Data mining and pathway analysis of glucose-6-phosphate dehydrogenase with natural language processing

PubMed Central

Chen, Long; Zhang, Chunhua; Wang, Yanling; Li, Yuqian; Han, Qiaoqiao; Yang, Huixin; Zhu, Yuechun

2017-01-01

Human glucose-6-phosphate dehydrogenase (G6PD) is a crucial enzyme in the pentose phosphate pathway, and serves an important role in biosynthesis and the redox balance. G6PD deficiency is a major cause of neonatal jaundice and acute hemolyticanemia, and recently, G6PD has been associated with diseases including inflammation and cancer. The aim of the present study was to conduct a search of the National Center for Biotechnology Information PubMed library for articles discussing G6PD. Genes that were identified to be associated with G6PD were recorded, and the frequency at which each gene appeared was calculated. Gene ontology (GO), pathway and network analyses were then performed. A total of 98 G6PD-associated genes and 33 microRNAs (miRNAs) that potentially regulate G6PD were identified. The 98 G6PD-associated genes were then sub-classified into three functional groups by GO analysis, followed by analysis of function, pathway, network, and disease association. Out of the 47 signaling pathways identified, seven were significantly correlated with G6PD-associated genes. At least two out of four independent programs identified the 33 miRNAs that were predicted to target G6PD. miR-1207-5P, miR-1 and miR-125a-5p were predicted by all four software programs to target G6PD. The results of the present study revealed that dysregulation of G6PD was associated with cancer, autoimmune diseases, and oxidative stress-induced disorders. These results revealed the potential roles of G6PD-regulated signaling and metabolic pathways in the etiology of these diseases. PMID:28627690

MetaFluxNet: the management of metabolic reaction information and quantitative metabolic flux analysis.

PubMed

Lee, Dong-Yup; Yun, Hongsoek; Park, Sunwon; Lee, Sang Yup

2003-11-01

MetaFluxNet is a program package for managing information on the metabolic reaction network and for quantitatively analyzing metabolic fluxes in an interactive and customized way. It allows users to interpret and examine metabolic behavior in response to genetic and/or environmental modifications. As a result, quantitative in silico simulations of metabolic pathways can be carried out to understand the metabolic status and to design the metabolic engineering strategies. The main features of the program include a well-developed model construction environment, user-friendly interface for metabolic flux analysis (MFA), comparative MFA of strains having different genotypes under various environmental conditions, and automated pathway layout creation. http://mbel.kaist.ac.kr/ A manual for MetaFluxNet is available as PDF file.

5 CFR 362.102 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PATHWAYS PROGRAMS General... written agreement between the agency and each Pathways Participant. Program Participant or Pathways Participant means any individual appointed under a Pathways Program. Qualifying educational institution means...

5 CFR 362.102 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PATHWAYS PROGRAMS General... written agreement between the agency and each Pathways Participant. Program Participant or Pathways Participant means any individual appointed under a Pathways Program. Qualifying educational institution means...

Text mining-based in silico drug discovery in oral mucositis caused by high-dose cancer therapy.

PubMed

Kirk, Jon; Shah, Nirav; Noll, Braxton; Stevens, Craig B; Lawler, Marshall; Mougeot, Farah B; Mougeot, Jean-Luc C

2018-08-01

Oral mucositis (OM) is a major dose-limiting side effect of chemotherapy and radiation used in cancer treatment. Due to the complex nature of OM, currently available drug-based treatments are of limited efficacy. Our objectives were (i) to determine genes and molecular pathways associated with OM and wound healing using computational tools and publicly available data and (ii) to identify drugs formulated for topical use targeting the relevant OM molecular pathways. OM and wound healing-associated genes were determined by text mining, and the intersection of the two gene sets was selected for gene ontology analysis using the GeneCodis program. Protein interaction network analysis was performed using STRING-db. Enriched gene sets belonging to the identified pathways were queried against the Drug-Gene Interaction database to find drug candidates for topical use in OM. Our analysis identified 447 genes common to both the "OM" and "wound healing" text mining concepts. Gene enrichment analysis yielded 20 genes representing six pathways and targetable by a total of 32 drugs which could possibly be formulated for topical application. A manual search on ClinicalTrials.gov confirmed no relevant pathway/drug candidate had been overlooked. Twenty-five of the 32 drugs can directly affect the PTGS2 (COX-2) pathway, the pathway that has been targeted in previous clinical trials with limited success. Drug discovery using in silico text mining and pathway analysis tools can facilitate the identification of existing drugs that have the potential of topical administration to improve OM treatment.

Differential Expression and Pathway Analysis in Drug-Resistant Triple-Negative Breast Cancer Cell Lines Using RNASeq Analysis.

PubMed

Shaheen, Safa; Fawaz, Febin; Shah, Shaheen; Büsselberg, Dietrich

2018-06-19

Triple-negative breast cancer (TNBC) is among the most notorious types of breast cancer, the treatment of which does not give consistent results due to the absence of the three receptors (estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) as well as high amount of molecular variability. Drug resistance also contributes to treatment unresponsiveness. We studied differentially expressed genes, their biological roles, as well as pathways from RNA-Seq datasets of two different TNBC drug-resistant cell lines of Basal B subtype SUM159 and MDA-MB-231 treated with drugs JQ1 and Dexamethasone, respectively, to elucidate the mechanism of drug resistance. RNA sequencing(RNA-Seq) data analysis was done using edgeR which is an efficient program for determining the most significant Differentially Expressed Genes (DEGs), Gene Ontology (GO) terms, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. iPathway analysis was further used to obtain validated results using analysis that takes into consideration type, function, and interactions of genes in the pathway. The significant similarities and differences throw light into the molecular heterogeneity of TNBC, giving clues into the aspects that can be focused to overcome drug resistance. From this study, cytokine-cytokine receptor interaction pathway appeared to be a key factor in TNBC drug resistance.

BeHealthy Charities Aid Foundation Program, Russia: a Program Impact Pathways (PIP) analysis.

PubMed

Mukhina, Marina; Novikova, Irina

2014-09-01

In 2007, the Charities Aid Foundation Branch in Russia, under the initiative of and with financial support from the Mondelēz International Foundation and Mondelēz International, launched the charitable BeHealthy Program. The program's main focus is the implementation of four interrelated activities: conducting lessons for schoolchildren on healthy nutrition, with an emphasis on breakfast; healthy cooking lessons with children; cultivating nutritional plants; and providing conditions to encourage children to engage in more physical activity. The program serves more than 13,000 children attending public schools in the Leningrad (Lomonosovskii District), Vladimir, and Novgorod regions. BeHealthy provides funding for schools and comprehensive educational materials to help schoolchildren develop habits of healthy nutrition and physical activity, as well as consulting and expert support for school staff and other key stakeholders. The program brings in experts on program implementation and training for teachers. Curriculum support also includes printed and Web-based healthy lifestyle educational materials on best practices and positive experience, as well as meetings and conferences with school representatives and local authorities. One of the biggest challenges for program managers is to fully understand the complexities of the program, and why and how it is expected to induce changes in healthy lifestyle behaviors of the schoolchildren. For more comprehensive understanding, we performed a Program Impact Pathways (PIP) analysis to identify Critical Quality Control Points (CCPs) and a suite of core indicators of the program's impact on healthy lifestyles. The findings were presented at the Healthy Life-styles Program Evaluation Workshop held in Granada, Spain, 13-14 September 2013, under the auspices of the Mondelēz International Foundation. First, we developed an updated logic model based on how the program was executed. We then translated the logic model into a PIP diagram, where pathways that lead from one activity to the next were defined as the program processes. The PIP diagram is a road map to help ensure that the program inputs and activities lead to expected outcomes. Based on this road map, the program identifies and tracks its CCPs. Ensuring implementation of program activities and evaluating pre-post knowledge and behavior of participants were identified as CCPs. The PIP analysis was very useful for understanding realistic expectations for the potential of BeHealthy and its inputs. As a result, we now plan to evaluate the impact of the program and, on this basis, further improve the program's implementation and dissemination to other locations.

Blockade of the Programmed Death-1 Pathway Restores Sarcoidosis CD4+ T-Cell Proliferative Capacity

PubMed Central

Braun, Nicole A.; Celada, Lindsay J.; Herazo-Maya, Jose D.; Abraham, Susamma; Shaginurova, Guzel; Sevin, Carla M.; Grutters, Jan; Culver, Daniel A.; Dworski, Ryszard; Sheller, James; Massion, Pierre P.; Polosukhin, Vasiliy V.; Johnson, Joyce E.; Kaminski, Naftali; Wilkes, David S.; Oswald-Richter, Kyra A.

2014-01-01

Rationale: Effective therapeutic interventions for chronic, idiopathic lung diseases remain elusive. Normalized T-cell function is an important contributor to spontaneous resolution of pulmonary sarcoidosis. Up-regulation of inhibitor receptors, such as programmed death-1 (PD-1) and its ligand, PD-L1, are important inhibitors of T-cell function. Objectives: To determine the effects of PD-1 pathway blockade on sarcoidosis CD4+ T-cell proliferative capacity. Methods: Gene expression profiles of sarcoidosis and healthy control peripheral blood mononuclear cells were analyzed at baseline and follow-up. Flow cytometry was used to measure ex vivo expression of PD-1 and PD-L1 on systemic and bronchoalveolar lavage–derived cells of subjects with sarcoidosis and control subjects, as well as the effects of PD-1 pathway blockade on cellular proliferation after T-cell receptor stimulation. Immunohistochemistry analysis for PD-1/PD-L1 expression was conducted on sarcoidosis, malignant, and healthy control lung specimens. Measurements and Main Results: Microarray analysis demonstrates longitudinal increase in PDCD1 gene expression in sarcoidosis peripheral blood mononuclear cells. Immunohistochemistry analysis revealed increased PD-L1 expression within sarcoidosis granulomas and lung malignancy, but this was absent in healthy lungs. Increased numbers of sarcoidosis PD-1+ CD4+ T cells are present systemically, compared with healthy control subjects (P < 0.0001). Lymphocytes with reduced proliferative capacity exhibited increased proliferation with PD-1 pathway blockade. Longitudinal analysis of subjects with sarcoidosis revealed reduced PD-1+ CD4+ T cells with spontaneous clinical resolution but not with disease progression. Conclusions: Analogous to the effects in other chronic lung diseases, these findings demonstrate that the PD-1 pathway is an important contributor to sarcoidosis CD4+ T-cell proliferative capacity and clinical outcome. Blockade of the PD-1 pathway may be a viable therapeutic target to optimize clinical outcomes. PMID:25073001

5 CFR 362.101 - Program administration.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 362.101 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PATHWAYS PROGRAMS General Provisions § 362.101 Program administration. (a) The Pathways Programs authorized under... includes the Pathways Program name identified in paragraph (a) of this section, e.g., Treasury Internship...

5 CFR 362.101 - Program administration.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 362.101 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PATHWAYS PROGRAMS General Provisions § 362.101 Program administration. (a) The Pathways Programs authorized under... includes the Pathways Program name identified in paragraph (a) of this section, e.g., Treasury Internship...

Interaction of Herbal Compounds with Biological Targets: A Case Study with Berberine

PubMed Central

Chen, Xiao-Wu; Di, Yuan Ming; Zhang, Jian; Zhou, Zhi-Wei; Li, Chun Guang; Zhou, Shu-Feng

2012-01-01

Berberine is one of the main alkaloids found in the Chinese herb Huang lian (Rhizoma Coptidis), which has been reported to have multiple pharmacological activities. This study aimed to analyze the molecular targets of berberine based on literature data followed by a pathway analysis using the PANTHER program. PANTHER analysis of berberine targets showed that the most classes of molecular functions include receptor binding, kinase activity, protein binding, transcription activity, DNA binding, and kinase regulator activity. Based on the biological process classification of in vitro berberine targets, those targets related to signal transduction, intracellular signalling cascade, cell surface receptor-linked signal transduction, cell motion, cell cycle control, immunity system process, and protein metabolic process are most frequently involved. In addition, berberine was found to interact with a mixture of biological pathways, such as Alzheimer's disease-presenilin and -secretase pathways, angiogenesis, apoptosis signalling pathway, FAS signalling pathway, Hungtington disease, inflammation mediated by chemokine and cytokine signalling pathways, interleukin signalling pathway, and p53 pathways. We also explored the possible mechanism of action for the anti-diabetic effect of berberine. Further studies are warranted to elucidate the mechanisms of action of berberine using systems biology approach. PMID:23213296

5 CFR 362.108 - Program oversight.

Code of Federal Regulations, 2013 CFR

2013-01-01

....108 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PATHWAYS... of Pathways Participants who may be appointed or converted in any Pathways Program within a specific... Governmentwide use of the Pathways Programs, input from the Executive agencies, and consideration of the...

5 CFR 362.108 - Program oversight.

Code of Federal Regulations, 2014 CFR

2014-01-01

....108 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PATHWAYS... of Pathways Participants who may be appointed or converted in any Pathways Program within a specific... Governmentwide use of the Pathways Programs, input from the Executive agencies, and consideration of the...

5 CFR 362.109 - Reporting requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 362.109 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PATHWAYS... each Pathways Program; (2) The percentage of the agency's overall hires made from each Pathways Program; (3) The number of Pathways Participants, per Program, converted to the competitive service; and (4...

5 CFR 362.109 - Reporting requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 362.109 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PATHWAYS... each Pathways Program; (2) The percentage of the agency's overall hires made from each Pathways Program; (3) The number of Pathways Participants, per Program, converted to the competitive service; and (4...

Robotic surgical training.

PubMed

Ben-Or, Sharon; Nifong, L Wiley; Chitwood, W Randolph

2013-01-01

In July 2000, the da Vinci Surgical System (Intuitive Surgical, Inc) received Food and Drug Administration approval for intracardiac applications, and the first mitral valve repair was done at the East Carolina Heart Institute in May 2000. The system is now approved and used in many surgical specialties. With this disruptive technology and accepted use, surgeons and hospitals are seeking the most efficacious training pathway leading to safe use and responsible credentialing.One of the most important issues related to safe use is assembling the appropriate team of professionals involved with patient care. Moreover, proper patient selection and setting obtainable goals are also important.Creation and maintenance of a successful program are discussed in the article focusing on realistic goals. This begins with a partnership between surgeon leaders, hospital administrators, and industry support. Through this partnership, an appropriate training pathway and clinical pathway for success can be outlined. A timeline can then be created with periods of data analysis and adjustments as necessary. A successful program is attainable by following this pathway and attending to every detail along the journey.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ohi, J.

Supporting analysis and assessments can provide a sound analytic foundation and focus for program planning, evaluation, and coordination, particularly if issues of hydrogen production, distribution, storage, safety, and infrastructure can be analyzed in a comprehensive and systematic manner. The overall purpose of this activity is to coordinate all key analytic tasks-such as technology and market status, opportunities, and trends; environmental costs and benefits; and regulatory constraints and opportunities-within a long-term and systematic analytic foundation for program planning and evaluation. Within this context, the purpose of the project is to help develop and evaluate programmatic pathway options that incorporate near andmore » mid-term strategies to achieve the long-term goals of the Hydrogen Program. In FY 95, NREL will develop a comprehensive effort with industry, state and local agencies, and other federal agencies to identify and evaluate programmatic pathway options to achieve the long-term goals of the Program. Activity to date is reported.« less

Revealing pathways from payments for ecosystem services to socioeconomic outcomes

PubMed Central

Zhang, Jindong

2018-01-01

Payments for ecosystem services (PES) programs have been widely implemented as a promising tool to conserve ecosystems while facilitating socioeconomic development. However, the underlying pathways (or processes) through which PES programs affect socioeconomic outcomes remain elusive, and existing literature provides little guidance to quantify them. By integrating linkages among PES programs, livelihood activities, and socioeconomic outcomes, we develop a framework to reveal pathways from PES programs to socioeconomic outcomes. We empirically demonstrate the framework’s operationalization and uncover the pathways that lead to unexpected negative effects of two important PES programs on participating households’ income. With improved understanding of the pathways (for example, the programs decreased income through reducing crop production), we provide recommendations to enhance the PES programs’ outcomes in our demonstration site and beyond. Our study highlights the finding that elucidating the pathways from PES programs to their outcomes can help identify specific strategies to achieve ecosystem conservation and socioeconomic development simultaneously. PMID:29750187

A Biologically Informed Framework for the Analysis of the PPAR Signaling Pathway using a Bayesian Network

EPA Science Inventory

The US EPA’s ToxCastTM program seeks to combine advances in high-throughput screening technology with methodologies from statistics and computer science to develop high-throughput decision support tools for assessing chemical hazard and risk. To develop new methods of analysis of...

Exploring Student and Advisor Experiences in a College-University Pathway Program: A Study of the Bachelor of Commerce Pathway

ERIC Educational Resources Information Center

Percival, Jennifer; DiGiuseppe, Maurice; Goodman, Bill; LeSage, Ann; Hinch, Ron; Samis, John; Sanchez, Otto; Rodrigues, Anna; Raby, Phil; Longo, Fabiola; De La Rocha, Arlene

2015-01-01

Currently, there is great interest across Ontario in the expansion of pathway programs between colleges and universities. Through strategic partnerships, two Ontario-based postsecondary institutions (a college and a university) have developed innovative and effective pathway programs that facilitate the transition of students between institutions…

A Systematic Genetic Screen to Dissect the MicroRNA Pathway in Drosophila.

PubMed

Pressman, Sigal; Reinke, Catherine A; Wang, Xiaohong; Carthew, Richard W

2012-04-01

A central goal of microRNA biology is to elucidate the genetic program of miRNA function and regulation. However, relatively few of the effectors that execute miRNA repression have been identified. Because such genes may function in many developmental processes, mutations in them are expected to be pleiotropic and thus are discarded in most standard genetic screens. Here, we describe a systematic screen designed to identify all Drosophila genes in ∼40% of the genome that function in the miRNA pathway. To identify potentially pleiotropic genes, the screen analyzed clones of homozygous mutant cells in heterozygous animals. We identified 45 mutations representing 24 genes, and we molecularly characterized 9 genes. These include 4 previously known genes that encode core components of the miRNA pathway, including Drosha, Pasha, Dicer-1, and Ago1. The rest are new genes that function through chromatin remodeling, signaling, and mRNA decapping. The results suggest genetic screens that use clonal analysis can elucidate the miRNA program and that ∼100 genes are required to execute the miRNA program.

RSK is a principal effector of the RAS-ERK pathway for eliciting a coordinate, pro-motile/invasive gene program and phenotype in epithelial cells

PubMed Central

Doehn, Ulrik; Hauge, Camilla; Frank, Scott R.; Jensen, Claus J.; Duda, Katarzyna; Nielsen, Jakob V.; Cohen, Michael S.; Johansen, Jens V.; Winther, Benny R.; Lund, Leif R.; Winther, Ole; Taunton, Jack; Hansen, Steen H.; Frödin, Morten

2013-01-01

SUMMARY The RAS-stimulated RAF-MEK-ERK pathway confers epithelial cells with critical motile and invasive capacities during embryonic development, tissue regeneration and carcinoma progression. Yet many mechanisms by which ERK exerts this control remain elusive. Here, we demonstrate that the ERK-activated kinase RSK is necessary to induce motility and invasive capacities in non-transformed epithelial cells and carcinoma cells. RSK is moreover sufficient to induce certain motile responses. Expression profiling analysis revealed that a primary role of RSK is to induce transcription of potent pro-motile/invasive gene program by FRA1-dependent and independent mechanisms. Strikingly, the program enables RSK to coordinately modulate the extracellular environment, the intracellular motility apparatus, and receptors mediating communication between these compartments to stimulate motility and invasion. These findings uncover a general mechanism whereby the RAS-ERK pathway controls epithelial cell motility by identifying RSK as a key effector, from which emanates multiple highly coordinate transcription-dependent mechanisms for stimulation of motility and invasive properties. PMID:19716794

Altered Placental Tryptophan Metabolism: A Crucial Molecular Pathway for the Fetal Programming of Neurodevelopmental Disorders

DTIC Science & Technology

2014-07-01

Molecular Pathway for the Fetal Programming of Neurodevelopmental Disorders PRINCIPAL INVESTIGATOR: Alexandre Bonnin, PhD CONTRACTING...Fetal Programming of Neurodevelopmental Disorders 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Alexandre Bonnin, PhD; Betty...metabolism by maternal inflammation during early gestation constitutes a new molecular pathway for the fetal programming of neurodevelopmental

Integrative pathway analysis of a genome-wide association study of V̇o2max response to exercise training

PubMed Central

Vivar, Juan C.; Sarzynski, Mark A.; Sung, Yun Ju; Timmons, James A.; Bouchard, Claude; Rankinen, Tuomo

2013-01-01

We previously reported the findings from a genome-wide association study of the response of maximal oxygen uptake (V̇o2max) to an exercise program. Here we follow up on these results to generate hypotheses on genes, pathways, and systems involved in the ability to respond to exercise training. A systems biology approach can help us better establish a comprehensive physiological description of what underlies V̇o2maxtrainability. The primary material for this exploration was the individual single-nucleotide polymorphism (SNP), SNP-gene mapping, and statistical significance levels. We aimed to generate novel hypotheses through analyses that go beyond statistical association of single-locus markers. This was accomplished through three complementary approaches: 1) building de novo evidence of gene candidacy through informatics-driven literature mining; 2) aggregating evidence from statistical associations to link variant enrichment in biological pathways to V̇o2max trainability; and 3) predicting possible consequences of variants residing in the pathways of interest. We started with candidate gene prioritization followed by pathway analysis focused on overrepresentation analysis and gene set enrichment analysis. Subsequently, leads were followed using in silico analysis of predicted SNP functions. Pathways related to cellular energetics (pantothenate and CoA biosynthesis; PPAR signaling) and immune functions (complement and coagulation cascades) had the highest levels of SNP burden. In particular, long-chain fatty acid transport and fatty acid oxidation genes and sequence variants were found to influence differences in V̇o2max trainability. Together, these methods allow for the hypothesis-driven ranking and prioritization of genes and pathways for future experimental testing and validation. PMID:23990238

Health for Life in Primary Schools Program, United Kingdom: a Program Impact Pathways (PIP) analysis.

PubMed

Passmore, Sandra; Donovan, Martin

2014-09-01

The Health for Life in Primary Schools Program helps schools promote healthy, active lifestyles through curriculum support related to healthy eating and cooking, growing food, physical activity, and family involvement. These interrelated strands are shown to have the greatest impact on healthy lifestyles, and the Health for Life in Primary Schools Program seeks to make these not one-off lessons, but a sustainable part of a school's culture. Each school involved with the program develops its own Action Plan in order to achieve program goals. Each school is assessed by an audit of facilities, skills, and curriculum at baseline and follow-up, and the pupils complete an on-line questionnaire at baseline and follow-up. Other impact measures are individual to the school and relate to its own Action Plan. Health for Life in Primary Schools sought to assess the cohesiveness and strength of the program using the Program Impact Pathways (PIP) model. The program was deconstructed to its individual parts, with each part assessed in terms of its contribution to the overall program and constraints upon its effectiveness. The PIP analysis helped clarify the logic and structure of the program, whether its objectives can be achieved, the Critical Quality Control Points (CCPs), and the impact measures required to demonstrate success. The core indicators identified for impact evaluation were knowledge, attitudes, and behaviors of pupils around healthy eating cooking, growing food, and physical activity. The PIP model confirmed that the Health for Life in Primary Schools Program is well structured and is well suited to achieve its goals. The findings were presented at the Healthy Lifestyles Program Evaluation Workshop held in Granada, Spain, 13-14 September 2013, under the auspices of the Mondelēz International Foundation.

Characterization of Steroid Receptor RNA Activator Protein Function in Modulating the Estrogen Signaling Pathway

DTIC Science & Technology

2007-05-01

Signaling Pathway 5b. GRANT NUMBER W81XWH-05-1-0245 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Yi Yan 5e. TASK NUMBER...negative control to identify proteins non-specifically precipitated. Tandem mass spectrometric analysis of immunoprecipitated samples identified a...immunoprecipitated sample and negative control. It is important to note that, SRAP was present among the remaining specifically precipitated 87 proteins. Using the

From Biological to Program Efficacy: Promoting Dialogue among the Research, Policy, and Program Communities12

PubMed Central

Habicht, Jean-Pierre; Pelto, Gretel H.

2014-01-01

The biological efficacy of nutritional supplements to complement usual diets in poor populations is well established. This knowledge rests on decades of methodologic research development and, more recently, on codification of methods to compile and interpret results across studies. The challenge now is to develop implementation (delivery) science knowledge and achieve a similar consensus on efficacy criteria for the delivery of these nutrients by public health and other organizations. This requires analysis of the major policy instruments for delivery and well-designed program delivery studies that examine the flow of a nutrient through a program impact pathway. This article discusses the differences between biological and program efficacy, and why elucidating the fidelity of delivery along the program impact pathways is essential for implementing a program efficacy trial and for assessing its internal and external validity. Research on program efficacy is expanding, but there is a lack of adequate frameworks to facilitate the process of harmonizing concepts and vocabulary, which is essential for communication among scientists, policy planners, and program implementers. There is an urgent need to elaborate these frameworks at national and program levels not only for program efficacy studies but also for the broader research agenda to support and improve the science of delivering adequate nutrition to those who need it most. PMID:24425719

Transcriptomic meta-analysis identifies gene expression characteristics in various samples of HIV-infected patients with nonprogressive disease.

PubMed

Zhang, Le-Le; Zhang, Zi-Ning; Wu, Xian; Jiang, Yong-Jun; Fu, Ya-Jing; Shang, Hong

2017-09-12

A small proportion of HIV-infected patients remain clinically and/or immunologically stable for years, including elite controllers (ECs) who have undetectable viremia (<50 copies/ml) and long-term nonprogressors (LTNPs) who maintain normal CD4 + T cell counts for prolonged periods (>10 years). However, the mechanism of nonprogression needs to be further resolved. In this study, a transcriptome meta-analysis was performed on nonprogressor and progressor microarray data to identify differential transcriptome pathways and potential biomarkers. Using the INMEX (integrative meta-analysis of expression data) program, we performed the meta-analysis to identify consistently differentially expressed genes (DEGs) in nonprogressors and further performed functional interpretation (gene ontology analysis and pathway analysis) of the DEGs identified in the meta-analysis. Five microarray datasets (81 cases and 98 controls in total), including whole blood, CD4 + and CD8 + T cells, were collected for meta-analysis. We determined that nonprogressors have reduced expression of important interferon-stimulated genes (ISGs), CD38, lymphocyte activation gene 3 (LAG-3) in whole blood, CD4 + and CD8 + T cells. Gene ontology (GO) analysis showed a significant enrichment in DEGs that function in the type I interferon signaling pathway. Upregulated pathways, including the PI3K-Akt signaling pathway in whole blood, cytokine-cytokine receptor interaction in CD4 + T cells and the MAPK signaling pathway in CD8 + T cells, were identified in nonprogressors compared with progressors. In each metabolic functional category, the number of downregulated DEGs was more than the upregulated DEGs, and almost all genes were downregulated DEGs in the oxidative phosphorylation (OXPHOS) and tricarboxylic acid (TCA) cycle in the three types of samples. Our transcriptomic meta-analysis provides a comprehensive evaluation of the gene expression profiles in major blood types of nonprogressors, providing new insights in the understanding of HIV pathogenesis and developing strategies to delay HIV disease progression.

Program impact pathway analysis of a social franchise model shows potential to improve infant and young child feeding practices in Vietnam.

PubMed

Nguyen, Phuong H; Menon, Purnima; Keithly, Sarah C; Kim, Sunny S; Hajeebhoy, Nemat; Tran, Lan M; Ruel, Marie T; Rawat, Rahul

2014-10-01

By mapping the mechanisms through which interventions are expected to achieve impact, program impact pathway (PIP) analysis lays out the theoretical causal links between program activities, outcomes, and impacts. This study examines the pathways through which the Alive & Thrive (A&T) social franchise model is intended to improve infant and young child feeding (IYCF) practices in Vietnam. Mixed methods were used, including qualitative interviews with franchise management board members (n = 12), surveys with health providers (n = 120), counseling observations (n = 160), and household surveys (n = 2045). Six PIP components were assessed: 1) franchise management, 2) training and IYCF knowledge of health providers, 3) service delivery, 4) program exposure and utilization, 5) maternal behavioral determinants (knowledge, beliefs, and intentions) toward optimal IYCF practices, and 6) IYCF practices. Data were collected from A&T-intensive areas (A&T-I; mass media + social franchise) and A&T-nonintensive areas (A&T-NI; mass media only) by using a cluster-randomized controlled trial design. Data from 2013 were compared with baseline where similar measures were available. Results indicate that mechanisms are in place for effective management of the franchise system, despite challenges to routine monitoring. A&T training was associated with increased capacity of providers, resulting in higher-quality IYCF counseling (greater technical knowledge and communication skills during counseling) in A&T-I areas. Franchise utilization increased from 10% in 2012 to 45% in 2013 but fell below the expected frequency of 9-15 contacts per mother-child dyad. Improvements in breastfeeding knowledge, beliefs, intentions, and practices were greater among mothers in A&T-I areas than among those in A&T-NI areas. In conclusion, there are many positive changes along the impact pathway of the franchise services, but challenges in utilization and demand creation should be addressed to achieve the full intended impact. © 2014 American Society for Nutrition.

Third Space Strategists: International Students Negotiating the Transition from Pathway Program to Postgraduate Coursework Degree

ERIC Educational Resources Information Center

Benzie, Helen

2015-01-01

Pathway programs exist to prepare students for progression into university degrees but the transition experience for many students may not be as smooth as is suggested by the notion of the pathway. While attending a pathway program and at the beginning of their university degree, students may be in a third space, a liminal space where they engage…

Altered Placental Tryptophan Metabolism: A Crucial Molecular Pathway for the Fetal Programming of Neurodevelopmental Disorders

DTIC Science & Technology

2015-07-01

Programming of Neurodevelopmental Disorders PRINCIPAL INVESTIGATOR: Alexandre Bonnin, PhD CONTRACTING ORGANIZATION: University of Southern...Molecular Pathway for the Fetal Programming of Neurodevelopmental Disorders 5a. CONTRACT NUMBER W81XWH-13-1-0135 Pathway for the Fetal Programming of... Neurodevelopmental Disorders 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Alexandre Bonnin, PhD; 5d. PROJECT NUMBER Nick Goeden

Renewable Fuel Pathways II Final Rule to Identify Additional Fuel Pathways under Renewable Fuel Standard Program

EPA Pesticide Factsheets

This final rule describes EPA’s evaluation of biofuels derived from biogas fuel pathways under the RFS program and other minor amendments related to survey requirements associated with ULSD program and misfueling mitigation regulations for E15.

Academic Provenance: Mapping Geoscience Students' Academic Pathways to their Career Trajectories

NASA Astrophysics Data System (ADS)

Houlton, H. R.; Gonzales, L. M.; Keane, C. M.

2011-12-01

Targeted recruitment and retention efforts for the geosciences have become increasingly important with the growing concerns about program visibility on campuses, and given that geoscience degree production remains low relative to the demand for new geoscience graduates. Furthermore, understanding the career trajectories of geoscience degree recipients is essential for proper occupational placement. A theoretical framework was developed by Houlton (2010) to focus recruitment and retention efforts. This "pathway model" explicitly maps undergraduate students' geoscience career trajectories, which can be used to refine existing methods for recruiting students into particular occupations. Houlton's (2010) framework identified three main student population groups: Natives, Immigrants or Refugees. Each student followed a unique pathway, which consisted of six pathway steps. Each pathway step was comprised of critical incidents that influenced students' overall career trajectories. An aggregate analysis of students' pathways (Academic Provenance Analysis) showed that different populations' pathways exhibited a deviation in career direction: Natives indicated intentions to pursue industry or government sectors, while Immigrants intended to pursue academic or research-based careers. We expanded on Houlton's (2010) research by conducting a follow-up study to determine if the original participants followed the career trajectories they initially indicated in the 2010 study. A voluntary, 5-question, short-answer survey was administered via email. We investigated students' current pathway steps, pathway deviations, students' goals for the near future and their ultimate career ambitions. This information may help refine Houlton's (2010) "pathway model" and may aid geoscience employers in recruiting the new generation of professionals for their respective sectors.

Two programmed cell death systems in Escherichia coli: an apoptotic-like death is inhibited by the mazEF-mediated death pathway.

PubMed

Erental, Ariel; Sharon, Idith; Engelberg-Kulka, Hanna

2012-01-01

In eukaryotes, the classical form of programmed cell death (PCD) is apoptosis, which has as its specific characteristics DNA fragmentation and membrane depolarization. In Escherichia coli a different PCD system has been reported. It is mediated by the toxin-antitoxin system module mazEF. The E. coli mazEF module is one of the most thoroughly studied toxin-antitoxin systems. mazF encodes a stable toxin, MazF, and mazE encodes a labile antitoxin, MazE, which prevents the lethal effect of MazF. mazEF-mediated cell death is a population phenomenon requiring the quorum-sensing pentapeptide NNWNN designated Extracellular Death Factor (EDF). mazEF is triggered by several stressful conditions, including severe damage to the DNA. Here, using confocal microscopy and FACS analysis, we show that under conditions of severe DNA damage, the triggered mazEF-mediated cell death pathway leads to the inhibition of a second cell death pathway. The latter is an apoptotic-like death (ALD); ALD is mediated by recA and lexA. The mazEF-mediated pathway reduces recA mRNA levels. Based on these results, we offer a molecular model for the maintenance of an altruistic characteristic in cell populations. In our model, the ALD pathway is inhibited by the altruistic EDF-mazEF-mediated death pathway.

5 CFR 362.107 - Conversion to the competitive service.

Code of Federal Regulations, 2013 CFR

2013-01-01

... REGULATIONS PATHWAYS PROGRAMS General Provisions § 362.107 Conversion to the competitive service. (a) Subject... Pathways Program, an agency may noncompetitively convert an eligible Pathways Participant to a term or permanent competitive service position. (b) A Pathways Participant who is noncompetitively converted to a...

5 CFR 362.107 - Conversion to the competitive service.

Code of Federal Regulations, 2014 CFR

2014-01-01

... REGULATIONS PATHWAYS PROGRAMS General Provisions § 362.107 Conversion to the competitive service. (a) Subject... Pathways Program, an agency may noncompetitively convert an eligible Pathways Participant to a term or permanent competitive service position. (b) A Pathways Participant who is noncompetitively converted to a...

Implementation and evaluation of a clinical pathway for TRAM breast reconstruction.

PubMed

Hwang, T G; Wilkins, E G; Lowery, J C; Gentile, J

2000-02-01

Among strategies recently proposed to reduce practice variation, promote quality, and control costs in health care delivery, the concept of the clinical pathway has received considerable attention. Because transverse rectus abdominis musculocutaneous (TRAM) breast reconstruction is a common and often costly intervention, this institution sought to evaluate cost and quality outcomes of a clinical pathways program for this procedure. The TRAM reconstruction clinical pathway was implemented in April of 1996 to standardize postoperative care in this patient population. Outcomes of consecutive pathway cases for the first 14 months of the program were assessed in a retrospective cohort design, by using all nonpathway TRAM cases from the 18 months immediately before pathway implementation as controls. Outcomes assessed included length of hospital stay, postoperative complications, total postoperative charges, and total postoperative costs in relative value units. Data on these dependent variables were collected from hospital charts and billing records. The effects of pathway implementation on the outcomes of interest were analyzed by using analysis of covariance to control for potential confounding by other independent variables, including surgical site (unilateral versus bilateral reconstructions), technique (pedicle versus free TRAMs), timing (immediate versus delayed reconstructions), and patient age. Finally, a comparison of variances in the outcomes of interest between the two groups was analyzed by using an Ftest. For all statistical tests, p values of < or = 0.05 were considered significant. Twenty-nine patients were treated in the TRAM pathway group, whereas the control population included 40 nonpathway patients. After implementation of the TRAM pathway, length of stay decreased from 6.0 to 5.2 days; total postoperative charges were reduced from $8587 to $7744; and total postoperative relative value unit utilization declined from 1686 to 1104. Analysis of covariance showed that the decreases in length of hospital stay and relative value units in the TRAM pathway were statistically significant (p = 0.05 and p = 0.007, respectively). By contrast, no significant increase in complications was observed after pathway implementation. Variability in the TRAM pathway group, as measured by SD, decreased significantly for both length of hospital stay (p = 0.039) and relative value units (p = 0.023). Implementation of the TRAM reconstruction clinical pathway resulted in significant declines in length of hospital stay and total costs. These decreases in resource utilization had no significant effect on postoperative complication rates. Although additional research is needed to further assess the impact of clinical pathways, this approach offers considerable promise for improving the cost-effectiveness of health care.

The Charlotte/Mecklenburg Area Pathways to Employment Program

ERIC Educational Resources Information Center

Embrey, Lindsey

2006-01-01

This paper describes an innovative public and private strategic workforce development alliance, the Pathways to Employment Program (Pathways), developed by the Central Piedmont Community College (CPCC) in Charlotte, North Carolina. Pathways is a partnership of CPCC, the Charlotte Department of Social Services, 12 community businesses, 6 social…

Exploring Factors Facilitating and Hindering College-University Pathway Program Completion

ERIC Educational Resources Information Center

Percival, Jennifer; DiGiuseppe, Maurice; Goodman, Bill; LeSage, Ann; Longo, Fabiola; De La Rocha, Arlene; Hinch, Ron; Samis, John; Sanchez, Otto; Augusto Rodrigues, Anna; Raby, Phil

2016-01-01

Purpose: The purpose of this paper is to explore not only the academic measures such as grade point average of success of college-to-university transfer programs (Pathway Programs), but also the social-cultural facilitators and barriers throughout the students' Pathway experience. Design/methodology/approach: The experience of students and…

The metabolic co-regulator PGC1α suppresses prostate cancer metastasis

PubMed Central

Cortazar, Ana Rosa; Liu, Xiaojing; Urosevic, Jelena; Castillo-Martin, Mireia; Fernández-Ruiz, Sonia; Morciano, Giampaolo; Caro-Maldonado, Alfredo; Guiu, Marc; Zúñiga-García, Patricia; Graupera, Mariona; Bellmunt, Anna; Pandya, Pahini; Lorente, Mar; Martín-Martín, Natalia; Sutherland, James David; Sanchez-Mosquera, Pilar; Bozal-Basterra, Laura; Zabala-Letona, Amaia; Arruabarrena-Aristorena, Amaia; Berenguer, Antonio; Embade, Nieves; Ugalde-Olano, Aitziber; Lacasa-Viscasillas, Isabel; Loizaga-Iriarte, Ana; Unda-Urzaiz, Miguel; Schultz, Nikolaus; Aransay, Ana Maria; Sanz-Moreno, Victoria; Barrio, Rosa; Velasco, Guillermo; Pinton, Paolo; Cordon-Cardo, Carlos; Carracedo, Arkaitz

2016-01-01

Cellular transformation and cancer progression is accompanied by changes in the metabolic landscape. Master co-regulators of metabolism orchestrate the modulation of multiple metabolic pathways through transcriptional programs, and hence constitute a probabilistically parsimonious mechanism for general metabolic rewiring. Here we show that the transcriptional co-activator PGC1α suppresses prostate cancer progression and metastasis. A metabolic co-regulator data mining analysis unveiled that PGC1α is down-regulated in prostate cancer and associated to disease progression. Using genetically engineered mouse models and xenografts, we demonstrated that PGC1α opposes prostate cancer progression and metastasis. Mechanistically, the use of integrative metabolomics and transcriptomics revealed that PGC1α activates an Oestrogen-related receptor alpha (ERRα)-dependent transcriptional program to elicit a catabolic state and metastasis suppression. Importantly, a signature based on the PGC1α-ERRα pathway exhibited prognostic potential in prostate cancer, thus uncovering the relevance of monitoring and manipulating this pathway for prostate cancer stratification and treatment. PMID:27214280

Community College Pathways: 2012-2013 Descriptive Report

ERIC Educational Resources Information Center

Van Campen, James; Sowers, Nicole; Strother, Scott

2013-01-01

The Community College Pathways (CCP) program had an outstanding second year. In 2012-2013, the program reproduced the positive outcomes realized in the first year of implementation, including successful course completion rates of over 50 percent for both Pathways. Simultaneously, the administration of the Pathways has continued to develop and…

Implementing Guided Pathways: Early Insights from the AACC Pathways Colleges

ERIC Educational Resources Information Center

Jenkins, Davis; Lahr, Hana; Fink, John

2017-01-01

Across the United States, a growing number of colleges are redesigning their programs and student support services according to the "guided pathways" model. Central to this approach are efforts to clarify pathways to program completion, career advancement, and further education. Equally essential are efforts to help students explore…

Integrating genomics and proteomics data to predict drug effects using binary linear programming.

PubMed

Ji, Zhiwei; Su, Jing; Liu, Chenglin; Wang, Hongyan; Huang, Deshuang; Zhou, Xiaobo

2014-01-01

The Library of Integrated Network-Based Cellular Signatures (LINCS) project aims to create a network-based understanding of biology by cataloging changes in gene expression and signal transduction that occur when cells are exposed to a variety of perturbations. It is helpful for understanding cell pathways and facilitating drug discovery. Here, we developed a novel approach to infer cell-specific pathways and identify a compound's effects using gene expression and phosphoproteomics data under treatments with different compounds. Gene expression data were employed to infer potential targets of compounds and create a generic pathway map. Binary linear programming (BLP) was then developed to optimize the generic pathway topology based on the mid-stage signaling response of phosphorylation. To demonstrate effectiveness of this approach, we built a generic pathway map for the MCF7 breast cancer cell line and inferred the cell-specific pathways by BLP. The first group of 11 compounds was utilized to optimize the generic pathways, and then 4 compounds were used to identify effects based on the inferred cell-specific pathways. Cross-validation indicated that the cell-specific pathways reliably predicted a compound's effects. Finally, we applied BLP to re-optimize the cell-specific pathways to predict the effects of 4 compounds (trichostatin A, MS-275, staurosporine, and digoxigenin) according to compound-induced topological alterations. Trichostatin A and MS-275 (both HDAC inhibitors) inhibited the downstream pathway of HDAC1 and caused cell growth arrest via activation of p53 and p21; the effects of digoxigenin were totally opposite. Staurosporine blocked the cell cycle via p53 and p21, but also promoted cell growth via activated HDAC1 and its downstream pathway. Our approach was also applied to the PC3 prostate cancer cell line, and the cross-validation analysis showed very good accuracy in predicting effects of 4 compounds. In summary, our computational model can be used to elucidate potential mechanisms of a compound's efficacy.

Pathways into Science for High-School Girls

NASA Astrophysics Data System (ADS)

Simmons, Elizabeth

2004-03-01

This talk discusses the Pathways program ( www.bu.edu/lernet/pathways ) which I founded to provide encouragement and role models for young women interested in pursuing studies and careers in science, mathematics or engineering. I will describe the observations which led me to found Pathways, explain how the program has operated for the past 10 years, and then discuss its effect on the young women who attend... and the science and engineering professionals who volunteer to run the program.

Widespread activation of immunity and pro-inflammatory programs in peripheral blood leukocytes of HIV-infected patients with impaired lung gas exchange.

PubMed

Crothers, Kristina; Petrache, Irina; Wongtrakool, Cherry; Lee, Patty J; Schnapp, Lynn M; Gharib, Sina A

2016-04-01

HIV infection is associated with impaired lung gas transfer as indicated by a low diffusing capacity (DLCO), but the mechanisms are not well understood. We hypothesized that HIV-associated gas exchange impairment is indicative of system-wide perturbations that could be reflected by alterations in peripheral blood leukocyte (PBL) gene expression. Forty HIV-infected (HIV(+)) and uninfected (HIV(-)) men with preserved versus low DLCO were enrolled. All subjects were current smokers and those with acute illness, lung diseases other than COPD or asthma were excluded. Total RNA was extracted from PBLs and hybridized to whole-genome microarrays. Gene set enrichment analysis (GSEA) was performed between HIV(+) versus HIV(-) subjects with preserved DLCO and those with low DLCO to identify differentially activated pathways. Using pathway-based analyses, we found that in subjects with preserved DLCO, HIV infection is associated with activation of processes involved in immunity, cell cycle, and apoptosis. Applying a similar analysis to subjects with low DLCO, we identified a much broader repertoire of pro-inflammatory and immune-related pathways in HIV(+) patients relative to HIV(-) subjects, with up-regulation of multiple interleukin pathways, interferon signaling, and toll-like receptor signaling. We confirmed elevated circulating levels of IL-6 in HIV(+) patients with low DLCO relative to the other groups. Our findings reveal that PBLs of subjects with HIV infection and low DLCO are distinguished by widespread enrichment of immuno-inflammatory programs. Activation of these pathways may alter the biology of circulating leukocytes and play a role in the pathogenesis of HIV-associated gas exchange impairment. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Pathways Intern Report

NASA Technical Reports Server (NTRS)

Huggett, Daniel James

2017-01-01

The National Aeronautics and Space Administration (NASA) provides a formal training program for prospective employees titled, Pathways Intern Employment. The Pathways program targets graduate and undergraduate students who strive to become an active contributor to NASA's goal of space exploration. The report herein provides an account of Daniel Huggett's Pathways experience for the Spring and Summer 2017 semesters.

Intrauterine Growth Restriction Programs the Hypothalamus of Adult Male Rats: Integrated Analysis of Proteomic and Metabolomic Data.

PubMed

Pedroso, Amanda P; Souza, Adriana P; Dornellas, Ana P S; Oyama, Lila M; Nascimento, Cláudia M O; Santos, Gianni M S; Rosa, José C; Bertolla, Ricardo P; Klawitter, Jelena; Christians, Uwe; Tashima, Alexandre K; Ribeiro, Eliane B

2017-04-07

Programming of hypothalamic functions regulating energy homeostasis may play a role in intrauterine growth restriction (IUGR)-induced adulthood obesity. The present study investigated the effects of IUGR on the hypothalamus proteome and metabolome of adult rats submitted to 50% protein-energy restriction throughout pregnancy. Proteomic and metabolomic analyzes were performed by data independent acquisition mass spectrometry and multiple reaction monitoring, respectively. At age 4 months, the restricted rats showed elevated adiposity, increased leptin and signs of insulin resistance. 1356 proteins were identified and 348 quantified while 127 metabolites were quantified. The restricted hypothalamus showed down-regulation of 36 proteins and 5 metabolites and up-regulation of 21 proteins and 9 metabolites. Integrated pathway analysis of the proteomics and metabolomics data indicated impairment of hypothalamic glucose metabolism, increased flux through the hexosamine pathway, deregulation of TCA cycle and the respiratory chain, and alterations in glutathione metabolism. The data suggest IUGR modulation of energy metabolism and redox homeostasis in the hypothalamus of male adult rats. The present results indicated deleterious consequences of IUGR on hypothalamic pathways involved in pivotal physiological functions. These results provide guidance for future mechanistic studies assessing the role of intrauterine malnutrition in the development of metabolic diseases later in life.

Molecular genetic pathway analysis of Asian longhorned beetle

Treesearch

Evan Braswell

2011-01-01

The Asian longhorned beetle, Anoplophora glabripennis, is a destructive pest of hardwood trees. Historically, A. glabripennis was geographically restricted within China and Korea and not of economic importance. However, as a result of massive reforestation programs designed to combat desertification, the species emerged as a pest...

Pathways to Healing: Person-centered Responses to Complementary Services

PubMed Central

Bertrand, Sharon W.; Fermon, Barbara; Coleman, Julie Foley

2014-01-01

Objectives: This research study assessed perceived changes in quality-of-life measures related to participation in complementary services consisting of a variety of nontraditional therapies and/or programs at Pathways: A Health Crisis Resource Center in Minneapolis, Minnesota. Design: Survey data were used to assess perceived changes participants ascribed to their experience with complementary services at Pathways. Quantitative data analysis was conducted using participant demographics together with participant ratings of items from the “Self-Assessment of Change” (SAC) measure developed at the University of Arizona, Tucson. Qualitative data analysis was conducted on written responses to an additional survey question: “To what extent has your participation at Pathways influenced your healing process?” Setting/Location: Pathways offers a variety of services, including one-to-one sessions using nontraditional healing therapies, support groups, educational classes, and practice groups such as yoga and meditation for those facing serious health challenges. These services are offered free of charge through community financial support using volunteer practitioners. Participants: People (126) diagnosed with serious health challenges who used Pathways services from 2007 through 2009. Interventions: Participation in self-selected Pathways services. Measures: Responses to items on the SAC measure plus written responses to the question, “To what extent has your participation at Pathways influenced your healing process?” Results: Quantitative findings: Participants reported experiencing significant changes across all components of the SAC measure. Qualitative findings: Responses to the open-ended survey question identified perspectives on the culture of Pathways and a shift in participants' perceptions of well-being based on their experience of Pathways services. Conclusions: Participation in services provided by the Pathways organization improved perceptions of quality of life and well-being and led to more active involvement in the experience of a healing process. PMID:24753990

U.S. Army Base Closure Program, Final Decision Document, Cameron Station, Alexandria, Virginia

DTIC Science & Technology

1993-11-01

POTENTIAL CONCERN AT THE CAMERON STATION SITE TABLE 2-7 CHEMICALS CONTRIBUTING TO EXCESS CANCER RISK AT A PATHWAY LEVEL OF 1E-6 OR GREATER TABLE 2-8...CANCER RISK AT A PATHWAY LEVEL OF 1E-6 OR GREATER TABLE 2-8 SUMMARY OF DETAILED ANALYSIS OU-1 PCB TRANSFORMER SERVICE, STORAGE AND SPILL AREAS TABLE 2-9...Restrictions MCL Maximum Contaminant Level mg milligram 3001riOOh:bfsrod~acronyms.Ri November 18, 1993 v LIST OF ACRONYMS AND ABBREVIATIONS, CONTINUED O&M

5 CFR 315.713 - Conversion based on service in a Pathways Program under part 362 of this chapter.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Conversion based on service in a Pathways... in a Pathways Program under part 362 of this chapter. (a) Agency authority. An agency may convert to..., the following Pathways Participants: (1) An Intern who has satisfactorily completed the Internship...

5 CFR 315.713 - Conversion based on service in a Pathways Program under part 362 of this chapter.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Conversion based on service in a Pathways... in a Pathways Program under part 362 of this chapter. (a) Agency authority. An agency may convert to..., the following Pathways Participants: (1) An Intern who has satisfactorily completed the Internship...

Community College Pathways to the STEM Workforce: What Are They, Who Follows Them, and How?

ERIC Educational Resources Information Center

Van Noy, Michelle; Zeidenberg, Matthew

2017-01-01

This chapter describes community college STEM programs, including transfer-oriented science and engineering (S&E) programs and workforce-oriented technician programs, and the characteristics and educational pathways of the students who enroll in these programs.

Disrupting the Pipeline: Critical Analyses of Student Pathways through Postsecondary STEM Education

ERIC Educational Resources Information Center

Metcalf, Heather E.

2014-01-01

Critical mixed methods approaches allow us to reflect upon the ways in which we collect, measure, interpret, and analyze data, providing novel alternatives for quantitative analysis. For institutional researchers, whose work influences institutional policies, programs, and practices, the approach has the transformative ability to expose and create…

Traditional or Alternative--Finding New Teachers along Different Pathways

ERIC Educational Resources Information Center

Reese, Susan

2010-01-01

In 2009, the National Center for Policy Analysis (NCPA) brief, "Alternative Certification Programs: Meeting the Demand for Effective Teachers," noted that each state had its own requirements for alternative certification, and while some states and school districts have become more open to alternative certification, other states are very…

Roadmap for creating an accelerated three-year medical education program

PubMed Central

Leong, Shou Ling; Cangiarella, Joan; Fancher, Tonya; Dodson, Lisa; Grochowski, Colleen; Harnik, Vicky; Hustedde, Carol; Jones, Betsy; Kelly, Christina; Macerollo, Allison; Reboli, Annette C.; Rosenfeld, Melvin; Rundell, Kristen; Thompson, Tina; Whyte, Robert; Pusic, Martin

2017-01-01

ABSTRACT Medical education is undergoing significant transformation. Many medical schools are moving away from the concept of seat time to competency-based education and introducing flexibility in the curriculum that allows individualization. In response to rising student debt and the anticipated physician shortage, 35% of US medical schools are considering the development of accelerated pathways. The roadmap described in this paper is grounded in the experiences of the Consortium of Accelerated Medical Pathway Programs (CAMPP) members in the development, implementation, and evaluation of one type of accelerated pathway: the three-year MD program. Strategies include developing a mission that guides curricular development – meeting regulatory requirements, attaining institutional buy-in and resources necessary to support the programs, including student assessment and mentoring – and program evaluation. Accelerated programs offer opportunities to innovate and integrate a mission benefitting students and the public. Abbreviations: CAMPP: Consortium of accelerated medical pathway programs; GME: Graduate medical education; LCME: Liaison committee on medical education; NRMP: National residency matching program; UME: Undergraduate medical education PMID:29117817

Roadmap for creating an accelerated three-year medical education program.

PubMed

Leong, Shou Ling; Cangiarella, Joan; Fancher, Tonya; Dodson, Lisa; Grochowski, Colleen; Harnik, Vicky; Hustedde, Carol; Jones, Betsy; Kelly, Christina; Macerollo, Allison; Reboli, Annette C; Rosenfeld, Melvin; Rundell, Kristen; Thompson, Tina; Whyte, Robert; Pusic, Martin

2017-01-01

Medical education is undergoing significant transformation. Many medical schools are moving away from the concept of seat time to competency-based education and introducing flexibility in the curriculum that allows individualization. In response to rising student debt and the anticipated physician shortage, 35% of US medical schools are considering the development of accelerated pathways. The roadmap described in this paper is grounded in the experiences of the Consortium of Accelerated Medical Pathway Programs (CAMPP) members in the development, implementation, and evaluation of one type of accelerated pathway: the three-year MD program. Strategies include developing a mission that guides curricular development - meeting regulatory requirements, attaining institutional buy-in and resources necessary to support the programs, including student assessment and mentoring - and program evaluation. Accelerated programs offer opportunities to innovate and integrate a mission benefitting students and the public. CAMPP: Consortium of accelerated medical pathway programs; GME: Graduate medical education; LCME: Liaison committee on medical education; NRMP: National residency matching program; UME: Undergraduate medical education.

An editor for pathway drawing and data visualization in the Biopathways Workbench.

PubMed

Byrnes, Robert W; Cotter, Dawn; Maer, Andreia; Li, Joshua; Nadeau, David; Subramaniam, Shankar

2009-10-02

Pathway models serve as the basis for much of systems biology. They are often built using programs designed for the purpose. Constructing new models generally requires simultaneous access to experimental data of diverse types, to databases of well-characterized biological compounds and molecular intermediates, and to reference model pathways. However, few if any software applications provide all such capabilities within a single user interface. The Pathway Editor is a program written in the Java programming language that allows de-novo pathway creation and downloading of LIPID MAPS (Lipid Metabolites and Pathways Strategy) and KEGG lipid metabolic pathways, and of measured time-dependent changes to lipid components of metabolism. Accessed through Java Web Start, the program downloads pathways from the LIPID MAPS Pathway database (Pathway) as well as from the LIPID MAPS web server http://www.lipidmaps.org. Data arises from metabolomic (lipidomic), microarray, and protein array experiments performed by the LIPID MAPS consortium of laboratories and is arranged by experiment. Facility is provided to create, connect, and annotate nodes and processes on a drawing panel with reference to database objects and time course data. Node and interaction layout as well as data display may be configured in pathway diagrams as desired. Users may extend diagrams, and may also read and write data and non-lipidomic KEGG pathways to and from files. Pathway diagrams in XML format, containing database identifiers referencing specific compounds and experiments, can be saved to a local file for subsequent use. The program is built upon a library of classes, referred to as the Biopathways Workbench, that convert between different file formats and database objects. An example of this feature is provided in the form of read/construct/write access to models in SBML (Systems Biology Markup Language) contained in the local file system. Inclusion of access to multiple experimental data types and of pathway diagrams within a single interface, automatic updating through connectivity to an online database, and a focus on annotation, including reference to standardized lipid nomenclature as well as common lipid names, supports the view that the Pathway Editor represents a significant, practicable contribution to current pathway modeling tools.

The New Interventional Radiology Pathways: Options for Implementation.

PubMed

Recht, Michael; McKinney, J Mark; Alleman, Anthony M; Lowe, Lisa H; Spies, James B

2016-07-01

The new interventional radiology (IR) pathways have generated much discussion with articles and editorials pointing out perceived advantages and disadvantages compared to the current pathways. To briefly review, under the new system, there are three pathways to enter IR: the integrated (INT) IR residency, the independent (IND) IR residency, and the early specialization in interventional radiology (ESIR) program. The pathways have been designed to provide maximum flexibility to programs for implementation and to radiology residents for planning their subspecialty training. As a result, there are many potential permutations for these training programs, and understanding the variety of options can be a challenge at first. We offer three potential solutions, based on the different circumstances or requirements a department might face. The first two solutions involve integrated programs created through newly funded and converted diagnostic radiology slots, respectively. The third involves establishing ESIR and IND programs only. Hopefully, the examples provided will be useful for those currently planning for the future of their IR training programs. Copyright © 2016 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

A Quantitative Proteomic Analysis of Hemogenic Endothelium Reveals Differential Regulation of Hematopoiesis by SOX17

PubMed Central

Clarke, Raedun L.; Robitaille, Aaron M.; Moon, Randall T.; Keller, Gordon

2015-01-01

Summary The in vitro derivation of hematopoietic stem cells (HSCs) from pluripotent stem cells (PSCs) is complicated by the existence of multiple overlapping embryonic blood cell programs called primitive, erythromyeloid progenitor (EMP), and definitive. As HSCs are only generated during the definitive stage of hematopoiesis, deciphering the regulatory pathways that control the emergence of this program and identifying markers that distinguish it from the other programs are essential. To identify definitive specific pathways and marker sets, we used label-free proteomics to determine the proteome of embryo-derived and mouse embryonic stem cell-derived VE-CADHERIN+CD45− definitive hematopoietic progenitors. With this approach, we identified Stat1 as a marker that distinguishes the definitive erythroid lineage from the primitive- and EMP-derived lineages. Additionally, we provide evidence that the generation of the Stat1+ definitive lineage is dependent on Sox17. These findings establish an approach for monitoring the emergence of definitive hematopoiesis in the PSC differentiation cultures. PMID:26267830

A Spatio-Temporal Understanding of Growth Regulation during the Salt Stress Response in Arabidopsis[W

PubMed Central

Geng, Yu; Wu, Rui; Wee, Choon Wei; Xie, Fei; Wei, Xueliang; Chan, Penny Mei Yeen; Tham, Cliff; Duan, Lina; Dinneny, José R.

2013-01-01

Plant environmental responses involve dynamic changes in growth and signaling, yet little is understood as to how progress through these events is regulated. Here, we explored the phenotypic and transcriptional events involved in the acclimation of the Arabidopsis thaliana seedling root to a rapid change in salinity. Using live-imaging analysis, we show that growth is dynamically regulated with a period of quiescence followed by recovery then homeostasis. Through the use of a new high-resolution spatio-temporal transcriptional map, we identify the key hormone signaling pathways that regulate specific transcriptional programs, predict their spatial domain of action, and link the activity of these pathways to the regulation of specific phases of growth. We use tissue-specific approaches to suppress the abscisic acid (ABA) signaling pathway and demonstrate that ABA likely acts in select tissue layers to regulate spatially localized transcriptional programs and promote growth recovery. Finally, we show that salt also regulates many tissue-specific and time point–specific transcriptional responses that are expected to modify water transport, Casparian strip formation, and protein translation. Together, our data reveal a sophisticated assortment of regulatory programs acting together to coordinate spatially patterned biological changes involved in the immediate and long-term response to a stressful shift in environment. PMID:23898029

Response to Hyperosmotic Stress

PubMed Central

Saito, Haruo; Posas, Francesc

2012-01-01

An appropriate response and adaptation to hyperosmolarity, i.e., an external osmolarity that is higher than the physiological range, can be a matter of life or death for all cells. It is especially important for free-living organisms such as the yeast Saccharomyces cerevisiae. When exposed to hyperosmotic stress, the yeast initiates a complex adaptive program that includes temporary arrest of cell-cycle progression, adjustment of transcription and translation patterns, and the synthesis and retention of the compatible osmolyte glycerol. These adaptive responses are mostly governed by the high osmolarity glycerol (HOG) pathway, which is composed of membrane-associated osmosensors, an intracellular signaling pathway whose core is the Hog1 MAP kinase (MAPK) cascade, and cytoplasmic and nuclear effector functions. The entire pathway is conserved in diverse fungal species, while the Hog1 MAPK cascade is conserved even in higher eukaryotes including humans. This conservation is illustrated by the fact that the mammalian stress-responsive p38 MAPK can rescue the osmosensitivity of hog1Δ mutations in response to hyperosmotic challenge. As the HOG pathway is one of the best-understood eukaryotic signal transduction pathways, it is useful not only as a model for analysis of osmostress responses, but also as a model for mathematical analysis of signal transduction pathways. In this review, we have summarized the current understanding of both the upstream signaling mechanism and the downstream adaptive responses to hyperosmotic stress in yeast. PMID:23028184

5 CFR 213.3402 - Entire executive civil service; Pathways Programs.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Entire executive civil service; Pathways Programs. 213.3402 Section 213.3402 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS EXCEPTED SERVICE Excepted Schedules Schedule D § 213.3402 Entire executive civil service; Pathways...

5 CFR 213.3402 - Entire executive civil service; Pathways Programs.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Entire executive civil service; Pathways Programs. 213.3402 Section 213.3402 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS EXCEPTED SERVICE Excepted Schedules Schedule D § 213.3402 Entire executive civil service; Pathways...

Implementing Guided Pathways: Tips and Tools

ERIC Educational Resources Information Center

Bailey, Thomas; Jaggars, Shanna Smith; Jenkins, Davis

2015-01-01

A growing number of community colleges and four-year universities are seeking to improve student outcomes by redesigning academic programs and student support services following the guided pathways approach. These institutions are mapping out highly structured, educationally coherent program pathways for students to follow by starting with the end…

LWRS ATR Irradiation Testing Readiness Status

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kristine Barrett

2012-09-01

The Light Water Reactor Sustainability (LWRS) Program was established by the U.S. Department of Energy Office of Nuclear Energy (DOE-NE) to develop technologies and other solutions that can improve the reliability, sustain the safety, and extend the life of the current reactors. The LWRS Program is divided into four R&D Pathways: (1) Materials Aging and Degradation; (2) Advanced Light Water Reactor Nuclear Fuels; (3) Advanced Instrumentation, Information and Control Systems; and (4) Risk-Informed Safety Margin Characterization. This report describes an irradiation testing readiness analysis in preparation of LWRS experiments for irradiation testing at the Idaho National Laboratory (INL) Advanced Testmore » Reactor (ATR) under Pathway (2). The focus of the Advanced LWR Nuclear Fuels Pathway is to improve the scientific knowledge basis for understanding and predicting fundamental performance of advanced nuclear fuel and cladding in nuclear power plants during both nominal and off-nominal conditions. This information will be applied in the design and development of high-performance, high burn-up fuels with improved safety, cladding integrity, and improved nuclear fuel cycle economics« less

BioRuby: bioinformatics software for the Ruby programming language.

PubMed

Goto, Naohisa; Prins, Pjotr; Nakao, Mitsuteru; Bonnal, Raoul; Aerts, Jan; Katayama, Toshiaki

2010-10-15

The BioRuby software toolkit contains a comprehensive set of free development tools and libraries for bioinformatics and molecular biology, written in the Ruby programming language. BioRuby has components for sequence analysis, pathway analysis, protein modelling and phylogenetic analysis; it supports many widely used data formats and provides easy access to databases, external programs and public web services, including BLAST, KEGG, GenBank, MEDLINE and GO. BioRuby comes with a tutorial, documentation and an interactive environment, which can be used in the shell, and in the web browser. BioRuby is free and open source software, made available under the Ruby license. BioRuby runs on all platforms that support Ruby, including Linux, Mac OS X and Windows. And, with JRuby, BioRuby runs on the Java Virtual Machine. The source code is available from http://www.bioruby.org/. katayama@bioruby.org

Research on Youth Employment and Employability Development. Youth Employment Policies and Programs for the 1890s. Background Analysis for the Department of Labor Employment and Training Components of the Youth Act of 1980. Youth Knowledge Development Report 2.12.

ERIC Educational Resources Information Center

Taggart, Robert

Prepared as a basic background document for an interagency task force on youth employment, this report analyzes youth employment policies and programs for the 1980s. The main body of the report consists of three sections. Section 1, entitled "Policy Perspectives on the Youth Employment Problem," contains a discussion of pathways to…

Career Pathways in Indiana

ERIC Educational Resources Information Center

McCaskey, Steve; Johnson, Tricia

2010-01-01

The revisions to the Carl D. Perkins Career and Technical Education Act of 2006 require that career and technical education (CTE) programs provide students with a clear pathway from secondary to postsecondary education, and into high-wage, high-skill and high-demand careers. States nationwide are developing programs, called career pathways, to…

Federal Employees Health Benefits Program and Federal Employees Dental and Vision Insurance Program: eligibility for Pathway Programs participants. Interim final rule with request for comments.

PubMed

2014-01-06

The U.S. Office of Personnel Management (OPM) is issuing an interim final regulation to update the Federal Employees Health Benefits Program (FEHBP) and the Federal Employees Dental and Vision Insurance Program (FEDVIP) regulations to reflect updated election opportunities for participants in the Pathways Programs. The Pathways Programs were created by Executive Order (E.O.) 13562, signed by the President on December 27, 2010, and are designed to enable the Federal Government to compete effectively for students and recent graduates by improving its recruitment efforts through internships and similar programs with Federal agencies. This interim final rule furthers these recruitment and retention efforts by providing health insurance, as well as dental and vision benefits, to eligible program participants and their families.

Exploring Complex Engineering Learning over Time with Epistemic Network Analysis

ERIC Educational Resources Information Center

Svarovsky, Gina Navoa

2011-01-01

Recently, K-12 engineering education has received increased attention as a pathway to building stronger foundations in math and science and introducing young people to the profession. However, the National Academy of Engineering found that many K-12 engineering programs focus heavily on engineering design and science and math learning while…

The Pathway Program: How a Collaborative, Distributed Learning Program Showed Us the Future of Social Work Education

ERIC Educational Resources Information Center

Morris, Teresa; Mathias, Christine; Swartz, Ronnie; Jones, Celeste A; Klungtvet-Morano, Meka

2013-01-01

This paper describes a three-campus collaborative, distributed learning program that delivers social work education to remote rural and desert communities in California via distance learning modalities. This "Pathway Program" provides accredited social work education for a career ladder beginning with advising and developing an academic…

Mondelēz Hope Kitchen Program, China: a Program Impact Pathways (PIP) analysis.

PubMed

Li, Yanran; Yao, Xiaoxun; Gu, Lan

2014-09-01

Mondelēz Hope Kitchen is a community program initiated jointly in 2009 by Mondelēz International and the China Youth Development Foundation (CYDF). In response to the urgent needs of students, parents, and teachers at primary and middle schools in poverty-stricken rural areas of China, the program addresses the complex and intertwined issues of undernutrition and obesity. By funding both kitchen equipment and teacher training in health and nutrition, the Mondelēz Hope Kitchen Program improves the capacity of schools to supply healthy meals, helping students to access safe and nutritious foods and, ultimately, to improve their nutritional status and health. In 2011, the Mondelēz International Foundation awarded CYDF a grant to formally assess the impact of the original program design. The Mondelēz International Foundation encouraged CYDF and six other healthy lifestyles-focused community partners around the world to participate in this program evaluation workshop. The goals of this study were to describe the logic model of the Mondelēz Hope Kitchen Program, summarize a recent evaluation of the Mondelēz Hope Kitchen Program, and conduct a Program Impact Pathways (PIP) analysis to identify Critical Quality Control Points (CCPs) and a suite of impact indicators. The findings were presented at the Healthy Lifestyles Program Evaluation Workshop held in Granada, Spain, 13-14 September 2013, under the auspices of the Mondelēz International Foundation. The authors developed the program's PIP diagram based on deliberations involving the program managers and Director and consulting the "Hope Kitchen Management Rules "and "Hope Kitchen Inspection and Acceptance Report". The PIP analyses identified three CCPs: buy-in from schools, kitchen infrastructure, and changes in teachers' knowledge of nutrition after training. In addition, changes in children's knowledge of nutrition will be added to the core suite of impact evaluation indicators that also includes children's dietary behaviors. Participation in this program evaluation workshop provided the Mondelēz Hope Kitchen team with the tools to improve the program using a sound monitoring system.

Using program impact pathways to understand and improve program delivery, utilization, and potential for impact of Helen Keller International's homestead food production program in Cambodia.

PubMed

Olney, Deanna K; Vicheka, Sao; Kro, Meng; Chakriya, Chhom; Kroeun, Hou; Hoing, Ly Sok; Talukder, Aminzzaman; Quinn, Victoria; Iannotti, Lora; Becker, Elisabeth; Roopnaraine, Terry

2013-06-01

Evidence of the impact of homestead food production programs on nutrition outcomes such as anemia and growth is scant. In the absence of information on program impact pathways, it is difficult to understand why these programs, which have been successful in increasing intake of micronutrient-rich foods, have had such limited documented impact on nutrition outcomes. To conduct a process evaluation of Helen Keller International's (HKI's) homestead food production program in Cambodia to assess whether the program was operating as planned (in terms of design, delivery, and utilization) and to identify ways in which the program might need to be strengthened in order to increase its potential for impact. A program theory framework, which laid out the primary components along the hypothesized program impact pathways, was developed in collaboration with HKI and used to design the research. Semistructured interviews and focus group discussions with program beneficiaries (n = 36 and 12, respectively), nonbeneficiaries (n = 12), and program implementers (n = 17 and 2, respectively) and observations of key program delivery points, including health and nutrition training sessions (n = 6), village model farms (n = 6), and household gardens of beneficiaries (n = 36) and nonbeneficiaries (n = 12), were conducted to assess the delivery and utilization of the primary program components along the impact pathways. The majority of program components were being delivered and utilized as planned. However, challenges with some of the key components posited to improve outcomes such as anemia and growth were noted. Among these were a gap in the expected pathway from poultry production to increased intake of eggs and poultry meat, and some weaknesses in the delivery of the health and nutrition training sessions and related improvements in knowledge among the village health volunteers and beneficiaries. Although the program has been successful in delivering the majority of the program components as planned and has documented achievements in improving household production and intake of micronutrient-rich foods, it is likely that strengthening delivery and increasing utilization of some program components would increase its potential for nutritional impacts. This research has highlighted the importance of designing a program theory framework and assessing the components that lie along the primary program impact pathways to optimize program service delivery and utilization and, in turn, potential for impact.

