Generative Roles: Assessing Sustained Involvement in Generativity

Abstract Generative roles refer to observable, behavioral community positions that embody aspects of teaching and nurturing that are central to the concept of generativity. Two studies are presented that describe generative roles in a community sample and provide psychometric data for a short index of generative roles. The first study also provides reliability and validity data from a second informant. The second study examines generative roles at different stages of adolescence and adulthood. Participants were asked 8 yes/no questions about a variety of community roles. The validity of the GRI was supported by significant correlations with the Loyola Generativity Scale, a widely used measure of generative concern (r=.33), and measures of related constructs. The correlations were similar across age categories. The Generative Roles Index has good psychometric qualities and complements existing measures of generativity by providing behavioral, observable data on roles

Performance analysis of a parallel, multi-node pipeline for DNA sequencing

Post-sequencing DNA analysis typically consists of read mapping followed by variant calling and is very time-consuming, even on a multi-core machine. Recently, we proposed Halvade, a parallel, multi-node implementation of a DNA sequencing pipeline according to the GATK Best Practices recommendations. The MapReduce programming model is used to distribute the workload among different workers. In this paper, we study the impact of different hardware configurations on the performance of Halvade. Benchmarks indicate that especially the lack of good multithreading capabilities in the existing tools (BWA, SAMtools, Picard, GATK) cause suboptimal scaling behavior. We demonstrate that it is possible to circumvent this bottleneck by using multiprocessing on high-memory machines rather than using multithreading. Using a 15-node cluster with 360 CPU cores in total, this results in a runtime of 1 h 31 min. Compared to a single-threaded runtime of similar to 12 days, this corresponds to an overall parallel efficiency of 53%

Values Narratives for Personal Growth: Formative Evaluation of the Laws of Life Essay Program

Evidence that even very brief writing exercises can change the way people see themselves and promote more positive mental and physical health has led to increased interest in their use in school settings and elsewhere. To date, however, research designs rely heavily on samples of college students and experimental studies of writing tasks carried out in the lab. There has been less investigation of the potential impact of more naturally occurring expressive writing exercises that exist in places like schools and that focus on adolescents. The current study was a process evaluation of the Laws of Life Essay, a values-based narrative program that was part of participants’ secondary school experience. It examined participants’ views of the impact of the program on their personal growth and, given the age range of participants, allowed for process evaluation of its perceived short- and long-term effects. Qualitative, semistructured interviews with 55 adolescent and adult participants were collected. Themes in participants’ responses included the importance of reflection and reappraisal of values, adversity, and relationships. Participants also discussed the importance of an audience for their writing, a novel finding that suggests one possible way to increase the impact of other narrative programs. Participants described variability in their engagement with expressive writing. This is one of the few studies that examined participants’ own views of the value of expressive writing and their responses suggest directions for future research and implications for designing expressive writing tasks to support social emotional learning and character education in schools and promote well-being at key developmental moments

A Model-Based Analysis of GC-Biased Gene Conversion in the Human and Chimpanzee Genomes

GC-biased gene conversion (gBGC) is a recombination-associated process that favors the fixation of G/C alleles over A/T alleles. In mammals, gBGC is hypothesized to contribute to variation in GC content, rapidly evolving sequences, and the fixation of deleterious mutations, but its prevalence and general functional consequences remain poorly understood. gBGC is difficult to incorporate into models of molecular evolution and so far has primarily been studied using summary statistics from genomic comparisons. Here, we introduce a new probabilistic model that captures the joint effects of natural selection and gBGC on nucleotide substitution patterns, while allowing for correlations along the genome in these effects. We implemented our model in a computer program, called phastBias, that can accurately detect gBGC tracts about 1 kilobase or longer in simulated sequence alignments. When applied to real primate genome sequences, phastBias predicts gBGC tracts that cover roughly 0.3% of the human and chimpanzee genomes and account for 1.2% of human-chimpanzee nucleotide differences. These tracts fall in clusters, particularly in subtelomeric regions; they are enriched for recombination hotspots and fast-evolving sequences; and they display an ongoing fixation preference for G and C alleles. They are also significantly enriched for disease-associated polymorphisms, suggesting that they contribute to the fixation of deleterious alleles. The gBGC tracts provide a unique window into historical recombination processes along the human and chimpanzee lineages. They supply additional evidence of long-term conservation of megabase-scale recombination rates accompanied by rapid turnover of hotspots. Together, these findings shed new light on the evolutionary, functional, and disease implications of gBGC. The phastBias program and our predicted tracts are freely available. © 2013 Capra et al

