Primary EBV infection induces an expression profile distinct from other viruses but similar to hemophagocytic syndromes.

PubMed

Dunmire, Samantha K; Odumade, Oludare A; Porter, Jean L; Reyes-Genere, Juan; Schmeling, David O; Bilgic, Hatice; Fan, Danhua; Baechler, Emily C; Balfour, Henry H; Hogquist, Kristin A

2014-01-01

Epstein-Barr Virus (EBV) causes infectious mononucleosis and establishes lifelong infection associated with cancer and autoimmune disease. To better understand immunity to EBV, we performed a prospective study of natural infection in healthy humans. Transcriptome analysis defined a striking and reproducible expression profile during acute infection but no lasting gene changes were apparent during latent infection. Comparing the EBV response profile to multiple other acute viral infections, including influenza A (influenza), respiratory syncytial virus (RSV), human rhinovirus (HRV), attenuated yellow fever virus (YFV), and Dengue fever virus (DENV), revealed similarity only to DENV. The signature shared by EBV and DENV was also present in patients with hemophagocytic syndromes, suggesting these two viruses cause uncontrolled inflammatory responses. Interestingly, while EBV induced a strong type I interferon response, a subset of interferon induced genes, including MX1, HERC5, and OAS1, were not upregulated, suggesting a mechanism by which viral antagonism of immunity results in a profound inflammatory response. These data provide an important first description of the response to a natural herpesvirus infection in humans.

Prospective Molecular Profiling of Canine Cancers Provides a Clinically Relevant Comparative Model for Evaluating Personalized Medicine (PMed) Trials

PubMed Central

Mazcko, Christina; Cherba, David; Hendricks, William; Lana, Susan; Ehrhart, E. J.; Charles, Brad; Fehling, Heather; Kumar, Leena; Vail, David; Henson, Michael; Childress, Michael; Kitchell, Barbara; Kingsley, Christopher; Kim, Seungchan; Neff, Mark; Davis, Barbara

2014-01-01

Background Molecularly-guided trials (i.e. PMed) now seek to aid clinical decision-making by matching cancer targets with therapeutic options. Progress has been hampered by the lack of cancer models that account for individual-to-individual heterogeneity within and across cancer types. Naturally occurring cancers in pet animals are heterogeneous and thus provide an opportunity to answer questions about these PMed strategies and optimize translation to human patients. In order to realize this opportunity, it is now necessary to demonstrate the feasibility of conducting molecularly-guided analysis of tumors from dogs with naturally occurring cancer in a clinically relevant setting. Methodology A proof-of-concept study was conducted by the Comparative Oncology Trials Consortium (COTC) to determine if tumor collection, prospective molecular profiling, and PMed report generation within 1 week was feasible in dogs. Thirty-one dogs with cancers of varying histologies were enrolled. Twenty-four of 31 samples (77%) successfully met all predefined QA/QC criteria and were analyzed via Affymetrix gene expression profiling. A subsequent bioinformatics workflow transformed genomic data into a personalized drug report. Average turnaround from biopsy to report generation was 116 hours (4.8 days). Unsupervised clustering of canine tumor expression data clustered by cancer type, but supervised clustering of tumors based on the personalized drug report clustered by drug class rather than cancer type. Conclusions Collection and turnaround of high quality canine tumor samples, centralized pathology, analyte generation, array hybridization, and bioinformatic analyses matching gene expression to therapeutic options is achievable in a practical clinical window (<1 week). Clustering data show robust signatures by cancer type but also showed patient-to-patient heterogeneity in drug predictions. This lends further support to the inclusion of a heterogeneous population of dogs with cancer into the preclinical modeling of personalized medicine. Future comparative oncology studies optimizing the delivery of PMed strategies may aid cancer drug development. PMID:24637659

Prospective molecular profiling of canine cancers provides a clinically relevant comparative model for evaluating personalized medicine (PMed) trials.

PubMed

Paoloni, Melissa; Webb, Craig; Mazcko, Christina; Cherba, David; Hendricks, William; Lana, Susan; Ehrhart, E J; Charles, Brad; Fehling, Heather; Kumar, Leena; Vail, David; Henson, Michael; Childress, Michael; Kitchell, Barbara; Kingsley, Christopher; Kim, Seungchan; Neff, Mark; Davis, Barbara; Khanna, Chand; Trent, Jeffrey

2014-01-01

Molecularly-guided trials (i.e. PMed) now seek to aid clinical decision-making by matching cancer targets with therapeutic options. Progress has been hampered by the lack of cancer models that account for individual-to-individual heterogeneity within and across cancer types. Naturally occurring cancers in pet animals are heterogeneous and thus provide an opportunity to answer questions about these PMed strategies and optimize translation to human patients. In order to realize this opportunity, it is now necessary to demonstrate the feasibility of conducting molecularly-guided analysis of tumors from dogs with naturally occurring cancer in a clinically relevant setting. A proof-of-concept study was conducted by the Comparative Oncology Trials Consortium (COTC) to determine if tumor collection, prospective molecular profiling, and PMed report generation within 1 week was feasible in dogs. Thirty-one dogs with cancers of varying histologies were enrolled. Twenty-four of 31 samples (77%) successfully met all predefined QA/QC criteria and were analyzed via Affymetrix gene expression profiling. A subsequent bioinformatics workflow transformed genomic data into a personalized drug report. Average turnaround from biopsy to report generation was 116 hours (4.8 days). Unsupervised clustering of canine tumor expression data clustered by cancer type, but supervised clustering of tumors based on the personalized drug report clustered by drug class rather than cancer type. Collection and turnaround of high quality canine tumor samples, centralized pathology, analyte generation, array hybridization, and bioinformatic analyses matching gene expression to therapeutic options is achievable in a practical clinical window (<1 week). Clustering data show robust signatures by cancer type but also showed patient-to-patient heterogeneity in drug predictions. This lends further support to the inclusion of a heterogeneous population of dogs with cancer into the preclinical modeling of personalized medicine. Future comparative oncology studies optimizing the delivery of PMed strategies may aid cancer drug development.

Kidney Transplant Rejection and Tissue Injury by Gene Profiling of Biopsies and Peripheral Blood Lymphocytes

PubMed Central

Flechner, Stuart M.; Kurian, Sunil M.; Head, Steven R.; Sharp, Starlette M.; Whisenant, Thomas C.; Zhang, Jie; Chismar, Jeffrey D.; Horvath, Steve; Mondala, Tony; Gilmartin, Timothy; Cook, Daniel J.; Kay, Steven A.; Walker, John R.; Salomon, Daniel R.

2007-01-01

A major challenge for kidney transplantation is balancing the need for immunosuppression to prevent rejection, while minimizing drug-induced toxicities. We used DNA microarrays (HG-U95Av2 GeneChips, Affymetrix) to determine gene expression profiles for kidney biopsies and peripheral blood lymphocytes (PBLs) in transplant patients including normal donor kidneys, well-functioning transplants without rejection, kidneys undergoing acute rejection, and transplants with renal dysfunction without rejection. We developed a data analysis schema based on expression signal determination, class comparison and prediction, hierarchical clustering, statistical power analysis and real-time quantitative PCR validation. We identified distinct gene expression signatures for both biopsies and PBLs that correlated significantly with each of the different classes of transplant patients. This is the most complete report to date using commercial arrays to identify unique expression signatures in transplant biopsies distinguishing acute rejection, acute dysfunction without rejection and well-functioning transplants with no rejection history. We demonstrate for the first time the successful application of high density DNA chip analysis of PBL as a diagnostic tool for transplantation. The significance of these results, if validated in a multicenter prospective trial, would be the establishment of a metric based on gene expression signatures for monitoring the immune status and immunosuppression of transplanted patients. PMID:15307835

A New Gene Expression Signature for Triple-Negative Breast Cancer Using Frozen Fresh Tissue before Neoadjuvant Chemotherapy

PubMed Central

Santuario-Facio, Sandra K; Cardona-Huerta, Servando; Perez-Paramo, Yadira X; Trevino, Victor; Hernandez-Cabrera, Francisco; Rojas-Martinez, Augusto; Uscanga-Perales, Grecia; Martinez-Rodriguez, Jorge L; Martinez-Jacobo, Lizeth; Padilla-Rivas, Gerardo; Muñoz-Maldonado, Gerardo; Gonzalez-Guerrero, Juan Francisco; Valero-Gomez, Javier; Vazquez-Guerrero, Ana L; Martinez-Rodriguez, Herminia G; Barboza-Quintana, Alvaro; Barboza-Quintana, Oralia; Garza-Guajardo, Raquel; Ortiz-Lopez, Rocio

2017-01-01

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer tumors. Comparisons between TNBC and non–triple-negative breast cancer (nTNBC) may help to differentiate key components involved in TNBC neoplasms. The purpose of the study was to analyze the expression profile of TNBC versus nTNBC tumors in a homogeneous population from northeastern Mexico. A prospective study of 50 patients (25 TNBC and 25 nTNBC) was conducted. Clinic parameters were equally distributed for TNBC and nTNBC: age at diagnosis (51 versus 47 years, p = 0.1), glucose level (107 mg/dl versus 104 mg/dl, p = 0.64), and body mass index (28 versus 29, p = 0.14). Core biopsies were collected for histopathological diagnosis and gene expression analysis. Total RNA was isolated and expression profiling was performed. Forty genes showed differential expression pattern in TNBC tumors. Among these, nine overexpressed genes (PRKX/PRKY, UGT8, HMGA1, LPIN1, HAPLN3, FAM171A1, BCL141A, FOXC1, and ANKRD11), and one underexpressed gene (ANX9) are involved in general metabolism. Based on this biochemical peculiarity and the overexpression of BCL11A and FOXC1 (involved in tumor growth and metastasis, respectively), we validated by quantitative polymerase chain reaction the expression profiles of seven genes out of the signature. In this report, a new gene signature for TNBC is proposed. To our knowledge, this is the first TNBC signature that describes genes involved in general metabolism. The findings may be pertinent for Mexican patients and require evaluation in other ethnic groups and populations. PMID:28474731

Gene expression profiling of prostate tissue identifies chromatin regulation as a potential link between obesity and lethal prostate cancer.

PubMed

Ebot, Ericka M; Gerke, Travis; Labbé, David P; Sinnott, Jennifer A; Zadra, Giorgia; Rider, Jennifer R; Tyekucheva, Svitlana; Wilson, Kathryn M; Kelly, Rachel S; Shui, Irene M; Loda, Massimo; Kantoff, Philip W; Finn, Stephen; Vander Heiden, Matthew G; Brown, Myles; Giovannucci, Edward L; Mucci, Lorelei A

2017-11-01

Obese men are at higher risk of advanced prostate cancer and cancer-specific mortality; however, the biology underlying this association remains unclear. This study examined gene expression profiles of prostate tissue to identify biological processes differentially expressed by obesity status and lethal prostate cancer. Gene expression profiling was performed on tumor (n = 402) and adjacent normal (n = 200) prostate tissue from participants in 2 prospective cohorts who had been diagnosed with prostate cancer from 1982 to 2005. Body mass index (BMI) was calculated from the questionnaire immediately preceding cancer diagnosis. Men were followed for metastases or prostate cancer-specific death (lethal disease) through 2011. Gene Ontology biological processes differentially expressed by BMI were identified using gene set enrichment analysis. Pathway scores were computed by averaging the signal intensities of member genes. Odds ratios (ORs) for lethal prostate cancer were estimated with logistic regression. Among 402 men, 48% were healthy weight, 31% were overweight, and 21% were very overweight/obese. Fifteen gene sets were enriched in tumor tissue, but not normal tissue, of very overweight/obese men versus healthy-weight men; 5 of these were related to chromatin modification and remodeling (false-discovery rate < 0.25). Patients with high tumor expression of chromatin-related genes had worse clinical characteristics (Gleason grade > 7, 41% vs 17%; P = 2 × 10 -4 ) and an increased risk of lethal disease that was independent of grade and stage (OR, 5.26; 95% confidence interval, 2.37-12.25). This study improves our understanding of the biology of aggressive prostate cancer and identifies a potential mechanistic link between obesity and prostate cancer death that warrants further study. Cancer 2017;123:4130-4138. © 2017 American Cancer Society. © 2017 American Cancer Society.

PROSPECT (Profiling of Resistance Patterns & Oncogenic Signaling Pathways in Evaluation of Cancers of the Thorax and Therapeutic Target Identification

DTIC Science & Technology

2009-06-01

47,000 transcripts representing most of the human genes. The Core facility scanned the chips and has delivered the data to Dr. Kevin Coombes ... Coombes ) (Figure 3). From the preliminary analysis, at least 3 groups of patients have been identified by the expression of the IHC markers examined. The...Director: Dr. J. Jack Lee; Co-Director: Kevin Coombes ) In close collaboration with the Pathology Core and each of the five main projects, the

Female choice for male cuticular hydrocarbon profile in decorated crickets is not based on similarity to their own profile.

PubMed

Steiger, S; Capodeanu-Nägler, A; Gershman, S N; Weddle, C B; Rapkin, J; Sakaluk, S K; Hunt, J

2015-12-01

Indirect genetic benefits derived from female mate choice comprise additive (good genes) and nonadditive genetic benefits (genetic compatibility). Although good genes can be revealed by condition-dependent display traits, the mechanism by which compatibility alleles are detected is unclear because evaluation of the genetic similarity of a prospective mate requires the female to assess the genotype of the male and compare it to her own. Cuticular hydrocarbons (CHCs), lipids coating the exoskeleton of most insects, influence female mate choice in a number of species and offer a way for females to assess genetic similarity of prospective mates. Here, we determine whether female mate choice in decorated crickets is based on male CHCs and whether it is influenced by females' own CHC profiles. We used multivariate selection analysis to estimate the strength and form of selection acting on male CHCs through female mate choice, and employed different measures of multivariate dissimilarity to determine whether a female's preference for male CHCs is based on similarity to her own CHC profile. Female mating preferences were significantly influenced by CHC profiles of males. Male CHC attractiveness was not, however, contingent on the CHC profile of the choosing female, as certain male CHC phenotypes were equally attractive to most females, evidenced by significant linear and stabilizing selection gradients. These results suggest that additive genetic benefits, rather than nonadditive genetic benefits, accrue to female mate choice, in support of earlier work showing that CHC expression of males, but not females, is condition dependent. © 2015 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2015 European Society For Evolutionary Biology.

From genes to genomes: a new paradigm for studying fungal pathogenesis in Magnaporthe oryzae.

PubMed

Xu, Jin-Rong; Zhao, Xinhua; Dean, Ralph A

2007-01-01

Magnaporthe oryzae is the most destructive fungal pathogen of rice worldwide and because of its amenability to classical and molecular genetic manipulation, availability of a genome sequence, and other resources it has emerged as a leading model system to study host-pathogen interactions. This chapter reviews recent progress toward elucidation of the molecular basis of infection-related morphogenesis, host penetration, invasive growth, and host-pathogen interactions. Related information on genome analysis and genomic studies of plant infection processes is summarized under specific topics where appropriate. Particular emphasis is placed on the role of MAP kinase and cAMP signal transduction pathways and unique features in the genome such as repetitive sequences and expanded gene families. Emerging developments in functional genome analysis through large-scale insertional mutagenesis and gene expression profiling are detailed. The chapter concludes with new prospects in the area of systems biology, such as protein expression profiling, and highlighting remaining crucial information needed to fully appreciate host-pathogen interactions.

Impact of environmental conditions and chemicals on the neuronal epigenome.

PubMed

Del Blanco, Beatriz; Barco, Angel

2018-06-15

During development, chromatin changes contribute to establishing and maintaining the distinct gene-expression profiles of each individual cell type in a multicellular organism. This feat is especially remarkable in the human brain considering the sheer number of distinct cell types that make up this organ. This epigenetic programing is sensitive to environmental influences such as the presence of toxicants, diet, temperature, maternal behavior and many other external factors that can lead to sustained differences in neuronal gene expression. Here, we review a number of studies that demonstrate the existence of these environmental fingerprints in the neuronal epigenome and discuss the current challenges and prospects of environmental neuroepigenetics research. Copyright © 2018 Elsevier Ltd. All rights reserved.

TP53, STK11 and EGFR Mutations Predict Tumor Immune Profile and the Response to anti-PD-1 in Lung Adenocarcinoma.

PubMed

Biton, Jerome; Mansuet-Lupo, Audrey; Pécuchet, Nicolas; Alifano, Marco; Ouakrim, Hanane; Arrondeau, Jennifer; Boudou-Rouquette, Pascaline; Goldwasser, Francois; Leroy, Karen; Goc, Jeremy; Wislez, Marie; Germain, Claire; Laurent-Puig, Pierre; Dieu-Nosjean, Marie-Caroline; Cremer, Isabelle; Herbst, Ronald; Blons, Hélène F; Damotte, Diane

2018-05-15

By unlocking anti-tumor immunity, antibodies targeting programmed cell death 1 (PD-1) exhibit impressive clinical results in non-small cell lung cancer, underlining the strong interactions between tumor and immune cells. However, factors that can robustly predict long-lasting responses are still needed. We performed in depth immune profiling of lung adenocarcinoma using an integrative analysis based on immunohistochemistry, flow-cytometry and transcriptomic data. Tumor mutational status was investigated using next-generation sequencing. The response to PD-1 blockers was analyzed from a prospective cohort according to tumor mutational profiles and to PD-L1 expression, and a public clinical database was used to validate the results obtained. We showed that distinct combinations of STK11 , EGFR and TP53 mutations, were major determinants of the tumor immune profile (TIP) and of the expression of PD-L1 by malignant cells. Indeed, the presence of TP53 mutations without co-occurring STK11 or EGFR alterations ( TP53 -mut/ STK11 - EGFR -WT), independently of KRAS mutations, identified the group of tumors with the highest CD8 T cell density and PD-L1 expression. In this tumor subtype, pathways related to T cell chemotaxis, immune cell cytotoxicity, and antigen processing were up-regulated. Finally, a prolonged progression-free survival (PFS: HR=0.32; 95% CI, 0.16-0.63, p <0.001) was observed in anti-PD-1 treated patients harboring TP53 -mut/ STK11 - EGFR -WT tumors. This clinical benefit was even more remarkable in patients with associated strong PD-L1 expression. Our study reveals that different combinations of TP53 , EGFR and STK11 mutations , together with PD-L1 expression by tumor cells, represent robust parameters to identify best responders to PD-1 blockade. Copyright ©2018, American Association for Cancer Research.

Current status and clinical association of beta-catenin with juvenile nasopharyngeal angiofibroma.

PubMed

Mishra, A; Singh, V; Verma, V; Pandey, S; Trivedi, R; Singh, H P; Kumar, S; Dwivedi, R C; Mishra, S C

2016-10-01

A possible role of the APC/beta-catenin pathway in the pathogenesis of sporadic juvenile nasopharyngeal angiofibroma has been suggested. This paper presents its current status and clinical association in our patients. A prospective observational study was conducted at King George Medical University and Central Drug Research Institute, in Lucknow, India. Western blot analysis was undertaken in 16 cases to examine beta-catenin expression. The clinical details were recorded along with follow up observations, to determine associations. Up-regulation of beta-catenin expression was seen in 69 per cent of cases. The clinical variables did not reveal significant differences between patients with extremes of expression (extreme under- vs over-expression). However, absent expression was shown exclusively in young adults aged over 18 years, while enhanced expression was associated with an altered facial profile. Although a beta-catenin association was seen in a subset of our sporadic juvenile nasopharyngeal angiofibroma cases, its expression was not homogeneous. This is in contrast to the Western literature that suggests a universal (homogenous) enhanced expression in the majority. Hence, further research is required to better define its molecular cascade.

A Cross-Species Analysis in Pancreatic Neuroendocrine Tumors Reveals Molecular Subtypes with Distinctive Clinical, Metastatic, Developmental, and Metabolic Characteristics

PubMed Central

Sadanandam, Anguraj; Wullschleger, Stephan; Lyssiotis, Costas A.; Grötzinger, Carsten; Barbi, Stefano; Bersani, Samantha; Körner, Jan; Wafy, Ismael; Mafficini, Andrea; Lawlor, Rita T.; Simbolo, Michele; Asara, John M.; Bläker, Hendrik; Cantley, Lewis C.; Wiedenmann, Bertram; Scarpa, Aldo; Hanahan, Douglas

2016-01-01

Seeking to assess the representative and instructive value of an engineered mouse model of pancreatic neuroendocrine tumors (PanNET) for its cognate human cancer, we profiled and compared mRNA and miRNA transcriptomes of tumors from both. Mouse PanNET tumors could be classified into two distinctive subtypes, well-differentiated islet/insulinoma tumors (IT) and poorly differentiated tumors associated with liver metastases, dubbed metastasis-like primary (MLP). Human PanNETs were independently classified into these same two subtypes, along with a third, specific gene mutation–enriched subtype. The MLP subtypes in human and mouse were similar to liver metastases in terms of miRNA and mRNA transcriptome profiles and signature genes. The human/mouse MLP subtypes also similarly expressed genes known to regulate early pancreas development, whereas the IT subtypes expressed genes characteristic of mature islet cells, suggesting different tumorigenesis pathways. In addition, these subtypes exhibit distinct metabolic profiles marked by differential pyruvate metabolism, substantiating the significance of their separate identities. SIGNIFICANCE This study involves a comprehensive cross-species integrated analysis of multi-omics profiles and histology to stratify PanNETs into subtypes with distinctive characteristics. We provide support for the RIP1-TAG2 mouse model as representative of its cognate human cancer with prospects to better understand PanNET heterogeneity and consider future applications of personalized cancer therapy. PMID:26446169

A Cross-Species Analysis in Pancreatic Neuroendocrine Tumors Reveals Molecular Subtypes with Distinctive Clinical, Metastatic, Developmental, and Metabolic Characteristics.

PubMed

Sadanandam, Anguraj; Wullschleger, Stephan; Lyssiotis, Costas A; Grötzinger, Carsten; Barbi, Stefano; Bersani, Samantha; Körner, Jan; Wafy, Ismael; Mafficini, Andrea; Lawlor, Rita T; Simbolo, Michele; Asara, John M; Bläker, Hendrik; Cantley, Lewis C; Wiedenmann, Bertram; Scarpa, Aldo; Hanahan, Douglas

2015-12-01

Seeking to assess the representative and instructive value of an engineered mouse model of pancreatic neuroendocrine tumors (PanNET) for its cognate human cancer, we profiled and compared mRNA and miRNA transcriptomes of tumors from both. Mouse PanNET tumors could be classified into two distinctive subtypes, well-differentiated islet/insulinoma tumors (IT) and poorly differentiated tumors associated with liver metastases, dubbed metastasis-like primary (MLP). Human PanNETs were independently classified into these same two subtypes, along with a third, specific gene mutation-enriched subtype. The MLP subtypes in human and mouse were similar to liver metastases in terms of miRNA and mRNA transcriptome profiles and signature genes. The human/mouse MLP subtypes also similarly expressed genes known to regulate early pancreas development, whereas the IT subtypes expressed genes characteristic of mature islet cells, suggesting different tumorigenesis pathways. In addition, these subtypes exhibit distinct metabolic profiles marked by differential pyruvate metabolism, substantiating the significance of their separate identities. This study involves a comprehensive cross-species integrated analysis of multi-omics profiles and histology to stratify PanNETs into subtypes with distinctive characteristics. We provide support for the RIP1-TAG2 mouse model as representative of its cognate human cancer with prospects to better understand PanNET heterogeneity and consider future applications of personalized cancer therapy. ©2015 American Association for Cancer Research.

Plant-pathogen interactions: what microarray tells about it?

PubMed

Lodha, T D; Basak, J

2012-01-01

Plant defense responses are mediated by elementary regulatory proteins that affect expression of thousands of genes. Over the last decade, microarray technology has played a key role in deciphering the underlying networks of gene regulation in plants that lead to a wide variety of defence responses. Microarray is an important tool to quantify and profile the expression of thousands of genes simultaneously, with two main aims: (1) gene discovery and (2) global expression profiling. Several microarray technologies are currently in use; most include a glass slide platform with spotted cDNA or oligonucleotides. Till date, microarray technology has been used in the identification of regulatory genes, end-point defence genes, to understand the signal transduction processes underlying disease resistance and its intimate links to other physiological pathways. Microarray technology can be used for in-depth, simultaneous profiling of host/pathogen genes as the disease progresses from infection to resistance/susceptibility at different developmental stages of the host, which can be done in different environments, for clearer understanding of the processes involved. A thorough knowledge of plant disease resistance using successful combination of microarray and other high throughput techniques, as well as biochemical, genetic, and cell biological experiments is needed for practical application to secure and stabilize yield of many crop plants. This review starts with a brief introduction to microarray technology, followed by the basics of plant-pathogen interaction, the use of DNA microarrays over the last decade to unravel the mysteries of plant-pathogen interaction, and ends with the future prospects of this technology.

Single-Cell Sequencing for Precise Cancer Research: Progress and Prospects.

PubMed

Zhang, Xiaoyan; Marjani, Sadie L; Hu, Zhaoyang; Weissman, Sherman M; Pan, Xinghua; Wu, Shixiu

2016-03-15

Advances in genomic technology have enabled the faithful detection and measurement of mutations and the gene expression profile of cancer cells at the single-cell level. Recently, several single-cell sequencing methods have been developed that permit the comprehensive and precise analysis of the cancer-cell genome, transcriptome, and epigenome. The use of these methods to analyze cancer cells has led to a series of unanticipated discoveries, such as the high heterogeneity and stochastic changes in cancer-cell populations, the new driver mutations and the complicated clonal evolution mechanisms, and the novel identification of biomarkers of variant tumors. These methods and the knowledge gained from their utilization could potentially improve the early detection and monitoring of rare cancer cells, such as circulating tumor cells and disseminated tumor cells, and promote the development of personalized and highly precise cancer therapy. Here, we discuss the current methods for single cancer-cell sequencing, with a strong focus on those practically used or potentially valuable in cancer research, including single-cell isolation, whole genome and transcriptome amplification, epigenome profiling, multi-dimensional sequencing, and next-generation sequencing and analysis. We also examine the current applications, challenges, and prospects of single cancer-cell sequencing. ©2016 American Association for Cancer Research.