Integrative analysis of environmental sequences using MEGAN4.

PubMed

Huson, Daniel H; Mitra, Suparna; Ruscheweyh, Hans-Joachim; Weber, Nico; Schuster, Stephan C

2011-09-01

A major challenge in the analysis of environmental sequences is data integration. The question is how to analyze different types of data in a unified approach, addressing both the taxonomic and functional aspects. To facilitate such analyses, we have substantially extended MEGAN, a widely used taxonomic analysis program. The new program, MEGAN4, provides an integrated approach to the taxonomic and functional analysis of metagenomic, metatranscriptomic, metaproteomic, and rRNA data. While taxonomic analysis is performed based on the NCBI taxonomy, functional analysis is performed using the SEED classification of subsystems and functional roles or the KEGG classification of pathways and enzymes. A number of examples illustrate how such analyses can be performed, and show that one can also import and compare classification results obtained using others' tools. MEGAN4 is freely available for academic purposes, and installers for all three major operating systems can be downloaded from www-ab.informatik.uni-tuebingen.de/software/megan.

5 CFR 362.401 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Definitions. 362.401 Section 362.401 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PATHWAYS PROGRAMS Presidential... Program-related activities of PMFs appointed in his or her agency. The agency Pathways Programs Officer...

5 CFR 362.401 - Definitions.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Definitions. 362.401 Section 362.401 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PATHWAYS PROGRAMS Presidential... Program-related activities of PMFs appointed in his or her agency. The agency Pathways Programs Officer...

Connecting people with cancer to physical activity and exercise programs: a pathway to create accessibility and engagement.

PubMed

Mina, D Santa; Sabiston, C M; Au, D; Fong, A J; Capozzi, L C; Langelier, D; Chasen, M; Chiarotto, J; Tomasone, J R; Jones, J M; Chang, E; Culos-Reed, S N

2018-04-01

Recent guidelines concerning exercise for people with cancer provide evidence-based direction for exercise assessment and prescription for clinicians and their patients. Although the guidelines promote exercise integration into clinical care for people with cancer, they do not support strategies for bridging the guidelines with related resources or programs. Exercise program accessibility remains a challenge in implementing the guidelines, but that challenge might be mitigated with conceptual frameworks ("pathways") that connect patients with exercise-related resources. In the present paper, we describe a pathway model and related resources that were developed by an expert panel of practitioners and researchers in the field of exercise and rehabilitation in oncology and that support the transition from health care practitioner to exercise programs or services for people with cancer. The model acknowledges the nuanced distinctions between research and exercise programming, as well as physical activity promotion, that, depending on the available programming in the local community or region, might influence practitioner use. Furthermore, the pathway identifies and provides examples of processes for referral, screening, medical clearance, and programming for people after a cancer diagnosis. The pathway supports the implementation of exercise guidelines and should serve as a model of enhanced care delivery to increase the health and well-being of people with cancer.

AACSD: An atomistic analyzer for crystal structure and defects

NASA Astrophysics Data System (ADS)

Liu, Z. R.; Zhang, R. F.

2018-01-01

We have developed an efficient command-line program named AACSD (Atomistic Analyzer for Crystal Structure and Defects) for the post-analysis of atomic configurations generated by various atomistic simulation codes. The program has implemented not only the traditional filter methods like the excess potential energy (EPE), the centrosymmetry parameter (CSP), the common neighbor analysis (CNA), the common neighborhood parameter (CNP), the bond angle analysis (BAA), and the neighbor distance analysis (NDA), but also the newly developed ones including the modified centrosymmetry parameter (m-CSP), the orientation imaging map (OIM) and the local crystallographic orientation (LCO). The newly proposed OIM and LCO methods have been extended for all three crystal structures including face centered cubic, body centered cubic and hexagonal close packed. More specially, AACSD can be easily used for the atomistic analysis of metallic nanocomposite with each phase to be analyzed independently, which provides a unique pathway to capture their dynamic evolution of various defects on the fly. In this paper, we provide not only a throughout overview on various theoretical methods and their implementation into AACSD program, but some critical evaluations, specific testing and applications, demonstrating the capability of the program on each functionality.

Comparative genome analysis of the Flavobacteriales bacterium strain UJ101, isolated from the gut of Atergatis reticulatus.

PubMed

Yang, Jhung-Ahn; Yang, Sung-Hyun; Kim, Junghee; Kwon, Kae Kyoung; Oh, Hyun-Myung

2017-07-01

Here we report the comparative genomic analysis of strain UJ101 with 15 strains from the family Flavobacteriaceae, using the CGExplorer program. Flavobacteriales bacterium strain UJ101 was isolated from a xanthid crab, Atergatis reticulatus, from the East Sea near Korea. The complete genome of strain UJ101 is a 3,074,209 bp, single, circular chromosome with 30.74% GC content. While the UJ101 genome contains a number of annotated genes for many metabolic pathways, such as the Embden-Meyerhof pathway, the pentose phosphate pathway, the tricarboxylic acid (TCA) cycle, and the glyoxylate cycle, genes for the Entner-Douddoroff pathway are not found in the UJ101 genome. Overall, carbon fixation processes were absent but nitrate reduction and denitrification pathways were conserved. The UJ101 genome was compared to genomes from other marine animals (three invertebrate strains and 5 fish strains) and other marine animal- derived genera. Notable results by genome comparisons showed that UJ101 is capable of denitrification and nitrate reduction, and that biotin-thiamine pathway participation varies among marine bacteria; fish-dwelling bacteria, freeliving bacteria, invertebrate-dwelling bacteria, and strain UJ101. Pan-genome analysis of the 16 strains in this study included 7,220 non-redundant genes that covered 62% of the pan-genome. A core-genome of 994 genes was present and consisted of 8% of the genes from the pan-genome. Strain UJ101 is a symbiotic hetero-organotroph isolated from xanthid crab, and is a metabolic generalist with nitrate-reducing abilities but without the ability to synthesize biotin. There is a general tendency of UJ101 and some fish pathogens to prefer thiamine-dependent glycolysis to gluconeogenesis. Biotin and thiamine auxotrophy or prototrophy may be used as important markers in microbial community studies.

Examining Provider Perspectives within Housing First and Traditional Programs

PubMed Central

Henwood, Benjamin F.; Shinn, Marybeth; Tsemberis, Sam; Padgett, Deborah K.

2014-01-01

Pathways’ Housing First represents a radical departure from traditional programs that serve individuals experiencing homelessness and co-occurring psychiatric and substance use disorders. This paper considered two federally funded comparison studies of Pathways’ Housing First and traditional programs to examine whether differences were reflected in the perspectives of frontline providers. Both quantitative analysis of responses to structured questions with close-ended responses and qualitative analysis of open-ended responses to semistructured questions showed that Pathways providers had greater endorsement of consumer values, lesser endorsement of systems values, and greater tolerance for abnormal behavior that did not result in harm to others than their counterparts in traditional programs. Comparing provider perspectives also revealed an “implementation paradox”; traditional providers were inhibited from engaging consumers in treatment and services without housing, whereas HF providers could focus on issues other than securing housing. As programs increasingly adopt a Housing First approach, implementation challenges remain due to an existing workforce habituated to traditional services. PMID:24659925

Origin and function of myofibroblasts in kidney fibrosis.

PubMed

LeBleu, Valerie S; Taduri, Gangadhar; O'Connell, Joyce; Teng, Yingqi; Cooke, Vesselina G; Woda, Craig; Sugimoto, Hikaru; Kalluri, Raghu

2013-08-01

Myofibroblasts are associated with organ fibrosis, but their precise origin and functional role remain unknown. We used multiple genetically engineered mice to track, fate map and ablate cells to determine the source and function of myofibroblasts in kidney fibrosis. Through this comprehensive analysis, we identified that the total pool of myofibroblasts is split, with 50% arising from local resident fibroblasts through proliferation. The nonproliferating myofibroblasts derive through differentiation from bone marrow (35%), the endothelial-to-mesenchymal transition program (10%) and the epithelial-to-mesenchymal transition program (5%). Specific deletion of Tgfbr2 in α-smooth muscle actin (αSMA)(+) cells revealed the importance of this pathway in the recruitment of myofibroblasts through differentiation. Using genetic mouse models and a fate-mapping strategy, we determined that vascular pericytes probably do not contribute to the emergence of myofibroblasts or fibrosis. Our data suggest that targeting diverse pathways is required to substantially inhibit the composite accumulation of myofibroblasts in kidney fibrosis.

Origin and Function of Myofibroblasts in Kidney Fibrosis

PubMed Central

LeBleu, Valerie S.; Taduri, Gangadhar; O’Connell, Joyce; Teng, Yingqi; Cooke, Vesselina G.; Woda, Craig; Sugimoto, Hikaru; Kalluri, Raghu

2014-01-01

Myofibroblasts are associated with organ fibrosis but their precise origin and functional role remain unknown. We employed multiple genetically engineered mice to track, fate-map and ablate cells to determine the source and function of myofibroblasts in kidney fibrosis. Such comprehensive analysis identified that the total pool of myofibroblasts is split, with 50% arising from local resident fibroblasts via proliferation. The non-proliferating myofibroblasts derive via differentiation from bone marrow (35%), endothelial to mesenchymal transition (EndMT) program (10%) and epithelial to mesenchymal transition (EMT) program (5%). Specific deletion of Tgfbr2 in αSMA+ cells revealed the importance of this pathway in recruitment of myofibroblasts via differentiation. Using genetic mouse models and fate-mapping strategy we determined that vascular pericytes likely do not contribute to the emergence of myofibroblasts or fibrosis. This study suggests that targeting diverse pathways is required to significantly inhibit composite accumulation of myofibroblasts in kidney fibrosis. PMID:23817022

Overview of the ToxCast Research Program: Applications to Predictive Toxicology and Chemical Prioritization

EPA Science Inventory

EPA’s ToxCast program, the NTP’s HTS initiative, and the NCGC’s Molecular Libraries Initiative into a collaborative research program focused on identifying toxicity pathways and developing in vitro assays to characterize the ability of chemicals to perturb those pathways. The go...

Comprehensive transcriptome analysis reveals distinct regulatory programs during vernalization and floral bud development of orchardgrass (Dactylis glomerata L.).

PubMed

Feng, Guangyan; Huang, Linkai; Li, Ji; Wang, Jianping; Xu, Lei; Pan, Ling; Zhao, Xinxin; Wang, Xia; Huang, Ting; Zhang, Xinquan

2017-11-22

Vernalization and the transition from vegetative to reproductive growth involve multiple pathways, vital for controlling floral organ formation and flowering time. However, little transcription information is available about the mechanisms behind environmental adaption and growth regulation. Here, we used high-throughput sequencing to analyze the comprehensive transcriptome of Dactylis glomerata L. during six different growth periods. During vernalization, 4689 differentially expressed genes (DEGs) significantly increased in abundance, while 3841 decreased. Furthermore, 12,967 DEGs were identified during booting stage and flowering stage, including 7750 up-regulated and 5219 down-regulated DEGs. Pathway analysis indicated that transcripts related to circadian rhythm, photoperiod, photosynthesis, flavonoid biosynthesis, starch, and sucrose metabolism changed significantly at different stages. Coexpression and weighted correlation network analysis (WGCNA) analysis linked different stages to transcriptional changes and provided evidence of inner relation modules associated with signal transduction, stress responses, cell division, and hormonal transport. We found enrichment in transcription factors (TFs) related to WRKY, NAC, AP2/EREBP, AUX/IAA, MADS-BOX, ABI3/VP1, bHLH, and the CCAAT family during vernalization and floral bud development. TFs expression patterns revealed intricate temporal variations, suggesting relatively separate regulatory programs of TF modules. Further study will unlock insights into the ability of the circadian rhythm and photoperiod to regulate vernalization and flowering time in perennial grass.

Career Pathways: Aligning Public Resources to Support Individual and Regional Economic Advancement in the Knowledge Economy

ERIC Educational Resources Information Center

Jenkins, Davis

2006-01-01

This paper describes career pathways, a framework or approach by which regions can better align publicly supported systems and programs to build a knowledge-economy workforce customized to the needs of local labor markets. A career pathway is a series of connected education and training programs and support services that enable individuals to…

The Pathway Program: A Collaboration between 3 Universities to Deliver a Social Work Distance Education (DL) Program to Underserved Areas of California

ERIC Educational Resources Information Center

Morris, Teresa; Jones, Celeste A.; Sehrawats, Seema

2016-01-01

This paper describes the development of a partnership between three campuses to develop a (DL) education program-serving employees of county and tribal Health and Human Service Departments in remote rural areas of California. Specifically, the program supports the development of a career pathway for students living in isolated regions of Northern…

Using Career Pathways to Guide Students through Programs of Study

ERIC Educational Resources Information Center

Bragg, Debra D.; Krismer, Marianne

2016-01-01

This chapter describes career pathways that evolved through a Trade Adjustment Assistance Community College and Career Training consortium grant designed to help students complete programs of study and enter health care careers.

Southern Pennsylvania's Industrial Pipeline: "Pathways" Program Helps Local Manufacturers Find Quality Workers

ERIC Educational Resources Information Center

Dixon, John; Girifalco, Tony; Yakabosky, Walt

2008-01-01

This article describes the Applied Engineering Technology (AET) Career and Educational Pathways Program, which helps local manufacturers find quality workers. The program features 32 high schools, three community colleges, and 10 four-year institutions offering an integrated regional system of applied engineering education. The goal is to enroll…

Pathways for Academic Career and Employment (PACE) Program: Fiscal Year 2014 Report

ERIC Educational Resources Information Center

Iowa Department of Education, 2014

2014-01-01

Community colleges across Iowa are working with business and industry through sector boards to develop training programs for jobs that have applicant shortages. The state Pathways for Academic Career and Employment (PACE) program enables community colleges to offer in-demand training, making education affordable for low income or unemployed…

Application of the critical pathway and integrated case teaching method to nursing orientation.

PubMed

Goodman, D

1997-01-01

Nursing staff development programs must be responsive to current changes in healthcare. New nursing staff must be prepared to manage continuous change and to function competently in clinical practice. The orientation pathway, based on a case management model, is used as a structure for the orientation phase of staff development. The integrated case is incorporated as a teaching strategy in orientation. The integrated case method is based on discussion and analysis of patient situations with emphasis on role modeling and integration of theory and skill. The orientation pathway and integrated case teaching method provide a useful framework for orientation of new staff. Educators, preceptors and orientees find the structure provided by the orientation pathway very useful. Orientation that is developed, implemented and evaluated based on a case management model with the use of an orientation pathway and incorporation of an integrated case teaching method provides a standardized structure for orientation of new staff. This approach is designed for the adult learner, promotes conceptual reasoning, and encourages the social and contextual basis for continued learning.

ΔNp63α promotes breast cancer cell motility through the selective activation of components of the epithelial-to-mesenchymal transition program

PubMed Central

Dang, Tuyen T.; Esparza, Matthew A.; Maine, Erin A.; Westcott, Jill M.; Pearson, Gray W.

2015-01-01

Cell identity signals influence the invasive capability of tumor cells, as demonstrated by the selection for programs of epithelial-to-mesenchymal transition (EMT) during malignant progression. Breast cancer cells retain canonical epithelial traits and invade collectively as cohesive groups of cells, but the signaling pathways critical to their invasive capabilities are still incompletely understood. Here we report that the transcription factor ΔNp63α drives the migration of basal-like breast cancer (BLBC) cells by inducing a hybrid mesenchymal/epithelial state. Through a combination of expression analysis and functional testing across multiple BLBC cell populations, we determined that ΔNp63α induces migration by elevating the expression of the EMT program components Slug and Axl. Interestingly, ΔNp63α also increased the expression of miR205, which can silence ZEB1/2 to prevent the loss of epithelial character caused by EMT induction. In clinical specimens, co-expression of various elements of the ΔNp63α pathway confirmed its implication in motility signaling in BLBC. We observed that activation of the ΔNp63α pathway occurred during the transition from noninvasive ductal carcinoma in situ to invasive breast cancer. Notably, in an orthotopic tumor model, Slug expression was sufficient to induce collective invasion of E-cadherin expressing BLBC cells. Together, our results illustrate how ΔNp63α can drive breast cancer cell invasion by selectively engaging pro-migratory components of the EMT program while, in parallel, still promoting the retention of epithelial character. PMID:26292362

t4 workshop report--lessons learned, challenges, and opportunities: the U.S. Endocrine Disruptor Screening Program.

PubMed

Juberg, Daland R; Borghoff, Susan J; Becker, Richard A; Casey, Warren; Hartung, Thomas; Holsapple, Michael P; Marty, M Sue; Mihaich, Ellen M; Van Der Kraak, Glen; Wade, Michael G; Willett, Catherine E; Andersen, Melvin E; Borgert, Christopher J; Coady, Katherine K; Dourson, Michael L; Fowle, John R; Gray, L Earl; Lamb, James C; Ortego, Lisa S; Schug, Thaddeus T; Toole, Colleen M; Zorrilla, Leah M; Kroner, Oliver L; Patterson, Jacqueline; Rinckel, Lori A; Jones, Brett R

2014-01-01

In 1996, the U.S. Congress passed the Food Quality Protection Act and amended the Safe Drinking Water Act (SDWA) requiring the U.S. Environmental Protection Agency (EPA) to implement a screening program to investigate the potential of pesticide chemicals and drinking water contaminants to adversely affect endocrine pathways. Consequently, the EPA launched the Endocrine Disruptor Screening Program (EDSP) to develop and validate estrogen, androgen, and thyroid (EAT) pathway screening assays and to produce standardized and harmonized test guidelines for regulatory application. In 2009, the EPA issued the first set of test orders for EDSP screening and a total of 50 pesticide actives and 2 inert ingredients have been evaluated using the battery of EDSP Tier 1 screening assays (i.e., five in vitro assays and six in vivo assays). To provide a framework for retrospective analysis of the data generated and to collect the insight of multiple stakeholders involved in the testing, more than 240 scientists from government, industry, academia, and non-profit organizations recently participated in a workshop titled "Lessons Learned, Challenges, and Opportunities: The U.S. Endocrine Disruptor Screening Program." The workshop focused on the science and experience to date and was organized into three focal sessions: (a) Performance of the EDSP Tier 1 Screening Assays for Estrogen, Androgen, and Thyroid Pathways; (b) Practical Applications of Tier 1 Data; and (c) Indications and Opportunities for Future Endocrine Testing. A number of key learnings and recommendations related to future EDSP evaluations emanated from the collective sessions.

The US EPA ToxCast Program: Moving from Data Generation ...

EPA Pesticide Factsheets

The U.S. EPA ToxCast program is entering its tenth year. Significant learning and progress have occurred towards collection, analysis, and interpretation of the data. The library of ~1,800 chemicals has been subject to ongoing characterization (e.g., identity, purity, stability) and is unique in its scope, structural diversity, and use scenarios making it ideally suited to investigate the underlying molecular mechanisms of toxicity. The ~700 high-throughput in vitro assay endpoints cover 327 genes and 293 pathways as well as other integrated cellular processes and responses. The integrated analysis of high-throughput screening data has shown that most environmental and industrial chemicals are very non-selective in the biological targets they perturb, while a small subset of chemicals are relatively selective for specific biological targets. The selectivity of a chemical informs interpretation of the screening results while also guiding future mode-of-action or adverse outcome pathway approaches. Coupling the high-throughput in vitro assays with medium-throughput pharmacokinetic assays and reverse dosimetry allows conversion of the potency estimates to an administered dose. Comparison of the administered dose to human exposure provides a risk-based context. The lessons learned from this effort will be presented and discussed towards application to chemical safety decision making and the future of the computational toxicology program at the U.S. EPA. SOT pr

Participant outcomes, perceptions, and experiences in the Internationally Educated Engineers Qualification Program, University of Manitoba: An exploratory study

NASA Astrophysics Data System (ADS)

Friesen, Marcia R.

Immigration, economic, and regulatory trends in Canada have challenged all professions to examine the processes by which immigrant professionals (international graduates) achieve professional licensure and meaningful employment in Canada. The Internationally Educated Engineers Qualification Program (IEEQ) at the University of Manitoba was developed as an alternate pathway to integrate international engineering graduates into the engineering profession in Manitoba. However, universities have the neither mandate nor the historical practice to facilitate licensure for immigrant professionals and, thus, the knowledge base for program development and delivery is predominantly experiential. This study was developed to address the void in the knowledge base and support the program's ongoing development by conducting a critical, exploratory, participant-oriented evaluation of the IEEQ Program for both formative and summative purposes. The research questions focussed on how the IEEQ participants perceived and described their experiences in the IEEQ Program, and how the participants' outcomes in the IEEQ Program compared to international engineering graduates pursuing other licensing pathways. The study was built on an interpretivist theoretical approach that supported a primarily qualitative methodology with selected quantitative elements. Data collection was grounded in focus group interviews, written questionnaires, student reports, and program records for data collection, with inductive data analysis for qualitative data and descriptive statistics for quantitative data. The findings yielded rich understandings of participants' experiences in the IEEQ Program, their outcomes relative to international engineering graduates (IEGs) pursuing other licensing pathways, and their perceptions of their own adaptation to the Canadian engineering profession. Specifically, the study suggests that foreign credentials recognition processes have tended to focus on the recognition and translation of human and/or institutional capital. Yet, access to and acquisition of social and cultural capital need to receive equal attention. Further, the study suggested that, while it is reasonable that language fluency is a pre-requisite for successful professional integration, there is also a fundamental link between language and cognition in that international engineering graduates are challenged to understand and assimilate information for which they may not possess useful language or the underlying mental constructs. The findings have implications for our collective understanding of the scope of the professional engineering body of knowledge.

5 CFR 362.110 - Transition.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Transition. 362.110 Section 362.110 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PATHWAYS PROGRAMS General... applicable Pathways Program and may revise that guidance as necessary. ...

5 CFR 362.110 - Transition.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Transition. 362.110 Section 362.110 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PATHWAYS PROGRAMS General... applicable Pathways Program and may revise that guidance as necessary. ...

A proposed model for the flowering signaling pathway of sugarcane under photoperiodic control.

PubMed

Coelho, C P; Costa Netto, A P; Colasanti, J; Chalfun-Júnior, A

2013-04-25

Molecular analysis of floral induction in Arabidopsis has identified several flowering time genes related to 4 response networks defined by the autonomous, gibberellin, photoperiod, and vernalization pathways. Although grass flowering processes include ancestral functions shared by both mono- and dicots, they have developed their own mechanisms to transmit floral induction signals. Despite its high production capacity and its important role in biofuel production, almost no information is available about the flowering process in sugarcane. We searched the Sugarcane Expressed Sequence Tags database to look for elements of the flowering signaling pathway under photoperiodic control. Sequences showing significant similarity to flowering time genes of other species were clustered, annotated, and analyzed for conserved domains. Multiple alignments comparing the sequences found in the sugarcane database and those from other species were performed and their phylogenetic relationship assessed using the MEGA 4.0 software. Electronic Northerns were run with Cluster and TreeView programs, allowing us to identify putative members of the photoperiod-controlled flowering pathway of sugarcane.

Pan-Cancer Analysis Links PARK2 to BCL-XL-Dependent Control of Apoptosis.

PubMed

Gong, Yongxing; Schumacher, Steven E; Wu, Wei H; Tang, Fanying; Beroukhim, Rameen; Chan, Timothy A

2017-02-01

Mutation of the PARK2 gene can promote both Parkinson's Disease and cancer, yet the underlying mechanisms of how PARK2 controls cellular physiology is incompletely understood. Here, we show that the PARK2 tumor suppressor controls the apoptotic regulator BCL-XL and modulates programmed cell death. Analysis of approximately 10,000 tumor genomes uncovers a striking pattern of mutual exclusivity between PARK2 genetic loss and amplification of BCL2L1, implicating these genes in a common pathway. PARK2 directly binds to and ubiquitinates BCL-XL. Inactivation of PARK2 leads to aberrant accumulation of BCL-XL both in vitro and in vivo, and cancer-specific mutations in PARK2 abrogate the ability of the ubiquitin E3 ligase to target BCL-XL for degradation. Furthermore, PARK2 modulates mitochondrial depolarization and apoptosis in a BCL-XL-dependent manner. Thus, like genes at the nodal points of growth arrest pathways such as p53, the PARK2 tumor suppressor is able to exert its antiproliferative effects by regulating both cell cycle progression and programmed cell death. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

LENS: web-based lens for enrichment and network studies of human proteins

PubMed Central

2015-01-01

Background Network analysis is a common approach for the study of genetic view of diseases and biological pathways. Typically, when a set of genes are identified to be of interest in relation to a disease, say through a genome wide association study (GWAS) or a different gene expression study, these genes are typically analyzed in the context of their protein-protein interaction (PPI) networks. Further analysis is carried out to compute the enrichment of known pathways and disease-associations in the network. Having tools for such analysis at the fingertips of biologists without the requirement for computer programming or curation of data would accelerate the characterization of genes of interest. Currently available tools do not integrate network and enrichment analysis and their visualizations, and most of them present results in formats not most conducive to human cognition. Results We developed the tool Lens for Enrichment and Network Studies of human proteins (LENS) that performs network and pathway and diseases enrichment analyses on genes of interest to users. The tool creates a visualization of the network, provides easy to read statistics on network connectivity, and displays Venn diagrams with statistical significance values of the network's association with drugs, diseases, pathways, and GWASs. We used the tool to analyze gene sets related to craniofacial development, autism, and schizophrenia. Conclusion LENS is a web-based tool that does not require and download or plugins to use. The tool is free and does not require login for use, and is available at http://severus.dbmi.pitt.edu/LENS. PMID:26680011

Pathways to the Geosciences through 2YR Community Colleges: A Strategic Recruitment Approach being used at Texas A&M University

NASA Astrophysics Data System (ADS)

Houser, C.; Nunez, J.; Miller, K. C.

2016-12-01

Department and college operating budgets are increasingly tide to enrollment and student credit hour production, which requires geoscience programs to develop strategic recruitment programs to ensure long-term stability, but also to increase institutional support. There is evidence that proactive high school recruitment programs are successful in engaging students in the geosciences, particularly those that involve the parents, but these programs typically have relatively low-yields and are relatively expensive. This means that increased enrollment of undergraduates in geosciences programs and participation by under-represented groups depends on innovative and effective recruitment and retention practices. The College of Geosciences at Texas A&M University has recently developed a Pathways to the Geosciences program that facilitates the transfer of students from 2-year institutions by providing direction to students interested in the geosciences from one of our partner institutions: Blinn College, Lee College, Houston Community College, San Jacinto College and Lone Star College. Each of the partner institutions offer disciplinary majors related to the geosciences, providing a gateway for students to discover and consider the geosciences starting in their freshman year. The guided pathways provide much needed direction without restricting options and allow students to see connections between courses and their career goals. In its first year, the Pathways to the Geosciences program has resulted in a significant increase in transfer applications and admissions from the partner institutions by 74% and 107% respectively. The program has been successful because we have been proactive in helping students at the partner institutions find the information they need to effectively transfer to a 4-year program. The increase in applications is evidence that students from our partner institutions are being intentional in following a pathway to a major in the College of Geosciences.

Automated Discovery of Functional Generality of Human Gene Expression Programs

PubMed Central

Gerber, Georg K; Dowell, Robin D; Jaakkola, Tommi S; Gifford, David K

2007-01-01

An important research problem in computational biology is the identification of expression programs, sets of co-expressed genes orchestrating normal or pathological processes, and the characterization of the functional breadth of these programs. The use of human expression data compendia for discovery of such programs presents several challenges including cellular inhomogeneity within samples, genetic and environmental variation across samples, uncertainty in the numbers of programs and sample populations, and temporal behavior. We developed GeneProgram, a new unsupervised computational framework based on Hierarchical Dirichlet Processes that addresses each of the above challenges. GeneProgram uses expression data to simultaneously organize tissues into groups and genes into overlapping programs with consistent temporal behavior, to produce maps of expression programs, which are sorted by generality scores that exploit the automatically learned groupings. Using synthetic and real gene expression data, we showed that GeneProgram outperformed several popular expression analysis methods. We applied GeneProgram to a compendium of 62 short time-series gene expression datasets exploring the responses of human cells to infectious agents and immune-modulating molecules. GeneProgram produced a map of 104 expression programs, a substantial number of which were significantly enriched for genes involved in key signaling pathways and/or bound by NF-κB transcription factors in genome-wide experiments. Further, GeneProgram discovered expression programs that appear to implicate surprising signaling pathways or receptor types in the response to infection, including Wnt signaling and neurotransmitter receptors. We believe the discovered map of expression programs involved in the response to infection will be useful for guiding future biological experiments; genes from programs with low generality scores might serve as new drug targets that exhibit minimal “cross-talk,” and genes from high generality programs may maintain common physiological responses that go awry in disease states. Further, our method is multipurpose, and can be applied readily to novel compendia of biological data. PMID:17696603

Applications of pathology-assisted image analysis of immunohistochemistry-based biomarkers in oncology.

PubMed

Shinde, V; Burke, K E; Chakravarty, A; Fleming, M; McDonald, A A; Berger, A; Ecsedy, J; Blakemore, S J; Tirrell, S M; Bowman, D

2014-01-01

Immunohistochemistry-based biomarkers are commonly used to understand target inhibition in key cancer pathways in preclinical models and clinical studies. Automated slide-scanning and advanced high-throughput image analysis software technologies have evolved into a routine methodology for quantitative analysis of immunohistochemistry-based biomarkers. Alongside the traditional pathology H-score based on physical slides, the pathology world is welcoming digital pathology and advanced quantitative image analysis, which have enabled tissue- and cellular-level analysis. An automated workflow was implemented that includes automated staining, slide-scanning, and image analysis methodologies to explore biomarkers involved in 2 cancer targets: Aurora A and NEDD8-activating enzyme (NAE). The 2 workflows highlight the evolution of our immunohistochemistry laboratory and the different needs and requirements of each biological assay. Skin biopsies obtained from MLN8237 (Aurora A inhibitor) phase 1 clinical trials were evaluated for mitotic and apoptotic index, while mitotic index and defects in chromosome alignment and spindles were assessed in tumor biopsies to demonstrate Aurora A inhibition. Additionally, in both preclinical xenograft models and an acute myeloid leukemia phase 1 trial of the NAE inhibitor MLN4924, development of a novel image algorithm enabled measurement of downstream pathway modulation upon NAE inhibition. In the highlighted studies, developing a biomarker strategy based on automated image analysis solutions enabled project teams to confirm target and pathway inhibition and understand downstream outcomes of target inhibition with increased throughput and quantitative accuracy. These case studies demonstrate a strategy that combines a pathologist's expertise with automated image analysis to support oncology drug discovery and development programs.

Opening the black box: the impact of an oncology management program consisting of level I pathways and an outbound nurse call system.

PubMed

Hoverman, J Russell; Klein, Ira; Harrison, Debra W; Hayes, Jad E; Garey, Jody S; Harrell, Robyn; Sipala, Maria; Houldin, Scott; Jameson, Melissa D; Abdullahpour, Mitra; McQueen, Jessica; Nelson, Greg; Verrilli, Diana K; Neubauer, Marcus

2014-01-01

The Innovent Oncology Program aims to improve the value of cancer care delivered to patients. McKesson Specialty Health and Texas Oncology (TXO) collaborated with Aetna to launch a pilot program. The study objectives were to evaluate the impact of Innovent on Level I Pathway compliance, implement the Patient Support Services program, and measure the rate and costs associated with chemotherapy-related emergency room (ER) visits and hospital admissions. This was a prospective, nonrandomized evaluation of patients enrolled in Innovent from June 1, 2010, through May 31, 2012. Data from the iKnowMed electronic health record, the McKesson Specialty Health financial data warehouse, and Aetna claims data warehouse were analyzed. A total of 221 patients were included and stratified according to disease and age groups; 76% of ordered regimens were on pathway; 24% were off pathway. Pathway adherence improved from TXO baseline adherence of 63%. Of the 221 patients, 81% enrolled in PSS. Within the breast, colorectal, and lung cancer groups, 14% and 24% of patients had an ER visit and in-patient admission (IPA; baseline) versus 10% and 18% in Innovent, respectively; average in-patient days decreased from 2.1 to 1.2 days, respectively. Total savings combined for the program was $506,481. Implementation of Innovent positively affected patient care in several ways: Fewer ER visits and IPAs occurred, in-patient days decreased, cancer-related use costs were reduced, and on-pathway adherence increased.

Farther, Faster: Six Promising Programs Show How Career Pathway Bridges Help Basic Skills Students Earn Credentials That Matter

ERIC Educational Resources Information Center

Strawn, Julie

2011-01-01

Students forced to complete a long sequence of remedial or English language classes before they can begin their postsecondary program rarely earn college certificates or degrees. This brief highlights six promising programs that show how career pathway bridges help lower-skilled students move farther and faster along college and career paths…

The Pathways Program: A Model for Increasing the Number of Teachers of Color

ERIC Educational Resources Information Center

Lau, Kam Fui; Dandy, Evelyn B.; Hoffman, Lorrie

2007-01-01

The Pathways to Teaching Careers Program was a national recruitment effort started in 1989 to bring teachers of color into the teaching profession. This effort was instrumental in forging the investment of some $50 million for a series of grants that included 26 programs in 66 colleges and universities, located in 43 cities in 26 states (the…

Connecting people with cancer to physical activity and exercise programs: a pathway to create accessibility and engagement

PubMed Central

Mina, D. Santa; Sabiston, C.M.; Au, D.; Fong, A.J.; Capozzi, L.C.; Langelier, D.; Chasen, M.; Chiarotto, J.; Tomasone, J.R.; Jones, J.M.; Chang, E.; Culos-Reed, S.N.

2018-01-01

Recent guidelines concerning exercise for people with cancer provide evidence-based direction for exercise assessment and prescription for clinicians and their patients. Although the guidelines promote exercise integration into clinical care for people with cancer, they do not support strategies for bridging the guidelines with related resources or programs. Exercise program accessibility remains a challenge in implementing the guidelines, but that challenge might be mitigated with conceptual frameworks (“pathways”) that connect patients with exercise-related resources. In the present paper, we describe a pathway model and related resources that were developed by an expert panel of practitioners and researchers in the field of exercise and rehabilitation in oncology and that support the transition from health care practitioner to exercise programs or services for people with cancer. The model acknowledges the nuanced distinctions between research and exercise programming, as well as physical activity promotion, that, depending on the available programming in the local community or region, might influence practitioner use. Furthermore, the pathway identifies and provides examples of processes for referral, screening, medical clearance, and programming for people after a cancer diagnosis. The pathway supports the implementation of exercise guidelines and should serve as a model of enhanced care delivery to increase the health and well-being of people with cancer. PMID:29719431

Pathways for Ethanol Dehydrogenation and Dehydration Catalyzed by Ceria (111) and (100) Surfaces

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beste, Ariana; Steven Overbury

2015-01-08

We have performed computations to better understand how surface structure affects selectivity in dehydrogenation and dehydration reactions of alcohols. Ethanol reactions on the (111) and (100) ceria surfaces were studied starting from the dominant surface species, ethoxy. We used DFT (PBE+U) to explore reaction pathways leading to ethylene and acetaldehyde and calculated estimates of rate constants employing transition state theory. To assess pathway contributions, we carried out kinetic analysis. Our results show that intermediate and transition state structures are stabilized on the (100) surface compared to the (111) surface. Formation of acetaldehyde over ethylene is kinetically and thermodynamically preferred onmore » both surfaces. Our results are consistent with temperature programmed surface reaction and steady-state experiments, where acetaldehyde was found as the main product and evidence was presented that ethylene formation at higher temperature originates from changes in adsorbate and surface structure.« less

Statistical and methodological issues in the evaluation of case management studies.

PubMed

Lesser, M L; Robertson, S; Kohn, N; Cooper, D J; Dlugacz, Y D

1996-01-01

For the past 3 years, the nursing case management team at North Shore University Hospital in Manhasset, NY, has been involved in a project to implement more than 50 clinical pathways, which provide a written "time line" for clinical events that should occur during a patient's hospital stay. A major objective of this project was to evaluate the efficacy of these pathways with respect to a number of important outcomes, such as length of stay, hospital costs, quality of patient care, and nursing and patient satisfaction. This article discusses several statistics-related issues in the design and evaluation of such case management studies. In particular, the role of a research approach in implementing and evaluating hospital programs, the choice of a comparison (control) group, the exclusion of selected patients from analysis, and the problems of equating pathways with diagnosis-related groups are addressed.

Mangiferin Has an Additive Effect on the Apoptotic Properties of Hesperidin in Cyclopia sp. Tea Extracts

PubMed Central

Bartoszewski, Rafal; Hering, Anna; Marszałł, Marcin; Stefanowicz Hajduk, Justyna; Bartoszewska, Sylwia; Kapoor, Niren; Kochan, Kinga; Ochocka, Renata

2014-01-01

A variety of biological pro-health activities have been reported for mangiferin and hesperidin, two major phenolic compounds of Honeybush (Cyclopia sp.) tea extracts. Given their increasing popularity, there is a need for understanding the mechanisms underlying the biological effects of these compounds. In this study, we used real-time cytotoxicity cellular analysis of the Cyclopia sp. extracts on HeLa cells and found that the higher hesperidin content in non-fermented "green" extracts correlated with their higher cytotoxicity compared to the fermented extracts. We also found that mangiferin had a modulatory effect on the apoptotic effects of hesperidin. Quantitative PCR analysis of hesperidin-induced changes in apoptotic gene expression profile indicated that two death receptor pathway members, TRADD and TRAMP, were up regulated. The results of this study suggest that hesperidin mediates apoptosis in HeLa cells through extrinsic pathway for programmed cell death. PMID:24633329

The master degree: A critical transition in STEM doctoral education

NASA Astrophysics Data System (ADS)

Lange, Sheila Edwards

The need to broaden participation in the nation's science, technology, engineering, and mathematics (STEM) undergraduate and graduate programs is currently a matter of national urgency. The small number of women and underrepresented minorities (URM) earning doctoral degrees in STEM is particularly troubling given significant increases in the number of students earning master's degrees since 1990. In the decade between 1990 and 2000, the total number of master's recipients increased by 42%. During this same time period, the number of women earning master's degrees increased by 56%, African Americans increased by 132%, American Indians by 101%, Hispanics by 146%, and Asian Americans by 117% (Syverson, 2003). Growth in underrepresented group education at the master's level raises questions about the relationship between master's and doctoral education. Secondary data analysis of the Survey of Earned Doctorates (SED) was used to examine institutional pathways to the doctorate in STEM disciplines and transitions from master's to doctoral programs by race and gender. While the study revealed no significant gender differences in pathways, compared to White and Asian American students, URM students take significantly different pathways to the doctorate. URM students are significantly more likely to earn the bachelor's, master's, and doctoral degrees at three different institutions. Their path is significantly more likely to include earning a master's degree en route to the doctorate. Further, URM students are more likely to experience transition between the master's and doctoral degrees, and the transitions are not limited to those who earn master's degrees at master's-only institutions. These findings suggest that earning a master's degree is more often a stepping stone to the doctorate for URM students. Master's degree programs, therefore, have the potential to be a valuable resource for policymakers and graduate programs seeking to increase the diversity of URM students earning doctorates in STEM.

5 CFR 362.104 - Agency requirements.

Code of Federal Regulations, 2013 CFR

2013-01-01

....104 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PATHWAYS... make any appointment under a Pathways authority, a Memorandum of Understanding (Pathways MOU) must be... use of Pathways Programs, to be re-executed no less frequently than every 2 years. (b) The Director...

5 CFR 362.104 - Agency requirements.

Code of Federal Regulations, 2014 CFR

2014-01-01

....104 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PATHWAYS... make any appointment under a Pathways authority, a Memorandum of Understanding (Pathways MOU) must be... use of Pathways Programs, to be re-executed no less frequently than every 2 years. (b) The Director...

IntPath--an integrated pathway gene relationship database for model organisms and important pathogens.

PubMed

Zhou, Hufeng; Jin, Jingjing; Zhang, Haojun; Yi, Bo; Wozniak, Michal; Wong, Limsoon

2012-01-01

Pathway data are important for understanding the relationship between genes, proteins and many other molecules in living organisms. Pathway gene relationships are crucial information for guidance, prediction, reference and assessment in biochemistry, computational biology, and medicine. Many well-established databases--e.g., KEGG, WikiPathways, and BioCyc--are dedicated to collecting pathway data for public access. However, the effectiveness of these databases is hindered by issues such as incompatible data formats, inconsistent molecular representations, inconsistent molecular relationship representations, inconsistent referrals to pathway names, and incomprehensive data from different databases. In this paper, we overcome these issues through extraction, normalization and integration of pathway data from several major public databases (KEGG, WikiPathways, BioCyc, etc). We build a database that not only hosts our integrated pathway gene relationship data for public access but also maintains the necessary updates in the long run. This public repository is named IntPath (Integrated Pathway gene relationship database for model organisms and important pathogens). Four organisms--S. cerevisiae, M. tuberculosis H37Rv, H. Sapiens and M. musculus--are included in this version (V2.0) of IntPath. IntPath uses the "full unification" approach to ensure no deletion and no introduced noise in this process. Therefore, IntPath contains much richer pathway-gene and pathway-gene pair relationships and much larger number of non-redundant genes and gene pairs than any of the single-source databases. The gene relationships of each gene (measured by average node degree) per pathway are significantly richer. The gene relationships in each pathway (measured by average number of gene pairs per pathway) are also considerably richer in the integrated pathways. Moderate manual curation are involved to get rid of errors and noises from source data (e.g., the gene ID errors in WikiPathways and relationship errors in KEGG). We turn complicated and incompatible xml data formats and inconsistent gene and gene relationship representations from different source databases into normalized and unified pathway-gene and pathway-gene pair relationships neatly recorded in simple tab-delimited text format and MySQL tables, which facilitates convenient automatic computation and large-scale referencing in many related studies. IntPath data can be downloaded in text format or MySQL dump. IntPath data can also be retrieved and analyzed conveniently through web service by local programs or through web interface by mouse clicks. Several useful analysis tools are also provided in IntPath. We have overcome in IntPath the issues of compatibility, consistency, and comprehensiveness that often hamper effective use of pathway databases. We have included four organisms in the current release of IntPath. Our methodology and programs described in this work can be easily applied to other organisms; and we will include more model organisms and important pathogens in future releases of IntPath. IntPath maintains regular updates and is freely available at http://compbio.ddns.comp.nus.edu.sg:8080/IntPath.

Research fellowship programs as a pathway for training independent clinical pharmacy scientists.

PubMed

Mueller, Eric W; Bishop, Jeffrey R; Kanaan, Abir O; Kiser, Tyree H; Phan, Hanna; Yang, Katherine Y

2015-03-01

The American College of Clinical Pharmacy (ACCP) Research Affairs Committee published a commentary in 2013 on training clinical pharmacy scientists in the context of changes in economic, professional, political, and research environments. The commentary centered on the opportunities for pharmacists in clinical/translational research including strategies for ACCP, colleges of pharmacy, and the profession to increase the number and impact of clinical pharmacy scientists. A postdoctoral fellowship is cited as a current training pathway, capable of producing independent and productive pharmacy researchers. However, a decline in the number of programs, decreased funding availability, and variability in fellowship program activities and research focus have brought into question the relevance of this research training pathway to meet demand and opportunities. In response to these points, this commentary examines the state of research fellowship training including the current ACCP research fellowship review process, the need for standardization of research fellowship programs, and strategies to strengthen and promote research fellowships as relevant researcher training pathways. © 2015 Pharmacotherapy Publications, Inc.

[The German program for disease management guidelines--implementation with pathways and quality management].

PubMed

Ollenschläger, Günter; Lelgemann, Monika; Kopp, Ina

2007-07-15

In Germany, physicians enrolled in disease management programs are legally obliged to follow evidence-based clinical practice guidelines. That is why a Program for National Disease Management Guidelines (German DM-CPG Program) was established in 2002 aiming at implementation of best-practice evidence-based recommendations for nationwide as well as regional disease management programs. Against this background the article reviews programs, methods and tools for implementing DM-CPGs via clinical pathways as well as regional guidelines for outpatient care. Special reference is given to the institutionalized program of adapting DM-CPGs for regional use by primary-care physicians in the State of Hesse.

Programmed cell death as a defence against infection

PubMed Central

Jorgensen, Ine; Rayamajhi, Manira; Miao, Edward A.

2017-01-01

Eukaryotic cells can die from physical trauma, resulting in necrosis. Alternately, they can die via programmed cell death upon stimulation of specific signalling pathways. Here we discuss the utility of four cell death pathways in innate immune defence against bacterial and viral infection: apoptosis, necroptosis, pyroptosis and NETosis. We describe the interactions that interweave different programmed cell death pathways, which create complex signalling networks that cross-guard each other in the evolutionary arms race with pathogens. Finally, we describe how the resulting cell corpses — apoptotic bodies, pore-induced intracellular traps (PITs) and neutrophil extracellular traps (NETs) — promote clearance of infection. PMID:28138137

An economic inquisition of water quality trading programs, with a case study of Jordan Lake, NC.

PubMed

Motallebi, Marzieh; Hoag, Dana L; Tasdighi, Ali; Arabi, Mazdak; Osmond, Deanna L

2017-05-15

A water quality trading (WQT) program was promulgated in North Carolina to address water quality issues related to nutrients in the highly urbanizing Jordan Lake Watershed. Although WQT programs are appealing in theory, the concept has not proved feasible in several attempts between point and nonpoint polluters in the United States. Many application hurdles that create wedges between success and failure have been evaluated in the literature. Most programs, however, face multiple hurdles; eliminating one may not clear a pathway to success. Therefore, we identify and evaluate the combined impact of four different wedges including baseline, transaction cost, trading ratio, and trading cost in the Jordan Lake Watershed program. Unfortunately, when applied to the Jordan Lake program, the analysis clearly shows that a traditional WQT program will not be feasible or address nutrient management needs in a meaningful way. The hurdles individually would be difficult to overcome, but together they appear to be unsurmountable. This analysis shows that there is enough information to pre-identify potential hurdles that could inform policy makers where, and how, the concept might work. It would have saved time, energy, and financial resources if North Carolina had done so before embarking to implement their program in the Jordan Lake Watershed. Copyright © 2017 Elsevier Ltd. All rights reserved.

Strong and healthy in Primary School Klasse2000 Program, Germany: a Program Impact Pathways (PIP) analysis.

PubMed

Dokter, Andrea; Horst, Brigitte

2014-09-01

Developing a Program Impact Pathways (PIP) diagram helps identify and clarify the key objectives, processes, activities, and evaluation indicators of school-based nutrition programs. The Mondelēz International Foundation has recently supported the development of PIP analyses for programs in seven countries around the world. The results were shared with other project organizers at a Healthy Lifestyles Program Evaluation Workshop held in Granada, Spain, 13-14 September 2013, under the auspices of the Mondelēz International Foundation. The objectives were to develop the PIP assessment of the Strong and Healthy in Primary School Klasse2000 Program in order to refine the primary, secondary, and tertiary objectives of the program; identify Critical Quality Control Points (CCPs); and identify core indicators of the program's impact on healthy lifestyles. The PIP report was developed based on detailed instructions provided prior to the workshop, taking into account the Klasse2000 Program evaluation reports. The following CCPs were identified: monitoring the qualifications and motivation of teaching staff (external health promoters and schoolteachers); assessing involvement of the students' environmental influences, including families, schools, and sponsors; and assessing the children's healthy lifestyle knowledge, attitudes, and behaviors before and after program exposure. The healthy lifestyle indicators identified were children's knowledge of healthy diets and health-enhancing physical activities; the availability of healthy breakfast and snacks; the frequency of consumption of fruits, vegetables, sweetened and unsweetened drinks,fast food, and sweets, as well as attitudes toward physical activity; and the frequency and extent of physical activity in school and during free time. Body mass index (BMI) was identified as the final outcome indicator. Developing a PIP report helped to focus the objectives of the program. Identifying CCPs helped draw attention to the processes linking critical program activities. As a result, plans for the upcoming school year include conducting a PIP-informed survey of participating parents and children to gauge their satisfaction with the program.

Expression of programmed cell death ligand 1 is associated with poor overall survival in patients with diffuse large B-cell lymphoma

PubMed Central

Kiyasu, Junichi; Miyoshi, Hiroaki; Hirata, Akie; Arakawa, Fumiko; Ichikawa, Ayako; Niino, Daisuke; Sugita, Yasuo; Yufu, Yuji; Choi, Ilseung; Abe, Yasunobu; Uike, Naokuni; Nagafuji, Koji; Okamura, Takashi; Akashi, Koichi; Takayanagi, Ryoichi; Shiratsuchi, Motoaki

2015-01-01

Programmed cell death ligand 1 (PD-L1) is expressed on both select diffuse large B-cell lymphoma (DLBCL) tumor cells and on tumor-infiltrating nonmalignant cells. The programmed cell death 1 (PD-1)/PD-L1 pathway inhibits host antitumor responses; however, little is known about how this pathway functions in the tumor microenvironment. The aim of this study was to determine the clinicopathological impact of PD-L1+ DLBCL. We performed PD-L1/PAX5 double immunostaining in 1253 DLBCL biopsy samples and established a new definition of PD-L1+ DLBCL. We also defined the criteria for microenvironmental PD-L1+ (mPD-L1+) DLBCL (ie, PD-L1– DLBCL in which PD-L1+ nonmalignant cells are abundant in the tumor microenvironment). Of the 273 patients whose clinical information was available, quantitative analysis of PD-1+ tumor-infiltrating lymphocytes (TILs) was performed. The prevalence rates of PD-L1+ and mPD-L1+ DLBCL were 11% and 15.3%, respectively. Both PD-L1+ and mPD-L1+ DLBCL were significantly associated with non–germinal center B-cell (GCB) type and Epstein-Barr virus positivity. The number of PD-1+ TILs was significantly higher in GCB-type tumors and lower in mPD-L1– and PD-L1+ DLBCL. Patients with PD-L1+ DLBCL had inferior overall survival (OS) compared with that in patients with PD-L1– DLBCL (P = .0009). In contrast, there was no significant difference in OS between mPD-L1+ and mPD-L1– DLBCL (P = .31). The expression of PD-L1 maintained prognostic value for OS in multivariate analysis (P = .0323). This is the first report describing the clinicopathological features and outcomes of PD-L1+ DLBCL. Immunotherapy targeting the PD-1/PD-L1 pathway should be considered in this distinct DLBCL subgroup. PMID:26239088

Pathways: a culturally appropriate obesity-prevention program for American Indian schoolchildren1–3

PubMed Central

Davis, Sally M; Going, Scott B; Helitzer, Deborah L; Teufel, Nicolette I; Snyder, Patricia; Gittelsohn, Joel; Metcalfe, Lauve; Arviso, Vivian; Evans, Marguerite; Smyth, Mary; Brice, Richard; Altaha, Jackie

2016-01-01

Pathways, a culturally appropriate obesity prevention study for third-, fourth-, and fifth-grade American Indian schoolchildren includes an intervention that promotes increased physical activity and healthful eating behaviors. The Pathways intervention, developed through a collaboration of universities and American Indian nations, schools, and families, focuses on individual, behavioral, and environmental factors and merges constructs from social learning theory with American Indian customs and practices. We describe the Pathways program developed during 3 y of feasibility testing in American Indian schools, with special emphasis on the activities developed for the third grade; review the theoretical and cultural underpinnings of the program; outline the construction process of the intervention; detail the curriculum and physical education components of the intervention; and summarize the formative assessment and the school food service and family components of the intervention. PMID:10195605

A linear programming computational framework integrates phosphor-proteomics and prior knowledge to predict drug efficacy.

PubMed

Ji, Zhiwei; Wang, Bing; Yan, Ke; Dong, Ligang; Meng, Guanmin; Shi, Lei

2017-12-21

In recent years, the integration of 'omics' technologies, high performance computation, and mathematical modeling of biological processes marks that the systems biology has started to fundamentally impact the way of approaching drug discovery. The LINCS public data warehouse provides detailed information about cell responses with various genetic and environmental stressors. It can be greatly helpful in developing new drugs and therapeutics, as well as improving the situations of lacking effective drugs, drug resistance and relapse in cancer therapies, etc. In this study, we developed a Ternary status based Integer Linear Programming (TILP) method to infer cell-specific signaling pathway network and predict compounds' treatment efficacy. The novelty of our study is that phosphor-proteomic data and prior knowledge are combined for modeling and optimizing the signaling network. To test the power of our approach, a generic pathway network was constructed for a human breast cancer cell line MCF7; and the TILP model was used to infer MCF7-specific pathways with a set of phosphor-proteomic data collected from ten representative small molecule chemical compounds (most of them were studied in breast cancer treatment). Cross-validation indicated that the MCF7-specific pathway network inferred by TILP were reliable predicting a compound's efficacy. Finally, we applied TILP to re-optimize the inferred cell-specific pathways and predict the outcomes of five small compounds (carmustine, doxorubicin, GW-8510, daunorubicin, and verapamil), which were rarely used in clinic for breast cancer. In the simulation, the proposed approach facilitates us to identify a compound's treatment efficacy qualitatively and quantitatively, and the cross validation analysis indicated good accuracy in predicting effects of five compounds. In summary, the TILP model is useful for discovering new drugs for clinic use, and also elucidating the potential mechanisms of a compound to targets.

[A prediction model for internet game addiction in adolescents: using a decision tree analysis].

PubMed

Kim, Ki Sook; Kim, Kyung Hee

2010-06-01

This study was designed to build a theoretical frame to provide practical help to prevent and manage adolescent internet game addiction by developing a prediction model through a comprehensive analysis of related factors. The participants were 1,318 students studying in elementary, middle, and high schools in Seoul and Gyeonggi Province, Korea. Collected data were analyzed using the SPSS program. Decision Tree Analysis using the Clementine program was applied to build an optimum and significant prediction model to predict internet game addiction related to various factors, especially parent related factors. From the data analyses, the prediction model for factors related to internet game addiction presented with 5 pathways. Causative factors included gender, type of school, siblings, economic status, religion, time spent alone, gaming place, payment to Internet café, frequency, duration, parent's ability to use internet, occupation (mother), trust (father), expectations regarding adolescent's study (mother), supervising (both parents), rearing attitude (both parents). The results suggest preventive and managerial nursing programs for specific groups by path. Use of this predictive model can expand the role of school nurses, not only in counseling addicted adolescents but also, in developing and carrying out programs with parents and approaching adolescents individually through databases and computer programming.

Adverse outcome pathway (AOP) development and evaluation ...

EPA Pesticide Factsheets

The Adverse Outcome Pathway provides a construct for assembling mechanistic information at different levels of biological organization in a form designed to support regulatory decision making. In particular, it frames the link between molecular and cellular events that can be measured in high throughput toxicity testing and the organism or population-level events that are commonly relevant in defining risk. Recognizing the importance of this emerging framework, the Organisation for Economic Co-operation and Development (OECD) launched a program to support the development, documentation and consideration of AOPs by the international community in 2012 (http://www.oecd.org/chemicalsafety/testing/adverse-outcome-pathways-molecular-screening-and-toxicogenomics.htm). In 2014, a handbook (https://aopkb.org/common/AOP_Handbook.pdf) was developed to guide users in the documentation and evaluation of AOPs and their entry into an official knowledgebase. The handbook draws on longstanding experience in consideration of mechanistic data (e.g., mode of action analysis) to inform risk assessment. To further assist users, a training program was developed by members of the OECD Extended Advisory Group to teach users the basic principles of AOP development and the best practices as outlined in the OECD AOP handbook. Training sessions began in early 2015, and this course will provide training for interested SOT scientists. Following this course, all participants will be familiar w

Risk analysis and bovine tuberculosis, a re-emerging zoonosis.

PubMed

Etter, Eric; Donado, Pilar; Jori, Ferran; Caron, Alexandre; Goutard, Flavie; Roger, François

2006-10-01

The widespread of immunodeficiency with AIDS, the consequence of poverty on sanitary protection and information at both individual and state levels lead control of tuberculosis (TB) to be one of the priorities of World Health Organization programs. The impact of bovine tuberculosis (BTB) on humans is poorly documented. However, BTB remains a major problem for livestock in developing countries particularly in Africa and wildlife is responsible for the failure of TB eradication programs. In Africa, the consumption of raw milk and raw meat, and the development of bushmeat consumption as a cheap source of proteins, represent one of the principal routes for human contaminations with BTB. The exploration of these different pathways using tools as participatory epidemiology allows the risk analysis of the impact of BTB on human health in Africa. This analysis represents a management support and decision tool in the study and the control of zoonotic BTB.

Communication of Career Pathways Through Associate Degree Program Web Sites: A Baseline Assessment.

PubMed

Becker, Ellen A; Vargas, Jenny

2018-05-08

The American Association for Respiratory Care sponsored a series of conferences that addressed the competency of the future workforce of respiratory therapists (RTs). Based upon the findings from those conferences, several initiatives emerged that support RTs earning a baccalaureate (or bachelor's) degree. The objective of this study was to identify the ways that associate degree programs communicate career pathways toward a baccalaureate degree through their Web sites. This cross-sectional observational study used a random sample of 100 of the 362 associate degree programs approved by the Commission on Accreditation for Respiratory Care. Data were collected from 3 specific categories: demographic data, baccalaureate completion information, and the Web page location for the program. The presence of statements related to any pathway toward a bachelor's degree, transfer credits, articulation agreements, and links for baccalaureate completion were recorded. The descriptive statistics in this study were reported as total numbers and percentages. Of the 100 programs in the random sample, only 89 were included in the study. Only 39 (44%) programs had links on their program Web site that had any content related to bachelor's degrees, 16 (18%) identified college transfer courses toward a bachelor's degree, and 26 (29%) programs included baccalaureate articulation agreements on their Web site. A minority of associate degree programs communicated career pathway information to their prospective and current students through program Web sites. An informative Web site would make the path more transparent for entry-level students to meet their future educational needs as their careers progress. Copyright © 2018 by Daedalus Enterprises.

New Pathways to Medical Education: Learning To Learn at Harvard Medical School.

ERIC Educational Resources Information Center

Tosteson, Daniel C., Ed.; And Others

This book details how Harvard Medical School (Massachusetts) overcame prevailing educational inertia and developed a curriculum and educational program consistent with preparing students to practice medicine in the 21st century. The New Pathway in General Medical Education program emphasizes both acquiring current knowledge and developing learning…

Career Pathways of Female High School Principals in the United States

ERIC Educational Resources Information Center

Walker, Tiffany Harris

2013-01-01

The purpose of this research was to identify the career pathways of female high school principals for women pursuing a career in educational leadership and female leaders interested in obtaining executive level leadership positions. Despite increased enrollment and of women in educational leadership programs, leadership certification programs, and…

Standardized input for Hanford environmental impact statements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Napier, B.A.

1981-05-01

Models and computer programs for simulating the environmental behavior of radionuclides in the environment and the resulting radiation dose to humans have been developed over the years by the Environmental Analysis Section staff, Ecological Sciences Department at the Pacific Northwest Laboratory (PNL). Methodologies have evolved for calculating raidation doses from many exposure pathways for any type of release mechanism. Depending on the situation or process being simulated, different sets of computer programs, assumptions, and modeling techniques must be used. This report is a compilation of recommended computer programs and necessary input information for use in calculating doses to members ofmore » the general public for environmental impact statements prepared for DOE activities to be conducted on or near the Hanford Reservation.« less

Identification of interactive gene networks: a novel approach in gene array profiling of myometrial events during guinea pig pregnancy.

PubMed

Mason, Clifford W; Swaan, Peter W; Weiner, Carl P

2006-06-01

The transition from myometrial quiescence to activation is poorly understood, and the analysis of array data is limited by the available data mining tools. We applied functional analysis and logical operations along regulatory gene networks to identify molecular processes and pathways underlying quiescence and activation. We analyzed some 18,400 transcripts and variants in guinea pig myometrium at stages corresponding to quiescence and activation, and compared them to the nonpregnant (control) counterpart using a functional mapping tool, MetaCore (GeneGo, St Joseph, MI) to identify novel gene networks composed of biological pathways during mid (MP) and late (LP) pregnancy. Genes altered during quiescence and or activation were identified following gene specific comparisons with myometrium from nonpregnant animals, and then linked to curated pathways and formulated networks. The MP and LP networks were subtracted from each other to identify unique genomic events during those periods. For example, changes 2-fold or greater in genes mediating protein biosynthesis, programmed cell death, microtubule polymerization, and microtubule based movement were noted during the transition to LP. We describe a novel approach combining microarrays and genetic data to identify networks associated with normal myometrial events. The resulting insights help identify potential biomarkers and permit future targeted investigations of these pathways or networks to confirm or refute their importance.

Quantitative Assays for RAS Pathway Proteins and Phosphorylation States

Cancer.gov

The NCI CPTAC program is applying its expertise in quantitative proteomics to develop assays for RAS pathway proteins. Targets include key phosphopeptides that should increase our understanding of how the RAS pathway is regulated.

A detailed pathway analysis of the chemical reaction system generating the Martian vertical ozone profile

NASA Astrophysics Data System (ADS)

Stock, Joachim W.; Blaszczak-Boxe, Christopher S.; Lehmann, Ralph; Grenfell, J. Lee; Patzer, A. Beate C.; Rauer, Heike; Yung, Yuk L.

2017-07-01

Atmospheric chemical composition is crucial in determining a planet's atmospheric structure, stability, and evolution. Attaining a quantitative understanding of the essential chemical mechanisms governing atmospheric composition is nontrivial due to complex interactions between chemical species. Trace species, for example, can participate in catalytic cycles - affecting the abundance of major and other trace gas species. Specifically, for Mars, such cycles dictate the abundance of its primary atmospheric constituent, carbon dioxide (CO2), but also for one of its trace gases, ozone (O3). The identification of chemical pathways/cycles by hand is extremely demanding; hence, the application of numerical methods, such as the Pathway Analysis Program (PAP), is crucial to analyze and quantitatively exemplify chemical reaction networks. Here, we carry out the first automated quantitative chemical pathway analysis of Mars' atmosphere with respect to O3. PAP was applied to JPL/Caltech's 1-D updated photochemical Mars model's output data. We determine all significant chemical pathways and their contribution to O3 production and consumption (up to 80 km) in order to investigate the mechanisms causing the characteristic shape of the O3 volume mixing ratio profile, i.e. a ground layer maximum and an ozone layer at ∼50 km. These pathways explain why an O3 layer is present, why it is located at that particular altitude and what the different processes forming the near-surface and middle atmosphere O3 maxima are. Furthermore, we show that the Martian atmosphere can be divided into two chemically distinct regions according to the O(3P):O3 ratio. In the lower region (below approximately 24 km altitude) O3 is the most abundant Ox (= O3 + O(3P)) species. In the upper region (above approximately 24 km altitude), where the O3 layer is located, O(3P) is the most abundant Ox species. Earlier results concerning the formation of O3 on Mars can now be explained with the help of chemical pathways leading to a better understanding of the vertical O3 profile.

Programs of Study as a State Policy Mandate: A Longitudinal Study of the South Carolina Personal Pathways to Success Initiative. Unabridged Final Technical Report (Years 1-5)

ERIC Educational Resources Information Center

Hammond, Cathy; Withington, Cairen; Sharp, Julia L.; Mobley, Catherine; Drew, Sam F.; Stringfield, Samuel C.; Stipanovic, Natalie; Swiger, Caroline M.; Daugherty, Lindsay; Griffith, Cathy

2014-01-01

This final report presents findings from data collection and analysis conducted during a five-year study by the National Dropout Prevention Center (NDPC) at Clemson University, in conjunction with colleagues from the National Research Center for Career and Technical Education (NRCCTE) at the University of Louisville. This project was one of three…

Proteome reference map and regulation network of neonatal rat cardiomyocyte

PubMed Central

Li, Zi-jian; Liu, Ning; Han, Qi-de; Zhang, You-yi

2011-01-01

Aim: To study and establish a proteome reference map and regulation network of neonatal rat cardiomyocyte. Methods: Cultured cardiomyocytes of neonatal rats were used. All proteins expressed in the cardiomyocytes were separated and identified by two-dimensional polyacrylamide gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). Biological networks and pathways of the neonatal rat cardiomyocytes were analyzed using the Ingenuity Pathway Analysis (IPA) program (www.ingenuity.com). A 2-DE database was made accessible on-line by Make2ddb package on a web server. Results: More than 1000 proteins were separated on 2D gels, and 148 proteins were identified. The identified proteins were used for the construction of an extensible markup language-based database. Biological networks and pathways were constructed to analyze the functions associate with cardiomyocyte proteins in the database. The 2-DE database of rat cardiomyocyte proteins can be accessed at http://2d.bjmu.edu.cn. Conclusion: A proteome reference map and regulation network of the neonatal rat cardiomyocytes have been established, which may serve as an international platform for storage, analysis and visualization of cardiomyocyte proteomic data. PMID:21841810

Differentiating pathway-specific from nonspecific effects in high-throughput toxicity data: A foundation for prioritizing adverse outcome pathway development

EPA Science Inventory

The U.S. Environmental Protection Agency’s ToxCast program has screened thousands of chemicals for biological activity, primarily using high-throughput in vitro bioassays. Adverse outcome pathways (AOPs) offer a means to link pathway-specific biological activities with potential ...

Proteomic analysis of the signaling pathway mediated by the heterotrimeric Gα protein Pga1 of Penicillium chrysogenum.

PubMed

Carrasco-Navarro, Ulises; Vera-Estrella, Rosario; Barkla, Bronwyn J; Zúñiga-León, Eduardo; Reyes-Vivas, Horacio; Fernández, Francisco J; Fierro, Francisco

2016-10-06

The heterotrimeric Gα protein Pga1-mediated signaling pathway regulates the entire developmental program in Penicillium chrysogenum, from spore germination to the formation of conidia. In addition it participates in the regulation of penicillin biosynthesis. We aimed to advance the understanding of this key signaling pathway using a proteomics approach, a powerful tool to identify effectors participating in signal transduction pathways. Penicillium chrysogenum mutants with different levels of activity of the Pga1-mediated signaling pathway were used to perform comparative proteomic analyses by 2D-DIGE and LC-MS/MS. Thirty proteins were identified which showed differences in abundance dependent on Pga1 activity level. By modifying the intracellular levels of cAMP we could establish cAMP-dependent and cAMP-independent pathways in Pga1-mediated signaling. Pga1 was shown to regulate abundance of enzymes in primary metabolic pathways involved in ATP, NADPH and cysteine biosynthesis, compounds that are needed for high levels of penicillin production. An in vivo phosphorylated protein containing a pleckstrin homology domain was identified; this protein is a candidate for signal transduction activity. Proteins with possible roles in purine metabolism, protein folding, stress response and morphogenesis were also identified whose abundance was regulated by Pga1 signaling. Thirty proteins whose abundance was regulated by the Pga1-mediated signaling pathway were identified. These proteins are involved in primary metabolism, stress response, development and signal transduction. A model describing the pathways through which Pga1 signaling regulates different cellular processes is proposed.

5 CFR 362.106 - Participant Agreement.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 362.106 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PATHWAYS... Agreement with each Pathways Participant that clearly identifies expectations, including but not limited to... permanent competitive service employment according to the requirements of the applicable Pathways Program. ...

5 CFR 362.105 - Filling positions.

Code of Federal Regulations, 2013 CFR

2013-01-01

....105 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PATHWAYS... an adequate number of permanent positions will be available to convert Pathways Participants who... outside its own workforce, it must provide OPM information concerning Pathways Programs job opportunities...

5 CFR 362.105 - Filling positions.

Code of Federal Regulations, 2014 CFR

2014-01-01

....105 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PATHWAYS... an adequate number of permanent positions will be available to convert Pathways Participants who... outside its own workforce, it must provide OPM information concerning Pathways Programs job opportunities...

78 FR 36041 - Regulation of Fuels and Fuel Additives: RFS Pathways II and Technical Amendments to the RFS 2...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-14

...In this Notice of Proposed Rulemaking, EPA is proposing amendments to three separate sets of regulations relating to fuels. First, EPA is proposing to amend certain of the renewable fuels standard (RFS2) program regulations. We believe these proposals will facilitate the introduction of new renewable fuels as well as improve implementation of the program. This proposal includes various changes related to biogas, including changes related to the revised compressed natural gas (CNG)/liquefied natural gas (LNG) pathway and amendments to various associated registration, recordkeeping, and reporting provisions. This proposed regulation includes the addition of new pathways for renewable diesel, renewable naphtha, and renewable electricity (used in electric vehicles) produced from landfill biogas. Adding these new pathways will enhance the ability of the biofuels industry to supply advanced biofuels, including cellulosic biofuels, which greatly reduce the greenhouse gas emissions (GHG) compared to the petroleum-based fuels they replace. It also addresses ``nameplate capacity'' issues for certain production facilities that do not claim exemption from the 20% greenhouse gas (GHG) reduction threshold. In this notice, EPA addresses issues related to crop residue and corn kernel fiber and proposes an approach to determining the volume of cellulosic RINs produced from various cellulosic feedstocks. We also include a lifecycle analysis of advanced butanol and discuss the potential to allow for commingling of compliant products at the retail facility level as long as the environmental performance of the fuels would not be detrimental. Several other amendments to the RFS2 program are included. Second, EPA is also proposing various changes to the E15 misfueling mitigation regulations (E15 MMR). Among the E15 changes proposed are technical corrections and amendments to sections dealing with labeling, E15 surveys, product transfer documents, and prohibited acts. We also propose to amend the definitions in order to address a concern about the rounding of test results for ethanol content violations. Lastly, EPA is proposing changes to the survey requirements associated with the ultra-low sulfur diesel (ULSD) program.

