better able to compare the laboratory and clinical results. Estimates of adhesive effects in a linear mixed model were used to summarize the clinical performance of each adhesive between 12 and 36 months. Spearman correlations between these clinical performances and the µTBS values were calculated subsequently. RESULTS: Thirty-six clinical studies with 15 adhesive/restorative systems for which µTBS data were also available were included in the statistical analysis. In general 3-step and 2-step etch-and-rinse systems showed higher bond strength values than the 2-step/3-step self-etching systems, which, however, produced higher values than the 1-step self-etching and the resin modified glass ionomer systems. Prolonged water storage of specimens resulted in a significant decrease of the mean bond strength values in 5 adhesive systems (Wilcoxon, p<0.05). There was a significant correlation between µTBS values both after 8h and 6 months of storage and marginal discoloration (r=0.54 and r=0.67, respectively). However, the same correlation was not found between µTBS values and the retention rate, clinical index or marginal integrity. SIGNIFICANCE: As µTBS data of adhesive systems, especially after water storage for 6 months, showed a good correlation with marginal discoloration in short-term clinical Class V restorations, longitudinal clinical trials should explore whether early marginal staining is predictive for future retention loss in non-carious cervical restorations.

Field Data Collection and Reporting Study, HR-377, 1997

A review of the Iowa Department of Transportation's field data collection and reporting system has been performed. Included were several systems used by the Office of Construction and Local Jurisdictions. The entire field data collection and reporting systems for asphalt cement concrete (ACC) paving, portland cement concrete (PCC) paving, and PCC structures were streamlined and computerized. The field procedures for materials acceptance were also reviewed. Best practices were identified and a method was developed to prioritize materials so transportation agencies could focus their efforts on high priority materials. Iowa State University researchers facilitated a discussion about Equal Employment Opportunity (EEO) and Affirmative Action (AA) procedures between the Office of Construction field staff and the Office of Contracts. A set of alternative procedures was developed. Later the Office of Contracts considered these alternatives as they developed new procedures that are currently being implemented. The job close-out package was reviewed and two unnecessary procedures were eliminated. Numerous other procedures were reviewed and flowcharted. Several changes have been recommended that will increase efficiency and allow staff time to be devoted to higher priority activities. It is estimated the improvements in ACC paving, PCC paving and structural concrete will by similar to three full time equivalent (FTE) positions to field construction, field materials and Office of Materials. Elimination of EEO interviews will be equivalent to one FTE position. It is estimated that other miscellaneous changes will be equivalent to at least one other FTE person. This is a total five FTEs. These are conservative estimates based on savings that are easily quantified. It is likely that total positive effect is greater when items that are difficult to quantify are considered.

Space Competition and Time Delays in Human Range Expansions. Application to the Neolithic Transition

Space competition effects are well-known in many microbiological and ecological systems. Here we analyze such an effectin human populations. The Neolithic transition (change from foraging to farming) was mainly the outcome of a demographic process that spread gradually throughout Europe from the Near East. In Northern Europe, archaeological data show a slowdown on the Neolithic rate of spread that can be related to a high indigenous (Mesolithic) population density hindering the advance as a result of the space competition between the two populations. We measure this slowdown from a database of 902 Early Neolithic sites and develop a time-delayed reaction-diffusion model with space competition between Neolithic and Mesolithic populations, to predict the observed speeds. The comparison of the predicted speed with the observations and with a previous non-delayed model show that both effects, the time delay effect due to the generation lag and the space competition between populations, are crucial in order to understand the observations