Milestone in English Language Teacher Education: How to Use European Profiling Grid in the Assessment of Prospective EFL Teachers' Qualifications

ERIC Educational Resources Information Center

Su Bergil, Ayfer; Sariçoban, Arif

2016-01-01

This research intends to exemplify one of the new practices that can be used for the assessment of prospective English language teachers' qualifications. Thus, the scope of this research covers the prospective EFL teachers and the implementation of European Profiling Grid (EPG) aimed to be commonly used for language teacher education in Europe.…

First Trimester Pregnancy Loss and the Expression of Alternatively Spliced NKp30 Isoforms in Maternal Blood and Placental Tissue

PubMed Central

Shemesh, Avishai; Tirosh, Dan; Sheiner, Eyal; Benshalom-Tirosh, Neta; Brusilovsky, Michael; Segev, Rotem; Rosental, Benyamin; Porgador, Angel

2015-01-01

Capsule: We observed that first trimester pregnancy loss is associated with an altered expression profile of the three isoforms of the NK receptor NKp30 expressed by NKs in PBMC and placental tissue. In this study, we aimed to investigate whether first trimester pregnancy loss is associated with differences in expression of NKp30 splice variants (isoforms) in maternal peripheral blood or placental tissue. We conducted a prospective case–control study; a total of 33 women undergoing dilation and curettage due to first trimester pregnancy loss were further subdivided into groups with sporadic or recurrent pregnancy loss. The control group comprises women undergoing elective termination of pregnancy. The qPCR approach was employed to assess the relative expression of NKp30 isoforms as well as the total expression of NKp30 and NKp46 receptors between the selected groups. Results show that in both PBMC and placental tissue, NKp46 and NKp30 expressions were mildly elevated in the pregnancy loss groups compared with the elective group. In particular, NKp46 elevation was significant. Moreover, expression analysis of NKp30 isoforms manifested a different profile between PBMC and the placenta. NKp30-a and NKp30-b isoforms in the placental tissue, but not in PBMC, showed a significant increase in the pregnancy loss groups compared with the elective group. Placental expression of NKp30 activating isoforms-a and -b in the pregnancy loss groups was negatively correlated with PLGF expression. By contrast, placental expression of these isoforms in the elective group was positively correlated with TNFα, IL-10, and VEGF-A expression. The altered expression of NKp30 activating isoforms in placental tissue from patients with pregnancy loss compared to the elective group and the different correlations with cytokine expression point to the involvement of NKp30-mediated function in pregnancy loss. PMID:26082773

Distinct iris gene expression profiles of primary angle closure glaucoma and primary open angle glaucoma and their interaction with ocular biometric parameters.

PubMed

Seet, Li-Fong; Narayanaswamy, Arun; Finger, Sharon N; Htoon, Hla M; Nongpiur, Monisha E; Toh, Li Zhen; Ho, Henrietta; Perera, Shamira A; Wong, Tina T

2016-11-01

This study aimed to evaluate differences in iris gene expression profiles between primary angle closure glaucoma (PACG) and primary open angle glaucoma (POAG) and their interaction with biometric characteristics. Prospective study. Thirty-five subjects with PACG and thirty-three subjects with POAG who required trabeculectomy were enrolled at the Singapore National Eye Centre, Singapore. Iris specimens, obtained by iridectomy, were analysed by real-time polymerase chain reaction for expression of type I collagen, vascular endothelial growth factor (VEGF)-A, -B and -C, as well as VEGF receptors (VEGFRs) 1 and 2. Anterior segment optical coherence tomography (ASOCT) imaging for biometric parameters, including anterior chamber depth (ACD), anterior chamber volume (ACV) and lens vault (LV), was also performed pre-operatively. Relative mRNA levels between PACG and POAG irises, biometric measurements, discriminant analyses using genes and biometric parameters. COL1A1, VEGFB, VEGFC and VEGFR2 mRNA expression was higher in PACG compared to POAG irises. LV, ACD and ACV were significantly different between the two subgroups. Discriminant analyses based on gene expression, biometric parameters or a combination of both gene expression and biometrics (LV and ACV), correctly classified 94.1%, 85.3% and 94.1% of the original PACG and POAG cases, respectively. The discriminant function combining genes and biometrics demonstrated the highest accuracy in cross-validated classification of the two glaucoma subtypes. Distinct iris gene expression supports the pathophysiological differences that exist between PACG and POAG. Biometric parameters can combine with iris gene expression to more accurately define PACG from POAG. © 2016 The Authors. Clinical & Experimental Ophthalmology published by John Wiley & Sons Australia, Ltd on behalf of Royal Australian and New Zealand College of Ophthalmologists.

Connectivity Mapping for Candidate Therapeutics Identification Using Next Generation Sequencing RNA-Seq Data

PubMed Central

McArt, Darragh G.; Dunne, Philip D.; Blayney, Jaine K.; Salto-Tellez, Manuel; Van Schaeybroeck, Sandra; Hamilton, Peter W.; Zhang, Shu-Dong

2013-01-01

The advent of next generation sequencing technologies (NGS) has expanded the area of genomic research, offering high coverage and increased sensitivity over older microarray platforms. Although the current cost of next generation sequencing is still exceeding that of microarray approaches, the rapid advances in NGS will likely make it the platform of choice for future research in differential gene expression. Connectivity mapping is a procedure for examining the connections among diseases, genes and drugs by differential gene expression initially based on microarray technology, with which a large collection of compound-induced reference gene expression profiles have been accumulated. In this work, we aim to test the feasibility of incorporating NGS RNA-Seq data into the current connectivity mapping framework by utilizing the microarray based reference profiles and the construction of a differentially expressed gene signature from a NGS dataset. This would allow for the establishment of connections between the NGS gene signature and those microarray reference profiles, alleviating the associated incurring cost of re-creating drug profiles with NGS technology. We examined the connectivity mapping approach on a publicly available NGS dataset with androgen stimulation of LNCaP cells in order to extract candidate compounds that could inhibit the proliferative phenotype of LNCaP cells and to elucidate their potential in a laboratory setting. In addition, we also analyzed an independent microarray dataset of similar experimental settings. We found a high level of concordance between the top compounds identified using the gene signatures from the two datasets. The nicotine derivative cotinine was returned as the top candidate among the overlapping compounds with potential to suppress this proliferative phenotype. Subsequent lab experiments validated this connectivity mapping hit, showing that cotinine inhibits cell proliferation in an androgen dependent manner. Thus the results in this study suggest a promising prospect of integrating NGS data with connectivity mapping. PMID:23840550

Immunologic and gene expression profiles of spontaneous canine oligodendrogliomas.

PubMed

Filley, Anna; Henriquez, Mario; Bhowmik, Tanmoy; Tewari, Brij Nath; Rao, Xi; Wan, Jun; Miller, Margaret A; Liu, Yunlong; Bentley, R Timothy; Dey, Mahua

2018-05-01

Malignant glioma (MG), the most common primary brain tumor in adults, is extremely aggressive and uniformly fatal. Several treatment strategies have shown significant preclinical promise in murine models of glioma; however, none have produced meaningful clinical responses in human patients. We hypothesize that introduction of an additional preclinical animal model better approximating the complexity of human MG, particularly in interactions with host immune responses, will bridge the existing gap between these two stages of testing. Here, we characterize the immunologic landscape and gene expression profiles of spontaneous canine glioma and evaluate its potential for serving as such a translational model. RNA in situ hybridization, flowcytometry, and RNA sequencing were used to evaluate immune cell presence and gene expression in healthy and glioma-bearing canines. Similar to human MGs, canine gliomas demonstrated increased intratumoral immune cell infiltration (CD4+, CD8+ and CD4+Foxp3+ T cells). The peripheral blood of glioma-bearing dogs also contained a relatively greater proportion of CD4+Foxp3+ regulatory T cells and plasmacytoid dendritic cells. Tumors were strongly positive for PD-L1 expression and glioma-bearing animals also possessed a greater proportion of immune cells expressing the immune checkpoint receptors CTLA-4 and PD-1. Analysis of differentially expressed genes in our canine populations revealed several genetic changes paralleling those known to occur in human disease. Naturally occurring canine glioma has many characteristics closely resembling human disease, particularly with respect to genetic dysregulation and host immune responses to tumors, supporting its use as a translational model in the preclinical testing of prospective anti-glioma therapies proven successful in murine studies.

Genomic analysis of hepatoblastoma identifies distinct molecular and prognostic subgroups.

PubMed

Sumazin, Pavel; Chen, Yidong; Treviño, Lisa R; Sarabia, Stephen F; Hampton, Oliver A; Patel, Kayuri; Mistretta, Toni-Ann; Zorman, Barry; Thompson, Patrick; Heczey, Andras; Comerford, Sarah; Wheeler, David A; Chintagumpala, Murali; Meyers, Rebecka; Rakheja, Dinesh; Finegold, Milton J; Tomlinson, Gail; Parsons, D Williams; López-Terrada, Dolores

2017-01-01

Despite being the most common liver cancer in children, hepatoblastoma (HB) is a rare neoplasm. Consequently, few pretreatment tumors have been molecularly profiled, and there are no validated prognostic or therapeutic biomarkers for HB patients. We report on the first large-scale effort to profile pretreatment HBs at diagnosis. Our analysis of 88 clinically annotated HBs revealed three risk-stratifying molecular subtypes that are characterized by differential activation of hepatic progenitor cell markers and metabolic pathways: high-risk tumors were characterized by up-regulated nuclear factor, erythroid 2-like 2 activity; high lin-28 homolog B, high mobility group AT-hook 2, spalt-like transcription factor 4, and alpha-fetoprotein expression; and high coordinated expression of oncofetal proteins and stem-cell markers, while low-risk tumors had low lin-28 homolog B and lethal-7 expression and high hepatic nuclear factor 1 alpha activity. Analysis of immunohistochemical assays using antibodies targeting these genes in a prospective study of 35 HBs suggested that these candidate biomarkers have the potential to improve risk stratification and guide treatment decisions for HB patients at diagnosis; our results pave the way for clinical collaborative studies to validate candidate biomarkers and test their potential to improve outcome for HB patients. (Hepatology 2017;65:104-121). © 2016 by the American Association for the Study of Liver Diseases.

Cytokine expression profile in the bone-anchored hearing system: 12-week results from a prospective randomized, controlled study.

PubMed

Calon, Tim George Ate; van Tongeren, Joost; Omar, Omar; Johansson, Martin Lars; Stokroos, Robert-Jan

2018-04-27

To study the effect of implanting the percutaneous bone-anchored hearing system (BAHS) itself and inflammation of the peri-abutment skin warrant clarification. In this study, we aimed to acquire further insight into the immune responses related to BAHS surgery and peri-implant skin inflammation. During surgery and 12 weeks post-implantation, skin biopsies were obtained. If applicable, additional biopsies were taken during cases of inflammation. The mRNA expression of IL-1β, IL-6, IL-8, TNFα, IL-17, IL-10, TGF-ß, MIP-1α, MMP-9, TIMP-1, COL1α1, VEGF-A, FGF-2 TLR-2, and TLR-4 was quantified using qRT-PCR. Thirty-five patients agreed to the surgery and 12-week biopsy. Twenty-two patients had mRNA of sufficient quality for analysis. Ten were fitted with a BAHS using the minimally invasive Ponto surgery technique. Twelve were fitted with a BAHS using the linear incision technique with soft-tissue preservation. Five biopsies were obtained during episodes of inflammation. The post-implantation mRNA expression of IL-1β (P = .002), IL-8 (P = .003), MMP9 (P = .005), TIMP-1 (P = .002), and COL1α1 (P < .001) was significantly up-regulated. IL-6 (P = .009) and FGF-2 (P = .004) mRNA expression was significantly down-regulated after implantation. Within patients, no difference between post-implantation mRNA expression (at 12 weeks) and when inflammation was observed. Between patients, the expression of IL-1β (P = .015) and IL-17 (P = .02) was higher during cases of inflammation compared with patients who had no inflammation at 12-week follow-up. As part of a randomized, prospective, clinical trial, the present study reports the molecular profile of selected cytokines in the soft tissue around BAHS. Within the limit of this study, the results showed that 12 weeks after BAHS implantation the gene expression of some inflammatory cytokines (IL-8 and IL-1β) is still relatively high compared with the baseline, steady-state, expression. The up-regulation of anabolic (COL1α1) and tissue-remodeling (MMP-9 and TIMP1) genes indicates an ongoing remodeling process after 12 weeks of implantation. The results suggest that IL-1β, IL-17, and TNF-α may be interesting markers associated with inflammation. © 2018 The Authors. Clinical Implant Dentistry and Related Research published by Wiley Periodicals, Inc.

Gene expression profiling in multiple myeloma--reporting of entities, risk, and targets in clinical routine.

PubMed

Meissner, Tobias; Seckinger, Anja; Rème, Thierry; Hielscher, Thomas; Möhler, Thomas; Neben, Kai; Goldschmidt, Hartmut; Klein, Bernard; Hose, Dirk

2011-12-01

Multiple myeloma is an incurable malignant plasma cell disease characterized by survival ranging from several months to more than 15 years. Assessment of risk and underlying molecular heterogeneity can be excellently done by gene expression profiling (GEP), but its way into clinical routine is hampered by the lack of an appropriate reporting tool and the integration with other prognostic factors into a single "meta" risk stratification. The GEP-report (GEP-R) was built as an open-source software developed in R for gene expression reporting in clinical practice using Affymetrix microarrays. GEP-R processes new samples by applying a documentation-by-value strategy to the raw data to be able to assign thresholds and grouping algorithms defined on a reference cohort of 262 patients with multiple myeloma. Furthermore, we integrated expression-based and conventional prognostic factors within one risk stratification (HM-metascore). The GEP-R comprises (i) quality control, (ii) sample identity control, (iii) biologic classification, (iv) risk stratification, and (v) assessment of target genes. The resulting HM-metascore is defined as the sum over the weighted factors gene expression-based risk-assessment (UAMS-, IFM-score), proliferation, International Staging System (ISS) stage, t(4;14), and expression of prognostic target genes (AURKA, IGF1R) for which clinical grade inhibitors exist. The HM-score delineates three significantly different groups of 13.1%, 72.1%, and 14.7% of patients with a 6-year survival rate of 89.3%, 60.6%, and 18.6%, respectively. GEP reporting allows prospective assessment of risk and target gene expression and integration of current prognostic factors in clinical routine, being customizable about novel parameters or other cancer entities. ©2011 AACR.

Prospective Molecular Profiling of Melanoma Metastases Suggests Classifiers of Immune Responsiveness

PubMed Central

Wang, Ena; Miller, Lance D.; Ohnmacht, Galen A.; Mocellin, Simone; Perez-Diez, Ainhoa; Petersen, David; Zhao, Yingdong; Simon, Richard; Powell, John I.; Asaki, Esther; Alexander, H. Richard; Duray, Paul H.; Herlyn, Meenhard; Restifo, Nicholas P.; Liu, Edison T.; Rosenberg, Steven A.; Marincola, Francesco M.

2008-01-01

We amplified RNAs from 63 fine needle aspiration (FNA) samples from 37 s.c. melanoma metastases from 25 patients undergoing immunotherapy for hybridization to a 6108-gene human cDNA chip. By prospectively following the history of the lesions, we could correlate transcript patterns with clinical outcome. Cluster analysis revealed a tight relationship among autologous synchronously sampled tumors compared with unrelated lesions (average Pearson's r = 0.83 and 0.7, respectively, P < 0.0003). As reported previously, two subgroups of metastatic melanoma lesions were identified that, however, had no predictive correlation with clinical outcome. Ranking of gene expression data from pretreatment samples identified ∼30 genes predictive of clinical response (P < 0.001). Analysis of their annotations denoted that approximately half of them were related to T-cell regulation, suggesting that immune responsiveness might be predetermined by a tumor microenvironment conducive to immune recognition. PMID:12097256

Clinical Value of miR-101-3p and Biological Analysis of its Prospective Targets in Breast Cancer: A Study Based on The Cancer Genome Atlas (TCGA) and Bioinformatics.

PubMed

Li, Chun-Yao; Xiong, Dan-Dan; Huang, Chun-Qin; He, Rong-Quan; Liang, Hai-Wei; Pan, Deng-Hua; Wang, Han-Lin; Wang, Yi-Wen; Zhu, Hua-Wei; Chen, Gang

2017-04-18

BACKGROUND MiR-101-3p can promote apoptosis and inhibit proliferation, invasion, and metastasis in breast cancer (BC) cells. However, its mechanisms in BC are not fully understood. Therefore, a comprehensive analysis of the target genes, pathways, and networks of miR-101-3p in BC is necessary. MATERIAL AND METHODS The miR-101 profiles for 781 patients with BC from The Cancer Genome Atlas (TCGA) were analyzed. Gene expression profiling of GSE31397 with miR-101-3p transfected MCF-7 cells and scramble control cells was downloaded from Gene Expression Omnibus (GEO), and the differentially expressed genes (DEGs) were identified. The potential genes targeted by miR-101-3p were also predicted. Gene Ontology (GO) and pathway and network analyses were constructed for the DEGs and predicted genes. RESULTS In the TCGA data, a low level of miR-101-2 expression might represent a diagnostic (AUC: 0.63) marker, and the miR-101-1 was a prognostic (HR=1.79) marker. MiR-101-1 was linked to the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), and miR-101-2 was associated with the tumor (T), lymph node (N), and metastasis (M) stages of BC. Moreover, 427 genes were selected from the 921 DEGs in GEO and the 7924 potential target genes from the prediction databases. These genes were related to transcription, metabolism, biosynthesis, and proliferation. The results were also significantly enriched in the VEGF, mTOR, focal adhesion, Wnt, and chemokine signaling pathways. CONCLUSIONS MiR-101-1 and miR-101-2 may be prospective biomarkers for the prognosis and diagnosis of BC, respectively, and are associated with diverse clinical parameters. The target genes of miR-101-3p regulate the development and progression of BC. These results provide insight into the pathogenic mechanism and potential therapies for BC.

MiRNA-513a-5p inhibits progesterone receptor expression and constitutes a risk factor for breast cancer: the hOrmone and Diet in the ETiology of breast cancer prospective study.

PubMed

Muti, Paola; Donzelli, Sara; Sacconi, Andrea; Hossain, Ahmed; Ganci, Federica; Frixa, Tania; Sieri, Sabina; Krogh, Vittorio; Berrino, Franco; Biagioni, Francesca; Strano, Sabrina; Beyene, Joseph; Yarden, Yosef; Blandino, Giovanni

2018-02-09

MicroRNAs (miRNAs) might be considered both predictors and players of cancer development. The aim of the present report was to investigate whether many years before the diagnosis of breast cancer miRNA expression is already disregulated. In order to test this hypothesis, we compared miRNAs extracted from leukocytes in healthy women who later developed breast cancer and in women who remain healthy during the whole 15-year follow-up time. Accordantly, we used a case-control study design nested in the hOrmone and Diet in the ETiology of breast cancer (ORDET) prospective cohort study addressing the possibility that miRNAs can serve as both early biomarkers and components of the hormonal etiological pathways leading to breast cancer development in premenopausal women. We compared leukocyte miRNA profiles of 191 incident premenopausal breast cancer cases and profiles of 191 women who remained healthy over a follow-up period of 20 years. The analysis identified 20 differentially expressed miRNAs in women candidate to develop breast cancer versus control women. The upregulated miRNAs, miR-513-a-5p, miR-513b-5p and miR-513c-5p were among the most significantly deregulated miRNAs. In multivariate analysis, miR-513a-5p upregulation was directly and statistically significant associated with breast cancer risk (OR = 1.69; 95% CI 1.08-2.64; P = 0.0293). In addition, the upregulation of miR-513-a-5p displayed the strongest direct association with serum progesterone and testosterone levels. The experimental data corroborated the inhibitory function of miR-513a-5p on progesterone receptor expression confirming that progesterone receptor is a target of miR-513a-5p. The identification of upregulated miR-513a-5p with its oncogenic potential further validates the use of miRNAs as long-term biomarker of breast cancer risk. © The Author(s) 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Identification of differentially expressed small RNAs and prediction of target genes in Italian Large White pigs with divergent backfat deposition.

PubMed

Davoli, R; Gaffo, E; Zappaterra, M; Bortoluzzi, S; Zambonelli, P

2018-06-01

The identification of the molecular mechanisms regulating pathways associated with the potential for fat deposition in pigs can lead to the detection of key genes and markers for the genetic improvement of fat traits. Interactions of microRNAs (miRNAs) with target RNAs regulate gene expression and modulate pathway activation in cells and tissues. In pigs, miRNA discovery is far from saturation, and the knowledge of miRNA expression in backfat tissue and particularly of the impact of miRNA variations is still fragmentary. Using RNA-seq, we characterized the small RNA (sRNA) expression profiles in Italian Large White pig backfat tissue. Comparing two groups of pigs divergent for backfat deposition, we detected 31 significant differentially expressed (DE) sRNAs: 14 up-regulated (including ssc-miR-132, ssc-miR-146b, ssc-miR-221-5p, ssc-miR-365-5p and the moRNA ssc-moR-21-5p) and 17 down-regulated (including ssc-miR-136, ssc-miR-195, ssc-miR-199a-5p and ssc-miR-335). To understand the biological impact of the observed miRNA expression variations, we used the expression correlation of DE miRNA target transcripts expressed in the same samples to define a regulatory network of 193 interactions between DE miRNAs and 40 DE target transcripts showing opposite expression profiles and being involved in specific pathways. Several miRNAs and mRNAs in the network were found to be expressed from backfat-related pig QTL. These results are informative for the complex mechanisms influencing fat traits, shed light on a new aspect of the genetic regulation of fat deposition in pigs and facilitate the prospective implementation of innovative strategies of pig genetic improvement based on genomic markers. © 2018 Stichting International Foundation for Animal Genetics.

Degrees of Resilience: Profiling Psychological Resilience and Prospective Academic Achievement in University Inductees

ERIC Educational Resources Information Center

Allan, John F.; McKenna, Jim; Dominey, Susan

2014-01-01

University inductees may be increasingly vulnerable to stressors during transition into higher education (HE), requiring psychological resilience to achieve academic success. This study aimed to profile inductees' resilience and to investigate links to prospective end of year academic outcomes. Scores for resilience were based on a validated…

Genome and transcriptome sequencing in prospective metastatic triple-negative breast cancer uncovers therapeutic vulnerabilities.

PubMed

Craig, David W; O'Shaughnessy, Joyce A; Kiefer, Jeffrey A; Aldrich, Jessica; Sinari, Shripad; Moses, Tracy M; Wong, Shukmei; Dinh, Jennifer; Christoforides, Alexis; Blum, Joanne L; Aitelli, Cristi L; Osborne, Cynthia R; Izatt, Tyler; Kurdoglu, Ahmet; Baker, Angela; Koeman, Julie; Barbacioru, Catalin; Sakarya, Onur; De La Vega, Francisco M; Siddiqui, Asim; Hoang, Linh; Billings, Paul R; Salhia, Bodour; Tolcher, Anthony W; Trent, Jeffrey M; Mousses, Spyro; Von Hoff, Daniel; Carpten, John D

2013-01-01

Triple-negative breast cancer (TNBC) is characterized by the absence of expression of estrogen receptor, progesterone receptor, and HER-2. Thirty percent of patients recur after first-line treatment, and metastatic TNBC (mTNBC) has a poor prognosis with median survival of one year. Here, we present initial analyses of whole genome and transcriptome sequencing data from 14 prospective mTNBC. We have cataloged the collection of somatic genomic alterations in these advanced tumors, particularly those that may inform targeted therapies. Genes mutated in multiple tumors included TP53, LRP1B, HERC1, CDH5, RB1, and NF1. Notable genes involved in focal structural events were CTNNA1, PTEN, FBXW7, BRCA2, WT1, FGFR1, KRAS, HRAS, ARAF, BRAF, and PGCP. Homozygous deletion of CTNNA1 was detected in 2 of 6 African Americans. RNA sequencing revealed consistent overexpression of the FOXM1 gene when tumor gene expression was compared with nonmalignant breast samples. Using an outlier analysis of gene expression comparing one cancer with all the others, we detected expression patterns unique to each patient's tumor. Integrative DNA/RNA analysis provided evidence for deregulation of mutated genes, including the monoallelic expression of TP53 mutations. Finally, molecular alterations in several cancers supported targeted therapeutic intervention on clinical trials with known inhibitors, particularly for alterations in the RAS/RAF/MEK/ERK and PI3K/AKT/mTOR pathways. In conclusion, whole genome and transcriptome profiling of mTNBC have provided insights into somatic events occurring in this difficult to treat cancer. These genomic data have guided patients to investigational treatment trials and provide hypotheses for future trials in this irremediable cancer.

Prospective assessment of a gene signature potentially predictive of clinical benefit in metastatic melanoma patients following MAGE-A3 immunotherapeutic (PREDICT).