BioLayout(Java): versatile network visualisation of structural and functional relationships.

PubMed

Goldovsky, Leon; Cases, Ildefonso; Enright, Anton J; Ouzounis, Christos A

2005-01-01

Visualisation of biological networks is becoming a common task for the analysis of high-throughput data. These networks correspond to a wide variety of biological relationships, such as sequence similarity, metabolic pathways, gene regulatory cascades and protein interactions. We present a general approach for the representation and analysis of networks of variable type, size and complexity. The application is based on the original BioLayout program (C-language implementation of the Fruchterman-Rheingold layout algorithm), entirely re-written in Java to guarantee portability across platforms. BioLayout(Java) provides broader functionality, various analysis techniques, extensions for better visualisation and a new user interface. Examples of analysis of biological networks using BioLayout(Java) are presented.

Programmed Effects in Neurobehavior and Antioxidative Physiology in Zebrafish Embryonically Exposed to Cadmium: Observations and Hypothesized Adverse Outcome Pathway Framework.

PubMed

Ruiter, Sander; Sippel, Josefine; Bouwmeester, Manon C; Lommelaars, Tobias; Beekhof, Piet; Hodemaekers, Hennie M; Bakker, Frank; van den Brandhof, Evert-Jan; Pennings, Jeroen L A; van der Ven, Leo T M

2016-11-02

Non-communicable diseases (NCDs) are a major cause of premature mortality. Recent studies show that predispositions for NCDs may arise from early-life exposure to low concentrations of environmental contaminants. This developmental origins of health and disease (DOHaD) paradigm suggests that programming of an embryo can be disrupted, changing the homeostatic set point of biological functions. Epigenetic alterations are a possible underlying mechanism. Here, we investigated the DOHaD paradigm by exposing zebrafish to subtoxic concentrations of the ubiquitous contaminant cadmium during embryogenesis, followed by growth under normal conditions. Prolonged behavioral responses to physical stress and altered antioxidative physiology were observed approximately ten weeks after termination of embryonal exposure, at concentrations that were 50-3200-fold below the direct embryotoxic concentration, and interpreted as altered developmental programming. Literature was explored for possible mechanistic pathways that link embryonic subtoxic cadmium to the observed apical phenotypes, more specifically, the probability of molecular mechanisms induced by cadmium exposure leading to altered DNA methylation and subsequently to the observed apical phenotypes. This was done using the adverse outcome pathway model framework, and assessing key event relationship plausibility by tailored Bradford-Hill analysis. Thus, cadmium interaction with thiols appeared to be the major contributor to late-life effects. Cadmium-thiol interactions may lead to depletion of the methyl donor S -adenosyl-methionine, resulting in methylome alterations, and may, additionally, result in oxidative stress, which may lead to DNA oxidation, and subsequently altered DNA methyltransferase activity. In this way, DNA methylation may be affected at a critical developmental stage, causing the observed apical phenotypes.

Shared molecular networks in orofacial and neural tube development.

PubMed

Kousa, Youssef A; Mansour, Tamer A; Seada, Haitham; Matoo, Samaneh; Schutte, Brian C

2017-01-30

Single genetic variants can affect multiple tissues during development. Thus it is possible that disruption of shared gene regulatory networks might underlie syndromic presentations. In this study, we explore this idea through examination of two critical developmental programs that control orofacial and neural tube development and identify shared regulatory factors and networks. Identification of these networks has the potential to yield additional candidate genes for poorly understood developmental disorders and assist in modeling and perhaps managing risk factors to prevent morbidly and mortality. We reviewed the literature to identify genes common between orofacial and neural tube defects and development. We then conducted a bioinformatic analysis to identify shared molecular targets and pathways in the development of these tissues. Finally, we examine publicly available RNA-Seq data to identify which of these genes are expressed in both tissues during development. We identify common regulatory factors in orofacial and neural tube development. Pathway enrichment analysis shows that folate, cancer and hedgehog signaling pathways are shared in neural tube and orofacial development. Developing neural tissues differentially express mouse exencephaly and cleft palate genes, whereas developing orofacial tissues were enriched for both clefting and neural tube defect genes. These data suggest that key developmental factors and pathways are shared between orofacial and neural tube defects. We conclude that it might be most beneficial to focus on common regulatory factors and pathways to better understand pathology and develop preventative measures for these birth defects. Birth Defects Research 109:169-179, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Pathway enrichment analysis approach based on topological structure and updated annotation of pathway.

PubMed

Yang, Qian; Wang, Shuyuan; Dai, Enyu; Zhou, Shunheng; Liu, Dianming; Liu, Haizhou; Meng, Qianqian; Jiang, Bin; Jiang, Wei

2017-08-16

Pathway enrichment analysis has been widely used to identify cancer risk pathways, and contributes to elucidating the mechanism of tumorigenesis. However, most of the existing approaches use the outdated pathway information and neglect the complex gene interactions in pathway. Here, we first reviewed the existing widely used pathway enrichment analysis approaches briefly, and then, we proposed a novel topology-based pathway enrichment analysis (TPEA) method, which integrated topological properties and global upstream/downstream positions of genes in pathways. We compared TPEA with four widely used pathway enrichment analysis tools, including database for annotation, visualization and integrated discovery (DAVID), gene set enrichment analysis (GSEA), centrality-based pathway enrichment (CePa) and signaling pathway impact analysis (SPIA), through analyzing six gene expression profiles of three tumor types (colorectal cancer, thyroid cancer and endometrial cancer). As a result, we identified several well-known cancer risk pathways that could not be obtained by the existing tools, and the results of TPEA were more stable than that of the other tools in analyzing different data sets of the same cancer. Ultimately, we developed an R package to implement TPEA, which could online update KEGG pathway information and is available at the Comprehensive R Archive Network (CRAN): https://cran.r-project.org/web/packages/TPEA/. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

78 FR 65715 - Request for Comments on the Program Solicitation for the Advanced Technological Education Program...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-01

... academic institutions and industry to promote improvement in the education of science and engineering...; professional development of college faculty and secondary school teachers; career pathways to two-year colleges from secondary schools and from two-year colleges to four-year institutions; career pathways that lead...

More than a Network: Building Professional Communities for Educational Improvement

ERIC Educational Resources Information Center

Dolle, Jonathan R.; Gomez, Louis M.; Russell, Jennifer Lin; Bryk, Anthony S.

2013-01-01

This chapter is a case study of the Carnegie Foundation for the Advancement of Teaching's Pathways [TM] program. The goal of the Statway [Registered Trademark] and Quantway [Registered Trademark] pathways is to improve the success rate of community college students who place into developmental mathematics. What makes these programs unique is…

"OnTrack" to University: Understanding Mechanisms of Student Retention in an Australian Pre-University Enabling Program

ERIC Educational Resources Information Center

Lisciandro, Joanne G.; Gibbs, Gael

2016-01-01

University-based enabling programs have become an important pathway to university for non-traditional students. There is increasing interest in understanding the mechanisms that facilitate retention and success of enabling pathway students, with the aim of developing effective strategies for maximising opportunities for university access and…

Creating Opportunity for All: Building Pathways from Continuing Education to Credit Programs

ERIC Educational Resources Information Center

Price, Derek V.; Sedlak, Wendy

2018-01-01

Community college students start college with goals including transferring to earn a bachelor's degree and gaining the skills and credentials that have immediate labor market value. These goals are not mutually exclusive. Students deserve access to clear pathways, whether they enroll in short-term education and training programs or in college…

76 FR 11285 - Notice of Funding Opportunity and Solicitation for Grant Applications (SGA) for the Career...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-01

... Solicitation for Grant Applications (SGA) for the Career Pathways Innovation Fund Grants Program AGENCY... in grant funds authorized by Workforce Investment Act of 1998, Public Law 105-220 to develop and... four goals, including strengthening the role of the public workforce system in career pathway programs...

Social Network and Content Analysis of the North American Carbon Program as a Scientific Community of Practice

NASA Technical Reports Server (NTRS)

Brown, Molly E.; Ihli, Monica; Hendrick, Oscar; Delgado-Arias, Sabrina; Escobar, Vanessa M.; Griffith, Peter

2015-01-01

The North American Carbon Program (NACP) was formed to further the scientific understanding of sources, sinks, and stocks of carbon in Earth's environment. Carbon cycle science integrates multidisciplinary research, providing decision-support information for managing climate and carbon-related change across multiple sectors of society. This investigation uses the conceptual framework of com-munities of practice (CoP) to explore the role that the NACP has played in connecting researchers into a carbon cycle knowledge network, and in enabling them to conduct physical science that includes ideas from social science. A CoP describes the communities formed when people consistently engage in shared communication and activities toward a common passion or learning goal. We apply the CoP model by using keyword analysis of abstracts from scientific publications to analyze the research outputs of the NACP in terms of its knowledge domain. We also construct a co-authorship network from the publications of core NACP members, describe the structure and social pathways within the community. Results of the content analysis indicate that the NACP community of practice has substantially expanded its research on human and social impacts on the carbon cycle, contributing to a better understanding of how human and physical processes interact with one another. Results of the co-authorship social network analysis demonstrate that the NACP has formed a tightly connected community with many social pathways through which knowledge may flow, and that it has also expanded its network of institutions involved in carbon cycle research over the past seven years.

Pathway cross-talk network analysis identifies critical pathways in neonatal sepsis.

PubMed

Meng, Yu-Xiu; Liu, Quan-Hong; Chen, Deng-Hong; Meng, Ying

2017-06-01

Despite advances in neonatal care, sepsis remains a major cause of morbidity and mortality in neonates worldwide. Pathway cross-talk analysis might contribute to the inference of the driving forces in bacterial sepsis and facilitate a better understanding of underlying pathogenesis of neonatal sepsis. This study aimed to explore the critical pathways associated with the progression of neonatal sepsis by the pathway cross-talk analysis. By integrating neonatal transcriptome data with known pathway data and protein-protein interaction data, we systematically uncovered the disease pathway cross-talks and constructed a disease pathway cross-talk network for neonatal sepsis. Then, attract method was employed to explore the dysregulated pathways associated with neonatal sepsis. To determine the critical pathways in neonatal sepsis, rank product (RP) algorithm, centrality analysis and impact factor (IF) were introduced sequentially, which synthetically considered the differential expression of genes and pathways, pathways cross-talks and pathway parameters in the network. The dysregulated pathways with the highest IF values as well as RP<0.01 were defined as critical pathways in neonatal sepsis. By integrating three kinds of data, only 6919 common genes were included to perform the pathway cross-talk analysis. By statistic analysis, a total of 1249 significant pathway cross-talks were selected to construct the pathway cross-talk network. Moreover, 47 dys-regulated pathways were identified via attract method, 20 pathways were identified under RP<0.01, and the top 10 pathways with the highest IF were also screened from the pathway cross-talk network. Among them, we selected 8 common pathways, i.e. critical pathways. In this study, we systematically tracked 8 critical pathways involved in neonatal sepsis by integrating attract method and pathway cross-talk network. These pathways might be responsible for the host response in infection, and of great value for advancing diagnosis and therapy of neonatal sepsis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Application of Adverse Outcome Pathways to U.S. EPA’s Endocrine Disruptor Screening Program

PubMed Central

Noyes, Pamela D.; Casey, Warren M.; Dix, David J.

2017-01-01

Background: The U.S. EPA’s Endocrine Disruptor Screening Program (EDSP) screens and tests environmental chemicals for potential effects in estrogen, androgen, and thyroid hormone pathways, and it is one of the only regulatory programs designed around chemical mode of action. Objectives: This review describes the EDSP’s use of adverse outcome pathway (AOP) and toxicity pathway frameworks to organize and integrate diverse biological data for evaluating the endocrine activity of chemicals. Using these frameworks helps to establish biologically plausible links between endocrine mechanisms and apical responses when those end points are not measured in the same assay. Results: Pathway frameworks can facilitate a weight of evidence determination of a chemical’s potential endocrine activity, identify data gaps, aid study design, direct assay development, and guide testing strategies. Pathway frameworks also can be used to evaluate the performance of computational approaches as alternatives for low-throughput and animal-based assays and predict downstream key events. In cases where computational methods can be validated based on performance, they may be considered as alternatives to specific assays or end points. Conclusions: A variety of biological systems affect apical end points used in regulatory risk assessments, and without mechanistic data, an endocrine mode of action cannot be determined. Because the EDSP was designed to consider mode of action, toxicity pathway and AOP concepts are a natural fit. Pathway frameworks have diverse applications to endocrine screening and testing. An estrogen pathway example is presented, and similar approaches are being used to evaluate alternative methods and develop predictive models for androgen and thyroid pathways. https://doi.org/10.1289/EHP1304 PMID:28934726

Prioritizing biological pathways by recognizing context in time-series gene expression data.

PubMed

Lee, Jusang; Jo, Kyuri; Lee, Sunwon; Kang, Jaewoo; Kim, Sun

2016-12-23

The primary goal of pathway analysis using transcriptome data is to find significantly perturbed pathways. However, pathway analysis is not always successful in identifying pathways that are truly relevant to the context under study. A major reason for this difficulty is that a single gene is involved in multiple pathways. In the KEGG pathway database, there are 146 genes, each of which is involved in more than 20 pathways. Thus activation of even a single gene will result in activation of many pathways. This complex relationship often makes the pathway analysis very difficult. While we need much more powerful pathway analysis methods, a readily available alternative way is to incorporate the literature information. In this study, we propose a novel approach for prioritizing pathways by combining results from both pathway analysis tools and literature information. The basic idea is as follows. Whenever there are enough articles that provide evidence on which pathways are relevant to the context, we can be assured that the pathways are indeed related to the context, which is termed as relevance in this paper. However, if there are few or no articles reported, then we should rely on the results from the pathway analysis tools, which is termed as significance in this paper. We realized this concept as an algorithm by introducing Context Score and Impact Score and then combining the two into a single score. Our method ranked truly relevant pathways significantly higher than existing pathway analysis tools in experiments with two data sets. Our novel framework was implemented as ContextTRAP by utilizing two existing tools, TRAP and BEST. ContextTRAP will be a useful tool for the pathway based analysis of gene expression data since the user can specify the context of the biological experiment in a set of keywords. The web version of ContextTRAP is available at http://biohealth.snu.ac.kr/software/contextTRAP .

IntPath--an integrated pathway gene relationship database for model organisms and important pathogens

PubMed Central

2012-01-01

Background Pathway data are important for understanding the relationship between genes, proteins and many other molecules in living organisms. Pathway gene relationships are crucial information for guidance, prediction, reference and assessment in biochemistry, computational biology, and medicine. Many well-established databases--e.g., KEGG, WikiPathways, and BioCyc--are dedicated to collecting pathway data for public access. However, the effectiveness of these databases is hindered by issues such as incompatible data formats, inconsistent molecular representations, inconsistent molecular relationship representations, inconsistent referrals to pathway names, and incomprehensive data from different databases. Results In this paper, we overcome these issues through extraction, normalization and integration of pathway data from several major public databases (KEGG, WikiPathways, BioCyc, etc). We build a database that not only hosts our integrated pathway gene relationship data for public access but also maintains the necessary updates in the long run. This public repository is named IntPath (Integrated Pathway gene relationship database for model organisms and important pathogens). Four organisms--S. cerevisiae, M. tuberculosis H37Rv, H. Sapiens and M. musculus--are included in this version (V2.0) of IntPath. IntPath uses the "full unification" approach to ensure no deletion and no introduced noise in this process. Therefore, IntPath contains much richer pathway-gene and pathway-gene pair relationships and much larger number of non-redundant genes and gene pairs than any of the single-source databases. The gene relationships of each gene (measured by average node degree) per pathway are significantly richer. The gene relationships in each pathway (measured by average number of gene pairs per pathway) are also considerably richer in the integrated pathways. Moderate manual curation are involved to get rid of errors and noises from source data (e.g., the gene ID errors in WikiPathways and relationship errors in KEGG). We turn complicated and incompatible xml data formats and inconsistent gene and gene relationship representations from different source databases into normalized and unified pathway-gene and pathway-gene pair relationships neatly recorded in simple tab-delimited text format and MySQL tables, which facilitates convenient automatic computation and large-scale referencing in many related studies. IntPath data can be downloaded in text format or MySQL dump. IntPath data can also be retrieved and analyzed conveniently through web service by local programs or through web interface by mouse clicks. Several useful analysis tools are also provided in IntPath. Conclusions We have overcome in IntPath the issues of compatibility, consistency, and comprehensiveness that often hamper effective use of pathway databases. We have included four organisms in the current release of IntPath. Our methodology and programs described in this work can be easily applied to other organisms; and we will include more model organisms and important pathogens in future releases of IntPath. IntPath maintains regular updates and is freely available at http://compbio.ddns.comp.nus.edu.sg:8080/IntPath. PMID:23282057

Who Benefits from Which Reading Intervention in the Primary Years? Match the Intervention with the Reading Profile

ERIC Educational Resources Information Center

Munro, John

2017-01-01

Reading difficulties may have multiple causes. Effective approaches to reading intervention need to target the specific causes for individual readers. The Early Reading Intervention Knowledge program comprises three intervention pathways: a phonological-phonemic pathway, a phonic-orthographic pathway, and an oral language pathway. This study…

Differentiating pathway-specific from non-specific effects in high-throughput toxicity data: A foundation for prioritizing adverse outcome pathway development

EPA Science Inventory

The U.S. Environmental Protection Agency’s ToxCast program has screened thousands of chemicals for biological activity, primarily using high-throughput in vitro bioassays. Adverse outcome pathways (AOPs) offer a means to link pathway-specific biological activities with pote...

What Do Students Think of Guided Pathways? CCRC Research Brief. Number 66

ERIC Educational Resources Information Center

Fink, John

2017-01-01

Increasingly, colleges and universities across the country are adopting "guided pathways" reforms to create clearly defined, educationally coherent pathways into and through programs of study for their students. Facilitated by built-in supports, the goal of guided pathways is to increase learning and graduation rates, and to help more…

Molecular Signatures Discriminating the Male and the Female Sexual Pathways in the Pearl Oyster Pinctada margaritifera

PubMed Central

Teaniniuraitemoana, Vaihiti; Huvet, Arnaud; Levy, Peva; Gaertner-Mazouni, Nabila; Gueguen, Yannick; Le Moullac, Gilles

2015-01-01

The genomics of economically important marine bivalves is studied to provide better understanding of the molecular mechanisms underlying their different reproductive strategies. The recently available gonad transcriptome of the black-lip pearl oyster Pinctada margaritifera is a novel and powerful resource to study these mechanisms in marine mollusks displaying hermaphroditic features. In this study, RNAseq quantification data of the P. margaritifera gonad transcriptome were analyzed to identify candidate genes in histologically-characterized gonad samples to provide molecular signatures of the female and male sexual pathway in this pearl oyster. Based on the RNAseq data set, stringent expression analysis identified 1,937 contigs that were differentially expressed between the gonad histological categories. From the hierarchical clustering analysis, a new reproduction model is proposed, based on a dual histo-molecular analytical approach. Nine candidate genes were identified as markers of the sexual pathway: 7 for the female pathway and 2 for the male one. Their mRNA levels were assayed by real-time PCR on a new set of gonadic samples. A clustering method revealed four principal expression patterns based on the relative gene expression ratio. A multivariate regression tree realized on these new samples and validated on the previously analyzed RNAseq samples showed that the sexual pathway of P. margaritifera can be predicted by a 3-gene-pair expression ratio model of 4 different genes: pmarg-43476, pmarg-foxl2, pmarg-54338 and pmarg-fem1-like. This 3-gene-pair expression ratio model strongly suggests only the implication of pmarg-foxl2 and pmarg-fem1-like in the sex inversion of P. margaritifera. This work provides the first histo-molecular model of P. margaritifera reproduction and a gene expression signature of its sexual pathway discriminating the male and female pathways. These represent useful tools for understanding and studying sex inversion, sex differentiation and sex determinism in this species and other related species for aquaculture purposes such as genetic selection programs. PMID:25815473

The Evolution of an Innovative Community-Engaged Health Navigator Program to Address Social Determinants of Health.

PubMed

Page-Reeves, Janet; Moffett, Maurice L; Steimel, Leah; Smith, Daryl T

Health navigators and other types of community health workers (CHWs) have become recognized as essential components of quality care, and key for addressing health disparities owing to the complex health care services landscape presents almost insurmountable challenges for vulnerable individuals. Bernalillo County, New Mexico, has high rates of uninsurance, poverty, and food insecurity. The design of the Pathways to a Healthy Bernalillo County Program (BP) has evolved innovations that are unique in terms of program stability and security, expansive reach, and community capacity across six domains: sustainable public mechanism for program funding, involvement of community organizations in designing the program, expanded focus to address the broader social determinants of health with targeted outreach, an integrated, community-based implementation structure, an outcomes-based payment structure, and using an adaptive program design that actively incorporates navigators in the process. In 2008, the Pathways to a Healthy Bernalillo County Program (BP), located in the Albuquerque metropolitan area in central New Mexico, was established to provide navigation and support for the most vulnerable county residents. BP is funded through a 1% carve out of county mill levy funds. The pathways model is an outcome-based approach for health and social services coordination that uses culturally competent CHW as "navigators" trained to connect at-risk individuals to needed health and social services. One of the important innovations of the pathways approach is a shift in focus from merely providing discrete services to confirming healthy outcomes for the individual patient.

NeAT: a toolbox for the analysis of biological networks, clusters, classes and pathways.

PubMed

Brohée, Sylvain; Faust, Karoline; Lima-Mendez, Gipsi; Sand, Olivier; Janky, Rekin's; Vanderstocken, Gilles; Deville, Yves; van Helden, Jacques

2008-07-01

The network analysis tools (NeAT) (http://rsat.ulb.ac.be/neat/) provide a user-friendly web access to a collection of modular tools for the analysis of networks (graphs) and clusters (e.g. microarray clusters, functional classes, etc.). A first set of tools supports basic operations on graphs (comparison between two graphs, neighborhood of a set of input nodes, path finding and graph randomization). Another set of programs makes the connection between networks and clusters (graph-based clustering, cliques discovery and mapping of clusters onto a network). The toolbox also includes programs for detecting significant intersections between clusters/classes (e.g. clusters of co-expression versus functional classes of genes). NeAT are designed to cope with large datasets and provide a flexible toolbox for analyzing biological networks stored in various databases (protein interactions, regulation and metabolism) or obtained from high-throughput experiments (two-hybrid, mass-spectrometry and microarrays). The web interface interconnects the programs in predefined analysis flows, enabling to address a series of questions about networks of interest. Each tool can also be used separately by entering custom data for a specific analysis. NeAT can also be used as web services (SOAP/WSDL interface), in order to design programmatic workflows and integrate them with other available resources.

Finding the Missing Patients With Tuberculosis: Lessons Learned From Patient-Pathway Analyses in 5 Countries.

PubMed

Hanson, Christy; Osberg, Mike; Brown, Jessie; Durham, George; Chin, Daniel P

2017-11-06

Despite significant progress in diagnosis and treatment of tuberculosis over the past 2 decades, millions of patients with tuberculosis go unreported every year. The patient-pathway analysis (PPA) is designed to assess the alignment between tuberculosis care-seeking patterns and the availability of tuberculosis services. The PPA can help programs understand where they might find the missing patients with tuberculosis. This analysis aggregates and compares the PPAs from case studies in Kenya, Ethiopia, Indonesia, the Philippines, and Pakistan. Across the 5 countries, 24% of patients with tuberculosis initiated care seeking in a facility with tuberculosis diagnostic capacity. Forty-two percent of patients sought care at level 0 facilities, where there was generally no tuberculosis diagnostic capacity; another 42% of patients sought care at level 1 facilities, of which 39% had diagnostic capacity. Sixty-six percent of patients initially sought care in private facilities, which had considerably less tuberculosis diagnostic capacity than public facilities; only 7% of notified cases were from the private sector. The GeneXpert system was available in 14%-41% of level 2 facilities in the 3 countries for which there were data. Tuberculosis treatment capacity tracked closely with the availability of diagnostic capacity. There were substantial subnational differences in care-seeking patterns and service availability. The PPA can be a valuable planning and programming tool to ensure that diagnostic and treatment services are available to patients where they seek care. Patient-centered care will require closing the diagnostic gap and engaging the private sector. Extensive subnational differences in patient pathways to care call for differentiated approaches to patient-centered care. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Finding the Missing Patients With Tuberculosis: Lessons Learned From Patient-Pathway Analyses in 5 Countries

PubMed Central

Hanson, Christy; Osberg, Mike; Brown, Jessie; Durham, George; Chin, Daniel P

2017-01-01

Abstract Background Despite significant progress in diagnosis and treatment of tuberculosis over the past 2 decades, millions of patients with tuberculosis go unreported every year. The patient-pathway analysis (PPA) is designed to assess the alignment between tuberculosis care-seeking patterns and the availability of tuberculosis services. The PPA can help programs understand where they might find the missing patients with tuberculosis. Methods This analysis aggregates and compares the PPAs from case studies in Kenya, Ethiopia, Indonesia, the Philippines, and Pakistan. Results Across the 5 countries, 24% of patients with tuberculosis initiated care seeking in a facility with tuberculosis diagnostic capacity. Forty-two percent of patients sought care at level 0 facilities, where there was generally no tuberculosis diagnostic capacity; another 42% of patients sought care at level 1 facilities, of which 39% had diagnostic capacity. Sixty-six percent of patients initially sought care in private facilities, which had considerably less tuberculosis diagnostic capacity than public facilities; only 7% of notified cases were from the private sector. The GeneXpert system was available in 14%–41% of level 2 facilities in the 3 countries for which there were data. Tuberculosis treatment capacity tracked closely with the availability of diagnostic capacity. There were substantial subnational differences in care-seeking patterns and service availability. Discussion The PPA can be a valuable planning and programming tool to ensure that diagnostic and treatment services are available to patients where they seek care. Patient-centered care will require closing the diagnostic gap and engaging the private sector. Extensive subnational differences in patient pathways to care call for differentiated approaches to patient-centered care. PMID:29117351

5 CFR 362.303 - Filling positions.

Code of Federal Regulations, 2013 CFR

2013-01-01

....303 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PATHWAYS... to the Recent Graduates Program, pursuant to a Pathways MOU executed with the OPM, under Schedule D... situations. The agency's Pathways MOU must identify criteria for approving extensions. (d) Qualifications. An...

5 CFR 362.303 - Filling positions.

Code of Federal Regulations, 2014 CFR

2014-01-01

....303 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PATHWAYS... to the Recent Graduates Program, pursuant to a Pathways MOU executed with the OPM, under Schedule D... situations. The agency's Pathways MOU must identify criteria for approving extensions. (d) Qualifications. An...

A program in global biology. [biota-environment interaction important to life

NASA Technical Reports Server (NTRS)

Mooneyhan, D. W.

1983-01-01

NASA's Global Biology Research Program and its goals for greater understanding of planetary biological processes are discussed. Consideration is given to assessing major pathways and rates of exchange of elements such as carbon and nitrogen, extrapolating local rates of anaerobic activities, determining exchange rates of ocean nutrients, and developing models for the global cycles of carbon, nitrogen, sulfur, and phosphorus. Satellites and sensors operating today are covered: the Nimbus, NOAA, and Landsat series. Block diagrams of the software and hardware for a typical ground data processing and analysis system are provided. Samples of the surface cover data achieved with the Advanced Very High Resolution Radiometer, the Multispectral Scanner, and the Thematic Mapper are presented, as well as a productive capacity model for coastal wetlands. Finally, attention is given to future goals, their engineering requirements, and the necessary data analysis system.

Bcl-2 Blocks a Caspase-Dependent Pathway of Apoptosis Activated by Herpes Simplex Virus 1 Infection in HEp-2 Cells

PubMed Central

Galvan, Veronica; Brandimarti, Renato; Munger, Joshua; Roizman, Bernard

2000-01-01

Earlier reports have shown that herpes simplex virus 1 (HSV-1) mutants induce programmed cell death and that wild-type virus blocks the execution of the cell death program triggered by expression of viral genes, by the Fas and tumor necrosis factor pathways, or by nonspecific stress agents. In particular, an earlier report from this laboratory showed that the mutant virus d120 lacking the genes encoding infected cell protein 4 (ICP4), the major regulatory protein of the virus, induces a caspase-3-independent pathway of apoptosis in human SK-N-SH cells. Here we report that the pathway of apoptosis induced by the d120 mutant in human HEp-2 cells is caspase dependent. Specifically, in HEp-2 cells infected with d120, (i) a broad-range inhibitor of caspase activity, z-vad-FMK, efficiently blocked DNA fragmentation, (ii) cytochrome c was released into the cytoplasm, (iii) caspase-3 was activated inasmuch as poly(ADP-ribose) polymerase was cleaved, and (iv) chromatin condensation and fragmentation of cellular DNA were observed. In parallel studies, HEp-2 cells were transfected with a plasmid encoding human Bcl-2 and a clone (VAX-3) expressing high levels of Bcl-2 was selected. This report shows that Bcl-2 blocked all of the manifestations associated with programmed cell death caused by infection with the d120 mutant. Consistent with their resistance to programmed cell death, VAX-3 cells overproduced infected cell protein 0 (ICP0). An unexpected observation was that ICP0 encoded by the d120 mutant accumulated late in infection in small, quasi-uniform vesicle-like structures in all cell lines tested. Immunofluorescence-based colocalization studies indicated that these structures were not mitochondria or components of the endoplasmic reticulum or the late endosomal compartment. These studies affirm the conclusion that HSV can induce programmed cell death at multiple steps in the course of its replication, that the d120 mutant can induce both caspase-dependent and -independent pathways of programmed cell death, and that virus-induced stimuli of programmed cell death may differ with respect to the pathway that they activate. PMID:10644366

Economic evaluation of a comprehensive teenage pregnancy prevention program: pilot program.

PubMed

Rosenthal, Marjorie S; Ross, Joseph S; Bilodeau, Roseanne; Richter, Rosemary S; Palley, Jane E; Bradley, Elizabeth H

2009-12-01

Previous research has suggested that comprehensive teenage pregnancy prevention programs that address sexual education and life skills development and provide academic support are effective in reducing births among enrolled teenagers. However, there have been limited data on the costs and cost effectiveness of such programs. The study used a community-based participatory research approach to develop estimates of the cost-benefit of the Pathways/Senderos Center, a comprehensive neighborhood-based program to prevent unintended pregnancies and promote positive development for adolescents. Using data from 1997-2003, an in-time intervention analysis was conducted to determine program cost-benefit while teenagers were enrolled; an extrapolation analysis was then used to estimate accrued economic benefits and cost-benefit up to age 30 years. The program operating costs totaled $3,228,152.59 and reduced the teenage childbearing rate from 94.10 to 40.00 per 1000 teenage girls, averting $52,297.84 in total societal costs, with an economic benefit to society from program participation of $2,673,153.11. Therefore, total costs to society exceeded economic benefits by $559,677.05, or $1599.08 per adolescent per year. In an extrapolation analysis, benefits to society exceed costs by $10,474.77 per adolescent per year by age 30 years on average, with social benefits outweighing total social costs by age 20.1 years. This comprehensive teenage pregnancy prevention program is estimated to provide societal economic benefits once participants are young adults, suggesting the need to expand beyond pilot demonstrations and evaluate the long-range cost effectiveness of similarly comprehensive programs when they are implemented more widely in high-risk neighborhoods.

Economic Evaluation of a Comprehensive Teenage Pregnancy Prevention Program: Pilot Program

PubMed Central

Rosenthal, Marjorie S.; Ross, Joseph S.; Bilodeau, RoseAnne; Richter, Rosemary S.; Palley, Jane E.; Bradley, Elizabeth H.

2011-01-01

Background Previous research has suggested that comprehensive teenage pregnancy prevention programs that address sexual education and life skills development and provide academic are effective in reducing births among enrolled teenagers. However, there have been limited data on costs and cost-effectiveness of such programs. Objectives To use a community-based participatory research approach, to develop estimates of the cost-benefit of the Pathways/Senderos Center, a comprehensive neighborhood-based program to prevent unintended pregnancies and promote positive development for adolescents. Methods Using data from 1997-2003, we conducted an in-time intervention analysis to determine program cost-benefit while teenagers were enrolled and then used an extrapolation analysis to estimate accyrred economibc benefits and cost-benefit up to age 30. Results The program operating costs totaled $3,228,152.59 and reduced the teenage childbearing rate from 94.10 to 40.00 per 1000 teenage females, averting $52,297.84 in total societal costs, with an economic benefit to society from program participation of $2,673,153.11. Therefore, total costs to society exceeded economic benefits by $559,677.05, or $1,599.08 per adolescent per year. In an extrapolation analysis, benefits to society exceed costs by $10,474.77 per adolescent per year by age 30 on average, with social benefits outweighing total social costs by age 20.1. Conclusions We estimate that this comprehensive teenage pregnancy prevention program would provide societal economic benefits once participants are young adults, suggesting the need to expand beyond pilot demonstrations and evaluate the long-range cost-effectiveness of similarly comprehensive programs when implemented more widely in high-risk neighborhoods. PMID:19896030

Guided Pathways to College Completion. Policy Snapshot

ERIC Educational Resources Information Center

Fulton, Mary

2017-01-01

Guided pathways are emerging as a strategy to help students complete a credential in a timely manner by encouraging or requiring them to select a program, and develop a degree plan or map, on a specified timeline. At a minimum, institutions may ask students to identify a meta-major, which is a broad area of academic programs with related courses…

Postsecondary Student Persistence and Pathways: Evidence from the YITS-A in Canada

ERIC Educational Resources Information Center

Childs, Stephen E.; Finnie, Ross; Martinello, Felice

2017-01-01

The Youth in Transition Survey is used to follow the postsecondary education (PSE) pathways and outcomes of Canadian youth over the mid 2000s. Students starting at community colleges and four year universities are analyzed separately. First program outcomes are reported, showing the proportions of students who leave their first programs but remain…

Community College Pathways' Program Success: Assessing the First Two Years' Effectiveness of Statway®

ERIC Educational Resources Information Center

Yamada, Hiroyuki

2014-01-01

Statway® is one of the Community College Pathways initiatives developed by the Carnegie Foundation for the Advancement of Teaching to promote students' progress beginning in developmental math to and through college math credit. Early descriptive results suggested that the Statway program has tripled the success rate for students in half the time…

Vocations: The Link between Post-Compulsory Education and the Labour Market. What the Research Says For... Industry

ERIC Educational Resources Information Center

Wheelahan, Leesa; Buchanan, John; Yu, Serena

2015-01-01

This summary brings together the relevant key findings for industry from the research program "Vocations: The Link between Post-Compulsory Education and the Labour Market." The program was comprised of three different strands: (1) pathways from VET in Schools, (2) pathways within and between vocational education and training (VET) and…

Accelerating Opportunity: A Portrait of Students and Their Program Experiences from the 2014 Student Survey

ERIC Educational Resources Information Center

Spaulding, Shayne; Martin-Caughey, Ananda

2015-01-01

This report presents findings from a survey of students enrolled in Accelerating Opportunity (AO) career pathways in spring 2014. AO provides grants to help community colleges create career pathway programs to enroll students with low basic skills into for-credit career and technical education courses to improve educational and employment…

Pathways for Academic Career and Employment (PACE) Program: Fiscal Year 2015 Report

ERIC Educational Resources Information Center

Iowa Department of Education, 2016

2016-01-01

The pathways for academic career and employment program (PACE) is established to provide funding to community colleges for the development of projects that will lead to gainful, quality, in-state employment for members of target populations by providing them with both effective academic and employment training to ensure gain. This is the second…

Articulation to and from the Applied Associate Degree: Challenges and Opportunities

ERIC Educational Resources Information Center

Ignash, Jan M.

2012-01-01

This chapter discusses the "tangled knot" of articulating associate degrees in applied fields and reviews sample programs from applied associate (A.A.S.) to baccalaureate degrees using three distinct pathways, comparing the resulting A.A.S. to baccalaureate degree pathways to similar B.A. or B.S. programs. It focuses predominantly on curricular…

Pathways Triple P and the Child Welfare System: A Promising Fit.

PubMed

Petra, Megan; Kohl, Patricia

2010-04-01

Parents referred to the child welfare system following maltreatment allegations are often ill-prepared to constructively address child disruptive behaviors, despite the high prevalence of these behaviors among this population. Evidence-based parent-mediated interventions are effective in improving parenting skills; however, they are rarely offered within the child welfare system. The purpose of this pilot project was to evaluate the fit and acceptability of one parent-mediated training program (Pathways Triple P) to case managers and parents within this system of care. We implemented Pathways Triple P and subsequently interviewed referring case managers and parents who had participated in the program. Case managers felt the program would work well within the existing child welfare system and would help them to better serve parents. They felt the program had potential to improve parenting skills and prevent future maltreatment. Parents appreciated the program's use of diverse methods, and the variety of parenting techniques taught. In keeping with case manager expectations, participants reported that their enhanced parenting skills and new ability to use non-physical discipline resulted in a better home life. We conclude that Pathways Triple P fits well within the child welfare system and is acceptable to both case managers and parents within this system.

Life Course Associations between Victimization and Aggression: Distinct and Cumulative Contributions

PubMed Central

Logan-Greene, Patricia; Nurius, Paula S.; Hooven, Carole; Thompson, Elaine Adams

2014-01-01

The connections between early maltreatment and later aggression are well established in the literature, however gaps remain in our understanding of developmental processes. This study investigates the cascading lifecourse linkages between victimization experiences from childhood through early adulthood andlater aggressive behavior. The diverse, at-risk sample is of particular importance to child and adolescent specialists, as it represents highly vulnerable youth accessible through conventional school settings. In addition to direct pathways from proximal life periods, path analysis revealed significant indirect mediated pathways through which earlier life victimizationcontributes to aggressive behaviors in later life periods as well as revictimization. Multivariateregressions support theorized cumulative effects of multi-form victimization as well as distinct contributions of victimization domains (emotional, witnessing, physical, property, and sexual) in explaining aggressive behavior.Consistent with theorizing about the developmental impact of early maltreatment, results bolster the importance of interrupting pathways from victimization to revictimization and later aggression. Findings are evaluated in light of implications for early identification and prevention programming. PMID:26190899

Life Course Associations between Victimization and Aggression: Distinctive and Cumulative Contributions

PubMed Central

Logan-Greene, Patricia; Nurius, Paula S.; Hooven, Carole; Thompson, Elaine Adams

2014-01-01

The connections between early maltreatment and later aggression are well established in the literature, however gaps remain in our understanding of developmental processes. This study investigates the cascading life course linkages between victimization experiences from childhood through early adulthood and later aggressive behavior. The diverse, at-risk sample is of particular importance to child and adolescent specialists, as it represents highly vulnerable youth accessible through conventional school settings. In addition to direct pathways from proximal life periods, path analysis revealed significant indirect mediated pathways through which earlier life victimization contributes to aggressive behaviors in later life periods as well as revictimization. Multivariate regressions support theorized cumulative effects of multi-form victimization as well as distinct contributions of victimization domains (emotional, witnessing, physical, property, and sexual) in explaining aggressive behavior. Consistent with theorizing about the developmental impact of early maltreatment, results bolster the importance of interrupting pathways from victimization to revictimization and later aggression. Findings are evaluated in light of implications for early identification and prevention programming. PMID:26190900

Combining medical informatics and bioinformatics toward tools for personalized medicine.

PubMed

Sarachan, B D; Simmons, M K; Subramanian, P; Temkin, J M

2003-01-01

Key bioinformatics and medical informatics research areas need to be identified to advance knowledge and understanding of disease risk factors and molecular disease pathology in the 21 st century toward new diagnoses, prognoses, and treatments. Three high-impact informatics areas are identified: predictive medicine (to identify significant correlations within clinical data using statistical and artificial intelligence methods), along with pathway informatics and cellular simulations (that combine biological knowledge with advanced informatics to elucidate molecular disease pathology). Initial predictive models have been developed for a pilot study in Huntington's disease. An initial bioinformatics platform has been developed for the reconstruction and analysis of pathways, and work has begun on pathway simulation. A bioinformatics research program has been established at GE Global Research Center as an important technology toward next generation medical diagnostics. We anticipate that 21 st century medical research will be a combination of informatics tools with traditional biology wet lab research, and that this will translate to increased use of informatics techniques in the clinic.

Developmental alterations in Huntington’s disease neural cells and pharmacological rescue in cells and mice

PubMed Central

2017-01-01

Neural cultures derived from Huntington’s disease (HD) patient-derived induced pluripotent stem cells were used for ‘omics’ analyses to identify mechanisms underlying neurodegeneration. RNA-seq analysis identified genes in glutamate and GABA signaling, axonal guidance and calcium influx whose expression was decreased in HD cultures. One-third of gene changes were in pathways regulating neuronal development and maturation. When mapped to stages of mouse striatal development, the profiles aligned with earlier embryonic stages of neuronal differentiation. We observed a strong correlation between HD-related histone marks, gene expression and unique peak profiles associated with dysregulated genes, suggesting a coordinated epigenetic program. Treatment with isoxazole-9, which targets key dysregulated pathways, led to amelioration of expanded polyglutamine repeat-associated phenotypes in neural cells and of cognitive impairment and synaptic pathology in HD model R6/2 mice. These data suggest that mutant huntingtin impairs neurodevelopmental pathways that could disrupt synaptic homeostasis and increase vulnerability to the pathologic consequence of expanded polyglutamine repeats over time. PMID:28319609

Remodelling of lace plant leaves: antioxidants and ROS are key regulators of programmed cell death.

PubMed

Dauphinee, Adrian N; Fletcher, Jacob I; Denbigh, Georgia L; Lacroix, Christian R; Gunawardena, Arunika H L A N

2017-07-01

Antioxidants and reactive oxygen species are integral for programmed cell death signaling during perforation formation in the lace plant ( Aponogeton madagascariensis ). The lace plant is an excellent model system for studying developmentally regulated programmed cell death (PCD). During early lace plant leaf development, PCD systematically deletes cells resulting in a perforated leaf morphology that is unique in planta. A distinct feature in young lace plant leaves is an abundance of anthocyanins, which have antioxidant properties. The first sign of PCD induction is the loss of anthocyanin pigmentation in cells that are targeted for destruction, which results in a visible gradient of cell death. The cellular dynamics and time course of lace plant PCD are well documented; however, the signals involved in the pathway remain elusive. This study investigates the roles of antioxidants and ROS in developmental PCD signaling during lace plant perforation formation. The involvement of antioxidants and ROS in the pathway was determined using a variety of techniques including pharmacological whole plant experimentation, long-term live cell imaging, the 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid anti-radical activity assay, and western blot analysis. Results indicate that antioxidants and ROS are key regulators of PCD during the remodelling of lace plant leaves.

PATHWAYS - ELECTRON TUNNELING PATHWAYS IN PROTEINS

NASA Technical Reports Server (NTRS)

Beratan, D. N.

1994-01-01

The key to understanding the mechanisms of many important biological processes such as photosynthesis and respiration is a better understanding of the electron transfer processes which take place between metal atoms (and other groups) fixed within large protein molecules. Research is currently focused on the rate of electron transfer and the factors that influence it, such as protein composition and the distance between metal atoms. Current models explain the swift transfer of electrons over considerable distances by postulating bridge-mediated tunneling, or physical tunneling pathways, made up of interacting bonds in the medium around and between donor and acceptor sites. The program PATHWAYS is designed to predict the route along which electrons travel in the transfer processes. The basic strategy of PATHWAYS is to begin by recording each possible path element on a connectivity list, including in each entry which two atoms are connected and what contribution the connection would make to the overall rate if it were included in a pathway. The list begins with the bonded molecular structure (including the backbone sequence and side chain connectivity), and then adds probable hydrogen bond links and through-space contacts. Once this list is completed, the program runs a tree search from the donor to the acceptor site to find the dominant pathways. The speed and efficiency of the computer search offers an improvement over manual techniques. PATHWAYS is written in FORTRAN 77 for execution on DEC VAX series computers running VMS. The program inputs data from four data sets and one structure file. The software was written to input BIOGRAF (old format) structure files based on x-ray crystal structures and outputs ASCII files listing the best pathways and BIOGRAF vector files containing the paths. Relatively minor changes could be made in the input format statements for compatibility with other graphics software. The executable and source code are included with the distribution. The main memory requirement for execution is 2.6 Mb. This program is available in DEC VAX BACKUP format on a 9-track 1600 BPI magnetic tape (standard distribution) or on a TK50 tape cartridge. PATHWAYS was developed in 1988. PATHWAYS is a copyrighted work with all copyright vested in NASA. DEC, VAX, VMS, and TK50 are trademarks of Digital Equipment Corporation. BIOGRAF is a trademark of Molecular Simulations, Inc., Sunnyvale, CA.

Lexical bundles in an advanced INTOCSU writing class and engineering texts: A functional analysis

NASA Astrophysics Data System (ADS)

Alquraishi, Mohammed Abdulrahman

The purpose of this study is to investigate the functions of lexical bundles in two corpora: a corpus of engineering academic texts and a corpus of IEP advanced writing class texts. This study is concerned with the nature of formulaic language in Pathway IEPs and engineering texts, and whether those types of texts show similar or distinctive formulaic functions. Moreover, the study looked into lexical bundles found in an engineering 1.26 million-word corpus and an ESL 65000-word corpus using a concordancing program. The study then analyzed the functions of those lexical bundles and compared them statistically using chi-square tests. Additionally, the results of this investigation showed 236 unique frequent lexical bundles in the engineering corpus and 37 bundles in the pathway corpus. Also, the study identified several differences between the density and functions of lexical bundles in the two corpora. These differences were evident in the distribution of functions of lexical bundles and the minimal overlap of lexical bundles found in the two corpora. The results of this study call for more attention to formulaic language at ESP and EAP programs.

Using Answer Set Programming to Integrate RNA Expression with Signalling Pathway Information to Infer How Mutations Affect Ageing

PubMed Central

Papatheodorou, Irene; Ziehm, Matthias; Wieser, Daniela; Alic, Nazif; Partridge, Linda; Thornton, Janet M.

2012-01-01

A challenge of systems biology is to integrate incomplete knowledge on pathways with existing experimental data sets and relate these to measured phenotypes. Research on ageing often generates such incomplete data, creating difficulties in integrating RNA expression with information about biological processes and the phenotypes of ageing, including longevity. Here, we develop a logic-based method that employs Answer Set Programming, and use it to infer signalling effects of genetic perturbations, based on a model of the insulin signalling pathway. We apply our method to RNA expression data from Drosophila mutants in the insulin pathway that alter lifespan, in a foxo dependent fashion. We use this information to deduce how the pathway influences lifespan in the mutant animals. We also develop a method for inferring the largest common sub-paths within each of our signalling predictions. Our comparisons reveal consistent homeostatic mechanisms across both long- and short-lived mutants. The transcriptional changes observed in each mutation usually provide negative feedback to signalling predicted for that mutation. We also identify an S6K-mediated feedback in two long-lived mutants that suggests a crosstalk between these pathways in mutants of the insulin pathway, in vivo. By formulating the problem as a logic-based theory in a qualitative fashion, we are able to use the efficient search facilities of Answer Set Programming, allowing us to explore larger pathways, combine molecular changes with pathways and phenotype and infer effects on signalling in in vivo, whole-organism, mutants, where direct signalling stimulation assays are difficult to perform. Our methods are available in the web-service NetEffects: http://www.ebi.ac.uk/thornton-srv/software/NetEffects. PMID:23251396

Using answer set programming to integrate RNA expression with signalling pathway information to infer how mutations affect ageing.

PubMed

Papatheodorou, Irene; Ziehm, Matthias; Wieser, Daniela; Alic, Nazif; Partridge, Linda; Thornton, Janet M

2012-01-01

A challenge of systems biology is to integrate incomplete knowledge on pathways with existing experimental data sets and relate these to measured phenotypes. Research on ageing often generates such incomplete data, creating difficulties in integrating RNA expression with information about biological processes and the phenotypes of ageing, including longevity. Here, we develop a logic-based method that employs Answer Set Programming, and use it to infer signalling effects of genetic perturbations, based on a model of the insulin signalling pathway. We apply our method to RNA expression data from Drosophila mutants in the insulin pathway that alter lifespan, in a foxo dependent fashion. We use this information to deduce how the pathway influences lifespan in the mutant animals. We also develop a method for inferring the largest common sub-paths within each of our signalling predictions. Our comparisons reveal consistent homeostatic mechanisms across both long- and short-lived mutants. The transcriptional changes observed in each mutation usually provide negative feedback to signalling predicted for that mutation. We also identify an S6K-mediated feedback in two long-lived mutants that suggests a crosstalk between these pathways in mutants of the insulin pathway, in vivo. By formulating the problem as a logic-based theory in a qualitative fashion, we are able to use the efficient search facilities of Answer Set Programming, allowing us to explore larger pathways, combine molecular changes with pathways and phenotype and infer effects on signalling in in vivo, whole-organism, mutants, where direct signalling stimulation assays are difficult to perform. Our methods are available in the web-service NetEffects: http://www.ebi.ac.uk/thornton-srv/software/NetEffects.

Development, implementation, and compliance of treatment pathways in radiation medicine.

PubMed

Potters, Louis; Raince, Jadeep; Chou, Henry; Kapur, Ajay; Bulanowski, Daniel; Stanzione, Regina; Lee, Lucille

2013-01-01

While much emphasis on safety in the radiation oncology clinic is placed on process, there remains considerable opportunity to increase safety, enhance outcomes, and avoid ad hoc care by instituting detailed treatment pathways. The purpose of this study was to review the process of developing evidence and consensus-based, outcomes-oriented treatment pathways that standardize treatment and patient management in a large multi-center radiation oncology practice. Further, we reviewed our compliance in incorporating these directives into our day-to-day clinical practice. Using the Institute of Medicine guideline for developing treatment pathways, 87 disease specific pathways were developed and incorporated into the electronic medical system in our multi-facility radiation oncology department. Compliance in incorporating treatment pathways was assessed by mining our electronic medical records (EMR) data from January 1, 2010 through February 2012 for patients with breast and prostate cancer. This retrospective analysis of data from EMR found overall compliance to breast and prostate cancer treatment pathways to be 97 and 99%, respectively. The reason for non-compliance proved to be either a failure to complete the prescribed care based on grade II or III toxicity (n = 1 breast, 3 prostate) or patient elected discontinuance of care (n = 1 prostate) or the physician chose a higher dose for positive/close margins (n = 3 breast). This study demonstrates that consensus and evidence-based treatment pathways can be developed and implemented in a multi-center department of radiation oncology. And that for prostate and breast cancer there was a high degree of compliance using these directives. The development and implementation of these pathways serve as a key component of our safety program, most notably in our effort to facilitate consistent decision-making and reducing variation between physicians.

Decomposition of complex microbial behaviors into resource-based stress responses

PubMed Central

Carlson, Ross P.

2009-01-01

Motivation: Highly redundant metabolic networks and experimental data from cultures likely adapting simultaneously to multiple stresses can complicate the analysis of cellular behaviors. It is proposed that the explicit consideration of these factors is critical to understanding the competitive basis of microbial strategies. Results: Wide ranging, seemingly unrelated Escherichia coli physiological fluxes can be simply and accurately described as linear combinations of a few ecologically relevant stress adaptations. These strategies were identified by decomposing the central metabolism of E.coli into elementary modes (mathematically defined biochemical pathways) and assessing the resource investment cost–benefit properties for each pathway. The approach capitalizes on the inherent tradeoffs related to investing finite resources like nitrogen into different pathway enzymes when the pathways have varying metabolic efficiencies. The subset of ecologically competitive pathways represented 0.02% of the total permissible pathways. The biological relevance of the assembled strategies was tested against 10 000 randomly constructed pathway subsets. None of the randomly assembled collections were able to describe all of the considered experimental data as accurately as the cost-based subset. The results suggest these metabolic strategies are biologically significant. The current descriptions were compared with linear programming (LP)-based flux descriptions using the Euclidean distance metric. The current study's pathway subset described the experimental fluxes with better accuracy than the LP results without having to test multiple objective functions or constraints and while providing additional ecological insight into microbial behavior. The assembled pathways seem to represent a generalized set of strategies that can describe a wide range of microbial responses and hint at evolutionary processes where a handful of successful metabolic strategies are utilized simultaneously in different combinations to adapt to diverse conditions. Contact: rossc@biofilms.montana.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:19008248

The alignment of enzymatic steps reveals similar metabolic pathways and probable recruitment events in Gammaproteobacteria.

PubMed

Poot-Hernandez, Augusto Cesar; Rodriguez-Vazquez, Katya; Perez-Rueda, Ernesto

2015-11-17

It is generally accepted that gene duplication followed by functional divergence is one of the main sources of metabolic diversity. In this regard, there is an increasing interest in the development of methods that allow the systematic identification of these evolutionary events in metabolism. Here, we used a method not based on biomolecular sequence analysis to compare and identify common and variable routes in the metabolism of 40 Gammaproteobacteria species. The metabolic maps deposited in the KEGG database were transformed into linear Enzymatic Step Sequences (ESS) by using the breadth-first search algorithm. These ESS represent subsequent enzymes linked to each other, where their catalytic activities are encoded in the Enzyme Commission numbers. The ESS were compared in an all-against-all (pairwise comparisons) approach by using a dynamic programming algorithm, leaving only a set of significant pairs. From these comparisons, we identified a set of functionally conserved enzymatic steps in different metabolic maps, in which cell wall components and fatty acid and lysine biosynthesis were included. In addition, we found that pathways associated with biosynthesis share a higher proportion of similar ESS than degradation pathways and secondary metabolism pathways. Also, maps associated with the metabolism of similar compounds contain a high proportion of similar ESS, such as those maps from nucleotide metabolism pathways, in particular the inosine monophosphate pathway. Furthermore, diverse ESS associated with the low part of the glycolysis pathway were identified as functionally similar to multiple metabolic pathways. In summary, our comparisons may help to identify similar reactions in different metabolic pathways and could reinforce the patchwork model in the evolution of metabolism in Gammaproteobacteria.

Causal pathways linking Farm to School to childhood obesity prevention.

PubMed

Joshi, Anupama; Ratcliffe, Michelle M

2012-08-01

Farm to School programs are rapidly gaining attention as a potential strategy for preventing childhood obesity; however, the causal linkages between Farm to School activities and health outcomes are not well documented. To capitalize on the increased interest in and momentum for Farm to School, researchers and practitioners need to move from developing and implementing evidence informed programs and policies to ones that are evidence-based. The purpose of this article is to outline a framework for facilitating an evidence base for Farm to School programs and policies through a systematic and coordinated approach. Employing the concepts of causal pathways, the authors introduce a proposed framework for organizing and systematically testing out multiple hypotheses (or potential causal links) for how, why, and under what conditions Farm to School Inputs and Activities may result in what Outputs, Effects, and Impacts. Using the causal pathways framework may help develop and test competing hypotheses, identify multicausality, strength, and interactions of causes, and discern the difference between catalysts and causes. In this article, we introduce causal pathways, present menus of potential independent and dependent variables from which to create and test causal pathways linking Farm to School interventions and their role in preventing childhood obesity, discuss their applicability to Farm to School research and practice, and outline proposed next steps for developing a coordinated research framework for Farm to School programs.

A gene encoding maize caffeoyl-CoA O-methyltransferase confers quantitative resistance to multiple pathogens.

PubMed

Yang, Qin; He, Yijian; Kabahuma, Mercy; Chaya, Timothy; Kelly, Amy; Borrego, Eli; Bian, Yang; El Kasmi, Farid; Yang, Li; Teixeira, Paulo; Kolkman, Judith; Nelson, Rebecca; Kolomiets, Michael; L Dangl, Jeffery; Wisser, Randall; Caplan, Jeffrey; Li, Xu; Lauter, Nick; Balint-Kurti, Peter

2017-09-01

Alleles that confer multiple disease resistance (MDR) are valuable in crop improvement, although the molecular mechanisms underlying their functions remain largely unknown. A quantitative trait locus, qMdr 9.02 , associated with resistance to three important foliar maize diseases-southern leaf blight, gray leaf spot and northern leaf blight-has been identified on maize chromosome 9. Through fine-mapping, association analysis, expression analysis, insertional mutagenesis and transgenic validation, we demonstrate that ZmCCoAOMT2, which encodes a caffeoyl-CoA O-methyltransferase associated with the phenylpropanoid pathway and lignin production, is the gene within qMdr 9.02 conferring quantitative resistance to both southern leaf blight and gray leaf spot. We suggest that resistance might be caused by allelic variation at the level of both gene expression and amino acid sequence, thus resulting in differences in levels of lignin and other metabolites of the phenylpropanoid pathway and regulation of programmed cell death.

Single gene and gene interaction effects on fertilization and embryonic survival rates in cattle.

PubMed

Khatib, H; Huang, W; Wang, X; Tran, A H; Bindrim, A B; Schutzkus, V; Monson, R L; Yandell, B S

2009-05-01

Decrease in fertility and conception rates is a major cause of economic loss and cow culling in dairy herds. Conception rate is the product of fertilization rate and embryonic survival rate. Identification of genetic factors that cause the death of embryos is the first step in eliminating this problem from the population and thereby increasing reproductive efficiency. A candidate pathway approach was used to identify candidate genes affecting fertilization and embryo survival rates using an in vitro fertilization experimental system. A total of 7,413 in vitro fertilizations were performed using oocytes from 504 ovaries and semen samples from 10 different bulls. Fertilization rate was calculated as the number of cleaved embryos 48 h postfertilization out of the total number of oocytes exposed to sperm. Survival rate of embryos was calculated as the number of blastocysts on d 7 of development out of the number of total embryos cultured. All ovaries were genotyped for 8 genes in the POU1F1 signaling pathway. Single-gene analysis revealed significant associations of GHR, PRLR, STAT5A, and UTMP with survival rate and of POU1F1, GHR, STAT5A, and OPN with fertilization rate. To further characterize the contribution of the entire integrated POU1F1 pathway to fertilization and early embryonic survival, a model selection procedure was applied. Comparisons among the different models showed that interactions between adjacent genes in the pathway revealed a significant contribution to the variation in fertility traits compared with other models that analyzed only bull information or only genes without interactions. Moreover, some genes that were not significant in the single-gene analysis showed significant effects in the interaction analysis. Thus, we propose that single genes as well as an entire pathway can be used in selection programs to improve reproduction performance in dairy cattle.

5 CFR 362.301 - Program administration.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Program administration. 362.301 Section 362.301 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PATHWAYS PROGRAMS Recent Graduates Program § 362.301 Program administration. The Recent Graduates Program provides...

5 CFR 362.301 - Program administration.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Program administration. 362.301 Section 362.301 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PATHWAYS PROGRAMS Recent Graduates Program § 362.301 Program administration. The Recent Graduates Program provides...

[Accelerated postoperative recovery after colorectal surgery].

PubMed

Alfonsi, P; Schaack, E

2007-01-01

Accelerated recovery programs are clinical pathways which outline the stages, and streamline the means, and techniques aiming toward the desired end a rapid return of the patient to his pre-operative physical and psychological status. Recovery from colo-rectal surgery may be slowed by the patient's general health, surgical stress, post-surgical pain, and post-operative ileus. Both surgeons and anesthesiologists participate throughout the peri-operative period in a clinical pathway aimed at minimizing these delaying factors. Key elements of this pathway include avoidance of pre-operative colonic cleansing, early enteral feeding, and effective post-operative pain management permitting early ambulation (usually via thoracic epidural anesthesia). Pre-operative information and motivation of the patient is also a key to the success of this accelerated recovery program. Studies of such programs have shown decreased duration of post-operative ileus and hospital stay without an increase in complications or re-admissions. The elements of the clinical pathway must be regularly re-evaluated and updated according to local experience and published data.

5 CFR 362.404 - Appointment and extension.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Section 362.404 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PATHWAYS...) An agency may make 2-year appointments to the PMF Program, pursuant to a Pathways MOU executed with... unusual circumstances or situations. The agency's Pathways MOU must identify the criteria for approving...

5 CFR 362.404 - Appointment and extension.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Section 362.404 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PATHWAYS...) An agency may make 2-year appointments to the PMF Program, pursuant to a Pathways MOU executed with... unusual circumstances or situations. The agency's Pathways MOU must identify the criteria for approving...

Molecular Mechanisms Underlying Cardiac Adaptation to Exercise

PubMed Central

Vega, Rick B.; Konhilas, John P.; Kelly, Daniel P.; Leinwand, Leslie A.

2017-01-01

Exercise elicits coordinated multi-organ responses including skeletal muscle, vasculature, heart and lung. In the short term, the output of the heart increases to meet the demand of strenuous exercise. Long term exercise instigates remodeling of the heart including growth and adaptive molecular and cellular re-programming. Signaling pathways such as the insulin-like growth factor 1/PI3K/Akt pathway mediate many of these responses. Exercise-induced, or physiologic, cardiac growth contrasts with growth elicited by pathological stimuli such as hypertension. Comparing the molecular and cellular underpinnings of physiologic and pathologic cardiac growth has unveiled phenotype-specific signaling pathways and transcriptional regulatory programs. Studies suggest that exercise pathways likely antagonize pathological pathways, and exercise training is often recommended for patients with chronic stable heart failure or following myocardial infarction. Herein, we summarize the current understanding of the structural and functional cardiac responses to exercise as well as signaling pathways and downstream effector molecules responsible for these adaptations. PMID:28467921

Translating Evidence Based Violence and Drug Use Prevention to Obesity Prevention: Development and Construction of the Pathways Program

ERIC Educational Resources Information Center

Sakuma, Kari-Lyn K.; Riggs, Nathaniel R.; Pentz, Mary Ann

2012-01-01

Effective school-based obesity prevention programs are needed to prevent and reduce the growing obesity risk among youth. Utilizing the evidence-rich areas of violence and substance use prevention, translation science may provide an efficient means for developing curricula across multiple health behaviors. This paper introduces Pathways to Health,…

International Students in American Pathway Programs: Learning English and Culture through Service-Learning

ERIC Educational Resources Information Center

Miller, Julie; Berkey, Becca; Griffin, Francis

2015-01-01

As the number of international students studying in the United States continues to grow, the body of literature about service-learning in English Language Learning (ELL) curricula is growing in tandem. The primary goal of this paper is to explore how service-learning impacts the development and transition of pathway program students in the United…

Community College Students with Criminal Justice Histories and Human Services Education: Glass Ceiling, Brick Wall, or a Pathway to Success

ERIC Educational Resources Information Center

Rose, Lisa Hale

2015-01-01

In spite of open access to community college education, specifically human service associate degree programs, students with criminal justice histories do not necessarily have an unobstructed pathway to obtaining the degree and admission to the baccalaureate programs in human services and social work that are almost always selective. The first…

Basic Education for Adults: Pathways to College and Careers for Washington's Emerging Workforce. Washington's Community and Technical Colleges

ERIC Educational Resources Information Center

Washington State Board for Community and Technical Colleges, 2015

2015-01-01

This brief describes the Basic Education for Adults (BEdA) programs that bridge the gap between school and work, thereby creating pathways to college and careers for Washington's emerging workforce. BEdA programs teach foundational skills--reading, writing, math, technology and English language--so adults can move through college and into…

Vocations: The Link between Post-Compulsory Education and the Labour Market. What the Research Says For... Tertiary Education Providers & School Educators

ERIC Educational Resources Information Center

Wheelahan, Leesa; Buchanan, John; Yu, Serena

2015-01-01

This summary brings together the relevant key findings for tertiary education providers and school educators from the research program "Vocations: The Link between Post-Compulsory Education and the Labour Market." The program was comprised of three different strands: (1) pathways from VET in Schools, (2) pathways within and between…

Vocations: The Link between Post-Compulsory Education and the Labour Market. What the Research Says For... Qualification & Approval Bodies

ERIC Educational Resources Information Center

Wheelahan, Leesa; Buchanan, John; Yu, Serena

2015-01-01

This summary pulls together the relevant key findings for qualification and approval bodies from the research program "Vocations: The Link between Post-Compulsory Education and the Labour Market." The program was comprised of three different strands: (1) pathways from VET in Schools, (2) pathways within and between vocational education…

Vocations: The Link between Post-Compulsory Education and the Labour Market. What the Research Says For... Government & Policy-Makers

ERIC Educational Resources Information Center

Wheelahan, Leesa; Buchanan, John; Yu, Serena

2015-01-01

This summary brings together the relevant key findings for government and policy-makers from the research program "Vocations: The Link between Post-Compulsory Education and the Labour Market." The program was comprised of three different strands: (1) pathways from VET in Schools, (2) pathways within and between vocational education and…

Recruiting, Preparing and Retaining Teachers for America's Schools Progress Report: Pathways to Teaching Careers.

ERIC Educational Resources Information Center

DeWitt Wallace/Reader's Digest Fund, Pleasantville, NY.

This report describes the DeWitt Wallace-Reader's Digest Fund's Pathways to Teaching Careers Program, which is designed to help increase and diversify the supply of well-trained public school teachers willing to work in low-income schools. Program design drew on findings of leading educational researchers that made a strong case for investing in…

ESEA: Discovering the Dysregulated Pathways based on Edge Set Enrichment Analysis

PubMed Central

Han, Junwei; Shi, Xinrui; Zhang, Yunpeng; Xu, Yanjun; Jiang, Ying; Zhang, Chunlong; Feng, Li; Yang, Haixiu; Shang, Desi; Sun, Zeguo; Su, Fei; Li, Chunquan; Li, Xia

2015-01-01

Pathway analyses are playing an increasingly important role in understanding biological mechanism, cellular function and disease states. Current pathway-identification methods generally focus on only the changes of gene expression levels; however, the biological relationships among genes are also the fundamental components of pathways, and the dysregulated relationships may also alter the pathway activities. We propose a powerful computational method, Edge Set Enrichment Analysis (ESEA), for the identification of dysregulated pathways. This provides a novel way of pathway analysis by investigating the changes of biological relationships of pathways in the context of gene expression data. Simulation studies illustrate the power and performance of ESEA under various simulated conditions. Using real datasets from p53 mutation, Type 2 diabetes and lung cancer, we validate effectiveness of ESEA in identifying dysregulated pathways. We further compare our results with five other pathway enrichment analysis methods. With these analyses, we show that ESEA is able to help uncover dysregulated biological pathways underlying complex traits and human diseases via specific use of the dysregulated biological relationships. We develop a freely available R-based tool of ESEA. Currently, ESEA can support pathway analysis of the seven public databases (KEGG; Reactome; Biocarta; NCI; SPIKE; HumanCyc; Panther). PMID:26267116

Elementary Mode Analysis: A Useful Metabolic Pathway Analysis Tool for Characterizing Cellular Metabolism

PubMed Central

Trinh, Cong T.; Wlaschin, Aaron; Srienc, Friedrich

2010-01-01

Elementary Mode Analysis is a useful Metabolic Pathway Analysis tool to identify the structure of a metabolic network that links the cellular phenotype to the corresponding genotype. The analysis can decompose the intricate metabolic network comprised of highly interconnected reactions into uniquely organized pathways. These pathways consisting of a minimal set of enzymes that can support steady state operation of cellular metabolism represent independent cellular physiological states. Such pathway definition provides a rigorous basis to systematically characterize cellular phenotypes, metabolic network regulation, robustness, and fragility that facilitate understanding of cell physiology and implementation of metabolic engineering strategies. This mini-review aims to overview the development and application of elementary mode analysis as a metabolic pathway analysis tool in studying cell physiology and as a basis of metabolic engineering. PMID:19015845

Pathways to labor force exit: work transitions and work instability.

PubMed

Mutchler, J E; Burr, J A; Pienta, A M; Massagli, M P

1997-01-01

The purpose of this study is to examine alternative pathways to labor force exit among older men. Based on the life course perspective, we distinguish between crisp exits from the labor force, which are characterized as being unidirectional, and blurred transition patterns, which include repeated exists, entrances, and unemployment spells. Using longitudinal data from the 1984 Survey of Income and Program Participation, we find that one-quarter of the sample of men aged 55 to 74 at first interview experienced at least one transition in labor force status over a 28-month observation period. Fewer than half of these can be characterized as crisp exists from the labor force. Our multivariate analysis suggests that blurred transition patterns are likely part of an effort to maintain economic status in later life.

Immunoinformatics Features Linked to Leishmania Vaccine Development: Data Integration of Experimental and In Silico Studies

PubMed Central

Brito, Rory C. F.; Guimarães, Frederico G.; Velloso, João P. L.; Corrêa-Oliveira, Rodrigo; Ruiz, Jeronimo C.; Reis, Alexandre B.; Resende, Daniela M.

2017-01-01

Leishmaniasis is a wide-spectrum disease caused by parasites from Leishmania genus. There is no human vaccine available and it is considered by many studies as apotential effective tool for disease control. To discover novel antigens, computational programs have been used in reverse vaccinology strategies. In this work, we developed a validation antigen approach that integrates prediction of B and T cell epitopes, analysis of Protein-Protein Interaction (PPI) networks and metabolic pathways. We selected twenty candidate proteins from Leishmania tested in murine model, with experimental outcome published in the literature. The predictions for CD4+ and CD8+ T cell epitopes were correlated with protection in experimental outcomes. We also mapped immunogenic proteins on PPI networks in order to find Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with them. Our results suggest that non-protective antigens have lowest frequency of predicted T CD4+ and T CD8+ epitopes, compared with protective ones. T CD4+ and T CD8+ cells are more related to leishmaniasis protection in experimental outcomes than B cell predicted epitopes. Considering KEGG analysis, the proteins considered protective are connected to nodes with few pathways, including those associated with ribosome biosynthesis and purine metabolism. PMID:28208616

Immunoinformatics Features Linked to Leishmania Vaccine Development: Data Integration of Experimental and In Silico Studies.