Characteristics of transposable element exonization within human and mouse

Insertion of transposed elements within mammalian genes is thought to be an important contributor to mammalian evolution and speciation. Insertion of transposed elements into introns can lead to their activation as alternatively spliced cassette exons, an event called exonization. Elucidation of the evolutionary constraints that have shaped fixation of transposed elements within human and mouse protein coding genes and subsequent exonization is important for understanding of how the exonization process has affected transcriptome and proteome complexities. Here we show that exonization of transposed elements is biased towards the beginning of the coding sequence in both human and mouse genes. Analysis of single nucleotide polymorphisms (SNPs) revealed that exonization of transposed elements can be population-specific, implying that exonizations may enhance divergence and lead to speciation. SNP density analysis revealed differences between Alu and other transposed elements. Finally, we identified cases of primate-specific Alu elements that depend on RNA editing for their exonization. These results shed light on TE fixation and the exonization process within human and mouse genes.Comment: 11 pages, 4 figure

Solitary metastatic adenocarcinoma of the sternum treated by total sternectomy and chest wall reconstruction using a Gore-Tex patch and myocutaneous flap: a case report

<p>Abstract</p> <p>Introduction</p> <p>The consequences of bone metastasis are often devastating. Although the exact incidence of bone metastasis is unknown, it is estimated that 350,000 people die of bone metastasis annually in the United States. The incidence of local recurrences after mastectomy and breast-conserving therapy varies between 5% and 40% depending on the risk factors and primary therapy utilized. So far, a standard therapy of local recurrence has not been defined, while indications of resection and reconstruction considerations have been infrequently described. This case report reviews the use of sternectomy for breast cancer recurrence, highlights the need for thorough clinical and radiologic evaluation to ensure the absence of other systemic diseases, and suggests the use of serratus anterior muscle flap as a pedicle graft to cover full-thickness defects of the anterior chest wall.</p> <p>Case presentation</p> <p>We report the case of a 70-year-old Caucasian woman who was referred to our hospital for the management of a retrosternal mediastinal mass. She had undergone radical mastectomy in 1999. Computed tomography and magnetic resonance imaging revealed a 74.23 × 37.7 × 133.6-mm mass in the anterior mediastinum adjacent to the main pulmonary artery, the right ventricle and the ascending aorta. We performed total sternectomy at all layers encompassing the skin, the subcutaneous tissues, the right pectoralis major muscle, all the costal cartilages, and the anterior part of the pericardium. The defect was immediately closed using a 0.6 mm Gore-Tex cardiovascular patch combined with a serratus anterior muscle flap. Our patient had remained asymptomatic during her follow-up examination after 18 months.</p> <p>Conclusion</p> <p>Chest wall resection has become a critical component of the thoracic surgeon's armamentarium. It may be performed to treat either benign conditions (osteoradionecrosis, osteomyelitis) or malignant diseases. There are, however, very few reports on the results of full-thickness complete chest wall resections for locally recurrent breast cancer with sufficient safety margins, and even fewer reports that describe the operative technique of using the serratus anterior muscle as a pedicled flap.</p

Defects in the acid phosphatase ACPT cause recessive hypoplastic amelogenesis imperfecta