PubMed

Saiag, P; Gutzmer, R; Ascierto, P A; Maio, M; Grob, J-J; Murawa, P; Dreno, B; Ross, M; Weber, J; Hauschild, A; Rutkowski, P; Testori, A; Levchenko, E; Enk, A; Misery, L; Vanden Abeele, C; Vojtek, I; Peeters, O; Brichard, V G; Therasse, P

2016-10-01

Genomic profiling of tumor tissue may aid in identifying predictive or prognostic gene signatures (GS) in some cancers. Retrospective gene expression profiling of melanoma and non-small-cell lung cancer led to the characterization of a GS associated with clinical benefit, including improved overall survival (OS), following immunization with the MAGE-A3 immunotherapeutic. The goal of the present study was to prospectively evaluate the predictive value of the previously characterized GS. An open-label prospective phase II trial ('PREDICT') in patients with MAGE-A3-positive unresectable stage IIIB-C/IV-M1a melanoma. Of 123 subjects who received the MAGE-A3 immunotherapeutic, 71 (58.7%) displayed the predictive GS (GS+). The 1-year OS rate was 83.1%/83.3% in the GS+/GS- populations. The rate of progression-free survival at 12 months was 5.8%/4.1% in GS+/GS- patients. The median time-to-treatment failure was 2.7/2.4 months (GS+/GS-). There was one complete response (GS-) and two partial responses (GS+). The MAGE-A3 immunotherapeutic was similarly immunogenic in both populations and had a clinically acceptable safety profile. Treatment of patients with MAGE-A3-positive unresectable stage IIIB-C/IV-M1a melanoma with the MAGE-A3 immunotherapeutic demonstrated an overall 1-year OS rate of 83.5%. GS- and GS+ patients had similar 1-year OS rates, indicating that in this study, GS was not predictive of outcome. Unexpectedly, the objective response rate was lower in this study than in other studies carried out in the same setting with the MAGE-A3 immunotherapeutic. Investigation of a GS to predict clinical benefit to adjuvant MAGE-A3 immunotherapeutic treatment is ongoing in another melanoma study.This study is registered at www.clinicatrials.gov NCT00942162. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

Evaluation of a 30-gene paclitaxel, fluorouracil, doxorubicin and cyclophosphamide chemotherapy response predictor in a multicenter randomized trial in breast cancer

PubMed Central

Tabchy, Adel; Valero, Vicente; Vidaurre, Tatiana; Lluch, Ana; Gomez, Henry; Martin, Miguel; Qi, Yuan; Barajas-Figueroa, Luis Javier; Souchon, Eduardo; Coutant, Charles; Doimi, Franco D; Ibrahim, Nuhad K; Gong, Yun; Hortobagyi, Gabriel N; Hess, Kenneth R; Symmans, W Fraser; Pusztai, Lajos

2010-01-01

Purpose We examined in a prospective, randomized, international clinical trial the performance of a previously defined 30-gene predictor (DLDA-30) of pathologic complete response (pCR) to preoperative weekly paclitaxel and fluorouracil, doxorubicin, cyclophosphamide (T/FAC) chemotherapy, and assessed if DLDA-30 also predicts increased sensitivity to FAC-only chemotherapy. We compared the pCR rates after T/FAC versus FAC×6 preoperative chemotherapy. We also performed an exploratory analysis to identify novel candidate genes that differentially predict response in the two treatment arms. Experimental Design 273 patients were randomly assigned to receive either weekly paclitaxel × 12 followed by FAC × 4 (T/FAC, n=138), or FAC × 6 (n=135) neoadjuvant chemotherapy. All patients underwent a pretreatment FNA biopsy of the tumor for gene expression profiling and treatment response prediction. Results The pCR rates were 19% and 9% in the T/FAC and FAC arms, respectively (p<0.05). In the T/FAC arm, the positive predictive value (PPV) of the genomic predictor was 38% (95%CI:21–56%), the negative predictive value (NPV) 88% (CI:77–95%) and the AUC 0.711. In the FAC arm, the PPV was 9% (CI:1–29%) and the AUC 0.584. This suggests that the genomic predictor may have regimen-specificity. Its performance was similar to a clinical variable-based predictor nomogram. Conclusions Gene expression profiling for prospective response prediction was feasible in this international trial. The 30-gene predictor can identify patients with greater than average sensitivity to T/FAC chemotherapy. However, it captured molecular equivalents of clinical phenotype. Next generation predictive markers will need to be developed separately for different molecular subsets of breast cancers. PMID:20829329

Neural cell adhesion molecule-deficient beta-cell tumorigenesis results in diminished extracellular matrix molecule expression and tumour cell-matrix adhesion.

PubMed

Håkansson, Joakim; Xian, Xiaojie; He, Liqun; Ståhlberg, Anders; Nelander, Sven; Samuelsson, Tore; Kubista, Mikael; Semb, Henrik

2005-01-01

To understand by which mechanism neural cell adhesion molecule (N-CAM) limits beta tumour cell disaggregation and dissemination, we searched for potential downstream genes of N-CAM during beta tumour cell progression by gene expression profiling. Here, we show that N-CAM-deficient beta-cell tumorigenesis is associated with changes in the expression of genes involved in cell-matrix adhesion and cytoskeletal dynamics, biological processes known to affect the invasive and metastatic behaviour of tumour cells. The extracellular matrix (ECM) molecules emerged as the primary target, i.e. N-CAM deficiency resulted in down-regulated mRNA expression of a broad range of ECM molecules. Consistent with this result, deficient deposition of major ECM stromal components, such as fibronectin, laminin 1 and collagen IV, was observed. Moreover, N-CAM-deficient tumour cells displayed defective matrix adhesion. These results offer a potential mechanism for tumour cell disaggregation during N-CAM-deficient beta tumour cell progression. Prospective consequences of these findings for the role of N-CAM in beta tumour cell dissemination are discussed.

Profile of Prospective Physics Teachers on Assessment Literacy

NASA Astrophysics Data System (ADS)

Efendi, R.; Rustaman, N. Y.; Kaniawati, I.

2017-02-01

A study about assessment literacy of prospective Physics teachers was conducted with the involvement of 45 prospective physics teachers. Data collected by using test consisted of seven competencies. The profile of prospective physics teachers on assessment literacy determined in descriptive statistics, in the form of respondent average values. Research finding shows that prospective physics teachers were weak at all competency areas. The average values of the Choosing assessment methods appropriate for instructional decisions is the highest average values and the average values of the communicating assessment results to students, parents, other lay audiences, and other educators is the lowest average values. In depth study to detect the reason underlined the results was still in progress so far, as another aspect was planned to be administered on the next semester.

Dose profiles for lung and breast regions at prospective and retrospective CT coronary angiography using optically stimulated luminescence dosimeters on a 64-detector CT scanner.

PubMed

Funama, Yoshinori; Taguchi, Katsuyuki; Utsunomiya, Daisuke; Oda, Seitaro; Murasaki, Hiroo; Yamashita, Yasuyuki; Awai, Kazuo

2012-01-01

The purpose of our study was to acquire dose profiles at critical organs of lung and breast regions using optically stimulated luminescence (OSL) dosimeters; assess the actual radiation dose delivered at retrospective and prospective computed tomography coronary angiography (CTCA). Using a chest CT phantom we applied a prospectively-gated step-and-shoot- and a retrospectively-gated helical mode on a 64-detector row CT scanner. Retrospective scan mode was used with and without electrocardiogram (ECG) based tube current modulation. OSL dosimeters were used to measure dose profiles. In the both scan modes we acquired dose profiles and determined the mean and maximum dose in left lung and in left breast regions. In prospective mode, the mean dose was 21.53 mGy in left lung- and 23.59 mGy in left breast region. With respect to the retrospective mode, the mean dose with tube current modulation was 38.63 mGy for left lung- and 46.02 mGy for left breast region, i.e. 0.56 and 0.55 times lower than the mean dose without modulation. The OSL dosimeter is useful for measurement of the actual radiation dose along z-axis at lung and breast regions in the prospective and the retrospective CTCA. Copyright © 2011 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Profiling of ABC transporters ABCB5, ABCF2 and nestin-positive stem cells in nevi, in situ and invasive melanoma.

PubMed

Setia, Namrata; Abbas, Ossama; Sousa, Yessica; Garb, Jane L; Mahalingam, Meera

2012-08-01

Distinct ABCB5 forms and ABCF2, members of the ATP-binding cassette (ABC) superfamily of transporters, are normally expressed in various tissues and cells, and enhanced expression of both has been demonstrated in select cancers. In melanoma cell lines, gene expression profiling of ABC transporters has revealed enhanced expression of melanocyte-specific ABCB5 and ABCF2 proteins. Given this, our primary aim was to ascertain immunohistochemical expression of the ABC transporters ABCB5 and ABCF2 and, the stem cell marker, nestin in a spectrum of benign and malignant nevomelanocytic proliferations, including nevi (n=30), in situ (n=31) and invasive (n=24) primary cutaneous melanomas to assess their role in the stepwise development of malignancy. In addition, their expression was compared with established melanoma prognosticators to ascertain their utility as independent prognosticators. A semiquantitative scoring system was utilized by deriving a cumulative score (based on percentage positivity cells and intensity of expression) and statistical analyses was carried out using analysis of variance with linear contrasts. Mean cumulative score in nevi, in situ and invasive melanoma were as follows: 3.8, 4.4 and 5.3 for ABCB5, respectively (P<0.005 for all), and 4.6, 4.6 and 5.3 for nestin, respectively (P=not significant for all). No appreciable expression of ABCF2 was noted in any of the groups. While ulcerated lesions of melanoma demonstrated lower levels of expression of ABCB5 and nestin than non-ulcerated lesions, and nestin expression was lower in lesions with mitoses >1, after controlling for the presence of ulceration and mitotic activity, the expression of both proteins did not significantly correlate with known melanoma prognosticators. The gradual increase in the expression of ABCB5 from benign nevus to in situ to invasive melanoma suggests that it plays a role in melanomagenesis. On the basis of our findings, a prospective study with follow-up data is required to ascertain the utility of ABCB5 as a therapeutic target.

EGFR molecular profiling in advanced NSCLC: a prospective phase II study in molecularly/clinically selected patients pretreated with chemotherapy.

PubMed

Milella, Michele; Nuzzo, Carmen; Bria, Emilio; Sperduti, Isabella; Visca, Paolo; Buttitta, Fiamma; Antoniani, Barbara; Merola, Roberta; Gelibter, Alain; Cuppone, Federica; D'Alicandro, Valerio; Ceribelli, Anna; Rinaldi, Massimo; Cianciulli, Anna; Felicioni, Lara; Malatesta, Sara; Marchetti, Antonio; Mottolese, Marcella; Cognetti, Francesco

2012-04-01

The optimal use of epidermal growth factor receptor (EGFR)-related molecular markers to prospectively identify tyrosine kinase inhibitor (TKI)-sensitive patients, particularly after a previous chemotherapy treatment, is currently under debate. We designed a prospective phase II study to evaluate the activity of EGFR-TKI in four different patient groups, according to the combination of molecular (EGFR gene mutations, EGFR gene copy number and protein expression, and phosphorylated AKT expression, pAKT) and clinicopathological (histology and smoking habits) factors. Correlations between molecular alterations and clinical outcome were also explored retrospectively for first-line chemotherapy and EGFR-TKI treatment. Patients who had progressed during or after first-line chemotherapy were prospectively assigned to EGFR-TKI treatment as follows: (G1) EGFR mutation (n = 12); (G2) highly polysomic/amplified EGFR (n = 18); (G3) EGFR and/or pAKT positive (n = 41); (G4) adenocarcinoma/bronchoalveolar carcinoma and no smoking history (n = 15). G1 and G4 had the best and second-best overall response rate (25% and 20%, respectively), whereas the worst outcome was observed in G2 (ORR, 6%; p = 0.05). Disease control was highest in G1 and G4 (>50%) and lowest in G3 (<20%) (p = 0.02). Patients selected by EGFR mutation or clinical parameters (G1 and G4) also had significantly better progression-free survival and overall survival (p = 0.02 and p = 0.01, respectively). Multivariate analysis confirmed the impact of sex, smoking history, EGFR/KRAS mutation, and pAKT on outcomes and allowed us to derive an efficient predictive model. Histology, EGFR mutations, and pAKT were independent predictors of response to first-line chemotherapy at retrospective analysis, whereas pAKT and human epidermal growth factor receptor 2 expression were the only independent predictors of progression-free survival and overall survival. Selection of patients based on either EGFR mutation or clinical characteristics seems an effective approach to optimize EGFR-TKI treatment in chemotherapy-pretreated non-small-cell lung cancer patients.

Thickness and an Altered miRNA Expression in the Epicardial Adipose Tissue Is Associated With Coronary Heart Disease in Sudden Death Victims.

PubMed

Marí-Alexandre, Josep; Barceló-Molina, Moises; Sanz-Sánchez, Jorge; Molina, Pilar; Sancho, Jennifer; Abellán, Yolanda; Santaolaria-Ayora, María Luisa; Giner, Juan; Martínez-Dolz, Luis; Estelles, Amparo; Braza-Boïls, Aitana; Zorio, Esther

2018-02-10

An increased epicardial adipose tissue (EAT) thickness has become a new risk factor for coronary heart disease (CHD). We aimed to study the role of EAT dysfunction as a CHD marker by focusing on its thickness and microRNA (miRNA) expression profile, and the potential factors possibly influencing them. One hundred and fifty-five CHD sudden cardiac death victims and 84 non-CHD-sudden death controls were prospectively enrolled at autopsy. A representative subset underwent EAT thickness measurements and EAT miRNA expression profiling. Epicardial adipose tissue thickness was increased and allowed an accurate diagnosis of patient status (among other measurements, EAT score area under the curve 0.718, P < .001). Epicardial adipose tissue from patients showed 14 up- and 14 down-regulated miRNAs and miR-34a-3p, -34a-5p, -124-3p, -125a-5p, 628-5p, -1303 and -4286 were validated by quantitative real-time polymerase chain reaction. Patients exhibited higher EAT levels of miR-34a-3p and -34a-5p than controls (with a positive trend considering EAT from coronaries without stenosis, with stable stenosis and complicated plaques) and correlated with age only in controls. The mild positive correlation between liver and EAT miR-34a-5p levels in patients (r = 0.295, P = .020) dramatically increased in EAT from complicated plaques (r = 0.799, P = .017). Similar correlations were observed for high-sensitivity-C-reactive protein levels and miR-34a-5p levels both in EAT and liver extracts. Increased age-independent levels of miR-34a-3p and -34a-5p characterize the EAT miRNA expression profile of CHD regardless of EAT thickness, anthropometric parameters, and the presence of underlying atherosclerotic plaques. Copyright © 2018 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.

The search for biomarkers of human embryo developmental potential in IVF: a comprehensive proteomic approach.

PubMed

Nyalwidhe, Julius; Burch, Tanya; Bocca, Silvina; Cazares, Lisa; Green-Mitchell, Shamina; Cooke, Marissa; Birdsall, Paige; Basu, Gaurav; Semmes, O John; Oehninger, Sergio

2013-04-01

The objective of these studies was to identify differentially expressed peptides/proteins in the culture media of embryos grown during in vitro fertilization (IVF) treatment to establish their value as biomarkers predictive of implantation potential and live birth. Micro-droplets of embryo culture media from IVF patients (conditioned) and control media maintained under identical culture conditions were collected and frozen at -80°C on Days 2-3 of in vitro development prior to analysis. The embryos were transferred on Day 3. The peptides were affinity purified based on their physico-chemical properties and profiled by mass spectrometry for differential expression. The identified proteins were further characterized by western blot and ELISA, and absolute quantification was achieved by multiple reaction monitoring (MRM). We identified up to 14 differentially regulated peptides after capture using paramagnetic beads with different affinities. These differentially expressed peptides were used to generate genetic algorithms (GAs) with a recognition capability of 71-84% for embryo transfer cycles resulting in pregnancy and 75-89% for those with failed implantation. Several peptides were further identified as fragments of Apolipoprotein A-1, which showed consistent and significantly reduced expression in the embryo media samples from embryo transfer cycles resulting in viable pregnancies. Western blot and ELISA, as well as quantitative MRM results, were confirmatory. These results demonstrated that peptide/protein profiles from the culture medium during early human in vitro development can discriminate embryos with highest and lowest implantation competence following uterine transfer. Further prospective studies are needed to establish validated thresholds for clinical application.

Gene Expression Profiling of Benign and Malignant Pheochromocytoma

PubMed Central

BROUWERS, FREDERIEKE M.; ELKAHLOUN, ABDEL G.; MUNSON, PETER J.; EISENHOFER, GRAEME; BARB, JENNIFER; LINEHAN, W. MARSTON; LENDERS, JACQUES W.M.; DE KRIJGER, RONALD; MANNELLI, MASSIMO; UDELSMAN, ROBERT; OCAL, IDRIS T.; SHULKIN, BARRY L.; BORNSTEIN, STEFAN R.; BREZA, JAN; KSINANTOVA, LUCIA; PACAK, KAREL

2016-01-01

There are currently no reliable diagnostic and prognostic markers or effective treatments for malignant pheochromocytoma. This study used oligonucleotide microarrays to examine gene expression profiles in pheochromocytomas from 90 patients, including 20 with malignant tumors, the latter including metastases and primary tumors from which metastases developed. Other subgroups of tumors included those defined by tissue norepinephrine compared to epinephrine contents (i.e., noradrenergic versus adrenergic phenotypes), adrenal versus extra-adrenal locations, and presence of germline mutations of genes pre-disposing to the tumor. Correcting for the confounding influence of nora-drenergic versus adrenergic catecholamine phenotype by the analysis of variance revealed a larger and more accurate number of genes that discriminated benign from malignant pheochromocytomas than when the confounding influence of catecholamine phenotype was not considered. Seventy percent of these genes were underexpressed in malignant compared to benign tumors. Similarly, 89% of genes were underexpressed in malignant primary tumors compared to benign tumors, suggesting that malignant potential is largely characterized by a less-differentiated pattern of gene expression. The present database of differentially expressed genes provides a unique resource for mapping the pathways leading to malignancy and for establishing new targets for treatment and diagnostic and prognostic markers of malignant disease. The database may also be useful for examining mechanisms of tumorigenesis and genotype–phenotype relationships. Further progress on the basis of this database can be made from follow-up confirmatory studies, application of bioinformatics approaches for data mining and pathway analyses, testing in pheochromocytoma cell culture and animal model systems, and retrospective and prospective studies of diagnostic markers. PMID:17102123

Gene Expression Changes Underlying Idiopathic Central Hypogonadism in Cryptorchidism with Defective Mini-Puberty.

PubMed

Hadziselimovic, Faruk; Gegenschatz-Schmid, Katharina; Verkauskas, Gilvydas; Docampo-Garcia, Maria J; Demougin, Philippe; Bilius, Vytautas; Malcius, Dalius; Dasevicius, Darius; Stadtler, Michael B

2016-01-01

The whole genome RNA profiling of testicular biopsies by DNA strand-specific RNA sequencing was examined to determine a potential causative role of isolated congenital cryptorchidism in azoospermia and/or infertility in the context of our previously published GeneChip data. Cryptorchid patients, aged 7 months to 5 years and otherwise healthy, were enrolled in this prospective study. During surgery, testicular tissue biopsies were obtained for histological examination and RNA sequencing. Fifteen patients were selected based on the histological results and were divided into 2 groups. Seven were classified as belonging to the high infertility risk (HIR) and 8 to the low infertility risk (LIR) group. Cryptorchid boys in the HIR group lacked transformation of gonocytes into Ad spermatogonia due to impaired mini-puberty. This group of patients will be infertile despite successful surgery. The new important finding was a decreased PROK2, CHD7, FGFR1, and SPRY4 gene expression in the HIR group. Furthermore, identification of multiple differences in gene expression between HIR and LIR groups underscores the importance of an intact hypothalamic-pituitary-gonadal axis for fertility development. Our RNA profiling data strongly support the theory that in the HIR group of cryptorchid boys insufficient PROK2/CHD7/FGFR1/SPRY4 gene expression induces deficient LH secretion, resulting in impaired mini-puberty and infertility. We therefore recommend hormonal treatment for this cohort of cryptorchid boys with defective mini-puberty following a seemingly successful orchidopexy. © 2016 The Author(s) Published by S. Karger AG, Basel.

Tumour-associated and non-tumour-associated microbiota in colorectal cancer

PubMed Central

Flemer, Burkhardt; Lynch, Denise B; Brown, Jillian M R; Jeffery, Ian B; Ryan, Feargal J; Claesson, Marcus J; O'Riordain, Micheal; Shanahan, Fergus; O'Toole, Paul W

2017-01-01

Objective A signature that unifies the colorectal cancer (CRC) microbiota across multiple studies has not been identified. In addition to methodological variance, heterogeneity may be caused by both microbial and host response differences, which was addressed in this study. Design We prospectively studied the colonic microbiota and the expression of specific host response genes using faecal and mucosal samples (‘ON’ and ‘OFF’ the tumour, proximal and distal) from 59 patients undergoing surgery for CRC, 21 individuals with polyps and 56 healthy controls. Microbiota composition was determined by 16S rRNA amplicon sequencing; expression of host genes involved in CRC progression and immune response was quantified by real-time quantitative PCR. Results The microbiota of patients with CRC differed from that of controls, but alterations were not restricted to the cancerous tissue. Differences between distal and proximal cancers were detected and faecal microbiota only partially reflected mucosal microbiota in CRC. Patients with CRC can be stratified based on higher level structures of mucosal-associated bacterial co-abundance groups (CAGs) that resemble the previously formulated concept of enterotypes. Of these, Bacteroidetes Cluster 1 and Firmicutes Cluster 1 were in decreased abundance in CRC mucosa, whereas Bacteroidetes Cluster 2, Firmicutes Cluster 2, Pathogen Cluster and Prevotella Cluster showed increased abundance in CRC mucosa. CRC-associated CAGs were differentially correlated with the expression of host immunoinflammatory response genes. Conclusions CRC-associated microbiota profiles differ from those in healthy subjects and are linked with distinct mucosal gene-expression profiles. Compositional alterations in the microbiota are not restricted to cancerous tissue and differ between distal and proximal cancers. PMID:26992426

Oligonucleotide therapeutics in neurodegenerative diseases.

PubMed

Scoles, Daniel R; Pulst, Stefan M

2018-03-21

Therapeutics that directly target RNAs are promising for a broad spectrum of disorders, including the neurodegenerative diseases. This is exemplified by the FDA approval of Nusinersen, an antisense oligonucleotide (ASO) therapeutic for spinal muscular atrophy (SMA). RNA targeting therapeutics are currently under development for amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and spinocerebellar ataxias. We have used an ASO approach toward developing a treatment for spinocerebellar ataxia type 2 (SCA2), for targeting the causative gene ATXN2. We demonstrated that reduction of ATXN2 expression in SCA2 mice treated by intracerebroventicular injection (ICV) of ATXN2 ASO delayed motor phenotype onset, improved the expression of several genes demonstrated abnormally reduced by transcriptomic profiling of SCA2 mice, and restored abnormal Purkinje cell firing frequency in acute cerebellar sections. Here we discuss RNA abnormalities in disease and the prospects of targeting neurodegenerative diseases at the level of RNA control using ASOs and other RNA-targeted therapeutics.

Steroid profiling for congenital adrenal hyperplasia by tandem mass spectrometry as a second-tier test reduces follow-up burdens in a tertiary care hospital: a retrospective and prospective evaluation.

PubMed

Seo, Ja Young; Park, Hyung-Doo; Kim, Jong Won; Oh, Hyeon Ju; Yang, Jeong Soo; Chang, Yun Sil; Park, Won Soon; Lee, Soo-Youn

2014-01-01

Newborn screening for congenital adrenal hyperplasia (CAH) based on measuring 17-hydroxyprogesterone (17-OHP) by immunoassay generates a number of false-positive results, especially in preterm neonates. We applied steroid profiling by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) as a second-tier test in newborns with positive CAH screening and evaluated its clinical utility in a tertiary care hospital setting. By performing a 4-year retrospective data review, we were able to test 121 dried blood spots from newborns with positive CAH screening for 17-OHP, androstenedione and cortisol levels by LC-MS/MS. We prospectively evaluated the clinical utility of steroid profiling after the implementation of steroid profiling as a second-tier test in our routine clinical practice. During the 2-year prospective study period, 104 cases with positive initial screening by FIA were tested by LC-MS/MS. Clinical and laboratory follow-up were performed for at least 6 months. The preterm neonates accounted for 50.7% (76/150) and 70.4% (88/125) of screening-positive cases in retrospective and prospective cohorts, respectively. By applying steroid profiling as a second-tier test for positive CAH screening, we eliminated all false-positive results and decreased the median follow-up time from 75 to 8 days. Our data showed that steroid profiling reduced the burden of follow-up exams by improving the positive predictive value of the CAH screening program. The use of steroid profiling as a second-tier test for positive CAH screening will improve clinical practice particularly in a tertiary care hospital setting where positive CAH screening from preterm neonates is frequently encountered.

Onset of human preterm and term birth is related to unique inflammatory transcriptome profiles at the maternal fetal interface.

PubMed

Bukowski, Radek; Sadovsky, Yoel; Goodarzi, Hani; Zhang, Heping; Biggio, Joseph R; Varner, Michael; Parry, Samuel; Xiao, Feifei; Esplin, Sean M; Andrews, William; Saade, George R; Ilekis, John V; Reddy, Uma M; Baldwin, Donald A

2017-01-01

Preterm birth is a main determinant of neonatal mortality and morbidity and a major contributor to the overall mortality and burden of disease. However, research of the preterm birth is hindered by the imprecise definition of the clinical phenotype and complexity of the molecular phenotype due to multiple pregnancy tissue types and molecular processes that may contribute to the preterm birth. Here we comprehensively evaluate the mRNA transcriptome that characterizes preterm and term labor in tissues comprising the pregnancy using precisely phenotyped samples. The four complementary phenotypes together provide comprehensive insight into preterm and term parturition. Samples of maternal blood, chorion, amnion, placenta, decidua, fetal blood, and myometrium from the uterine fundus and lower segment ( n  = 183) were obtained during cesarean delivery from women with four complementary phenotypes: delivering preterm with (PL) and without labor (PNL), term with (TL) and without labor (TNL). Enrolled were 35 pregnant women with four precisely and prospectively defined phenotypes: PL ( n  = 8), PNL ( n  = 10), TL ( n  = 7) and TNL ( n  = 10). Gene expression data were analyzed using shrunken centroid analysis to identify a minimal set of genes that uniquely characterizes each of the four phenotypes. Expression profiles of 73 genes and non-coding RNA sequences uniquely identified each of the four phenotypes. The shrunken centroid analysis and 10 times 10-fold cross-validation was also used to minimize false positive finings and overfitting. Identified were the pathways and molecular processes associated with and the cis-regulatory elements in gene's 5' promoter or 3'-UTR regions of the set of genes which expression uniquely characterized the four phenotypes. The largest differences in gene expression among the four groups occurred at maternal fetal interface in decidua, chorion and amnion. The gene expression profiles showed suppression of chemokines expression in TNL, withdrawal of this suppression in TL, activation of multiple pathways of inflammation in PL, and an immune rejection profile in PNL. The genes constituting expression signatures showed over-representation of three putative regulatory elements in their 5'and 3' UTR regions. The results suggest that pregnancy is maintained by downregulation of chemokines at the maternal-fetal interface. Withdrawal of this downregulation results in the term birth and its overriding by the activation of multiple pathways of the immune system in the preterm birth. Complications of the pregnancy associated with impairment of placental function, which necessitated premature delivery of the fetus in the absence of labor, show gene expression patterns associated with immune rejection.