PubMed

Brito, Rory C F; Guimarães, Frederico G; Velloso, João P L; Corrêa-Oliveira, Rodrigo; Ruiz, Jeronimo C; Reis, Alexandre B; Resende, Daniela M

2017-02-10

Leishmaniasis is a wide-spectrum disease caused by parasites from Leishmania genus. There is no human vaccine available and it is considered by many studies as apotential effective tool for disease control. To discover novel antigens, computational programs have been used in reverse vaccinology strategies. In this work, we developed a validation antigen approach that integrates prediction of B and T cell epitopes, analysis of Protein-Protein Interaction (PPI) networks and metabolic pathways. We selected twenty candidate proteins from Leishmania tested in murine model, with experimental outcome published in the literature. The predictions for CD4⁺ and CD8⁺ T cell epitopes were correlated with protection in experimental outcomes. We also mapped immunogenic proteins on PPI networks in order to find Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with them. Our results suggest that non-protective antigens have lowest frequency of predicted T CD4⁺ and T CD8⁺ epitopes, compared with protective ones. T CD4⁺ and T CD8⁺ cells are more related to leishmaniasis protection in experimental outcomes than B cell predicted epitopes. Considering KEGG analysis, the proteins considered protective are connected to nodes with few pathways, including those associated with ribosome biosynthesis and purine metabolism.

From pipelines to pathways: the Memorial experience in educating doctors for rural generalist practice.

PubMed

Rourke, James; Asghari, Shabnam; Hurley, Oliver; Ravalia, Mohamed; Jong, Michael; Parsons, Wanda; Duggan, Norah; Stringer, Katherine; O'Keefe, Danielle; Moffatt, Scott; Graham, Wendy; Sturge Sparkes, Carolyn; Hippe, Janelle; Harris Walsh, Kristin; McKay, Donald; Samarasena, Asoka

2018-03-01

This report describes the community context, concept and mission of The Faculty of Medicine at Memorial University of Newfoundland (Memorial), Canada, and its 'pathways to rural practice' approach, which includes influences at the pre-medical school, medical school experience, postgraduate residency training, and physician practice levels. Memorial's pathways to practice helped Memorial to fulfill its social accountability mandate to populate the province with highly skilled rural generalist practitioners. Programs/interventions/initiatives: The 'pathways to rural practice' include initiatives in four stages: (1) before admission to medical school; (2) during undergraduate medical training (medical degree (MD) program); (3) during postgraduate vocational residency training; and (4) after postgraduate vocational residency training. Memorial's Learners & Locations (L&L) database tracks students through these stages. The Aboriginal initiative - the MedQuest program and the admissions process that considers geographic or minority representation in terms of those selecting candidates and the candidates themselves - occurs before the student is admitted. Once a student starts Memorial's MD program, the student has ample opportunities to have rural-based experiences through pre-clerkship and clerkship, of which some take place exclusively outside of St. John's tertiary hospitals. Memorial's postgraduate (PG) Family Medicine (FM) residency (vocational) training program allows for deeper community integration and longer periods of training within the same community, which increases the likelihood of a physician choosing rural family medicine. After postgraduate training, rural physicians were given many opportunities for professional development as well as faculty development opportunities. Each of the programs and initiatives were assessed through geospatial rurality analysis of administrative data collected upon entry into and during the MD program and PG training (L&L). Among Memorial MD-graduating classes of 2011-2020, 56% spent the majority of their lives before their 18th birthday in a rural location and 44% in an urban location. As of September 2016, 23 Memorial MD students self-identified as Aboriginal, of which 2 (9%) were from an urban location and 20 (91%) were from rural locations. For Year 3 Family Medicine, graduating classes 2011 to 2019, 89% of placement weeks took place in rural communities and 8% took place in rural towns. For Memorial MD graduating classes 2011-2013 who completed Memorial Family Medicine vocational training residencies, (N=49), 100% completed some rural training. For these 49 residents (vocational trainees), the average amount of time spent in rural areas was 52 weeks out of a total average FM training time of 95 weeks. For Family Medicine residencies from July 2011 to October 2016, 29% of all placement weeks took place in rural communities and 21% of all placement weeks took place in rural towns. For 2016-2017 first-year residents, 53% of the first year training is completed in rural locations, reflecting an even greater rural experiential learning focus. Memorial's pathways approach has allowed for the comprehensive training of rural generalists for Newfoundland and Labrador and the rest of Canada and may be applicable to other settings. More challenges remain, requiring ongoing collaboration with governments, medical associations, health authorities, communities, and their physicians to help achieve reliable and feasible healthcare delivery for those living in rural and remote areas.

Programmed Effects in Neurobehavior and Antioxidative Physiology in Zebrafish Embryonically Exposed to Cadmium: Observations and Hypothesized Adverse Outcome Pathway Framework

PubMed Central

Ruiter, Sander; Sippel, Josefine; Bouwmeester, Manon C.; Lommelaars, Tobias; Beekhof, Piet; Hodemaekers, Hennie M.; Bakker, Frank; van den Brandhof, Evert-Jan; Pennings, Jeroen L. A.; van der Ven, Leo T. M.

2016-01-01

Non-communicable diseases (NCDs) are a major cause of premature mortality. Recent studies show that predispositions for NCDs may arise from early-life exposure to low concentrations of environmental contaminants. This developmental origins of health and disease (DOHaD) paradigm suggests that programming of an embryo can be disrupted, changing the homeostatic set point of biological functions. Epigenetic alterations are a possible underlying mechanism. Here, we investigated the DOHaD paradigm by exposing zebrafish to subtoxic concentrations of the ubiquitous contaminant cadmium during embryogenesis, followed by growth under normal conditions. Prolonged behavioral responses to physical stress and altered antioxidative physiology were observed approximately ten weeks after termination of embryonal exposure, at concentrations that were 50–3200-fold below the direct embryotoxic concentration, and interpreted as altered developmental programming. Literature was explored for possible mechanistic pathways that link embryonic subtoxic cadmium to the observed apical phenotypes, more specifically, the probability of molecular mechanisms induced by cadmium exposure leading to altered DNA methylation and subsequently to the observed apical phenotypes. This was done using the adverse outcome pathway model framework, and assessing key event relationship plausibility by tailored Bradford-Hill analysis. Thus, cadmium interaction with thiols appeared to be the major contributor to late-life effects. Cadmium-thiol interactions may lead to depletion of the methyl donor S-adenosyl-methionine, resulting in methylome alterations, and may, additionally, result in oxidative stress, which may lead to DNA oxidation, and subsequently altered DNA methyltransferase activity. In this way, DNA methylation may be affected at a critical developmental stage, causing the observed apical phenotypes. PMID:27827847

Correlation analysis of targeted proteins and metabolites to assess and engineer microbial isopentenol production.

PubMed

George, Kevin W; Chen, Amy; Jain, Aakriti; Batth, Tanveer S; Baidoo, Edward E K; Wang, George; Adams, Paul D; Petzold, Christopher J; Keasling, Jay D; Lee, Taek Soon

2014-08-01

The ability to rapidly assess and optimize heterologous pathway function is critical for effective metabolic engineering. Here, we develop a systematic approach to pathway analysis based on correlations between targeted proteins and metabolites and apply it to the microbial production of isopentenol, a promising biofuel. Starting with a seven-gene pathway, we performed a correlation analysis to reduce pathway complexity and identified two pathway proteins as the primary determinants of efficient isopentenol production. Aided by the targeted quantification of relevant pathway intermediates, we constructed and subsequently validated a conceptual model of isopentenol pathway function. Informed by our analysis, we assembled a strain which produced isopentenol at a titer 1.5 g/L, or 46% of theoretical yield. Our engineering approach allowed us to accurately identify bottlenecks and determine appropriate pathway balance. Paired with high-throughput cloning techniques and analytics, this strategy should prove useful for the analysis and optimization of increasingly complex heterologous pathways. © 2014 Wiley Periodicals, Inc.

The interaction of social networks and child obesity prevention program effects: the pathways trial.

PubMed

Shin, Hee-Sung; Valente, Thomas W; Riggs, Nathaniel R; Huh, Jimi; Spruijt-Metz, Donna; Chou, Chih-Ping; Ann Pentz, Mary

2014-06-01

Social network analysis was used to examine whether peer influence from one's social networks moderates obesity prevention program effects on obesity-related behaviors: healthful and unhealthful. Participants included 557 children residing in Southern California. The survey assessed health-promoting behaviors (i.e., physical activity at school, physical activity outside of school, and fruit and vegetable intake), as well as unhealthful behaviors (high-calorie, low-nutrient intake and sedentary activity), and peer exposure calculated from social network nominations as indicators of peer influence. Multilevel models were conducted separately on outcomes predicted by program participation, peer exposure, and program participation by peer exposure. Results indicated that peer exposure was positively associated with one's own healthful and unhealthful behaviors. Program participation effects were moderated by peer influence, but only when unhealthful peer influence was present. Results suggest that peer influence can diminish or amplify prevention programs Future interventions should consider peer-led components to promote healthful influence of peers on healthful and unhealthful behaviors, and programs should be mindful that their effects are moderated by social networks. Copyright © 2014 The Obesity Society.

Metabolome Integrated Analysis of High-Temperature Response in Pinus radiata.

PubMed

Escandón, Mónica; Meijón, Mónica; Valledor, Luis; Pascual, Jesús; Pinto, Gloria; Cañal, María Jesús

2018-01-01

The integrative omics approach is crucial to identify the molecular mechanisms underlying high-temperature response in non-model species. Based on future scenarios of heat increase, Pinus radiata plants were exposed to a temperature of 40°C for a period of 5 days, including recovered plants (30 days after last exposure to 40°C) in the analysis. The analysis of the metabolome using complementary mass spectrometry techniques (GC-MS and LC-Orbitrap-MS) allowed the reliable quantification of 2,287 metabolites. The analysis of identified metabolites and highlighter metabolic pathways across heat time exposure reveal the dynamism of the metabolome in relation to high-temperature response in P. radiata , identifying the existence of a turning point (on day 3) at which P. radiata plants changed from an initial stress response program (shorter-term response) to an acclimation one (longer-term response). Furthermore, the integration of metabolome and physiological measurements, which cover from the photosynthetic state to hormonal profile, suggests a complex metabolic pathway interaction network related to heat-stress response. Cytokinins (CKs), fatty acid metabolism and flavonoid and terpenoid biosynthesis were revealed as the most important pathways involved in heat-stress response in P. radiata , with zeatin riboside (ZR) and isopentenyl adenosine (iPA) as the key hormones coordinating these multiple and complex interactions. On the other hand, the integrative approach allowed elucidation of crucial metabolic mechanisms involved in heat response in P. radiata , as well as the identification of thermotolerance metabolic biomarkers (L-phenylalanine, hexadecanoic acid, and dihydromyricetin), crucial metabolites which can reschedule the metabolic strategy to adapt to high temperature.

Metabolome Integrated Analysis of High-Temperature Response in Pinus radiata

PubMed Central

Escandón, Mónica; Meijón, Mónica; Valledor, Luis; Pascual, Jesús; Pinto, Gloria; Cañal, María Jesús

2018-01-01

The integrative omics approach is crucial to identify the molecular mechanisms underlying high-temperature response in non-model species. Based on future scenarios of heat increase, Pinus radiata plants were exposed to a temperature of 40°C for a period of 5 days, including recovered plants (30 days after last exposure to 40°C) in the analysis. The analysis of the metabolome using complementary mass spectrometry techniques (GC-MS and LC-Orbitrap-MS) allowed the reliable quantification of 2,287 metabolites. The analysis of identified metabolites and highlighter metabolic pathways across heat time exposure reveal the dynamism of the metabolome in relation to high-temperature response in P. radiata, identifying the existence of a turning point (on day 3) at which P. radiata plants changed from an initial stress response program (shorter-term response) to an acclimation one (longer-term response). Furthermore, the integration of metabolome and physiological measurements, which cover from the photosynthetic state to hormonal profile, suggests a complex metabolic pathway interaction network related to heat-stress response. Cytokinins (CKs), fatty acid metabolism and flavonoid and terpenoid biosynthesis were revealed as the most important pathways involved in heat-stress response in P. radiata, with zeatin riboside (ZR) and isopentenyl adenosine (iPA) as the key hormones coordinating these multiple and complex interactions. On the other hand, the integrative approach allowed elucidation of crucial metabolic mechanisms involved in heat response in P. radiata, as well as the identification of thermotolerance metabolic biomarkers (L-phenylalanine, hexadecanoic acid, and dihydromyricetin), crucial metabolites which can reschedule the metabolic strategy to adapt to high temperature. PMID:29719546

Pathways to Program Success: A Qualitative Comparative Analysis (QCA) of Communities Putting Prevention to Work Case Study Programs

PubMed Central

Kane, Heather; Hinnant, Laurie; Day, Kristine; Council, Mary; Tzeng, Janice; Soler, Robin; Chambard, Megan; Roussel, Amy; Heirendt, Wendy

2016-01-01

Objective To examine the elements of capacity, a measure of organizational resources supporting program implementation that result in successful completion of public health program objectives in a public health initiative serving 50 communities. Design We used crisp set Qualitative Comparative Analysis (QCA) to analyze case study and quantitative data collected during the evaluation of the Communities Putting Prevention to Work (CPPW) program. Setting CPPW awardee program staff and partners implemented evidence-based public health improvements in counties, cities, and organizations (eg, worksites, schools). Participants Data came from case studies of 22 CPPW awardee programs that implemented evidence-based, community-and organizational-level public health improvements. Intervention Program staff implemented a range of evidence-based public health improvements related to tobacco control and obesity prevention. Main Outcome Measure The outcome measure was completion of approximately 60% of work plan objectives. Results Analysis of the capacity conditions revealed 2 combinations for completing most work plan objectives: (1) having experience implementing public health improvements in combination with having a history of collaboration with partners; and (2) not having experience implementing public health improvements in combination with having leadership support. Conclusion Awardees have varying levels of capacity. The combinations identified in this analysis provide important insights into how awardees with different combinations of elements of capacity achieved most of their work plan objectives. Even when awardees lack some elements of capacity, they can build it through strategies such as hiring staff and engaging new partners with expertise. In some instances, lacking 1 or more elements of capacity did not prevent an awardee from successfully completing objectives. Implications for Policy & Practice These findings can help funders and practitioners recognize and assemble different aspects of capacity to achieve more successful programs; awardees can draw on extant organizational strengths to compensate when other aspects of capacity are absent. PMID:27598714

5 CFR 362.402 - Program administration.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Program administration. 362.402 Section 362.402 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PATHWAYS PROGRAMS Presidential Management Fellows Program § 362.402 Program administration. (a) The Director may...

5 CFR 362.402 - Program administration.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Program administration. 362.402 Section 362.402 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PATHWAYS PROGRAMS Presidential Management Fellows Program § 362.402 Program administration. (a) The Director may...

77 FR 28193 - Excepted Service, Career and Career-Conditional Employment; and Pathways Programs

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-11

... advancement opportunities to Pathways Participants who are ``fast-tracked'' into desirable positions. The union's concern is misplaced. As an initial matter, the Pathways Participants are not being ``fast...-the-job experience that they otherwise would not be able to obtain. Indeed, rather than being ``fast...

Pathway Inspector: a pathway based web application for RNAseq analysis of model and non-model organisms.

PubMed

Bianco, Luca; Riccadonna, Samantha; Lavezzo, Enrico; Falda, Marco; Formentin, Elide; Cavalieri, Duccio; Toppo, Stefano; Fontana, Paolo

2017-02-01

Pathway Inspector is an easy-to-use web application helping researchers to find patterns of expression in complex RNAseq experiments. The tool combines two standard approaches for RNAseq analysis: the identification of differentially expressed genes and a topology-based analysis of enriched pathways. Pathway Inspector is equipped with ad hoc interactive graphical interfaces simplifying the discovery of modulated pathways and the integration of the differentially expressed genes in the corresponding pathway topology. Pathway Inspector is available at the website http://admiral.fmach.it/PI and has been developed in Python, making use of the Django Web Framework. Contact:paolo.fontana@fmach.it

What We Know about Guided Pathways: Helping Students to Complete Programs Faster. Research Overview

ERIC Educational Resources Information Center

Bailey, Thomas; Jaggars, Shanna Smith; Jenkins, Davis

2015-01-01

The idea behind guided pathways is straightforward. College students are more likely to complete a degree in a timely fashion if they choose a program and develop an academic plan early on, have a clear road map of the courses they need to take to complete a credential, and receive guidance and support to help them stay on plan. However, most…

[Programmed necrosis and necroptosis - molecular mechanisms].

PubMed

Giżycka, Agata; Chorostowska-Wynimko, Joanna

2015-12-16

Programmed necrosis has been proven vital for organism development and homeostasis maintenance. Its regulatory effects on functional activity of the immune system, as well as on pathways regulating the death mechanisms in cells with diminished apoptotic activity, including malignant cells, have been confirmed. There is also increasing evidence indicating necrosis involvement in many human pathologies. Contrary to previous beliefs, necrosis is not only a passive, pathological, gene-independent process. However, the current knowledge regarding molecular regulation of programmed necrosis is scarce. In part this is due to the multiplicity and complexity of signaling pathways involved in programmed necrosis, as well as the absence of specific cellular markers identifying this process, but also the ambiguous and imprecise international terminology. This review presents the current state of the art on molecular mechanisms of programmed necrosis. In particular, its specific and frequent form, necroptosis, is discussed. The role of RIP1 and RIP3 kinases in this process is presented, as well as the diverse pathways induced by ligation of tumor necrosis factor α, to its receptor, TNFR1, i.e. cell survival, apoptosis or necroptosis.

Correlation between messenger RNA expression and protein expression of immune checkpoint-associated molecules in bladder urothelial carcinoma: A retrospective study.

PubMed

Le Goux, Constance; Damotte, Diane; Vacher, Sophie; Sibony, Mathilde; Delongchamps, Nicolas Barry; Schnitzler, Anne; Terris, Benoit; Zerbib, Marc; Bieche, Ivan; Pignot, Géraldine

2017-05-01

Immunotherapy for bladder cancer seems to have promising results. Here, we evaluated the association between messenger RNA (mRNA) and protein levels and possible prognostic value of the programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA4) immune checkpoint pathways during bladder carcinogenesis. Tumor samples were obtained from 155 patients (84 with muscle-invasive bladder cancer [MIBC], and 71 non-muscle-invasive bladder cancer [NMIBC]) and normal bladder tissue from 15 patients. We evaluated the mRNA expression of 3 genes in the PD-1 pathway (PD-1, PD-L1, and PD-L2) and 4 in the CTLA4 pathway (CTLA4, CD28, CD80, and CD86) in normal and tumoral human bladder samples by quantitative real-time reverse transcription polymerase chain reaction, with immunohistochemistry used to evaluate the protein expression of PD-1 and PD-L1 in tumor and immune cells. Results of molecular analyses were compared with survival analyses. As compared with normal bladder tissue, MIBC tissue showed PD-1, PD-L1, CTLA4, and CD80 overexpression (59.5%, 60.7%, 84.5%, and 92.9%, respectively), whereas overexpression was lower in NMIBC tissue (22.5%, 4.2%, 35.2%, and 46.5%, respectively). The results of reverse transcription polymerase chain reaction analysis were confirmed by immunohistochemistry, with a high correlation between mRNA and protein expression. On multivariate analyses, overexpression of the studied genes was not associated with prognosis in relapse or progression of NMIBC or in recurrence-free and overall survival of MIBC. The CTLA4 pathway appears to be deregulated along with the PD-1/PD-L1 pathway in bladder carcinogenesis, with good correlation between mRNA and protein expression endorsing the useful role of immune checkpoints, especially for a large subgroup of MIBC. Copyright © 2017 Elsevier Inc. All rights reserved.

Pathways to suicidality across ethnic groups in Canadian adults: the possible role of social stress.

PubMed

Clarke, D E; Colantonio, A; Rhodes, A E; Escobar, M

2008-03-01

Ethnicity is an important determinant of mental health outcomes including suicidality (i.e. suicidal ideation and suicide attempt). Understanding ethnic differences in the pathways to suicidality is important for suicide prevention efforts in ethnically diverse populations. These pathways can be conceptualized within a social stress framework. The study examines ethnic differences in the pathways to suicidality in Canada within a social stress framework. Using data from the Canadian Community Health Survey Cycle 1.1 (CCHS 1.1) and path analysis, we examined the hypotheses that variations in (1) socio-economic status (SES), (2) sense of community belonging (SCB), (3) SES and SCB combined, and (4) SES, SCB and clinical factors combined can explain ethnic differences in suicidality. Francophone whites and Aboriginals were more likely to report suicidality compared to Anglophone whites whereas visible minorities and Foreign-born whites were least likely. Disadvantages in income, income and education, income and its combined effect with depression and alcohol dependence/abuse led to high rates even among the low-risk visible minority group. Indirect pathways for Asians differed from that of Blacks and South Asians, specifically through SCB. With the exception of SCB, Aboriginals were most disadvantaged, which exacerbated their risk for suicidality. However, their strong SCB buffered the risk for suicidality across pathways. Disadvantages in education, income and SCB were associated with the high risk for suicidality in Francophone whites. Francophone whites and Aboriginals had higher odds of suicidality compared to Anglophone whites; however, some pathways differed, indicating the need for targeted program planning and prevention efforts.

GeneMesh: a web-based microarray analysis tool for relating differentially expressed genes to MeSH terms.

PubMed

Jani, Saurin D; Argraves, Gary L; Barth, Jeremy L; Argraves, W Scott

2010-04-01

An important objective of DNA microarray-based gene expression experimentation is determining inter-relationships that exist between differentially expressed genes and biological processes, molecular functions, cellular components, signaling pathways, physiologic processes and diseases. Here we describe GeneMesh, a web-based program that facilitates analysis of DNA microarray gene expression data. GeneMesh relates genes in a query set to categories available in the Medical Subject Headings (MeSH) hierarchical index. The interface enables hypothesis driven relational analysis to a specific MeSH subcategory (e.g., Cardiovascular System, Genetic Processes, Immune System Diseases etc.) or unbiased relational analysis to broader MeSH categories (e.g., Anatomy, Biological Sciences, Disease etc.). Genes found associated with a given MeSH category are dynamically linked to facilitate tabular and graphical depiction of Entrez Gene information, Gene Ontology information, KEGG metabolic pathway diagrams and intermolecular interaction information. Expression intensity values of groups of genes that cluster in relation to a given MeSH category, gene ontology or pathway can be displayed as heat maps of Z score-normalized values. GeneMesh operates on gene expression data derived from a number of commercial microarray platforms including Affymetrix, Agilent and Illumina. GeneMesh is a versatile web-based tool for testing and developing new hypotheses through relating genes in a query set (e.g., differentially expressed genes from a DNA microarray experiment) to descriptors making up the hierarchical structure of the National Library of Medicine controlled vocabulary thesaurus, MeSH. The system further enhances the discovery process by providing links between sets of genes associated with a given MeSH category to a rich set of html linked tabular and graphic information including Entrez Gene summaries, gene ontologies, intermolecular interactions, overlays of genes onto KEGG pathway diagrams and heatmaps of expression intensity values. GeneMesh is freely available online at http://proteogenomics.musc.edu/genemesh/.

Process modeling and supply chain design for advanced biofuel production based on bio-oil gasification

NASA Astrophysics Data System (ADS)

Li, Qi

As a potential substitute for petroleum-based fuel, second generation biofuels are playing an increasingly important role due to their economic, environmental, and social benefits. With the rapid development of biofuel industry, there has been an increasing literature on the techno-economic analysis and supply chain design for biofuel production based on a variety of production pathways. A recently proposed production pathway of advanced biofuel is to convert biomass to bio-oil at widely distributed small-scale fast pyrolysis plants, then gasify the bio-oil to syngas and upgrade the syngas to transportation fuels in centralized biorefinery. This thesis aims to investigate two types of assessments on this bio-oil gasification pathway: techno-economic analysis based on process modeling and literature data; supply chain design with a focus on optimal decisions for number of facilities to build, facility capacities and logistic decisions considering uncertainties. A detailed process modeling with corn stover as feedstock and liquid fuels as the final products is presented. Techno-economic analysis of the bio-oil gasification pathway is also discussed to assess the economic feasibility. Some preliminary results show a capital investment of 438 million dollar and minimum fuel selling price (MSP) of $5.6 per gallon of gasoline equivalent. The sensitivity analysis finds that MSP is most sensitive to internal rate of return (IRR), biomass feedstock cost, and fixed capital cost. A two-stage stochastic programming is formulated to solve the supply chain design problem considering uncertainties in biomass availability, technology advancement, and biofuel price. The first-stage makes the capital investment decisions including the locations and capacities of the decentralized fast pyrolysis plants and the centralized biorefinery while the second-stage determines the biomass and biofuel flows. The numerical results and case study illustrate that considering uncertainties can be pivotal in this supply chain design and optimization problem. Also, farmers' participation has a significant effect on the decision making process.

Are critical pathways and implant standardization programs effective in reducing costs in total knee replacement operations?

PubMed

Ho, David M; Huo, Michael H

2007-07-01

Total knee replacement (TKR) operation is one of the most effective procedures, both clinically and in terms of cost. Because of increased volume and cost for this procedure during the past 3 decades, TKRs are often targeted for cost reduction. The purpose of this study was to evaluate the efficacy of two cost reducing methodologies, establishment of critical clinical pathways, and standardization of implant costs. Ninety patients (90 knees) were randomly selected from a population undergoing primary TKR during a 2-year period at a tertiary teaching hospital. Patients were assigned to three groups that corresponded to different strategies implemented during the evolution of the joint-replacement program. Medical records were reviewed for type of anesthesia, operative time, length of stay, and any perioperative complications. Financial information for each patient was compared among the three groups. Data analysis demonstrated that the institution of a critical pathway significantly shortened length of hospital stay and was effective in reducing the hospital costs by 18% (p < 0.05). In addition, standardization of surgical techniques under the care of a single surgeon substantially reduced the operative time. Selection of implants from a single vendor did not have any substantial effect in additionally reducing the costs. Standardized postoperative management protocols and critical clinical pathways can reduce costs and operative time. Future efforts must focus on lowering the costs of the prostheses, particularly with competitive bidding or capitation of prostheses costs. Although a single-vendor approach was not effective in this study, it is possible that a cost reduction could have been realized if more TKRs were performed, because the pricing contract was based on projected volume of TKRs to be done by the hospital.

Analysis of porcine granulosa cell death signaling pathways induced by vinclozolin.

PubMed

Knet, Malgorzata; Wartalski, Kamil; Hoja-Lukowicz, Dorota; Tabarowski, Zbigniew; Slomczynska, Maria; Duda, Malgorzata

2015-10-01

Recent studies suggest that disturbing androgen-signaling pathways in porcine ovarian follicles may cause granulosa cell (GC) death. For this reason, we investigated which apoptotic pathway is initiated after GC exposure to an environmental antiandrogen, vinclozolin (Vnz), in vitro. Immunocytochemistry, Western blots, and fluorometric assays were used to quantify caspase-3 and -9 expression and activity. To elucidate the specific mechanism of Vnz action and toxicity, GCs were assessed for viability, cytotoxicity, and apoptotic activity using the ApoTox-Glo Triplex Assay. To further determine the mechanism of GC death induced by Vnz, we used the Apoptosis Antibody Array Kit. In response to Vnz stimulus, we found an increased level of caspase-3 protein expression (P ≤ 0.001) and an increase in caspase-3 proteolytic activity (P ≤ 0.001), confirming that Vnz is a potent proapoptotic factor. The strong immunoreaction of caspase-9 after Vnz treatment (P ≤ 0.001) suggests that intrinsic mitochondrial apoptosis pathway was activated during GC death. On the other hand, caspase-8, being a part of the extrinsic receptor pathway, was also activated (P ≤ 0.001). Therefore, it is possible that Vnz induces porcine granulosal apoptosis also through a parallel pathway. Activation of these two pathways was confirmed by the Apoptosis Antibody Array Kit. In conclusion, it is possible that the intrinsic signaling pathway may not act as an initial trigger for GC apoptosis but might contribute to the amplification and propagation of apoptotic cell death in the granulosa layer after treatment with this antiandrogen. Moreover, Vnz disturbs the physiological process of programmed cell death. Consequently, this could explain why atretic follicles are rapidly removed and suggests that normal function of the ovarian follicle may be destroyed. Copyright © 2015 Elsevier Inc. All rights reserved.

Pathway modeling of microarray data: A case study of pathway activity changes in the testis following in utero exposure to dibutyl phthalate (DBP)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ovacik, Meric A.; Sen, Banalata; Euling, Susan Y.

Pathway activity level analysis, the approach pursued in this study, focuses on all genes that are known to be members of metabolic and signaling pathways as defined by the KEGG database. The pathway activity level analysis entails singular value decomposition (SVD) of the expression data of the genes constituting a given pathway. We explore an extension of the pathway activity methodology for application to time-course microarray data. We show that pathway analysis enhances our ability to detect biologically relevant changes in pathway activity using synthetic data. As a case study, we apply the pathway activity level formulation coupled with significancemore » analysis to microarray data from two different rat testes exposed in utero to Dibutyl Phthalate (DBP). In utero DBP exposure in the rat results in developmental toxicity of a number of male reproductive organs, including the testes. One well-characterized mode of action for DBP and the male reproductive developmental effects is the repression of expression of genes involved in cholesterol transport, steroid biosynthesis and testosterone synthesis that lead to a decreased fetal testicular testosterone. Previous analyses of DBP testes microarray data focused on either individual gene expression changes or changes in the expression of specific genes that are hypothesized, or known, to be important in testicular development and testosterone synthesis. However, a pathway analysis may inform whether there are additional affected pathways that could inform additional modes of action linked to DBP developmental toxicity. We show that Pathway activity analysis may be considered for a more comprehensive analysis of microarray data.« less

Dissecting Germ Cell Metabolism through Network Modeling.

PubMed

Whitmore, Leanne S; Ye, Ping

2015-01-01

Metabolic pathways are increasingly postulated to be vital in programming cell fate, including stemness, differentiation, proliferation, and apoptosis. The commitment to meiosis is a critical fate decision for mammalian germ cells, and requires a metabolic derivative of vitamin A, retinoic acid (RA). Recent evidence showed that a pulse of RA is generated in the testis of male mice thereby triggering meiotic commitment. However, enzymes and reactions that regulate this RA pulse have yet to be identified. We developed a mouse germ cell-specific metabolic network with a curated vitamin A pathway. Using this network, we implemented flux balance analysis throughout the initial wave of spermatogenesis to elucidate important reactions and enzymes for the generation and degradation of RA. Our results indicate that primary RA sources in the germ cell include RA import from the extracellular region, release of RA from binding proteins, and metabolism of retinal to RA. Further, in silico knockouts of genes and reactions in the vitamin A pathway predict that deletion of Lipe, hormone-sensitive lipase, disrupts the RA pulse thereby causing spermatogenic defects. Examination of other metabolic pathways reveals that the citric acid cycle is the most active pathway. In addition, we discover that fatty acid synthesis/oxidation are the primary energy sources in the germ cell. In summary, this study predicts enzymes, reactions, and pathways important for germ cell commitment to meiosis. These findings enhance our understanding of the metabolic control of germ cell differentiation and will help guide future experiments to improve reproductive health.

Androgen-induced programs for prostate epithelial growth and invasion arise in embryogenesis and are reactivated in cancer

PubMed Central

Schaeffer, EM; Marchionni, L; Huang, Z; Simons, B; Blackman, A; Yu, W; Parmigiani, G; Berman, DM

2008-01-01

Cancer cells differentiate along specific lineages that largely determine their clinical and biologic behavior. Distinct cancer phenotypes from different cells and organs likely result from unique gene expression repertoires established in the embryo and maintained after malignant transformation. We used comprehensive gene expression analysis to examine this concept in the prostate, an organ with a tractable developmental program and a high propensity for cancer. We focused on gene expression in the murine prostate rudiment at three time points during the first 48 h of exposure to androgen, which initiates proliferation and invasion of prostate epithelial buds into surrounding urogenital sinus mesenchyme. Here, we show that androgen exposure regulates genes previously implicated in prostate carcinogenesis comprising pathways for the phosphatase and tensin homolog (PTEN), fibroblast growth factor (FGF)/mitogen-activated protein kinase (MAPK), and Wnt signaling along with cellular programs regulating such ‘hallmarks’ of cancer as angiogenesis, apoptosis, migration and proliferation. We found statistically significant evidence for novel androgeninduced gene regulation events that establish and/or maintain prostate cell fate. These include modulation of gene expression through microRNAs, expression of specific transcription factors, and regulation of their predicted targets. By querying public gene expression databases from other tissues, we found that rather than generally characterizing androgen exposure or epithelial budding, the early prostate development program more closely resembles the program for human prostate cancer. Most importantly, early androgen-regulated genes and functional themes associated with prostate development were highly enriched in contrasts between increasingly lethal forms of prostate cancer, confirming a ‘reactivation’ of embryonic pathways for proliferation and invasion in prostate cancer progression. Among the genes with the most significant links to the development and cancer, we highlight coordinate induction of the transcription factor Sox9 and suppression of the proapoptotic phospholipid-binding protein Annexin A1 that link early prostate development to early prostate carcinogenesis. These results credential early prostate development as a reliable and valid model system for the investigation of genes and pathways that drive prostate cancer. PMID:18794802

PathFinder: reconstruction and dynamic visualization of metabolic pathways.

PubMed

Goesmann, Alexander; Haubrock, Martin; Meyer, Folker; Kalinowski, Jörn; Giegerich, Robert

2002-01-01

Beyond methods for a gene-wise annotation and analysis of sequenced genomes new automated methods for functional analysis on a higher level are needed. The identification of realized metabolic pathways provides valuable information on gene expression and regulation. Detection of incomplete pathways helps to improve a constantly evolving genome annotation or discover alternative biochemical pathways. To utilize automated genome analysis on the level of metabolic pathways new methods for the dynamic representation and visualization of pathways are needed. PathFinder is a tool for the dynamic visualization of metabolic pathways based on annotation data. Pathways are represented as directed acyclic graphs, graph layout algorithms accomplish the dynamic drawing and visualization of the metabolic maps. A more detailed analysis of the input data on the level of biochemical pathways helps to identify genes and detect improper parts of annotations. As an Relational Database Management System (RDBMS) based internet application PathFinder reads a list of EC-numbers or a given annotation in EMBL- or Genbank-format and dynamically generates pathway graphs.

Pathways to Youth Empowerment and Community Connectedness: A Study of Youth-Adult Partnership in Malaysian After-School, Co-Curricular Programs.

PubMed

Zeldin, Shepherd; Krauss, Steven Eric; Kim, Taehan; Collura, Jessica; Abdullah, Haslinda

2016-08-01

After-school programs are prevalent across the world, but there is a paucity of research that examines quality within the "black box" of programs at the point of service. Grounded in current theory, this research examined hypothesized pathways between the experience of youth-adult partnership (youth voice in decision-making; supportive adult relationships), the mediators of program safety and engagement, and the developmental outcomes of youth empowerment (leadership competence, policy control) and community connectedness (community connections, school attachment). Surveys were administered to 207 ethnically diverse (47.3 % female; 63.3 % Malay) youth, age 15-16, attending after-school co-curricular programs in Kuala Lumpur, Malaysia. Results showed that youth voice in program decision-making predicted both indicators of youth empowerment. Neither youth voice nor supportive adult relationships was directly associated with community connectedness, however. Program engagement mediated the associations between youth-adult partnership and empowerment. In contrast, program safety mediated the associations between youth-adult partnership and community connectedness. The findings indicate that the two core components of youth-adult partnership-youth voice and supportive adult relationships-may operate through different, yet complementary, pathways of program quality to predict developmental outcomes. Implications for future research are highlighted. For reasons of youth development and youth rights, the immediate challenge is to create opportunities for youth to speak on issues of program concern and to elevate those adults who are able and willing to help youth exercise their voice.

A new model to understand the career choice and practice location decisions of medical graduates.

PubMed

Stagg, P; Greenhill, J; Worley, P S

2009-01-01

Australian medical education is increasingly influenced by rural workforce policy. Therefore, understanding the influences on medical graduates' practice location and specialty choice is crucial for medical educators and medical workforce planners. The South Australian Flinders University Parallel Rural Community Curriculum (PRCC) was funded by the Australian Government to help address the rural doctor workforce shortage. The PRCC was the first community based medical education program in Australia to teach a full academic year of medicine in South Australian rural general practices. The aim of this research was to identify what factors influence the career choices of PRCC graduates. A retrospective survey of all contactable graduates of the PRCC was undertaken. Quantitative data were analysed using SPSS 14.0 for Windows. Qualitative data were entered into NVIVO 7 software for coding, and analysed using content analysis. Usable data were collected from 46 of the 86 contactable graduates (53%). More than half of the respondents (54%) reported being on a rural career path. A significant relationship exists between being on a rural career pathway and making the decision prior to or during medical school (p = 0.027), and between graduates in vocational training who are on an urban career path and making a decision on career specialty after graduation from medical school (p = .004). Graduates in a general practice vocational training program are more likely to be on a rural career pathway than graduates in a specialty other than general practice (p = .003). A key influence on graduates' practice location is geographic location prior to entering medical school. Key influences on graduates choosing a rural career pathway are: having a spouse/partner with a rural background; clinical teachers and mentors; the extended rural based undergraduate learning experience; and a specialty preference for general practice. A lack of rural based internships and specialist training places is influencing both urban- and rural-origin graduates to practise in urban locations. Further analysis of graduates' career pathway choices (rural or urban) and geographic background (rural or urban) was conducted. This resulted in the development of a new model, 'The Four Qs Model'. This model consists of four quadrants derived from the variables career pathway choice (rural or urban) and geographic background (rural or urban). Clustering of consistent demographic and qualitative trends unique to each quadrant was demonstrated. The distinctive clustering that emerged from the data resulted in the quadrants being renamed 'The True Believers', 'The Convertibles' 'The Frustrated' and 'The Metro Docs'. The PRCC is influencing graduates to choose a rural career path. The PRCC program affirms the career preferences of rural origin students while graduates with little rural exposure prior to the PRCC report being positively influenced to pursue a rural career path. The Four Qs Model is a useful model in that it demonstrates consistent themes in the characteristics of PRCC graduates and assists understanding of why they choose a rural medical career. This could be relevant to the selection of medical students into rural medical education programs and in the construction of rural curricula. The model also offers a useful framework for further research in this field.

Exploring pathway interactions in insulin resistant mouse liver

PubMed Central

2011-01-01

Background Complex phenotypes such as insulin resistance involve different biological pathways that may interact and influence each other. Interpretation of related experimental data would be facilitated by identifying relevant pathway interactions in the context of the dataset. Results We developed an analysis approach to study interactions between pathways by integrating gene and protein interaction networks, biological pathway information and high-throughput data. This approach was applied to a transcriptomics dataset to investigate pathway interactions in insulin resistant mouse liver in response to a glucose challenge. We identified regulated pathway interactions at different time points following the glucose challenge and also studied the underlying protein interactions to find possible mechanisms and key proteins involved in pathway cross-talk. A large number of pathway interactions were found for the comparison between the two diet groups at t = 0. The initial response to the glucose challenge (t = 0.6) was typed by an acute stress response and pathway interactions showed large overlap between the two diet groups, while the pathway interaction networks for the late response were more dissimilar. Conclusions Studying pathway interactions provides a new perspective on the data that complements established pathway analysis methods such as enrichment analysis. This study provided new insights in how interactions between pathways may be affected by insulin resistance. In addition, the analysis approach described here can be generally applied to different types of high-throughput data and will therefore be useful for analysis of other complex datasets as well. PMID:21843341

Assessing national provision of care: variability in bariatric clinical care pathways.

PubMed

Telem, Dana A; Majid, Saniea F; Powers, Kinga; DeMaria, Eric; Morton, John; Jones, Daniel B

2017-02-01

The American Society for Metabolic and Bariatric Surgery (ASMBS) Quality Improvement and Patient Safety (QIPS) Committee hypothesized that collecting and sharing clinical pathways could provide a valuable resource to new and existing bariatric programs. To shed light on the variability in practice patterns across the country by analyzing pathways. United States Centers of Excellence METHODS: From June 2014 to April 2015, clinical pathways pertaining to preoperative, intraoperative, and postoperative management of bariatric patients were solicited from the ASMBS executive council (EC), QIPS committee members, and state chapter presidents. Pathways were de-identified and then analyzed based on predetermined metrics pertaining to preoperative, intraoperative, and postoperative care. Concordance and discordance were then analyzed. In total, 31 pathways were collected; response rate was 80% from the EC, 77% from the QIPS committee, and 21% from state chapter presidents. The number of pathways sent in ranged from 1 to 10 with a median of 3 pathways per individual or institution. The majority of pathways centered on perioperative care (80%). Binary assessment (presence or absence) of variables found a high concordance (defined by greater than 65% of pathways accounting for that parameter) in only 6 variables: nutritional evaluation, psychological evaluation, intraoperative venous thromboembolism (VTE) prophylaxis, utilization of antiemetics in the postoperative period, a dedicated pain pathway, and postoperative laboratory evaluation. There is considerable national variation in clinical pathways among practicing bariatric surgeons. Most pathways center on Metabolic and Bariatric Surgery Accredited Quality Improvement Program (MBSAQIP) accreditation parameters, patient satisfaction, or Surgical Care Improvement Protocol (SCIP) measures. These pathways provide a path toward standardization of improved care. Copyright © 2016. Published by Elsevier Inc.

Separate enrichment analysis of pathways for up- and downregulated genes.

PubMed

Hong, Guini; Zhang, Wenjing; Li, Hongdong; Shen, Xiaopei; Guo, Zheng

2014-03-06

Two strategies are often adopted for enrichment analysis of pathways: the analysis of all differentially expressed (DE) genes together or the analysis of up- and downregulated genes separately. However, few studies have examined the rationales of these enrichment analysis strategies. Using both microarray and RNA-seq data, we show that gene pairs with functional links in pathways tended to have positively correlated expression levels, which could result in an imbalance between the up- and downregulated genes in particular pathways. We then show that the imbalance could greatly reduce the statistical power for finding disease-associated pathways through the analysis of all-DE genes. Further, using gene expression profiles from five types of tumours, we illustrate that the separate analysis of up- and downregulated genes could identify more pathways that are really pertinent to phenotypic difference. In conclusion, analysing up- and downregulated genes separately is more powerful than analysing all of the DE genes together.

Does Research Training During Residency Promote Scholarship and Influence Career Choice? A Cross-Sectional Analysis of a 10-Year Cohort of the UCSF-PRIME Internal Medicine Residency Program.

PubMed

Kohlwes, Jeffrey; O'Brien, Bridget; Stanley, Marion; Grant, Ross; Shunk, Rebecca; Connor, Denise; Cornett, Patricia; Hollander, Harry

2016-01-01

The Association of Program Directors in Internal Medicine, the Accreditation Council for Graduate Medical Education, the Alliance for Academic Internal Medicine, and the Carnegie Foundation report on medical education recommend creating individualized learning pathways during medical training so that learners can experience broader professional roles beyond patient care. Little data exist to support the success of these specialized pathways in graduate medical education. We present the 10-year experience of the Primary Care Medicine Education (PRIME) track, a clinical-outcomes research pathway for internal medicine residents at the University of California San Francisco (UCSF). We hypothesized that participation in an individualized learning track, PRIME, would lead to a greater likelihood of publishing research from residency and accessing adequate career mentorship and would be influential on subsequent alumni careers. We performed a cross-sectional survey of internal medicine residency alumni from UCSF who graduated in 2001 through 2010. We compared responses of PRIME and non-PRIME categorical alumni. We used Pearson's chi-square and Student's t test to compare PRIME and non-PRIME alumni on categorical and continuous variables. Sixty-six percent (211/319) of alumni responded to the survey. A higher percentage of PRIME alumni published residency research projects compared to non-PRIME alumni (64% vs. 40%; p = .002). The number of PRIME alumni identifying research as their primary career role was not significantly different from non-PRIME internal medicine residency graduates (35% of PRIME vs. 29% non-PRIME). Process measures that could explain these findings include adequate access to mentors (M 4.4 for PRIME vs. 3.6 for non-PRIME alumni, p < .001, on a 5-point Likert scale) and agreeing that mentoring relationships affected career choice (M 4.2 for PRIME vs. 3.7 for categorical alumni, p = .001). Finally, 63% of PRIME alumni agreed that their research experience during residency influenced their subsequent career choice versus 46% of non-PRIME alumni (p = .023). Our results support the concept that providing residents with an individualized learning pathway focusing on clinical outcomes research during residency enables them to successfully publish manuscripts and access mentorship, and may influence subsequent career choice. Implementation of individualized residency program tracks that nurture academic interests along with clinical skills can support career development within medicine residency programs.

Seeking unique and common biological themes in multiple gene lists or datasets: pathway pattern extraction pipeline for pathway-level comparative analysis.

PubMed

Yi, Ming; Mudunuri, Uma; Che, Anney; Stephens, Robert M

2009-06-29

One of the challenges in the analysis of microarray data is to integrate and compare the selected (e.g., differential) gene lists from multiple experiments for common or unique underlying biological themes. A common way to approach this problem is to extract common genes from these gene lists and then subject these genes to enrichment analysis to reveal the underlying biology. However, the capacity of this approach is largely restricted by the limited number of common genes shared by datasets from multiple experiments, which could be caused by the complexity of the biological system itself. We now introduce a new Pathway Pattern Extraction Pipeline (PPEP), which extends the existing WPS application by providing a new pathway-level comparative analysis scheme. To facilitate comparing and correlating results from different studies and sources, PPEP contains new interfaces that allow evaluation of the pathway-level enrichment patterns across multiple gene lists. As an exploratory tool, this analysis pipeline may help reveal the underlying biological themes at both the pathway and gene levels. The analysis scheme provided by PPEP begins with multiple gene lists, which may be derived from different studies in terms of the biological contexts, applied technologies, or methodologies. These lists are then subjected to pathway-level comparative analysis for extraction of pathway-level patterns. This analysis pipeline helps to explore the commonality or uniqueness of these lists at the level of pathways or biological processes from different but relevant biological systems using a combination of statistical enrichment measurements, pathway-level pattern extraction, and graphical display of the relationships of genes and their associated pathways as Gene-Term Association Networks (GTANs) within the WPS platform. As a proof of concept, we have used the new method to analyze many datasets from our collaborators as well as some public microarray datasets. This tool provides a new pathway-level analysis scheme for integrative and comparative analysis of data derived from different but relevant systems. The tool is freely available as a Pathway Pattern Extraction Pipeline implemented in our existing software package WPS, which can be obtained at http://www.abcc.ncifcrf.gov/wps/wps_index.php.

Pathway Inspector: a pathway based web application for RNAseq analysis of model and non-model organisms

PubMed Central

Bianco, Luca; Riccadonna, Samantha; Lavezzo, Enrico; Falda, Marco; Formentin, Elide; Cavalieri, Duccio; Toppo, Stefano

2017-01-01

Abstract Summary: Pathway Inspector is an easy-to-use web application helping researchers to find patterns of expression in complex RNAseq experiments. The tool combines two standard approaches for RNAseq analysis: the identification of differentially expressed genes and a topology-based analysis of enriched pathways. Pathway Inspector is equipped with ad hoc interactive graphical interfaces simplifying the discovery of modulated pathways and the integration of the differentially expressed genes in the corresponding pathway topology. Availability and Implementation: Pathway Inspector is available at the website http://admiral.fmach.it/PI and has been developed in Python, making use of the Django Web Framework. Contact: paolo.fontana@fmach.it PMID:28158604

MinePath: Mining for Phenotype Differential Sub-paths in Molecular Pathways

PubMed Central

Koumakis, Lefteris; Kartsaki, Evgenia; Chatzimina, Maria; Zervakis, Michalis; Vassou, Despoina; Marias, Kostas; Moustakis, Vassilis; Potamias, George

2016-01-01

Pathway analysis methodologies couple traditional gene expression analysis with knowledge encoded in established molecular pathway networks, offering a promising approach towards the biological interpretation of phenotype differentiating genes. Early pathway analysis methodologies, named as gene set analysis (GSA), view pathways just as plain lists of genes without taking into account either the underlying pathway network topology or the involved gene regulatory relations. These approaches, even if they achieve computational efficiency and simplicity, consider pathways that involve the same genes as equivalent in terms of their gene enrichment characteristics. Most recent pathway analysis approaches take into account the underlying gene regulatory relations by examining their consistency with gene expression profiles and computing a score for each profile. Even with this approach, assessing and scoring single-relations limits the ability to reveal key gene regulation mechanisms hidden in longer pathway sub-paths. We introduce MinePath, a pathway analysis methodology that addresses and overcomes the aforementioned problems. MinePath facilitates the decomposition of pathways into their constituent sub-paths. Decomposition leads to the transformation of single-relations to complex regulation sub-paths. Regulation sub-paths are then matched with gene expression sample profiles in order to evaluate their functional status and to assess phenotype differential power. Assessment of differential power supports the identification of the most discriminant profiles. In addition, MinePath assess the significance of the pathways as a whole, ranking them by their p-values. Comparison results with state-of-the-art pathway analysis systems are indicative for the soundness and reliability of the MinePath approach. In contrast with many pathway analysis tools, MinePath is a web-based system (www.minepath.org) offering dynamic and rich pathway visualization functionality, with the unique characteristic to color regulatory relations between genes and reveal their phenotype inclination. This unique characteristic makes MinePath a valuable tool for in silico molecular biology experimentation as it serves the biomedical researchers’ exploratory needs to reveal and interpret the regulatory mechanisms that underlie and putatively govern the expression of target phenotypes. PMID:27832067

MinePath: Mining for Phenotype Differential Sub-paths in Molecular Pathways.

PubMed

Koumakis, Lefteris; Kanterakis, Alexandros; Kartsaki, Evgenia; Chatzimina, Maria; Zervakis, Michalis; Tsiknakis, Manolis; Vassou, Despoina; Kafetzopoulos, Dimitris; Marias, Kostas; Moustakis, Vassilis; Potamias, George

2016-11-01

Pathway analysis methodologies couple traditional gene expression analysis with knowledge encoded in established molecular pathway networks, offering a promising approach towards the biological interpretation of phenotype differentiating genes. Early pathway analysis methodologies, named as gene set analysis (GSA), view pathways just as plain lists of genes without taking into account either the underlying pathway network topology or the involved gene regulatory relations. These approaches, even if they achieve computational efficiency and simplicity, consider pathways that involve the same genes as equivalent in terms of their gene enrichment characteristics. Most recent pathway analysis approaches take into account the underlying gene regulatory relations by examining their consistency with gene expression profiles and computing a score for each profile. Even with this approach, assessing and scoring single-relations limits the ability to reveal key gene regulation mechanisms hidden in longer pathway sub-paths. We introduce MinePath, a pathway analysis methodology that addresses and overcomes the aforementioned problems. MinePath facilitates the decomposition of pathways into their constituent sub-paths. Decomposition leads to the transformation of single-relations to complex regulation sub-paths. Regulation sub-paths are then matched with gene expression sample profiles in order to evaluate their functional status and to assess phenotype differential power. Assessment of differential power supports the identification of the most discriminant profiles. In addition, MinePath assess the significance of the pathways as a whole, ranking them by their p-values. Comparison results with state-of-the-art pathway analysis systems are indicative for the soundness and reliability of the MinePath approach. In contrast with many pathway analysis tools, MinePath is a web-based system (www.minepath.org) offering dynamic and rich pathway visualization functionality, with the unique characteristic to color regulatory relations between genes and reveal their phenotype inclination. This unique characteristic makes MinePath a valuable tool for in silico molecular biology experimentation as it serves the biomedical researchers' exploratory needs to reveal and interpret the regulatory mechanisms that underlie and putatively govern the expression of target phenotypes.

Pathway-GPS and SIGORA: identifying relevant pathways based on the over-representation of their gene-pair signatures

PubMed Central

Foroushani, Amir B.K.; Brinkman, Fiona S.L.

2013-01-01

Motivation. Predominant pathway analysis approaches treat pathways as collections of individual genes and consider all pathway members as equally informative. As a result, at times spurious and misleading pathways are inappropriately identified as statistically significant, solely due to components that they share with the more relevant pathways. Results. We introduce the concept of Pathway Gene-Pair Signatures (Pathway-GPS) as pairs of genes that, as a combination, are specific to a single pathway. We devised and implemented a novel approach to pathway analysis, Signature Over-representation Analysis (SIGORA), which focuses on the statistically significant enrichment of Pathway-GPS in a user-specified gene list of interest. In a comparative evaluation of several published datasets, SIGORA outperformed traditional methods by delivering biologically more plausible and relevant results. Availability. An efficient implementation of SIGORA, as an R package with precompiled GPS data for several human and mouse pathway repositories is available for download from http://sigora.googlecode.com/svn/. PMID:24432194

Pathways to URM Retention: IBP's Professional Development and Mentoring Activities

NASA Astrophysics Data System (ADS)

Johnson, A.; Williamson Whitney, V.; Ricciardi, L.; Detrick, L.; Siegfried, D.; Fauver, A.; Ithier-Guzman, W.; Thomas, S. H.; Valaitis, S.

2013-05-01

As a not for profit organization, the Institute for Broadening Participation (IBP) hosts a variety of initiatives designed to increase the retention of underrepresented minority (URM) students pursuing pathways in STEM. IBP also assists with formative program evaluation design and implementation to help strengthen URM recruitment and retention elements. Successful initiatives include virtual and face-to-face components that bring together URM students with established URM and other scientists in academia, government and industry. These connections provide URMs with mentoring, networking opportunities, and professional skill development contributing to an improved retention rate of URM students. IBP's initiatives include the NASA One Stop Shopping Initiative (NASA OSSI), Pathways to Ocean Science and Engineering, and the Minorities Striving and Pursuing Higher Degrees of Success (MS PHD'S) in Earth System Science (ESS) Professional Development Program. The NASA OSSI recruits and facilitates student engagement in NASA education and employment opportunities. Pathways to Ocean Science connects and supports URM students with Ocean Science REU programs and serves as a resource for REU program directors. Pathways to Engineering has synthesized mentoring resources into an online mentoring manual for URM students that has been extensively vetted by mentoring experts throughout the country. The mentoring manual, which is organized by roles, provides undergraduates, graduates, postdocs, faculty and project directors with valuable resources. MS PHD'S, one of IBP's longest running and most successful initiatives, focuses on increasing the retention rate of URM students receiving advanced degrees in ESS. The program addresses barriers to retention in ESS including isolation, lack of preparation and professional development, and lack of mentoring. Program activities center on peer-to-peer community building, professional development exercises, networking experiences, one-on-one mentoring, and a facilitated virtual community. MS PHD'S students report a reduced sense of isolation, an increased sense of community, and a higher level of confidence about their ability to succeed in their chosen field. 42 MS PHD'S alumni have completed their PhD and are actively engaged in the ESS workforce.

Genetic and Molecular Analysis of the Mechanisms by which TSC Regulates Neuronal Differentiation

DTIC Science & Technology

2009-03-01

2004 Programmed autophagy in the Drosophila fat body is in- duced by ecdysone through regulation of the PI3K pathway. Dev. Cell 7: 179–192. Sarbassov...embryonic Drosophila CNS. Mech. Dev. 64: 137–151. Scott, R. C., O. Schuldiner and T. P. Neufeld, 2004 Role and reg- ulation of starvation-induced autophagy ...in The Development of Drosophila melanogaster , edited by M. Bates and A. Martinez-Arias. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY

Developing Breast Cancer Program at Xavier: Genomic and Proteomic Analysis of Signaling Pathways Involved in Xenohormone and MEK5 Regulation of Breast Cancer

DTIC Science & Technology

2005-05-01

purification of intermediates to antibiotic medicines Hangzhou First Pharmaceutical Company Hangzhou, P. R. China Research chemist September 1987...NAME OF RESPONSIBLE PERSON OF ABSTRACT OF PAGES a. REPORT b. ABSTRACT c . THIS PAGE LTU 19b. TELEPHONE NUMBER (include area U U U 32 code) Standard Form...used as the second-dimension system c . BioRad PROTEAN® d. VersaDocTM Imaging Systems with PDQUEST software Preliminary results Using the newly installed

Developing Breast Cancer Program at Xavier; Genomic and Proteomic Analysis of Signaling Pathways Involved in Xenohormone and MEK5 Regulation of Breast

DTIC Science & Technology

2008-05-01

will build a core of human talent that will address scientific problems such as drug resistance and the effect of environmental agents on breast...normal for Xavier University after the continuing effects of Hurricane Katrina. Xavier University of Louisiana did an amazing recovery from the...an increase in expression of ERβ . To determine the effects of MEK5 on ER signaling we used an ERE-luciferase reporter assay. Parental MCF-7 cells

Are Universities Providing Non-STEM Students the Mathematics Preparation Required by Their Programs?: A Case Study of A Quantitative Literacy Pathway and Vertical Alignment from Remediation to Degree Completion

ERIC Educational Resources Information Center

Allen, Charles

2017-01-01

Informed by Gagne's belief in the necessity of prerequisite knowledge for new learning, and Bruner's Spiral Curriculum Theory, the objective of this case study was to explore the postsecondary pathway from remedial mathematics, through one gateway mathematics course, and into the quantitative literacy requirements of various non-STEM programs of…

Programmed Cell Death-1/Programmed Death-ligand 1 Pathway: A New Target for Sepsis.

PubMed

Liu, Qiang; Li, Chun-Sheng

2017-04-20

Sepsis remains a leading cause of death in many Intensive Care Units worldwide. Immunosuppression has been a primary focus of sepsis research as a key pathophysiological mechanism. Given the important role of the negative costimulatory molecules programmed cell death-1 (PD-1) and programmed death-ligand 1 (PD-L1) in the occurrence of immunosuppression during sepsis, we reviewed literatures related to the PD-1/PD-L1 pathway to examine its potential as a new target for sepsis treatment. Studies of the association between PD-1/PD-L1 and sepsis published up to January 31, 2017, were obtained by searching the PubMed database. English language studies, including those based on animal models, clinical research, and reviews, with data related to PD-1/PD-L1 and sepsis, were evaluated. Immunomodulatory therapeutics could reverse the deactivation of immune cells caused by sepsis and restore immune cell activation and function. Blockade of the PD-1/PD-L1 pathway could reduce the exhaustion of T-cells and enhance the proliferation and activation of T-cells. The anti-PD-1/PD-L1 pathway shows promise as a new target for sepsis treatment. This review provides a basis for clinical trials and future studies aimed at revaluating the efficacy and safety of this targeted approach.

Career Choice of "Fifth Pathway" Graduates from New York State Medical Schools.

ERIC Educational Resources Information Center

Stimmel, Barry; Smith, Harry, Jr.

1985-01-01

Graduates of "fifth pathway" programs at medical schools in New York state between 1976-1978 were studied to determine their professional careers and choice of medical specialties. Fifth pathway graduates, 95 percent from Mexican medical schools, were more likely to select nonprimary care than primary care specialties. (Author/MLW)

Building Competency-Based Pathways: Successes and Challenges from Leaders in the Field. A Forum

ERIC Educational Resources Information Center

American Youth Policy Forum, 2011

2011-01-01

This forum provided an overview of competency-based pathways to education and described programs that have successfully utilized these pathways to move all students to success in high school and beyond. Speakers highlighted how innovative learning environments that base student advancement upon mastery of measurable learning objectives have been…

A System-Level Pathway-Phenotype Association Analysis Using Synthetic Feature Random Forest

PubMed Central

Pan, Qinxin; Hu, Ting; Malley, James D.; Andrew, Angeline S.; Karagas, Margaret R.; Moore, Jason H.

2015-01-01

As the cost of genome-wide genotyping decreases, the number of genome-wide association studies (GWAS) has increased considerably. However, the transition from GWAS findings to the underlying biology of various phenotypes remains challenging. As a result, due to its system-level interpretability, pathway analysis has become a popular tool for gaining insights on the underlying biology from high-throughput genetic association data. In pathway analyses, gene sets representing particular biological processes are tested for significant associations with a given phenotype. Most existing pathway analysis approaches rely on single-marker statistics and assume that pathways are independent of each other. As biological systems are driven by complex biomolecular interactions, embracing the complex relationships between single-nucleotide polymorphisms (SNPs) and pathways needs to be addressed. To incorporate the complexity of gene-gene interactions and pathway-pathway relationships, we propose a system-level pathway analysis approach, synthetic feature random forest (SF-RF), which is designed to detect pathway-phenotype associations without making assumptions about the relationships among SNPs or pathways. In our approach, the genotypes of SNPs in a particular pathway are aggregated into a synthetic feature representing that pathway via Random Forest (RF). Multiple synthetic features are analyzed using RF simultaneously and the significance of a synthetic feature indicates the significance of the corresponding pathway. We further complement SF-RF with pathway-based Statistical Epistasis Network (SEN) analysis that evaluates interactions among pathways. By investigating the pathway SEN, we hope to gain additional insights into the genetic mechanisms contributing to the pathway-phenotype association. We apply SF-RF to a population-based genetic study of bladder cancer and further investigate the mechanisms that help explain the pathway-phenotype associations using SEN. The bladder cancer associated pathways we found are both consistent with existing biological knowledge and reveal novel and plausible hypotheses for future biological validations. PMID:24535726

Genome Expression Pathway Analysis Tool – Analysis and visualization of microarray gene expression data under genomic, proteomic and metabolic context

PubMed Central

Weniger, Markus; Engelmann, Julia C; Schultz, Jörg

2007-01-01

Background Regulation of gene expression is relevant to many areas of biology and medicine, in the study of treatments, diseases, and developmental stages. Microarrays can be used to measure the expression level of thousands of mRNAs at the same time, allowing insight into or comparison of different cellular conditions. The data derived out of microarray experiments is highly dimensional and often noisy, and interpretation of the results can get intricate. Although programs for the statistical analysis of microarray data exist, most of them lack an integration of analysis results and biological interpretation. Results We have developed GEPAT, Genome Expression Pathway Analysis Tool, offering an analysis of gene expression data under genomic, proteomic and metabolic context. We provide an integration of statistical methods for data import and data analysis together with a biological interpretation for subsets of probes or single probes on the chip. GEPAT imports various types of oligonucleotide and cDNA array data formats. Different normalization methods can be applied to the data, afterwards data annotation is performed. After import, GEPAT offers various statistical data analysis methods, as hierarchical, k-means and PCA clustering, a linear model based t-test or chromosomal profile comparison. The results of the analysis can be interpreted by enrichment of biological terms, pathway analysis or interaction networks. Different biological databases are included, to give various information for each probe on the chip. GEPAT offers no linear work flow, but allows the usage of any subset of probes and samples as a start for a new data analysis. GEPAT relies on established data analysis packages, offers a modular approach for an easy extension, and can be run on a computer grid to allow a large number of users. It is freely available under the LGPL open source license for academic and commercial users at . Conclusion GEPAT is a modular, scalable and professional-grade software integrating analysis and interpretation of microarray gene expression data. An installation available for academic users can be found at . PMID:17543125

Developmental programming modulates olfactory behavior in C. elegans via endogenous RNAi pathways

PubMed Central

Sims, Jennie R; Ow, Maria C; Nishiguchi, Mailyn A; Kim, Kyuhyung; Sengupta, Piali; Hall, Sarah E

2016-01-01

Environmental stress during early development can impact adult phenotypes via programmed changes in gene expression. C. elegans larvae respond to environmental stress by entering the stress-resistant dauer diapause pathway and resume development once conditions improve (postdauers). Here we show that the osm-9 TRPV channel gene is a target of developmental programming and is down-regulated specifically in the ADL chemosensory neurons of postdauer adults, resulting in a corresponding altered olfactory behavior that is mediated by ADL in an OSM-9-dependent manner. We identify a cis-acting motif bound by the DAF-3 SMAD and ZFP-1 (AF10) proteins that is necessary for the differential regulation of osm-9, and demonstrate that both chromatin remodeling and endo-siRNA pathways are major contributors to the transcriptional silencing of the osm-9 locus. This work describes an elegant mechanism by which developmental experience influences adult phenotypes by establishing and maintaining transcriptional changes via RNAi and chromatin remodeling pathways. DOI: http://dx.doi.org/10.7554/eLife.11642.001 PMID:27351255

A Multi-step Transcriptional and Chromatin State Cascade Underlies Motor Neuron Programming from Embryonic Stem Cells.

PubMed

Velasco, Silvia; Ibrahim, Mahmoud M; Kakumanu, Akshay; Garipler, Görkem; Aydin, Begüm; Al-Sayegh, Mohamed Ahmed; Hirsekorn, Antje; Abdul-Rahman, Farah; Satija, Rahul; Ohler, Uwe; Mahony, Shaun; Mazzoni, Esteban O

2017-02-02

Direct cell programming via overexpression of transcription factors (TFs) aims to control cell fate with the degree of precision needed for clinical applications. However, the regulatory steps involved in successful terminal cell fate programming remain obscure. We have investigated the underlying mechanisms by looking at gene expression, chromatin states, and TF binding during the uniquely efficient Ngn2, Isl1, and Lhx3 motor neuron programming pathway. Our analysis reveals a highly dynamic process in which Ngn2 and the Isl1/Lhx3 pair initially engage distinct regulatory regions. Subsequently, Isl1/Lhx3 binding shifts from one set of targets to another, controlling regulatory region activity and gene expression as cell differentiation progresses. Binding of Isl1/Lhx3 to later motor neuron enhancers depends on the Ebf and Onecut TFs, which are induced by Ngn2 during the programming process. Thus, motor neuron programming is the product of two initially independent transcriptional modules that converge with a feedforward transcriptional logic. Copyright © 2017 Elsevier Inc. All rights reserved.

Trust Pathways, Trust Catalysts, Theory of Change and Citizen Science: A COASST Case Study

NASA Astrophysics Data System (ADS)

Burgess, H. K.; Parrish, J.; Dolliver, J.; Metes, J.; Ballard, H. L.

2017-12-01

Environmental challenges, from local water quality to the effects of global climate change, are overwhelming the mainstream science community. We need help. Citizen science offers one solution pathway - in the ideal, thousands of participants engaged in authentic science that delivers high quality information not otherwise obtainable. But in the real world, are citizen science data used? And more broadly: what are the interactions between citizen science and natural resource management in service of conserving or protecting system structure and function? The Coastal Observation and Seabird Survey Team (COASST) is a rigoros citizen science program focused on documenting patterns of beached bird and marine debris abundance on beaches along the coast of the Pacific Northwest and Alaska. Housed at the University of Washington, COASST partners directly with a wide range of local, tribal, state and federal agencies to effect positive change and a wide range of scientific, community and educational outcomes. Following from years of trial, error and adaptive management, we propose a "trust pathway" between citizen science and agencies that moves from an initial contact and multiple interaction types to eventual partnership and capacity sharing. Along the way are trust catalysts, including but not limited to: stakeholder engagement, data QA/QC, interactive data analysis, housing at an academic institution, and timely, repeated communication. In this presentation, we will discuss strategies and outcomes employed by COASST for fostering trust and successful partnerships, drawing on 20 years of program experience as well as reflections from a variety of partners and stakholdres.

High-Fat Diet During Mouse Pregnancy and Lactation Targets GIP-Regulated Metabolic Pathways in Adult Male Offspring.

PubMed

Kruse, Michael; Keyhani-Nejad, Farnaz; Isken, Frank; Nitz, Barbara; Kretschmer, Anja; Reischl, Eva; de las Heras Gala, Tonia; Osterhoff, Martin A; Grallert, Harald; Pfeiffer, Andreas F H

2016-03-01

Maternal obesity is a worldwide problem associated with increased risk of metabolic diseases in the offspring. Genetic deletion of the gastric inhibitory polypeptide (GIP) receptor (GIPR) prevents high-fat diet (HFD)-induced obesity in mice due to specific changes in energy and fat cell metabolism. We investigated whether GIP-associated pathways may be targeted by fetal programming and mimicked the situation by exposing pregnant mice to control or HFD during pregnancy (intrauterine [IU]) and lactation (L). Male wild-type (WT) and Gipr(-/-) offspring received control chow until 25 weeks of age followed by 20 weeks of HFD. Gipr(-/-) offspring of mice exposed to HFD during IU/L became insulin resistant and obese and exhibited increased adipose tissue inflammation and decreased peripheral tissue substrate utilization after being reintroduced to HFD, similar to WT mice on regular chow during IU/L. They showed decreased hypothalamic insulin sensitivity compared with Gipr(-/-) mice on control diet during IU/L. DNA methylation analysis revealed increased methylation of CpG dinucleotides and differential transcription factor binding of promoter regions of genes involved in lipid oxidation in the muscle of Gipr(-/-) offspring on HFD during IU/L, which were inversely correlated with gene expression levels. Our data identify GIP-regulated metabolic pathways that are targeted by fetal programming. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Differential proteomics analysis to identify proteins and pathways associated with male sterility of soybean using iTRAQ-based strategy.