We identified two homozygous missense variants (c.428C>T, p.(T143M) and c.746C>T, p.(P249L)) in ACPT, the gene encoding Acid Phosphatase, Testicular, which segregate with hypoplastic Amelogenesis imperfecta (AI) in two unrelated families. ACPT is reported to play a role in odontoblast differentiation and mineralisation by supplying phosphate during dentine formation. Analysis by computerised tomography and scanning electron microscopy of a primary molar tooth from an individual homozygous for the c.746C>T variant, revealed an enamel layer that was hypoplastic but mineralised with prismatic architecture. These findings implicate variants in ACPT as a cause of early failure of amelogenesis during the secretory phase

microPIR: An Integrated Database of MicroRNA Target Sites within Human Promoter Sequences

Background: microRNAs are generally understood to regulate gene expression through binding to target sequences within 39-UTRs of mRNAs. Therefore, computational prediction of target sites is usually restricted to these gene regions. Recent experimental studies though have suggested that microRNAs may alternatively modulate gene expression by interacting with promoters. A database of potential microRNA target sites in promoters would stimulate research in this field leading to more understanding of complex microRNA regulatory mechanism. Methodology: We developed a database hosting predicted microRNA target sites located within human promoter sequences and their associated genomic features, called microPIR (microRNA-Promoter Interaction Resource). microRNA seed sequences were used to identify perfect complementary matching sequences in the human promoters and the potential target sites were predicted using the RNAhybrid program..15 million target sites were identified which are located within 5000 bp upstream of all human genes, on both sense and antisense strands. The experimentally confirmed argonaute (AGO) binding sites and EST expression data including the sequence conservation across vertebrate species of each predicted target are presented for researchers to appraise the quality of predicted target sites. The microPIR database integrates various annotated genomic sequence databases, e.g. repetitive elements, transcription factor binding sites, CpG islands, and SNPs, offering users the facility to extensively explore relationships among target sites and other genomi

Rule based classifier for the analysis of gene-gene and gene-environment interactions in genetic association studies

<p>Abstract</p> <p>Background</p> <p>Several methods have been presented for the analysis of complex interactions between genetic polymorphisms and/or environmental factors. Despite the available methods, there is still a need for alternative methods, because no single method will perform well in all scenarios. The aim of this work was to evaluate the performance of three selected rule based classifier algorithms, RIPPER, RIDOR and PART, for the analysis of genetic association studies.</p> <p>Methods</p> <p>Overall, 42 datasets were simulated with three different case-control models, a varying number of subjects (300, 600), SNPs (500, 1500, 3000) and noise (5%, 10%, 20%). The algorithms were applied to each of the datasets with a set of algorithm-specific settings. Results were further investigated with respect to a) the Model, b) the Rules, and c) the Attribute level. Data analysis was performed using WEKA, SAS and PERL.</p> <p>Results</p> <p>The RIPPER algorithm discovered the true case-control model at least once in >33% of the datasets. The RIDOR and PART algorithm performed poorly for model detection. The RIPPER, RIDOR and PART algorithm discovered the true case-control rules in more than 83%, 83% and 44% of the datasets, respectively. All three algorithms were able to detect the attributes utilized in the respective case-control models in most datasets.</p> <p>Conclusions</p> <p>The current analyses substantiate the utility of rule based classifiers such as RIPPER, RIDOR and PART for the detection of gene-gene/gene-environment interactions in genetic association studies. These classifiers could provide a valuable new method, complementing existing approaches, in the analysis of genetic association studies. The methods provide an advantage in being able to handle both categorical and continuous variable types. Further, because the outputs of the analyses are easy to interpret, the rule based classifier approach could quickly generate testable hypotheses for additional evaluation. Since the algorithms are computationally inexpensive, they may serve as valuable tools for preselection of attributes to be used in more complex, computationally intensive approaches. Whether used in isolation or in conjunction with other tools, rule based classifiers are an important addition to the armamentarium of tools available for analyses of complex genetic association studies.</p