Onset of human preterm and term birth is related to unique inflammatory transcriptome profiles at the maternal fetal interface

PubMed Central

Sadovsky, Yoel; Goodarzi, Hani; Zhang, Heping; Biggio, Joseph R.; Varner, Michael; Parry, Samuel; Xiao, Feifei; Esplin, Sean M.; Andrews, William; Saade, George R.; Ilekis, John V.; Reddy, Uma M.; Baldwin, Donald A.

2017-01-01

Background Preterm birth is a main determinant of neonatal mortality and morbidity and a major contributor to the overall mortality and burden of disease. However, research of the preterm birth is hindered by the imprecise definition of the clinical phenotype and complexity of the molecular phenotype due to multiple pregnancy tissue types and molecular processes that may contribute to the preterm birth. Here we comprehensively evaluate the mRNA transcriptome that characterizes preterm and term labor in tissues comprising the pregnancy using precisely phenotyped samples. The four complementary phenotypes together provide comprehensive insight into preterm and term parturition. Methods Samples of maternal blood, chorion, amnion, placenta, decidua, fetal blood, and myometrium from the uterine fundus and lower segment (n = 183) were obtained during cesarean delivery from women with four complementary phenotypes: delivering preterm with (PL) and without labor (PNL), term with (TL) and without labor (TNL). Enrolled were 35 pregnant women with four precisely and prospectively defined phenotypes: PL (n = 8), PNL (n = 10), TL (n = 7) and TNL (n = 10). Gene expression data were analyzed using shrunken centroid analysis to identify a minimal set of genes that uniquely characterizes each of the four phenotypes. Expression profiles of 73 genes and non-coding RNA sequences uniquely identified each of the four phenotypes. The shrunken centroid analysis and 10 times 10-fold cross-validation was also used to minimize false positive finings and overfitting. Identified were the pathways and molecular processes associated with and the cis-regulatory elements in gene’s 5′ promoter or 3′-UTR regions of the set of genes which expression uniquely characterized the four phenotypes. Results The largest differences in gene expression among the four groups occurred at maternal fetal interface in decidua, chorion and amnion. The gene expression profiles showed suppression of chemokines expression in TNL, withdrawal of this suppression in TL, activation of multiple pathways of inflammation in PL, and an immune rejection profile in PNL. The genes constituting expression signatures showed over-representation of three putative regulatory elements in their 5′and 3′ UTR regions. Conclusions The results suggest that pregnancy is maintained by downregulation of chemokines at the maternal-fetal interface. Withdrawal of this downregulation results in the term birth and its overriding by the activation of multiple pathways of the immune system in the preterm birth. Complications of the pregnancy associated with impairment of placental function, which necessitated premature delivery of the fetus in the absence of labor, show gene expression patterns associated with immune rejection. PMID:28879060

21 CFR 862.1163 - Cardiac allograft gene expression profiling test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cardiac allograft gene expression profiling test... Chemistry Test Systems § 862.1163 Cardiac allograft gene expression profiling test system. (a) Identification. A cardiac allograft gene expression profiling test system is a device that measures the...

Deregulation of SYCP2 predicts early stage human papillomavirus-positive oropharyngeal carcinoma: A prospective whole transcriptome analysis.

PubMed

Masterson, Liam; Sorgeloos, Frederic; Winder, David; Lechner, Matt; Marker, Alison; Malhotra, Shalini; Sudhoff, Holger; Jani, Piyush; Goon, Peter; Sterling, Jane

2015-11-01

This study was designed to identify significant differences in gene expression profiles of human papillomavirus (HPV)-positive and HPV-negative oropharyngeal squamous cell carcinomas (OPSCC) and to better understand the functional and biological effects of HPV infection in the premalignant pathway. Twenty-four consecutive patients with locally advanced primary OPSCC were included in a prospective clinical trial. Fresh tissue samples (tumor vs. matched normal epithelium) were subjected to whole transcriptome analysis and the results validated on the same cohort with RT-quantitative real-time PCR. In a separate retrospective cohort of 27 OPSCC patients, laser capture microdissection of formalin-fixed, paraffin-embedded tissue allowed RNA extraction from adjacent regions of normal epithelium, carcinoma in situ (premalignant) and invasive SCC tissue. The majority of patients showed evidence of high-risk HPV16 positivity (80.4%). Predictable fold changes of RNA expression in HPV-associated disease included multiple transcripts within the p53 oncogenic pathway (e.g. CDKN2A/CCND1). Other candidate transcripts found to have altered levels of expression in this study have not previously been established (SFRP1, CRCT1, DLG2, SYCP2, and CRNN). Of these, SYCP2 showed the most consistent fold change from baseline in premalignant tissue; aberrant expression of this protein may contribute to genetic instability during HPV-associated cancer development. If further corroborated, this data may contribute to the development of a non-invasive screening tool. This study is registered with the UK Clinical Research Network (ref.: 11945). © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Integrated analysis of DNA methylation, immunohistochemistry and mRNA expression, data identifies a Methylation Expression Index (MEI) robustly associated with survival of ER-positive breast cancer patients

PubMed Central

Garcia-Closas, Montserrat; Davis, Sean; Meltzer, Paul; Lissowska, Jolanta; Horne, Hisani N.; Sherman, Mark E.; Lee, Maxwell

2015-01-01

Identification of prognostic gene expression signatures may enable improved decisions about management of breast cancer. To identify a prognostic signature for breast cancer, we performed DNA methylation profiling and identified methylation markers that were associated with expression of ER, PR, HER2, CK5/6 and EGFR proteins. Methylation markers that were correlated with corresponding mRNA expression levels were identified using 208 invasive tumors from a population-based case-control study conducted in Poland. Using this approach, we defined the Methylation Expression Index (MEI) signature that was based on a weighted sum of mRNA levels of 57 genes. Classification of cases as low or high MEI scores were related to survival using Cox regression models. In the Polish study, women with ER-positive low MEI cancers had reduced survival at a median of 5.20 years of follow-up, HR=2.85 95%CI=1.25-6.47. Low MEI was also related to decreased survival in four independent datasets totaling over 2500 ER-positive breast cancers. These results suggest that integrated analysis of tumor expression markers, DNA methylation, and mRNA data can be an important approach for identifying breast cancer prognostic signatures. Prospective assessment of MEI along with other prognostic signatures should be evaluated in future studies. PMID:25773928

Opposing Shh and Fgf signals initiate nasotemporal patterning of the zebrafish retina.

PubMed

Hernández-Bejarano, María; Gestri, Gaia; Spawls, Lana; Nieto-López, Francisco; Picker, Alexander; Tada, Masazumi; Brand, Michael; Bovolenta, Paola; Wilson, Stephen W; Cavodeassi, Florencia

2015-11-15

The earliest known determinants of retinal nasotemporal identity are the transcriptional regulators Foxg1, which is expressed in the prospective nasal optic vesicle, and Foxd1, which is expressed in the prospective temporal optic vesicle. Previous work has shown that, in zebrafish, Fgf signals from the dorsal forebrain and olfactory primordia are required to specify nasal identity in the dorsal, prospective nasal, optic vesicle. Here, we show that Hh signalling from the ventral forebrain is required for specification of temporal identity in the ventral optic vesicle and is sufficient to induce temporal character when activated in the prospective nasal retina. Consequently, the evaginating optic vesicles become partitioned into prospective nasal and temporal domains by the opposing actions of Fgfs and Shh emanating from dorsal and ventral domains of the forebrain primordium. In absence of Fgf activity, foxd1 expression is established irrespective of levels of Hh signalling, indicating that the role of Shh in promoting foxd1 expression is only required in the presence of Fgf activity. Once the spatially complementary expression of foxd1 and foxg1 is established, the boundary between expression domains is maintained by mutual repression between Foxd1 and Foxg1. © 2015. Published by The Company of Biologists Ltd.

Causal network analysis of head and neck keloid tissue identifies potential master regulators.

PubMed

Garcia-Rodriguez, Laura; Jones, Lamont; Chen, Kang Mei; Datta, Indrani; Divine, George; Worsham, Maria J

2016-10-01

To generate novel insights and hypotheses in keloid development from potential master regulators. Prospective cohort. Six fresh keloid and six normal skin samples from 12 anonymous donors were used in a prospective cohort study. Genome-wide profiling was done previously on the cohort using the Infinium HumanMethylation450 BeadChip (Illumina, San Diego, CA). The 190 statistically significant CpG islands between keloid and normal tissue mapped to 152 genes (P < .05). The top 10 statistically significant genes (VAMP5, ACTR3C, GALNT3, KCNAB2, LRRC61, SCML4, SYNGR1, TNS1, PLEKHG5, PPP1R13-α, false discovery rate <.015) were uploaded into the Ingenuity Pathway Analysis software's Causal Network Analysis (QIAGEN, Redwood City, CA). To reflect expected gene expression direction in the context of methylation changes, the inverse of the methylation ratio from keloid versus normal tissue was used for the analysis. Causal Network Analysis identified disease-specific master regulator molecules based on downstream differentially expressed keloid-specific genes and expected directionality of expression (hypermethylated vs. hypomethylated). Causal Network Analysis software identified four hierarchical networks that included four master regulators (pyroxamide, tributyrin, PRKG2, and PENK) and 19 intermediate regulators. Causal Network Analysis of differentiated methylated gene data of keloid versus normal skin demonstrated four causal networks with four master regulators. These hierarchical networks suggest potential driver roles for their downstream keloid gene targets in the pathogenesis of the keloid phenotype, likely triggered due to perturbation/injury to normal tissue. NA Laryngoscope, 126:E319-E324, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Whole Blood mRNA Expression-Based Prognosis of Metastatic Renal Cell Carcinoma.

PubMed

Giridhar, Karthik V; Sosa, Carlos P; Hillman, David W; Sanhueza, Cristobal; Dalpiaz, Candace L; Costello, Brian A; Quevedo, Fernando J; Pitot, Henry C; Dronca, Roxana S; Ertz, Donna; Cheville, John C; Donkena, Krishna Vanaja; Kohli, Manish

2017-11-03

The Memorial Sloan Kettering Cancer Center (MSKCC) prognostic score is based on clinical parameters. We analyzed whole blood mRNA expression in metastatic clear cell renal cell carcinoma (mCCRCC) patients and compared it to the MSKCC score for predicting overall survival. In a discovery set of 19 patients with mRCC, we performed whole transcriptome RNA sequencing and selected eighteen candidate genes for further evaluation based on associations with overall survival and statistical significance. In an independent validation of set of 47 patients with mCCRCC, transcript expression of the 18 candidate genes were quantified using a customized NanoString probeset. Cox regression multivariate analysis confirmed that two of the candidate genes were significantly associated with overall survival. Higher expression of BAG1 [hazard ratio (HR) of 0.14, p < 0.0001, 95% confidence interval (CI) 0.04-0.36] and NOP56 (HR 0.13, p < 0.0001, 95% CI 0.05-0.34) were associated with better prognosis. A prognostic model incorporating expression of BAG1 and NOP56 into the MSKCC score improved prognostication significantly over a model using the MSKCC prognostic score only ( p < 0.0001). Prognostic value of using whole blood mRNA gene profiling in mCCRCC is feasible and should be prospectively confirmed in larger studies.

Whole Blood mRNA Expression-Based Prognosis of Metastatic Renal Cell Carcinoma

PubMed Central

Sosa, Carlos P.; Hillman, David W.; Sanhueza, Cristobal; Dalpiaz, Candace L.; Costello, Brian A.; Quevedo, Fernando J.; Pitot, Henry C.; Dronca, Roxana S.; Ertz, Donna; Cheville, John C.; Donkena, Krishna Vanaja; Kohli, Manish

2017-01-01

The Memorial Sloan Kettering Cancer Center (MSKCC) prognostic score is based on clinical parameters. We analyzed whole blood mRNA expression in metastatic clear cell renal cell carcinoma (mCCRCC) patients and compared it to the MSKCC score for predicting overall survival. In a discovery set of 19 patients with mRCC, we performed whole transcriptome RNA sequencing and selected eighteen candidate genes for further evaluation based on associations with overall survival and statistical significance. In an independent validation of set of 47 patients with mCCRCC, transcript expression of the 18 candidate genes were quantified using a customized NanoString probeset. Cox regression multivariate analysis confirmed that two of the candidate genes were significantly associated with overall survival. Higher expression of BAG1 [hazard ratio (HR) of 0.14, p < 0.0001, 95% confidence interval (CI) 0.04–0.36] and NOP56 (HR 0.13, p < 0.0001, 95% CI 0.05–0.34) were associated with better prognosis. A prognostic model incorporating expression of BAG1 and NOP56 into the MSKCC score improved prognostication significantly over a model using the MSKCC prognostic score only (p < 0.0001). Prognostic value of using whole blood mRNA gene profiling in mCCRCC is feasible and should be prospectively confirmed in larger studies. PMID:29099775

PROGNOSTIC SIGNIFICANCE OF CLINICAL, HISTOPATHOLOGICAL, AND MOLECULAR CHARACTERISTICS OF MEDULLOBLASTOMAS IN THE PROSPECTIVE HIT2000 MULTICENTER CLINICAL TRIAL COHORT

PubMed Central

Pietsch, Torsten; Schmidt, Rene; Remke, Marc; Korshunov, Andrey; Hovestadt, Volker; Jones, David TW; Felsberg, Jörg; Kaulich, Kerstin; Goschzik, Tobias; Kool, Marcel; Northcott, Paul A.; von Hoff, Katja; von Bueren, André O.; Friedrich, Carsten; Skladny, Heyko; Fleischhack, Gudrun; Taylor, Michael D.; Cremer, Friedrich; Lichter, Peter; Faldum, Andreas; Reifenberger, Guido; Rutkowski, Stefan; Pfister, Stefan M.

2014-01-01

BACKGROUND: This study aimed to prospectively evaluate clinical, histopathological and molecular variables for outcome prediction in medulloblastoma patients. METHODS: Patients from the HIT2000 cooperative clinical trial were prospectively enrolled based on the availability of sufficient tumor material and complete clinical information. This revealed a cohort of 184 patients (median age 7.6 years), which was randomly split at a 2:1 ratio into a training (n = 127), and a validation (n = 57) dataset. All samples were subjected to thorough histopathological investigation, CTNNB1 mutation analysis, quantitative PCR, MLPA and FISH analyses for cytogenetic variables, and methylome analysis. RESULTS: By univariable analysis, clinical factors (M-stage), histopathological variables (large cell component, endothelial proliferation, synaptophysin pattern), and molecular features (chromosome 6q status, MYC amplification, TOP2A copy-number, subgrouping) were found to be prognostic. Molecular consensus subgrouping (WNT, SHH, Group 3, Group 4) was validated as an independent feature to stratify patients into different risk groups. When comparing methods for the identification of WNT-driven medulloblastoma, this study identified CTNNB1 sequencing and methylation profiling to most reliably identify these patients. After removing patients with particularly favorable (CTNNB1 mutation, extensive nodularity) or unfavorable (MYC amplification) markers, a risk score for the remaining “intermediate molecular risk” population dependent on age, M-stage, pattern of synaptophysin expression, and MYCN copy-number status was identified and validated, with speckled synaptophysin expression indicating worse outcome. CONCLUSIONS: Methylation subgrouping and CTNNB1 mutation status represent robust tools for the risk-stratification of medulloblastoma. A simple clinico-pathological risk score for “intermediate molecular risk” patients was identified, which deserves further validation. SECONDARY CATEGORY: Pediatrics.

Prediction of incidence and stability of alcohol use disorders by latent internalizing psychopathology risk profiles in adolescence and young adulthood.

PubMed

Behrendt, Silke; Bühringer, Gerhard; Höfler, Michael; Lieb, Roselind; Beesdo-Baum, Katja

2017-10-01

Comorbid internalizing mental disorders in alcohol use disorders (AUD) can be understood as putative independent risk factors for AUD or as expressions of underlying shared psychopathology vulnerabilities. However, it remains unclear whether: 1) specific latent internalizing psychopathology risk-profiles predict AUD-incidence and 2) specific latent internalizing comorbidity-profiles in AUD predict AUD-stability. To investigate baseline latent internalizing psychopathology risk profiles as predictors of subsequent AUD-incidence and -stability in adolescents and young adults. Data from the prospective-longitudinal EDSP study (baseline age 14-24 years) were used. The study-design included up to three follow-up assessments in up to ten years. DSM-IV mental disorders were assessed with the DIA-X/M-CIDI. To investigate risk-profiles and their associations with AUD-outcomes, latent class analysis with auxiliary outcome variables was applied. AUD-incidence: a 4-class model (N=1683) was identified (classes: normative-male [45.9%], normative-female [44.2%], internalizing [5.3%], nicotine dependence [4.5%]). Compared to the normative-female class, all other classes were associated with a higher risk of subsequent incident alcohol dependence (p<0.05). AUD-stability: a 3-class model (N=1940) was identified with only one class (11.6%) with high probabilities for baseline AUD. This class was further characterized by elevated substance use disorder (SUD) probabilities and predicted any subsequent AUD (OR 8.5, 95% CI 5.4-13.3). An internalizing vulnerability may constitute a pathway to AUD incidence in adolescence and young adulthood. In contrast, no indication for a role of internalizing comorbidity profiles in AUD-stability was found, which may indicate a limited importance of such profiles - in contrast to SUD-related profiles - in AUD stability. Copyright © 2017 Elsevier B.V. All rights reserved.

The emerging genomics and systems biology research lead to systems genomics studies.

PubMed

Yang, Mary Qu; Yoshigoe, Kenji; Yang, William; Tong, Weida; Qin, Xiang; Dunker, A; Chen, Zhongxue; Arbania, Hamid R; Liu, Jun S; Niemierko, Andrzej; Yang, Jack Y

2014-01-01

Synergistically integrating multi-layer genomic data at systems level not only can lead to deeper insights into the molecular mechanisms related to disease initiation and progression, but also can guide pathway-based biomarker and drug target identification. With the advent of high-throughput next-generation sequencing technologies, sequencing both DNA and RNA has generated multi-layer genomic data that can provide DNA polymorphism, non-coding RNA, messenger RNA, gene expression, isoform and alternative splicing information. Systems biology on the other hand studies complex biological systems, particularly systematic study of complex molecular interactions within specific cells or organisms. Genomics and molecular systems biology can be merged into the study of genomic profiles and implicated biological functions at cellular or organism level. The prospectively emerging field can be referred to as systems genomics or genomic systems biology. The Mid-South Bioinformatics Centre (MBC) and Joint Bioinformatics Ph.D. Program of University of Arkansas at Little Rock and University of Arkansas for Medical Sciences are particularly interested in promoting education and research advancement in this prospectively emerging field. Based on past investigations and research outcomes, MBC is further utilizing differential gene and isoform/exon expression from RNA-seq and co-regulation from the ChiP-seq specific for different phenotypes in combination with protein-protein interactions, and protein-DNA interactions to construct high-level gene networks for an integrative genome-phoneme investigation at systems biology level.

Technical variables in high-throughput miRNA expression profiling: much work remains to be done.

PubMed

Nelson, Peter T; Wang, Wang-Xia; Wilfred, Bernard R; Tang, Guiliang

2008-11-01

MicroRNA (miRNA) gene expression profiling has provided important insights into plant and animal biology. However, there has not been ample published work about pitfalls associated with technical parameters in miRNA gene expression profiling. One source of pertinent information about technical variables in gene expression profiling is the separate and more well-established literature regarding mRNA expression profiling. However, many aspects of miRNA biochemistry are unique. For example, the cellular processing and compartmentation of miRNAs, the differential stability of specific miRNAs, and aspects of global miRNA expression regulation require specific consideration. Additional possible sources of systematic bias in miRNA expression studies include the differential impact of pre-analytical variables, substrate specificity of nucleic acid processing enzymes used in labeling and amplification, and issues regarding new miRNA discovery and annotation. We conclude that greater focus on technical parameters is required to bolster the validity, reliability, and cultural credibility of miRNA gene expression profiling studies.

Consistency between Constructivist Profiles and Instructional Practices of Prospective Physics Teachers

ERIC Educational Resources Information Center

Ates, Ozlem; Unal Coban, Gul; Kaya Sengoren, Serap

2018-01-01

This study aims to explain the extent to which prospective physics teachers' views and practices are consistent with the constructivist framework. A case study design was employed as the research approach. The study was conducted with 11 prospective physics teachers attending a state university in Turkey. Data was collected through semi-structured…

Trait Anger, Anger Expression, and Suicide Attempts among Adolescents and Young Adults: A Prospective Study

ERIC Educational Resources Information Center

Daniel, Stephanie S.; Goldston, David B.; Erkanli, Alaattin; Franklin, Joseph C.; Mayfield, Andrew M.

2009-01-01

Previous studies of the relationship between anger, anger expression, and suicidal behavior have been largely cross-sectional and have yielded mixed findings. In a prospective, naturalistic study, we examined how trait anger and anger expression influenced the likelihood of suicide attempts among 180 adolescents followed for up to 13.3 years after…

Global aphasia without hemiparesis: language profiles and lesion distribution

PubMed Central

Hanlon, R.; Lux, W.; Dromerick, A.

1999-01-01

OBJECTIVES—Global aphasia without hemiparesis (GAWH) is an uncommon stroke syndrome involving receptive and expressive language impairment, without the hemiparesis typically manifested by patients with global aphasia after large left perisylvian lesions. A few cases of GAWH have been reported with conflicting conclusions regarding pathogenesis, lesion localisation, and recovery. The current study was conducted to attempt to clarify these issues.
METHODS—Ten cases of GAWH were prospectively studied with language profiles and lesion analysis; five patients had multiple lesions, four patients had a single lesion, and one had a subarachnoid haemorrhage. Eight patients met criteria for cardioembolic ischaemic stroke.
RESULTS—Cluster analysis based on acute language profiles disclosed three subtypes of patients with GAWH; these clusters persisted on follow up language assessment. Each cluster evolved into a different aphasia subtype: persistent GAWH, Wernicke's aphasia, or transcortical motor aphasia (TCM). Composite lesion analysis showed that persistent GAWH was related to lesioning of the left superior temporal gyrus. Patients with acute GAWH who evolved into TCM type aphasia had common lesioning of the left inferior frontal gyrus and adjacent subcortical white matter. Patients with acute GAWH who evolved into Wernicke's type aphasia were characterised by lesioning of the left precentral and postcentral gyri. Recovery of language was poor in all but one patient.
CONCLUSIONS—Although patients with acute GAWH are similar on neurological examination, they are heterogeneous with respect to early aphasia profile, language recovery, and lesion profile.

 PMID:10084536

Digital sorting of complex tissues for cell type-specific gene expression profiles.

PubMed

Zhong, Yi; Wan, Ying-Wooi; Pang, Kaifang; Chow, Lionel M L; Liu, Zhandong

2013-03-07

Cellular heterogeneity is present in almost all gene expression profiles. However, transcriptome analysis of tissue specimens often ignores the cellular heterogeneity present in these samples. Standard deconvolution algorithms require prior knowledge of the cell type frequencies within a tissue or their in vitro expression profiles. Furthermore, these algorithms tend to report biased estimations. Here, we describe a Digital Sorting Algorithm (DSA) for extracting cell-type specific gene expression profiles from mixed tissue samples that is unbiased and does not require prior knowledge of cell type frequencies. The results suggest that DSA is a specific and sensitivity algorithm in gene expression profile deconvolution and will be useful in studying individual cell types of complex tissues.

Immunotherapeutic approaches in triple-negative breast cancer: latest research and clinical prospects.

PubMed

Stagg, John; Allard, Bertrand

2013-05-01

Triple-negative breast cancer (TNBC), as defined by the absence of estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 expression, is a challenging disease with the poorest prognosis of all breast cancer subtypes. Importantly, there are currently no known molecular targets for this subgroup of patients. Recent advances in genomics and gene expression profiling have shed new light on the molecule heterogeneity of TNBC. We present an overview of the scientific evidence suggesting that clinical outcome in TNBC is affected by tumor-infiltrating immune cells. We also describe tumor-associated antigens recently identified in TNBC. Finally, we review the current literature on promising immunotherapies for TNBC, including tumor vaccine approaches, immune-checkpoint inhibitors, antagonists of immunosuppressive molecules and adoptive cell therapies. It is our contention that selected patients with TNBC with lymphocytic tumor infiltrates at diagnosis may benefit from immune-based therapies and that these immunotherapies will be most beneficial in combination with cytotoxic drugs that potentiate adaptive anti-tumor immunity.

A comparison of honeybee (Apis mellifera) queen, worker and drone larvae by RNA-Seq.

PubMed

He, Xu-Jiang; Jiang, Wu-Jun; Zhou, Mi; Barron, Andrew B; Zeng, Zhi-Jiang

2017-11-06

Honeybees (Apis mellifera) have haplodiploid sex determination: males develop from unfertilized eggs and females develop from fertilized ones. The differences in larval food also determine the development of females. Here we compared the total somatic gene expression profiles of 2-day and 4-day-old drone, queen and worker larvae by RNA-Seq. The results from a co-expression network analysis on all expressed genes showed that 2-day-old drone and worker larvae were closer in gene expression profiles than 2-day-old queen larvae. This indicated that for young larvae (2-day-old) environmental factors such as larval diet have a greater effect on gene expression profiles than ploidy or sex determination. Drones had the most distinct gene expression profiles at the 4-day larval stage, suggesting that haploidy, or sex dramatically affects the gene expression of honeybee larvae. Drone larvae showed fewer differences in gene expression profiles at the 2-day and 4-day time points than the worker and queen larval comparisons (598 against 1190 and 1181), suggesting a different pattern of gene expression regulation during the larval development of haploid males compared to diploid females. This study indicates that early in development the queen caste has the most distinct gene expression profile, perhaps reflecting the very rapid growth and morphological specialization of this caste compared to workers and drones. Later in development the haploid male drones have the most distinct gene expression profile, perhaps reflecting the influence of ploidy or sex determination on gene expression. © 2017 Institute of Zoology, Chinese Academy of Sciences.