PubMed

Li, Jiajia; Ding, Xianlong; Han, Shaohuai; He, Tingting; Zhang, Hao; Yang, Longshu; Yang, Shouping; Gai, Junyi

2016-04-14

To further elucidate the molecular mechanism of cytoplasmic male sterility (CMS) in soybean, a differential proteomic analysis was completed between the CMS line NJCMS1A and its maintainer NJCMS1B using iTRAQ-based strategy. As a result, 180 differential abundance proteins (DAPs) were identified, of which, 60 were down-regulated and 120 were up-regulated in NJCMS1A compared with NJCMS1B. Bioinformatic analysis showed that 167 DAPs were annotated in 41 Gene Ontology functional groups, 106 DAPs were classified into 20 clusters of orthologous groups of protein categories, and 128 DAPs were enrichment in 53 KEGG pathways. Fifteen differential level proteins/genes with the same expression pattern were identified in the further conjoint analysis of DAPs and the previously reported differential expression genes. Moreover, multiple reaction monitoring test, qRT-PCR analysis and enzyme activity assay validated that the iTRAQ results were reliable. Based on functional analysis of DAPs, we concluded that male sterility in NJCMS1A might be related to insufficiencies in energy supply, unbalance of protein synthesis and degradation, disruption of flavonoid synthesis, programmed cell death, abnormalities of substance metabolism, etc. These results might facilitate our understanding of the molecular mechanisms behind CMS in soybean. Soybean is an important global crop that provides protein and oil. Heterosis is a significantly potential approach to increase the yield of soybean. Cytoplasmic male sterility (CMS) plays a vital role in the production of hybrid seeds. However, the genetic and molecular mechanisms of male sterility in soybean still need to be further elucidated. In the present paper, a differential proteomic analysis was carried out and the results showed that several key proteins involved in key pathways were associated with male sterility in soybean. This work provides a new insight to understand the genetic and molecular mechanisms underlying CMS in soybean. Copyright © 2016 Elsevier B.V. All rights reserved.

Genome-wide DNA methylation profiling in infants born to gestational diabetes mellitus.

PubMed

Weng, Xiaoling; Liu, Fatao; Zhang, Hong; Kan, Mengyuan; Wang, Ting; Dong, Mingyue; Liu, Yun

2018-03-26

Offspring exposed to gestational diabetes mellitus (GDM) are at a high risk for metabolic diseases. The mechanisms behind the association between offspring exposed to GDM in utero and an increased risk of health consequences later in life remain unclear. The aim of this study was to clarify the changes in methylation levels in the foetuses of women with GDM and to explore the possible mechanisms linking maternal GDM with a high risk of metabolic diseases in offspring later in life. A genome-wide comparative methylome analysis on the umbilical cord blood of infants born to 30 women with GDM and 33 women with normal pregnancy was performed using Infinium HumanMethylation 450 BeadChip assays. A quantitative methylation analysis of 18 CpG dinucleotides was verified in the validation umbilical cord blood samples from 102 newborns exposed to GDM and 103 newborns who experienced normal pregnancy by MassARRAY EpiTYPER. A total of 4485 differentially methylated sites (DMSs), including 2150 hypermethylated sites and 2335 hypomethylated sites, with a mean β-value difference of >0.05, were identified by the 450k array. Good agreement was observed between the massarray validation data and the 450k array data (R 2 > 0.99; P < 0.0001). Thirty-seven CpGs (representing 20 genes) with a β-value difference of >0.15 between the GDM and healthy groups were identified and showed potential as clinical biomarkers for GDM. "hsa04940: Type I diabetes mellitus" was the most significant Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, with a P-value = 3.20E-07 and 1.36E-02 in the hypermethylated and hypomethylated genepathway enrichment analyses, respectively. In the Gene Ontology (GO) pathway analyses, immune MHC-related pathways and neuron development-related pathways were significantly enriched. Our results suggest that GDM has epigenetic effects on genes that are preferentially involved in the Type I diabetes mellitus pathway, immune MHC (major histocompatibility complex)-related pathways and neuron development-related pathways, with consequences on fetal growth and development, and provide supportive evidence that DNA methylation is involved in fetal metabolic programming. Copyright © 2018. Published by Elsevier B.V.

EERE Wind and Hydropower Technologies Program Technology Review (Deep Dive) for Under Secretaries Johnson and Koonin

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

2009-09-01

September 4, 2009 presentation highlighting the Wind and Hydropower Program, addressing program goals and objectives, budgets, technology pathways, breakthroughs, and DOE solutions to market barriers.

EERE Wind and Hydropower Technologies Program Technology Review (Deep Dive) for Under Secretaries Johnson and Koonin

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCluer, Megan

2009-09-04

September 4, 2009 presentation highlighting the Wind and Hydropower Program, addressing program goals and objectives, budgets, technology pathways, breakthroughs, and DOE solutions to market barriers.

Using Ambystoma mexicanum (Mexican Axolotl) Embryos, Chemical Genetics, and Microarray Analysis to Identify Signaling Pathways Associated with Tissue Regeneration

PubMed Central

Ponomareva, Larissa V.; Athippozhy, Antony; Thorson, Jon S.; Voss, S. Randal

2015-01-01

Amphibian vertebrates are important models in regenerative biology because they present exceptional regenerative capabilities throughout life. However, it takes considerable effort to rear amphibians to juvenile and adult stages for regeneration studies and the relatively large sizes that frogs and salamanders achieve during development make them difficult to use in chemical screens. Here we introduce a new tail regeneration model using late stage Mexican axolotl embryos. We show that axolotl embryos completely regenerate amputated tails in 7 days before they exhaust their yolk supply and begin to feed. Further, we show that axolotl embryos can be efficiently reared in microtiter plates to achieve moderate throughput screening of soluble chemicals to investigate toxicity and identify molecules that alter regenerative outcome. As proof of principle, we identified integration 1 / wingless (Wnt), transforming growth factor beta (Tgf-β), and fibroblast growth factor (Fgf) pathway antagonists that completely block tail regeneration and additional chemicals that significantly affected tail outgrowth. Furthermore, we used microarray analysis to show that inhibition of Wnt signaling broadly affects transcription of genes associated with Wnt, Fgf, Tgf-β, epidermal growth factor (Egf), Notch, nerve growth factor (Ngf), homeotic gene (Hox), rat sarcoma/mitogen-activated protein kinase (Ras/Mapk), myelocytomatosis viral oncogene (Myc), tumor protein 53 (p53), and retinoic acid (RA) pathways. Punctuated changes in the expression of genes known to regulate vertebrate development were observed; this suggests the tail regeneration transcriptional program is hierarchically structured and temporally ordered. Our study establishes the axolotl as a chemical screening model to investigate signaling pathways associated with tissue regeneration. PMID:26092703

Altered Pathway Analyzer: A gene expression dataset analysis tool for identification and prioritization of differentially regulated and network rewired pathways

PubMed Central

Kaushik, Abhinav; Ali, Shakir; Gupta, Dinesh

2017-01-01

Gene connection rewiring is an essential feature of gene network dynamics. Apart from its normal functional role, it may also lead to dysregulated functional states by disturbing pathway homeostasis. Very few computational tools measure rewiring within gene co-expression and its corresponding regulatory networks in order to identify and prioritize altered pathways which may or may not be differentially regulated. We have developed Altered Pathway Analyzer (APA), a microarray dataset analysis tool for identification and prioritization of altered pathways, including those which are differentially regulated by TFs, by quantifying rewired sub-network topology. Moreover, APA also helps in re-prioritization of APA shortlisted altered pathways enriched with context-specific genes. We performed APA analysis of simulated datasets and p53 status NCI-60 cell line microarray data to demonstrate potential of APA for identification of several case-specific altered pathways. APA analysis reveals several altered pathways not detected by other tools evaluated by us. APA analysis of unrelated prostate cancer datasets identifies sample-specific as well as conserved altered biological processes, mainly associated with lipid metabolism, cellular differentiation and proliferation. APA is designed as a cross platform tool which may be transparently customized to perform pathway analysis in different gene expression datasets. APA is freely available at http://bioinfo.icgeb.res.in/APA. PMID:28084397

A novel approach to select differential pathways associated with hypertrophic cardiomyopathy based on gene co‑expression analysis.

PubMed

Chen, Xiao-Min; Feng, Ming-Jun; Shen, Cai-Jie; He, Bin; Du, Xian-Feng; Yu, Yi-Bo; Liu, Jing; Chu, Hui-Min

2017-07-01

The present study was designed to develop a novel method for identifying significant pathways associated with human hypertrophic cardiomyopathy (HCM), based on gene co‑expression analysis. The microarray dataset associated with HCM (E‑GEOD‑36961) was obtained from the European Molecular Biology Laboratory‑European Bioinformatics Institute database. Informative pathways were selected based on the Reactome pathway database and screening treatments. An empirical Bayes method was utilized to construct co‑expression networks for informative pathways, and a weight value was assigned to each pathway. Differential pathways were extracted based on weight threshold, which was calculated using a random model. In order to assess whether the co‑expression method was feasible, it was compared with traditional pathway enrichment analysis of differentially expressed genes, which were identified using the significance analysis of microarrays package. A total of 1,074 informative pathways were screened out for subsequent investigations and their weight values were also obtained. According to the threshold of weight value of 0.01057, 447 differential pathways, including folding of actin by chaperonin containing T‑complex protein 1 (CCT)/T‑complex protein 1 ring complex (TRiC), purine ribonucleoside monophosphate biosynthesis and ubiquinol biosynthesis, were obtained. Compared with traditional pathway enrichment analysis, the number of pathways obtained from the co‑expression approach was increased. The results of the present study demonstrated that this method may be useful to predict marker pathways for HCM. The pathways of folding of actin by CCT/TRiC and purine ribonucleoside monophosphate biosynthesis may provide evidence of the underlying molecular mechanisms of HCM, and offer novel therapeutic directions for HCM.

Programmed cell death in trypanosomatids and other unicellular organisms.

PubMed

Debrabant, Alain; Lee, Nancy; Bertholet, Sylvie; Duncan, Robert; Nakhasi, Hira L

2003-03-01

In multicellular organisms, cellular growth and development can be controlled by programmed cell death (PCD), which is defined by a sequence of regulated events. However, PCD is thought to have evolved not only to regulate growth and development in multicellular organisms but also to have a functional role in the biology of unicellular organisms. In protozoan parasites and in other unicellular organisms, features of PCD similar to those in multicellular organisms have been reported, suggesting some commonality in the PCD pathway between unicellular and multicellular organisms. However, more extensive studies are needed to fully characterise the PCD pathway and to define the factors that control PCD in the unicellular organisms. The understanding of the PCD pathway in unicellular organisms could delineate the evolutionary origin of this pathway. Further characterisation of the PCD pathway in the unicellular parasites could provide information regarding their pathogenesis, which could be exploited to target new drugs to limit their growth and treat the disease they cause.

Evaluating Programs That Promote Climate and Energy Education-Meeting Teacher Needs for Online Resources

NASA Astrophysics Data System (ADS)

Lynds, S. E.; Buhr, S. M.

2011-12-01

The Climate Literacy and Energy Awareness Network (CLEAN) Pathway, is a National Science Digital Library (NSDL) Pathways project that was begun in 2010. The main goal of CLEAN is to generate a reviewed collection of educational resources that are aligned with the Essential Principles of Climate Science (EPCS). Another goal of the project is to support a community that will assist students, teachers, and citizens in climate literacy. A complementary program begun in 2010 is the ICEE (Inspiring Climate Education Excellence) program, which is developing online modules and courses designed around the climate literacy principles for use by teachers and other interested citizens. In these projects, we learn about teacher needs through a variety of evaluation mechanisms. The programs use evaluation to assist in the process of providing easy access to high quality climate and energy learning resources that meet classroom requirements. The internal evaluation of the CLEAN program is multidimensional. At the CLEAN resource review camps, teachers and scientists work together in small groups to assess the value of online resources for use in the classroom. The review camps are evaluated using observation and feedback surveys; the resulting evaluation reports provide information to managers to fine-tune future camps. In this way, a model for effective climate resource development meetings has been refined. Evaluation methods used in ICEE and CLEAN include teacher needs assessment surveys, teacher feedback at professional development opportunities, scientist feedback at resource review workshops, and regular analysis of online usage of resources, forums, and education modules. This paper will review the most successful strategies for evaluating the effectiveness of online climate and energy education resources and their use by educators and the general public.

Anti-CHMP5 single chain variable fragment antibody retrovirus infection induces programmed cell death of AML leukemic cells in vitro.

PubMed

Wang, Hai-rong; Xiao, Zhen-yu; Chen, Miao; Wang, Fei-long; Liu, Jia; Zhong, Hua; Zhong, Ji-hua; Ou-Yang, Ren-rong; Shen, Yan-lin; Pan, Shu-ming

2012-06-01

Over-expressed CHMP5 was found to act as oncogene that probably participated in leukemogenesis. In this study, we constructed the CHMP5 single chain variable fragment antibody (CHMP5-scFv) retrovirus and studied the changes of programmed cell death (PCD) of AML leukemic cells after infection by the retrovirus. The anti-CHMP5 KC14 hybridoma cell line was constructed to generate monoclonal antibody of CHMP5. The protein expression of CHMP5 was studied using immunofluorescence analysis. pMIG-CHMP5 scFv antibody expressible retroviral vector was constructed to prepare CHMP5-scFv retrovirus. AML leukemic U937 cells were infected with the retrovirus, and programmed cell death was studied using confocal microscope, FCM and Western blot. We obtained a monoclonal antibody of CHMP5, and found the expression of CHMP5 was up-regulated in the leukemic cells. After U937 cells were infected with CHMP5-scFv retrovirus, CHMP5 protein was neutralized. Moreover, the infection resulted in a significant increase in apoptosis and necrosis of U937 cells. In U937 cells infected with CHMP5-scFv retrovirus, apoptosis-inducing factor (AIF)-mediated caspase-independent necrotic PCD was activated, but autophagic programmed cell death was not observed. Neither the intrinsic nor extrinsic apoptotic PCD pathway was activated. The granzyme B/perforin-mediated caspase-dependent apoptotic PCD pathway was not activated. CHMP5-scFv retrovirus can neutralize the abnormally high levels of the CHMP5 protein in the cytosol of AML leukemic U937 cells, thereby inducing the programmed cell death of the leukemic cells via AIF-mediated caspase-independent necrosis and apoptosis.

Strengthening insights into host responses to mastitis infection in ruminants by combining heterogeneous microarray data sources

PubMed Central

2011-01-01

Background Gene expression profiling studies of mastitis in ruminants have provided key but fragmented knowledge for the understanding of the disease. A systematic combination of different expression profiling studies via meta-analysis techniques has the potential to test the extensibility of conclusions based on single studies. Using the program Pointillist, we performed meta-analysis of transcription-profiling data from six independent studies of infections with mammary gland pathogens, including samples from cattle challenged in vivo with S. aureus, E. coli, and S. uberis, samples from goats challenged in vivo with S. aureus, as well as cattle macrophages and ovine dendritic cells infected in vitro with S. aureus. We combined different time points from those studies, testing different responses to mastitis infection: overall (common signature), early stage, late stage, and cattle-specific. Results Ingenuity Pathway Analysis of affected genes showed that the four meta-analysis combinations share biological functions and pathways (e.g. protein ubiquitination and polyamine regulation) which are intrinsic to the general disease response. In the overall response, pathways related to immune response and inflammation, as well as biological functions related to lipid metabolism were altered. This latter observation is consistent with the milk fat content depression commonly observed during mastitis infection. Complementarities between early and late stage responses were found, with a prominence of metabolic and stress signals in the early stage and of the immune response related to the lipid metabolism in the late stage; both mechanisms apparently modulated by few genes, including XBP1 and SREBF1. The cattle-specific response was characterized by alteration of the immune response and by modification of lipid metabolism. Comparison of E. coli and S. aureus infections in cattle in vivo revealed that affected genes showing opposite regulation had the same altered biological functions and provided evidence that E. coli caused a stronger host response. Conclusions This meta-analysis approach reinforces previous findings but also reveals several novel themes, including the involvement of genes, biological functions, and pathways that were not identified in individual studies. As such, it provides an interesting proof of principle for future studies combining information from diverse heterogeneous sources. PMID:21569310

Development of a gene expression database and related analysis programs for evaluation of anticancer compounds.

PubMed

Ushijima, Masaru; Mashima, Tetsuo; Tomida, Akihiro; Dan, Shingo; Saito, Sakae; Furuno, Aki; Tsukahara, Satomi; Seimiya, Hiroyuki; Yamori, Takao; Matsuura, Masaaki

2013-03-01

Genome-wide transcriptional expression analysis is a powerful strategy for characterizing the biological activity of anticancer compounds. It is often instructive to identify gene sets involved in the activity of a given drug compound for comparison with different compounds. Currently, however, there is no comprehensive gene expression database and related application system that is; (i) specialized in anticancer agents; (ii) easy to use; and (iii) open to the public. To develop a public gene expression database of antitumor agents, we first examined gene expression profiles in human cancer cells after exposure to 35 compounds including 25 clinically used anticancer agents. Gene signatures were extracted that were classified as upregulated or downregulated after exposure to the drug. Hierarchical clustering showed that drugs with similar mechanisms of action, such as genotoxic drugs, were clustered. Connectivity map analysis further revealed that our gene signature data reflected modes of action of the respective agents. Together with the database, we developed analysis programs that calculate scores for ranking changes in gene expression and for searching statistically significant pathways from the Kyoto Encyclopedia of Genes and Genomes database in order to analyze the datasets more easily. Our database and the analysis programs are available online at our website (http://scads.jfcr.or.jp/db/cs/). Using these systems, we successfully showed that proteasome inhibitors are selectively classified as endoplasmic reticulum stress inducers and induce atypical endoplasmic reticulum stress. Thus, our public access database and related analysis programs constitute a set of efficient tools to evaluate the mode of action of novel compounds and identify promising anticancer lead compounds. © 2012 Japanese Cancer Association.

GProX, a user-friendly platform for bioinformatics analysis and visualization of quantitative proteomics data.

PubMed

Rigbolt, Kristoffer T G; Vanselow, Jens T; Blagoev, Blagoy

2011-08-01

Recent technological advances have made it possible to identify and quantify thousands of proteins in a single proteomics experiment. As a result of these developments, the analysis of data has become the bottleneck of proteomics experiment. To provide the proteomics community with a user-friendly platform for comprehensive analysis, inspection and visualization of quantitative proteomics data we developed the Graphical Proteomics Data Explorer (GProX)(1). The program requires no special bioinformatics training, as all functions of GProX are accessible within its graphical user-friendly interface which will be intuitive to most users. Basic features facilitate the uncomplicated management and organization of large data sets and complex experimental setups as well as the inspection and graphical plotting of quantitative data. These are complemented by readily available high-level analysis options such as database querying, clustering based on abundance ratios, feature enrichment tests for e.g. GO terms and pathway analysis tools. A number of plotting options for visualization of quantitative proteomics data is available and most analysis functions in GProX create customizable high quality graphical displays in both vector and bitmap formats. The generic import requirements allow data originating from essentially all mass spectrometry platforms, quantitation strategies and software to be analyzed in the program. GProX represents a powerful approach to proteomics data analysis providing proteomics experimenters with a toolbox for bioinformatics analysis of quantitative proteomics data. The program is released as open-source and can be freely downloaded from the project webpage at http://gprox.sourceforge.net.

GProX, a User-Friendly Platform for Bioinformatics Analysis and Visualization of Quantitative Proteomics Data*

PubMed Central

Rigbolt, Kristoffer T. G.; Vanselow, Jens T.; Blagoev, Blagoy

2011-01-01

Recent technological advances have made it possible to identify and quantify thousands of proteins in a single proteomics experiment. As a result of these developments, the analysis of data has become the bottleneck of proteomics experiment. To provide the proteomics community with a user-friendly platform for comprehensive analysis, inspection and visualization of quantitative proteomics data we developed the Graphical Proteomics Data Explorer (GProX)1. The program requires no special bioinformatics training, as all functions of GProX are accessible within its graphical user-friendly interface which will be intuitive to most users. Basic features facilitate the uncomplicated management and organization of large data sets and complex experimental setups as well as the inspection and graphical plotting of quantitative data. These are complemented by readily available high-level analysis options such as database querying, clustering based on abundance ratios, feature enrichment tests for e.g. GO terms and pathway analysis tools. A number of plotting options for visualization of quantitative proteomics data is available and most analysis functions in GProX create customizable high quality graphical displays in both vector and bitmap formats. The generic import requirements allow data originating from essentially all mass spectrometry platforms, quantitation strategies and software to be analyzed in the program. GProX represents a powerful approach to proteomics data analysis providing proteomics experimenters with a toolbox for bioinformatics analysis of quantitative proteomics data. The program is released as open-source and can be freely downloaded from the project webpage at http://gprox.sourceforge.net. PMID:21602510

Sex differences in prenatal epigenetic programming of stress pathways.

PubMed

Bale, Tracy L

2011-07-01

Maternal stress experience is associated with neurodevelopmental disorders including schizophrenia and autism. Recent studies have examined mechanisms by which changes in the maternal milieu may be transmitted to the developing embryo and potentially translated into programming of the epigenome. Animal models of prenatal stress have identified important sex- and temporal-specific effects on offspring stress responsivity. As dysregulation of stress pathways is a common feature in most neuropsychiatric diseases, molecular and epigenetic analyses at the maternal-embryo interface, especially in the placenta, may provide unique insight into identifying much-needed predictive biomarkers. In addition, as most neurodevelopmental disorders present with a sex bias, examination of sex differences in the inheritance of phenotypic outcomes may pinpoint gene targets and specific windows of vulnerability in neurodevelopment, which have been disrupted. This review discusses the association and possible contributing mechanisms of prenatal stress in programming offspring stress pathway dysregulation and the importance of sex.

The Tbr2 Molecular Network Controls Cortical Neuronal Differentiation Through Complementary Genetic and Epigenetic Pathways.

PubMed

Sessa, Alessandro; Ciabatti, Ernesto; Drechsel, Daniela; Massimino, Luca; Colasante, Gaia; Giannelli, Serena; Satoh, Takashi; Akira, Shizuo; Guillemot, Francois; Broccoli, Vania

2017-06-01

The T-box containing Tbr2 gene encodes for a transcription factor essential for the specification of the intermediate neural progenitors (INPs) originating the excitatory neurons of the cerebral cortex. However, its overall mechanism of action, direct target genes and cofactors remain unknown. Herein, we carried out global gene expression profiling combined with genome-wide binding site identification to determine the molecular pathways regulated by TBR2 in INPs. This analysis led to the identification of novel protein-protein interactions that control multiple features of INPs including cell-type identity, morphology, proliferation and migration dynamics. In particular, NEUROG2 and JMJD3 were found to associate with TBR2 revealing unexplored TBR2-dependent mechanisms. These interactions can explain, at least in part, the role of this transcription factor in the implementation of the molecular program controlling developmental milestones during corticogenesis. These data identify TBR2 as a major determinant of the INP-specific traits by regulating both genetic and epigenetic pathways. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Pathway analysis of genome-wide association datasets of personality traits.

PubMed

Kim, H-N; Kim, B-H; Cho, J; Ryu, S; Shin, H; Sung, J; Shin, C; Cho, N H; Sung, Y A; Choi, B-O; Kim, H-L

2015-04-01

Although several genome-wide association (GWA) studies of human personality have been recently published, genetic variants that are highly associated with certain personality traits remain unknown, due to difficulty reproducing results. To further investigate these genetic variants, we assessed biological pathways using GWA datasets. Pathway analysis using GWA data was performed on 1089 Korean women whose personality traits were measured with the Revised NEO Personality Inventory for the 5-factor model of personality. A total of 1042 pathways containing 8297 genes were included in our study. Of these, 14 pathways were highly enriched with association signals that were validated in 1490 independent samples. These pathways include association of: Neuroticism with axon guidance [L1 cell adhesion molecule (L1CAM) interactions]; Extraversion with neuronal system and voltage-gated potassium channels; Agreeableness with L1CAM interaction, neurotransmitter receptor binding and downstream transmission in postsynaptic cells; and Conscientiousness with the interferon-gamma and platelet-derived growth factor receptor beta polypeptide pathways. Several genes that contribute to top-ranked pathways in this study were previously identified in GWA studies or by pathway analysis in schizophrenia or other neuropsychiatric disorders. Here we report the first pathway analysis of all five personality traits. Importantly, our analysis identified novel pathways that contribute to understanding the etiology of personality traits. © 2015 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.

Pathways from College to University: A Social Science Example from Ontario

ERIC Educational Resources Information Center

LeSage, Ann; Samis, John; Hinch, Ron; Longo, Fabiola; DiGiuseppe, Maurice; Goodman, William; Percival, Jennifer; De La Rocha, Arlene; Rodrigues, Anna; Raby, Phil; Sanchez, Otto

2014-01-01

This study evaluates the impact of a College to University Pathway Program in the Faculty of Social Science and Humanities at The University of Ontario Institute of Technology. The findings support the assertion that Pathway students perform as well as or better than students who enter university directly from secondary school. This finding is…

Integrating genome-wide association studies and gene expression data highlights dysregulated multiple sclerosis risk pathways.

PubMed

Liu, Guiyou; Zhang, Fang; Jiang, Yongshuai; Hu, Yang; Gong, Zhongying; Liu, Shoufeng; Chen, Xiuju; Jiang, Qinghua; Hao, Junwei

2017-02-01

Much effort has been expended on identifying the genetic determinants of multiple sclerosis (MS). Existing large-scale genome-wide association study (GWAS) datasets provide strong support for using pathway and network-based analysis methods to investigate the mechanisms underlying MS. However, no shared genetic pathways have been identified to date. We hypothesize that shared genetic pathways may indeed exist in different MS-GWAS datasets. Here, we report results from a three-stage analysis of GWAS and expression datasets. In stage 1, we conducted multiple pathway analyses of two MS-GWAS datasets. In stage 2, we performed a candidate pathway analysis of the large-scale MS-GWAS dataset. In stage 3, we performed a pathway analysis using the dysregulated MS gene list from seven human MS case-control expression datasets. In stage 1, we identified 15 shared pathways. In stage 2, we successfully replicated 14 of these 15 significant pathways. In stage 3, we found that dysregulated MS genes were significantly enriched in 10 of 15 MS risk pathways identified in stages 1 and 2. We report shared genetic pathways in different MS-GWAS datasets and highlight some new MS risk pathways. Our findings provide new insights on the genetic determinants of MS.

Theoretical and Conceptual Framework for a High School Pathways to Pharmacy Program

PubMed Central

Bauman, Jerry

2010-01-01

Objectives To determine whether participation in the University of Illinois at Chicago College of Pharmacy (UIC-COP) Pathways to Pharmacy, an early urban pipeline program, motivated underrepresented minority students to pursue a prepharmacy curriculum in college and choose pharmacy as a career. Methods Over a 4-year period, underrepresented minority high school students participated in a comprehensive 6-week program that included 3 weeks of prepharmacy curriculum and intensive socialization and 3 weeks working as a pharmacy technician in a chain pharmacy. The High School Survey of Student Engagement (HSSSE) was administered 3 times to 120 program participants from 2005-2008, with 4 open-ended questions added to the pretest, 3 open-ended questions added to the test administered at the midpoint of the program, and 7 open-ended questions added to the posttest. Results After completing the program, 88 (75%) of the 120 students enrolled in the college's prepharmacy curriculum and planned to pursue a career in pharmacy, 10 (8%) were not interested in pursuing a career in pharmacy, and 20 (17%) were undecided, compared to the pretest data which showed that 40 (33%) were interested in a career in pharmacy, and 80 (67%) were undecided (p < 0.0001). Conclusions Participation in a Pathways to Pharmacy program grounded in both a theoretical and conceptual socialization model framework increased the number of underrepresented minority students in the pipeline to pharmacy schools. PMID:21179260

Theoretical and conceptual framework for a high school pathways to pharmacy program.

PubMed

Awé, Clara; Bauman, Jerry

2010-10-11

To determine whether participation in the University of Illinois at Chicago College of Pharmacy (UIC-COP) Pathways to Pharmacy, an early urban pipeline program, motivated underrepresented minority students to pursue a prepharmacy curriculum in college and choose pharmacy as a career. Over a 4-year period, underrepresented minority high school students participated in a comprehensive 6-week program that included 3 weeks of prepharmacy curriculum and intensive socialization and 3 weeks working as a pharmacy technician in a chain pharmacy. The High School Survey of Student Engagement (HSSSE) was administered 3 times to 120 program participants from 2005-2008, with 4 open-ended questions added to the pretest, 3 open-ended questions added to the test administered at the midpoint of the program, and 7 open-ended questions added to the posttest. After completing the program, 88 (75%) of the 120 students enrolled in the college's prepharmacy curriculum and planned to pursue a career in pharmacy, 10 (8%) were not interested in pursuing a career in pharmacy, and 20 (17%) were undecided, compared to the pretest data which showed that 40 (33%) were interested in a career in pharmacy, and 80 (67%) were undecided (p < 0.0001). Participation in a Pathways to Pharmacy program grounded in both a theoretical and conceptual socialization model framework increased the number of underrepresented minority students in the pipeline to pharmacy schools.

An optimization model for metabolic pathways.

PubMed

Planes, F J; Beasley, J E

2009-10-15

Different mathematical methods have emerged in the post-genomic era to determine metabolic pathways. These methods can be divided into stoichiometric methods and path finding methods. In this paper we detail a novel optimization model, based upon integer linear programming, to determine metabolic pathways. Our model links reaction stoichiometry with path finding in a single approach. We test the ability of our model to determine 40 annotated Escherichia coli metabolic pathways. We show that our model is able to determine 36 of these 40 pathways in a computationally effective manner.

Pathway and network-based analysis of genome-wide association studies and RT-PCR validation in polycystic ovary syndrome

PubMed Central

Shen, Haoran; Liang, Zhou; Zheng, Saihua; Li, Xuelian

2017-01-01

The purpose of this study was to identify promising candidate genes and pathways in polycystic ovary syndrome (PCOS). Microarray dataset GSE345269 obtained from the Gene Expression Omnibus database includes 7 granulosa cell samples from PCOS patients, and 3 normal granulosa cell samples. Differentially expressed genes (DEGs) were screened between PCOS and normal samples. Pathway enrichment analysis was conducted for DEGs using ClueGO and CluePedia plugin of Cytoscape. A Reactome functional interaction (FI) network of the DEGs was built using ReactomeFIViz, and then network modules were extracted, followed by pathway enrichment analysis for the modules. Expression of DEGs in granulosa cell samples was measured using quantitative RT-PCR. A total of 674 DEGs were retained, which were significantly enriched with inflammation and immune-related pathways. Eight modules were extracted from the Reactome FI network. Pathway enrichment analysis revealed significant pathways of each module: module 0, Regulation of RhoA activity and Signaling by Rho GTPases pathways shared ARHGAP4 and ARHGAP9; module 2, GlycoProtein VI-mediated activation cascade pathway was enriched with RHOG; module 3, Thromboxane A2 receptor signaling, Chemokine signaling pathway, CXCR4-mediated signaling events pathways were enriched with LYN, the hub gene of module 3. Results of RT-PCR confirmed the finding of the bioinformatic analysis that ARHGAP4, ARHGAP9, RHOG and LYN were significantly upregulated in PCOS. RhoA-related pathways, GlycoProtein VI-mediated activation cascade pathway, ARHGAP4, ARHGAP9, RHOG and LYN may be involved in the pathogenesis of PCOS. PMID:28949383

Directed random walks and constraint programming reveal active pathways in hepatocyte growth factor signaling.

PubMed

Kittas, Aristotelis; Delobelle, Aurélien; Schmitt, Sabrina; Breuhahn, Kai; Guziolowski, Carito; Grabe, Niels

2016-01-01

An effective means to analyze mRNA expression data is to take advantage of established knowledge from pathway databases, using methods such as pathway-enrichment analyses. However, pathway databases are not case-specific and expression data could be used to infer gene-regulation patterns in the context of specific pathways. In addition, canonical pathways may not always describe the signaling mechanisms properly, because interactions can frequently occur between genes in different pathways. Relatively few methods have been proposed to date for generating and analyzing such networks, preserving the causality between gene interactions and reasoning over the qualitative logic of regulatory effects. We present an algorithm (MCWalk) integrated with a logic programming approach, to discover subgraphs in large-scale signaling networks by random walks in a fully automated pipeline. As an exemplary application, we uncover the signal transduction mechanisms in a gene interaction network describing hepatocyte growth factor-stimulated cell migration and proliferation from gene-expression measured with microarray and RT-qPCR using in-house perturbation experiments in a keratinocyte-fibroblast co-culture. The resulting subgraphs illustrate possible associations of hepatocyte growth factor receptor c-Met nodes, differentially expressed genes and cellular states. Using perturbation experiments and Answer Set programming, we are able to select those which are more consistent with the experimental data. We discover key regulator nodes by measuring the frequency with which they are traversed when connecting signaling between receptors and significantly regulated genes and predict their expression-shift consistently with the measured data. The Java implementation of MCWalk is publicly available under the MIT license at: https://bitbucket.org/akittas/biosubg. © 2015 FEBS.

The SUMO Pathway Is Developmentally Regulated and Required for Programmed DNA Elimination in Paramecium tetraurelia† ‡

PubMed Central

Matsuda, Atsushi; Forney, James D.

2006-01-01

Extensive genome-wide remodeling occurs during the formation of the somatic macronuclei from the germ line micronuclei in ciliated protozoa. This process is limited to sexual reproduction and includes DNA amplification, chromosome fragmentation, and the elimination of internal segments of DNA. Our efforts to define the pathways regulating these events revealed a gene encoding a homologue of ubiquitin activating enzyme 2 (UBA2) that is upregulated at the onset of macronuclear development in Paramecium tetraurelia. Uba2 enzymes are known to activate the protein called small ubiquitin-related modifier (SUMO) that is covalently attached to target proteins. Consistent with this relationship, Northern analysis showed increased abundance of SUMO transcripts during sexual reproduction in Paramecium. RNA interference (RNAi) against UBA2 or SUMO during vegetative growth had little effect on cell survival or fission rates. In contrast, RNAi of mating cells resulted in failure to form a functional macronucleus. Despite normal amplification of the genome, excision of internal eliminated sequences was completely blocked. Additional experiments showed that the homologous UBA2 and SUMO genes in Tetrahymena thermophila are also upregulated during conjugation. These results provide evidence for the developmental regulation of the SUMO pathway in ciliates and suggest a key role for the pathway in controlling genome remodeling. PMID:16682458

Seed desiccation mechanisms co-opted for vegetative desiccation in the resurrection grass Oropetium thomaeum.

PubMed

VanBuren, Robert; Wai, Ching Man; Zhang, Qingwei; Song, Xiaomin; Edger, Patrick P; Bryant, Doug; Michael, Todd P; Mockler, Todd C; Bartels, Dorothea

2017-10-01

Resurrection plants desiccate during periods of prolonged drought stress, then resume normal cellular metabolism upon water availability. Desiccation tolerance has multiple origins in flowering plants, and it likely evolved through rewiring seed desiccation pathways. Oropetium thomaeum is an emerging model for extreme drought tolerance, and its genome, which is the smallest among surveyed grasses, was recently sequenced. Combining RNA-seq, targeted metabolite analysis and comparative genomics, we show evidence for co-option of seed-specific pathways during vegetative desiccation. Desiccation-related gene co-expression clusters are enriched in functions related to seed development including several seed-specific transcription factors. Across the metabolic network, pathways involved in programmed cell death inhibition, ABA signalling and others are activated during dehydration. Oleosins and oil bodies that typically function in seed storage are highly abundant in desiccated leaves and may function for membrane stability and storage. Orthologs to seed-specific LEA proteins from rice and maize have neofunctionalized in Oropetium with high expression during desiccation. Accumulation of sucrose, raffinose and stachyose in drying leaves mirrors sugar accumulation patterns in maturing seeds. Together, these results connect vegetative desiccation with existing seed desiccation and drought responsive pathways and provide some key candidate genes for engineering improved drought tolerance in crop plants. © 2017 John Wiley & Sons Ltd.

Pathway analysis of high-throughput biological data within a Bayesian network framework.

PubMed

Isci, Senol; Ozturk, Cengizhan; Jones, Jon; Otu, Hasan H

2011-06-15

Most current approaches to high-throughput biological data (HTBD) analysis either perform individual gene/protein analysis or, gene/protein set enrichment analysis for a list of biologically relevant molecules. Bayesian Networks (BNs) capture linear and non-linear interactions, handle stochastic events accounting for noise, and focus on local interactions, which can be related to causal inference. Here, we describe for the first time an algorithm that models biological pathways as BNs and identifies pathways that best explain given HTBD by scoring fitness of each network. Proposed method takes into account the connectivity and relatedness between nodes of the pathway through factoring pathway topology in its model. Our simulations using synthetic data demonstrated robustness of our approach. We tested proposed method, Bayesian Pathway Analysis (BPA), on human microarray data regarding renal cell carcinoma (RCC) and compared our results with gene set enrichment analysis. BPA was able to find broader and more specific pathways related to RCC. Accompanying BPA software (BPAS) package is freely available for academic use at http://bumil.boun.edu.tr/bpa.

Analysis of the miRNA Profiles of Melanoma Exosomes Derived Under Normoxic and Hypoxic Culture Conditions.

PubMed

Wozniak, Michal; Peczek, Lukasz; Czernek, Liliana; Düchler, Markus

2017-12-01

MicroRNAs (miRNAs) transported in melanoma-derived exosomes function as intercellular messengers supporting tumor survival and progression. Hypoxia increases melanoma phenotypic plasticity, drug resistance, and metastasis. We determined the miRNA profiles in exosomes derived from melanoma cells grown under hypoxic and normoxic conditions by microarray analyses and reverse transcription-polymerase chain reaction (RT-PCR) in order to analyze the potential influence of vesicle-transported miRNAs on cancer-related pathways and transcriptional programs. Despite phenotypical differences of the four cell lines used, their exosomes shared the majority of miRNAs. The levels of three miRNAs were higher in normoxic exosomes, whereas 15 miRNAs were significantly more abundant under hypoxic conditions. Pathway analysis pointed at several cellular processes contributing to proliferation, drug resistance, and modification of the tumor microenvironment, including immunosuppression. The miRNA-expression profiles of exosomes from patient-derived melanoma cells are modified by oxygen concentration and reflect the phenotypic changes of melanoma cells under different growth conditions. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Migrant Nurses and Federal Caregiver Programs in Canada: Migration and Health Human Resources Paradox.

PubMed

Salami, Bukola

2016-06-01

Despite the links between health human resources policy, immigration policy, and education policy, silos persist in the policy-making process that complicate the professional integration of internationally educated nurses in Canada. Drawing on the literature on nurse migration to Canada through the Live-in Caregiver Program, this paper sheds light on the contradictions between immigration and health human resources policy and their effect on the integration of internationally educated nurses in Canada. The analysis reveals a series of paradoxes within and across immigration and health human resources policy that affect the process of professional integration of this group of health professionals into the nursing workforce in Canada. I will further link the discussion to the recently implemented Caregiver Program, which provides a unique pathway for healthcare workers, including nurses, to migrate to Canada. Given recent introduction of the Canadian Caregiver Program, major policy implications include the need to bridge the gap between health human resources policy and immigration policy to ensure the maximum integration of migrant nurses in Canada.

Comparative study on gene set and pathway topology-based enrichment methods.

PubMed

Bayerlová, Michaela; Jung, Klaus; Kramer, Frank; Klemm, Florian; Bleckmann, Annalen; Beißbarth, Tim

2015-10-22

Enrichment analysis is a popular approach to identify pathways or sets of genes which are significantly enriched in the context of differentially expressed genes. The traditional gene set enrichment approach considers a pathway as a simple gene list disregarding any knowledge of gene or protein interactions. In contrast, the new group of so called pathway topology-based methods integrates the topological structure of a pathway into the analysis. We comparatively investigated gene set and pathway topology-based enrichment approaches, considering three gene set and four topological methods. These methods were compared in two extensive simulation studies and on a benchmark of 36 real datasets, providing the same pathway input data for all methods. In the benchmark data analysis both types of methods showed a comparable ability to detect enriched pathways. The first simulation study was conducted with KEGG pathways, which showed considerable gene overlaps between each other. In this study with original KEGG pathways, none of the topology-based methods outperformed the gene set approach. Therefore, a second simulation study was performed on non-overlapping pathways created by unique gene IDs. Here, methods accounting for pathway topology reached higher accuracy than the gene set methods, however their sensitivity was lower. We conducted one of the first comprehensive comparative works on evaluating gene set against pathway topology-based enrichment methods. The topological methods showed better performance in the simulation scenarios with non-overlapping pathways, however, they were not conclusively better in the other scenarios. This suggests that simple gene set approach might be sufficient to detect an enriched pathway under realistic circumstances. Nevertheless, more extensive studies and further benchmark data are needed to systematically evaluate these methods and to assess what gain and cost pathway topology information introduces into enrichment analysis. Both types of methods for enrichment analysis require further improvements in order to deal with the problem of pathway overlaps.

NRASG12V oncogene facilitates self-renewal in a murine model of acute myelogenous leukemia

PubMed Central

LaRue, Rebecca S.; Nguyen, Hanh T.; Sachs, Karen; Noble, Klara E.; Mohd Hassan, Nurul Azyan; Diaz-Flores, Ernesto; Rathe, Susan K.; Sarver, Aaron L.; Bendall, Sean C.; Ha, Ngoc A.; Diers, Miechaleen D.; Nolan, Garry P.; Shannon, Kevin M.; Largaespada, David A.

2014-01-01

Mutant RAS oncoproteins activate signaling molecules that drive oncogenesis in multiple human tumors including acute myelogenous leukemia (AML). However, the specific functions of these pathways in AML are unclear, thwarting the rational application of targeted therapeutics. To elucidate the downstream functions of activated NRAS in AML, we used a murine model that harbors Mll-AF9 and a tetracycline-repressible, activated NRAS (NRASG12V). Using computational approaches to explore our gene-expression data sets, we found that NRASG12V enforced the leukemia self-renewal gene-expression signature and was required to maintain an MLL-AF9– and Myb-dependent leukemia self-renewal gene-expression program. NRASG12V was required for leukemia self-renewal independent of its effects on growth and survival. Analysis of the gene-expression patterns of leukemic subpopulations revealed that the NRASG12V-mediated leukemia self-renewal signature is preferentially expressed in the leukemia stem cell–enriched subpopulation. In a multiplexed analysis of RAS-dependent signaling, Mac-1Low cells, which harbor leukemia stem cells, were preferentially sensitive to NRASG12V withdrawal. NRASG12V maintained leukemia self-renewal through mTOR and MEK pathway activation, implicating these pathways as potential targets for cancer stem cell–specific therapies. Together, these experimental results define a RAS oncogene–driven function that is critical for leukemia maintenance and represents a novel mechanism of oncogene addiction. PMID:25316678

PathwayAccess: CellDesigner plugins for pathway databases.

PubMed

Van Hemert, John L; Dickerson, Julie A

2010-09-15

CellDesigner provides a user-friendly interface for graphical biochemical pathway description. Many pathway databases are not directly exportable to CellDesigner models. PathwayAccess is an extensible suite of CellDesigner plugins, which connect CellDesigner directly to pathway databases using respective Java application programming interfaces. The process is streamlined for creating new PathwayAccess plugins for specific pathway databases. Three PathwayAccess plugins, MetNetAccess, BioCycAccess and ReactomeAccess, directly connect CellDesigner to the pathway databases MetNetDB, BioCyc and Reactome. PathwayAccess plugins enable CellDesigner users to expose pathway data to analytical CellDesigner functions, curate their pathway databases and visually integrate pathway data from different databases using standard Systems Biology Markup Language and Systems Biology Graphical Notation. Implemented in Java, PathwayAccess plugins run with CellDesigner version 4.0.1 and were tested on Ubuntu Linux, Windows XP and 7, and MacOSX. Source code, binaries, documentation and video walkthroughs are freely available at http://vrac.iastate.edu/~jlv.

The Case for Evaluating Student Outcomes and Equity Gaps to Improve Pathways and Programs of Study

ERIC Educational Resources Information Center

Bragg, Debra D.

2017-01-01

When linked to program review and improvement, program evaluation can help practitioners to ensure that career-technical education (CTE) and science, technology, engineering, and mathematics (STEM) programs offer equitable access and outcomes for underserved student groups.

Pathways to rural family practice at Memorial University of Newfoundland

PubMed Central

Rourke, James; O’Keefe, Danielle; Ravalia, Mohamed; Moffatt, Scott; Parsons, Wanda; Duggan, Norah; Stringer, Katherine; Jong, Michael; Walsh, Kristin Harris; Hippe, Janelle

2018-01-01

Abstract Objective To assess Memorial University of Newfoundland’s (MUN’s) commitment to a comprehensive pathways approach to rural family practice, and to determine the national and provincial effects of applying this approach. Design Analysis of anonymized secondary data. Setting Canada. Participants Memorial’s medical degree (MD) graduates practising family medicine in Newfoundland and Labrador as of January 2015 (N = 305), MUN’s 2011 and 2012 MD graduates (N = 120), and physicians who completed family medicine training programs in Canada between 2004 and 2013 and who were practising in Canada 2 years after completion of their postgraduate training (N = 8091). Main outcome measures National effect was measured by the proportion of MUN’s family medicine program graduates practising in rural Canada compared with those from other Canadian family medicine training programs. Provincial effect was measured by the location of MUN’s MD graduates practising family medicine in Newfoundland and Labrador as of January 2015. Commitment to a comprehensive pathways approach to rural family practice was measured by anonymized geographic data on admissions, educational placements, and practice locations of MUN’s 2011 and 2012 MD graduates, including those who completed family medicine residencies at MUN. Results Memorial’s comprehensive pathways approach to training physicians for rural practice was successful on both national and provincial levels: 26.9% of MUN family medicine program graduates were in a rural practice location 2 years after exiting their post-MD training from 2004 to 2013 compared with the national rate of 13.3% (national effect); 305 of MUN’s MD graduates were practising family medicine in Newfoundland and Labrador as of 2015, with 36% practising in rural areas (provincial effect). Of 114 MD students with known background who graduated in 2011 and 2012, 32% had rural backgrounds. Memorial’s 2011 and 2012 MD graduates spent 20% of all clinical placement weeks in rural areas; of note, 90% of all first-year placements and 95% of third-year family medicine clerkship placements were rural. For the 25 MUN 2011 and 2012 MD graduates who also completed family medicine residencies at MUN, 38% of family medicine placement weeks were spent in rural communities or rural towns. Of the 30 MUN 2011 and 2012 MD graduates practising family medicine in Canada as of January 2015, 42% were practising in rural communities or rural towns; 73% were practising in Newfoundland and Labrador and half of those were in rural communities and rural towns. Conclusion A comprehensive rural pathways approach that includes recruiting rural students and exposing all medical students to extensive rural placements and all family medicine residents to rural family practice training has resulted in more rural generalist physicians in family practice in Newfoundland and Labrador and across Canada. PMID:29540400

Pathways to rural family practice at Memorial University of Newfoundland.

PubMed

Rourke, James; O'Keefe, Danielle; Ravalia, Mohamed; Moffatt, Scott; Parsons, Wanda; Duggan, Norah; Stringer, Katherine; Jong, Michael; Walsh, Kristin Harris; Hippe, Janelle

2018-03-01

To assess Memorial University of Newfoundland's (MUN's) commitment to a comprehensive pathways approach to rural family practice, and to determine the national and provincial effects of applying this approach. Analysis of anonymized secondary data. Canada. Memorial's medical degree (MD) graduates practising family medicine in Newfoundland and Labrador as of January 2015 (N = 305), MUN's 2011 and 2012 MD graduates (N = 120), and physicians who completed family medicine training programs in Canada between 2004 and 2013 and who were practising in Canada 2 years after completion of their postgraduate training (N = 8091). National effect was measured by the proportion of MUN's family medicine program graduates practising in rural Canada compared with those from other Canadian family medicine training programs. Provincial effect was measured by the location of MUN's MD graduates practising family medicine in Newfoundland and Labrador as of January 2015. Commitment to a comprehensive pathways approach to rural family practice was measured by anonymized geographic data on admissions, educational placements, and practice locations of MUN's 2011 and 2012 MD graduates, including those who completed family medicine residencies at MUN. Memorial's comprehensive pathways approach to training physicians for rural practice was successful on both national and provincial levels: 26.9% of MUN family medicine program graduates were in a rural practice location 2 years after exiting their post-MD training from 2004 to 2013 compared with the national rate of 13.3% (national effect); 305 of MUN's MD graduates were practising family medicine in Newfoundland and Labrador as of 2015, with 36% practising in rural areas (provincial effect). Of 114 MD students with known background who graduated in 2011 and 2012, 32% had rural backgrounds. Memorial's 2011 and 2012 MD graduates spent 20% of all clinical placement weeks in rural areas; of note, 90% of all first-year placements and 95% of third-year family medicine clerkship placements were rural. For the 25 MUN 2011 and 2012 MD graduates who also completed family medicine residencies at MUN, 38% of family medicine placement weeks were spent in rural communities or rural towns. Of the 30 MUN 2011 and 2012 MD graduates practising family medicine in Canada as of January 2015, 42% were practising in rural communities or rural towns; 73% were practising in Newfoundland and Labrador and half of those were in rural communities and rural towns. A comprehensive rural pathways approach that includes recruiting rural students and exposing all medical students to extensive rural placements and all family medicine residents to rural family practice training has resulted in more rural generalist physicians in family practice in Newfoundland and Labrador and across Canada. Copyright© the College of Family Physicians of Canada.

Note of the methodological flaws in the paper entitled "Polymorphisms in IL-4/IL-13 pathway genes and glioma risk: an updated meta-analysis".

PubMed

Wang, Ting-Ting; Li, Jin-Mei; Zhou, Dong

2016-01-01

With great interest, we read the paper "Polymorphisms in IL-4/IL-13 pathway genes and glioma risk: an updated meta-analysis" (by Chen PQ et al.) [1], which has reached important conclusions about the relationship between polymorphisms in interleukin (IL)-4/IL-13 pathway genes and glioma risk. Through quantitative analysis, the meta-analysis found no association between IL-4/IL-13 pathway genetic polymorphisms and glioma risk (Chen et al. in Tumor Biol 36:121-127, 2015). The meta-analysis is the most comprehensive study of polymorphisms in the IL-4/IL-13 pathway and glioma risk. Nevertheless, some deficiencies still exist in this meta-analysis that we would like to raise.

Living with death: The evolution of the mitochondrial pathway of apoptosis in animals

PubMed Central

Oberst, Andrew; Bender, Cheryl; Green, Douglas R.

2008-01-01

The mitochondrial pathway of cell death, in which apoptosis proceeds following mitochondrial outer membrane permeablization (MOMP), release of cytochrome c, and APAF-1 apoptosome-mediated caspase activation, represents the major pathway of physiological apoptosis in vertebrates. However, the well-characterized apoptotic pathways of the invertebrates C. elegans and D. melanogaster indicate that this apoptotic pathway is not universally conserved among animals. This review will compare the role of the mitochondria in the apoptotic programs of mammals, nematodes, and flies, and will survey our knowledge of the apoptotic pathways of other, less familiar model organisms in an effort to explore the evolutionary origins of the mitochondrial pathway of apoptosis. PMID:18451868

A Call for Nominations of Quantitative High-Throughput ...

EPA Pesticide Factsheets

The National Research Council of the United States National Academies of Science has recently released a document outlining a long-range vision and strategy for transforming toxicity testing from largely whole animal-based testing to one based on in vitro assays. “Toxicity Testing in the 21st Century: A Vision and a Strategy” advises a focus on relevant human toxicity pathway assays. Toxicity pathways are defined in the document as “Cellular response pathways that, when sufficiently perturbed, are expected to result in adverse health effects”. Results of such pathway screens would serve as a filter to drive selection of more specific, targeted testing that will complement and validate the pathway assays. In response to this report, the US EPA has partnered with two NIH organizations, the National Toxicology Program and the NIH Chemical Genomics Center (NCGC), in a program named Tox21. A major goal of this collaboration is to screen chemical libraries consisting of known toxicants, chemicals of environmental and occupational exposure concern, and human pharmaceuticals in cell-based pathway assays. Currently, approximately 3000 compounds (increasing to 9000 by the end of 2009) are being validated and screened in quantitative high-throughput (qHTS) format at the NCGC producing extensive concentration-response data for a diverse set of potential toxicity pathways. The Tox21 collaboration is extremely interested in accessing additional toxicity pathway assa

Next generation of immune checkpoint therapy in cancer: new developments and challenges.

PubMed

Marin-Acevedo, Julian A; Dholaria, Bhagirathbhai; Soyano, Aixa E; Knutson, Keith L; Chumsri, Saranya; Lou, Yanyan

2018-03-15

Immune checkpoints consist of inhibitory and stimulatory pathways that maintain self-tolerance and assist with immune response. In cancer, immune checkpoint pathways are often activated to inhibit the nascent anti-tumor immune response. Immune checkpoint therapies act by blocking or stimulating these pathways and enhance the body's immunological activity against tumors. Cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), programmed cell death receptor-1 (PD-1), and programmed cell death ligand-1(PD-L1) are the most widely studied and recognized inhibitory checkpoint pathways. Drugs blocking these pathways are currently utilized for a wide variety of malignancies and have demonstrated durable clinical activities in a subset of cancer patients. This approach is rapidly extending beyond CTLA-4 and PD-1/PD-L1. New inhibitory pathways are under investigation, and drugs blocking LAG-3, TIM-3, TIGIT, VISTA, or B7/H3 are being investigated. Furthermore, agonists of stimulatory checkpoint pathways such as OX40, ICOS, GITR, 4-1BB, CD40, or molecules targeting tumor microenvironment components like IDO or TLR are under investigation. In this article, we have provided a comprehensive review of immune checkpoint pathways involved in cancer immunotherapy, and discuss their mechanisms and the therapeutic interventions currently under investigation in phase I/II clinical trials. We also reviewed the limitations, toxicities, and challenges and outline the possible future research directions.

In silico Pathway Activation Network Decomposition Analysis (iPANDA) as a method for biomarker development.

PubMed

Ozerov, Ivan V; Lezhnina, Ksenia V; Izumchenko, Evgeny; Artemov, Artem V; Medintsev, Sergey; Vanhaelen, Quentin; Aliper, Alexander; Vijg, Jan; Osipov, Andreyan N; Labat, Ivan; West, Michael D; Buzdin, Anton; Cantor, Charles R; Nikolsky, Yuri; Borisov, Nikolay; Irincheeva, Irina; Khokhlovich, Edward; Sidransky, David; Camargo, Miguel Luiz; Zhavoronkov, Alex

2016-11-16

Signalling pathway activation analysis is a powerful approach for extracting biologically relevant features from large-scale transcriptomic and proteomic data. However, modern pathway-based methods often fail to provide stable pathway signatures of a specific phenotype or reliable disease biomarkers. In the present study, we introduce the in silico Pathway Activation Network Decomposition Analysis (iPANDA) as a scalable robust method for biomarker identification using gene expression data. The iPANDA method combines precalculated gene coexpression data with gene importance factors based on the degree of differential gene expression and pathway topology decomposition for obtaining pathway activation scores. Using Microarray Analysis Quality Control (MAQC) data sets and pretreatment data on Taxol-based neoadjuvant breast cancer therapy from multiple sources, we demonstrate that iPANDA provides significant noise reduction in transcriptomic data and identifies highly robust sets of biologically relevant pathway signatures. We successfully apply iPANDA for stratifying breast cancer patients according to their sensitivity to neoadjuvant therapy.

In silico Pathway Activation Network Decomposition Analysis (iPANDA) as a method for biomarker development

PubMed Central

Ozerov, Ivan V.; Lezhnina, Ksenia V.; Izumchenko, Evgeny; Artemov, Artem V.; Medintsev, Sergey; Vanhaelen, Quentin; Aliper, Alexander; Vijg, Jan; Osipov, Andreyan N.; Labat, Ivan; West, Michael D.; Buzdin, Anton; Cantor, Charles R.; Nikolsky, Yuri; Borisov, Nikolay; Irincheeva, Irina; Khokhlovich, Edward; Sidransky, David; Camargo, Miguel Luiz; Zhavoronkov, Alex

2016-01-01

Signalling pathway activation analysis is a powerful approach for extracting biologically relevant features from large-scale transcriptomic and proteomic data. However, modern pathway-based methods often fail to provide stable pathway signatures of a specific phenotype or reliable disease biomarkers. In the present study, we introduce the in silico Pathway Activation Network Decomposition Analysis (iPANDA) as a scalable robust method for biomarker identification using gene expression data. The iPANDA method combines precalculated gene coexpression data with gene importance factors based on the degree of differential gene expression and pathway topology decomposition for obtaining pathway activation scores. Using Microarray Analysis Quality Control (MAQC) data sets and pretreatment data on Taxol-based neoadjuvant breast cancer therapy from multiple sources, we demonstrate that iPANDA provides significant noise reduction in transcriptomic data and identifies highly robust sets of biologically relevant pathway signatures. We successfully apply iPANDA for stratifying breast cancer patients according to their sensitivity to neoadjuvant therapy. PMID:27848968

44 CFR 354.5 - Description of site-specific, plume pathway EPZ biennial exercise-related component services and...

Code of Federal Regulations, 2010 CFR

2010-10-01

... Control Program Directors, and the Nuclear Energy Institute. (21) Implement and coordinate REP Program... from our REP Program Strategic Review implementation and oversight working group activities. (24) Costs...

44 CFR 354.5 - Description of site-specific, plume pathway EPZ biennial exercise-related component services and...

Code of Federal Regulations, 2014 CFR

2014-10-01

... Control Program Directors, and the Nuclear Energy Institute. (21) Implement and coordinate REP Program... from our REP Program Strategic Review implementation and oversight working group activities. (24) Costs...

44 CFR 354.5 - Description of site-specific, plume pathway EPZ biennial exercise-related component services and...

Code of Federal Regulations, 2013 CFR

2013-10-01

... Control Program Directors, and the Nuclear Energy Institute. (21) Implement and coordinate REP Program... from our REP Program Strategic Review implementation and oversight working group activities. (24) Costs...

44 CFR 354.5 - Description of site-specific, plume pathway EPZ biennial exercise-related component services and...

Code of Federal Regulations, 2011 CFR

2011-10-01

... Control Program Directors, and the Nuclear Energy Institute. (21) Implement and coordinate REP Program... from our REP Program Strategic Review implementation and oversight working group activities. (24) Costs...

Non Linear Programming (NLP) Formulation for Quantitative Modeling of Protein Signal Transduction Pathways

PubMed Central

Morris, Melody K.; Saez-Rodriguez, Julio; Lauffenburger, Douglas A.; Alexopoulos, Leonidas G.

2012-01-01

Modeling of signal transduction pathways plays a major role in understanding cells' function and predicting cellular response. Mathematical formalisms based on a logic formalism are relatively simple but can describe how signals propagate from one protein to the next and have led to the construction of models that simulate the cells response to environmental or other perturbations. Constrained fuzzy logic was recently introduced to train models to cell specific data to result in quantitative pathway models of the specific cellular behavior. There are two major issues in this pathway optimization: i) excessive CPU time requirements and ii) loosely constrained optimization problem due to lack of data with respect to large signaling pathways. Herein, we address both issues: the former by reformulating the pathway optimization as a regular nonlinear optimization problem; and the latter by enhanced algorithms to pre/post-process the signaling network to remove parts that cannot be identified given the experimental conditions. As a case study, we tackle the construction of cell type specific pathways in normal and transformed hepatocytes using medium and large-scale functional phosphoproteomic datasets. The proposed Non Linear Programming (NLP) formulation allows for fast optimization of signaling topologies by combining the versatile nature of logic modeling with state of the art optimization algorithms. PMID:23226239

Non Linear Programming (NLP) formulation for quantitative modeling of protein signal transduction pathways.

PubMed

Mitsos, Alexander; Melas, Ioannis N; Morris, Melody K; Saez-Rodriguez, Julio; Lauffenburger, Douglas A; Alexopoulos, Leonidas G

2012-01-01

Modeling of signal transduction pathways plays a major role in understanding cells' function and predicting cellular response. Mathematical formalisms based on a logic formalism are relatively simple but can describe how signals propagate from one protein to the next and have led to the construction of models that simulate the cells response to environmental or other perturbations. Constrained fuzzy logic was recently introduced to train models to cell specific data to result in quantitative pathway models of the specific cellular behavior. There are two major issues in this pathway optimization: i) excessive CPU time requirements and ii) loosely constrained optimization problem due to lack of data with respect to large signaling pathways. Herein, we address both issues: the former by reformulating the pathway optimization as a regular nonlinear optimization problem; and the latter by enhanced algorithms to pre/post-process the signaling network to remove parts that cannot be identified given the experimental conditions. As a case study, we tackle the construction of cell type specific pathways in normal and transformed hepatocytes using medium and large-scale functional phosphoproteomic datasets. The proposed Non Linear Programming (NLP) formulation allows for fast optimization of signaling topologies by combining the versatile nature of logic modeling with state of the art optimization algorithms.

Implementing best practice in hospital multidisciplinary nutritional care: an example of using the knowledge-to-action process for a research program.

PubMed

Laur, Celia; Keller, Heather H

2015-01-01

Prospective use of knowledge translation and implementation science frameworks can increase the likelihood of meaningful improvements in health care practices. An example of this creation and application of knowledge is the series of studies conducted by and with the Canadian Malnutrition Task Force (CMTF). Following a cohort study and synthesis of evidence regarding best practice for identification, treatment, and prevention of malnutrition in hospitals, CMTF created an evidence-informed, consensus-based pathway for nutritional care in hospitals. The purpose of this paper is to detail the steps taken in this research program, through four studies, as an example of the knowledge-to-action (KTA) process. The KTA process includes knowledge creation and action cycles. The steps of the action cycle within this program of research are iterative, and up to this point have been informed by three studies, with a fourth underway. The first study identified the magnitude of the malnutrition problem upon admission to hospital and how it is undetected and undertreated (study 1). Knowledge creation resulted in an evidence-based pathway established to address care gaps (study 2) and the development of monitoring tools (study 3). The study was then adapted to local context: focus groups validated face validate the evidence-based pathway; during the final phase, study site implementation teams will continue to adapt the pathway (studies 2 and 4). Barriers to implementation were also assessed; focus groups and interviews were conducted to inform the pathway implementation (studies 1, 2, and 4). In the next step, specific interventions were selected, tailored, and implemented. In the final study in this research program, plan-do-study-act cycles will be used to make changes and to implement the pathway (study 4). To monitor knowledge use and to evaluate outcomes, audits, staff surveys, patient outcomes, etc will be used to record process evaluations (studies 3 and 4). Finally, a sustainability plan will be incorporated into the final study of the program (study 4) to sustain knowledge use. Use of frameworks can increase the likelihood of meaningful and sustainable improvements in health care practice. The example of this program of research demonstrates how existing evidence has been used to identify, create, and adapt knowledge, and how multidisciplinary teams have been used to effect changes in the hospital setting. Effective implementation is essential in nutritional health care, and this multidisciplinary program of research provides an example of how the KTA process can facilitate implementation and promote sustainability.

A novel method to identify hub pathways of rheumatoid arthritis based on differential pathway networks.

PubMed

Wei, Shi-Tong; Sun, Yong-Hua; Zong, Shi-Hua

2017-09-01

The aim of the current study was to identify hub pathways of rheumatoid arthritis (RA) using a novel method based on differential pathway network (DPN) analysis. The present study proposed a DPN where protein‑protein interaction (PPI) network was integrated with pathway‑pathway interactions. Pathway data was obtained from background PPI network and the Reactome pathway database. Subsequently, pathway interactions were extracted from the pathway data by building randomized gene‑gene interactions and a weight value was assigned to each pathway interaction using Spearman correlation coefficient (SCC) to identify differential pathway interactions. Differential pathway interactions were visualized using Cytoscape to construct a DPN. Topological analysis was conducted to identify hub pathways that possessed the top 5% degree distribution of DPN. Modules of DPN were mined according to ClusterONE. A total of 855 pathways were selected to build pathway interactions. By filtrating pathway interactions of weight values >0.7, a DPN with 312 nodes and 791 edges was obtained. Topological degree analysis revealed 15 hub pathways, such as heparan sulfate/heparin‑glycosaminoglycan (HS‑GAG) degradation, HS‑GAG metabolism and keratan sulfate degradation for RA based on DPN. Furthermore, hub pathways were also important in modules, which validated the significance of hub pathways. In conclusion, the proposed method is a computationally efficient way to identify hub pathways of RA, which identified 15 hub pathways that may be potential biomarkers and provide insight to future investigation and treatment of RA.

Identification of metabolic pathways using pathfinding approaches: a systematic review.

PubMed

Abd Algfoor, Zeyad; Shahrizal Sunar, Mohd; Abdullah, Afnizanfaizal; Kolivand, Hoshang

2017-03-01

Metabolic pathways have become increasingly available for various microorganisms. Such pathways have spurred the development of a wide array of computational tools, in particular, mathematical pathfinding approaches. This article can facilitate the understanding of computational analysis of metabolic pathways in genomics. Moreover, stoichiometric and pathfinding approaches in metabolic pathway analysis are discussed. Three major types of studies are elaborated: stoichiometric identification models, pathway-based graph analysis and pathfinding approaches in cellular metabolism. Furthermore, evaluation of the outcomes of the pathways with mathematical benchmarking metrics is provided. This review would lead to better comprehension of metabolism behaviors in living cells, in terms of computed pathfinding approaches. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Smoking-related microRNAs and mRNAs in human peripheral blood mononuclear cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Su, Ming-Wei

Teenager smoking is of great importance in public health. Functional roles of microRNAs have been documented in smoke-induced gene expression changes, but comprehensive mechanisms of microRNA-mRNA regulation and benefits remained poorly understood. We conducted the Teenager Smoking Reduction Trial (TSRT) to investigate the causal association between active smoking reduction and whole-genome microRNA and mRNA expression changes in human peripheral blood mononuclear cells (PBMC). A total of 12 teenagers with a substantial reduction in smoke quantity and a decrease in urine cotinine/creatinine ratio were enrolled in genomic analyses. In Gene Set Enrichment Analysis (GSEA) and Ingenuity Pathway Analysis (IPA), differentially expressedmore » genes altered by smoke reduction were mainly associated with glucocorticoid receptor signaling pathway. The integrative analysis of microRNA and mRNA found eleven differentially expressed microRNAs negatively correlated with predicted target genes. CD83 molecule regulated by miR-4498 in human PBMC, was critical for the canonical pathway of communication between innate and adaptive immune cells. Our data demonstrated that microRNAs could regulate immune responses in human PBMC after habitual smokers quit smoking and support the potential translational value of microRNAs in regulating disease-relevant gene expression caused by tobacco smoke. - Highlights: • We conducted a smoke reduction trial program and investigated the causal relationship between smoke and gene regulation. • MicroRNA and mRNA expression changes were examined in human PBMC. • MicroRNAs are important in regulating disease-causal genes after tobacco smoke reduction.« less

Construction and analysis of a modular model of caspase activation in apoptosis

PubMed Central

Harrington, Heather A; Ho, Kenneth L; Ghosh, Samik; Tung, KC

2008-01-01

Background A key physiological mechanism employed by multicellular organisms is apoptosis, or programmed cell death. Apoptosis is triggered by the activation of caspases in response to both extracellular (extrinsic) and intracellular (intrinsic) signals. The extrinsic and intrinsic pathways are characterized by the formation of the death-inducing signaling complex (DISC) and the apoptosome, respectively; both the DISC and the apoptosome are oligomers with complex formation dynamics. Additionally, the extrinsic and intrinsic pathways are coupled through the mitochondrial apoptosis-induced channel via the Bcl-2 family of proteins. Results A model of caspase activation is constructed and analyzed. The apoptosis signaling network is simplified through modularization methodologies and equilibrium abstractions for three functional modules. The mathematical model is composed of a system of ordinary differential equations which is numerically solved. Multiple linear regression analysis investigates the role of each module and reduced models are constructed to identify key contributions of the extrinsic and intrinsic pathways in triggering apoptosis for different cell lines. Conclusion Through linear regression techniques, we identified the feedbacks, dissociation of complexes, and negative regulators as the key components in apoptosis. The analysis and reduced models for our model formulation reveal that the chosen cell lines predominately exhibit strong extrinsic caspase, typical of type I cell, behavior. Furthermore, under the simplified model framework, the selected cells lines exhibit different modes by which caspase activation may occur. Finally the proposed modularized model of apoptosis may generalize behavior for additional cells and tissues, specifically identifying and predicting components responsible for the transition from type I to type II cell behavior. PMID:19077196

The CWI Pathway: Regulation of the Transcriptional Adaptive Response to Cell Wall Stress in Yeast

PubMed Central

Sanz, Ana Belén; García, Raúl; Rodríguez-Peña, José M.; Arroyo, Javier

2017-01-01

Fungi are surrounded by an essential structure, the cell wall, which not only confers cell shape but also protects cells from environmental stress. As a consequence, yeast cells growing under cell wall damage conditions elicit rescue mechanisms to provide maintenance of cellular integrity and fungal survival. Through transcriptional reprogramming, yeast modulate the expression of genes important for cell wall biogenesis and remodeling, metabolism and energy generation, morphogenesis, signal transduction and stress. The yeast cell wall integrity (CWI) pathway, which is very well conserved in other fungi, is the key pathway for the regulation of this adaptive response. In this review, we summarize the current knowledge of the yeast transcriptional program elicited to counterbalance cell wall stress situations, the role of the CWI pathway in the regulation of this program and the importance of the transcriptional input received by other pathways. Modulation of this adaptive response through the CWI pathway by positive and negative transcriptional feedbacks is also discussed. Since all these regulatory mechanisms are well conserved in pathogenic fungi, improving our knowledge about them will have an impact in the developing of new antifungal therapies. PMID:29371494

Pathways to Commercial Success: Technologies and Products Supported by the Fuel Cell Technologies Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weakley, Steven A.

The purpose of the project described in this report is to identify and document the commercial and emerging (projected to be commercialized within the next 3 years) hydrogen and fuel cell technologies and products that resulted from Department of Energy support through the Fuel Cell Technologies (FCT) Program in the Office of Energy Efficiency and Renewable Energy (EERE). Pacific Northwest National Laboratory (PNNL) undertook two efforts simultaneously to accomplish this project. The first effort was a patent search and analysis to identify patents related to hydrogen and fuel cells that are associated with FCT-funded projects (or projects conducted by DOE-EEREmore » predecessor programs) and to ascertain the patents’ current status, as well as any commercial products that may have used the technology documented in the patent. The second effort was a series of interviews with current and past FCT personnel, a review of relevant program annual reports, and an examination of grants made under the Small Business Innovation Research and Small Business Technology Transfer Programs that are related to hydrogen and fuel cells.« less

Pathways to Commercial Success: Technologies and Products Supported by the Fuel Cell Technologies Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weakley, Steven A.; Brown, Scott A.