An integrated molecular analysis of lung adenocarcinomas identifies potential therapeutic targets among TTF1-negative tumors including DNA repair proteins and Nrf2

PubMed Central

Cardnell, Robert J.G.; Behrens, Carmen; Diao, Lixia; Fan, YouHong; Tang, Ximing; Tong, Pan; John D., Minna; Mills, Gordon B.; Heymach, John V.; Wistuba, Ignacio I.; Wang, Jing; Byers., Lauren A.

2015-01-01

Purpose Thyroid transcription factor-1 (TTF1) immunohistochemistry (IHC) is used clinically to differentiate primary lung adenocarcinomas (LUAD) from squamous lung cancers and metastatic adenocarcinomas from other primary sites. However, a subset of LUAD (15-20%) does not express TTF1 and TTF1-negative patients have worse clinical outcomes. As there are no established targeted agents with activity in TTF1-negative LUAD, we performed an integrated molecular analysis to identify potential therapeutic targets. Experimental Design Using two clinical LUAD cohorts (274 tumors), one from our institution (PROSPECT) and the TCGA, we interrogated proteomic profiles (by reverse-phase protein array (RPPA)), gene expression, and mutational data. Drug response data from 74 cell lines were used to validate potential therapeutic agents. Results Strong correlations were observed between TTF1 IHC and TTF1 measurements by RPPA (Rho=0.57, p<0.001) and gene expression (NKX2-1, Rho=0.61, p<0.001). Established driver mutations (e.g. BRAF and EGFR) were associated with high TTF1 expression. In contrast, TTF1-negative LUAD had a higher frequency of inactivating KEAP1 mutations (p=0.001). Proteomic profiling identified increased expression of DNA repair proteins (e.g., Chk1 and the DNA repair score) and suppressed PI3K/MAPK signaling among TTF1-negative tumors, with differences in total proteins confirmed at the mRNA level. Cell line analysis showed drugs targeting DNA repair to be more active in TTF1-low cell lines. Conclusions Combined genomic and proteomic analyses demonstrated infrequent alteration of validated lung cancer targets (including the absence of BRAF mutations in TTF1-negative LUAD), but identified novel potential targets for TTF1-negative LUAD includingKEAP1/Nrf2 and DNA repair pathways. PMID:25878335

Profile of epigenetic mechanisms in lung tumors of patients with underlying chronic respiratory conditions.

PubMed

Mateu-Jimenez, Mercè; Curull, Víctor; Rodríguez-Fuster, Alberto; Aguiló, Rafael; Sánchez-Font, Albert; Pijuan, Lara; Gea, Joaquim; Barreiro, Esther

2018-01-01

Chronic lung diseases such as chronic obstructive pulmonary disease (COPD) and epigenetic events underlie lung cancer (LC) development. The study objective was that lung tumor expression levels of specific microRNAs and their downstream biomarkers may be differentially regulated in patients with and without COPD. In lung specimens (tumor and non-tumor), microRNAs known to be involved in lung tumorigenesis (miR-21, miR-200b, miR-126, miR-451, miR-210, miR-let7c, miR-30a-30p, miR-155 and miR-let7a, qRT-PCR), DNA methylation, and downstream biomarkers were determined (qRT-PCR and immunoblotting) in 40 patients with LC (prospective study, subdivided into LC-COPD and LC, N  = 20/group). Expression of miR-21, miR-200b, miR-210, and miR-let7c and DNA methylation were greater in lung tumor specimens of LC-COPD than of LC patients. Expression of downstream markers PTEN , MARCKs , TPM-1 , PDCD4 , SPRY-2 , ETS-1 , ZEB-2 , FGFRL-1 , EFNA-3 , and k-RAS together with P53 were selectively downregulated in tumor samples of LC-COPD patients. In these patients, tumor expression of miR-126 and miR-451 and that of the biomarkers PTEN , MARCKs , FGFRL-1 , SNAIL-1 , P63 , and k-RAS were reduced. Biomarkers of mechanisms involved in tumor growth, angiogenesis, migration, and apoptosis were differentially expressed in tumors of patients with underlying respiratory disease. These findings shed light into the underlying biology of the reported greater risk to develop LC seen in patients with chronic respiratory conditions. The presence of an underlying respiratory disease should be identified in all patients with LC as the differential biological profile may help determine tumor progression and the therapeutic response. Additionally, epigenetic events offer a niche for pharmacological therapeutic targets.

Early diffusion of gene expression profiling in breast cancer patients associated with areas of high income inequality.

PubMed

Ponce, Ninez A; Ko, Michelle; Liang, Su-Ying; Armstrong, Joanne; Toscano, Michele; Chanfreau-Coffinier, Catherine; Haas, Jennifer S

2015-04-01

With the Affordable Care Act reducing coverage disparities, social factors could prominently determine where and for whom innovations first diffuse in health care markets. Gene expression profiling is a potentially cost-effective innovation that guides chemotherapy decisions in early-stage breast cancer, but adoption has been uneven across the United States. Using a sample of commercially insured women, we evaluated whether income inequality in metropolitan areas was associated with receipt of gene expression profiling during its initial diffusion in 2006-07. In areas with high income inequality, gene expression profiling receipt was higher than elsewhere, but it was associated with a 10.6-percentage-point gap between high- and low-income women. In areas with low rates of income inequality, gene expression profiling receipt was lower, with no significant differences by income. Even among insured women, income inequality may indirectly shape diffusion of gene expression profiling, with benefits accruing to the highest-income patients in the most unequal places. Policies reducing gene expression profiling disparities should address low-inequality areas and, in unequal places, practice settings serving low-income patients. Project HOPE—The People-to-People Health Foundation, Inc.

The zebrafish orphan nuclear receptor genes nr2e1 and nr2e3 are expressed in developing eye and forebrain.

PubMed

Kitambi, Satish Srinivas; Hauptmann, Giselbert

2007-02-01

Mammalian Nr2e1 (Tailless, Mtll or Tlx) and Nr2e3 (photoreceptor-specific nuclear receptor, Pnr) are highly related orphan nuclear receptors, that are expressed in eye and forebrain-derived structures. In this study, we analyzed the developmental expression patterns of zebrafish nr2e1 and nr2e3. RT-PCR analysis showed that nr2e1 and nr2e3 are both expressed during embryonic and post-embryonic development. To examine the spatial distribution of nr2e1 and nr2e3 during development whole-mount in situ hybridization was performed. At tailbud stage, initial nr2e1 expression was localized to the rostral brain rudiment anterior to pax2.1 and eng2 expression at the prospective midbrain-hindbrain boundary. During subsequent stages, nr2e1 became widely expressed in fore- and midbrain primordia, eye and olfactory placodes. At 24hpf, strong nr2e1 expression was detected in telencephalon, hypothalamus, dorsal thalamus, pretectum, midbrain tectum, and retina. At 2dpf, the initially widespread nr2e1 expression became more restricted to distinct regions within the fore- and midbrain and to the retinal ciliary margin, the germinal zone which gives rise to retina and presumptive iris. Expression of nr2e3 was exclusively found in the developing retina and epiphysis. In both structures, nr2e3 expression was found in photoreceptor cells. The developmental expression profile of zebrafish nr2e1 and nr2e3 is consistent with evolutionary conserved functions in eye and rostral brain structures.

RNA-Stabilized Whole Blood Samples but Not Peripheral Blood Mononuclear Cells Can Be Stored for Prolonged Time Periods Prior to Transcriptome Analysis

PubMed Central

Debey-Pascher, Svenja; Hofmann, Andrea; Kreusch, Fatima; Schuler, Gerold; Schuler-Thurner, Beatrice; Schultze, Joachim L.; Staratschek-Jox, Andrea

2011-01-01

Microarray-based transcriptome analysis of peripheral blood as surrogate tissue has become an important approach in clinical implementations. However, application of gene expression profiling in routine clinical settings requires careful consideration of the influence of sample handling and RNA isolation methods on gene expression profile outcome. We evaluated the effect of different sample preservation strategies (eg, cryopreservation of peripheral blood mononuclear cells or freezing of PAXgene-stabilized whole blood samples) on gene expression profiles. Expression profiles obtained from cryopreserved peripheral blood mononuclear cells differed substantially from those of their nonfrozen counterpart samples. Furthermore, expression profiles in cryopreserved peripheral blood mononuclear cell samples were found to undergo significant alterations with increasing storage period, whereas long-term freezing of PAXgene RNA stabilized whole blood samples did not significantly affect stability of gene expression profiles. This report describes important technical aspects contributing toward the establishment of robust and reliable guidance for gene expression studies using peripheral blood and provides a promising strategy for reliable implementation in routine handling for diagnostic purposes. PMID:21704280

Monocyte NOTCH2 expression predicts IFN-β immunogenicity in multiple sclerosis patients.

PubMed

Adriani, Marsilio; Nytrova, Petra; Mbogning, Cyprien; Hässler, Signe; Medek, Karel; Jensen, Poul Erik H; Creeke, Paul; Warnke, Clemens; Ingenhoven, Kathleen; Hemmer, Bernhard; Sievers, Claudia; Lindberg Gasser, Raija Lp; Fissolo, Nicolas; Deisenhammer, Florian; Bocskei, Zsolt; Mikol, Vincent; Fogdell-Hahn, Anna; Kubala Havrdova, Eva; Broët, Philippe; Dönnes, Pierre; Mauri, Claudia; Jury, Elizabeth C

2018-06-07

Multiple sclerosis (MS) is an autoimmune disease characterized by CNS inflammation leading to demyelination and axonal damage. IFN-β is an established treatment for MS; however, up to 30% of IFN-β-treated MS patients develop neutralizing antidrug antibodies (nADA), leading to reduced drug bioactivity and efficacy. Mechanisms driving antidrug immunogenicity remain uncertain, and reliable biomarkers to predict immunogenicity development are lacking. Using high-throughput flow cytometry, NOTCH2 expression on CD14+ monocytes and increased frequency of proinflammatory monocyte subsets were identified as baseline predictors of nADA development in MS patients treated with IFN-β. The association of this monocyte profile with nADA development was validated in 2 independent cross-sectional MS patient cohorts and a prospective cohort followed before and after IFN-β administration. Reduced monocyte NOTCH2 expression in nADA+ MS patients was associated with NOTCH2 activation measured by increased expression of Notch-responsive genes, polarization of monocytes toward a nonclassical phenotype, and increased proinflammatory IL-6 production. NOTCH2 activation was T cell dependent and was only triggered in the presence of serum from nADA+ patients. Thus, nADA development was driven by a proinflammatory environment that triggered activation of the NOTCH2 signaling pathway prior to first IFN-β administration.

Profiling Pre-MicroRNA and Mature MicroRNA Expressions Using a Single Microarray and Avoiding Separate Sample Preparation

PubMed Central

Gan, Lin; Denecke, Bernd

2013-01-01

Mature microRNA is a crucial component in the gene expression regulation network. At the same time, microRNA gene expression and procession is regulated in a precise and collaborated way. Pre-microRNAs mediate products during the microRNA transcription process, they can provide hints of microRNA gene expression regulation or can serve as alternative biomarkers. To date, little effort has been devoted to pre-microRNA expression profiling. In this study, three human and three mouse microRNA profile data sets, based on the Affymetrix miRNA 2.0 array, have been re-analyzed for both mature and pre-microRNA signals as a primary test of parallel mature/pre-microRNA expression profiling on a single platform. The results not only demonstrated a glimpse of pre-microRNA expression in human and mouse, but also the relationship of microRNA expressions between pre- and mature forms. The study also showed a possible application of currently available microRNA microarrays in profiling pre-microRNA expression in a time and cost effective manner. PMID:27605179

Association of a murine leukaemia stem cell gene signature based on nucleostemin promoter activity with prognosis of acute myeloid leukaemia in patients.

PubMed

Ali, Mohamed A E; Naka, Kazuhito; Yoshida, Akiyo; Fuse, Kyoko; Kasada, Atsuo; Hoshii, Takayuki; Tadokoro, Yuko; Ueno, Masaya; Ohta, Kumiko; Kobayashi, Masahiko; Takahashi, Chiaki; Hirao, Atsushi

2014-07-18

Acute myeloid leukaemia (AML) is a heterogeneous neoplastic disorder in which a subset of cells function as leukaemia-initiating cells (LICs). In this study, we prospectively evaluated the leukaemia-initiating capacity of AML cells fractionated according to the expression of a nucleolar GTP binding protein, nucleostemin (NS). To monitor NS expression in living AML cells, we generated a mouse AML model in which green fluorescent protein (GFP) is expressed under the control of a region of the NS promoter (NS-GFP). In AML cells, NS-GFP levels were correlated with endogenous NS mRNA. AML cells with the highest expression of NS-GFP were very immature blast-like cells, efficiently formed leukaemia colonies in vitro, and exhibited the highest leukaemia-initiating capacity in vivo. Gene expression profiling analysis revealed that cell cycle regulators and nucleotide metabolism-related genes were highly enriched in a gene set associated with leukaemia-initiating capacity that we termed the 'leukaemia stem cell gene signature'. This gene signature stratified human AML patients into distinct clusters that reflected prognosis, demonstrating that the mouse leukaemia stem cell gene signature is significantly associated with the malignant properties of human AML. Further analyses of gene regulation in leukaemia stem cells could provide novel insights into diagnostic and therapeutic approaches to AML. Copyright © 2014 Elsevier Inc. All rights reserved.

MicroRNAs show a wide diversity of expression profiles in the developing and mature central nervous system

PubMed Central

Kapsimali, Marika; Kloosterman, Wigard P; de Bruijn, Ewart; Rosa, Frederic; Plasterk, Ronald HA; Wilson, Stephen W

2007-01-01

Background MicroRNA (miRNA) encoding genes are abundant in vertebrate genomes but very few have been studied in any detail. Bioinformatic tools allow prediction of miRNA targets and this information coupled with knowledge of miRNA expression profiles facilitates formulation of hypotheses of miRNA function. Although the central nervous system (CNS) is a prominent site of miRNA expression, virtually nothing is known about the spatial and temporal expression profiles of miRNAs in the brain. To provide an overview of the breadth of miRNA expression in the CNS, we performed a comprehensive analysis of the neuroanatomical expression profiles of 38 abundant conserved miRNAs in developing and adult zebrafish brain. Results Our results show miRNAs have a wide variety of different expression profiles in neural cells, including: expression in neuronal precursors and stem cells (for example, miR-92b); expression associated with transition from proliferation to differentiation (for example, miR-124); constitutive expression in mature neurons (miR-124 again); expression in both proliferative cells and their differentiated progeny (for example, miR-9); regionally restricted expression (for example, miR-222 in telencephalon); and cell-type specific expression (for example, miR-218a in motor neurons). Conclusion The data we present facilitate prediction of likely modes of miRNA function in the CNS and many miRNA expression profiles are consistent with the mutual exclusion mode of function in which there is spatial or temporal exclusion of miRNAs and their targets. However, some miRNAs, such as those with cell-type specific expression, are more likely to be co-expressed with their targets. Our data provide an important resource for future functional studies of miRNAs in the CNS. PMID:17711588

Potential errors in using one anemometer to characterize the wind power over an entire rotor disk

NASA Technical Reports Server (NTRS)

Simon, R. L.

1982-01-01

Wind data collected at four levels on a 90-m tower in a prospective wind farm area are used to evaluate how well the 10-m wind speed data with and without intermittent vertical profile measurements compare with the 90-m tower data. If a standard, or even predictable, wind speed profile existed, there would be no need for a large, expensive tower. This cost differential becomes even more significant if several towers are needed to study a prospective wind farm.

Molecular Profiling of Post-Reperfusion Milieu Determines Acute Kidney Injury after Liver Transplantation: a Prospective Study.

PubMed

Pulitano, Carlo; Ho, Phong; Verran, Deborah; Sandroussi, Charbel; Joseph, David; Bowen, David G; McCaughan, Geoffrey W; Crawford, Michael; Shackel, Nicholas

2018-04-23

Acute kidney injury (AKI) after liver transplantation (LT) is a common event, but its pathogenesis remains unclear. The aim of this prospective study is to investigate the potential relationship between post-reperfusion gene expression, serum mediators, and the onset of AKI after LT. Sixty-five consecutive patients undergoing LT were included in the study. Reverse transcription polymerase chain reaction (RT- PCR), was performed on liver biopsies. Gene expression of 23 genes involved in ischemia reperfusion injury (IRI) was evaluated. The serum concentrations of endothelin-1 (ET-1), and inflammatory cytokines were analyzed. AKI after LT developed in 21 (32%) recipients (AKI group). RT-PCR of reperfusion biopsy in AKI group showed higher expression of several genes involved in IRI compared to non-AKI group. Fold changes in the gene expression of ET-1, IL-18, and TNF-α were associated with creatinine peak value. AKI patients had also significantly higher ET-1, IL-18, and TNF-α postoperative serum levels. Multivariate analysis showed that ET-1 (OR 16.7, 95% CI 3.34-83.42, P = 0.001) and IL-18 (OR 5.27, 95% CI 0.99-27.82, P = 0.048) serum levels on POD1 were independently predictor of AKI. Receiver operator characteristic (ROC) analysis demonstrated that the combination of biomarkers ET-1+IL-18 was highly predictive of AKI (ROC-AUC 0.91, 95% CI: 0.83-0.99). Early allograft dysfunction and chronic kidney disease stage ≥ 2 occurred more frequently in AKI patients. These results suggest that the graft itself, rather than intraoperative hemodynamic instability plays a main role in AKI after LT. This data may have mechanistic and diagnostic implications for AKI after LT. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

The Breast Cancer to Bone (B2B) Metastases Research Program: a multi-disciplinary investigation of bone metastases from breast cancer.

PubMed

Brockton, Nigel T; Gill, Stephanie J; Laborge, Stephanie L; Paterson, Alexander H G; Cook, Linda S; Vogel, Hans J; Shemanko, Carrie S; Hanley, David A; Magliocco, Anthony M; Friedenreich, Christine M

2015-07-10

Bone is the most common site of breast cancer distant metastasis, affecting 50-70 % of patients who develop metastatic disease. Despite decades of informative research, the effective prevention, prediction and treatment of these lesions remains elusive. The Breast Cancer to Bone (B2B) Metastases Research Program consists of a prospective cohort of incident breast cancer patients and four sub-projects that are investigating priority areas in breast cancer bone metastases. These include the impact of lifestyle factors and inflammation on risk of bone metastases, the gene expression features of the primary tumour, the potential role for metabolomics in early detection of bone metastatic disease and the signalling pathways that drive the metastatic lesions in the bone. The B2B Research Program is enrolling a prospective cohort of 600 newly diagnosed, incident, stage I-IIIc breast cancer survivors in Alberta, Canada over a five year period. At baseline, pre-treatment/surgery blood samples are collected and detailed epidemiologic data is collected by in-person interview and self-administered questionnaires. Additional self-administered questionnaires and blood samples are completed at specified follow-up intervals (24, 48 and 72 months). Vital status is obtained prior to each follow-up through record linkages with the Alberta Cancer Registry. Recurrences are identified through medical chart abstractions. Each of the four projects applies specific methods and analyses to assess the impact of serum vitamin D and cytokine concentrations, tumour transcript and protein expression, serum metabolomic profiles and in vitro cell signalling on breast cancer bone metastases. The B2B Research Program will address key issues in breast cancer bone metastases including the association between lifestyle factors (particularly a comprehensive assessment of vitamin D status) inflammation and bone metastases, the significance or primary tumour gene expression in tissue tropism, the potential of metabolomic profiles for risk assessment and early detection and the signalling pathways controlling the metastatic tumour microenvironment. There is substantial synergy between the four projects and it is hoped that this integrated program of research will advance our understanding of key aspects of bone metastases from breast cancer to improve the prevention, prediction, detection, and treatment of these lesions.

American Association of Nurse Anesthetists

MedlinePlus

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Effect of bariatric surgery on adiposity and metabolic profiles: A prospective cohort study in Middle-Eastern patients.

PubMed

Mazidi, Mohsen; Rezaie, Peyman; Jangjoo, Ali; Tavassoli, Alireza; Rajabi, Mohammad Taghi; Kengne, Andre Pascal; Nematy, Mohsen

2017-07-15

To investigate changes in adiposity and cardio-metabolic risk profile following Roux-en-Y gastric bypass in patients of Middle Eastern ethnicity with severe obesity. This prospective cohort study involved 92 patients who met the indications of bariatric surgery. Post-procedure markers of obesity and cardiometabolic profile were monitored regularly for a year. Mean body mass index decreased by 29.5% from 41.9 to 29.5 kg/m 2 between baseline and 12-mo follow-up, while mean fat mass decreased by 45.9% from 64.2 kg to 34.7 kg. An improvement was also observed in the gluco-metabolic profile with both fasting glucose and HbA1c substantially decreasing ( P < 0.001). The present study shows the short to medium term (1 year) health benefits of bariatric surgery for patients of Middle Eastern ethnicity.

Comparative prion disease gene expression profiling using the prion disease mimetic, cuprizone

PubMed Central

Moody, Laura R; Herbst, Allen J; Yoo, Han Sang; Vanderloo, Joshua P

2009-01-01

Identification of genes expressed in response to prion infection may elucidate biomarkers for disease, identify factors involved in agent replication, mechanisms of neuropathology and therapeutic targets. Although several groups have sought to identify gene expression changes specific to prion disease, expression profiles rife with cell population changes have consistently been identified. Cuprizone, a neurotoxicant, qualitatively mimics the cell population changes observed in prion disease, resulting in both spongiform change and astrocytosis. The use of cuprizone-treated animals as an experimental control during comparative expression profiling allows for the identification of transcripts whose expression increases during prion disease and remains unchanged during cuprizone-triggered neuropathology. In this study, expression profiles from the brains of mice preclinically and clinically infected with Rocky Mountain Laboratory (RML) mouse-adapted scrapie agent and age-matched controls were profiled using Affymetrix gene arrays. In total, 164 genes were differentially regulated during prion infection. Eighty-three of these transcripts have been previously undescribed as differentially regulated during prion disease. A 0.4% cuprizone diet was utilized as a control for comparative expression profiling. Cuprizone treatment induced spongiosis and astrocyte proliferation as indicated by glial fibrillary acidic protein (Gfap) transcriptional activation and immunohistochemistry. Gene expression profiles from brain tissue obtained from cuprizone-treated mice identified 307 differentially regulated transcript changes. After comparative analysis, 17 transcripts unaffected by cuprizone treatment but increasing in expression from preclinical to clinical prion infection were identified. Here we describe the novel use of the prion disease mimetic, cuprizone, to control for cell population changes in the brain during prion infection. PMID:19535908

Clonal analyses and gene profiling identify genetic biomarkers of the thermogenic potential of human brown and white preadipocytes.

PubMed

Xue, Ruidan; Lynes, Matthew D; Dreyfuss, Jonathan M; Shamsi, Farnaz; Schulz, Tim J; Zhang, Hongbin; Huang, Tian Lian; Townsend, Kristy L; Li, Yiming; Takahashi, Hirokazu; Weiner, Lauren S; White, Andrew P; Lynes, Maureen S; Rubin, Lee L; Goodyear, Laurie J; Cypess, Aaron M; Tseng, Yu-Hua

2015-07-01

Targeting brown adipose tissue (BAT) content or activity has therapeutic potential for treating obesity and the metabolic syndrome by increasing energy expenditure. However, both inter- and intra-individual differences contribute to heterogeneity in human BAT and potentially to differential thermogenic capacity in human populations. Here we generated clones of brown and white preadipocytes from human neck fat and characterized their adipogenic and thermogenic differentiation. We combined an uncoupling protein 1 (UCP1) reporter system and expression profiling to define novel sets of gene signatures in human preadipocytes that could predict the thermogenic potential of the cells once they were maturated. Knocking out the positive UCP1 regulators, PREX1 and EDNRB, in brown preadipocytes using CRISPR-Cas9 markedly abolished the high level of UCP1 in brown adipocytes differentiated from the preadipocytes. Finally, we were able to prospectively isolate adipose progenitors with great thermogenic potential using the cell surface marker CD29. These data provide new insights into the cellular heterogeneity in human fat and offer potential biomarkers for identifying thermogenically competent preadipocytes.

Changes in the expression profiles of claudins during gonocyte differentiation and in seminomas.

PubMed

Manku, G; Hueso, A; Brimo, F; Chan, P; Gonzalez-Peramato, P; Jabado, N; Gayden, T; Bourgey, M; Riazalhosseini, Y; Culty, M

2016-01-01

Testicular germ cell tumors (TGCTs) are the most common type of cancer in young men and their incidence has been steadily increasing for the past decades. TGCTs and their precursor carcinoma in situ (CIS) are thought to arise from the deficient differentiation of gonocytes, precursors of spermatogonial stem cells. However, the mechanisms relating failed gonocyte differentiation to CIS formation remain unknown. The goal of this study was to uncover genes regulated during gonocyte development that would show abnormal patterns of expression in testicular tumors, as prospective links between failed gonocyte development and TGCT. To identify common gene and protein signatures between gonocytes and seminomas, we first performed gene expression analyses of transitional rat gonocytes, spermatogonia, human normal testicular, and TGCT specimens. Gene expression arrays, pathway analysis, and quantitative real-time PCR analysis identified cell adhesion molecules as a functional gene category including genes downregulated during gonocyte differentiation and highly expressed in seminomas. In particular, the mRNA and protein expressions of claudins 6 and 7 were found to decrease during gonocyte transition to spermatogonia, and to be abnormally elevated in seminomas. The dynamic changes in these genes suggest that they may play important physiological roles during gonocyte development. Moreover, our findings support the idea that TGCTs arise from a disruption of gonocyte differentiation, and position claudins as interesting genes to further study in relation to testicular cancer. © 2015 American Society of Andrology and European Academy of Andrology.

Investigating the Receptive-Expressive Vocabulary Profile in Children with Idiopathic ASD and Comorbid ASD and Fragile X Syndrome.