The purpose of the project described in this report is to identify and document the commercial and emerging (projected to be commercialized within the next 3 years) hydrogen and fuel cell technologies and products that resulted from Department of Energy support through the Fuel Cell Technologies (FCT) Program in the Office of Energy Efficiency and Renewable Energy (EERE). To do this, Pacific Northwest National Laboratory (PNNL) undertook two efforts simultaneously to accomplish this project. The first effort was a patent search and analysis to identify hydrogen- and fuel-cell-related patents that are associated with FCT-funded projects (or projects conducted by DOE-EEREmore » predecessor programs) and to ascertain the patents current status, as well as any commercial products that may have used the technology documented in the patent. The second effort was a series of interviews with current and past FCT personnel, a review of relevant program annual reports, and an examination of hydrogen- and fuel-cell-related grants made under the Small Business Innovation Research and Small Business Technology Transfer Programs, and within the FCT portfolio.« less

Differential Expression of Programmed Cell Death on the Follicular Development in Normal and Miniature Pig Ovary

PubMed Central

Kim, Sang Hwan; Min, Kwan Sik; Kim, Nam Hyung; Yoon, Jong Taek

2012-01-01

Follicles are important in oocyte maturation. Successful estrous cycle requires remodeling of follicular cells, and proper execution of programmed cell death is crucial for normal follicular development. The objectives of the present study were to understand programmed cell death during follicle development, to analyze the differential follicle development patterns, and to assess the patterns of apoptosis and autophagy expression during follicle development in normal and miniature pigs. Through the analysis of differential patterns of programmed cell death during follicular development in porcine, MAP1LC3A, B and other autophagy-associated genes (ATG5, mTOR, Beclin-1) were found to increase in normal pigs, while it decreased in miniature pigs. However, for the apoptosis-associated genes, progression of genes during follicular development increased in miniature pigs, while it decreased in normal pigs. Thus, results show that normal and miniature pigs showed distinct patterns of follicular remodeling manifesting that programmed cell death largely depends on the types of pathway during follicular development (Type II or autophagy for normal pigs and Type I or apoptosis for miniature pigs). PMID:23056260

Pathway and network-based analysis of genome-wide association studies and RT-PCR validation in polycystic ovary syndrome.

PubMed

Shen, Haoran; Liang, Zhou; Zheng, Saihua; Li, Xuelian

2017-11-01

The purpose of this study was to identify promising candidate genes and pathways in polycystic ovary syndrome (PCOS). Microarray dataset GSE345269 obtained from the Gene Expression Omnibus database includes 7 granulosa cell samples from PCOS patients, and 3 normal granulosa cell samples. Differentially expressed genes (DEGs) were screened between PCOS and normal samples. Pathway enrichment analysis was conducted for DEGs using ClueGO and CluePedia plugin of Cytoscape. A Reactome functional interaction (FI) network of the DEGs was built using ReactomeFIViz, and then network modules were extracted, followed by pathway enrichment analysis for the modules. Expression of DEGs in granulosa cell samples was measured using quantitative RT-PCR. A total of 674 DEGs were retained, which were significantly enriched with inflammation and immune-related pathways. Eight modules were extracted from the Reactome FI network. Pathway enrichment analysis revealed significant pathways of each module: module 0, Regulation of RhoA activity and Signaling by Rho GTPases pathways shared ARHGAP4 and ARHGAP9; module 2, GlycoProtein VI-mediated activation cascade pathway was enriched with RHOG; module 3, Thromboxane A2 receptor signaling, Chemokine signaling pathway, CXCR4-mediated signaling events pathways were enriched with LYN, the hub gene of module 3. Results of RT-PCR confirmed the finding of the bioinformatic analysis that ARHGAP4, ARHGAP9, RHOG and LYN were significantly upregulated in PCOS. RhoA-related pathways, GlycoProtein VI-mediated activation cascade pathway, ARHGAP4, ARHGAP9, RHOG and LYN may be involved in the pathogenesis of PCOS.

A Single-Amino-Acid Substitution in Obg Activates a New Programmed Cell Death Pathway in Escherichia coli.

PubMed

Dewachter, Liselot; Verstraeten, Natalie; Monteyne, Daniel; Kint, Cyrielle Ines; Versées, Wim; Pérez-Morga, David; Michiels, Jan; Fauvart, Maarten

2015-12-22

Programmed cell death (PCD) is an important hallmark of multicellular organisms. Cells self-destruct through a regulated series of events for the benefit of the organism as a whole. The existence of PCD in bacteria has long been controversial due to the widely held belief that only multicellular organisms would profit from this kind of altruistic behavior at the cellular level. However, over the past decade, compelling experimental evidence has established the existence of such pathways in bacteria. Here, we report that expression of a mutant isoform of the essential GTPase ObgE causes rapid loss of viability in Escherichia coli. The physiological changes that occur upon expression of this mutant protein--including loss of membrane potential, chromosome condensation and fragmentation, exposure of phosphatidylserine on the cell surface, and membrane blebbing--point to a PCD mechanism. Importantly, key regulators and executioners of known bacterial PCD pathways were shown not to influence this cell death program. Collectively, our results suggest that the cell death pathway described in this work constitutes a new mode of bacterial PCD. Programmed cell death (PCD) is a well-known phenomenon in higher eukaryotes. In these organisms, PCD is essential for embryonic development--for example, the disappearance of the interdigital web--and also functions in tissue homeostasis and elimination of pathogen-invaded cells. The existence of PCD mechanisms in unicellular organisms like bacteria, on the other hand, has only recently begun to be recognized. We here demonstrate the existence of a bacterial PCD pathway that induces characteristics that are strikingly reminiscent of eukaryotic apoptosis, such as fragmentation of DNA, exposure of phosphatidylserine on the cell surface, and membrane blebbing. Our results can provide more insight into the mechanism and evolution of PCD pathways in higher eukaryotes. More importantly, especially in the light of the looming antibiotic crisis, they may point to a bacterial Achilles' heel and can inspire innovative ways of combating bacterial infections, directed at the targeted activation of PCD pathways. Copyright © 2015 Dewachter et al.

Pathway Analysis of Metabolic Syndrome Using a Genome-Wide Association Study of Korea Associated Resource (KARE) Cohorts.

PubMed

Shim, Unjin; Kim, Han-Na; Sung, Yeon-Ah; Kim, Hyung-Lae

2014-12-01

Metabolic syndrome (MetS) is a complex disorder related to insulin resistance, obesity, and inflammation. Genetic and environmental factors also contribute to the development of MetS, and through genome-wide association studies (GWASs), important susceptibility loci have been identified. However, GWASs focus more on individual single-nucleotide polymorphisms (SNPs), explaining only a small portion of genetic heritability. To overcome this limitation, pathway analyses are being applied to GWAS datasets. The aim of this study is to elucidate the biological pathways involved in the pathogenesis of MetS through pathway analysis. Cohort data from the Korea Associated Resource (KARE) was used for analysis, which include 8,842 individuals (age, 52.2 ± 8.9 years; body mass index, 24.6 ± 3.2 kg/m(2)). A total of 312,121 autosomal SNPs were obtained after quality control. Pathway analysis was conducted using Meta-analysis Gene-Set Enrichment of Variant Associations (MAGENTA) to discover the biological pathways associated with MetS. In the discovery phase, SNPs from chromosome 12, including rs11066280, rs2074356, and rs12229654, were associated with MetS (p < 5 × 10(-6)), and rs11066280 satisfied the Bonferroni-corrected cutoff (unadjusted p < 1.38 × 10(-7), Bonferroni-adjusted p < 0.05). Through pathway analysis, biological pathways, including electron carrier activity, signaling by platelet-derived growth factor (PDGF), the mitogen-activated protein kinase kinase kinase cascade, PDGF binding, peroxisome proliferator-activated receptor (PPAR) signaling, and DNA repair, were associated with MetS. Through pathway analysis of MetS, pathways related with PDGF, mitogen-activated protein kinase, and PPAR signaling, as well as nucleic acid binding, protein secretion, and DNA repair, were identified. Further studies will be needed to clarify the genetic pathogenesis leading to MetS.

Redundancy control in pathway databases (ReCiPa): an application for improving gene-set enrichment analysis in Omics studies and "Big data" biology.

PubMed

Vivar, Juan C; Pemu, Priscilla; McPherson, Ruth; Ghosh, Sujoy

2013-08-01

Abstract Unparalleled technological advances have fueled an explosive growth in the scope and scale of biological data and have propelled life sciences into the realm of "Big Data" that cannot be managed or analyzed by conventional approaches. Big Data in the life sciences are driven primarily via a diverse collection of 'omics'-based technologies, including genomics, proteomics, metabolomics, transcriptomics, metagenomics, and lipidomics. Gene-set enrichment analysis is a powerful approach for interrogating large 'omics' datasets, leading to the identification of biological mechanisms associated with observed outcomes. While several factors influence the results from such analysis, the impact from the contents of pathway databases is often under-appreciated. Pathway databases often contain variously named pathways that overlap with one another to varying degrees. Ignoring such redundancies during pathway analysis can lead to the designation of several pathways as being significant due to high content-similarity, rather than truly independent biological mechanisms. Statistically, such dependencies also result in correlated p values and overdispersion, leading to biased results. We investigated the level of redundancies in multiple pathway databases and observed large discrepancies in the nature and extent of pathway overlap. This prompted us to develop the application, ReCiPa (Redundancy Control in Pathway Databases), to control redundancies in pathway databases based on user-defined thresholds. Analysis of genomic and genetic datasets, using ReCiPa-generated overlap-controlled versions of KEGG and Reactome pathways, led to a reduction in redundancy among the top-scoring gene-sets and allowed for the inclusion of additional gene-sets representing possibly novel biological mechanisms. Using obesity as an example, bioinformatic analysis further demonstrated that gene-sets identified from overlap-controlled pathway databases show stronger evidence of prior association to obesity compared to pathways identified from the original databases.

Convergent evidence from systematic analysis of GWAS revealed genetic basis of esophageal cancer.

PubMed

Gao, Xue-Xin; Gao, Lei; Wang, Jiu-Qiang; Qu, Su-Su; Qu, Yue; Sun, Hong-Lei; Liu, Si-Dang; Shang, Ying-Li

2016-07-12

Recent genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with risk of esophageal cancer (EC). However, investigation of genetic basis from the perspective of systematic biology and integrative genomics remains scarce.In this study, we explored genetic basis of EC based on GWAS data and implemented a series of bioinformatics methods including functional annotation, expression quantitative trait loci (eQTL) analysis, pathway enrichment analysis and pathway grouped network analysis.Two hundred and thirteen risk SNPs were identified, in which 44 SNPs were found to have significantly differential gene expression in esophageal tissues by eQTL analysis. By pathway enrichment analysis, 170 risk genes mapped by risk SNPs were enriched into 38 significant GO terms and 17 significant KEGG pathways, which were significantly grouped into 9 sub-networks by pathway grouped network analysis. The 9 groups of interconnected pathways were mainly involved with muscle cell proliferation, cellular response to interleukin-6, cell adhesion molecules, and ethanol oxidation, which might participate in the development of EC.Our findings provide genetic evidence and new insight for exploring the molecular mechanisms of EC.

Insights into significant pathways and gene interaction networks underlying breast cancer cell line MCF-7 treated with 17β-estradiol (E2).

PubMed

Huan, Jinliang; Wang, Lishan; Xing, Li; Qin, Xianju; Feng, Lingbin; Pan, Xiaofeng; Zhu, Ling

2014-01-01

Estrogens are known to regulate the proliferation of breast cancer cells and to alter their cytoarchitectural and phenotypic properties, but the gene networks and pathways by which estrogenic hormones regulate these events are only partially understood. We used global gene expression profiling by Affymetrix GeneChip microarray analysis, with KEGG pathway enrichment, PPI network construction, module analysis and text mining methods to identify patterns and time courses of genes that are either stimulated or inhibited by estradiol (E2) in estrogen receptor (ER)-positive MCF-7 human breast cancer cells. Of the genes queried on the Affymetrix Human Genome U133 plus 2.0 microarray, we identified 628 (12h), 852 (24h) and 880 (48 h) differentially expressed genes (DEGs) that showed a robust pattern of regulation by E2. From pathway enrichment analysis, we found out the changes of metabolic pathways of E2 treated samples at each time point. At 12h time point, the changes of metabolic pathways were mainly focused on pathways in cancer, focal adhesion, and chemokine signaling pathway. At 24h time point, the changes were mainly enriched in neuroactive ligand-receptor interaction, cytokine-cytokine receptor interaction and calcium signaling pathway. At 48 h time point, the significant pathways were pathways in cancer, regulation of actin cytoskeleton, cell adhesion molecules (CAMs), axon guidance and ErbB signaling pathway. Of interest, our PPI network analysis and module analysis found that E2 treatment induced enhancement of PRSS23 at the three time points and PRSS23 was in the central position of each module. Text mining results showed that the important genes of DEGs have relationship with signal pathways, such as ERbB pathway (AREG), Wnt pathway (NDP), MAPK pathway (NTRK3, TH), IP3 pathway (TRA@) and some transcript factors (TCF4, MAF). Our studies highlight the diverse gene networks and metabolic and cell regulatory pathways through which E2 operates to achieve its widespread effects on breast cancer cells. © 2013 Elsevier B.V. All rights reserved.

Overview of an internationally-harmonized program for adverse outcome pathway development

EPA Science Inventory

Adverse outcome pathways (AOPs) are critical frameworks for organizing knowledge concerning the scientifically-credible predictive linkages between toxicological observations made at molecular and cellular levels (e.g., via molecular screening assays, biomarker responses, or chem...

Reusable, extensible, and modifiable R scripts and Kepler workflows for comprehensive single set ChIP-seq analysis.

PubMed

Cormier, Nathan; Kolisnik, Tyler; Bieda, Mark

2016-07-05

There has been an enormous expansion of use of chromatin immunoprecipitation followed by sequencing (ChIP-seq) technologies. Analysis of large-scale ChIP-seq datasets involves a complex series of steps and production of several specialized graphical outputs. A number of systems have emphasized custom development of ChIP-seq pipelines. These systems are primarily based on custom programming of a single, complex pipeline or supply libraries of modules and do not produce the full range of outputs commonly produced for ChIP-seq datasets. It is desirable to have more comprehensive pipelines, in particular ones addressing common metadata tasks, such as pathway analysis, and pipelines producing standard complex graphical outputs. It is advantageous if these are highly modular systems, available as both turnkey pipelines and individual modules, that are easily comprehensible, modifiable and extensible to allow rapid alteration in response to new analysis developments in this growing area. Furthermore, it is advantageous if these pipelines allow data provenance tracking. We present a set of 20 ChIP-seq analysis software modules implemented in the Kepler workflow system; most (18/20) were also implemented as standalone, fully functional R scripts. The set consists of four full turnkey pipelines and 16 component modules. The turnkey pipelines in Kepler allow data provenance tracking. Implementation emphasized use of common R packages and widely-used external tools (e.g., MACS for peak finding), along with custom programming. This software presents comprehensive solutions and easily repurposed code blocks for ChIP-seq analysis and pipeline creation. Tasks include mapping raw reads, peakfinding via MACS, summary statistics, peak location statistics, summary plots centered on the transcription start site (TSS), gene ontology, pathway analysis, and de novo motif finding, among others. These pipelines range from those performing a single task to those performing full analyses of ChIP-seq data. The pipelines are supplied as both Kepler workflows, which allow data provenance tracking, and, in the majority of cases, as standalone R scripts. These pipelines are designed for ease of modification and repurposing.

Career Development and Learning Pathways of Paralympic Coaches With a Disability.

PubMed

Douglas, Scott; Falcão, William R; Bloom, Gordon A

2018-01-01

The purpose of this study was to gain an understanding of the career development and learning pathways of Paralympic head coaches who previously competed as Paralympic athletes. Each coach participated in a semistructured interview. A thematic analysis of the data revealed three higher order themes, which were called becoming a coach, learning to coach, and lifelong learning and teaching. Across these themes, participants discussed interactions with other coaches and athletes with a disability, learning from mentors and coaching clinics, as well as limited formal educational opportunities they experienced transitioning from athlete to head coach. The findings revealed that they acquired most of their knowledge from a combination of knowledge gained as athletes and informal sources, including trial and error. They also stressed the need for enhanced recruiting of parasport coaches and parasport coach education opportunities that would enhance programs for athletes with physical disabilities, from grassroots to Paralympic levels.

Analyzing cell fate control by cytokines through continuous single cell biochemistry.

PubMed

Rieger, Michael A; Schroeder, Timm

2009-10-01

Cytokines are important regulators of cell fates with high clinical and commercial relevance. However, despite decades of intense academic and industrial research, it proved surprisingly difficult to describe the biological functions of cytokines in a precise and comprehensive manner. The exact analysis of cytokine biology is complicated by the fact that individual cytokines control many different cell fates and activate a multitude of intracellular signaling pathways. Moreover, although activating different molecular programs, different cytokines can be redundant in their biological effects. In addition, cytokines with different biological effects can activate overlapping signaling pathways. This prospect article will outline the necessity of continuous single cell biochemistry to unravel the biological functions of molecular cytokine signaling. It focuses on potentials and limitations of recent technical developments in fluorescent time-lapse imaging and single cell tracking allowing constant long-term observation of molecules and behavior of single cells. (c) 2009 Wiley-Liss, Inc.

IBP's Four-Prong Approach for Broadening Participation in the STEM Community

NASA Astrophysics Data System (ADS)

Ricciardi, L.; Fauver, A.; Johnson, A.; Detrick, L.; Siegfried, D.; Thomas, S.; Valaitis, S.

2013-12-01

The goal of the Institute for Broadening Participation (IBP) is to increase diversity in the Science, Technology, Engineering and Mathematics (STEM) workforce. As a freestanding non-profit dedicated to this work IBP is uniquely positioned to provide resources to faculty and students that individual institutions and disciplinary based programs cannot. Through its initial work with the NSF Integrative Graduate Education and Research Traineeship (IGERT), Research Experiences for Undergraduates (REU), and Alliance for Graduate Education and the Professoriate (AGEP) programs, IBP developed a four-pronged approach open to all members of the STEM community nationally for addressing the problem of underrepresentation: Synthesizing information - compiling and translating best practices into materials and resources accessible and useful to a broad national audience; Creating and maintaining strategic web resources - making information on programs, best practices, and references easily available to a wide audience including students, faculty, and administrators; Extensive face-to-face and virtual outreach - drawing constituents to the resources available via IBP that support students and faculty through the entire STEM pathway; and Catalyzing partnerships - cultivating a community of practice and culture of diversity, to reduce isolation among diversity practitioners, and to increase information sharing. IBP is also home to several successful initiatives that use both virtual and face-to-face components to bring together underrepresented students with established underrepresented and other scientists in academia, government and industry. These connections provide underrepresented students with supportive mentoring, networking opportunities, and professional skill development contributing to an overall improved retention rate of underrepresented students majoring in STEM degrees. IBP's initiatives include the NASA One Stop Shopping Initiative (NASA OSSI), Pathways to Ocean Science, Pathways to Engineering, and the Minorities Striving and Pursuing Higher Degrees of Success (MS PHD'S) Professional Development program in Earth System Science (ESS). NASA OSSI recruits and facilitates student engagement in NASA student education and employment opportunities. Pathways to Ocean Science connects and supports underrepresented students with REU programs in Ocean Sciences and serves as a resource for REU program directors. Pathways to Engineering synthesized mentoring resources into an online mentoring manual for underrepresented STEM students that has been extensively vetted by mentoring experts throughout the country. MS PHD'S, an award-winning professional development program for underrepresented students, focuses on increasing the retention rate of underrepresented students receiving advanced degrees in ESS. As of August 2013, 213 students have participated in the program. 67 of those students are currently enrolled in a PhD. program. Another 47 have completed their PhD and are actively engaged in the ESS workforce.

Using a Participatory Approach to Investigate a Leadership Program's Theory of Change

ERIC Educational Resources Information Center

Burbaugh, Bradley; Seibel, Seibel,; Archibald, Thomas

2017-01-01

The linkages between interventions and outcomes of leadership initiatives have been insufficiently studied. To better understand these links, the Virginia agricultural leadership program conducted a pathway mapping session to investigate the program's theory of change. In this novel process, program participants engaged in collaborative…

Management of women at high risk of hereditary breast cancer in the Veneto Regional Program for Prevention.

PubMed

Del Sole, Annamaria; Cinquetti, Sandro; Fedato, Chiara; Montagna, Marco; Russo, Francesca; Sbrogiò, Luca Gino; Zorzi, Manuel

2015-01-01

Today it is well-known that high risk of genetic breast cancer concerns a very limited part of the population: no more than 2-3 women are affected every thousand and this condition as a whole accounts for no more than 3%-5% of all breast cancers. Following the directions contained in the 2014-2018 National Prevention Plan, Veneto's 2014-2018 Regional Program of Prevention (PRP), approved by Regional Council Resolution (DGR) No. 749 of 14.5.2015, consolidation of a pathway of diagnosis, observation, and prophylaxis for women at high risk of hereditary breast carcinoma is thus proposed. The principal activities of this policy will be the following: creation of a regional working group, survey of currently existing pathways for the identification of women at risk of hereditary breast cancer and adoption of the same, approval and consolidation of a structured regional pathway for women at high risk of hereditary breast and/or ovarian cancer, from paths of oncogenetic consultation and genetic testing to management of disease risk. Subsequent to the recognition of the pathway of diagnosis, observation, and prophylaxis for women at high risk of hereditary breast carcinoma, the Veneto region undertakes to develop a co-ordinated program of information and training on this pathway directed at the population and healthcare workers. It is firmly hoped that with the inclusion of a program for the management of women at high risk of hereditary breast cancer within the Veneto PRP this topic may become more defined and structured in terms of sustainability, integration with the existing regional networks (mammography network, Breast Unit), contrasting inequality, monitoring and evaluation, in this way pursuing the objectives of a reduction of cause-specific mortality and improvement of quality of life.

Identifying novel glioma associated pathways based on systems biology level meta-analysis.

PubMed

Hu, Yangfan; Li, Jinquan; Yan, Wenying; Chen, Jiajia; Li, Yin; Hu, Guang; Shen, Bairong

2013-01-01

With recent advances in microarray technology, including genomics, proteomics, and metabolomics, it brings a great challenge for integrating this "-omics" data to analysis complex disease. Glioma is an extremely aggressive and lethal form of brain tumor, and thus the study of the molecule mechanism underlying glioma remains very important. To date, most studies focus on detecting the differentially expressed genes in glioma. However, the meta-analysis for pathway analysis based on multiple microarray datasets has not been systematically pursued. In this study, we therefore developed a systems biology based approach by integrating three types of omics data to identify common pathways in glioma. Firstly, the meta-analysis has been performed to study the overlapping of signatures at different levels based on the microarray gene expression data of glioma. Among these gene expression datasets, 12 pathways were found in GeneGO database that shared by four stages. Then, microRNA expression profiles and ChIP-seq data were integrated for the further pathway enrichment analysis. As a result, we suggest 5 of these pathways could be served as putative pathways in glioma. Among them, the pathway of TGF-beta-dependent induction of EMT via SMAD is of particular importance. Our results demonstrate that the meta-analysis based on systems biology level provide a more useful approach to study the molecule mechanism of complex disease. The integration of different types of omics data, including gene expression microarrays, microRNA and ChIP-seq data, suggest some common pathways correlated with glioma. These findings will offer useful potential candidates for targeted therapeutic intervention of glioma.

WDR26 in Advanced Breast Cancer: A Novel Regulator of the P13K/AKT Pathway

DTIC Science & Technology

2017-10-01

AWARD NUMBER: W81XWH-14-1-0539 TITLE: WDR26 in Advanced Breast Cancer : A Novel Regulator of the P13K/ AKT Pathway PRINCIPAL INVESTIGATOR...SUBTITLE 5a. CONTRACT NUMBER WDR26 in Advanced Breast Cancer : A Novel Regulator of the P13K/AKT Pathway 5b. GRANT NUMBER W81XWH-14-1-0539 5c. PROGRAM...NOTES 14. ABSTRACT The PI3K/AKT pathway is one of the most deregulated pathways in breast cancers (>70%), and a major contributor to tumor progression

Genome-wide pathway-based association analysis identifies risk pathways associated with Parkinson's disease.

PubMed

Zhang, Mingming; Mu, Hongbo; Shang, Zhenwei; Kang, Kai; Lv, Hongchao; Duan, Lian; Li, Jin; Chen, Xinren; Teng, Yanbo; Jiang, Yongshuai; Zhang, Ruijie

2017-01-06

Parkinson's disease (PD) is the second most common neurodegenerative disease. It is generally believed that it is influenced by both genetic and environmental factors, but the precise pathogenesis of PD is unknown to date. In this study, we performed a pathway analysis based on genome-wide association study (GWAS) to detect risk pathways of PD in three GWAS datasets. We first mapped all SNP markers to autosomal genes in each GWAS dataset. Then, we evaluated gene risk values using the minimum P-value of the tagSNPs. We took a pathway as a unit to identify the risk pathways based on the cumulative risks of the genes in the pathway. Finally, we combine the analysis results of the three datasets to detect the high risk pathways associated with PD. We found there were five same pathways in the three datasets. Besides, we also found there were five pathways which were shared in two datasets. Most of these pathways are associated with nervoussystem. Five pathways had been reported to be PD-related pathways in the previous literature. Our findings also implied that there was a close association between immune response and PD. Continued investigation of these pathways will further help us explain the pathogenesis of PD. Copyright © 2016. Published by Elsevier Ltd.

A novel dysregulated pathway-identification analysis based on global influence of within-pathway effects and crosstalk between pathways

PubMed Central

Han, Junwei; Li, Chunquan; Yang, Haixiu; Xu, Yanjun; Zhang, Chunlong; Ma, Jiquan; Shi, Xinrui; Liu, Wei; Shang, Desi; Yao, Qianlan; Zhang, Yunpeng; Su, Fei; Feng, Li; Li, Xia

2015-01-01

Identifying dysregulated pathways from high-throughput experimental data in order to infer underlying biological insights is an important task. Current pathway-identification methods focus on single pathways in isolation; however, consideration of crosstalk between pathways could improve our understanding of alterations in biological states. We propose a novel method of pathway analysis based on global influence (PAGI) to identify dysregulated pathways, by considering both within-pathway effects and crosstalk between pathways. We constructed a global gene–gene network based on the relationships among genes extracted from a pathway database. We then evaluated the extent of differential expression for each gene, and mapped them to the global network. The random walk with restart algorithm was used to calculate the extent of genes affected by global influence. Finally, we used cumulative distribution functions to determine the significance values of the dysregulated pathways. We applied the PAGI method to five cancer microarray datasets, and compared our results with gene set enrichment analysis and five other methods. Based on these analyses, we demonstrated that PAGI can effectively identify dysregulated pathways associated with cancer, with strong reproducibility and robustness. We implemented PAGI using the freely available R-based and Web-based tools (http://bioinfo.hrbmu.edu.cn/PAGI). PMID:25551156

Meta-analysis of pathway enrichment: combining independent and dependent omics data sets.

PubMed

Kaever, Alexander; Landesfeind, Manuel; Feussner, Kirstin; Morgenstern, Burkhard; Feussner, Ivo; Meinicke, Peter

2014-01-01

A major challenge in current systems biology is the combination and integrative analysis of large data sets obtained from different high-throughput omics platforms, such as mass spectrometry based Metabolomics and Proteomics or DNA microarray or RNA-seq-based Transcriptomics. Especially in the case of non-targeted Metabolomics experiments, where it is often impossible to unambiguously map ion features from mass spectrometry analysis to metabolites, the integration of more reliable omics technologies is highly desirable. A popular method for the knowledge-based interpretation of single data sets is the (Gene) Set Enrichment Analysis. In order to combine the results from different analyses, we introduce a methodical framework for the meta-analysis of p-values obtained from Pathway Enrichment Analysis (Set Enrichment Analysis based on pathways) of multiple dependent or independent data sets from different omics platforms. For dependent data sets, e.g. obtained from the same biological samples, the framework utilizes a covariance estimation procedure based on the nonsignificant pathways in single data set enrichment analysis. The framework is evaluated and applied in the joint analysis of Metabolomics mass spectrometry and Transcriptomics DNA microarray data in the context of plant wounding. In extensive studies of simulated data set dependence, the introduced correlation could be fully reconstructed by means of the covariance estimation based on pathway enrichment. By restricting the range of p-values of pathways considered in the estimation, the overestimation of correlation, which is introduced by the significant pathways, could be reduced. When applying the proposed methods to the real data sets, the meta-analysis was shown not only to be a powerful tool to investigate the correlation between different data sets and summarize the results of multiple analyses but also to distinguish experiment-specific key pathways.

Tissue Non-Specific Genes and Pathways Associated with Diabetes: An Expression Meta-Analysis.

PubMed

Mei, Hao; Li, Lianna; Liu, Shijian; Jiang, Fan; Griswold, Michael; Mosley, Thomas

2017-01-21

We performed expression studies to identify tissue non-specific genes and pathways of diabetes by meta-analysis. We searched curated datasets of the Gene Expression Omnibus (GEO) database and identified 13 and five expression studies of diabetes and insulin responses at various tissues, respectively. We tested differential gene expression by empirical Bayes-based linear method and investigated gene set expression association by knowledge-based enrichment analysis. Meta-analysis by different methods was applied to identify tissue non-specific genes and gene sets. We also proposed pathway mapping analysis to infer functions of the identified gene sets, and correlation and independent analysis to evaluate expression association profile of genes and gene sets between studies and tissues. Our analysis showed that PGRMC1 and HADH genes were significant over diabetes studies, while IRS1 and MPST genes were significant over insulin response studies, and joint analysis showed that HADH and MPST genes were significant over all combined data sets. The pathway analysis identified six significant gene sets over all studies. The KEGG pathway mapping indicated that the significant gene sets are related to diabetes pathogenesis. The results also presented that 12.8% and 59.0% pairwise studies had significantly correlated expression association for genes and gene sets, respectively; moreover, 12.8% pairwise studies had independent expression association for genes, but no studies were observed significantly different for expression association of gene sets. Our analysis indicated that there are both tissue specific and non-specific genes and pathways associated with diabetes pathogenesis. Compared to the gene expression, pathway association tends to be tissue non-specific, and a common pathway influencing diabetes development is activated through different genes at different tissues.

Inhibition of Aurora A Kinase by Alisertib Induces Autophagy and Cell Cycle Arrest and Increases Chemosensitivity in Human Hepatocellular Carcinoma HepG2 Cells.

PubMed

Zhu, Qiaohua; Yu, Xinfa; Zhou, Zhi-Wei; Zhou, Chengyu; Chen, Xiao-Wu; Zhou, Shu-Feng

2017-01-01

Aurora A kinase represent a feasible target in cancer therapy. To evaluate the proteomic response of human liver carcinoma cells to alisertib (ALS) and identify the molecular targets of ALS, we examined the effects of ALS on the proliferation, cell cycle, autophagy, apoptosis, and chemosensitivity in HepG2 cells. The stable-isotope labeling by amino acids in cell culture (SILAC) based quantitative proteomic study was performed to evaluate the proteomic response to ALS. Cell cycle distribution and apoptosis were assessed using flow cytometry and autophagy was determined using flow cytometry and confocal microscopy. Our SILAC proteomic study showed that ALS regulated the expression of 914 proteins, with 407 molecules being up-regulated and 507 molecules being down-regulated in HepG2 cells. Ingenuity pathway analysis (IPA) and KEGG pathway analysis identified 146 and 32 signaling pathways were regulated by ALS, respectively, which were associated with cell survival, programmed cell death, and nutrition-energy metabolism. Subsequently, the verification experiments showed that ALS remarkably arrested HepG2 cells in G2/M phase and led to an accumulation of aneuploidy via regulating the expression of key cell cycle regulators. ALS induced a marked autophagy in a concentration- and time-dependent manner via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. Autophagy inhibition promoted the pro-apoptotic effect of ALS, indicating a cyto-protective role of ALS-induced autophagy. ALS increased the chemosensitivity of HepG2 cells to cisplatin and doxorubicin. Taken together, ALS induces autophagy and cell cycle arrest in HepG2 cells via PI3K/Akt/mTOR-mediated pathway. Autophagy inhibition may promote the anticancer effect of ALS and sensitize the chemotherapy in HepG2 cells. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Comparison of transcripts in Phalaenopsis bellina and Phalaenopsis equestris (Orchidaceae) flowers to deduce monoterpene biosynthesis pathway.

PubMed

Hsiao, Yu-Yun; Tsai, Wen-Chieh; Kuoh, Chang-Sheng; Huang, Tian-Hsiang; Wang, Hei-Chia; Wu, Tian-Shung; Leu, Yann-Lii; Chen, Wen-Huei; Chen, Hong-Hwa

2006-07-13

Floral scent is one of the important strategies for ensuring fertilization and for determining seed or fruit set. Research on plant scents has hampered mainly by the invisibility of this character, its dynamic nature, and complex mixtures of components that are present in very small quantities. Most progress in scent research, as in other areas of plant biology, has come from the use of molecular and biochemical techniques. Although volatile components have been identified in several orchid species, the biosynthetic pathways of orchid flower fragrance are far from understood. We investigated how flower fragrance was generated in certain Phalaenopsis orchids by determining the chemical components of the floral scent, identifying floral expressed-sequence-tags (ESTs), and deducing the pathways of floral scent biosynthesis in Phalaneopsis bellina by bioinformatics analysis. The main chemical components in the P. bellina flower were shown by gas chromatography-mass spectrometry to be monoterpenoids, benzenoids and phenylpropanoids. The set of floral scent producing enzymes in the biosynthetic pathway from glyceraldehyde-3-phosphate (G3P) to geraniol and linalool were recognized through data mining of the P. bellina floral EST database (dbEST). Transcripts preferentially expressed in P. bellina were distinguished by comparing the scent floral dbEST to that of a scentless species, P. equestris, and included those encoding lipoxygenase, epimerase, diacylglycerol kinase and geranyl diphosphate synthase. In addition, EST filtering results showed that transcripts encoding signal transduction and Myb transcription factors and methyltransferase, in addition to those for scent biosynthesis, were detected by in silico hybridization of the P. bellina unigene database against those of the scentless species, rice and Arabidopsis. Altogether, we pinpointed 66% of the biosynthetic steps from G3P to geraniol, linalool and their derivatives. This systems biology program combined chemical analysis, genomics and bioinformatics to elucidate the scent biosynthesis pathway and identify the relevant genes. It integrates the forward and reverse genetic approaches to knowledge discovery by which researchers can study non-model plants.

Tox21 Enricher: Web-based Chemical/Biological Functional Annotation Analysis Tool Based on Tox21 Toxicity Screening Platform.

PubMed

Hur, Junguk; Danes, Larson; Hsieh, Jui-Hua; McGregor, Brett; Krout, Dakota; Auerbach, Scott

2018-05-01

The US Toxicology Testing in the 21st Century (Tox21) program was established to develop more efficient and human-relevant toxicity assessment methods. The Tox21 program screens >10,000 chemicals using quantitative high-throughput screening (qHTS) of assays that measure effects on toxicity pathways. To date, more than 70 assays have yielded >12 million concentration-response curves. The patterns of activity across assays can be used to define similarity between chemicals. Assuming chemicals with similar activity profiles have similar toxicological properties, we may infer toxicological properties based on its neighbourhood. One approach to inference is chemical/biological annotation enrichment analysis. Here, we present Tox21 Enricher, a web-based chemical annotation enrichment tool for the Tox21 toxicity screening platform. Tox21 Enricher identifies over-represented chemical/biological annotations among lists of chemicals (neighbourhoods), facilitating the identification of the toxicological properties and mechanisms in the chemical set. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Using Ambystoma mexicanum (Mexican axolotl) embryos, chemical genetics, and microarray analysis to identify signaling pathways associated with tissue regeneration.

PubMed

Ponomareva, Larissa V; Athippozhy, Antony; Thorson, Jon S; Voss, S Randal

2015-12-01

Amphibian vertebrates are important models in regenerative biology because they present exceptional regenerative capabilities throughout life. However, it takes considerable effort to rear amphibians to juvenile and adult stages for regeneration studies, and the relatively large sizes that frogs and salamanders achieve during development make them difficult to use in chemical screens. Here, we introduce a new tail regeneration model using late stage Mexican axolotl embryos. We show that axolotl embryos completely regenerate amputated tails in 7days before they exhaust their yolk supply and begin to feed. Further, we show that axolotl embryos can be efficiently reared in microtiter plates to achieve moderate throughput screening of soluble chemicals to investigate toxicity and identify molecules that alter regenerative outcome. As proof of principle, we identified integration 1 / wingless (Wnt), transforming growth factor beta (Tgf-β), and fibroblast growth factor (Fgf) pathway antagonists that completely block tail regeneration and additional chemicals that significantly affected tail outgrowth. Furthermore, we used microarray analysis to show that inhibition of Wnt signaling broadly affects transcription of genes associated with Wnt, Fgf, Tgf-β, epidermal growth factor (Egf), Notch, nerve growth factor (Ngf), homeotic gene (Hox), rat sarcoma/mitogen-activated protein kinase (Ras/Mapk), myelocytomatosis viral oncogene (Myc), tumor protein 53 (p53), and retinoic acid (RA) pathways. Punctuated changes in the expression of genes known to regulate vertebrate development were observed; this suggests the tail regeneration transcriptional program is hierarchically structured and temporally ordered. Our study establishes the axolotl as a chemical screening model to investigate signaling pathways associated with tissue regeneration. Copyright © 2015 Elsevier Inc. All rights reserved.

Overcoming chemotherapy resistance of ovarian cancer cells by liposomal cisplatin: molecular mechanisms unveiled by gene expression profiling.

PubMed

Koch, Martin; Krieger, Michaela L; Stölting, Daniel; Brenner, Norbert; Beier, Manfred; Jaehde, Ulrich; Wiese, Michael; Royer, Hans-Dieter; Bendas, Gerd

2013-04-15

Previously we reported that liposomal cisplatin (CDDP) overcomes CDDP resistance of ovarian A2780cis cancer cells (Krieger et al., Int. J. Pharm. 389, 2010, 10-17). Here we find that the cytotoxic activity of liposomal CDDP is not associated with detectable DNA platination in resistant ovarian cancer cells. This suggests that the mode of action of liposomal CDDP is different from the free drug. To gain insight into mechanisms of liposomal CDDP activity, we performed a transcriptome analysis of untreated A2780cis cells, and A2780cis cells in response to exposure with IC50 values of free or liposomal CDDP. A process network analysis of upregulated genes showed that liposomal CDDP induced a highly different gene expression profile in comparison to the free drug. p53 was identified as a key player directing transcriptional responses to free or liposomal CDDP. The free drug induced expression of essential genes of the intrinsic (mitochondrial) apoptosis pathway (BAX, BID, CASP9) most likely through p38MAPK activation. In contrast, liposomal CDDP induced expression of genes from DNA damage pathways and several genes of the extrinsic pathway of apoptosis (TNFRSF10B-DR5, CD70-TNFSF7). It thus appears that liposomal CDDP overcomes CDDP resistance by inducing DNA damage and in consequence programmed cell death by the extrinsic pathway. Predictions from gene expression data with respect to apoptosis activation were confirmed at the protein level by an apoptosis antibody array. This sheds new light on liposomal drug carrier approaches in cancer and suggests liposomal CDDP as promising strategy for the treatment of CDDP resistant ovarian carcinomas. Copyright © 2013 Elsevier Inc. All rights reserved.

Integrating Contextualized Math in the MultiCraft Curricula at Sauk Valley Community College. Pathways to Results: Implementation Partnerships Strategy Brief

ERIC Educational Resources Information Center

Rockey, Marci

2016-01-01

Sauk Valley Community College (SVCC) has returned to the Pathways to Results (PTR) process to analyze and improve a new pathway each year for the last five years. They have become so invested in PTR that they have institutionalized its use into their approach to program review and continuous improvement, creating an institutional PTR team…

Pathways for scaling up public health interventions.

PubMed

Indig, Devon; Lee, Karen; Grunseit, Anne; Milat, Andrew; Bauman, Adrian

2017-08-01

To achieve population-wide health improvement, public health interventions found effective in selected samples need to be 'scaled up' and implemented more widely. The pathways through which interventions are scaled up are not well characterised. The aim of this paper is to identify examples of public health interventions which have been scaled up and to develop a conceptual framework which quantifies and describes this process. A multi-stage international literature search was undertaken to identify examples of public health interventions in high income countries that have been scaled up or implemented at scale. Initial abstract review identified articles which met all the criteria of being a: 1) public health intervention; 2) chronic disease prevention focus; 3) program delivered at a wide geographical scale (state, national or international). Interventions were reviewed and coded into a conceptual framework pathway to document their scaling up process. For each program, an in-depth review of the identified articles was undertaken along with a broad internet based search to determine the outcomes of the dissemination process. A conceptual framework of scaling up pathways was developed that involved four stages (development, efficacy testing, real world trial and dissemination) to which the 40 programs were mapped. The search identified 40 public health interventions that showed evidence of being scaled up. Four pathways were identified to capture the different scaling up trajectories taken which included: 'Type I - Comprehensive' (55%) which passed through all four stages, 'Type II - Efficacy omitters' (5%) which did not conduct efficacy testing, 'Type III - Trial omitters' (25%) which did not conduct a real world trial, and 'Type IV - At scale dissemination' (15%) which skipped both efficacy testing and a real world trial. This is the first study to classify and quantify the potential pathways through which public health interventions in high income countries are scaled up to reach the broader population. Mapping these pathways not only demonstrates the different trajectories that occur in scaling up public health interventions, but also allows the variation across scaling up pathways to be classified. The policy and practice determinants leading to each pathway remain for future study, especially to identify the conditions under which efficacy and replication stages are missing.

ABCs of Being Smart… P Is for Productivity

ERIC Educational Resources Information Center

Foster, Joanne

2014-01-01

In this article, the author presents pointers for--and perspectives on--pathways to productivity. The following pathways are presented and described: (1) Planning and Preparation; (2) Proper Programming; (3) Play; (4) Pay Attention; (5) Possible Problems; and (6) Practice and Persistence.

Pappas and Tepe's Pathways to Knowledge Model.

ERIC Educational Resources Information Center

Zimmerman, Nancy P.; Pappas, Marjorie L.; Tepe, Ann E.

2002-01-01

Describes the Pathways to Knowledge model for helping students achieve information literacy in library media programs. Discusses the searcher's thinking, information search or seeking, and instructional strategies; information skills; the six stages in the model, including appreciation, presearch, search, interpretation, communication, and…

Proof-of-Concept Demonstrations for Computation-Based Human Reliability Analysis. Modeling Operator Performance During Flooding Scenarios

DOE Office of Scientific and Technical Information (OSTI.GOV)

Joe, Jeffrey Clark; Boring, Ronald Laurids; Herberger, Sarah Elizabeth Marie

The United States (U.S.) Department of Energy (DOE) Light Water Reactor Sustainability (LWRS) program has the overall objective to help sustain the existing commercial nuclear power plants (NPPs). To accomplish this program objective, there are multiple LWRS “pathways,” or research and development (R&D) focus areas. One LWRS focus area is called the Risk-Informed Safety Margin and Characterization (RISMC) pathway. Initial efforts under this pathway to combine probabilistic and plant multi-physics models to quantify safety margins and support business decisions also included HRA, but in a somewhat simplified manner. HRA experts at Idaho National Laboratory (INL) have been collaborating with othermore » experts to develop a computational HRA approach, called the Human Unimodel for Nuclear Technology to Enhance Reliability (HUNTER), for inclusion into the RISMC framework. The basic premise of this research is to leverage applicable computational techniques, namely simulation and modeling, to develop and then, using RAVEN as a controller, seamlessly integrate virtual operator models (HUNTER) with 1) the dynamic computational MOOSE runtime environment that includes a full-scope plant model, and 2) the RISMC framework PRA models already in use. The HUNTER computational HRA approach is a hybrid approach that leverages past work from cognitive psychology, human performance modeling, and HRA, but it is also a significant departure from existing static and even dynamic HRA methods. This report is divided into five chapters that cover the development of an external flooding event test case and associated statistical modeling considerations.« less

Pathways to the PhD in Nursing: An Analysis of Similarities and Differences.

PubMed

Nehls, Nadine; Barber, Gale; Rice, Elizabeth

2016-01-01

New educational pathways are needed to increase the number of doctor of philosophy (PhD)-prepared nurses. To address this need, an early-entry PhD option designed to engage students in PhD coursework and research during the undergraduate nursing major was developed at the University of Wisconsin-Madison. An evaluation comparing the early-entry option with two more conventional entry points was conducted. Three groups (N = 84) comprised the sample: (a) early-entry students admitted as undergraduates or immediately upon graduation (N = 29), (b) mid-entry students with baccalaureate degrees and at least 1 year of work experience (N = 27), and (c) delayed-entry students with master's degrees and 1 or more years of work experience (N = 28). Qualitative and quantitative data were collected from the 3 groups of students who were admitted from 2002 to 2011. The sources of data were transcriptions of individual interviews and reviews of existing data. Seventy-seven percent of the sample participated in the individual interviews. The database review included all students who matriculated into the PhD program. Common themes among the 3 groups included a need for educational funding, the importance of a faculty mentor, and concern about preparation for the teaching role and the academic work environment. The groups were also comparable in terms of research productivity during doctoral study and postgraduation employment. Differences were found on measures of diversity, program progression, and perceptions of clinical competence. The findings provide needed data for the development and expansion of educational pathways to the PhD in nursing. Copyright © 2016 Elsevier Inc. All rights reserved.

Multi-membership gene regulation in pathway based microarray analysis

PubMed Central

2011-01-01

Background Gene expression analysis has been intensively researched for more than a decade. Recently, there has been elevated interest in the integration of microarray data analysis with other types of biological knowledge in a holistic analytical approach. We propose a methodology that can be facilitated for pathway based microarray data analysis, based on the observation that a substantial proportion of genes present in biochemical pathway databases are members of a number of distinct pathways. Our methodology aims towards establishing the state of individual pathways, by identifying those truly affected by the experimental conditions based on the behaviour of such genes. For that purpose it considers all the pathways in which a gene participates and the general census of gene expression per pathway. Results We utilise hill climbing, simulated annealing and a genetic algorithm to analyse the consistency of the produced results, through the application of fuzzy adjusted rand indexes and hamming distance. All algorithms produce highly consistent genes to pathways allocations, revealing the contribution of genes to pathway functionality, in agreement with current pathway state visualisation techniques, with the simulated annealing search proving slightly superior in terms of efficiency. Conclusions We show that the expression values of genes, which are members of a number of biochemical pathways or modules, are the net effect of the contribution of each gene to these biochemical processes. We show that by manipulating the pathway and module contribution of such genes to follow underlying trends we can interpret microarray results centred on the behaviour of these genes. PMID:21939531

Multi-membership gene regulation in pathway based microarray analysis.

PubMed

Pavlidis, Stelios P; Payne, Annette M; Swift, Stephen M

2011-09-22

Gene expression analysis has been intensively researched for more than a decade. Recently, there has been elevated interest in the integration of microarray data analysis with other types of biological knowledge in a holistic analytical approach. We propose a methodology that can be facilitated for pathway based microarray data analysis, based on the observation that a substantial proportion of genes present in biochemical pathway databases are members of a number of distinct pathways. Our methodology aims towards establishing the state of individual pathways, by identifying those truly affected by the experimental conditions based on the behaviour of such genes. For that purpose it considers all the pathways in which a gene participates and the general census of gene expression per pathway. We utilise hill climbing, simulated annealing and a genetic algorithm to analyse the consistency of the produced results, through the application of fuzzy adjusted rand indexes and hamming distance. All algorithms produce highly consistent genes to pathways allocations, revealing the contribution of genes to pathway functionality, in agreement with current pathway state visualisation techniques, with the simulated annealing search proving slightly superior in terms of efficiency. We show that the expression values of genes, which are members of a number of biochemical pathways or modules, are the net effect of the contribution of each gene to these biochemical processes. We show that by manipulating the pathway and module contribution of such genes to follow underlying trends we can interpret microarray results centred on the behaviour of these genes.

MetaMapR: pathway independent metabolomic network analysis incorporating unknowns.

PubMed

Grapov, Dmitry; Wanichthanarak, Kwanjeera; Fiehn, Oliver

2015-08-15

Metabolic network mapping is a widely used approach for integration of metabolomic experimental results with biological domain knowledge. However, current approaches can be limited by biochemical domain or pathway knowledge which results in sparse disconnected graphs for real world metabolomic experiments. MetaMapR integrates enzymatic transformations with metabolite structural similarity, mass spectral similarity and empirical associations to generate richly connected metabolic networks. This open source, web-based or desktop software, written in the R programming language, leverages KEGG and PubChem databases to derive associations between metabolites even in cases where biochemical domain or molecular annotations are unknown. Network calculation is enhanced through an interface to the Chemical Translation System, which allows metabolite identifier translation between >200 common biochemical databases. Analysis results are presented as interactive visualizations or can be exported as high-quality graphics and numerical tables which can be imported into common network analysis and visualization tools. Freely available at http://dgrapov.github.io/MetaMapR/. Requires R and a modern web browser. Installation instructions, tutorials and application examples are available at http://dgrapov.github.io/MetaMapR/. ofiehn@ucdavis.edu. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

ApoptoProteomics, an integrated database for analysis of proteomics data obtained from apoptotic cells.

PubMed

Arntzen, Magnus Ø; Thiede, Bernd

2012-02-01

Apoptosis is the most commonly described form of programmed cell death, and dysfunction is implicated in a large number of human diseases. Many quantitative proteome analyses of apoptosis have been performed to gain insight in proteins involved in the process. This resulted in large and complex data sets that are difficult to evaluate. Therefore, we developed the ApoptoProteomics database for storage, browsing, and analysis of the outcome of large scale proteome analyses of apoptosis derived from human, mouse, and rat. The proteomics data of 52 publications were integrated and unified with protein annotations from UniProt-KB, the caspase substrate database homepage (CASBAH), and gene ontology. Currently, more than 2300 records of more than 1500 unique proteins were included, covering a large proportion of the core signaling pathways of apoptosis. Analysis of the data set revealed a high level of agreement between the reported changes in directionality reported in proteomics studies and expected apoptosis-related function and may disclose proteins without a current recognized involvement in apoptosis based on gene ontology. Comparison between induction of apoptosis by the intrinsic and the extrinsic apoptotic signaling pathway revealed slight differences. Furthermore, proteomics has significantly contributed to the field of apoptosis in identifying hundreds of caspase substrates. The database is available at http://apoptoproteomics.uio.no.

ApoptoProteomics, an Integrated Database for Analysis of Proteomics Data Obtained from Apoptotic Cells*

PubMed Central

Arntzen, Magnus Ø.; Thiede, Bernd

2012-01-01

Apoptosis is the most commonly described form of programmed cell death, and dysfunction is implicated in a large number of human diseases. Many quantitative proteome analyses of apoptosis have been performed to gain insight in proteins involved in the process. This resulted in large and complex data sets that are difficult to evaluate. Therefore, we developed the ApoptoProteomics database for storage, browsing, and analysis of the outcome of large scale proteome analyses of apoptosis derived from human, mouse, and rat. The proteomics data of 52 publications were integrated and unified with protein annotations from UniProt-KB, the caspase substrate database homepage (CASBAH), and gene ontology. Currently, more than 2300 records of more than 1500 unique proteins were included, covering a large proportion of the core signaling pathways of apoptosis. Analysis of the data set revealed a high level of agreement between the reported changes in directionality reported in proteomics studies and expected apoptosis-related function and may disclose proteins without a current recognized involvement in apoptosis based on gene ontology. Comparison between induction of apoptosis by the intrinsic and the extrinsic apoptotic signaling pathway revealed slight differences. Furthermore, proteomics has significantly contributed to the field of apoptosis in identifying hundreds of caspase substrates. The database is available at http://apoptoproteomics.uio.no. PMID:22067098

Diversity of macro- and micronutrients in the seeds of lentil landraces.

PubMed

Karaköy, Tolga; Erdem, Halil; Baloch, Faheem S; Toklu, Faruk; Eker, Selim; Kilian, Benjamin; Özkan, Hakan

2012-01-01

Increasing the amount of bioavailable mineral elements in plant foods would help to improve the nutritional status of populations in developing countries. Legume seeds have the potential to provide many essential nutrients. It is important to have information on genetic variations among different lentil populations so that plant breeding programs can use new varieties in cross-breeding programs. The main objective of this study was to characterize the micro- and macronutrient concentrations of lentil landraces seeds collected from South-Eastern Turkey. We found impressive variation in the micro- and macroelement concentrations in 39 lentil landraces and 7 cultivars. We investigated the relationships of traits by correlation analysis and principal component analysis (PCA). The concentrations of several minerals, particularly Zn, were positively correlated with other minerals, suggesting that similar pathways or transporters control the uptake and transport of these minerals. Some genotypes had high mineral and protein content and potential to improve the nutritional value of cultivated lentil. Cross-breeding of numerous lentil landraces from Turkey with currently cultivated varieties could improve the levels of micro- and macronutrients of lentil and may contribute to the worldwide lentil quality breeding program.

The value transformation of health care: Impact on neuromuscular and electrodiagnostic medicine.

PubMed

Narayanaswami, Pushpa; Suk, Millie; Jones, Lyell K

2017-10-01

Beginning in 2017, most physicians who participate in Medicare are subject to the Medicare Access and CHIP Reauthorization Act (MACRA), the milestone legislation that signals the US health care system's transition from volume-based to value-based care. Here we review emerging trends in development of value-based healthcare systems in the US. MACRA and the resulting Quality Payment Program create 2 participation pathways, the Merit-based Incentive Payment System (MIPS) and the Advanced Alternative Payment Model (AAPM) pathway. Although there are several program incentives for AAPM participation, to date there have been few AAPM options for specialists. MIPS and its widening bonus and penalty window will likely be the primary participation pathway in the early years of the program. Value-based payment has the potential to reshape health care delivery in the United States, with implications for neuromuscular and electrodiagnostic (EDX) specialists. Meaningful quality measures are required for neuromuscular and EDX specialists. Muscle Nerve 56: 679-683, 2017. © 2017 Wiley Periodicals, Inc.

Combined blockade of vascular endothelial growth factor and programmed death 1 pathways in advanced kidney cancer.

PubMed

Einstein, David J; McDermott, David F

2017-06-01

Targeted and immune-based therapies have improved outcomes in advanced kidney cancer, yet novel strategies are needed to extend the duration of these benefits and expand them to more patients. Combined inhibition of vascular endothelial growth factor (VEGF) and the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathways with therapeutic agents already in clinical use may offer such a strategy. Here, we describe the development and clinical evaluation of VEGF inhibitors and, separately, PD-1/PD-L1 inhibitors. We present preclinical evidence of interaction between these pathways and the rationale for combined blockade. Beyond well-known effects on pathologic angiogenesis, VEGF blockade also may decrease immune tolerance and enhance PD-1/PD-L1 blockade. We conclude with the results of several early trials of combined VEGF and PD-1/PD-L1 blockade, which demonstrate encouraging antitumor activity, and we pose questions for future study.

DEVELOPING COMPUTATIONAL TOOLS FOR PREDICTING CHEMICAL FATE, METABOLISM, AND TOXICITY PATHWAYS

EPA Science Inventory

ORD's research program in Computational Toxicology (CompTox) will enable EPA Program Offices and other regulators to prioritize and reduce toxicity-testing requirements for potentially hazardous chemicals. The CompTox program defines the "toxicity process" as follows : 1) a stre...

5 CFR 362.201 - Agency authority.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Agency authority. 362.201 Section 362.201 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PATHWAYS PROGRAMS Internship Program § 362.201 Agency authority. The Internship Program provides students in high schools, colleges...

5 CFR 362.201 - Agency authority.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Agency authority. 362.201 Section 362.201 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PATHWAYS PROGRAMS Internship Program § 362.201 Agency authority. The Internship Program provides students in high schools, colleges...

minepath.org: a free interactive pathway analysis web server.

PubMed

Koumakis, Lefteris; Roussos, Panos; Potamias, George

2017-07-03

( www.minepath.org ) is a web-based platform that elaborates on, and radically extends the identification of differentially expressed sub-paths in molecular pathways. Besides the network topology, the underlying MinePath algorithmic processes exploit exact gene-gene molecular relationships (e.g. activation, inhibition) and are able to identify differentially expressed pathway parts. Each pathway is decomposed into all its constituent sub-paths, which in turn are matched with corresponding gene expression profiles. The highly ranked, and phenotype inclined sub-paths are kept. Apart from the pathway analysis algorithm, the fundamental innovation of the MinePath web-server concerns its advanced visualization and interactive capabilities. To our knowledge, this is the first pathway analysis server that introduces and offers visualization of the underlying and active pathway regulatory mechanisms instead of genes. Other features include live interaction, immediate visualization of functional sub-paths per phenotype and dynamic linked annotations for the engaged genes and molecular relations. The user can download not only the results but also the corresponding web viewer framework of the performed analysis. This feature provides the flexibility to immediately publish results without publishing source/expression data, and get all the functionality of a web based pathway analysis viewer. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

EXPRESSION PROFILING OF FIVE RAT STRAINS REVEAL TRANSCRIPTIONAL MODES IN THE ANTIGEN PROCESSING PATHWAY

EPA Science Inventory

Comparative gene expression profiling of rat strains with genetic predisposition to diverse cardiovascular diseases can help decode the transcriptional program that governs cellular behavior. We hypothesized that co-transcribed, intra-pathway, functionally coherent genes can be r...

Value-Based Payment Reform and the Medicare Access and Children's Health Insurance Program Reauthorization Act of 2015: A Primer for Plastic Surgeons.

PubMed

Squitieri, Lee; Chung, Kevin C

2017-07-01

In 2015, the U.S. Congress passed the Medicare Access and Children's Health Insurance Program Reauthorization Act, which effectively repealed the Centers for Medicare and Medicaid Services sustainable growth rate formula and established the Centers for Medicare and Medicaid Services Quality Payment Program. The Medicare Access and Children's Health Insurance Program Reauthorization Act represents an unparalleled acceleration toward value-based payment models and a departure from traditional volume-driven fee-for-service reimbursement. The Quality Payment Program includes two paths for provider participation: the Merit-Based Incentive Payment System and Advanced Alternative Payment Models. The Merit-Based Incentive Payment System pathway replaces existing quality reporting programs and adds several new measures to create a composite performance score for each provider (or provider group) that will be used to adjust reimbursed payment. The advanced alternative payment model pathway is available to providers who participate in qualifying Advanced Alternative Payment Models and is associated with an initial 5 percent payment incentive. The first performance period for the Merit-Based Incentive Payment System opens January 1, 2017, and closes on December 31, 2017, and is associated with payment adjustments in January of 2019. The Centers for Medicare and Medicaid Services estimates that the majority of providers will begin participation in 2017 through the Merit-Based Incentive Payment System pathway, but aims to have 50 percent of payments tied to quality or value through Advanced Alternative Payment Models by 2018. In this article, the authors describe key components of the Medicare Access and Children's Health Insurance Program Reauthorization Act to providers navigating through the Quality Payment Program and discuss how plastic surgeons may optimize their performance in this new value-based payment program.

Pathway Interaction Network Analysis Identifies Dysregulated Pathways in Human Monocytes Infected by Listeria monocytogenes.

PubMed

Fan, Wufeng; Zhou, Yuhan; Li, Hao

2017-01-01

In our study, we aimed to extract dysregulated pathways in human monocytes infected by Listeria monocytogenes (LM) based on pathway interaction network (PIN) which presented the functional dependency between pathways. After genes were aligned to the pathways, principal component analysis (PCA) was used to calculate the pathway activity for each pathway, followed by detecting seed pathway. A PIN was constructed based on gene expression profile, protein-protein interactions (PPIs), and cellular pathways. Identifying dysregulated pathways from the PIN was performed relying on seed pathway and classification accuracy. To evaluate whether the PIN method was feasible or not, we compared the introduced method with standard network centrality measures. The pathway of RNA polymerase II pretranscription events was selected as the seed pathway. Taking this seed pathway as start, one pathway set (9 dysregulated pathways) with AUC score of 1.00 was identified. Among the 5 hub pathways obtained using standard network centrality measures, 4 pathways were the common ones between the two methods. RNA polymerase II transcription and DNA replication owned a higher number of pathway genes and DEGs. These dysregulated pathways work together to influence the progression of LM infection, and they will be available as biomarkers to diagnose LM infection.

Characteristics and Postsecondary Pathways of Students Who Participate in Acceleration Programs in Minnesota. REL 2017-234

ERIC Educational Resources Information Center

Davis, Elisabeth; Smither, Cameron; Zhu, Bo; Stephan, Jennifer

2017-01-01

Acceleration programs are academically challenging courses in which high school students can simultaneously earn credit toward a high school diploma and a postsecondary degree (dual credit). These programs include Advanced Placement courses, concurrent-enrollment courses, Postsecondary Enrollment Options courses (a dual-enrollment program in…

The Experiences of Advanced Placement and International Baccalaureate Diploma Program Participants: A Systematic Review of Qualitative Research

ERIC Educational Resources Information Center

Park, Kelly; Caine, Vera; Wimmer, Randolph

2014-01-01

Enriched high school curricula like the Advanced Placement and International Baccalaureate Diploma programs are endorsed as "pathway programs" for postsecondary-bound students. Program participation is perceived to have benefits that appeal to a broad stakeholder group of universities, administrators, teachers, students, and parents. In…

A systematic analysis of a mi-RNA inter-pathway regulatory motif

PubMed Central

2013-01-01

Background The continuing discovery of new types and functions of small non-coding RNAs is suggesting the presence of regulatory mechanisms far more complex than the ones currently used to study and design Gene Regulatory Networks. Just focusing on the roles of micro RNAs (miRNAs), they have been found to be part of several intra-pathway regulatory motifs. However, inter-pathway regulatory mechanisms have been often neglected and require further investigation. Results In this paper we present the result of a systems biology study aimed at analyzing a high-level inter-pathway regulatory motif called Pathway Protection Loop, not previously described, in which miRNAs seem to play a crucial role in the successful behavior and activation of a pathway. Through the automatic analysis of a large set of public available databases, we found statistical evidence that this inter-pathway regulatory motif is very common in several classes of KEGG Homo Sapiens pathways and concurs in creating a complex regulatory network involving several pathways connected by this specific motif. The role of this motif seems also confirmed by a deeper review of other research activities on selected representative pathways. Conclusions Although previous studies suggested transcriptional regulation mechanism at the pathway level such as the Pathway Protection Loop, a high-level analysis like the one proposed in this paper is still missing. The understanding of higher-level regulatory motifs could, as instance, lead to new approaches in the identification of therapeutic targets because it could unveil new and “indirect” paths to activate or silence a target pathway. However, a lot of work still needs to be done to better uncover this high-level inter-pathway regulation including enlarging the analysis to other small non-coding RNA molecules. PMID:24152805

Conceptual framework of the eco-physiological phases of insect diapause development justified by transcriptomic profiling

PubMed Central

Štětina, Tomáš; Poupardin, Rodolphe; Korbelová, Jaroslava; Bruce, Alexander William

2017-01-01

Insects often overcome unfavorable seasons in a hormonally regulated state of diapause during which their activity ceases, development is arrested, metabolic rate is suppressed, and tolerance of environmental stress is bolstered. Diapausing insects pass through a stereotypic succession of eco-physiological phases termed “diapause development.” The phasing is varied in the literature, and the whole concept is sometimes criticized as being too artificial. Here we present the results of transcriptional profiling using custom microarrays representing 1,042 genes in the drosophilid fly, Chymomyza costata. Fully grown, third-instar larvae programmed for diapause by a photoperiodic (short-day) signal were assayed as they traversed the diapause developmental program. When analyzing the gradual dynamics in the transcriptomic profile, we could readily distinguish distinct diapause developmental phases associated with induction/initiation, maintenance, cold acclimation, and termination by cold or by photoperiodic signal. Accordingly, each phase is characterized by a specific pattern of gene expression, supporting the physiological relevance of the concept of diapause phasing. Further, we have dissected in greater detail the changes in transcript levels of elements of several signaling pathways considered critical for diapause regulation. The phase of diapause termination is associated with enhanced transcript levels in several positive elements stimulating direct development (the 20-hydroxyecdysone pathway: Ecr, Shd, Broad; the Wnt pathway: basket, c-jun) that are countered by up-regulation in some negative elements (the insulin-signaling pathway: Ilp8, PI3k, Akt; the target of rapamycin pathway: Tsc2 and 4EBP; the Wnt pathway: shaggy). We speculate such up-regulations may represent the early steps linked to termination of diapause programming. PMID:28720705

Conservation and divergence of the cyclic adenosine monophosphate-protein kinase A (cAMP-PKA) pathway in two plant-pathogenic fungi: Fusarium graminearum and F. verticillioides.

PubMed

Guo, Li; Breakspear, Andrew; Zhao, Guoyi; Gao, Lixin; Kistler, H Corby; Xu, Jin-Rong; Ma, Li-Jun

2016-02-01

The cyclic adenosine monophosphate-protein kinase A (cAMP-PKA) pathway is a central signalling cascade that transmits extracellular stimuli and governs cell responses through the second messenger cAMP. The importance of cAMP signalling in fungal biology has been well documented and the key conserved components, adenylate cyclase (AC) and the catalytic subunit of PKA (CPKA), have been functionally characterized. However, other genes involved in this signalling pathway and their regulation are not well understood in filamentous fungi. Here, we performed a comparative transcriptomics analysis of AC and CPKA mutants in two closely related fungi: Fusarium graminearum (Fg) and F. verticillioides (Fv). Combining available Fg transcriptomics and phenomics data, we reconstructed the Fg cAMP signalling pathway. We developed a computational program that combines sequence conservation and patterns of orthologous gene expression to facilitate global transcriptomics comparisons between different organisms. We observed highly correlated expression patterns for most orthologues (80%) between Fg and Fv. We also identified a subset of 482 (6%) diverged orthologues, whose expression under all conditions was at least 50% higher in one genome than in the other. This enabled us to dissect the conserved and unique portions of the cAMP-PKA pathway. Although the conserved portions controlled essential functions, such as metabolism, the cell cycle, chromatin remodelling and the oxidative stress response, the diverged portions had species-specific roles, such as the production and detoxification of secondary metabolites unique to each species. The evolution of the cAMP-PKA signalling pathway seems to have contributed directly to fungal divergence and niche adaptation. © 2015 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.

Differentiating Pathway-Specific From Nonspecific Effects in High-Throughput Toxicity Data: A Foundation for Prioritizing Adverse Outcome Pathway Development.

PubMed

Fay, Kellie A; Villeneuve, Daniel L; Swintek, Joe; Edwards, Stephen W; Nelms, Mark D; Blackwell, Brett R; Ankley, Gerald T

2018-06-01

The U.S. Environmental Protection Agency's ToxCast program has screened thousands of chemicals for biological activity, primarily using high-throughput in vitro bioassays. Adverse outcome pathways (AOPs) offer a means to link pathway-specific biological activities with potential apical effects relevant to risk assessors. Thus, efforts are underway to develop AOPs relevant to pathway-specific perturbations detected in ToxCast assays. Previous work identified a "cytotoxic burst" (CTB) phenomenon wherein large numbers of the ToxCast assays begin to respond at or near test chemical concentrations that elicit cytotoxicity, and a statistical approach to defining the bounds of the CTB was developed. To focus AOP development on the molecular targets corresponding to ToxCast assays indicating pathway-specific effects, we conducted a meta-analysis to identify which assays most frequently respond at concentrations below the CTB. A preliminary list of potentially important, target-specific assays was determined by ranking assays by the fraction of chemical hits below the CTB compared with the number of chemicals tested. Additional priority assays were identified using a diagnostic-odds-ratio approach which gives greater ranking to assays with high specificity but low responsivity. Combined, the two prioritization methods identified several novel targets (e.g., peripheral benzodiazepine and progesterone receptors) to prioritize for AOP development, and affirmed the importance of a number of existing AOPs aligned with ToxCast targets (e.g., thyroperoxidase, estrogen receptor, aromatase). The prioritization approaches did not appear to be influenced by inter-assay differences in chemical bioavailability. Furthermore, the outcomes were robust based on a variety of different parameters used to define the CTB.

What will it take? Pathways, time and funding: Australian medical students' perspective on clinician-scientist training.

PubMed

Eley, Diann S; Jensen, Charmaine; Thomas, Ranjeny; Benham, Helen

2017-12-08

Clinician-scientists are in decline worldwide. They represent a unique niche in medicine by bridging the gap between scientific discovery and patient care. A national, integrated approach to training clinician-scientists, typically programs that comprise a comprehensive MD-PhD pathway, are customary. Such a pathway is lacking in Australia. The objective was to gather perceptions from Australian medical students on factors they perceive would influence their decision to pursue clinician-scientist training. A cross-sectional mixed methods design used quantitative and qualitative questions in an online self-report survey with medical students from a four-year MD program. Quantitative measures comprised scaled response questions regarding prior experience and current involvement in research, and short- and long-term opinions about factors that influence their decisions to undertake a research higher degree (RHD) during medical school. Qualitative questions gathered broader perceptions of what a career pathway as a clinician-scientist would include and what factors are most conducive to a medical student's commitment to MD-PhD training. Respondents (N = 418; 51% female) indicated Time, Funding and Pathway as the major themes arising from the qualitative data, highlighting negative perceptions rather than possible benefits to RHD training. The lack of an evident Pathway was inter-related to Time and Funding. Themes were supported by the quantitative data. Sixty percent of students have previous research experience of varying forms, and 90% report a current interest, mainly to improve their career prospects. The data emphasise the need for an MD-PhD pathway in Australia. A model that provides an early, integrated, and exclusive approach to research training pathways across all stages of medical education is suggested as the best way to rejuvenate the clinician-scientist. A national pathway that addresses factors influencing career decision making throughout the medical education continuum should include an appropriate funding structure, and provide early and continuing advice and mentoring. It should be flexible, gender equitable, and include post-graduate training. The implications of implementing MD-PhD programs represent a substantial investment. However this should not be a deterrent to Australia's commitment to an MD-PhD pathway, but rather a challenge to help ensure our future healthcare is guided by highly trained and competent clinician-scientists.

Programs of Study as a State Policy Mandate: A Longitudinal Study of the South Carolina Personal Pathways to Success Initiative. Executive Summary

ERIC Educational Resources Information Center

Hammond, Cathy; Drew, Sam F.; Withington, Cairen; Griffith, Cathy; Swiger, Caroline M.; Mobley, Catherine; Sharp, Julia L.; Stringfield, Samuel C.; Stipanovic, Natalie; Daugherty, Lindsay

2013-01-01

This executive summary outlines key findings from the final technical report of a five-year study of South Carolina's Personal Pathways to Success Initiative, which was authorized by the state's Education and Economic Development Act (EEDA) in 2005. The Personal Pathways initiative is a K-16, career-focused school reform model intended to improve…

Training Internists to Meet Critical Care Needs in the United States: A Consensus Statement from the Critical Care Societies Collaborative (CCSC)

PubMed Central

Pastores, Stephen M.; Martin, Greg S.; Baumann, Michael H.; Curtis, J. Randall; Farmer, J. Christopher; Fessler, Henry E.; Gupta, Rakesh; Hill, Nicholas S.; Hyzy, Robert C.; Kvetan, Vladimir; MacGregor, Drew A.; O’Grady, Naomi P.; Ognibene, Frederick P.; Rubenfeld, Gordon D.; Sessler, Curtis N.; Siegal, Eric; Simpson, Steven Q.; Spevetz, Antoinette; Ward, Nicholas S.; Zimmerman, Janice L.

2014-01-01

Objectives Multiple training pathways are recognized by the Accreditation Council for Graduate Medical Education (ACGME) for internal medicine (IM) physicians to certify in critical care medicine (CCM) via the American Board of Internal Medicine. While each involves 1 year of clinical fellowship training in CCM, substantive differences in training requirements exist among the various pathways. The Critical Care Societies Collaborative convened a task force to review these CCM pathways and to provide recommendations for unified and coordinated training requirements for IM-based physicians. Participants A group of CCM professionals certified in pulmonary-CCM and/or IM-CCM from ACGME-accredited training programs who have expertise in education, administration, research, and clinical practice. Data Sources and Synthesis Relevant published literature was accessed through a MEDLINE search and references provided by all task force members. Material published by the ACGME, American Board of Internal Medicine, and other specialty organizations was also reviewed. Collaboratively and iteratively, the task force reached consensus using a roundtable meeting, electronic mail, and conference calls. Main Results Internal medicine-CCM–based fellowships have disparate program requirements compared to other internal medicine subspecialties and adult CCM fellowships. Differences between IM-CCM and pulmonary-CCM programs include the ratio of key clinical faculty to fellows and a requirement to perform 50 therapeutic bronchoscopies. Competency-based training was considered uniformly desirable for all CCM training pathways. Conclusions The task force concluded that requesting competency-based training and minimizing variations in the requirements for IM-based CCM fellowship programs will facilitate effective CCM training for both programs and trainees. PMID:24637881

A Case Study of URM Retention through IBP's Professional Development and Mentoring Activities

NASA Astrophysics Data System (ADS)

Johnson, A.; Williamson Whitney, V.; Ricciardi, L.; Detrick, L.; Siegfried, D.; Fauver, A.; Ithier-Guzman, W.; Thomas, S. H.; Valaitis, S.

2012-12-01

As a free-standing not for profit organization, the Institute for Broadening Participation (IBP) hosts a variety of initiatives designed to increase the retention of underrepresented minority (URM) students pursuing pathways in STEM. Successful initiatives include virtual and face-to-face components that bring together URM students with established URM and other scientists in academia, government and industry. These connections provide URM students with supportive mentoring, networking opportunities, and professional skill development contributing to an overall improved retention rate of URM students majoring in STEM degrees. IBP's initiatives include the NASA One Stop Shopping Initiative (NASA OSSI), Pathways to Ocean Science, Pathways to Engineering, and the Minorities Striving and Pursuing Higher Degrees of Success (MS PHD'S) Professional Development program in Earth System Science (ESS). The NASA OSSI initiative recruits and facilitates student engagement in NASA student education and employment opportunities. Through IBP's virtual and person-to-person communications, students learn how to identify, apply to, and participate in NASA programs. Pathways to Ocean Science connects and supports URM students with REU programs in the Ocean Sciences while serving as a resource for REU program directors. As one of IBP's newest initiatives, Pathways to Engineering has synthesized mentoring resources into an online mentoring manual for URM STEM students that has been extensively vetted by mentoring experts throughout the country. The manual which is organized by user groups serves as an e-forum providing undergraduates, graduates, postdocs, faculty members and project directors with valuable resources to facilitate a positive REU experience. This mentoring initiative also provides a mechanism for submitting new resources and inviting feedback in mentoring best practices throughout the STEM community. MS PHD'S, one of IBP's longest running and most successful initiatives, focuses on increasing the retention rate of URM students receiving advanced degrees in Earth system science. Through a three-phase structure of activities, the program addresses major barriers to retention in ESS including isolation, lack of preparation and professional development, and lack of mentoring. Program activities center on peer-to-peer community building, professional development exercises, networking experiences, one-on-one mentoring, and a facilitated virtual community. MS PHD'S participants report a reduced sense of isolation, an increased sense of community, and a higher level of confidence about their ability to succeed in their chosen field. As of August 2012, 189 students have participated in the program. 60 of those students are currently enrolled in a PhD. program. Another 35 have completed their PhD and are actively engaged in the ESS workforce.

Geoscience and the 21st Century Workforce

NASA Astrophysics Data System (ADS)

Manduca, C. A.; Bralower, T. J.; Blockstein, D.; Keane, C. M.; Kirk, K. B.; Schejbal, D.; Wilson, C. E.

2013-12-01

Geoscience knowledge and skills play new roles in the workforce as our society addresses the challenges of living safely and sustainably on Earth. As a result, we expect a wider range of future career opportunities for students with education in the geosciences and related fields. A workshop offered by the InTeGrate STEP Center on 'Geoscience and the 21st Century Workforce' brought together representatives from 24 programs with a substantial geoscience component, representatives from different employment sectors, and workforce scholars to explore the intersections between geoscience education and employment. As has been reported elsewhere, employment in energy, environmental and extractive sectors for geoscientists with core geology, quantitative and communication skills is expected to be robust over the next decade as demand for resources grow and a significant part of the current workforce retires. Relatively little is known about employment opportunities in emerging areas such as green energy or sustainability consulting. Employers at the workshop from all sectors are seeking the combination of strong technical, quantitative, communication, time management, and critical thinking skills. The specific technical skills are highly specific to the employer and employment needs. Thus there is not a single answer to the question 'What skills make a student employable?'. Employers at this workshop emphasized the value of data analysis, quantitative, and problem solving skills over broad awareness of policy issues. Employers value the ability to articulate an appropriate, effective, creative solution to problems. Employers are also very interested in enthusiasm and drive. Participants felt that the learning outcomes that their programs have in place were in line with the needs expressed by employers. Preparing students for the workforce requires attention to professional skills, as well as to the skills needed to identify career pathways and land a job. This critical work takes place both inside and outside of the classroom and occurs as a progression throughout the course of study. Professional skills were recognized as an area where outcomes could be strengthened. The challenge faced by geoscience programs is developing pathways into the workforce for students who bring different skills and interests to their studies. Workforce data suggest that in the past only 30% of undergraduate graduates have remained in the geosciences indicating that geoscience programs are playing an important role in developing the workforce beyond the geosciences. A collection of program descriptions describes what is known about career pathways from the programs represented at the workshop.

Methods and approaches in the topology-based analysis of biological pathways

PubMed Central

Mitrea, Cristina; Taghavi, Zeinab; Bokanizad, Behzad; Hanoudi, Samer; Tagett, Rebecca; Donato, Michele; Voichiţa, Călin; Drăghici, Sorin

2013-01-01

The goal of pathway analysis is to identify the pathways significantly impacted in a given phenotype. Many current methods are based on algorithms that consider pathways as simple gene lists, dramatically under-utilizing the knowledge that such pathways are meant to capture. During the past few years, a plethora of methods claiming to incorporate various aspects of the pathway topology have been proposed. These topology-based methods, sometimes referred to as “third generation,” have the potential to better model the phenomena described by pathways. Although there is now a large variety of approaches used for this purpose, no review is currently available to offer guidance for potential users and developers. This review covers 22 such topology-based pathway analysis methods published in the last decade. We compare these methods based on: type of pathways analyzed (e.g., signaling or metabolic), input (subset of genes, all genes, fold changes, gene p-values, etc.), mathematical models, pathway scoring approaches, output (one or more pathway scores, p-values, etc.) and implementation (web-based, standalone, etc.). We identify and discuss challenges, arising both in methodology and in pathway representation, including inconsistent terminology, different data formats, lack of meaningful benchmarks, and the lack of tissue and condition specificity. PMID:24133454

Modelling the structure of a ceRNA-theoretical, bipartite microRNA-mRNA interaction network regulating intestinal epithelial cellular pathways using R programming.

PubMed

Robinson, J M; Henderson, W A

2018-01-12

We report a method using functional-molecular databases and network modelling to identify hypothetical mRNA-miRNA interaction networks regulating intestinal epithelial barrier function. The model forms a data-analysis component of our cell culture experiments, which produce RNA expression data from Nanostring Technologies nCounter ® system. The epithelial tight-junction (TJ) and actin cytoskeleton interact as molecular components of the intestinal epithelial barrier. Upstream regulation of TJ-cytoskeleton interaction is effected by the Rac/Rock/Rho signaling pathway and other associated pathways which may be activated or suppressed by extracellular signaling from growth factors, hormones, and immune receptors. Pathway activations affect epithelial homeostasis, contributing to degradation of the epithelial barrier associated with osmotic dysregulation, inflammation, and tumor development. The complexity underlying miRNA-mRNA interaction networks represents a roadblock for prediction and validation of competing-endogenous RNA network function. We developed a network model to identify hypothetical co-regulatory motifs in a miRNA-mRNA interaction network related to epithelial function. A mRNA-miRNA interaction list was generated using KEGG and miRWalk2.0 databases. R-code was developed to quantify and visualize inherent network structures. We identified a sub-network with a high number of shared, targeting miRNAs, of genes associated with cellular proliferation and cancer, including c-MYC and Cyclin D.

Health information technology and implementation science: partners in progress in the VHA.

PubMed

Hynes, Denise M; Whittier, Erika R; Owens, Arika

2013-03-01

The Department of Veterans Affairs (VA) Quality Enhancement Research Initiative (QUERI) has demonstrated how implementation science can enhance the quality of health care. During this time an increasing number of implementation research projects have developed or utilized health information technology (HIT) innovations to leverage the VA's electronic health record and information systems. To describe the HIT approaches used and to characterize the facilitators and barriers to progress within implementation research projects in the VA QUERI program. Nine case studies were selected from among 88 projects and represented 8 of 14 HIT categories identified. Each case study included key informants whose roles on the project were principal investigator, implementation science and informatics development. We conducted documentation analysis and semistructured in-person interviews with key informants for each of the 9 case studies. We used qualitative analysis software to identify and thematically code information and interview responses. : Thematic analyses revealed 3 domains or pathways critical to progression through the QUERI steps. These pathways addressed: (1) compliance and collaboration with information technology policies and procedures; (2) operating within organizational policies and building collaborations with end users, clinicians, and administrators; and (3) obtaining and maintaining research resources and approvals. Sustained efforts in HIT innovation and in implementation science in the Veterans Health Administration demonstrates the interdependencies of these initiatives and the critical pathways that can contribute to progress. Other health care quality improvement efforts that rely on HIT can learn from the Veterans Health Administration experience.

Conservation of Toll-like receptor signaling pathways in teleost fish

USGS Publications Warehouse

Purcell, M.K.; Smith, K.D.; Aderem, A.; Hood, L.; Winton, J.R.; Roach, J.C.

2006-01-01

In mammals, toll-like receptors (TLR) recognize ligands, including pathogen-associated molecular patterns (PAMPs), and respond with ligand-specific induction of genes. In this study, we establish evolutionary conservation in teleost fish of key components of the TLR-signaling pathway that act as switches for differential gene induction, including MYD88, TIRAP, TRIF, TRAF6, IRF3, and IRF7. We further explore this conservation with a molecular phylogenetic analysis of MYD88. To the extent that current genomic analysis can establish, each vertebrate has one ortholog to each of these genes. For molecular tree construction and phylogeny inference, we demonstrate a methodology for including genes with only partial primary sequences without disrupting the topology provided by the high-confidence full-length sequences. Conservation of the TLR-signaling molecules suggests that the basic program of gene regulation by the TLR-signaling pathway is conserved across vertebrates. To test this hypothesis, leukocytes from a model fish, rainbow trout (Oncorhynchus mykiss), were stimulated with known mammalian TLR agonists including: diacylated and triacylated forms of lipoprotein, flagellin, two forms of LPS, synthetic double-stranded RNA, and two imidazoquinoline compounds (loxoribine and R848). Trout leukocytes responded in vitro to a number of these agonists with distinct patterns of cytokine expression that correspond to mammalian responses. Our results support the key prediction from our phylogenetic analyses that strong selective pressure of pathogenic microbes has preserved both TLR recognition and signaling functions during vertebrate evolution.

A Research Roadmap for Computation-Based Human Reliability Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boring, Ronald; Mandelli, Diego; Joe, Jeffrey

2015-08-01

The United States (U.S.) Department of Energy (DOE) is sponsoring research through the Light Water Reactor Sustainability (LWRS) program to extend the life of the currently operating fleet of commercial nuclear power plants. The Risk Informed Safety Margin Characterization (RISMC) research pathway within LWRS looks at ways to maintain and improve the safety margins of these plants. The RISMC pathway includes significant developments in the area of thermalhydraulics code modeling and the development of tools to facilitate dynamic probabilistic risk assessment (PRA). PRA is primarily concerned with the risk of hardware systems at the plant; yet, hardware reliability is oftenmore » secondary in overall risk significance to human errors that can trigger or compound undesirable events at the plant. This report highlights ongoing efforts to develop a computation-based approach to human reliability analysis (HRA). This computation-based approach differs from existing static and dynamic HRA approaches in that it: (i) interfaces with a dynamic computation engine that includes a full scope plant model, and (ii) interfaces with a PRA software toolset. The computation-based HRA approach presented in this report is called the Human Unimodels for Nuclear Technology to Enhance Reliability (HUNTER) and incorporates in a hybrid fashion elements of existing HRA methods to interface with new computational tools developed under the RISMC pathway. The goal of this research effort is to model human performance more accurately than existing approaches, thereby minimizing modeling uncertainty found in current plant risk models.« less

Evaluation of the scientific underpinnings for identifying ...

EPA Pesticide Factsheets

A major challenge in chemical risk assessment is extrapolation of toxicity data from tested to untested species. Successful cross-species extrapolation involves understanding similarities and differences in toxicokinetic and toxicodynamic processes among species. Herein we consider the toxicodynamic challenge, and propose a hierarchal framework, based on the adverse outcome pathway (AOP) concept, to transparently and systematically assess cross-species conservation of biological pathways that could be perturbed by toxic chemicals. The approach features consideration of computational, in vitro and in vivo evidence to assess molecular initiating and intermediate key events of an AOP in a systematic, comparative manner. To demonstrate practical application of the framework, we consider an assessment question arising from the legislatively-mandated USEPA endocrine disruptor screening program, which involves the degree to which data generated using mammalian systems can be translated to non-mammalian species. Specifically, there is a need to define cross-species conservation of pathways controlled by activation of estrogen receptor-á (ERá), as a basis for using mammalian (primarily human) high-throughput (HTP) in vitro data to prioritize subsequent testing to assess human health and ecological risks of estrogenic chemicals. The initial phase of our analysis revealed good structural conservation the ERá across vertebrate species in terms of amino acid sequence

Survey of checkpoints along the pathway to diverse biomedical research faculty

PubMed Central

Brown, Abigail M.; Moneta-Koehler, Liane; Chalkley, Roger

2018-01-01

There is a persistent shortage of underrepresented minority (URM) faculty who are involved in basic biomedical research at medical schools. We examined the entire training pathway of potential candidates to identify the points of greatest loss. Using a range of recent national data sources, including the National Science Foundation’s Survey of Earned Doctorates and Survey of Doctoral Recipients, we analyzed the demographics of the population of interest, specifically those from URM backgrounds with an interest in biomedical sciences. We examined the URM population from high school graduates through undergraduate, graduate, and postdoctoral training as well as the URM population in basic science tenure track faculty positions at medical schools. We find that URM and non-URM trainees are equally likely to transition into doctoral programs, to receive their doctoral degree, and to secure a postdoctoral position. However, the analysis reveals that the diversions from developing a faculty career are found primarily at two clearly identifiable places, specifically during undergraduate education and in transition from postdoctoral fellowship to tenure track faculty in the basic sciences at medical schools. We suggest focusing additional interventions on these two stages along the educational pathway. PMID:29338019

Analysis of Chemical Bioactivity through In Vitro Profiling ...

EPA Pesticide Factsheets

Safety assessment of drugs and environmental chemicals relies extensively on animal testing. However, the quantity of chemicals needing assessment and challenges of species extrapolation drive the development of alternative approaches. The EPA’s ToxCast and the multiagency Tox21 programs address this through use of an extensive in vitro screening program to generate data on a large library of important environmental chemicals. These in vitro assays encompass both cell-free, biochemical assays targeting proteins that may be potential molecular initiating events and cellular assays that provide coverage of critical signaling pathways and toxicity phenotypes. Effects on model organisms such as the developing zebrafish, are also part of the testing strategy. A variety of computational approaches are used to analyze the resulting complex data sets to gain insight in to inherent biological activity of chemicals and possible mechanisms of toxicity. Several case studies including identification of modulators of estrogen receptor and aromatic hydrocarbon receptor pathways with effects in primary human cell systems will be described. In addition, existing in vivo data from a subset of the chemicals was used to anchor predictive models using in vitro data for a number of adverse endpoints including reproductive and developmental toxicities. The strengths and weaknesses of this approach will be described. This work does not necessarily reflect official Agency policy. Pres

The Development of a Clinical Nurse Scholar in Baccalaureate Education.

PubMed

Beal, Judy A; Riley, Joan M

2015-01-01

The purpose of this national study was to explore the vision of chief academic officers for baccalaureate nursing education. We invited chief academic nursing officers, randomly selected from a representative sample of accredited baccalaureate nursing programs to participate in the study. Audiotaped interviews were conducted in focus groups at professional meetings or by telephone and were transcribed verbatim. Data collection continued until thematic saturation was reached (N = 29). Analysis of the findings revealed themes that described future vision for baccalaureate education that provides guidance to faculty as they develop curriculum. An overarching theme "We are all Stewards of the Profession" and three supporting themes emerged: "Learning Pathways are Varied," "Faculty Need to Grow," and "New Pedagogies Need to Focus on the Development of 'Who I Am' as a Clinical Scholar." Findings point to a future where diverse learning pathways are integrated throughout the curriculum. The curriculum of tomorrow will place greater emphasis on the development of professional identity as a nurse and calls for expanded stewardship for nursing education. Deans recommended that investing time and resources into well-designed faculty development programs will help all faculty, regardless of appointment, to adapt to changing student needs and rapidly evolving practice environments. Copyright © 2015 Elsevier Inc. All rights reserved.

MDRC Research on Career Pathways. Issue Brief

ERIC Educational Resources Information Center

Kazis, Richard

2016-01-01

As postsecondary credentials have become increasingly important to accessing higher-quality employment, a growing number of education and workforce programs are implementing "career pathways" approaches to help both youth and adults prepare for further education and better jobs. In recent years, the Manpower Demonstration Research…

Clinical pathways for acute coronary syndromes in China: protocol for a hospital quality improvement initiative.

PubMed

Rong, Ye; Turnbull, Fiona; Patel, Anushka; Du, Xin; Wu, Yangfeng; Gao, Runlin

2010-09-01

Clinical pathways have been shown to be effective in improving quality of care for patients admitted to hospital for acute coronary syndromes (ACS) in high-income countries. However, their utility has not formally been evaluated in low- or middle-income countries. The Clinical Pathways for Acute Coronary Syndromes in China program is a 7-year study with the overall goal of reducing evidence-practice gaps in the management of patients admitted to hospitals in China with suspected ACS. The program comprises 2 phases: a prospective survey of current management of ACS patients to identify the areas that evidence-based patient care can be potentially improved, and a quality care initiative to maximize the use of evidence-based investigations and treatments for ACS patients in China. In this article, we outline the details of the study protocol, including key aspects of the development, implementation, and evaluation of the quality improvement initiative (clinical pathway) for management of patients with suspected ACS.

The N-end rule pathway regulates pathogen responses in plants

PubMed Central

de Marchi, Rémi; Sorel, Maud; Mooney, Brian; Fudal, Isabelle; Goslin, Kevin; Kwaśniewska, Kamila; Ryan, Patrick T.; Pfalz, Marina; Kroymann, Juergen; Pollmann, Stephan; Feechan, Angela; Wellmer, Frank; Rivas, Susana; Graciet, Emmanuelle

2016-01-01

To efficiently counteract pathogens, plants rely on a complex set of immune responses that are tightly regulated to allow the timely activation, appropriate duration and adequate amplitude of defense programs. The coordination of the plant immune response is known to require the activity of the ubiquitin/proteasome system, which controls the stability of proteins in eukaryotes. Here, we demonstrate that the N-end rule pathway, a subset of the ubiquitin/proteasome system, regulates the defense against a wide range of bacterial and fungal pathogens in the model plant Arabidopsis thaliana. We show that this pathway positively regulates the biosynthesis of plant-defense metabolites such as glucosinolates, as well as the biosynthesis and response to the phytohormone jasmonic acid, which plays a key role in plant immunity. Our results also suggest that the arginylation branch of the N-end rule pathway regulates the timing and amplitude of the defense program against the model pathogen Pseudomonas syringae AvrRpm1. PMID:27173012

Influence maximization in time bounded network identifies transcription factors regulating perturbed pathways

PubMed Central

Jo, Kyuri; Jung, Inuk; Moon, Ji Hwan; Kim, Sun

2016-01-01

Motivation: To understand the dynamic nature of the biological process, it is crucial to identify perturbed pathways in an altered environment and also to infer regulators that trigger the response. Current time-series analysis methods, however, are not powerful enough to identify perturbed pathways and regulators simultaneously. Widely used methods include methods to determine gene sets such as differentially expressed genes or gene clusters and these genes sets need to be further interpreted in terms of biological pathways using other tools. Most pathway analysis methods are not designed for time series data and they do not consider gene-gene influence on the time dimension. Results: In this article, we propose a novel time-series analysis method TimeTP for determining transcription factors (TFs) regulating pathway perturbation, which narrows the focus to perturbed sub-pathways and utilizes the gene regulatory network and protein–protein interaction network to locate TFs triggering the perturbation. TimeTP first identifies perturbed sub-pathways that propagate the expression changes along the time. Starting points of the perturbed sub-pathways are mapped into the network and the most influential TFs are determined by influence maximization technique. The analysis result is visually summarized in TF-Pathway map in time clock. TimeTP was applied to PIK3CA knock-in dataset and found significant sub-pathways and their regulators relevant to the PIP3 signaling pathway. Availability and Implementation: TimeTP is implemented in Python and available at http://biohealth.snu.ac.kr/software/TimeTP/. Supplementary information: Supplementary data are available at Bioinformatics online. Contact: sunkim.bioinfo@snu.ac.kr PMID:27307609

Large-scale integrative network-based analysis identifies common pathways disrupted by copy number alterations across cancers

PubMed Central

2013-01-01

Background Many large-scale studies analyzed high-throughput genomic data to identify altered pathways essential to the development and progression of specific types of cancer. However, no previous study has been extended to provide a comprehensive analysis of pathways disrupted by copy number alterations across different human cancers. Towards this goal, we propose a network-based method to integrate copy number alteration data with human protein-protein interaction networks and pathway databases to identify pathways that are commonly disrupted in many different types of cancer. Results We applied our approach to a data set of 2,172 cancer patients across 16 different types of cancers, and discovered a set of commonly disrupted pathways, which are likely essential for tumor formation in majority of the cancers. We also identified pathways that are only disrupted in specific cancer types, providing molecular markers for different human cancers. Analysis with independent microarray gene expression datasets confirms that the commonly disrupted pathways can be used to identify patient subgroups with significantly different survival outcomes. We also provide a network view of disrupted pathways to explain how copy number alterations affect pathways that regulate cell growth, cycle, and differentiation for tumorigenesis. Conclusions In this work, we demonstrated that the network-based integrative analysis can help to identify pathways disrupted by copy number alterations across 16 types of human cancers, which are not readily identifiable by conventional overrepresentation-based and other pathway-based methods. All the results and source code are available at http://compbio.cs.umn.edu/NetPathID/. PMID:23822816

PyPathway: Python Package for Biological Network Analysis and Visualization.

PubMed

Xu, Yang; Luo, Xiao-Chun

2018-05-01

Life science studies represent one of the biggest generators of large data sets, mainly because of rapid sequencing technological advances. Biological networks including interactive networks and human curated pathways are essential to understand these high-throughput data sets. Biological network analysis offers a method to explore systematically not only the molecular complexity of a particular disease but also the molecular relationships among apparently distinct phenotypes. Currently, several packages for Python community have been developed, such as BioPython and Goatools. However, tools to perform comprehensive network analysis and visualization are still needed. Here, we have developed PyPathway, an extensible free and open source Python package for functional enrichment analysis, network modeling, and network visualization. The network process module supports various interaction network and pathway databases such as Reactome, WikiPathway, STRING, and BioGRID. The network analysis module implements overrepresentation analysis, gene set enrichment analysis, network-based enrichment, and de novo network modeling. Finally, the visualization and data publishing modules enable users to share their analysis by using an easy web application. For package availability, see the first Reference.

Comparison of a Traditional Probabilistic Risk Assessment Approach with Advanced Safety Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Curtis L; Mandelli, Diego; Zhegang Ma

2014-11-01

As part of the Light Water Sustainability Program (LWRS) [1], the purpose of the Risk Informed Safety Margin Characterization (RISMC) [2] Pathway research and development (R&D) is to support plant decisions for risk-informed margin management with the aim to improve economics, reliability, and sustain safety of current NPPs. In this paper, we describe the RISMC analysis process illustrating how mechanistic and probabilistic approaches are combined in order to estimate a safety margin. We use the scenario of a “station blackout” (SBO) wherein offsite power and onsite power is lost, thereby causing a challenge to plant safety systems. We describe themore » RISMC approach, illustrate the station blackout modeling, and contrast this with traditional risk analysis modeling for this type of accident scenario. We also describe our approach we are using to represent advanced flooding analysis.« less

PathwaySplice: An R package for unbiased pathway analysis of alternative splicing in RNA-Seq data.

PubMed

Yan, Aimin; Ban, Yuguang; Gao, Zhen; Chen, Xi; Wang, Lily

2018-04-24

Pathway analysis of alternative splicing would be biased without accounting for the different number of exons or junctions associated with each gene, because genes with higher number of exons or junctions are more likely to be included in the "significant" gene list in alternative splicing. We present PathwaySplice, an R package that (1) Performs pathway analysis that explicitly adjusts for the number of exons or junctions associated with each gene; (2) Visualizes selection bias due to different number of exons or junctions for each gene and formally tests for presence of bias using logistic regression; (3) Supports gene sets based on the Gene Ontology terms, as well as more broadly defined gene sets (e.g. MSigDB) or user defined gene sets; (4) Identifies the significant genes driving pathway significance and (5) Organizes significant pathways with an enrichment map, where pathways with large number of overlapping genes are grouped together in a network graph. https://bioconductor.org/packages/release/bioc/html/PathwaySplice.html. lily.wangg@gmail.com, xi.steven.chen@gmail.com.

A whole community approach to emergency management: Strategies and best practices of seven community programs.

PubMed

Sobelson, Robyn K; Wigington, Corinne J; Harp, Victoria; Bronson, Bernice B

2015-01-01

In 2011, the Federal Emergency Management Agency (FEMA) published the Whole Community Approach to Emergency Management: Principles, Themes, and Pathways for Action, outlining the need for increased individual preparedness and more widespread community engagement to enhance the overall resiliency and security of communities. However, there is limited evidence of how to build a whole community approach to emergency management that provides real-world, practical examples and applications. This article reports on the strategies and best practices gleaned from seven community programs fostering a whole community approach to emergency management. The project team engaged in informal conversations with community stakeholders to learn about their programs during routine monitoring activities, site visits, and during an in-person, facilitated workshop. A total of 88 community members associated with the programs examples contributed. Qualitative analysis was conducted. The findings highlighted best practices gleaned from the seven programs that other communities can leverage to build and maintain their own whole community programs. The findings from the programs also support and validate the three principles and six strategic themes outlined by FEMA. The findings, like the whole community document, highlight the importance of understanding the community, building relationships, empowering action, and fostering social capital to build a whole community approach.

On the usefulness of 'what' and 'where' pathways in vision.

PubMed

de Haan, Edward H F; Cowey, Alan

2011-10-01

The primate visual brain is classically portrayed as a large number of separate 'maps', each dedicated to the processing of specific visual cues, such as colour, motion or faces and their many features. In order to understand this fractionated architecture, the concept of cortical 'pathways' or 'streams' was introduced. In the currently prevailing view, the different maps are organised hierarchically into two major pathways, one involved in recognition and memory (the ventral stream or 'what' pathway) and the other in the programming of action (the dorsal stream or 'where' pathway). In this review, we question this heuristically influential but potentially misleading linear hierarchical pathway model and argue instead for a 'patchwork' or network model. Copyright © 2011 Elsevier Ltd. All rights reserved.

Pathway Analysis in Attention Deficit Hyperactivity Disorder: An Ensemble Approach

PubMed Central

Mooney, Michael A.; McWeeney, Shannon K.; Faraone, Stephen V.; Hinney, Anke; Hebebrand, Johannes; Nigg, Joel T.; Wilmot, Beth

2016-01-01

Despite a wealth of evidence for the role of genetics in attention deficit hyperactivity disorder (ADHD), specific and definitive genetic mechanisms have not been identified. Pathway analyses, a subset of gene-set analyses, extend the knowledge gained from genome-wide association studies (GWAS) by providing functional context for genetic associations. However, there are numerous methods for association testing of gene sets and no real consensus regarding the best approach. The present study applied six pathway analysis methods to identify pathways associated with ADHD in two GWAS datasets from the Psychiatric Genomics Consortium. Methods that utilize genotypes to model pathway-level effects identified more replicable pathway associations than methods using summary statistics. In addition, pathways implicated by more than one method were significantly more likely to replicate. A number of brain-relevant pathways, such as RhoA signaling, glycosaminoglycan biosynthesis, fibroblast growth factor receptor activity, and pathways containing potassium channel genes, were nominally significant by multiple methods in both datasets. These results support previous hypotheses about the role of regulation of neurotransmitter release, neurite outgrowth and axon guidance in contributing to the ADHD phenotype and suggest the value of cross-method convergence in evaluating pathway analysis results. PMID:27004716

PATHWAYS TO PROGRESS, A RESEARCH MONOGRAPH FROM OHIO'S PROGRAMS

ERIC Educational Resources Information Center

KOLB, DAVID A.

THE EFFECT OF A TRAINING PROGRAM IN ACHIEVEMENT MOTIVATION ON THE OF EDUCATION FOR THE ACADEMICALLY TALENTED STUDENT. AMONG PRESENTED. TWENTY BOYS WITH IQ'S ABOVE 120 AND SCHOOL GRADES BELOW C RECEIVED THE TRAINING PROGRAM IN ADDITION TO AN ACADEMIC SUMMER SCHOOL PROGRAM. THEY WERE COMPARED TO A CONTROL GROUP OF 37 SIMILAR BOYS WHO RECEIVED ONLY…

Responsibility Development Transfers across Contexts: Reciprocal Pathways between Home and Afterschool Programs

ERIC Educational Resources Information Center

Raffaelli, Marcela; Simpkins, Sandra D.; Tran, Steve P.; Larson, Reed W.

2018-01-01

We investigated adolescent responsibility across 2 developmental contexts, home and an afterschool program. Longitudinal data were collected from 355 ethnically diverse 11-20-year-old adolescents (M = 15.49; 55.9% female) in 14 project-based programs. Youth rated their responsibility in the program and at home at 4 time points; parents and leaders…

Designing optimal cell factories: integer programming couples elementary mode analysis with regulation

PubMed Central

2012-01-01

Background Elementary mode (EM) analysis is ideally suited for metabolic engineering as it allows for an unbiased decomposition of metabolic networks in biologically meaningful pathways. Recently, constrained minimal cut sets (cMCS) have been introduced to derive optimal design strategies for strain improvement by using the full potential of EM analysis. However, this approach does not allow for the inclusion of regulatory information. Results Here we present an alternative, novel and simple method for the prediction of cMCS, which allows to account for boolean transcriptional regulation. We use binary linear programming and show that the design of a regulated, optimal metabolic network of minimal functionality can be formulated as a standard optimization problem, where EM and regulation show up as constraints. We validated our tool by optimizing ethanol production in E. coli. Our study showed that up to 70% of the predicted cMCS contained non-enzymatic, non-annotated reactions, which are difficult to engineer. These cMCS are automatically excluded by our approach utilizing simple weight functions. Finally, due to efficient preprocessing, the binary program remains computationally feasible. Conclusions We used integer programming to predict efficient deletion strategies to metabolically engineer a production organism. Our formulation utilizes the full potential of cMCS but adds additional flexibility to the design process. In particular our method allows to integrate regulatory information into the metabolic design process and explicitly favors experimentally feasible deletions. Our method remains manageable even if millions or potentially billions of EM enter the analysis. We demonstrated that our approach is able to correctly predict the most efficient designs for ethanol production in E. coli. PMID:22898474

Epigenetic Profiling of H3K4Me3 Reveals Herbal Medicine Jinfukang-Induced Epigenetic Alteration Is Involved in Anti-Lung Cancer Activity.

PubMed

Lu, Jun; Zhang, Xiaoli; Shen, Tingting; Ma, Chao; Wu, Jun; Kong, Hualei; Tian, Jing; Shao, Zhifeng; Zhao, Xiaodong; Xu, Ling

2016-01-01

Traditional Chinese medicine Jinfukang (JFK) has been clinically used for treating lung cancer. To examine whether epigenetic modifications are involved in its anticancer activity, we performed a global profiling analysis of H3K4Me3, an epigenomic marker associated with active gene expression, in JFK-treated lung cancer cells. We identified 11,670 genes with significantly altered status of H3K4Me3 modification following JFK treatment (P < 0.05). Gene Ontology analysis indicates that these genes are involved in tumor-related pathways, including pathway in cancer, basal cell carcinoma, apoptosis, induction of programmed cell death, regulation of transcription (DNA-templated), intracellular signal transduction, and regulation of peptidase activity. In particular, we found that the levels of H3K4Me3 at the promoters of SUSD2, CCND2, BCL2A1, and TMEM158 are significantly altered in A549, NCI-H1975, NCI-H1650, and NCI-H2228 cells, when treated with JFK. Collectively, these findings provide the first evidence that the anticancer activity of JFK involves modulation of histone modification at many cancer-related gene loci.

Epigenetic Profiling of H3K4Me3 Reveals Herbal Medicine Jinfukang-Induced Epigenetic Alteration Is Involved in Anti-Lung Cancer Activity

PubMed Central

Lu, Jun; Zhang, Xiaoli; Shen, Tingting; Ma, Chao; Wu, Jun; Kong, Hualei; Tian, Jing; Shao, Zhifeng; Zhao, Xiaodong; Xu, Ling

2016-01-01

Traditional Chinese medicine Jinfukang (JFK) has been clinically used for treating lung cancer. To examine whether epigenetic modifications are involved in its anticancer activity, we performed a global profiling analysis of H3K4Me3, an epigenomic marker associated with active gene expression, in JFK-treated lung cancer cells. We identified 11,670 genes with significantly altered status of H3K4Me3 modification following JFK treatment (P < 0.05). Gene Ontology analysis indicates that these genes are involved in tumor-related pathways, including pathway in cancer, basal cell carcinoma, apoptosis, induction of programmed cell death, regulation of transcription (DNA-templated), intracellular signal transduction, and regulation of peptidase activity. In particular, we found that the levels of H3K4Me3 at the promoters of SUSD2, CCND2, BCL2A1, and TMEM158 are significantly altered in A549, NCI-H1975, NCI-H1650, and NCI-H2228 cells, when treated with JFK. Collectively, these findings provide the first evidence that the anticancer activity of JFK involves modulation of histone modification at many cancer-related gene loci. PMID:27087825

Using Patient-Pathway Analysis to Inform a Differentiated Program Response to Tuberculosis: The Case of Kenya

PubMed Central

Masini, Enos; Hanson, Christy; Ogoro, Jeremiah; Brown, Jessie; Ngari, Faith; Mingkwan, Pia; Makayova, Julia; Osberg, Mike

2017-01-01

Abstract Background A recent tuberculosis prevalence survey in Kenya found that the country is home to nearly twice as many patients with tuberculosis as previously estimated. Kenya has prioritized identifying and treating the unnotified or missing cases of tuberculosis. This requires a better understanding of patient care seeking and system weaknesses. Methods A patient-pathway analysis (PPA) was completed to assess the alignment between patient care seeking and the availability of tuberculosis diagnostic and treatment services at the national level and for all 47 counties at the subnational level in Kenya. Results It was estimated that more than half of patients initiate care in the public sector. Nationally, just under half of patients encountered tuberculosis diagnostic and treatment capacity where they initiated care. Overall, there was distinct variation in diagnostic and treatment availability across counties and facility levels. Discussion The PPA results emphasized the need for a differentiated approach to tuberculosis care, by county, and the distinct need for better referral systems. The majority of Kenyans actively sought care; improving diagnostic and treatment capacity in the formal and informal private sector, as well as in the public sector, could help identify the majority of missing cases. PMID:29117349

Language and hope in schizophrenia-spectrum disorders.

PubMed

Bonfils, Kelsey A; Luther, Lauren; Firmin, Ruth L; Lysaker, Paul H; Minor, Kyle S; Salyers, Michelle P

2016-11-30

Hope is integral to recovery for those with schizophrenia. Considering recent advancements in the examination of clients' lexical qualities, we were interested in how clients' words reflect hope. Using computerized lexical analysis, we examined social, emotion, and future words' relations to hope and its pathways and agency components. Forty-five clients provided detailed narratives about their life and mental illness. Transcripts were analyzed using the Linguistic Inquiry and Word Count program (LIWC), which assigns words to categories (e.g., "anxiety") based on a pre-existing dictionary. Correlations and linear multiple regression were used to examine relationships between lexical qualities and hope. Hope and its subcomponents had significant or trending bivariate correlations in expected directions with several emotion-related word categories (anger and sadness) but were not associated with expected categories such as social words, positive emotions, optimism, achievement, and future words. In linear multiple regressions, no LIWC variable significantly predicted hope agency, but anger words significantly predicted both total hope and hope pathways. Our findings indicate lexical analysis tools can be used to investigate recovery-oriented concepts such as hope, and results may inform clinical practice. Future research should aim to replicate our findings in larger samples. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Epigenomic profiling of men exposed to early-life stress reveals DNA methylation differences in association with current mental state.

PubMed

Khulan, B; Manning, J R; Dunbar, D R; Seckl, J R; Raikkonen, K; Eriksson, J G; Drake, A J

2014-09-23

Early-life stress (ELS) is known to be associated with an increased risk of neuropsychiatric and cardiometabolic disease in later life. One of the potential mechanisms underpinning this is through effects on the epigenome, particularly changes in DNA methylation. Using a well-phenotyped cohort of 83 men from the Helsinki Birth Cohort Study, who experienced ELS in the form of separation from their parents during childhood, and a group of 83 matched controls, we performed a genome-wide analysis of DNA methylation in peripheral blood. We found no differences in DNA methylation between men who were separated from their families and non-separated men; however, we did identify differences in DNA methylation in association with the development of at least mild depressive symptoms over the subsequent 5-10 years. Notably, hypomethylation was identified at a number of genes with roles in brain development and/or function in association with depressive symptoms. Pathway analysis revealed an enrichment of DNA methylation changes in pathways associated with development and morphogenesis, DNA and transcription factor binding and programmed cell death. Our results support the concept that DNA methylation differences may be important in the pathogenesis of psychiatric disease.

KEGGParser: parsing and editing KEGG pathway maps in Matlab.

PubMed

Arakelyan, Arsen; Nersisyan, Lilit

2013-02-15

KEGG pathway database is a collection of manually drawn pathway maps accompanied with KGML format files intended for use in automatic analysis. KGML files, however, do not contain the required information for complete reproduction of all the events indicated in the static image of a pathway map. Several parsers and editors of KEGG pathways exist for processing KGML files. We introduce KEGGParser-a MATLAB based tool for KEGG pathway parsing, semiautomatic fixing, editing, visualization and analysis in MATLAB environment. It also works with Scilab. The source code is available at http://www.mathworks.com/matlabcentral/fileexchange/37561.

Wnt signaling inhibits CTL memory programming

PubMed Central

Xiao, Zhengguo; Sun, Zhifeng; Smyth, Kendra; Li, Lei

2013-01-01

Induction of functional CTLs is one of the major goals for vaccine development and cancer therapy. Inflammatory cytokines are critical for memory CTL generation. Wnt signaling is important for CTL priming and memory formation, but its role in cytokine-driven memory CTL programming is unclear. We found that wnt signaling inhibited IL-12-driven CTL activation and memory programming. This impaired memory CTL programming was attributed to up-regulation of eomes and down-regulation of T-bet. Wnt signaling suppressed the mTOR pathway during CTL activation, which was different to its effects on other cell types. Interestingly, the impaired memory CTL programming by wnt was partially rescued by mTOR inhibitor rapamycin. In conclusion, we found that crosstalk between wnt and the IL-12 signaling inhibits T-bet and mTOR pathways and impairs memory programming which can be recovered in part by rapamycin. In addition, direct inhibition of wnt signaling during CTL activation does not affect CTL memory programming. Therefore, wnt signaling may serve as a new tool for CTL manipulation in autoimmune diseases and immune therapy for certain cancers. PMID:23911398

COMPUGIRLS: Stepping Stone to Future Computer-Based Technology Pathways

ERIC Educational Resources Information Center

Lee, Jieun; Husman, Jenefer; Scott, Kimberly A.; Eggum-Wilkens, Natalie D.

2015-01-01

The COMPUGIRLS: Culturally relevant technology program for adolescent girls was developed to promote underrepresented girls' future possible selves and career pathways in computer-related technology fields. We hypothesized that the COMPUGIRLS would promote academic possible selves and self-regulation to achieve these possible selves. We compared…

A Multipronged Approach to Improving Transitions and Outcomes for Nontraditional-Aged Students in Select Pathways at Oakton Community College. Pathways to Results: Implementation Partnerships Strategy Brief

ERIC Educational Resources Information Center

McCambly, Heather

2016-01-01

Oakton Community College (Oakton) launched a Pathways to Results (PTR) project for the first time in 2014, a decision that converged with the launch of an all-college student success team with the goal of making evidence-based decisions to significantly improve student success. Oakton chose to work initially on its manufacturing program.…

Evidence of cardiac involvement in the fetal inflammatory response syndrome: disruption of gene networks programming cardiac development in nonhuman primates.

PubMed

Mitchell, Timothy; MacDonald, James W; Srinouanpranchanh, Sengkeo; Bammler, Theodor K; Merillat, Sean; Boldenow, Erica; Coleman, Michelle; Agnew, Kathy; Baldessari, Audrey; Stencel-Baerenwald, Jennifer E; Tisoncik-Go, Jennifer; Green, Richard R; Gale, Michael J; Rajagopal, Lakshmi; Adams Waldorf, Kristina M

2018-04-01

Most early preterm births are associated with intraamniotic infection and inflammation, which can lead to systemic inflammation in the fetus. The fetal inflammatory response syndrome describes elevations in the fetal interleukin-6 level, which is a marker for inflammation and fetal organ injury. An understanding of the effects of inflammation on fetal cardiac development may lead to insight into the fetal origins of adult cardiovascular disease. The purpose of this study was to determine whether the fetal inflammatory response syndrome is associated with disruptions in gene networks that program fetal cardiac development. We obtained fetal cardiac tissue after necropsy from a well-described pregnant nonhuman primate model (pigtail macaque, Macaca nemestrina) of intrauterine infection (n=5) and controls (n=5). Cases with the fetal inflammatory response syndrome (fetal plasma interleukin-6 >11 pg/mL) were induced by either choriodecidual inoculation of a hypervirulent group B streptococcus strain (n=4) or intraamniotic inoculation of Escherichia coli (n=1). RNA and protein were extracted from fetal hearts and profiled by microarray and Luminex (Millipore, Billerica, MA) for cytokine analysis, respectively. Results were validated by quantitative reverse transcriptase polymerase chain reaction. Statistical and bioinformatics analyses included single gene analysis, gene set analysis, Ingenuity Pathway Analysis (Qiagen, Valencia, CA), and Wilcoxon rank sum. Severe fetal inflammation developed in the context of intraamniotic infection and a disseminated bacterial infection in the fetus. Interleukin-6 and -8 in fetal cardiac tissues were elevated significantly in fetal inflammatory response syndrome cases vs controls (P<.05). A total of 609 probe sets were expressed differentially (>1.5-fold change, P<.05) in the fetal heart (analysis of variance). Altered expression of select genes was validated by quantitative reverse transcriptase polymerase chain reaction that included several with known functions in cardiac injury, morphogenesis, angiogenesis, and tissue remodeling (eg, angiotensin I converting enzyme 2, STEAP family member 4, natriuretic peptide A, and secreted frizzled-related protein 4; all P<.05). Multiple gene sets and pathways that are involved in cardiac morphogenesis and vasculogenesis were downregulated significantly by gene set and Ingenuity Pathway Analysis (hallmark transforming growth factor beta signaling, cellular morphogenesis during differentiation, morphology of cardiovascular system; all P<.05). Disruption of gene networks for cardiac morphogenesis and vasculogenesis occurred in the preterm fetal heart of nonhuman primates with preterm labor, intraamniotic infection, and severe fetal inflammation. Inflammatory injury to the fetal heart in utero may contribute to the development of heart disease later in life. Development of preterm labor therapeutics must also target fetal inflammation to lessen organ injury and potential long-term effects on cardiac function. Copyright © 2018 Elsevier Inc. All rights reserved.

Construction and completion of flux balance models from pathway databases.

PubMed

Latendresse, Mario; Krummenacker, Markus; Trupp, Miles; Karp, Peter D

2012-02-01

Flux balance analysis (FBA) is a well-known technique for genome-scale modeling of metabolic flux. Typically, an FBA formulation requires the accurate specification of four sets: biochemical reactions, biomass metabolites, nutrients and secreted metabolites. The development of FBA models can be time consuming and tedious because of the difficulty in assembling completely accurate descriptions of these sets, and in identifying errors in the composition of these sets. For example, the presence of a single non-producible metabolite in the biomass will make the entire model infeasible. Other difficulties in FBA modeling are that model distributions, and predicted fluxes, can be cryptic and difficult to understand. We present a multiple gap-filling method to accelerate the development of FBA models using a new tool, called MetaFlux, based on mixed integer linear programming (MILP). The method suggests corrections to the sets of reactions, biomass metabolites, nutrients and secretions. The method generates FBA models directly from Pathway/Genome Databases. Thus, FBA models developed in this framework are easily queried and visualized using the Pathway Tools software. Predicted fluxes are more easily comprehended by visualizing them on diagrams of individual metabolic pathways or of metabolic maps. MetaFlux can also remove redundant high-flux loops, solve FBA models once they are generated and model the effects of gene knockouts. MetaFlux has been validated through construction of FBA models for Escherichia coli and Homo sapiens. Pathway Tools with MetaFlux is freely available to academic users, and for a fee to commercial users. Download from: biocyc.org/download.shtml. mario.latendresse@sri.com Supplementary data are available at Bioinformatics online.

BioASF: a framework for automatically generating executable pathway models specified in BioPAX.

PubMed

Haydarlou, Reza; Jacobsen, Annika; Bonzanni, Nicola; Feenstra, K Anton; Abeln, Sanne; Heringa, Jaap

2016-06-15

Biological pathways play a key role in most cellular functions. To better understand these functions, diverse computational and cell biology researchers use biological pathway data for various analysis and modeling purposes. For specifying these biological pathways, a community of researchers has defined BioPAX and provided various tools for creating, validating and visualizing BioPAX models. However, a generic software framework for simulating BioPAX models is missing. Here, we attempt to fill this gap by introducing a generic simulation framework for BioPAX. The framework explicitly separates the execution model from the model structure as provided by BioPAX, with the advantage that the modelling process becomes more reproducible and intrinsically more modular; this ensures natural biological constraints are satisfied upon execution. The framework is based on the principles of discrete event systems and multi-agent systems, and is capable of automatically generating a hierarchical multi-agent system for a given BioPAX model. To demonstrate the applicability of the framework, we simulated two types of biological network models: a gene regulatory network modeling the haematopoietic stem cell regulators and a signal transduction network modeling the Wnt/β-catenin signaling pathway. We observed that the results of the simulations performed using our framework were entirely consistent with the simulation results reported by the researchers who developed the original models in a proprietary language. The framework, implemented in Java, is open source and its source code, documentation and tutorial are available at http://www.ibi.vu.nl/programs/BioASF CONTACT: j.heringa@vu.nl. © The Author 2016. Published by Oxford University Press.

The identification of key genes and pathways in hepatocellular carcinoma by bioinformatics analysis of high-throughput data.

PubMed

Zhang, Chaoyang; Peng, Li; Zhang, Yaqin; Liu, Zhaoyang; Li, Wenling; Chen, Shilian; Li, Guancheng

2017-06-01

Liver cancer is a serious threat to public health and has fairly complicated pathogenesis. Therefore, the identification of key genes and pathways is of much importance for clarifying molecular mechanism of hepatocellular carcinoma (HCC) initiation and progression. HCC-associated gene expression dataset was downloaded from Gene Expression Omnibus database. Statistical software R was used for significance analysis of differentially expressed genes (DEGs) between liver cancer samples and normal samples. Gene Ontology (GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, based on R software, were applied for the identification of pathways in which DEGs significantly enriched. Cytoscape software was for the construction of protein-protein interaction (PPI) network and module analysis to find the hub genes and key pathways. Finally, weighted correlation network analysis (WGCNA) was conducted to further screen critical gene modules with similar expression pattern and explore their biological significance. Significance analysis identified 1230 DEGs with fold change >2, including 632 significantly down-regulated DEGs and 598 significantly up-regulated DEGs. GO term enrichment analysis suggested that up-regulated DEG significantly enriched in immune response, cell adhesion, cell migration, type I interferon signaling pathway, and cell proliferation, and the down-regulated DEG mainly enriched in response to endoplasmic reticulum stress and endoplasmic reticulum unfolded protein response. KEGG pathway analysis found DEGs significantly enriched in five pathways including complement and coagulation cascades, focal adhesion, ECM-receptor interaction, antigen processing and presentation, and protein processing in endoplasmic reticulum. The top 10 hub genes in HCC were separately GMPS, ACACA, ALB, TGFB1, KRAS, ERBB2, BCL2, EGFR, STAT3, and CD8A, which resulted from PPI network. The top 3 gene interaction modules in PPI network enriched in immune response, organ development, and response to other organism, respectively. WGCNA revealed that the confirmed eight gene modules significantly enriched in monooxygenase and oxidoreductase activity, response to endoplasmic reticulum stress, type I interferon signaling pathway, processing, presentation and binding of peptide antigen, cellular response to cadmium and zinc ion, cell locomotion and differentiation, ribonucleoprotein complex and RNA processing, and immune system process, respectively. In conclusion, we identified some key genes and pathways closely related with HCC initiation and progression by a series of bioinformatics analysis on DEGs. These screened genes and pathways provided for a more detailed molecular mechanism underlying HCC occurrence and progression, holding promise for acting as biomarkers and potential therapeutic targets.

Pathway activity inference for multiclass disease classification through a mathematical programming optimisation framework.

PubMed

Yang, Lingjian; Ainali, Chrysanthi; Tsoka, Sophia; Papageorgiou, Lazaros G

2014-12-05

Applying machine learning methods on microarray gene expression profiles for disease classification problems is a popular method to derive biomarkers, i.e. sets of genes that can predict disease state or outcome. Traditional approaches where expression of genes were treated independently suffer from low prediction accuracy and difficulty of biological interpretation. Current research efforts focus on integrating information on protein interactions through biochemical pathway datasets with expression profiles to propose pathway-based classifiers that can enhance disease diagnosis and prognosis. As most of the pathway activity inference methods in literature are either unsupervised or applied on two-class datasets, there is good scope to address such limitations by proposing novel methodologies. A supervised multiclass pathway activity inference method using optimisation techniques is reported. For each pathway expression dataset, patterns of its constituent genes are summarised into one composite feature, termed pathway activity, and a novel mathematical programming model is proposed to infer this feature as a weighted linear summation of expression of its constituent genes. Gene weights are determined by the optimisation model, in a way that the resulting pathway activity has the optimal discriminative power with regards to disease phenotypes. Classification is then performed on the resulting low-dimensional pathway activity profile. The model was evaluated through a variety of published gene expression profiles that cover different types of disease. We show that not only does it improve classification accuracy, but it can also perform well in multiclass disease datasets, a limitation of other approaches from the literature. Desirable features of the model include the ability to control the maximum number of genes that may participate in determining pathway activity, which may be pre-specified by the user. Overall, this work highlights the potential of building pathway-based multi-phenotype classifiers for accurate disease diagnosis and prognosis problems.

Systematic analysis of signaling pathways using an integrative environment.

PubMed

Visvanathan, Mahesh; Breit, Marc; Pfeifer, Bernhard; Baumgartner, Christian; Modre-Osprian, Robert; Tilg, Bernhard

2007-01-01

Understanding the biological processes of signaling pathways as a whole system requires an integrative software environment that has comprehensive capabilities. The environment should include tools for pathway design, visualization, simulation and a knowledge base concerning signaling pathways as one. In this paper we introduce a new integrative environment for the systematic analysis of signaling pathways. This system includes environments for pathway design, visualization, simulation and a knowledge base that combines biological and modeling information concerning signaling pathways that provides the basic understanding of the biological system, its structure and functioning. The system is designed with a client-server architecture. It contains a pathway designing environment and a simulation environment as upper layers with a relational knowledge base as the underlying layer. The TNFa-mediated NF-kB signal trans-duction pathway model was designed and tested using our integrative framework. It was also useful to define the structure of the knowledge base. Sensitivity analysis of this specific pathway was performed providing simulation data. Then the model was extended showing promising initial results. The proposed system offers a holistic view of pathways containing biological and modeling data. It will help us to perform biological interpretation of the simulation results and thus contribute to a better understanding of the biological system for drug identification.

Network design and analysis for multi-enzyme biocatalysis.

PubMed

Blaß, Lisa Katharina; Weyler, Christian; Heinzle, Elmar

2017-08-10

As more and more biological reaction data become available, the full exploration of the enzymatic potential for the synthesis of valuable products opens up exciting new opportunities but is becoming increasingly complex. The manual design of multi-step biosynthesis routes involving enzymes from different organisms is very challenging. To harness the full enzymatic potential, we developed a computational tool for the directed design of biosynthetic production pathways for multi-step catalysis with in vitro enzyme cascades, cell hydrolysates and permeabilized cells. We present a method which encompasses the reconstruction of a genome-scale pan-organism metabolic network, path-finding and the ranking of the resulting pathway candidates for proposing suitable synthesis pathways. The network is based on reaction and reaction pair data from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the thermodynamics calculator eQuilibrator. The pan-organism network is especially useful for finding the most suitable pathway to a target metabolite from a thermodynamic or economic standpoint. However, our method can be used with any network reconstruction, e.g. for a specific organism. We implemented a path-finding algorithm based on a mixed-integer linear program (MILP) which takes into account both topology and stoichiometry of the underlying network. Unlike other methods we do not specify a single starting metabolite, but our algorithm searches for pathways starting from arbitrary start metabolites to a target product of interest. Using a set of biochemical ranking criteria including pathway length, thermodynamics and other biological characteristics such as number of heterologous enzymes or cofactor requirement, it is possible to obtain well-designed meaningful pathway alternatives. In addition, a thermodynamic profile, the overall reactant balance and potential side reactions as well as an SBML file for visualization are generated for each pathway alternative. We present an in silico tool for the design of multi-enzyme biosynthetic production pathways starting from a pan-organism network. The method is highly customizable and each module can be adapted to the focus of the project at hand. This method is directly applicable for (i) in vitro enzyme cascades, (ii) cell hydrolysates and (iii) permeabilized cells.

Designing an evaluation for a multiple-strategy community intervention: the North Coast Stay on Your Feet program.

PubMed

van Beurden, E; Kempton, A; Sladden, T; Garner, E

1998-02-01

Evaluation of the North Coast Stay on Your Feet falls prevention program is described as a case study of a comprehensive evaluation design for multi-strategic community interventions. Qualitative and quantitative methods were used to evaluate the program at formative, process and outcome levels. Formative evaluation used literature review, focus groups, mail-out and telephone survey methods to gather evidence from publications, older people, health workers, local business, media and government bodies. It included an analysis of demographic and hospital databases and identified incidence, causal pathways, knowledge, attitudes, behaviour, consequences and effectiveness of potential strategies. Process evaluation employed auditing, monitoring and telephone surveys to maintain an inventory of intervention activities and to track the reach of the program. Outcome evaluation involved a longitudinal study of intervention and control cohorts, surveyed before, during and after the intervention by telephone to monitor changes in knowledge, attitudes, risk and falls incidence. The survey instrument was designed for both formative and outcome evaluation, and analysis reflected the research design by incorporating repeat measures and adjusting for bias and confounding. Outcome validity was cross-checked via hospital admission rates. A novel, integrated framework for presenting inputs, activities and outcomes from all stages of the program is described. This framework facilitated feedback to stakeholders and enabled subsequent rapid adjustment of the intervention. Rigorous evaluation combined with clear presentation of findings helped to engender intersectoral support and obtain funding grants for extended implementation and evaluation. It also helped Stay on Your Feet to become a model for other falls prevention programs within Australia and internationally.

Pioneering quality assessment in European cancer centers: a data analysis of the organization for European cancer institutes accreditation and designation program.

PubMed

Saghatchian, Mahasti; Thonon, Frédérique; Boomsma, Femke; Hummel, Henk; Koot, Bert; Harrison, Chris; Rajan, Abinaya; de Valeriola, Dominique; Otter, Renée; Laranja Pontes, José; Lombardo, Claudio; McGrath, Eoin; Ringborg, Ulrik; Tursz, Thomas; van Harten, Wim

2014-09-01

In order to improve the quality of care in Cancer Centers (CC) and designate Comprehensive Cancer Centers (CCCs), the Organization for European Cancer Institutes (OECI) launched an Accreditation and Designation (A&D) program. The program facilitates the collection of defined data and the assessment of cancer center quality. This study analyzes the results of the first 10 European centers that entered the program. The assessment included 927 items divided across qualitative and quantitative questionnaires. Data collected during self-assessment and peer-review from the 10 first participating centers were combined in a database for comparative analysis using simple statistics. Quantitative and qualitative results were validated by auditors during the peer review visits. Volumes of various functions and activities dedicated to care, research, and education varied widely among centers. There were no significant differences in resources for radiology, radiotherapy, pathologic diagnostic, and surgery. Differences were observed in the use of clinical pathways but not for the practices of holding multidisciplinary team meetings and conforming to guidelines. Regarding human resources, main differences were in the composition and number of supportive care and research staff. All 10 centers applied as CCCs; five obtained the label, and five were designated as CCs. The OECI A&D program allows comparisons between centers with regard to management, research, care, education, and designation as CCs or CCCs. Through the peer review system, recommendations for improvements are given. Assessing the added value of the program, as well as research and patient treatment outcomes, is the next step. Copyright © 2014 by American Society of Clinical Oncology.

Energy-efficient Public Procurement: Best Practice in Program Delivery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Payne, Christopher; Weber, Andrew; Semple, Abby

2013-02-15

This document illustrates the key issues and considerations involved in implementing energy-efficient public procurement. Our primary sources of information have been our partners in the Super Efficient Equipment and Appliance Deployment (SEAD) Initiative Procurement Working Group. Where applicable, we have highlighted specific ways in which working group participants have successfully overcome barriers to delivering effective programs. The following key points emerge from this analysis of programs for energy-efficient public procurement. Lessons for both developed and developing programs are highlighted throughout the guide. 1. Policy: Policy provides the initiative to begin a transition from first cost to life-cycle cost based purchasingmore » methods and culture. Effective policy is well-communicated, establishes accountability from top to bottom of organizations and simplifies the processes necessary to comply. Flexibility and responsiveness are essential in policy development and implementation. Mandatory and voluntary policies may complement one another. 2. Procurement Criteria: Procurement staff must be confident that energy-efficient procurement criteria offer the best long-term value for their organization’s money and represent real environmental gains. Involving multiple stakeholders at the early stages of the criteria creation process can result in greater levels of cooperation from private industry. Criteria should make comparison of products easy for purchasers and require minimal additional calculations. Criteria will need to be regularly updated to reflect market developments. 3. Training: Resources for the creation of training programs are usually very limited, but well-targeted training is necessary in order for a program to be effective. Training must emphasize a process that is efficient for purchasers and simplifies compliance. Purchaser resources and policy must be well designed for training to be effective. Training program development is an excellent opportunity for collaboration amongst public authorities. 4. Procurement Processes: Many tools and guides intended to help buyers comply with energy-efficient procurement policy are designed without detailed knowledge of the procurement process. A deeper understanding of purchasing pathways allows resources to be better directed. Current research by national and international bodies aims to analyze purchasing pathways and can assist in developing future resources.« less

Perspectives on the Use of Clinical Pathways in Oncology Care.

PubMed

Chiang, Anne C; Ellis, Peter; Zon, Robin

2017-01-01

Pathways and guidelines are valuable tools to provide evidence-based care in oncology. Pathways may be more restrictive than guidelines because they attempt (where possible) to reduce cost, add efficiency, and remove unwarranted variability. Pathways offer an opportunity to measure, report, and improve quality of care; they can drive to evidence-based targeted therapy where appropriate; they can enhance efficiency through standardization; and, finally, they can be a vehicle to enhance participation in clinical trials. Pathway implementation requires understanding and commitment on the part of the physician and leadership as they may initially disrupt workflow, but ultimately have the ability to enhance patient care. ASCO criteria have been published for the development and implementation of high-quality oncology pathway programs. Future challenges for pathways include incorporation of molecular testing and appropriate targeted care in a real-time precision oncology approach.

A Pathway to Learner Autonomy: A Self-Determination Theory Perspective

ERIC Educational Resources Information Center

Hu, Pingying; Zhang, Jiaxiu

2017-01-01

Concepts of learner autonomy and the self-determination theory provided a theoretical rationale for the action program for learner autonomy. The action program incorporated satisfying learners' basic psychological needs into English Foreign Language (EFL) course education. The action program was implemented for one academic year. Both qualitative…

Teachers-in-Residence: New Pathways into the Profession. Ask the Team

ERIC Educational Resources Information Center

Han, Grace; Doyle, Daniela

2013-01-01

Teacher residency programs are a relatively new method for building stronger teacher pipelines. Research assessing the impact of these programs is still limited, but some early reports suggest that residency programs hold promise for improving teacher effectiveness and retention rates (Barrett, Hovde, Hahn, & Rosqueta, 2011; Papay, West,…

Therapeutic targeting of epithelial plasticity programs – Focus on the epithelial-mesenchymal transition

PubMed Central

Malek, Reem; Wang, Hailun; Taparra, Kekoa; Tran, Phuoc T.

2017-01-01

Mounting data points to epithelial plasticity programs such as the epithelial-mesenchymal transition (EMT) as clinically relevant therapeutic targets for the treatment of malignant tumors. In addition to the widely realized role of EMT in increasing cancer cell invasiveness during cancer metastasis, the EMT has also been implicated in allowing cancer cells to avoid tumor suppressor pathways during early tumorigenesis. In addition, data linking EMT to innate and acquired treatment resistance further points towards the desire to develop pharmacological therapies to target epithelial plasticity in cancer. In this review we organized our discussion on pathways and agents that can be used to target the EMT in cancer into three groups: (1) extracellular inducers of EMT; (2) the transcription factors that orchestrate the EMT transcriptome; and, (3) the downstream effectors of EMT. We highlight only briefly specific canonical pathways known to be involved in EMT such as the signal transduction pathways TGFβ, EFGR and Axl-Gas6. We emphasize in more detail pathways that are we believe are emerging novel pathways and therapeutic targets such as epigenetic therapies, glycosylation pathways and immunotherapy. The heterogeneity of tumors and the dynamic nature of epithelial plasticity in cancer cells make it likely that targeting only one EMT related process will be unsuccessful or only transiently successful. We suggest with greater understanding of epithelial plasticity regulation such as with the EMT, a more systematic targeting of multiple EMT regulatory networks will be the best path forward to improve cancer outcomes. PMID:28214899

Identification of key target genes and pathways in laryngeal carcinoma

PubMed Central

Liu, Feng; Du, Jintao; Liu, Jun; Wen, Bei

2016-01-01

The purpose of the present study was to screen the key genes associated with laryngeal carcinoma and to investigate the molecular mechanism of laryngeal carcinoma progression. The gene expression profile of GSE10935 [Gene Expression Omnibus (GEO) accession number], including 12 specimens from laryngeal papillomas and 12 specimens from normal laryngeal epithelia controls, was downloaded from the GEO database. Differentially expressed genes (DEGs) were screened in laryngeal papillomas compared with normal controls using Limma package in R language, followed by Gene Ontology (GO) enrichment analysis and pathway enrichment analysis. Furthermore, the protein-protein interaction (PPI) network of DEGs was constructed using Cytoscape software and modules were analyzed using MCODE plugin from the PPI network. Furthermore, significant biological pathway regions (sub-pathway) were identified by using iSubpathwayMiner analysis. A total of 67 DEGs were identified, including 27 up-regulated genes and 40 down-regulated genes and they were involved in different GO terms and pathways. PPI network analysis revealed that Ras association (RalGDS/AF-6) domain family member 1 (RASSF1) was a hub protein. The sub-pathway analysis identified 9 significantly enriched sub-pathways, including glycolysis/gluconeogenesis and nitrogen metabolism. Genes such as phosphoglycerate kinase 1 (PGK1), carbonic anhydrase II (CA2), and carbonic anhydrase XII (CA12) whose node degrees were >10 were identified in the disease risk sub-pathway. Genes in the sub-pathway, such as RASSF1, PGK1, CA2 and CA12 were presumed to serve critical roles in laryngeal carcinoma. The present study identified DEGs and their sub-pathways in the disease, which may serve as potential targets for treatment of laryngeal carcinoma. PMID:27446427

Pathway-based factor analysis of gene expression data produces highly heritable phenotypes that associate with age.

PubMed

Anand Brown, Andrew; Ding, Zhihao; Viñuela, Ana; Glass, Dan; Parts, Leopold; Spector, Tim; Winn, John; Durbin, Richard

2015-03-09

Statistical factor analysis methods have previously been used to remove noise components from high-dimensional data prior to genetic association mapping and, in a guided fashion, to summarize biologically relevant sources of variation. Here, we show how the derived factors summarizing pathway expression can be used to analyze the relationships between expression, heritability, and aging. We used skin gene expression data from 647 twins from the MuTHER Consortium and applied factor analysis to concisely summarize patterns of gene expression to remove broad confounding influences and to produce concise pathway-level phenotypes. We derived 930 "pathway phenotypes" that summarized patterns of variation across 186 KEGG pathways (five phenotypes per pathway). We identified 69 significant associations of age with phenotype from 57 distinct KEGG pathways at a stringent Bonferroni threshold ([Formula: see text]). These phenotypes are more heritable ([Formula: see text]) than gene expression levels. On average, expression levels of 16% of genes within these pathways are associated with age. Several significant pathways relate to metabolizing sugars and fatty acids; others relate to insulin signaling. We have demonstrated that factor analysis methods combined with biological knowledge can produce more reliable phenotypes with less stochastic noise than the individual gene expression levels, which increases our power to discover biologically relevant associations. These phenotypes could also be applied to discover associations with other environmental factors. Copyright © 2015 Brown et al.

Pathway-Based Factor Analysis of Gene Expression Data Produces Highly Heritable Phenotypes That Associate with Age

PubMed Central

Anand Brown, Andrew; Ding, Zhihao; Viñuela, Ana; Glass, Dan; Parts, Leopold; Spector, Tim; Winn, John; Durbin, Richard

2015-01-01

Statistical factor analysis methods have previously been used to remove noise components from high-dimensional data prior to genetic association mapping and, in a guided fashion, to summarize biologically relevant sources of variation. Here, we show how the derived factors summarizing pathway expression can be used to analyze the relationships between expression, heritability, and aging. We used skin gene expression data from 647 twins from the MuTHER Consortium and applied factor analysis to concisely summarize patterns of gene expression to remove broad confounding influences and to produce concise pathway-level phenotypes. We derived 930 “pathway phenotypes” that summarized patterns of variation across 186 KEGG pathways (five phenotypes per pathway). We identified 69 significant associations of age with phenotype from 57 distinct KEGG pathways at a stringent Bonferroni threshold (P<5.38×10−5). These phenotypes are more heritable (h2=0.32) than gene expression levels. On average, expression levels of 16% of genes within these pathways are associated with age. Several significant pathways relate to metabolizing sugars and fatty acids; others relate to insulin signaling. We have demonstrated that factor analysis methods combined with biological knowledge can produce more reliable phenotypes with less stochastic noise than the individual gene expression levels, which increases our power to discover biologically relevant associations. These phenotypes could also be applied to discover associations with other environmental factors. PMID:25758824

Pathway Analysis and Omics Data Visualization Using Pathway Genome Databases: FragariaCyc, a Case Study.