PubMed

Haebig, Eileen; Sterling, Audra

2017-02-01

Previous work has noted that some children with autism spectrum disorder (ASD) display weaknesses in receptive vocabulary relative to expressive vocabulary abilities. The current study extended previous work by examining the receptive-expressive vocabulary profile in boys with idiopathic ASD and boys with concomitant ASD and fragile X syndrome (ASD + FXS). On average, boys with ASD + FXS did not display the same atypical receptive-expressive profile as boys with idiopathic ASD. Notably, there was variation in vocabulary abilities and profiles in both groups. Although we did not identify predictors of receptive-expressive differences, we demonstrated that nonverbal IQ and expressive vocabulary positively predicted concurrent receptive vocabulary knowledge and receptive vocabulary predicted expressive vocabulary. We discuss areas of overlap and divergence in subgroups of ASD.

Investigating the Receptive-Expressive Vocabulary Profile in Children with Idiopathic ASD and Comorbid ASD and Fragile X Syndrome

PubMed Central

Sterling, Audra

2016-01-01

Previous work has noted that some children with autism spectrum disorder (ASD) display weaknesses in receptive vocabulary relative to expressive vocabulary abilities. The current study extended previous work by examining the receptive-expressive vocabulary profile in boys with idiopathic ASD and boys with concomitant ASD and fragile X syndrome (ASD + FXS). On average, boys with ASD + FXS did not display the same atypical receptive-expressive profile as boys with idiopathic ASD. Notably, there was variation in vocabulary abilities and profiles in both groups. Although we did not identify predictors of receptive-expressive differences, we demonstrated that nonverbal IQ and expressive vocabulary positively predicted concurrent receptive vocabulary knowledge and receptive vocabulary predicted expressive vocabulary. We discuss areas of overlap and divergence in subgroups of ASD. PMID:27796729

Evaluation of CD44 and CD133 as markers of liver cancer stem cells in Egyptian patients with HCV-induced chronic liver diseases versus hepatocellular carcinoma

PubMed Central

Rozeik, Mohammed Saeed; Hammam, Olfat Ali; Ali, Ali Ibrahim; Magdy, Mona; Khalil, Heba; Anas, Amgad; Abo el Hassan, Ahmed Abdelaleem; Rahim, Ali Abdel; El-Shabasy, Ahmed Ibrahim

2017-01-01

Background Cancer stem cells (CSCs) play a critical role in tumor development, progression, metastasis and recurrence. Aim To evaluate hepatic expression of CD44 and CD133 in Egyptian patients with HCV-induced chronic liver diseases and hepatocellular carcinomas (HCCs), and to assess its correlation with inflammatory activity scores, stages of fibrosis (in chronic hepatitis with or without cirrhosis) and grades of HCC. Methods This prospective case-control study was conducted on eighty subjects who attended the Tropical Diseases Department, Al-Azhar University Hospital, and in collaboration with Theodor Bilharz Research Institute (2014–2016). They were divided as follows: A) Control healthy group: Ten individuals with serologically negative HCV-Ab and HBsAg, and histopathologically normal liver, B) Seventy patients subdivided into 3 groups; Twenty subjects each, as: HCV-Ab+ non-cirrhotic, HCV-Ab+ cirrhotic and HCC. Necroinflammatory activity and fibrosis in non-neoplastic liver biopsies were scored according to the METAVIR scoring system. CD44 and CD133 immunostaining was evaluated in all groups semi-quantitatively using H score. Statistical analysis was performed by SPSS version 22, using independent-samples t-test. Results Our study showed a significant increase of mean CD44 & CD133 expression values with disease progression among the groups (p<0.05). Their expressions increased significantly with the inflammatory activity scores and stages of fibrosis, reaching the highest values in A3F4 score compared to A1F1 (p<0.05). Moreover, there was a significant increase of their expressions across HCC grades (p<0.05), however with no significant correlation with focal lesions size. Conclusion CSCs clusters exhibiting CD133+ and/or CD44+ profiles were identified in chronic hepatitis, liver cirrhosis and HCC. CD133 and CD44 expressions significantly corresponded to the increased inflammatory activity, fibrosis stages and higher tumor grades. Therefore, evaluation of CD44 and CD133 expression profiles as CSCs markers in non-neoplastic liver and HCCs can help in development of novel therapeutic agents for HCC targeting and prevention. PMID:28894525

Problems and Prospects in Foreign Language Computing.

ERIC Educational Resources Information Center

Pusack, James P.

The problems and prospects of the field of foreign language computing are profiled through a survey of typical implementation, development, and research projects that language teachers may undertake. Basic concepts in instructional design, hardware, and software are first clarified. Implementation projects involving courseware evaluation, textbook…

Metal-cluster ionization energy: A profile-insensitive exact expression for the size effect

NASA Astrophysics Data System (ADS)

Seidl, Michael; Perdew, John P.; Brajczewska, Marta; Fiolhais, Carlos

1997-05-01

The ionization energy of a large spherical metal cluster of radius R is I(R)=W+(+c)/R, where W is the bulk work function and c~-0.1 is a material-dependent quantum correction to the electrostatic size effect. We present 'Koopmans' and 'displaced-profile change-in-self-consistent-field' expressions for W and c within the ordinary and stabilized-jellium models. These expressions are shown to be exact and equivalent when the exact density profile of a large neutral cluster is employed; these equivalences generalize the Budd-Vannimenus theorem. With an approximate profile obtained from a restricted variational calculation, the 'displaced-profile' expressions are the more accurate ones. This profile insensitivity is important, because it is not practical to extract c from solutions of the Kohn-Sham equations for small metal clusters.

Single cell gene expression profiling of cortical osteoblast lineage cells.

PubMed

Flynn, James M; Spusta, Steven C; Rosen, Clifford J; Melov, Simon

2013-03-01

In tissues with complex architectures such as bone, it is often difficult to purify and characterize specific cell types via molecular profiling. Single cell gene expression profiling is an emerging technology useful for characterizing transcriptional profiles of individual cells isolated from heterogeneous populations. In this study we describe a novel procedure for the isolation and characterization of gene expression profiles of single osteoblast lineage cells derived from cortical bone. Mixed populations of different cell types were isolated from adult long bones of C57BL/6J mice by enzymatic digestion, and subsequently subjected to FACS to purify and characterize osteoblast lineage cells via a selection strategy using antibodies against CD31, CD45, and alkaline phosphatase (AP), specific for mature osteoblasts. The purified individual osteoblast lineage cells were then profiled at the single cell level via nanofluidic PCR. This method permits robust gene expression profiling on single osteoblast lineage cells derived from mature bone, potentially from anatomically distinct sites. In conjunction with this technique, we have also shown that it is possible to carry out single cell profiling on cells purified from fixed and frozen bone samples without compromising the gene expression signal. The latter finding means the technique can be extended to biopsies of bone from diseased individuals. Our approach for single cell expression profiling provides a new dimension to the transcriptional profile of the primary osteoblast lineage population in vivo, and has the capacity to greatly expand our understanding of how these cells may function in vivo under normal and diseased states. Copyright © 2012 Elsevier Inc. All rights reserved.

Genomic and Expression Profiling of Benign and Malignant Nerve Sheath Profiling of Benign and Malignant Nerve Sheath

DTIC Science & Technology

2007-05-01

Benign and Malignant Nerve Sheath Tumors in Neurofibromatosis Patients PRINCIPAL INVESTIGATOR: Matt van de Rijn, M.D., Ph.D. Torsten...Annual 3. DATES COVERED 1 May 2006 –30 Apr 2007 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Genomic and Expression Profiling of Benign and Malignant Nerve...Award Number: DAMD17-03-1-0297 Title: Genomic and Expression Profiling of Benign and Malignant Nerve Sheath Tumors in Neurofibromatosis

Transcriptome Analysis of Orbital Adipose Tissue in Active Thyroid Eye Disease Using Next Generation RNA Sequencing Technology

PubMed Central

Lee, Bradford W.; Kumar, Virender B.; Biswas, Pooja; Ko, Audrey C.; Alameddine, Ramzi M.; Granet, David B.; Ayyagari, Radha; Kikkawa, Don O.; Korn, Bobby S.

2018-01-01

Objective: This study utilized Next Generation Sequencing (NGS) to identify differentially expressed transcripts in orbital adipose tissue from patients with active Thyroid Eye Disease (TED) versus healthy controls. Method: This prospective, case-control study enrolled three patients with severe, active thyroid eye disease undergoing orbital decompression, and three healthy controls undergoing routine eyelid surgery with removal of orbital fat. RNA Sequencing (RNA-Seq) was performed on freshly obtained orbital adipose tissue from study patients to analyze the transcriptome. Bioinformatics analysis was performed to determine pathways and processes enriched for the differential expression profile. Quantitative Reverse Transcriptase-Polymerase Chain Reaction (qRT-PCR) was performed to validate the differential expression of selected genes identified by RNA-Seq. Results: RNA-Seq identified 328 differentially expressed genes associated with active thyroid eye disease, many of which were responsible for mediating inflammation, cytokine signaling, adipogenesis, IGF-1 signaling, and glycosaminoglycan binding. The IL-5 and chemokine signaling pathways were highly enriched, and very-low-density-lipoprotein receptor activity and statin medications were implicated as having a potential role in TED. Conclusion: This study is the first to use RNA-Seq technology to elucidate differential gene expression associated with active, severe TED. This study suggests a transcriptional basis for the role of statins in modulating differentially expressed genes that mediate the pathogenesis of thyroid eye disease. Furthermore, the identification of genes with altered levels of expression in active, severe TED may inform the molecular pathways central to this clinical phenotype and guide the development of novel therapeutic agents. PMID:29760827

High levels of PROM1 (CD133) transcript are a potential predictor of poor prognosis in medulloblastoma

PubMed Central

Raso, Alessandro; Mascelli, Samantha; Biassoni, Roberto; Nozza, Paolo; Kool, Marcel; Pistorio, Angela; Ugolotti, Elisabetta; Milanaccio, Claudia; Pignatelli, Sara; Ferraro, Manuela; Pavanello, Marco; Ravegnani, Marcello; Cama, Armando; Garrè, Maria Luisa; Capra, Valeria

2011-01-01

The surface marker PROM1 is considered one of the most important markers of tumor-initiating cells, and its expression is believed to be an adverse prognostic factor in gliomas and in other malignancies. To date, to our knowledge, no specific studies of its expression in medulloblastoma series have been performed. The aims of our study were to evaluate the expression profile of the PROM1 gene in medulloblastoma and to assess its possible role as a prognostic factor. The PROM1 gene expression was evaluated by quantitative– polymerase chain reaction on 45 medulloblastoma samples by using specific dye-labeled probe systems. A significantly higher expression of PROM1 was found both in patients with poorer prognosis (P= .007) and in those with metastasis (P= .03). Kaplan–Meier analysis showed that both overall survival (OS) and progression-free survival (PFS) were shorter in patients with higher PROM1 mRNA levels than in patients with lower expression, even when the desmoplastic cases were excluded (P= .0004 and P= .002, for OS and PFS for all cases, respectively; P= .002 and P= .008 for OS and PFS for nondesmoplastic cases, respectively). Cox regression model demonstrated that PROM1 expression is an independent prognostic factor (hazard ratio, 4.56; P= .008). The result was validated on an independent cohort of 42 cases by microarray-based analysis (P= .019). This work suggests that high mRNA levels of PROM1 are associated with poor outcome in pediatric medulloblastoma. Furthermore, high PROM1 expression levels seem to increase the likelihood of metastases. Such results need to be confirmed in larger prospective series to possibly incorporate PROM1 gene expression into risk classification systems to be used in the clinical setting. PMID:21486962

Development in Children with Achondroplasia: A Prospective Clinical Cohort Study

ERIC Educational Resources Information Center

Ireland, Penelope J.; Donaghey, Samantha; McGill, James; Zankl, Andreas; Ware, Robert S.; Pacey, Verity; Ault, Jenny; Savarirayan, Ravi; Sillence, David; Thompson, Elizabeth; Townshend, Sharron; Johnston, Leanne M.

2012-01-01

Aim: Achondroplasia is characterized by delays in the development of communication and motor skills. While previously reported developmental profiles exist across gross motor, fine motor, feeding, and communication skills, there has been no prospective study of development across multiple areas simultaneously. Method: This Australasian…

Gene expression inference with deep learning.

PubMed

Chen, Yifei; Li, Yi; Narayan, Rajiv; Subramanian, Aravind; Xie, Xiaohui

2016-06-15

Large-scale gene expression profiling has been widely used to characterize cellular states in response to various disease conditions, genetic perturbations, etc. Although the cost of whole-genome expression profiles has been dropping steadily, generating a compendium of expression profiling over thousands of samples is still very expensive. Recognizing that gene expressions are often highly correlated, researchers from the NIH LINCS program have developed a cost-effective strategy of profiling only ∼1000 carefully selected landmark genes and relying on computational methods to infer the expression of remaining target genes. However, the computational approach adopted by the LINCS program is currently based on linear regression (LR), limiting its accuracy since it does not capture complex nonlinear relationship between expressions of genes. We present a deep learning method (abbreviated as D-GEX) to infer the expression of target genes from the expression of landmark genes. We used the microarray-based Gene Expression Omnibus dataset, consisting of 111K expression profiles, to train our model and compare its performance to those from other methods. In terms of mean absolute error averaged across all genes, deep learning significantly outperforms LR with 15.33% relative improvement. A gene-wise comparative analysis shows that deep learning achieves lower error than LR in 99.97% of the target genes. We also tested the performance of our learned model on an independent RNA-Seq-based GTEx dataset, which consists of 2921 expression profiles. Deep learning still outperforms LR with 6.57% relative improvement, and achieves lower error in 81.31% of the target genes. D-GEX is available at https://github.com/uci-cbcl/D-GEX CONTACT: xhx@ics.uci.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Gene expression inference with deep learning

PubMed Central

Chen, Yifei; Li, Yi; Narayan, Rajiv; Subramanian, Aravind; Xie, Xiaohui

2016-01-01

Motivation: Large-scale gene expression profiling has been widely used to characterize cellular states in response to various disease conditions, genetic perturbations, etc. Although the cost of whole-genome expression profiles has been dropping steadily, generating a compendium of expression profiling over thousands of samples is still very expensive. Recognizing that gene expressions are often highly correlated, researchers from the NIH LINCS program have developed a cost-effective strategy of profiling only ∼1000 carefully selected landmark genes and relying on computational methods to infer the expression of remaining target genes. However, the computational approach adopted by the LINCS program is currently based on linear regression (LR), limiting its accuracy since it does not capture complex nonlinear relationship between expressions of genes. Results: We present a deep learning method (abbreviated as D-GEX) to infer the expression of target genes from the expression of landmark genes. We used the microarray-based Gene Expression Omnibus dataset, consisting of 111K expression profiles, to train our model and compare its performance to those from other methods. In terms of mean absolute error averaged across all genes, deep learning significantly outperforms LR with 15.33% relative improvement. A gene-wise comparative analysis shows that deep learning achieves lower error than LR in 99.97% of the target genes. We also tested the performance of our learned model on an independent RNA-Seq-based GTEx dataset, which consists of 2921 expression profiles. Deep learning still outperforms LR with 6.57% relative improvement, and achieves lower error in 81.31% of the target genes. Availability and implementation: D-GEX is available at https://github.com/uci-cbcl/D-GEX. Contact: xhx@ics.uci.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26873929

PROFILES OF GENE EXPRESSION ASSOCIATED WITH TETRACYCLINE OVER EXPRESSION OF HSP70 IN MCF-7 BREAST CANCER CELLS

EPA Science Inventory

Profiles of gene expression associated with tetracycline over expression of HSP70 in MCF-7 breast cancer cells.

Heat shock proteins (HSPs) protect cells from damage through their function as molecular chaperones. Some cancers reveal high levels of HSP70 expression in asso...

1975 Manual of Freshman Profiles. Four-year Colleges and University Centers, State University of New York. 1976 Profile Supplement.

ERIC Educational Resources Information Center

State Univ. of New York, Albany. Office of Admissions and Financial Aid Affairs.

The State University of New York compiles an information manual about freshman admission to the baccalaureate programs throughout the state. A profile summary for the four-year colleges and university centers is charted. An outline of costs and financial assistance available is provided to help the prospective student understand and prepare for…

Similar protein expression profiles of ovarian and endometrial high-grade serous carcinomas.

PubMed

Hiramatsu, Kosuke; Yoshino, Kiyoshi; Serada, Satoshi; Yoshihara, Kosuke; Hori, Yumiko; Fujimoto, Minoru; Matsuzaki, Shinya; Egawa-Takata, Tomomi; Kobayashi, Eiji; Ueda, Yutaka; Morii, Eiichi; Enomoto, Takayuki; Naka, Tetsuji; Kimura, Tadashi

2016-03-01

Ovarian and endometrial high-grade serous carcinomas (HGSCs) have similar clinical and pathological characteristics; however, exhaustive protein expression profiling of these cancers has yet to be reported. We performed protein expression profiling on 14 cases of HGSCs (7 ovarian and 7 endometrial) and 18 endometrioid carcinomas (9 ovarian and 9 endometrial) using iTRAQ-based exhaustive and quantitative protein analysis. We identified 828 tumour-expressed proteins and evaluated the statistical similarity of protein expression profiles between ovarian and endometrial HGSCs using unsupervised hierarchical cluster analysis (P<0.01). Using 45 statistically highly expressed proteins in HGSCs, protein ontology analysis detected two enriched terms and proteins composing each term: IMP2 and MCM2. Immunohistochemical analyses confirmed the higher expression of IMP2 and MCM2 in ovarian and endometrial HGSCs as well as in tubal and peritoneal HGSCs than in endometrioid carcinomas (P<0.01). The knockdown of either IMP2 or MCM2 by siRNA interference significantly decreased the proliferation rate of ovarian HGSC cell line (P<0.01). We demonstrated the statistical similarity of the protein expression profiles of ovarian and endometrial HGSC beyond the organs. We suggest that increased IMP2 and MCM2 expression may underlie some of the rapid HGSC growth observed clinically.

Structure-related clustering of gene expression fingerprints of thp-1 cells exposed to smaller polycyclic aromatic hydrocarbons.

PubMed

Wan, B; Yarbrough, J W; Schultz, T W

2008-01-01

This study was undertaken to test the hypothesis that structurally similar PAHs induce similar gene expression profiles. THP-1 cells were exposed to a series of 12 selected PAHs at 50 microM for 24 hours and gene expressions profiles were analyzed using both unsupervised and supervised methods. Clustering analysis of gene expression profiles revealed that the 12 tested chemicals were grouped into five clusters. Within each cluster, the gene expression profiles are more similar to each other than to the ones outside the cluster. One-methylanthracene and 1-methylfluorene were found to have the most similar profiles; dibenzothiophene and dibenzofuran were found to share common profiles with fluorine. As expression pattern comparisons were expanded, similarity in genomic fingerprint dropped off dramatically. Prediction analysis of microarrays (PAM) based on the clustering pattern generated 49 predictor genes that can be used for sample discrimination. Moreover, a significant analysis of Microarrays (SAM) identified 598 genes being modulated by tested chemicals with a variety of biological processes, such as cell cycle, metabolism, and protein binding and KEGG pathways being significantly (p < 0.05) affected. It is feasible to distinguish structurally different PAHs based on their genomic fingerprints, which are mechanism based.

Determinants of Entrepreneurial Intention among Prospective Graduates of Higher Institutions Case of Wolaita Sodo University

ERIC Educational Resources Information Center

Tegegn, Tesfahun; Paulos, Mesfin; Desalegn, Yonatan

2016-01-01

This study entitled "Determinants of Entrepreneurial Intention among Prospective Graduates of Higher Institutions, Case of Wolaita Sodo University" aimed at profiling entrepreneurship among graduating class students at WSU and identify determinants of their entrepreneurial intentions. The study used survey design and collected…

Voir Dire Simulation.

ERIC Educational Resources Information Center

Van Camp, Julie

1986-01-01

This article provides background on the voir dire (jury selection) process, explaining its importance to the outcome of a trial. Offers a simulation experience which has students take the role of lawyers interviewing 29 prospective jurors for an alcohol-related traffic accident involving a 20-year-old driver. Profiles for prospective jurors and…

Institutional Image Indicators of Three Universities: Basis for Attracting Prospective Entrants

ERIC Educational Resources Information Center

Bringula, Rex P.; Basa, Roselle S.

2011-01-01

This study determined the student profile and enrollment of the three Universities in the University Belt. It also found out the respondents' level of consideration concerning the institutional image indicators that served as basis for attracting prospective entrants. Descriptive statistics revealed the following: most of the respondents belonged…

Spiritual Expressions' Prediction of Mindfulness: The Case of Prospective Teachers

ERIC Educational Resources Information Center

Yalçin, S. Barbaros

2018-01-01

The purpose of this research is to determine whether prospective teachers' spiritual expressions have predicted their mindfulness. The research was conducted in relational screening model. The study group consisted of 411 students (81.2%) females and 94 (18.6%) males, totally 505 undergraduate students who are studying in the last year and who…

Rare emergence of symptoms during long-term asymptomatic Escherichia coli 83972 carriage without an altered virulence factor repertoire.

PubMed

Köves, Béla; Salvador, Ellaine; Grönberg-Hernández, Jenny; Zdziarski, Jaroslaw; Wullt, Björn; Svanborg, Catharina; Dobrindt, Ulrich

2014-02-01

Asymptomatic bacteriuria established by intravesical inoculation of Escherichia coli 83972 is protective in patients with recurrent urinary tract infections. In this randomized, controlled crossover study a total of 3 symptomatic urinary tract infection episodes developed in 2 patients while they carried E. coli 83972. We examined whether virulence reacquisition by symptom isolates may account for the switch from asymptomatic bacteriuria to symptomatic urinary tract infection. We used E. coli 83972 re-isolates from 2 patients in a prospective study and from another 2 in whom symptoms developed after study completion. We phylogenetically classified the re-isolates, and identified the genomic restriction patterns and gene expression profiles as well as virulence gene structure and phenotypes. In vivo virulence was examined in the murine urinary tract infection model. The fim, pap, foc, hlyA, fyuA, iuc, iroN, kpsMT K5 and malX genotypes of the symptomatic re-isolates remained unchanged. Bacterial gene expression profiles of flagellated symptomatic re-isolates were unique to each host, providing no evidence of common deregulation. Symptomatic isolates did not differ in virulence from the wild-type strain, as defined in the murine urinary tract infection model by persistence, symptoms or innate immune activation. The switch from asymptomatic E. coli 83972 carriage to symptomatic urinary tract infection was not explained by reversion to a functional virulence gene repertoire. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

A method to identify differential expression profiles of time-course gene data with Fourier transformation.

PubMed

Kim, Jaehee; Ogden, Robert Todd; Kim, Haseong

2013-10-18

Time course gene expression experiments are an increasingly popular method for exploring biological processes. Temporal gene expression profiles provide an important characterization of gene function, as biological systems are both developmental and dynamic. With such data it is possible to study gene expression changes over time and thereby to detect differential genes. Much of the early work on analyzing time series expression data relied on methods developed originally for static data and thus there is a need for improved methodology. Since time series expression is a temporal process, its unique features such as autocorrelation between successive points should be incorporated into the analysis. This work aims to identify genes that show different gene expression profiles across time. We propose a statistical procedure to discover gene groups with similar profiles using a nonparametric representation that accounts for the autocorrelation in the data. In particular, we first represent each profile in terms of a Fourier basis, and then we screen out genes that are not differentially expressed based on the Fourier coefficients. Finally, we cluster the remaining gene profiles using a model-based approach in the Fourier domain. We evaluate the screening results in terms of sensitivity, specificity, FDR and FNR, compare with the Gaussian process regression screening in a simulation study and illustrate the results by application to yeast cell-cycle microarray expression data with alpha-factor synchronization.The key elements of the proposed methodology: (i) representation of gene profiles in the Fourier domain; (ii) automatic screening of genes based on the Fourier coefficients and taking into account autocorrelation in the data, while controlling the false discovery rate (FDR); (iii) model-based clustering of the remaining gene profiles. Using this method, we identified a set of cell-cycle-regulated time-course yeast genes. The proposed method is general and can be potentially used to identify genes which have the same patterns or biological processes, and help facing the present and forthcoming challenges of data analysis in functional genomics.

Molecular cloning and expression profile analysis of porcine TCAP gene.

PubMed

Cheng, Hunjun; Xu, Xuewen; Zhao, Shuhong; Liu, Bang; Yu, Mei; Fan, Bin

2010-03-01

The gradually discovered sarcomeric proteins play important roles for structural integrity and signal transduction of sarcomere during myofibril genesis. TCAP (also described as telethonin, T-cap), one of the sarcomeric protein genes, is regulated developmentally. In this study, we reported the molecular characteristics of porcine TCAP gene. A 979 bp TCAP cDNA nucleotide sequence was obtained in pig and the deduced amino acid sequence had 92 and 91% identity to those of human and mouse homologous genes, respectively. One SNP was discovered and the allele frequency analysis showed that G allele frequency was low among 221 unrelated pigs from seven breeds. The tissue distribution patterns revealed that TCAP mRNA was expressed abundantly in skeletal and heart muscle tissue. Real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) results displayed TCAP mRNA was up-regulated in both Tongcheng and Landrace pigs during prenatal skeletal muscle development stages. This study suggested that TCAP gene might be a prospective candidate gene affecting muscle mass and meat quality traits in the pig, and also implicated the possible significance of TCAP on sarcomere assembly.

Transcriptome profiles in sarcoidosis and their potential role in disease prediction.

PubMed

Schupp, Jonas C; Vukmirovic, Milica; Kaminski, Naftali; Prasse, Antje

2017-09-01

Sarcoidosis is a systemic disease defined by the presence of nonnecrotizing granuloma in the absence of any known cause. Although the heterogeneity of sarcoidosis is well characterized clinically, the transcriptome of sarcoidosis and underlying molecular mechanisms are not. The signal of all transcripts, small and long noncoding RNAs, can be detected using microarrays or RNA-Sequencing. Analyzing the transcriptome of tissues that are directly affected by granulomas is of great importance to understand biology of the disease and may be predictive of disease and treatment outcome. Multiple genome wide expression studies performed on sarcoidosis affected tissues were published in the last 11 years. Published studies focused on differences in gene expression between sarcoidosis vs. control tissues, stable vs. progressive sarcoidosis, as well as sarcoidosis vs. other diseases. Strikingly, all these transcriptomics data confirm the key role of TH1 immune response in sarcoidosis and particularly of interferon-γ (IFN-γ) and type I IFN-driven signaling pathways. The steps toward transcriptomics of sarcoidosis in precision medicine highlight the potentials of this approach. Large prospective follow-up studies are required to identify signatures predictive of disease progression and outcome.

Increased Expression Profile and Functionality of TLR6 in Peripheral Blood Mononuclear Cells and Hepatocytes of Morbidly Obese Patients with Non-Alcoholic Fatty Liver Disease.

PubMed

Arias-Loste, María Teresa; Iruzubieta, Paula; Puente, Ángela; Ramos, David; Santa Cruz, Carolina; Estébanez, Ángel; Llerena, Susana; Alonso-Martín, Carmen; San Segundo, David; Álvarez, Lorena; López Useros, Antonio; Fábrega, Emilio; López-Hoyos, Marcos; Crespo, Javier

2016-11-10

Current evidence suggests that gut dysbiosis drives obesity and non-alcoholic fatty liver disease (NAFLD) pathogenesis. Toll-like receptor 2 (TLR2) and TLR6 specifically recognize components of Gram-positive bacteria. Despite the potential implications of TLR2 in NAFLD pathogenesis, the role of TLR6 has not been addressed. Our aim is to study a potential role of TLR6 in obesity-related NAFLD. Forty morbidly obese patients undergoing bariatric surgery were prospectively studied. Cell surface expression of TLR2 and TLR6 was assessed on peripheral blood mononuclear cells (PBMCs) by flow cytometry. Freshly isolated monocytes were cultured with specific TLR2/TLR6 agonists and intracellular production of cytokines was determined by flow-cytometry. In liver biopsies, the expression of TLR2 and TLR6 was analyzed by immunohistochemistry and cytokine gene expression using RT-qPCR. TLR6 expression in PBMCs from non-alcoholic steatohepatitis (NASH) patients was significantly higher when compared to those from simple steatosis. The production of pro-inflammatory cytokines in response to TLR2/TLR6 stimulation was also significantly higher in patients with lobular inflammation. Hepatocyte expression of TLR6 but not that of TLR2 was increased in NAFLD patients compared to normal liver histology. Deregulated expression and activity of peripheral TLR6 in morbidly obese patients can mirror the liver inflammatory events that are well known drivers of obesity-related NASH pathogenesis. Moreover, TLR6 is also significantly overexpressed in the hepatocytes of NAFLD patients compared to their normal counterparts. Thus, deregulated TLR6 expression may potentiate TLR2-mediated liver inflammation in NAFLD pathogenesis, and also serve as a potential peripheral biomarker of obesity-related NASH.

Single Cell Gene Expression Profiling of Skeletal Muscle-Derived Cells.

PubMed

Gatto, Sole; Puri, Pier Lorenzo; Malecova, Barbora

2017-01-01

Single cell gene expression profiling is a fundamental tool for studying the heterogeneity of a cell population by addressing the phenotypic and functional characteristics of each cell. Technological advances that have coupled microfluidic technologies with high-throughput quantitative RT-PCR analyses have enabled detailed analyses of single cells in various biological contexts. In this chapter, we describe the procedure for isolating the skeletal muscle interstitial cells termed Fibro-Adipogenic Progenitors (FAPs ) and their gene expression profiling at the single cell level. Moreover, we accompany our bench protocol with bioinformatics analysis designed to process raw data as well as to visualize single cell gene expression data. Single cell gene expression profiling is therefore a useful tool in the investigation of FAPs heterogeneity and their contribution to muscle homeostasis.

GENE EXPRESSION PROFILES IN ARSENIC-TREATED MCF-7 BREAST CANCER CELLS EXPRESSING DIFFERENT LEVELS OF HSP70

EPA Science Inventory

Gene expression profiles in arsenic-treated MCF-7 breast cancer cells expressing different levels of HSP70

Gail Nelson, Susan Hester, Ernest Winkfield, Jill Barnes, James Allen
Environmental Carcinogenesis Division, NHEERL, ORD, US Environmental Protection Agency, Rese...

iPcc: a novel feature extraction method for accurate disease class discovery and prediction

PubMed Central

Ren, Xianwen; Wang, Yong; Zhang, Xiang-Sun; Jin, Qi

2013-01-01

Gene expression profiling has gradually become a routine procedure for disease diagnosis and classification. In the past decade, many computational methods have been proposed, resulting in great improvements on various levels, including feature selection and algorithms for classification and clustering. In this study, we present iPcc, a novel method from the feature extraction perspective to further propel gene expression profiling technologies from bench to bedside. We define ‘correlation feature space’ for samples based on the gene expression profiles by iterative employment of Pearson’s correlation coefficient. Numerical experiments on both simulated and real gene expression data sets demonstrate that iPcc can greatly highlight the latent patterns underlying noisy gene expression data and thus greatly improve the robustness and accuracy of the algorithms currently available for disease diagnosis and classification based on gene expression profiles. PMID:23761440

Renal Gene Expression Database (RGED): a relational database of gene expression profiles in kidney disease

PubMed Central

Zhang, Qingzhou; Yang, Bo; Chen, Xujiao; Xu, Jing; Mei, Changlin; Mao, Zhiguo

2014-01-01

We present a bioinformatics database named Renal Gene Expression Database (RGED), which contains comprehensive gene expression data sets from renal disease research. The web-based interface of RGED allows users to query the gene expression profiles in various kidney-related samples, including renal cell lines, human kidney tissues and murine model kidneys. Researchers can explore certain gene profiles, the relationships between genes of interests and identify biomarkers or even drug targets in kidney diseases. The aim of this work is to provide a user-friendly utility for the renal disease research community to query expression profiles of genes of their own interest without the requirement of advanced computational skills. Availability and implementation: Website is implemented in PHP, R, MySQL and Nginx and freely available from http://rged.wall-eva.net. Database URL: http://rged.wall-eva.net PMID:25252782

Renal Gene Expression Database (RGED): a relational database of gene expression profiles in kidney disease.

PubMed

Zhang, Qingzhou; Yang, Bo; Chen, Xujiao; Xu, Jing; Mei, Changlin; Mao, Zhiguo

2014-01-01

We present a bioinformatics database named Renal Gene Expression Database (RGED), which contains comprehensive gene expression data sets from renal disease research. The web-based interface of RGED allows users to query the gene expression profiles in various kidney-related samples, including renal cell lines, human kidney tissues and murine model kidneys. Researchers can explore certain gene profiles, the relationships between genes of interests and identify biomarkers or even drug targets in kidney diseases. The aim of this work is to provide a user-friendly utility for the renal disease research community to query expression profiles of genes of their own interest without the requirement of advanced computational skills. Website is implemented in PHP, R, MySQL and Nginx and freely available from http://rged.wall-eva.net. http://rged.wall-eva.net. © The Author(s) 2014. Published by Oxford University Press.

Dysregulation of miRNAs in bladder cancer: altered expression with aberrant biogenesis procedure

PubMed Central

Dong, Fan; Xu, Tianyuan; Shen, Yifan; Zhong, Shan; Chen, Shanwen; Ding, Qiang; Shen, Zhoujun

2017-01-01

Aberrant expression profiles of miRNAs are widely observed in the clinical tissue specimens and urine samples as well as the blood samples of bladder cancer patients. These profiles are closely related to the pathological features of bladder cancer, such as the tumour stage/grade, metastasis, recurrence and chemo-sensitivity. MiRNA biogenesis forms the basis of miRNA expression and function, and its dysregulation has been shown to be essential for variations in miRNA expression profiles as well as tumourigenesis and cancer progression. In this review, we summarize the up-to-date and widely reported miRNAs in bladder cancer that display significantly altered expression. We then compare the miRNA expression profiles among three different sample types (tissue, urine and blood) from patients with bladder cancer. Moreover, for the first time, we outline the dysregulated miRNA biogenesis network in bladder cancer from different levels and analyse its possible relationship with aberrant miRNA expression and the pathological characteristics of the disease. PMID:28187437

Molecular profiles of pre- and postoperative breast cancer tumours reveal differentially expressed genes.

PubMed

Riis, Margit L H; Lüders, Torben; Markert, Elke K; Haakensen, Vilde D; Nesbakken, Anne-Jorun; Kristensen, Vessela N; Bukholm, Ida R K

2012-01-01

Gene expression studies on breast cancer have generally been performed on tissue obtained at the time of surgery. In this study, we have compared the gene expression profiles in preoperative tissue (core needle biopsies) while tumor is still in its normal milieu to postoperative tissue from the same tumor obtained during surgery. Thirteen patients were included of which eleven had undergone sentinel node diagnosis procedure before operation. Microarray gene expression analysis was performed using total RNA from all the samples. Paired significance analysis of microarrays revealed 228 differently expressed genes, including several early response stress-related genes such as members of the fos and jun families as well as genes of which the expression has previously been associated with cancer. The expression profiles found in the analyses of breast cancer tissue must be evaluated with caution. Different profiles may simply be the result of differences in the surgical trauma and timing of when samples are taken and not necessarily associated with tumor biology.

Molecular Profiles of Pre- and Postoperative Breast Cancer Tumours Reveal Differentially Expressed Genes

PubMed Central

Riis, Margit L. H.; Lüders, Torben; Markert, Elke K.; Haakensen, Vilde D.; Nesbakken, Anne-Jorun; Kristensen, Vessela N.; Bukholm, Ida R. K.

2012-01-01

Gene expression studies on breast cancer have generally been performed on tissue obtained at the time of surgery. In this study, we have compared the gene expression profiles in preoperative tissue (core needle biopsies) while tumor is still in its normal milieu to postoperative tissue from the same tumor obtained during surgery. Thirteen patients were included of which eleven had undergone sentinel node diagnosis procedure before operation. Microarray gene expression analysis was performed using total RNA from all the samples. Paired significance analysis of microarrays revealed 228 differently expressed genes, including several early response stress-related genes such as members of the fos and jun families as well as genes of which the expression has previously been associated with cancer. The expression profiles found in the analyses of breast cancer tissue must be evaluated with caution. Different profiles may simply be the result of differences in the surgical trauma and timing of when samples are taken and not necessarily associated with tumor biology. PMID:23227362

Expression profiles of antimicrobial peptides (AMPs) and their regulation by Relish

NASA Astrophysics Data System (ADS)

Wang, Dongdong; Li, Fuhua; Li, Shihao; Wen, Rong; Xiang, Jianhai

2012-07-01

Antimicrobial peptides (AMPs), as key immune effectors, play important roles in the innate immune system of invertebrates. Different types of AMPs, including Penaeidin, Crustin, ALF (antilipopolysaccharide factor) have been identified in different penaeid shrimp; however, systematic analyses on the function of different AMPs in shrimp responsive to different types of bacteria are very limited. In this study, we analyzed the expression profiles of AMPs in the Chinese shrimps, Fenneropenaeus chinensis, simultaneously by real-time RT-PCR (reverse transcription-polymerase chain reaction) when shrimp were challenged with Micrococcus lysodeikticus (Gram-positive, G+) or Vibrio anguillarium (Gram-negative, G-). Different AMPs showed different expression profiles when shrimp were injected with one type of bacterium, and one AMP also showed different expression profiles when shrimp were challenged with different bacteria. Furthermore, the expression of these AMPs showed temporal expression profiles, suggesting that different AMPs function coordinately in bacteria-infected shrimp. An RNA interference approach was used to study the function of the Relish transcription factor in regulating the transcription of different AMPs. The current study showed that Relish could regulate the transcription of different AMPs in shrimp. Differential expression profiles of AMPs in shrimp injected with different types of bacteria indicated that a complicated antimicrobial response network existed in shrimp. These data contribute to our understanding of immunity in shrimp and may provide a strategy for the control of disease in shrimp.

Baculovirus induced transcripts in hemocytes from Heliothis virescens

USDA-ARS?s Scientific Manuscript database

Using RNA-sequencing digital difference expression profiling methods we have assessed the gene expression profiles of hemocytes harvested from Heliothis virescens that were challenged with Helicoverpa zea single nucleopolyhedrovirus (HzSNPV). A reference transcriptome of hemocyte-expressed transcri...

Influence of in vivo growth on human glioma cell line gene expression: Convergent profiles under orthotopic conditions

PubMed Central

Camphausen, Kevin; Purow, Benjamin; Sproull, Mary; Scott, Tamalee; Ozawa, Tomoko; Deen, Dennis F.; Tofilon, Philip J.

2005-01-01

Defining the molecules that regulate tumor cell survival is an essential prerequisite for the development of targeted approaches to cancer treatment. Whereas many studies aimed at identifying such targets use human tumor cells grown in vitro or as s.c. xenografts, it is unclear whether such experimental models replicate the phenotype of the in situ tumor cell. To begin addressing this issue, we have used microarray analysis to define the gene expression profile of two human glioma cell lines (U251 and U87) when grown in vitro and in vivo as s.c. or as intracerebral (i.c.) xenografts. For each cell line, the gene expression profile generated from tissue culture was significantly different from that generated from the s.c. tumor, which was significantly different from those grown i.c. The disparity between the i.c gene expression profiles and those generated from s.c. xenografts suggests that whereas an in vivo growth environment modulates gene expression, orthotopic growth conditions induce a different set of modifications. In this study the U251 and U87 gene expression profiles generated under the three growth conditions were also compared. As expected, the profiles of the two glioma cell lines were significantly different when grown as monolayer cultures. However, the glioma cell lines had similar gene expression profiles when grown i.c. These results suggest that tumor cell gene expression, and thus phenotype, as defined in vitro is affected not only by in vivo growth but also by orthotopic growth, which may have implications regarding the identification of relevant targets for cancer therapy. PMID:15928080

Match score affects activity profile and skill performance in professional Australian Football players.

PubMed

Sullivan, Courtney; Bilsborough, Johann C; Cianciosi, Michael; Hocking, Joel; Cordy, Justin; Coutts, Aaron J

2014-05-01

To examine the influence of quarter outcome and the margin of the score differential on both the physical activity profile and skill performance of players during professional Australian Football matches. Prospective, longitudinal. Physical activity profiles were assessed via microtechnology (Global Positioning System and accelerometer) from 40 professional AF players from the same team during 15 Australian Football League games. Skill performance measures (involvement and effectiveness) and player rank scores (Champion Data(©) Rank) were provided by a commercial statistical provider. The physical performance variables, skill involvements and individual player performance scores were expressed relative to playing time for each quarter. The influence of the quarter result (i.e. win vs. loss) and score margin (i.e. small: <9 points, moderate: 10-18 points, and large: >19 points) on activity profile and skill involvements and skill efficiency performance of players were examined. Skill involvements (total disposals/min, long kicks/min, marks/min, running bounces/min and player rank/min) were greater in quarters won (all p<0.01). In contrast, the players high speed running distance per minute (>14.5 km h(-1), HSR/min), sprints/min and peak speed were higher in losing quarters (all p<0.01). Smaller score margins were associated with increased physical activity (m/min, HSR/min, and body load/min, all p<0.05) and decreased skill efficiency (handball clangers/min and player rank/min, all p<0.05). Professional AF players are likely to have an increased physical activity profile and decreased skill involvement and proficiency when their team is less successful. Copyright © 2013 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Early Indicators of Autism Spectrum Disorders at 12 and 24 Months of Age: A Prospective, Longitudinal Comparative Study

ERIC Educational Resources Information Center

Veness, Carly; Prior, Margot; Bavin, Edith; Eadie, Patricia; Cini, Eileen; Reilly, Sheena

2012-01-01

Prospective questionnaire data from a longitudinal population sample on children with autism spectrum disorders (ASD), developmental delay, specific language impairment, or typical development (TD), were collected at ages eight, 12 and 24 months, via the Communication and Symbolic Behavior Scale Developmental Profile (CSBS)--Infant Toddler…

CA State Profile. California: California High School Exit Examination (CAHSEE)

ERIC Educational Resources Information Center

Center on Education Policy, 2010

2010-01-01

This paper provides information about California High School Exit Examination, a comprehensive standards-based exam. The purpose of the exam is to: (1) Determine prospective high school graduates' knowledge and skill levels relative to those needed for entry-level employment; (2) Determine prospective high school graduates' mastery of the state…

A gene expression resource generated by genome-wide lacZ profiling in the mouse

PubMed Central

Tuck, Elizabeth; Estabel, Jeanne; Oellrich, Anika; Maguire, Anna Karin; Adissu, Hibret A.; Souter, Luke; Siragher, Emma; Lillistone, Charlotte; Green, Angela L.; Wardle-Jones, Hannah; Carragher, Damian M.; Karp, Natasha A.; Smedley, Damian; Adams, Niels C.; Bussell, James N.; Adams, David J.; Ramírez-Solis, Ramiro; Steel, Karen P.; Galli, Antonella; White, Jacqueline K.

2015-01-01

ABSTRACT Knowledge of the expression profile of a gene is a critical piece of information required to build an understanding of the normal and essential functions of that gene and any role it may play in the development or progression of disease. High-throughput, large-scale efforts are on-going internationally to characterise reporter-tagged knockout mouse lines. As part of that effort, we report an open access adult mouse expression resource, in which the expression profile of 424 genes has been assessed in up to 47 different organs, tissues and sub-structures using a lacZ reporter gene. Many specific and informative expression patterns were noted. Expression was most commonly observed in the testis and brain and was most restricted in white adipose tissue and mammary gland. Over half of the assessed genes presented with an absent or localised expression pattern (categorised as 0-10 positive structures). A link between complexity of expression profile and viability of homozygous null animals was observed; inactivation of genes expressed in ≥21 structures was more likely to result in reduced viability by postnatal day 14 compared with more restricted expression profiles. For validation purposes, this mouse expression resource was compared with Bgee, a federated composite of RNA-based expression data sets. Strong agreement was observed, indicating a high degree of specificity in our data. Furthermore, there were 1207 observations of expression of a particular gene in an anatomical structure where Bgee had no data, indicating a large amount of novelty in our data set. Examples of expression data corroborating and extending genotype-phenotype associations and supporting disease gene candidacy are presented to demonstrate the potential of this powerful resource. PMID:26398943

Whole genome expression and biochemical correlates of extreme constitutional types defined in Ayurveda.

PubMed

Prasher, Bhavana; Negi, Sapna; Aggarwal, Shilpi; Mandal, Amit K; Sethi, Tav P; Deshmukh, Shailaja R; Purohit, Sudha G; Sengupta, Shantanu; Khanna, Sangeeta; Mohammad, Farhan; Garg, Gaurav; Brahmachari, Samir K; Mukerji, Mitali

2008-09-09

Ayurveda is an ancient system of personalized medicine documented and practiced in India since 1500 B.C. According to this system an individual's basic constitution to a large extent determines predisposition and prognosis to diseases as well as therapy and life-style regime. Ayurveda describes seven broad constitution types (Prakritis) each with a varying degree of predisposition to different diseases. Amongst these, three most contrasting types, Vata, Pitta, Kapha, are the most vulnerable to diseases. In the realm of modern predictive medicine, efforts are being directed towards capturing disease phenotypes with greater precision for successful identification of markers for prospective disease conditions. In this study, we explore whether the different constitution types as described in Ayurveda has molecular correlates. Normal individuals of the three most contrasting constitutional types were identified following phenotyping criteria described in Ayurveda in Indian population of Indo-European origin. The peripheral blood samples of these individuals were analysed for genome wide expression levels, biochemical and hematological parameters. Gene Ontology (GO) and pathway based analysis was carried out on differentially expressed genes to explore if there were significant enrichments of functional categories among Prakriti types. Individuals from the three most contrasting constitutional types exhibit striking differences with respect to biochemical and hematological parameters and at genome wide expression levels. Biochemical profiles like liver function tests, lipid profiles, and hematological parameters like haemoglobin exhibited differences between Prakriti types. Functional categories of genes showing differential expression among Prakriti types were significantly enriched in core biological processes like transport, regulation of cyclin dependent protein kinase activity, immune response and regulation of blood coagulation. A significant enrichment of housekeeping, disease related and hub genes were observed in these extreme constitution types. Ayurveda based method of phenotypic classification of extreme constitutional types allows us to uncover genes that may contribute to system level differences in normal individuals which could lead to differential disease predisposition. This is a first attempt towards unraveling the clinical phenotyping principle of a traditional system of medicine in terms of modern biology. An integration of Ayurveda with genomics holds potential and promise for future predictive medicine.

Whole genome expression and biochemical correlates of extreme constitutional types defined in Ayurveda

PubMed Central

Prasher, Bhavana; Negi, Sapna; Aggarwal, Shilpi; Mandal, Amit K; Sethi, Tav P; Deshmukh, Shailaja R; Purohit, Sudha G; Sengupta, Shantanu; Khanna, Sangeeta; Mohammad, Farhan; Garg, Gaurav; Brahmachari, Samir K; Mukerji, Mitali

2008-01-01

Background Ayurveda is an ancient system of personalized medicine documented and practiced in India since 1500 B.C. According to this system an individual's basic constitution to a large extent determines predisposition and prognosis to diseases as well as therapy and life-style regime. Ayurveda describes seven broad constitution types (Prakritis) each with a varying degree of predisposition to different diseases. Amongst these, three most contrasting types, Vata, Pitta, Kapha, are the most vulnerable to diseases. In the realm of modern predictive medicine, efforts are being directed towards capturing disease phenotypes with greater precision for successful identification of markers for prospective disease conditions. In this study, we explore whether the different constitution types as described in Ayurveda has molecular correlates. Methods Normal individuals of the three most contrasting constitutional types were identified following phenotyping criteria described in Ayurveda in Indian population of Indo-European origin. The peripheral blood samples of these individuals were analysed for genome wide expression levels, biochemical and hematological parameters. Gene Ontology (GO) and pathway based analysis was carried out on differentially expressed genes to explore if there were significant enrichments of functional categories among Prakriti types. Results Individuals from the three most contrasting constitutional types exhibit striking differences with respect to biochemical and hematological parameters and at genome wide expression levels. Biochemical profiles like liver function tests, lipid profiles, and hematological parameters like haemoglobin exhibited differences between Prakriti types. Functional categories of genes showing differential expression among Prakriti types were significantly enriched in core biological processes like transport, regulation of cyclin dependent protein kinase activity, immune response and regulation of blood coagulation. A significant enrichment of housekeeping, disease related and hub genes were observed in these extreme constitution types. Conclusion Ayurveda based method of phenotypic classification of extreme constitutional types allows us to uncover genes that may contribute to system level differences in normal individuals which could lead to differential disease predisposition. This is a first attempt towards unraveling the clinical phenotyping principle of a traditional system of medicine in terms of modern biology. An integration of Ayurveda with genomics holds potential and promise for future predictive medicine. PMID:18782426

Preferences for prolonging life: a prospect theory approach.

PubMed

Winter, Laraine; Lawton, M Powell; Ruckdeschel, Katy

2003-01-01

Kahneman and Tversky's (1979) Prospect theory was tested as a model of preferences for prolonging life under various hypothetical health statuses. A sample of 384 elderly people living in congregate housing (263 healthy, 131 frail) indicated how long (if at all) they would want to live under each of nine hypothetical health conditions (e.g., limited to bed or chair in a nursing home). Prospect theory, a decision model which takes into account the individual's point of reference, would predict that frail people would view prospective poorer health conditions as more tolerable and express preferences to live longer in worse health than would currently healthy people. In separate analyses of covariance, we evaluated preferences for continued life under four conditions of functional ability, four conditions of cognitive impairment, and three pain conditions--each as a function of participant's current health status (frail vs. healthy). The predicted interaction between frailty and declining prospective health status was obtained. Frail participants expressed preferences for longer life under more compromised health conditions than did healthy participants. The results imply that such preferences are malleable, changing as health deteriorates. They also help explain disparities between proxy decision-makers' and patients' own preferences as expressed in advance directives.

Longitudinal Studies of a B Cell Derived Signature of Tolerance in Renal Transplant Recipients

PubMed Central

Newell, Kenneth A.; Asare, Adam; Sanz, Ignacio; Wei, Chungwen; Rosenberg, Alexander; Gao, Zhong; Kanaparthi, Sai; Asare, Smita; Lim, Noha; Stahly, Michael; Howell, Michael; Knechtle, Stuart; Kirk, Allan; Marks, William H.; Kawai, Tatsuo; Spitzer, Thomas; Tolkoff-Rubin, Nina; Sykes, Megan; Sachs, David H.; Cosimi, A. Benedict; Burlingham, William J.; Phippard, Deborah; Turka, Laurence A.

2016-01-01

Biomarkers of transplant tolerance would enhance the safety and feasibility of clinical tolerance trials and potentially facilitate management of patients receiving immunosuppression. To this end, we examined blood from spontaneously tolerant renal transplant recipients and patients enrolled in two interventional tolerance trials using flow cytometry and gene expression profiling. Using a previously reported tolerant cohort as well as newly identified tolerant patients we confirmed our previous finding that tolerance was associated with increased expression of B cell-associated genes relative to immunosuppressed patients. This was not accounted for merely by an increase in total B cell numbers, but was associated with the increased frequencies of transitional and naïve B cells. Moreover, serial measurements of gene expression demonstrated that this pattern persisted over several years although patients receiving immunosuppression also displayed an increase in the two most dominant tolerance-related B cell genes, IGKV1D-13 and IGLL-1, over time. Importantly, patients rendered tolerant via induction of transient mixed chimerism, and those weaned to minimal immunosuppression, showed similar increases in IGKV1D-13 as did spontaneously tolerant individuals. Collectively, these findings support the notion that alterations in B cells may be a common theme for tolerant kidney transplant recipients, and a useful monitoring tool in prospective trials. PMID:26461968

Integrated analysis of long noncoding RNA and mRNA expression profile in children with obesity by microarray analysis.