PubMed

Naithani, Sushma; Jaiswal, Pankaj

2017-01-01

The species-specific plant Pathway Genome Databases (PGDBs) based on the BioCyc platform provide a conceptual model of the cellular metabolic network of an organism. Such frameworks allow analysis of the genome-scale expression data to understand changes in the overall metabolisms of an organism (or organs, tissues, and cells) in response to various extrinsic (e.g. developmental and differentiation) and/or extrinsic signals (e.g. pathogens and abiotic stresses) from the surrounding environment. Using FragariaCyc, a pathway database for the diploid strawberry Fragaria vesca, we show (1) the basic navigation across a PGDB; (2) a case study of pathway comparison across plant species; and (3) an example of RNA-Seq data analysis using Omics Viewer tool. The protocols described here generally apply to other Pathway Tools-based PGDBs.

Real-time cell toxicity profiling of Tox21 10K compounds reveals cytotoxicity dependent toxicity pathway linkage

PubMed Central

Huang, Ruili; Lin, Ja-An; Sedykh, Alexander; Zhao, Jinghua; Tice, Raymond R.; Paules, Richard S.; Xia, Menghang; Auerbach, Scott S.

2017-01-01

Cytotoxicity is a commonly used in vitro endpoint for evaluating chemical toxicity. In support of the U.S. Tox21 screening program, the cytotoxicity of ~10K chemicals was interrogated at 0, 8, 16, 24, 32, & 40 hours of exposure in a concentration dependent fashion in two cell lines (HEK293, HepG2) using two multiplexed, real-time assay technologies. One technology measures the metabolic activity of cells (i.e., cell viability, glo) while the other evaluates cell membrane integrity (i.e., cell death, flor). Using glo technology, more actives and greater temporal variations were seen in HEK293 cells, while results for the flor technology were more similar across the two cell types. Chemicals were grouped into classes based on their cytotoxicity kinetics profiles and these classes were evaluated for their associations with activity in the Tox21 nuclear receptor and stress response pathway assays. Some pathways, such as the activation of H2AX, were associated with the fast-responding cytotoxicity classes, while others, such as activation of TP53, were associated with the slow-responding cytotoxicity classes. By clustering pathways based on their degree of association to the different cytotoxicity kinetics labels, we identified clusters of pathways where active chemicals presented similar kinetics of cytotoxicity. Such linkages could be due to shared underlying biological processes between pathways, for example, activation of H2AX and heat shock factor. Others involving nuclear receptor activity are likely due to shared chemical structures rather than pathway level interactions. Based on the linkage between androgen receptor antagonism and Nrf2 activity, we surmise that a subclass of androgen receptor antagonists cause cytotoxicity via oxidative stress that is associated with Nrf2 activation. In summary, the real-time cytotoxicity screen provides informative chemical cytotoxicity kinetics data related to their cytotoxicity mechanisms, and with our analysis, it is possible to formulate mechanism-based hypotheses on the cytotoxic properties of the tested chemicals. PMID:28531190

A Community Health Worker "logic model": towards a theory of enhanced performance in low- and middle-income countries.

PubMed

Naimoli, Joseph F; Frymus, Diana E; Wuliji, Tana; Franco, Lynne M; Newsome, Martha H

2014-10-02

There has been a resurgence of interest in national Community Health Worker (CHW) programs in low- and middle-income countries (LMICs). A lack of strong research evidence persists, however, about the most efficient and effective strategies to ensure optimal, sustained performance of CHWs at scale. To facilitate learning and research to address this knowledge gap, the authors developed a generic CHW logic model that proposes a theoretical causal pathway to improved performance. The logic model draws upon available research and expert knowledge on CHWs in LMICs. Construction of the model entailed a multi-stage, inductive, two-year process. It began with the planning and implementation of a structured review of the existing research on community and health system support for enhanced CHW performance. It continued with a facilitated discussion of review findings with experts during a two-day consultation. The process culminated with the authors' review of consultation-generated documentation, additional analysis, and production of multiple iterations of the model. The generic CHW logic model posits that optimal CHW performance is a function of high quality CHW programming, which is reinforced, sustained, and brought to scale by robust, high-performing health and community systems, both of which mobilize inputs and put in place processes needed to fully achieve performance objectives. Multiple contextual factors can influence CHW programming, system functioning, and CHW performance. The model is a novel contribution to current thinking about CHWs. It places CHW performance at the center of the discussion about CHW programming, recognizes the strengths and limitations of discrete, targeted programs, and is comprehensive, reflecting the current state of both scientific and tacit knowledge about support for improving CHW performance. The model is also a practical tool that offers guidance for continuous learning about what works. Despite the model's limitations and several challenges in translating the potential for learning into tangible learning, the CHW generic logic model provides a solid basis for exploring and testing a causal pathway to improved performance.

Environmental surveillance and monitoring the next frontier for pathway-based high throughput screening

EPA Science Inventory

In response to a proposed vision and strategy for toxicity testing in the 21st century nascent high throughput toxicology (HTT) programs have tested thousands of chemicals in hundreds of pathway-based biological assays. Although, to date, use of HTT data for safety assessment of ...

Alternative Pathways into University: Are Tertiary Preparation Programs a Viable Option?

ERIC Educational Resources Information Center

Chesters, Jenny; Rutter, Kerry; Nelson, Karen; Watson, Louis

2018-01-01

During the past three decades, the student populations of Australian universities have become more heterogeneous as the higher education sector expanded and new alternative entry pathways were established. Broadening access to university study and, therefore, to professional and semi-professional occupations, provides avenues for social mobility.…

Pathways to Success: Using Technologies To Reach Distant Learners.

ERIC Educational Resources Information Center

Annenberg/CPB Project, Washington, DC.

This report contains information on institutions that submitted proposals for integrating technology in education to the Annenberg/CPB (Corporation for Public Broadcasting) Project's New Pathways to a Degree program. It is noted that, although the 243 proposals received contained a number of innovative ideas about how to use technologies to…

Developmental Education in Arkansas: Practices, Costs, and a Model Approach

ERIC Educational Resources Information Center

Carroll, Rhonda; Kersh, Lily; Sullivan, Ellen; Fincher, Mark

2012-01-01

This paper examines the origins of developmental education and explores the way developmental education is administered at selected colleges in Arkansas. Finally, the paper focuses on a model Career Pathways Initiative program at University of Arkansas Community College-Morrilton. Career Pathways invigorates partnerships between colleges and…

Disruption of the vacuolar calcium-ATPases in Arabidopsis results in the activation of a salicylic acid-dependent programmed cell death pathway.

PubMed

Boursiac, Yann; Lee, Sang Min; Romanowsky, Shawn; Blank, Robert; Sladek, Chris; Chung, Woo Sik; Harper, Jeffrey F

2010-11-01

Calcium (Ca(2+)) signals regulate many aspects of plant development, including a programmed cell death pathway that protects plants from pathogens (hypersensitive response). Cytosolic Ca(2+) signals result from a combined action of Ca(2+) influx through channels and Ca(2+) efflux through pumps and cotransporters. Plants utilize calmodulin-activated Ca(2+) pumps (autoinhibited Ca(2+)-ATPase [ACA]) at the plasma membrane, endoplasmic reticulum, and vacuole. Here, we show that a double knockout mutation of the vacuolar Ca(2+) pumps ACA4 and ACA11 in Arabidopsis (Arabidopsis thaliana) results in a high frequency of hypersensitive response-like lesions. The appearance of macrolesions could be suppressed by growing plants with increased levels (greater than 15 mm) of various anions, providing a method for conditional suppression. By removing plants from a conditional suppression, lesion initials were found to originate primarily in leaf mesophyll cells, as detected by aniline blue staining. Initiation and spread of lesions could also be suppressed by disrupting the production or accumulation of salicylic acid (SA), as shown by combining aca4/11 mutations with a sid 2 (for salicylic acid induction-deficient2) mutation or expression of the SA degradation enzyme NahG. This indicates that the loss of the vacuolar Ca(2+) pumps by itself does not cause a catastrophic defect in ion homeostasis but rather potentiates the activation of a SA-dependent programmed cell death pathway. Together, these results provide evidence linking the activity of the vacuolar Ca(2+) pumps to the control of a SA-dependent programmed cell death pathway in plants.

N-of-1-pathways MixEnrich: advancing precision medicine via single-subject analysis in discovering dynamic changes of transcriptomes.

PubMed

Li, Qike; Schissler, A Grant; Gardeux, Vincent; Achour, Ikbel; Kenost, Colleen; Berghout, Joanne; Li, Haiquan; Zhang, Hao Helen; Lussier, Yves A

2017-05-24

Transcriptome analytic tools are commonly used across patient cohorts to develop drugs and predict clinical outcomes. However, as precision medicine pursues more accurate and individualized treatment decisions, these methods are not designed to address single-patient transcriptome analyses. We previously developed and validated the N-of-1-pathways framework using two methods, Wilcoxon and Mahalanobis Distance (MD), for personal transcriptome analysis derived from a pair of samples of a single patient. Although, both methods uncover concordantly dysregulated pathways, they are not designed to detect dysregulated pathways with up- and down-regulated genes (bidirectional dysregulation) that are ubiquitous in biological systems. We developed N-of-1-pathways MixEnrich, a mixture model followed by a gene set enrichment test, to uncover bidirectional and concordantly dysregulated pathways one patient at a time. We assess its accuracy in a comprehensive simulation study and in a RNA-Seq data analysis of head and neck squamous cell carcinomas (HNSCCs). In presence of bidirectionally dysregulated genes in the pathway or in presence of high background noise, MixEnrich substantially outperforms previous single-subject transcriptome analysis methods, both in the simulation study and the HNSCCs data analysis (ROC Curves; higher true positive rates; lower false positive rates). Bidirectional and concordant dysregulated pathways uncovered by MixEnrich in each patient largely overlapped with the quasi-gold standard compared to other single-subject and cohort-based transcriptome analyses. The greater performance of MixEnrich presents an advantage over previous methods to meet the promise of providing accurate personal transcriptome analysis to support precision medicine at point of care.

RaMP: A Comprehensive Relational Database of Metabolomics Pathways for Pathway Enrichment Analysis of Genes and Metabolites

PubMed Central

Zhang, Bofei; Hu, Senyang; Baskin, Elizabeth; Patt, Andrew; Siddiqui, Jalal K.

2018-01-01

The value of metabolomics in translational research is undeniable, and metabolomics data are increasingly generated in large cohorts. The functional interpretation of disease-associated metabolites though is difficult, and the biological mechanisms that underlie cell type or disease-specific metabolomics profiles are oftentimes unknown. To help fully exploit metabolomics data and to aid in its interpretation, analysis of metabolomics data with other complementary omics data, including transcriptomics, is helpful. To facilitate such analyses at a pathway level, we have developed RaMP (Relational database of Metabolomics Pathways), which combines biological pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, WikiPathways, and the Human Metabolome DataBase (HMDB). To the best of our knowledge, an off-the-shelf, public database that maps genes and metabolites to biochemical/disease pathways and can readily be integrated into other existing software is currently lacking. For consistent and comprehensive analysis, RaMP enables batch and complex queries (e.g., list all metabolites involved in glycolysis and lung cancer), can readily be integrated into pathway analysis tools, and supports pathway overrepresentation analysis given a list of genes and/or metabolites of interest. For usability, we have developed a RaMP R package (https://github.com/Mathelab/RaMP-DB), including a user-friendly RShiny web application, that supports basic simple and batch queries, pathway overrepresentation analysis given a list of genes or metabolites of interest, and network visualization of gene-metabolite relationships. The package also includes the raw database file (mysql dump), thereby providing a stand-alone downloadable framework for public use and integration with other tools. In addition, the Python code needed to recreate the database on another system is also publicly available (https://github.com/Mathelab/RaMP-BackEnd). Updates for databases in RaMP will be checked multiple times a year and RaMP will be updated accordingly. PMID:29470400

RaMP: A Comprehensive Relational Database of Metabolomics Pathways for Pathway Enrichment Analysis of Genes and Metabolites.

PubMed

Zhang, Bofei; Hu, Senyang; Baskin, Elizabeth; Patt, Andrew; Siddiqui, Jalal K; Mathé, Ewy A

2018-02-22

The value of metabolomics in translational research is undeniable, and metabolomics data are increasingly generated in large cohorts. The functional interpretation of disease-associated metabolites though is difficult, and the biological mechanisms that underlie cell type or disease-specific metabolomics profiles are oftentimes unknown. To help fully exploit metabolomics data and to aid in its interpretation, analysis of metabolomics data with other complementary omics data, including transcriptomics, is helpful. To facilitate such analyses at a pathway level, we have developed RaMP (Relational database of Metabolomics Pathways), which combines biological pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, WikiPathways, and the Human Metabolome DataBase (HMDB). To the best of our knowledge, an off-the-shelf, public database that maps genes and metabolites to biochemical/disease pathways and can readily be integrated into other existing software is currently lacking. For consistent and comprehensive analysis, RaMP enables batch and complex queries (e.g., list all metabolites involved in glycolysis and lung cancer), can readily be integrated into pathway analysis tools, and supports pathway overrepresentation analysis given a list of genes and/or metabolites of interest. For usability, we have developed a RaMP R package (https://github.com/Mathelab/RaMP-DB), including a user-friendly RShiny web application, that supports basic simple and batch queries, pathway overrepresentation analysis given a list of genes or metabolites of interest, and network visualization of gene-metabolite relationships. The package also includes the raw database file (mysql dump), thereby providing a stand-alone downloadable framework for public use and integration with other tools. In addition, the Python code needed to recreate the database on another system is also publicly available (https://github.com/Mathelab/RaMP-BackEnd). Updates for databases in RaMP will be checked multiple times a year and RaMP will be updated accordingly.

[Exploration of common biological pathways for attention deficit hyperactivity disorder and low birth weight].

PubMed

Xiang, Bo; Yu, Minglan; Liang, Xuemei; Lei, Wei; Huang, Chaohua; Chen, Jing; He, Wenying; Zhang, Tao; Li, Tao; Liu, Kezhi

2017-12-10

To explore common biological pathways for attention deficit hyperactivity disorder (ADHD) and low birth weight (LBW). Thei-Gsea4GwasV2 software was used to analyze the result of genome-wide association analysis (GWAS) for LBW (pathways were derived from Reactome), and nominally significant (P< 0.05, FDR< 0.25) pathways were tested for replication in ADHD.Significant pathways were analyzed with DAPPLE and Reatome FI software to identify genes involved in such pathways, with each cluster enriched with the gene ontology (GO). The Centiscape2.0 software was used to calculate the degree of genetic networks and the betweenness value to explore the core node (gene). Weighed gene co-expression network analysis (WGCNA) was then used to explore the co-expression of genes in these pathways.With gene expression data derived from BrainSpan, GO enrichment was carried out for each gene module. Eleven significant biological pathways was identified in association with LBW, among which two (Selenoamino acid metabolism and Diseases associated with glycosaminoglycan metabolism) were replicated during subsequent ADHD analysis. Network analysis of 130 genes in these pathways revealed that some of the sub-networksare related with morphology of cerebellum, development of hippocampus, and plasticity of synaptic structure. Upon co-expression network analysis, 120 genes passed the quality control and were found to express in 3 gene modules. These modules are mainly related to the regulation of synaptic structure and activity regulation. ADHD and LBW share some biological regulation processes. Anomalies of such proces sesmay predispose to ADHD.

Pathway analysis with next-generation sequencing data.

PubMed

Zhao, Jinying; Zhu, Yun; Boerwinkle, Eric; Xiong, Momiao

2015-04-01

Although pathway analysis methods have been developed and successfully applied to association studies of common variants, the statistical methods for pathway-based association analysis of rare variants have not been well developed. Many investigators observed highly inflated false-positive rates and low power in pathway-based tests of association of rare variants. The inflated false-positive rates and low true-positive rates of the current methods are mainly due to their lack of ability to account for gametic phase disequilibrium. To overcome these serious limitations, we develop a novel statistic that is based on the smoothed functional principal component analysis (SFPCA) for pathway association tests with next-generation sequencing data. The developed statistic has the ability to capture position-level variant information and account for gametic phase disequilibrium. By intensive simulations, we demonstrate that the SFPCA-based statistic for testing pathway association with either rare or common or both rare and common variants has the correct type 1 error rates. Also the power of the SFPCA-based statistic and 22 additional existing statistics are evaluated. We found that the SFPCA-based statistic has a much higher power than other existing statistics in all the scenarios considered. To further evaluate its performance, the SFPCA-based statistic is applied to pathway analysis of exome sequencing data in the early-onset myocardial infarction (EOMI) project. We identify three pathways significantly associated with EOMI after the Bonferroni correction. In addition, our preliminary results show that the SFPCA-based statistic has much smaller P-values to identify pathway association than other existing methods.

The Development of Dynamic Human Reliability Analysis Simulations for Inclusion in Risk Informed Safety Margin Characterization Frameworks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jeffrey C. Joe; Diego Mandelli; Ronald L. Boring

2015-07-01

The United States Department of Energy is sponsoring the Light Water Reactor Sustainability program, which has the overall objective of supporting the near-term and the extended operation of commercial nuclear power plants. One key research and development (R&D) area in this program is the Risk-Informed Safety Margin Characterization pathway, which combines probabilistic risk simulation with thermohydraulic simulation codes to define and manage safety margins. The R&D efforts to date, however, have not included robust simulations of human operators, and how the reliability of human performance or lack thereof (i.e., human errors) can affect risk-margins and plant performance. This paper describesmore » current and planned research efforts to address the absence of robust human reliability simulations and thereby increase the fidelity of simulated accident scenarios.« less

Tubaramure, a Food-Assisted Integrated Health and Nutrition Program in Burundi, Increases Maternal and Child Hemoglobin Concentrations and Reduces Anemia: A Theory-Based Cluster-Randomized Controlled Intervention Trial.

PubMed

Leroy, Jef L; Olney, Deanna; Ruel, Marie

2016-08-01

Despite their popularity, food-assisted maternal and child health and nutrition (MCHN) programs have not been evaluated rigorously, and evidence of their impacts on maternal and child outcomes is scant. This study estimated the impact of Tubaramure, a food-assisted MCHN program implemented by Catholic Relief Services and partners in eastern Burundi, on hemoglobin and anemia (primary outcome) in children aged 0-23.9 mo and their mothers and explored the impact pathways. The program targeted women and their children during their first 1000 d of life and included 1) food rations, 2) strengthening and promotion of the use of health services, and 3) behavior change communication. This was a cluster-randomized controlled study to assess program impact by using cluster fixed-effects double-difference models with repeated cross-sectional data (baseline and follow-up 2 y later). We explored impact pathways by estimating impact on intermediary factors addressed by Tubaramure that are known determinants of hemoglobin and anemia and by regressing hemoglobin and anemia on each determinant to assess the plausibility that the effect operated through each determinant. Hemoglobin decreased and anemia increased markedly from baseline to follow-up, but Tubaramure had a significant (P < 0.05) beneficial effect on both children [6.1 percentage points (pps)] and mothers who had given birth in the previous 3 mo (34.9 pps). The program also had significant (P < 0.05) impacts on factors along the hypothesized impact pathways: dietary diversity, consumption of iron-rich foods, morbidity, and fever for child hemoglobin and dietary diversity, consumption of iron-rich foods, and current bed-net use for maternal anemia. We showed, for the first time to our knowledge, that a food-assisted MCHN program had a positive impact on anemia and hemoglobin in both mothers and children. The plausible pathways identified highlight the importance of addressing multiple determinants of anemia. This trial was registered at clinicaltrials.gov as NCT01072279. © 2016 American Society for Nutrition.

The grapevine expression atlas reveals a deep transcriptome shift driving the entire plant into a maturation program.

PubMed

Fasoli, Marianna; Dal Santo, Silvia; Zenoni, Sara; Tornielli, Giovanni Battista; Farina, Lorenzo; Zamboni, Anita; Porceddu, Andrea; Venturini, Luca; Bicego, Manuele; Murino, Vittorio; Ferrarini, Alberto; Delledonne, Massimo; Pezzotti, Mario

2012-09-01

We developed a genome-wide transcriptomic atlas of grapevine (Vitis vinifera) based on 54 samples representing green and woody tissues and organs at different developmental stages as well as specialized tissues such as pollen and senescent leaves. Together, these samples expressed ∼91% of the predicted grapevine genes. Pollen and senescent leaves had unique transcriptomes reflecting their specialized functions and physiological status. However, microarray and RNA-seq analysis grouped all the other samples into two major classes based on maturity rather than organ identity, namely, the vegetative/green and mature/woody categories. This division represents a fundamental transcriptomic reprogramming during the maturation process and was highlighted by three statistical approaches identifying the transcriptional relationships among samples (correlation analysis), putative biomarkers (O2PLS-DA approach), and sets of strongly and consistently expressed genes that define groups (topics) of similar samples (biclustering analysis). Gene coexpression analysis indicated that the mature/woody developmental program results from the reiterative coactivation of pathways that are largely inactive in vegetative/green tissues, often involving the coregulation of clusters of neighboring genes and global regulation based on codon preference. This global transcriptomic reprogramming during maturation has not been observed in herbaceous annual species and may be a defining characteristic of perennial woody plants.

Developing Breast Cancer Program at Xavier; Genomic and Proteomic Analysis of Signaling Pathways Involved in Xenohormone and MEK5 Regulation of Breast Cancer

DTIC Science & Technology

2009-05-01

that upregulations of Vimentin (VIM), Heat shock 70 kDa protein 4 (HSPA4), Glutathione S-transferase P ( GSTP1 ), and Creatine kinase B-type (CKB), and...MEK5 versus MCF-7-VEC cells, vimentin (VIM), glutathione-S-transferase P ( GSTP1 ), and creatine kinase B-type (CKB) were upregulated, and keratin 8...with distinct proteomic changes (upregulation of VIM/vim, GSTP1 / gstp1 , and CKB/ckb; and downregulation of KRT8/krt8, KRT19/krt19, and GSTM3/gstm3). We

Developing Breast Cancer Program at Xavier; Genomic and Proteomic Analysis of Signaling Pathways Involved in Xenohormone and MEK5 Regulation of Breast Cancer

DTIC Science & Technology

2010-05-01

Heat shock 70 kDa protein 4 (HSPA4), Glutathione S-transferase P ( GSTP1 ), and Creatine kinase B-type (CKB), and downregulations of Keratin 8 (KRT8...VIM), glutathione-S-transferase P ( GSTP1 ), and creatine kinase B-type (CKB) were upregulated, and keratin 8 (KRT8), keratin 19 (KRT19) and...upregulation of VIM/vim, GSTP1 / gstp1 , and CKB/ckb; and downregulation of KRT8/krt8, KRT19/krt19, and GSTM3/gstm3). We further demonstrate that MEK5

Developing Breast Cancer Program at Xavier; Genomic and Proteomic Analysis of Signaling Pathways Involved in Xenohormone and MEK5 Regulation of Breast Cancer

DTIC Science & Technology

2006-05-01

34039 44 42 4.25 5.7 unnamed protein product A04 12653057 17.1 16 6 3.8 Neucleoside-diphosphate kinase 1, isoform b A05 54696638 27 25 6 6.5 Heat shock...student traiing because the students is not able to generate a product. Both Dr. Wang and Wiese feel that the most effective student training...have developed the following idea for a mini- proposal: The protein p23 is up regulated in cancer cells. It is a co-chaperone of heat shock protein

The New Drug Conditional Approval Process in China: Challenges and Opportunities.

PubMed

Yao, Xuefang; Ding, Jinxi; Liu, Yingfang; Li, Penghui

2017-05-01

Our aim was to characterize the newly established new drug conditional approval process in China and discuss the challenges and opportunities with respect to new drug research and development and registration. We examined the new approval program through literature review, law analysis, and data analysis. Data were derived from published materials, such as journal articles, government publications, press releases, and news articles, along with statistical data from INSIGHT-China Pharma Databases, the China Food and Drug Administration website, the Center for Drug Evaluation website, the US Food and Drug Administration website, and search results published by Google. Currently, there is a large backlog of New Drug Applications in China, mainly because of the prolonged review time at the China Food and Drug Administration, resulting in a lag in drug approvals. In 2015, the Chinese government implemented the drug review and registration system reform and tackled this issue through various approaches, such as setting up a drug review fee system, adjusting the drug registration classification, and establishing innovative review pathways, including the conditional approval process. In Europe and the United States, programs comparable to the conditional approval program in China have been well developed. The conditional approval program recently established in China is an expedited new drug approval process that is expected to affect new drug development at home and abroad and profoundly influence the public health and the pharmaceutical industry in China. Like any program in its initial stage, the conditional approval program is facing several challenges, including setting up a robust system, formatting new drug clinical research requirements, and improving the regulatory agency's function for drug review and approval. The program is expected to evolve and improve as part of the government mandate of the drug registration system reform. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

WDR26 in Advanced Breast Cancer: A Novel Regulator of the P13K/AKT Pathway

DTIC Science & Technology

2015-10-01

AWARD NUMBER: W81XWH-14-1-0539 TITLE: WDR26 in Advanced Breast Cancer: A Novel Regulator of the P13K/ AKT Pathway PRINCIPAL INVESTIGATOR...5a. CONTRACT NUMBER WDR26 in Advanced Breast Cancer: A Novel Regulator of the P13K/ AKT Pathway 5b. GRANT NUMBER W81XWH-14-1-0539 5c. PROGRAM...growth and metastasis via dysregulation of the PI3K/AKT2 pathway. (months 1-24) Major Goal 1: Assess how WDR26 regulates PI3K/ AKT signaling in

An instrument based on protection motivation theory to predict Chinese adolescents' intention to engage in protective behaviors against schistosomiasis.

PubMed

Xiao, Han; Peng, Minjin; Yan, Hong; Gao, Mengting; Li, Jingjing; Yu, Bin; Wu, Hanbo; Li, Shiyue

2016-01-01

Further advancement in schistosomiasis prevention requires new tools to assess protective motivation, and promote innovative intervention program. This study aimed to develop and evaluate an instrument developed based on the Protection Motivation Theory (PMT) to predict protective behavior intention against schistosomiasis among adolescents in China. We developed the Schistosomiasis PMT Scale based on two appraisal pathways of protective motivation- threat appraisal pathway and coping appraisal pathway. Data from a large sample of middle school students ( n  = 2238, 51 % male, mean age 13.13 ± 1.10) recruited in Hubei, China was used to evaluated the validity and reliability of the scale. The final scale contains 18 items with seven sub-constructs. Cronbach's Alpha coefficients for the entire instrument was 0.76, and for the seven sub-constructs of severity, vulnerability, intrinsic reward, extrinsic reward, response efficacy, self-efficacy and response cost was 0.56, 0.82, 0.75, 0.80, 0.90, 0.72 and 0.70, respectively. The construct validity analysis revealed that the one level 7 sub-constructs model fitted data well (GFI = 0.98, CFI = 0.98, RMSEA = 0.03, Chi-sq/df = 3.90, p  < 0.001). Predictive validity showed that both the PMT instrument score and the 7 sub-construct scores were significantly correlated with the intention engaged in protective behavior against schistosomiasis ( p  < 0.05). This study provides a reliable and valid tool to measure protective motivation in schistosomiasis prevention control. Further studies are needed to develop more effective intervention programs for schistosomiasis prevention.

Exercise training causes differential changes in gene expression in diaphragm arteries and 2A arterioles of obese rats.

PubMed

Laughlin, M Harold; Padilla, Jaume; Jenkins, Nathan T; Thorne, Pamela K; Martin, Jeffrey S; Rector, R Scott; Akter, Sadia; Davis, J Wade

2015-09-15

We employed next-generation, transcriptome-wide RNA sequencing (RNA-Seq) technology to assess the effects of two different exercise training protocols on transcriptional profiles in diaphragm second-order arterioles (D2a) and in the diaphragm feed artery (DFA) from Otsuka Long Evans Tokushima Fatty (OLETF) rats. Arterioles were isolated from the diaphragm of OLETF rats that underwent an endurance exercise training program (EX; n = 13), interval sprint training program (SPRINT; n = 14), or remained sedentary (Sed; n = 12). Our hypothesis was that exercise training would have similar effects on gene expression in the diaphragm and soleus muscle arterioles because diaphragm blood flow increases during exercise to a similar extent as in soleus. Results reveal that several canonical pathways that were significantly altered by exercise in limb skeletal muscles were not among the pathways significantly changed in the diaphragm arterioles including actin cytoskeleton signaling, role of NFAT in regulation of immune response, protein kinase A signaling, and protein ubiquitination pathway. EX training altered the expression of a smaller number of genes than did SPRINT in the DFA but induced a larger number of genes with altered expression in the D2a than did SPRINT. In fact, FDR differential expression analysis (FDR, 10%) indicated that only two genes exhibited altered expression in D2a of SPRINT rats. Very few of the genes that exhibited altered expression in the DFA or D2a were also altered in limb muscle arterioles. Finally, results indicate that the 2a arterioles of soleus muscle (S2a) from endurance-trained animals and the DFA of SPRINT animals exhibited the largest number of genes with altered expression.

Early nutritional programming affects liver transcriptome in diploid and triploid Atlantic salmon, Salmo salar.

PubMed

Vera, L M; Metochis, C; Taylor, J F; Clarkson, M; Skjærven, K H; Migaud, H; Tocher, D R

2017-11-17

To ensure sustainability of aquaculture, plant-based ingredients are being used in feeds to replace marine-derived products. However, plants contain secondary metabolites which can affect food intake and nutrient utilisation of fish. The application of nutritional stimuli during early development can induce long-term changes in animal physiology. Recently, we successfully used this approach to improve the utilisation of plant-based diets in diploid and triploid Atlantic salmon. In the present study we explored the molecular mechanisms occurring in the liver of salmon when challenged with a plant-based diet in order to determine the metabolic processes affected, and the effect of ploidy. Microarray analysis revealed that nutritional history had a major impact on the expression of genes. Key pathways of intermediary metabolism were up-regulated, including oxidative phosphorylation, pyruvate metabolism, TCA cycle, glycolysis and fatty acid metabolism. Other differentially expressed pathways affected by diet included protein processing in endoplasmic reticulum, RNA transport, endocytosis and purine metabolism. The interaction between diet and ploidy also had an effect on the hepatic transcriptome of salmon. The biological pathways with the highest number of genes affected by this interaction were related to gene transcription and translation, and cell processes such as proliferation, differentiation, communication and membrane trafficking. The present study revealed that nutritional programming induced changes in a large number of metabolic processes in Atlantic salmon, which may be associated with the improved fish performance and nutrient utilisation demonstrated previously. In addition, differences between diploid and triploid salmon were found, supporting recent data that indicate nutritional requirements of triploid salmon may differ from those of their diploid counterparts.

Does Online Learning Deliver? A Comparison of Student Teacher Outcomes from Candidates in Face-to-Face and Online Program Pathways

ERIC Educational Resources Information Center

Mollenkopf, Dawn; Vu, Phu; Crow, Sherry; Black, Chilene

2017-01-01

Although a growing number of students are accessing online learning programs, there are concerns about the quality of these programs. Multiple reports examined online program quality, but many of those studies had methodology and design issues that make it difficult to interpret the findings conclusively. This study attempted to address the…

Workforce Investments: State Strategies to Preserve Higher-Cost Career Education Programs in Community and Technical Colleges

ERIC Educational Resources Information Center

Shulock, Nancy; Lewis, Jodi; Tan, Connie

2013-01-01

In today's highly-skilled economy, rewarding career pathways are available to those who acquire technical skills by enrolling in certificate and associate degree programs in a community or technical college. Such programs are often more costly to offer than liberal arts and sciences programs that prepare students to transfer to four-year…

Implementing critical pathways and a multidisciplinary team approach to cardiovascular disease management.

PubMed

Peterson, Eric D; Albert, Nancy M; Amin, Alpesh; Patterson, J Herbert; Fonarow, Gregg C

2008-09-08

According to several medical registries, there is a need to improve the care of post-myocardial infarction (MI) patients, especially those with left ventricular dysfunction (LVD) and heart failure. This can potentially be achieved by implementing disease management programs, which include critical pathways, patient education, and multidisciplinary hospital teams. Currently, algorithms for critical pathways, including discharge processes, are lacking for post-MI LVD patients. Such schemes can increase the use of evidence-based medicines proved to reduce mortality. Educational programs are aimed at increasing patients' awareness of their condition, promoting medication compliance, and encouraging the adoption of healthy behaviors; such programs have been shown to be effective in improving outcomes of post-MI LVD patients. Reductions in all-cause hospitalizations and medical costs as well as improved survival rates have been observed when a multidisciplinary team (a nurse, a pharmacist, and a hospitalist) is engaged in patient care. In addition, the use of the "pay for performance" method, which can be advantageous for patients, physicians, and hospitals, may potentially improve the care of post-MI patients with LVD.

Enhanced Recovery after Urological Surgery: A Contemporary Systematic Review of Outcomes, Key Elements, and Research Needs.

PubMed

Azhar, Raed A; Bochner, Bernard; Catto, James; Goh, Alvin C; Kelly, John; Patel, Hiten D; Pruthi, Raj S; Thalmann, George N; Desai, Mihir

2016-07-01

Enhanced Recovery after Surgery (ERAS) programs are multimodal care pathways that aim to decrease intra-operative blood loss, decrease postoperative complications, and reduce recovery times. To overview the use and key elements of ERAS pathways, and define needs for future clinical trials. A comprehensive systematic MEDLINE search was performed for English language reports published before May 2015 using the terms "postoperative period," "postoperative care," "enhanced recovery after surgery," "enhanced recovery," "accelerated recovery," "fast track recovery," "recovery program," "recovery pathway", "ERAS," and "urology" or "cystectomy" or "urologic surgery." We identified 18 eligible articles. Patient counseling, physical conditioning, avoiding excessive alcohol and smoking, and good nutrition appeared to protect against postoperative complications. Fasting from solid food for only 6h and perioperative liquid-carbohydrate loading up to 2h prior to surgery appeared to be safe and reduced recovery times. Restricted, balanced, and goal-directed fluid replacement is effective when individualized, depending on patient morbidity and surgical procedure. Decreased intraoperative blood loss may be achieved by several measures. Deep vein thrombosis prophylaxis, antibiotic prophylaxis, and thermoregulation were found to help reduce postsurgical complications, as was a multimodal approach to postoperative nausea, vomiting, and analgesia. Chewing gum, prokinetic agents, oral laxatives, and an early resumption to normal diet appear to aid faster return to normal bowel function. Further studies should compare anesthetic protocols, refine analgesia, and evaluate the importance of robot-assisted surgery and the need/timing for drains and catheters. ERAS regimens are multidisciplinary, multimodal pathways that optimize postoperative recovery. This review provides an overview of the use and key elements of Enhanced Recovery after Surgery programs, which are multimodal, multidisciplinary care pathways that aim to optimize postoperative recovery. Additional conclusions include identifying effective procedures within Enhanced Recovery after Surgery programs and defining needs for future clinical trials. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Fifth pathway in New Jersey. House officer preparatory course for US foreign medical graduates.

PubMed

McGrough, W E

1975-06-09

The Fifth Channel in New Jersey is a Fifth Pathway program for US foreign medical graduates. In its third year, 83 percent of its 81 graduates are house officers at 18 US medical school-affiliated hospitals. Performance as house officers is characterized as competitive with peers, including US graduates. Positive attitudes toward work load, fellow workers, and patients compared with those of fellow house staff are noted. Quality of performance as house officers correlates most strongly with the change in mean scores of two batteries of clinical National Board examinations taken during the Fifth Pathway and less strongly with mean scores of single batteries of National Boards, Intelligence quotient, Educational Council for Foreign Medical Graduates (ECFMG) examination, ang age. Recommendations concerning the implementing of similar programs in other states are presented.

Functional Analysis of OMICs Data and Small Molecule Compounds in an Integrated "Knowledge-Based" Platform.

PubMed

Dubovenko, Alexey; Nikolsky, Yuri; Rakhmatulin, Eugene; Nikolskaya, Tatiana

2017-01-01

Analysis of NGS and other sequencing data, gene variants, gene expression, proteomics, and other high-throughput (OMICs) data is challenging because of its biological complexity and high level of technical and biological noise. One way to deal with both problems is to perform analysis with a high fidelity annotated knowledgebase of protein interactions, pathways, and functional ontologies. This knowledgebase has to be structured in a computer-readable format and must include software tools for managing experimental data, analysis, and reporting. Here, we present MetaCore™ and Key Pathway Advisor (KPA), an integrated platform for functional data analysis. On the content side, MetaCore and KPA encompass a comprehensive database of molecular interactions of different types, pathways, network models, and ten functional ontologies covering human, mouse, and rat genes. The analytical toolkit includes tools for gene/protein list enrichment analysis, statistical "interactome" tool for the identification of over- and under-connected proteins in the dataset, and a biological network analysis module made up of network generation algorithms and filters. The suite also features Advanced Search, an application for combinatorial search of the database content, as well as a Java-based tool called Pathway Map Creator for drawing and editing custom pathway maps. Applications of MetaCore and KPA include molecular mode of action of disease research, identification of potential biomarkers and drug targets, pathway hypothesis generation, analysis of biological effects for novel small molecule compounds and clinical applications (analysis of large cohorts of patients, and translational and personalized medicine).

Health service resilience in Yobe state, Nigeria in the context of the Boko Haram insurgency: a systems dynamics analysis using group model building.

PubMed

Ager, Alastair K; Lembani, Martina; Mohammed, Abdulaziz; Mohammed Ashir, Garba; Abdulwahab, Ahmad; de Pinho, Helen; Delobelle, Peter; Zarowsky, Christina

2015-01-01

Yobe State has faced severe disruption of its health service as a result of the Boko Haram insurgency. A systems dynamics analysis was conducted to identify key pathways of threat to provision and emerging pathways of response and adaptation. Structured interviews were conducted with 39 stakeholders from three local government areas selected to represent the diversity of conflict experience across the state: Damaturu, Fune and Nguru, and with four officers of the PRRINN-MNCH program providing technical assistance for primary care development in the state. A group model building session was convened with 11 senior stakeholders, which used participatory scripts to review thematic analysis of interviews and develop a preliminary systems model linking identified variables. Population migration and transport restrictions have substantially impacted access to health provision. The human resource for health capability of the state has been severely diminished through the outward migration of (especially non-indigenous) health workers and the suspension of programmes providing external technical assistance. The political will of the Yobe State government to strengthen health provision - through lifting a moratorium on recruitment and providing incentives for retention and support of staff - has supported a recovery of health systems functioning. Policies of free-drug provision and decentralized drug supply appear to have been protective of the operation of the health system. Community resources and cohesion have been significant assets in combatting the impacts of the insurgency on service utilization and quality. Staff commitment and motivation - particularly amongst staff indigenous to the state - has protected health care quality and enabled flexibility of human resource deployment. A systems analysis using participatory group model building provided a mechanism to identify key pathways of threat and adaptation with regard to health service functioning. Generalizable systems characteristics supportive of resilience are suggested, and linked to wider discussion of the role of factors such as diversity, self-regulation and integration.

The Role of Vitamin D in the Transcriptional Program of Human Pregnancy

PubMed Central

Al-Garawi, Amal; Carey, Vincent J.; Chhabra, Divya; Morrow, Jarrett; Lasky-Su, Jessica; Qiu, Weiliang; Laranjo, Nancy; Litonjua, Augusto A.; Weiss, Scott T.

2016-01-01

Background Patterns of gene expression of human pregnancy are poorly understood. In a trial of vitamin D supplementation in pregnant women, peripheral blood transcriptomes were measured longitudinally on 30 women and used to characterize gene co-expression networks. Objective Studies suggest that increased maternal Vitamin D levels may reduce the risk of asthma in early life, yet the underlying mechanisms have not been examined. In this study, we used a network-based approach to examine changes in gene expression profiles during the course of normal pregnancy and evaluated their association with maternal Vitamin D levels. Design The VDAART study is a randomized clinical trial of vitamin D supplementation in pregnancy for reduction of pediatric asthma risk. The trial enrolled 881 women at 10–18 weeks of gestation. Longitudinal gene expression measures were obtained on thirty pregnant women, using RNA isolated from peripheral blood samples obtained in the first and third trimesters. Differentially expressed genes were identified using significance of analysis of microarrays (SAM), and clustered using a weighted gene co-expression network analysis (WGCNA). Gene-set enrichment was performed to identify major biological pathways. Results Comparison of transcriptional profiles between first and third trimesters of pregnancy identified 5839 significantly differentially expressed genes (FDR<0.05). Weighted gene co-expression network analysis clustered these transcripts into 14 co-expression modules of which two showed significant correlation with maternal vitamin D levels. Pathway analysis of these two modules revealed genes enriched in immune defense pathways and extracellular matrix reorganization as well as genes enriched in notch signaling and transcription factor networks. Conclusion Our data show that gene expression profiles of healthy pregnant women change during the course of pregnancy and suggest that maternal Vitamin D levels influence transcriptional profiles. These alterations of the maternal transcriptome may contribute to fetal immune imprinting and reduce allergic sensitization in early life. Trial Registration clinicaltrials.gov NCT00920621 PMID:27711190

The 2012 CASPER Physics Circus

NASA Astrophysics Data System (ADS)

Carmona Reyes, Jorge; Land-Zandstra, Anne; Cheng, Joyce; Douglass, Angela; Harris, Brandon; Zhang, Zhuanhao; Chen, Mudi; Matthews, Lorin; Hyde, Truell

2012-10-01

The CASPER Physics Circus is one component of a CASPER ongoing educational outreach initiative known as the CASPER Seamless Pathway. The Physics Circus is funded by the United States Department of Education and is designed to increase interest in, engagement with, and understanding of science, technology, engineering and mathematics (STEM) within students in grades 6 through 12. The program's material and curriculum is aligned with both TEKS (Texas Essentials Knowledge and Skills) and National Science and Mathematics Standards, with its components (theatre, hands-on exhibitions, game show, professional development and curriculum) reinforcing these goals in a creative and entertaining format. Pre- and post-assessments measuring both content understanding and attitude towards science were conducted for a representative sample of the cohort and the analyzed data will be presented. The role the Circus plays within CASPER's Seamless Pathway will also be discussed along with other current CASPER programs including its High School Scholars program, CASPER's Interns program and CASPER NSF funded REU/RET programs for college undergraduates and K-12 teachers.

Translating evidence based violence and drug use prevention to obesity prevention: development and construction of the pathways program.

PubMed

Sakuma, Kari-Lyn K; Riggs, Nathaniel R; Pentz, Mary Ann

2012-04-01

Effective school-based obesity prevention programs are needed to prevent and reduce the growing obesity risk among youth. Utilizing the evidence-rich areas of violence and substance use prevention, translation science may provide an efficient means for developing curricula across multiple health behaviors. This paper introduces Pathways to Health, a school-based obesity prevention program that was developed by translating from evidence-based violence and drug use prevention programs, Promoting Alternative THinking Strategies and the Midwestern Prevention Project STAR (STAR). We illustrate how a hypothesized underlying behavior change mechanism in two domains of risk behavior, violence and substance use, can be applied to obesity prevention. A 4-step translational process is provided and may be relevant for use in developing other curricula to address multiple health risk behaviors. Practical application and decision points are also provided.

Identifying Desistance Pathways in a Higher Education Program for Formerly Incarcerated Individuals.

PubMed

Runell, Lindsey Livingston

2017-06-01

The link between education and crime is a topic that requires special attention with respect to the converging influence of individual, social, and environmental factors. This article will investigate the educational pathways followed by students in a higher education program for formerly incarcerated individuals at a large state university in the northeastern United States. Specifically, it will explore the extent to which their postincarceration educational experiences served as a "hook for change" and also related impediments tied to street influences, financial constraints, stigma, academic and social development. Data were collected from a sample of 34 current and former students in the program, each of whom participated in a face-to-face interview. The higher education program played a key role in propelling the desistance process for research participants. This article will discuss how personal agency can be sustained through participation in higher education post release and the implications for future research on crime avoidance.

Translating evidence based violence and drug use prevention to obesity prevention: development and construction of the Pathways program

PubMed Central

Sakuma, Kari-Lyn K.; Riggs, Nathaniel R.; Pentz, Mary Ann

2012-01-01

Effective school-based obesity prevention programs are needed to prevent and reduce the growing obesity risk among youth. Utilizing the evidence-rich areas of violence and substance use prevention, translation science may provide an efficient means for developing curricula across multiple health behaviors. This paper introduces Pathways to Health, a school-based obesity prevention program that was developed by translating from evidence-based violence and drug use prevention programs, Promoting Alternative THinking Strategies and the Midwestern Prevention Project STAR (STAR). We illustrate how a hypothesized underlying behavior change mechanism in two domains of risk behavior, violence and substance use, can be applied to obesity prevention. A 4-step translational process is provided and may be relevant for use in developing other curricula to address multiple health risk behaviors. Practical application and decision points are also provided. PMID:21987475

A Powerful Procedure for Pathway-Based Meta-analysis Using Summary Statistics Identifies 43 Pathways Associated with Type II Diabetes in European Populations.

PubMed

Zhang, Han; Wheeler, William; Hyland, Paula L; Yang, Yifan; Shi, Jianxin; Chatterjee, Nilanjan; Yu, Kai

2016-06-01

Meta-analysis of multiple genome-wide association studies (GWAS) has become an effective approach for detecting single nucleotide polymorphism (SNP) associations with complex traits. However, it is difficult to integrate the readily accessible SNP-level summary statistics from a meta-analysis into more powerful multi-marker testing procedures, which generally require individual-level genetic data. We developed a general procedure called Summary based Adaptive Rank Truncated Product (sARTP) for conducting gene and pathway meta-analysis that uses only SNP-level summary statistics in combination with genotype correlation estimated from a panel of individual-level genetic data. We demonstrated the validity and power advantage of sARTP through empirical and simulated data. We conducted a comprehensive pathway-based meta-analysis with sARTP on type 2 diabetes (T2D) by integrating SNP-level summary statistics from two large studies consisting of 19,809 T2D cases and 111,181 controls with European ancestry. Among 4,713 candidate pathways from which genes in neighborhoods of 170 GWAS established T2D loci were excluded, we detected 43 T2D globally significant pathways (with Bonferroni corrected p-values < 0.05), which included the insulin signaling pathway and T2D pathway defined by KEGG, as well as the pathways defined according to specific gene expression patterns on pancreatic adenocarcinoma, hepatocellular carcinoma, and bladder carcinoma. Using summary data from 8 eastern Asian T2D GWAS with 6,952 cases and 11,865 controls, we showed 7 out of the 43 pathways identified in European populations remained to be significant in eastern Asians at the false discovery rate of 0.1. We created an R package and a web-based tool for sARTP with the capability to analyze pathways with thousands of genes and tens of thousands of SNPs.

A Powerful Procedure for Pathway-Based Meta-analysis Using Summary Statistics Identifies 43 Pathways Associated with Type II Diabetes in European Populations

PubMed Central

Zhang, Han; Wheeler, William; Hyland, Paula L.; Yang, Yifan; Shi, Jianxin; Chatterjee, Nilanjan; Yu, Kai

2016-01-01

Meta-analysis of multiple genome-wide association studies (GWAS) has become an effective approach for detecting single nucleotide polymorphism (SNP) associations with complex traits. However, it is difficult to integrate the readily accessible SNP-level summary statistics from a meta-analysis into more powerful multi-marker testing procedures, which generally require individual-level genetic data. We developed a general procedure called Summary based Adaptive Rank Truncated Product (sARTP) for conducting gene and pathway meta-analysis that uses only SNP-level summary statistics in combination with genotype correlation estimated from a panel of individual-level genetic data. We demonstrated the validity and power advantage of sARTP through empirical and simulated data. We conducted a comprehensive pathway-based meta-analysis with sARTP on type 2 diabetes (T2D) by integrating SNP-level summary statistics from two large studies consisting of 19,809 T2D cases and 111,181 controls with European ancestry. Among 4,713 candidate pathways from which genes in neighborhoods of 170 GWAS established T2D loci were excluded, we detected 43 T2D globally significant pathways (with Bonferroni corrected p-values < 0.05), which included the insulin signaling pathway and T2D pathway defined by KEGG, as well as the pathways defined according to specific gene expression patterns on pancreatic adenocarcinoma, hepatocellular carcinoma, and bladder carcinoma. Using summary data from 8 eastern Asian T2D GWAS with 6,952 cases and 11,865 controls, we showed 7 out of the 43 pathways identified in European populations remained to be significant in eastern Asians at the false discovery rate of 0.1. We created an R package and a web-based tool for sARTP with the capability to analyze pathways with thousands of genes and tens of thousands of SNPs. PMID:27362418

TabPath: interactive tables for metabolic pathway analysis.

PubMed

Moraes, Lauro Ângelo Gonçalves de; Felestrino, Érica Barbosa; Assis, Renata de Almeida Barbosa; Matos, Diogo; Lima, Joubert de Castro; Lima, Leandro de Araújo; Almeida, Nalvo Franco; Setubal, João Carlos; Garcia, Camila Carrião Machado; Moreira, Leandro Marcio

2018-03-15

Information about metabolic pathways in a comparative context is one of the most powerful tool to help the understanding of genome-based differences in phenotypes among organisms. Although several platforms exist that provide a wealth of information on metabolic pathways of diverse organisms, the comparison among organisms using metabolic pathways is still a difficult task. We present TabPath (Tables for Metabolic Pathway), a web-based tool to facilitate comparison of metabolic pathways in genomes based on KEGG. From a selection of pathways and genomes of interest on the menu, TabPath generates user-friendly tables that facilitate analysis of variations in metabolism among the selected organisms. TabPath is available at http://200.239.132.160:8686. lmmorei@gmail.com.

Rapid Evolution of piRNA Pathway in the Teleost Fish: Implication for an Adaptation to Transposon Diversity

PubMed Central

Yi, Minhan; Chen, Feng; Luo, Majing; Cheng, Yibin; Zhao, Huabin; Cheng, Hanhua; Zhou, Rongjia

2014-01-01

The Piwi-interacting RNA (piRNA) pathway is responsible for germline specification, gametogenesis, transposon silencing, and genome integrity. Transposable elements can disrupt genome and its functions. However, piRNA pathway evolution and its adaptation to transposon diversity in the teleost fish remain unknown. This article unveils evolutionary scene of piRNA pathway and its association with diverse transposons by systematically comparative analysis on diverse teleost fish genomes. Selective pressure analysis on piRNA pathway and miRNA/siRNA (microRNA/small interfering RNA) pathway genes between teleosts and mammals showed an accelerated evolution of piRNA pathway genes in the teleost lineages, and positive selection on functional PAZ (Piwi/Ago/Zwille) and Tudor domains involved in the Piwi–piRNA/Tudor interaction, suggesting that the amino acid substitutions are adaptive to their functions in piRNA pathway in the teleost fish species. Notably five piRNA pathway genes evolved faster in the swamp eel, a kind of protogynous hermaphrodite fish, than the other teleosts, indicating a differential evolution of piRNA pathway between the swamp eel and other gonochoristic fishes. In addition, genome-wide analysis showed higher diversity of transposons in the teleost fish species compared with mammals. Our results suggest that rapidly evolved piRNA pathway in the teleost fish is likely to be involved in the adaption to transposon diversity. PMID:24846630

Meta-analysis of human gene expression in response to Mycobacterium tuberculosis infection reveals potential therapeutic targets.

PubMed

Wang, Zhang; Arat, Seda; Magid-Slav, Michal; Brown, James R

2018-01-10

With the global emergence of multi-drug resistant strains of Mycobacterium tuberculosis, new strategies to treat tuberculosis are urgently needed such as therapeutics targeting potential human host factors. Here we performed a statistical meta-analysis of human gene expression in response to both latent and active pulmonary tuberculosis infections from nine published datasets. We found 1655 genes that were significantly differentially expressed during active tuberculosis infection. In contrast, no gene was significant for latent tuberculosis. Pathway enrichment analysis identified 90 significant canonical human pathways, including several pathways more commonly related to non-infectious diseases such as the LRRK2 pathway in Parkinson's disease, and PD-1/PD-L1 signaling pathway important for new immuno-oncology therapies. The analysis of human genome-wide association studies datasets revealed tuberculosis-associated genetic variants proximal to several genes in major histocompatibility complex for antigen presentation. We propose several new targets and drug-repurposing opportunities including intravenous immunoglobulin, ion-channel blockers and cancer immuno-therapeutics for development as combination therapeutics with anti-mycobacterial agents. Our meta-analysis provides novel insights into host genes and pathways important for tuberculosis and brings forth potential drug repurposing opportunities for host-directed therapies.

Critical radionuclide/critical pathway analysis for the U.S. Department of Energy's Savannah River Site.

PubMed

Jannik, G T

1999-06-01

Many different radionuclides have been released to the environment from the Savannah River Site (SRS) during the facility's operational history. However, as shown by this analysis, only a small number of the released radionuclides have been significant contributors to potential doses and risks to off-site people. This article documents the radiological critical contaminant/critical pathway analysis performed for SRS. If site missions and operations remain constant over the next 30 years, only tritium oxide releases are projected to exceed a maximally exposed individual (MEI) risk of 1.0E-06 for either the airborne or liquid pathways. The critical exposure pathways associated with site airborne releases are inhalation and vegetation consumption, whereas the critical exposure pathways associated with liquid releases are drinking water and fish consumption. For the SRS-specific, nontypical exposure pathways (i.e., recreational fishing and deer and hog hunting), cesium-137 is the critical radionuclide.

Maternal fructose-intake-induced renal programming in adult male offspring.

PubMed

Tain, You-Lin; Wu, Kay L H; Lee, Wei-Chia; Leu, Steve; Chan, Julie Y H

2015-06-01

Nutrition in pregnancy can elicit long-term effects on the health of offspring. Although fructose consumption has increased globally and is linked to metabolic syndrome, little is known about the long-term effects of maternal high-fructose (HF) exposure during gestation and lactation, especially on renal programming. We examined potential key genes and pathways that are associated with HF-induced renal programming using whole-genome RNA next-generation sequencing (NGS) to quantify the abundance of RNA transcripts in kidneys from 1-day-, 3-week-, and 3-month-old male offspring. Pregnant Sprague-Dawley rats received regular chow or chow supplemented with HF (60% diet by weight) during the entire period of pregnancy and lactation. Male offspring exhibited programmed hypertension at 3 months of age. Maternal HF intake modified over 200 renal transcripts from nephrogenesis stage to adulthood. We observed that 20 differentially expressed genes identified in 1-day-old kidney are related to regulation of blood pressure. Among them, Hmox1, Bdkrb2, Adra2b, Ptgs2, Col1a2 and Tbxa2r are associated with endothelium-derived hyperpolarizing factor (EDHF). NGS also identified genes in arachidonic acid metabolism (Cyp2c23, Hpgds, Ptgds and Ptges) that may be potential key genes/pathways contributing to renal programming and hypertension. Collectively, our NGS data suggest that maternal HF intake elicits a defective adaptation of interrelated EDHFs during nephrogenesis which may lead to renal programming and hypertension in later life. Moreover, our results highlight genes and pathways involved in renal programming as potential targets for therapeutic approaches to prevent metabolic-syndrome-related comorbidities in children with HF exposure in early life. Copyright © 2015 Elsevier Inc. All rights reserved.

Establishment of an effective acute stroke telemedicine program for Australia: protocol for the Victorian Stroke Telemedicine project.

PubMed

Cadilhac, Dominique A; Moloczij, Natasha; Denisenko, Sonia; Dewey, Helen; Disler, Peter; Winzar, Bruce; Mosley, Ian; Donnan, Geoffrey A; Bladin, Christopher

2014-02-01

Urgent treatment of acute stroke in rural Australia is problematic partly because of limited access to medical specialists. Utilization of telemedicine could improve delivery of acute stroke treatments in rural communities. The study aims to demonstrate enhanced clinical decision making for use of thrombolysis within 4·5 h of ischemic stroke symptom onset in a rural setting using a telemedicine specialist support model. A formative program evaluation research design was used. The Victorian Stroke Telemedicine program was developed and will be evaluated over five stages to ensure successful implementation. The phases include: (a) preimplementation phase to establish the Victorian Stroke Telemedicine program including the clinical pathway, data collection tools, and technology processes; (b) pilot clinical application phase to test the pathway in up to 10 patients; (c) modification phase to refine the program; (d) full clinical implementation phase where the program is maintained for one-year; and (e) a sustainability phase to assess project outcomes over five-years. Qualitative (clinician interviews) and quantitative data (patient, clinician, costs, and technology processes) are collected in each phase. The primary outcome is to achieve a minimum 10% absolute increase in eligible patients treated with thrombolysis. Secondary outcomes are utilization of the telestroke pathway and improvements in processes of stroke care (e.g., time to brain scan). We will report door to telemedicine consultation time, length of telemedicine consultation, clinical utility and acceptability from the perspective of clinicians, and 90-day patient outcomes. This research will provide evidence for an effective telestroke program for use in regional Australian hospitals. © 2013 The Authors. International Journal of Stroke © 2013 World Stroke Organization.

Pathways to Commercial Success. Technologies and Products Supported by the Fuel Cell Technologies Program - 2012

DOE Office of Scientific and Technical Information (OSTI.GOV)

none,

This FY 2012 report updates the results of an effort to identify and characterize commercial and near-commercial (emerging) technologies and products that benefited from the support of the Fuel Cell Technologies Program and its predecessor programs within DOE's Office of Energy Efficiency and Renewable Energy.

Pathways to Commercial Success. Technologies and Products Supported by the Fuel Cell Technologies Program

DOE Office of Scientific and Technical Information (OSTI.GOV)

none,

This FY 2011 report updates the results of an effort to identify and characterize commercial and near-commercial (emerging) technologies and products that benefited from the support of the Fuel Cell Technologies Program and its predecessor programs within DOE's Office of Energy Efficiency and Renewable Energy.

Guided Pathways to Careers: Four Dimensions of Structure in Community College Career-Technical Programs

ERIC Educational Resources Information Center

Van Noy, Michelle; Trimble, Madeline; Jenkins, Davis; Barnett, Elisabeth; Wachen, John

2016-01-01

Objective: Some have hypothesized that community college programs are not sufficiently structured to support student success and that students would benefit from more highly structured programs. This study examines the specific ways that structure is expressed in policy and practice at representative community colleges. Method: Using data obtained…

Pathways to Information Literacy: An Information Literacy Skills Program for B.S. Nursing Students.

ERIC Educational Resources Information Center

Fox, Lynne M.; And Others

A joint program of instruction was created between the University of Northern Colorado's Michener Library and School of Nursing. This expanded bibliographic instruction program was based on a proposal that outlined the need for information literacy instruction in nursing education, enumerated the possible benefits of such instruction to students…

An Exploration of Factors Associated with Student Attrition and Success in Enabling Programs

ERIC Educational Resources Information Center

Morison, Anthony; Cowley, Kym

2017-01-01

University-based enabling programs (EPs) provide a tertiary pathway for up to twenty percent of undergraduate enrolments at Australian universities. Attrition from these programs and the resulting costs to students, universities and society at large is an important issue deserving research attention. This research project aimed to investigate the…

Aligning Biochemistry to the Interests of Biology Students Using Haloperoxidase to Illustrate Reactions of Environmental and Biomedical Importance

ERIC Educational Resources Information Center

Jervis, Les; Jervis, Loretta M.; Giovannelli, Donato

2005-01-01

Undergraduate degree programs in the biosciences almost always include elements of biochemistry. In the United Kingdom, biosciences programs often have optional pathways to accommodate students of diverse interests. These programs rarely require students to demonstrate any school-level chemistry knowledge, and many students find biochemistry…

Pathways to College Access and Success

ERIC Educational Resources Information Center

Journal for Vocational Special Needs Education, 2006

2006-01-01

This report provides an in-depth look at five different programs, all of which currently, or are making efforts to, include a broad range of students. The five Credit-Based Transition Programs (CBTPs) studied are located in five states--California, Iowa, Minnesota, New York and Texas--and included two dual enrollment programs (one with a career…

A Community-Based Early Intervention Program for Toddlers with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Rollins, Pamela Rosenthal; Campbell, Michelle; Hoffman, Renee Thibodeau; Self, Kayli

2016-01-01

This study examined Pathways Early Autism Intervention, a community-based, parent-mediated, intensive behavioral and developmental intervention program for children with autism spectrum disorders that could be used as a model for state-funded early intervention programs. A single-subject, multiple-baseline, across-participants design was used.…

In Pursuit of Teacher Quality: Three Models of Success.

ERIC Educational Resources Information Center

Dandy, Evelyn; O'Dell, Sandra; McKinney, Marilyn; Perkins, Peggy G.; Miller, Susan Peterson; Reiman, Alan; Peace, Sandra DeAngelis; Williams, Doris Terry; Duncan, JoAnn Hines

This document is comprised of three papers by various authors, summarizing three different models of programs that successfully promote teacher quality that were introduced at the National Conference on Teacher Quality in January 2000, hosted by the U.S. Department of Education. The first program described, the Pathways to Teaching Program of…

Pathways to Success; A Resource Manual for the Dissemination of Successful Educational Programs.

ERIC Educational Resources Information Center

Soper, Dorothy

This manual is designed to describe and disseminate information about innovative New Jersey educational programs that have been validated by the standards and guidelines of the United States Office of Education as successful, cost effective, and exportable. Chapter 1 contains an overview of the development process for educational programs and…

Civic Engagement: A Pathway to Service and Learning

ERIC Educational Resources Information Center

Garcia, Rudy

2004-01-01

This article features a service learning program at Albuquerque TVI Community College which provides hands-on civic education to its students. The Service Learning Program began in 1994 with a $5,000 grant from the American Association of Community Colleges (AACC). The success of the program provided for the development of the Department of…

Fine-Tuning Summer Research Programs to Promote Underrepresented Students' Persistence in the STEM Pathway

ERIC Educational Resources Information Center

Ghee, Medeva; Keels, Micere; Collins, Deborah; Neal-Spence, Cynthia; Baker, Earnestine

2016-01-01

Although the importance of undergraduate research experiences in preparing students for graduate study and research careers is well documented, specific examination of program components is needed to assess the impact of these programs on underrepresented (UR) students. The Leadership Alliance, a consortium of leading PhD-granting and…

Deregulation upon DNA damage revealed by joint analysis of context-specific perturbation data

PubMed Central

2011-01-01

Background Deregulation between two different cell populations manifests itself in changing gene expression patterns and changing regulatory interactions. Accumulating knowledge about biological networks creates an opportunity to study these changes in their cellular context. Results We analyze re-wiring of regulatory networks based on cell population-specific perturbation data and knowledge about signaling pathways and their target genes. We quantify deregulation by merging regulatory signal from the two cell populations into one score. This joint approach, called JODA, proves advantageous over separate analysis of the cell populations and analysis without incorporation of knowledge. JODA is implemented and freely available in a Bioconductor package 'joda'. Conclusions Using JODA, we show wide-spread re-wiring of gene regulatory networks upon neocarzinostatin-induced DNA damage in Human cells. We recover 645 deregulated genes in thirteen functional clusters performing the rich program of response to damage. We find that the clusters contain many previously characterized neocarzinostatin target genes. We investigate connectivity between those genes, explaining their cooperation in performing the common functions. We review genes with the most extreme deregulation scores, reporting their involvement in response to DNA damage. Finally, we investigate the indirect impact of the ATM pathway on the deregulated genes, and build a hypothetical hierarchy of direct regulation. These results prove that JODA is a step forward to a systems level, mechanistic understanding of changes in gene regulation between different cell populations. PMID:21693013

Deregulation upon DNA damage revealed by joint analysis of context-specific perturbation data.

PubMed

Szczurek, Ewa; Markowetz, Florian; Gat-Viks, Irit; Biecek, Przemysław; Tiuryn, Jerzy; Vingron, Martin

2011-06-21

Deregulation between two different cell populations manifests itself in changing gene expression patterns and changing regulatory interactions. Accumulating knowledge about biological networks creates an opportunity to study these changes in their cellular context. We analyze re-wiring of regulatory networks based on cell population-specific perturbation data and knowledge about signaling pathways and their target genes. We quantify deregulation by merging regulatory signal from the two cell populations into one score. This joint approach, called JODA, proves advantageous over separate analysis of the cell populations and analysis without incorporation of knowledge. JODA is implemented and freely available in a Bioconductor package 'joda'. Using JODA, we show wide-spread re-wiring of gene regulatory networks upon neocarzinostatin-induced DNA damage in Human cells. We recover 645 deregulated genes in thirteen functional clusters performing the rich program of response to damage. We find that the clusters contain many previously characterized neocarzinostatin target genes. We investigate connectivity between those genes, explaining their cooperation in performing the common functions. We review genes with the most extreme deregulation scores, reporting their involvement in response to DNA damage. Finally, we investigate the indirect impact of the ATM pathway on the deregulated genes, and build a hypothetical hierarchy of direct regulation. These results prove that JODA is a step forward to a systems level, mechanistic understanding of changes in gene regulation between different cell populations.

Transcriptomic study of the toxic mechanism triggered by beauvericin in Jurkat cells.

PubMed

Escrivá, L; Jennen, D; Caiment, F; Manyes, L

2018-03-01

Beauvericin (BEA), an ionophoric cyclic hexadepsipeptide mycotoxin, is able to increase oxidative stress by altering membrane ion permeability and uncoupling oxidative phosphorylation. A toxicogenomic study was performed to investigate gene expression changes triggered by BEA exposure (1.5, 3 and 5 μM; 24 h) in Jurkat cells through RNA-sequencing and differential gene expression analysis. Perturbed gene expression was observed in a concentration dependent manner, with 43 differentially expressed genes (DEGs) overlapped in the three studied concentrations. Gene ontology (GO) analysis showed several biological processes related to electron transport chain, oxidative phosphorylation, and cellular respiration significantly altered. Molecular functions linked to mitochondrial respiratory chain and oxidoreductase activity were over-represented (q-value < 0.01). Pathway analysis revealed oxidative phosphorylation and electron transport chain as the most significantly altered pathways in all studied doses (z-score > 1.96; adj p-value < 0.05). 77 genes involved in the respiratory chain were significantly down-regulated at least at one dose. Moreover, 21 genes related to apoptosis and programmed cell death, and 12 genes related to caspase activity were significantly altered, mainly affecting initiator caspases 8, 9 and 10. The results demonstrated BEA-induced mitochondrial damage affecting the respiratory chain, and pointing to apoptosis through the caspase cascade in human lymphoblastic T cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Flux analysis of cholesterol biosynthesis in vivo reveals multiple tissue and cell-type specific pathways

PubMed Central

Mitsche, Matthew A; McDonald, Jeffrey G; Hobbs, Helen H; Cohen, Jonathan C

2015-01-01

Two parallel pathways produce cholesterol: the Bloch and Kandutsch-Russell pathways. Here we used stable isotope labeling and isotopomer analysis to trace sterol flux through the two pathways in mice. Surprisingly, no tissue used the canonical K–R pathway. Rather, a hybrid pathway was identified that we call the modified K–R (MK–R) pathway. Proportional flux through the Bloch pathway varied from 8% in preputial gland to 97% in testes, and the tissue-specificity observed in vivo was retained in cultured cells. The distribution of sterol isotopomers in plasma mirrored that of liver. Sterol depletion in cultured cells increased flux through the Bloch pathway, whereas overexpression of 24-dehydrocholesterol reductase (DHCR24) enhanced usage of the MK–R pathway. Thus, relative use of the Bloch and MK–R pathways is highly variable, tissue-specific, flux dependent, and epigenetically fixed. Maintenance of two interdigitated pathways permits production of diverse bioactive sterols that can be regulated independently of cholesterol. DOI: http://dx.doi.org/10.7554/eLife.07999.001 PMID:26114596

Genome-wide pathway analysis of memory impairment in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort implicates gene candidates, canonical pathways, and networks.

PubMed

Ramanan, Vijay K; Kim, Sungeun; Holohan, Kelly; Shen, Li; Nho, Kwangsik; Risacher, Shannon L; Foroud, Tatiana M; Mukherjee, Shubhabrata; Crane, Paul K; Aisen, Paul S; Petersen, Ronald C; Weiner, Michael W; Saykin, Andrew J

2012-12-01

Memory deficits are prominent features of mild cognitive impairment (MCI) and Alzheimer's disease (AD). The genetic architecture underlying these memory deficits likely involves the combined effects of multiple genetic variants operative within numerous biological pathways. In order to identify functional pathways associated with memory impairment, we performed a pathway enrichment analysis on genome-wide association data from 742 Alzheimer's Disease Neuroimaging Initiative (ADNI) participants. A composite measure of memory was generated as the phenotype for this analysis by applying modern psychometric theory to item-level data from the ADNI neuropsychological test battery. Using the GSA-SNP software tool, we identified 27 canonical, expertly-curated pathways with enrichment (FDR-corrected p-value < 0.05) against this composite memory score. Processes classically understood to be involved in memory consolidation, such as neurotransmitter receptor-mediated calcium signaling and long-term potentiation, were highly represented among the enriched pathways. In addition, pathways related to cell adhesion, neuronal differentiation and guided outgrowth, and glucose- and inflammation-related signaling were also enriched. Among genes that were highly-represented in these enriched pathways, we found indications of coordinated relationships, including one large gene set that is subject to regulation by the SP1 transcription factor, and another set that displays co-localized expression in normal brain tissue along with known AD risk genes. These results 1) demonstrate that psychometrically-derived composite memory scores are an effective phenotype for genetic investigations of memory impairment and 2) highlight the promise of pathway analysis in elucidating key mechanistic targets for future studies and for therapeutic interventions.