PubMed

Liu, Yuesheng; Ji, Yuqiang; Li, Min; Wang, Min; Yi, Xiaoqing; Yin, Chunyan; Wang, Sisi; Zhang, Meizhen; Zhao, Zhao; Xiao, Yanfeng

2018-06-08

Long noncoding RNAs (lncRNAs) have an important role in adipose tissue function and energy metabolism homeostasis, and abnormalities may lead to obesity. To investigate whether lncRNAs are involved in childhood obesity, we investigated the differential expression profile of lncRNAs in obese children compared with non-obese children. A total number of 1268 differentially expressed lncRNAs and 1085 differentially expressed mRNAs were identified. Gene Ontology (GO) and pathway analysis revealed that these lncRNAs were involved in varied biological processes, including the inflammatory response, lipid metabolic process, osteoclast differentiation and fatty acid metabolism. In addition, the lncRNA-mRNA co-expression network and the protein-protein interaction (PPI) network were constructed to identify hub regulatory lncRNAs and genes based on the microarray expression profiles. This study for the first time identifies an expression profile of differentially expressed lncRNAs in obese children and indicated hub lncRNA RP11-20G13.3 attenuated adipogenesis of preadipocytes, which is conducive to the search for new diagnostic and therapeutic strategies of childhood obesity.

Gene Expression Profiling Predicts the Development of Oral Cancer

PubMed Central

Saintigny, Pierre; Zhang, Li; Fan, You-Hong; El-Naggar, Adel K.; Papadimitrakopoulou, Vali; Feng, Lei; Lee, J. Jack; Kim, Edward S.; Hong, Waun Ki; Mao, Li

2011-01-01

Patients with oral preneoplastic lesion (OPL) have high risk of developing oral cancer. Although certain risk factors such as smoking status and histology are known, our ability to predict oral cancer risk remains poor. The study objective was to determine the value of gene expression profiling in predicting oral cancer development. Gene expression profile was measured in 86 of 162 OPL patients who were enrolled in a clinical chemoprevention trial that used the incidence of oral cancer development as a prespecified endpoint. The median follow-up time was 6.08 years and 35 of the 86 patients developed oral cancer over the course. Gene expression profiles were associated with oral cancer-free survival and used to develope multivariate predictive models for oral cancer prediction. We developed a 29-transcript predictive model which showed marked improvement in terms of prediction accuracy (with 8% predicting error rate) over the models using previously known clinico-pathological risk factors. Based on the gene expression profile data, we also identified 2182 transcripts significantly associated with oral cancer risk associated genes (P-value<0.01, single variate Cox proportional hazards model). Functional pathway analysis revealed proteasome machinery, MYC, and ribosomes components as the top gene sets associated with oral cancer risk. In multiple independent datasets, the expression profiles of the genes can differentiate head and neck cancer from normal mucosa. Our results show that gene expression profiles may improve the prediction of oral cancer risk in OPL patients and the significant genes identified may serve as potential targets for oral cancer chemoprevention. PMID:21292635

Integrated lipidomics and transcriptomic analysis of peripheral blood reveals significantly enriched pathways in type 2 diabetes mellitus.

PubMed

Zhao, Chen; Mao, Jinghe; Ai, Junmei; Shenwu, Ming; Shi, Tieliu; Zhang, Daqing; Wang, Xiaonan; Wang, Yunliang; Deng, Youping

2013-01-01

Insulin resistance is a key element in the pathogenesis of type 2 diabetes mellitus. Plasma free fatty acids were assumed to mediate the insulin resistance, while the relationship between lipid and glucose disposal remains to be demonstrated across liver, skeletal muscle and blood. We profiled both lipidomics and gene expression of 144 total peripheral blood samples, 84 from patients with T2D and 60 from healthy controls. Then, factor and partial least squares models were used to perform a combined analysis of lipidomics and gene expression profiles to uncover the bioprocesses that are associated with lipidomic profiles in type 2 diabetes. According to factor analysis of the lipidomic profile, several species of lipids were found to be correlated with different phenotypes, including diabetes-related C23:2CE, C23:3CE, C23:4CE, ePE36:4, ePE36:5, ePE36:6; race-related (African-American) PI36:1; and sex-related PE34:1 and LPC18:2. The major variance of gene expression profile was not caused by known factors and no significant difference can be directly derived from differential gene expression profile. However, the combination of lipidomic and gene expression analyses allows us to reveal the correlation between the altered lipid profile with significantly enriched pathways, such as one carbon pool by folate, arachidonic acid metabolism, insulin signaling pathway, amino sugar and nucleotide sugar metabolism, propanoate metabolism, and starch and sucrose metabolism. The genes in these pathways showed a good capability to classify diabetes samples. Combined analysis of gene expression and lipidomic profiling reveals type 2 diabetes-associated lipid species and enriched biological pathways in peripheral blood, while gene expression profile does not show direct correlation. Our findings provide a new clue to better understand the mechanism of disordered lipid metabolism in association with type 2 diabetes.

Mesenchymal stromal cells: main factor or helper in regenerative medicine?

PubMed

Zander, Axel R; Lange, Claudia; Westenfelder, Christof

2011-09-01

Mesenchymal stromal cells (mSCs) are presently studied for the prophylaxis and therapy of a variety of diseases such as acute graft-versus-host disease after allogeneic stem cell transplantation, cardiac indications, bone degeneration, Crohn's disease, and organ rejection, as well as prevention of acute renal failure in high-risk situations. mSCs appear to function through paracrine mechanisms that exert immunosuppressive, anti-inflammatory, anti-apoptotic, mitogenic, and other organ-protective and repair-stimulating actions. mSCs are either cultured in the presence of fetal calf serum (FCS) or platelet lysate (PL). PL lysate-generated mSCs exhibit faster doubling times, different gene expression profiles, and more potent immunosuppressive activity compared with FSC-generated mSCs. The utility of mSCs in the treatment of chronic inflammatory diseases is being evaluated in prospective studies.

Divergence between motoneurons: gene expression profiling provides a molecular characterization of functionally discrete somatic and autonomic motoneurons

PubMed Central

Cui, Dapeng; Dougherty, Kimberly J.; Machacek, David W.; Sawchuk, Michael; Hochman, Shawn; Baro, Deborah J.

2009-01-01

Studies in the developing spinal cord suggest that different motoneuron (MN) cell types express very different genetic programs, but the degree to which adult programs differ is unknown. To compare genetic programs between adult MN columnar cell types, we used laser capture micro-dissection (LCM) and Affymetrix microarrays to create expression profiles for three columnar cell types: lateral and medial MNs from lumbar segments and sympathetic preganglionic motoneurons located in the thoracic intermediolateral nucleus. A comparison of the three expression profiles indicated that ~7% (813/11,552) of the genes showed significant differences in their expression levels. The largest differences were observed between sympathetic preganglionic MNs and the lateral motor column, with 6% (706/11,552) of the genes being differentially expressed. Significant differences in expression were observed for 1.8% (207/11,552) of the genes when comparing sympathetic preganglionic MNs with the medial motor column. Lateral and medial MNs showed the least divergence, with 1.3% (150/11,552) of the genes being differentially expressed. These data indicate that the amount of divergence in expression profiles between identified columnar MNs does not strictly correlate with divergence of function as defined by innervation patterns (somatic/muscle vs. autonomic/viscera). Classification of the differentially expressed genes with regard to function showed that they underpin all fundamental cell systems and processes, although most differentially expressed genes encode proteins involved in signal transduction. Mining the expression profiles to examine transcription factors essential for MN development suggested that many of the same transcription factors participatein combinatorial codes in embryonic and adult neurons, but patterns of expression change significantly. PMID:16317082

Face in profile view reduces perceived facial expression intensity: an eye-tracking study.

PubMed

Guo, Kun; Shaw, Heather

2015-02-01

Recent studies measuring the facial expressions of emotion have focused primarily on the perception of frontal face images. As we frequently encounter expressive faces from different viewing angles, having a mechanism which allows invariant expression perception would be advantageous to our social interactions. Although a couple of studies have indicated comparable expression categorization accuracy across viewpoints, it is unknown how perceived expression intensity and associated gaze behaviour change across viewing angles. Differences could arise because diagnostic cues from local facial features for decoding expressions could vary with viewpoints. Here we manipulated orientation of faces (frontal, mid-profile, and profile view) displaying six common facial expressions of emotion, and measured participants' expression categorization accuracy, perceived expression intensity and associated gaze patterns. In comparison with frontal faces, profile faces slightly reduced identification rates for disgust and sad expressions, but significantly decreased perceived intensity for all tested expressions. Although quantitatively viewpoint had expression-specific influence on the proportion of fixations directed at local facial features, the qualitative gaze distribution within facial features (e.g., the eyes tended to attract the highest proportion of fixations, followed by the nose and then the mouth region) was independent of viewpoint and expression type. Our results suggest that the viewpoint-invariant facial expression processing is categorical perception, which could be linked to a viewpoint-invariant holistic gaze strategy for extracting expressive facial cues. Copyright © 2014 Elsevier B.V. All rights reserved.

Display technologies: application for the discovery of drug and gene delivery agents

PubMed Central

Sergeeva, Anna; Kolonin, Mikhail G.; Molldrem, Jeffrey J.; Pasqualini, Renata; Arap, Wadih

2007-01-01

Recognition of molecular diversity of cell surface proteomes in disease is essential for the development of targeted therapies. Progress in targeted therapeutics requires establishing effective approaches for high-throughput identification of agents specific for clinically relevant cell surface markers. Over the past decade, a number of platform strategies have been developed to screen polypeptide libraries for ligands targeting receptors selectively expressed in the context of various cell surface proteomes. Streamlined procedures for identification of ligand-receptor pairs that could serve as targets in disease diagnosis, profiling, imaging and therapy have relied on the display technologies, in which polypeptides with desired binding profiles can be serially selected, in a process called biopanning, based on their physical linkage with the encoding nucleic acid. These technologies include virus/phage display, cell display, ribosomal display, mRNA display and covalent DNA display (CDT), with phage display being by far the most utilized. The scope of this review is the recent advancements in the display technologies with a particular emphasis on molecular mapping of cell surface proteomes with peptide phage display. Prospective applications of targeted compounds derived from display libraries in the discovery of targeted drugs and gene therapy vectors are discussed. PMID:17123658

Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM): novel biological insights and development of early treatment strategies

PubMed Central

Kristinsson, Sigurdur Y.

2011-01-01

Monoclonal gammopathy of unknown significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic plasma cell dyscrasias, with a propensity to progress to symptomatic MM. In recent years there have been improvements in risk stratification models (involving molecular markers) of both disorders, which have led to better understanding of the biology and probability of progression of MGUS and SMM. In the context of numerous molecular events and heterogeneous risk of progression, developing individualized risk profiles for patients with MGUS and SMM represents an ongoing challenge that has to be addressed by prospective clinical monitoring and extensive correlative science. In this review we discuss the current standard of care of patients with MGUS and SMM, the use of risk models, including flow cytometry and free-light chain analyses, for predicting risk of progression. Emerging evidence from molecular studies on MGUS and SMM, involving cytogenetics, gene-expression profiling, and microRNA as well as molecular imaging is described. Finally, future directions for improving individualized management of MGUS and SMM patients, as well as the potential for developing early treatment strategies designed to delay and prevent development of MM are discussed. PMID:21441462

Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM): novel biological insights and development of early treatment strategies.

PubMed

Korde, Neha; Kristinsson, Sigurdur Y; Landgren, Ola

2011-05-26

Monoclonal gammopathy of unknown significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic plasma cell dyscrasias, with a propensity to progress to symptomatic MM. In recent years there have been improvements in risk stratification models (involving molecular markers) of both disorders, which have led to better understanding of the biology and probability of progression of MGUS and SMM. In the context of numerous molecular events and heterogeneous risk of progression, developing individualized risk profiles for patients with MGUS and SMM represents an ongoing challenge that has to be addressed by prospective clinical monitoring and extensive correlative science. In this review we discuss the current standard of care of patients with MGUS and SMM, the use of risk models, including flow cytometry and free-light chain analyses, for predicting risk of progression. Emerging evidence from molecular studies on MGUS and SMM, involving cytogenetics, gene-expression profiling, and microRNA as well as molecular imaging is described. Finally, future directions for improving individualized management of MGUS and SMM patients, as well as the potential for developing early treatment strategies designed to delay and prevent development of MM are discussed.

A method to identify differential expression profiles of time-course gene data with Fourier transformation

PubMed Central

2013-01-01

Background Time course gene expression experiments are an increasingly popular method for exploring biological processes. Temporal gene expression profiles provide an important characterization of gene function, as biological systems are both developmental and dynamic. With such data it is possible to study gene expression changes over time and thereby to detect differential genes. Much of the early work on analyzing time series expression data relied on methods developed originally for static data and thus there is a need for improved methodology. Since time series expression is a temporal process, its unique features such as autocorrelation between successive points should be incorporated into the analysis. Results This work aims to identify genes that show different gene expression profiles across time. We propose a statistical procedure to discover gene groups with similar profiles using a nonparametric representation that accounts for the autocorrelation in the data. In particular, we first represent each profile in terms of a Fourier basis, and then we screen out genes that are not differentially expressed based on the Fourier coefficients. Finally, we cluster the remaining gene profiles using a model-based approach in the Fourier domain. We evaluate the screening results in terms of sensitivity, specificity, FDR and FNR, compare with the Gaussian process regression screening in a simulation study and illustrate the results by application to yeast cell-cycle microarray expression data with alpha-factor synchronization. The key elements of the proposed methodology: (i) representation of gene profiles in the Fourier domain; (ii) automatic screening of genes based on the Fourier coefficients and taking into account autocorrelation in the data, while controlling the false discovery rate (FDR); (iii) model-based clustering of the remaining gene profiles. Conclusions Using this method, we identified a set of cell-cycle-regulated time-course yeast genes. The proposed method is general and can be potentially used to identify genes which have the same patterns or biological processes, and help facing the present and forthcoming challenges of data analysis in functional genomics. PMID:24134721

Shared Gene Expression Alterations in Nasal and Bronchial Epithelium for Lung Cancer Detection.

PubMed

2017-07-01

We previously derived and validated a bronchial epithelial gene expression biomarker to detect lung cancer in current and former smokers. Given that bronchial and nasal epithelial gene expression are similarly altered by cigarette smoke exposure, we sought to determine if cancer-associated gene expression might also be detectable in the more readily accessible nasal epithelium. Nasal epithelial brushings were prospectively collected from current and former smokers undergoing diagnostic evaluation for pulmonary lesions suspicious for lung cancer in the AEGIS-1 (n = 375) and AEGIS-2 (n = 130) clinical trials and gene expression profiled using microarrays. All statistical tests were two-sided. We identified 535 genes that were differentially expressed in the nasal epithelium of AEGIS-1 patients diagnosed with lung cancer vs those with benign disease after one year of follow-up ( P  < .001). Using bronchial gene expression data from the AEGIS-1 patients, we found statistically significant concordant cancer-associated gene expression alterations between the two airway sites ( P  < .001). Differentially expressed genes in the nose were enriched for genes associated with the regulation of apoptosis and immune system signaling. A nasal lung cancer classifier derived in the AEGIS-1 cohort that combined clinical factors (age, smoking status, time since quit, mass size) and nasal gene expression (30 genes) had statistically significantly higher area under the curve (0.81; 95% confidence interval [CI] = 0.74 to 0.89, P  = .01) and sensitivity (0.91; 95% CI = 0.81 to 0.97, P  = .03) than a clinical-factor only model in independent samples from the AEGIS-2 cohort. These results support that the airway epithelial field of lung cancer-associated injury in ever smokers extends to the nose and demonstrates the potential of using nasal gene expression as a noninvasive biomarker for lung cancer detection. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Loss of ATRX, associated with DNA methylation pattern of chromosome end, impacted biological behaviors of astrocytic tumors

PubMed Central

Zhang, Wei; Yang, Pei; Zhang, Chuanbao; Li, Mingyang; Yao, Kun; Wang, Hongjun; Li, Qingbin; Jiang, Chuanlu; Jiang, Tao

2015-01-01

Loss of ATRX leads to epigenetic alterations, including abnormal levels of DNA methylation at repetitive elements such as telomeres in murine cells. We conducted an extensive DNA methylation and mRNA expression profile study on a cohort of 82 patients with astrocytic tumors to study whether ATRX expression was associated with DNA methylation level in astrocytic tumors and in which cellular functions it participated. We observed that astrocytic tumors with lower ATRX expression harbored higher DNA methylation level at chromatin end and astrocytic tumors with ATRX-low had distinct gene expression profile and DNA methylation profile compared with ATRX-high tumors. Then, we uncovered that several ATRX associated biological functions in the DNA methylation and mRNA expression profile (GEP), including apoptotic process, DNA-dependent positive regulation of transcription, chromatin modification, and observed that ATRX expression was companied by MGMT methylation and expression. We also found that loss of ATRX caused by siRNA induced apoptotic cells increasing, reduced tumor cell proliferation and repressed the cell migration in glioma cells. Our results showed ATRX-related regulatory functions of the combined profiles from DNA methylation and mRNA expression in astrocytic tumors, and delineated that loss of ATRX impacted biological behaviors of astrocytic tumor cells, providing important resources for future dissection of ATRX role in glioma. PMID:25971279

Loss of ATRX, associated with DNA methylation pattern of chromosome end, impacted biological behaviors of astrocytic tumors.

PubMed

Cai, Jinquan; Chen, Jing; Zhang, Wei; Yang, Pei; Zhang, Chuanbao; Li, Mingyang; Yao, Kun; Wang, Hongjun; Li, Qingbin; Jiang, Chuanlu; Jiang, Tao

2015-07-20

Loss of ATRX leads to epigenetic alterations, including abnormal levels of DNA methylation at repetitive elements such as telomeres in murine cells. We conducted an extensive DNA methylation and mRNA expression profile study on a cohort of 82 patients with astrocytic tumors to study whether ATRX expression was associated with DNA methylation level in astrocytic tumors and in which cellular functions it participated. We observed that astrocytic tumors with lower ATRX expression harbored higher DNA methylation level at chromatin end and astrocytic tumors with ATRX-low had distinct gene expression profile and DNA methylation profile compared with ATRX-high tumors. Then, we uncovered that several ATRX associated biological functions in the DNA methylation and mRNA expression profile (GEP), including apoptotic process, DNA-dependent positive regulation of transcription, chromatin modification, and observed that ATRX expression was companied by MGMT methylation and expression. We also found that loss of ATRX caused by siRNA induced apoptotic cells increasing, reduced tumor cell proliferation and repressed the cell migration in glioma cells. Our results showed ATRX-related regulatory functions of the combined profiles from DNA methylation and mRNA expression in astrocytic tumors, and delineated that loss of ATRX impacted biological behaviors of astrocytic tumor cells, providing important resources for future dissection of ATRX role in glioma.

A microcosm of musical expression: II. Quantitative analysis of pianists' dynamics in the initial measures of Chopin's Etude in E major.

PubMed

Repp, B H

1999-03-01

Patterns of expressive dynamics were measured in bars 1-5 of 115 commercially recorded performances of Chopin's Etude in E major, op. 10, No. 3. The grand average pattern (or dynamic profile) was representative of many performances and highly similar to the average dynamic profile of a group of advanced student performances, which suggests a widely shared central norm of expressive dynamics. The individual dynamic profiles were subjected to principal components analysis, which yielded Varimax-rotated components, each representing a different, nonstandard dynamic profile associated with a small subset of performances. Most performances had dynamic patterns resembling a mixture of several components, and no clustering of of performances into distinct groups was apparent. Some weak relationships of dynamic profiles with sociocultural variables were found, most notably a tendency of female pianists to exhibit a greater dynamic range in the melody. Within the melody, there were no significant relationships between expressive timing [Repp, J. Acoust. Soc. Am. 104, 1085-1100 (1998)] and expressive dynamics. These two important dimensions seemed to be controlled independently at this local level and thus offer the artist many degrees of freedom in giving a melody expressive shape.

Medroxyprogesterone acetate-treated human, primary endometrial epithelial cells reveal unique gene expression signature linked to innate immunity and HIV-1 susceptibility.

PubMed

Woods, Matthew W; Zahoor, Muhammad Atif; Dizzell, Sara; Verschoor, Chris P; Kaushic, Charu

2018-01-01

Medroxyprogesterone acetate (MPA), a progestin-based hormonal contraceptive designed to mimic progesterone, has been linked to increased human immunodeficiency virus (HIV-1) susceptibility. Genital epithelial cells (GECs) form the mucosal lining of the female genital tract (FGT) and provide the first line of protection against HIV-1. The impact of endogenous sex hormones or MPA on the gene expression profile of GECs has not been comprehensively documented. Using microarray analysis, we characterized the transcriptional profile of primary endometrial epithelial cells grown in physiological levels of E2, P4, and MPA. Each hormone treatment altered the gene expression profile of GECs in a unique manner. Interestingly, although MPA is a progestogen, the gene expression profile induced by it was distinct from P4. MPA increased gene expression of genes related to inflammation and cholesterol synthesis linked to innate immunity and HIV-1 susceptibility. The analysis of gene expression profiles provides insights into the effects of sex hormones and MPA on GECs and allows us to posit possible mechanisms of the MPA-mediated increase in HIV-1 acquisition. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

DEVELOPMENT OF PROTEIN PROFILE TECHNOLOGY TO EVALUATE ECOLOGICAL EFFECTS OF ENVIRONMENTAL CHEMICALS USING A SMALL FISH MODEL

EPA Science Inventory

The rationale for this research is: i) Protein expression changes with life stage, disease, tissue type and environmental stressors; ii) Technology allows rapid analysis of large numbers of proteins to provide protein expression profiles; iii) Protein profiles are used as specifi...

Know Me or No Me--Finding Your Best Prospects for Enrollment

ERIC Educational Resources Information Center

Wassom, Jullie

2006-01-01

This article presents some questions on how to find, convert and keep the best prospects for enrollment in child care and education. First, what do I need to know? There are two types of profiles to look at to target specific audiences: (1) "demographics", indicates of a typical qualified buyer; and (2) "psychographics", addresses lifestyle…

Variation-preserving normalization unveils blind spots in gene expression profiling

PubMed Central

Roca, Carlos P.; Gomes, Susana I. L.; Amorim, Mónica J. B.; Scott-Fordsmand, Janeck J.

2017-01-01

RNA-Seq and gene expression microarrays provide comprehensive profiles of gene activity, but lack of reproducibility has hindered their application. A key challenge in the data analysis is the normalization of gene expression levels, which is currently performed following the implicit assumption that most genes are not differentially expressed. Here, we present a mathematical approach to normalization that makes no assumption of this sort. We have found that variation in gene expression is much larger than currently believed, and that it can be measured with available assays. Our results also explain, at least partially, the reproducibility problems encountered in transcriptomics studies. We expect that this improvement in detection will help efforts to realize the full potential of gene expression profiling, especially in analyses of cellular processes involving complex modulations of gene expression. PMID:28276435

Pump-assisted versus gravity-controlled enteral nutrition in long-term percutaneous endoscopic gastrostomy patients: a prospective controlled trial.

PubMed

Shang, Edward; Geiger, Nicole; Sturm, Joerg W; Post, Stefan

2003-01-01

Vomiting, aspiration, flatulence, and diarrhea are well-known negative side effects of enteral nutrition through percutaneous endoscopic gastrostomy (PEG). However, it is not yet clarified if pump-assisted (PA) or gravity-controlled (GC) application is the more comfortable and safe choice for long-term nutrition through PEG. This was a prospective, randomized, crossover study. Fifty long-term PEG patients were fed by PA nutrition (G1) and 50 patients were fed by GC nutrition (G2). Six weeks of observation (O1) was followed by a switch of method of nutritional application in both groups and an additional 6 weeks of observation (O2). Daily determination of comfort and safety was done with a standardized questionnaire. Evaluation of blood glucose levels on days 1, 21, and 42 during O1 and O2. The patients in both groups had the same medical conditions and were of the same age and sex. Far less flatulence (p < .0006) and epigastric fullness (p < .0003) was discovered in G1 during O1. Also, significantly less regurgitation (p < .0002) and vomiting of feeding diet (p < .0001) in G1 versus G2 could be observed. The rate of diarrhea (p < .0003) in G2 was higher than in G1. The daily profile of blood glucose was significantly better (p < .0008) in G1 than in G2. After the nutritional application was changed in O2, the PA group (G2) again showed a significantly better rate of flatulence, epigastric fullness, regurgitation, vomiting, diarrhea, and daily profile of blood glucose. Ninety-six percent of the patients in G2 preferred further nutrition by PA after finishing this study. All patients in G1 continued their accustomed nutrition by PA. Nutrition through PA showed not only a higher comfort rate but also increased safety, which was expressed through a low rate of regurgitation and vomiting. PA presented better glucose metabolization manifested in improved blood glucose levels. As a result of this prospective study, PA is preferable to GC and preferred by patients with long-term PEG nutrition.

Gene expression profiling of intestinal regeneration in the sea cucumber

PubMed Central

Ortiz-Pineda, Pablo A; Ramírez-Gómez, Francisco; Pérez-Ortiz, Judit; González-Díaz, Sebastián; Santiago-De Jesús, Francisco; Hernández-Pasos, Josue; Del Valle-Avila, Cristina; Rojas-Cartagena, Carmencita; Suárez-Castillo, Edna C; Tossas, Karen; Méndez-Merced, Ana T; Roig-López, José L; Ortiz-Zuazaga, Humberto; García-Arrarás, José E

2009-01-01

Background Among deuterostomes, the regenerative potential is maximally expressed in echinoderms, animals that can quickly replace most injured organs. In particular, sea cucumbers are excellent models for studying organ regeneration since they regenerate their digestive tract after evisceration. However, echinoderms have been sidelined in modern regeneration studies partially because of the lack of genome-wide profiling approaches afforded by modern genomic tools. For the last decade, our laboratory has been using the sea cucumber Holothuria glaberrima to dissect the cellular and molecular events that allow for such amazing regenerative processes. We have already established an EST database obtained from cDNA libraries of normal and regenerating intestine at two different regeneration stages. This database now has over 7000 sequences. Results In the present work we used a custom-made microchip from Agilent with 60-mer probes for these ESTs, to determine the gene expression profile during intestinal regeneration. Here we compared the expression profile of animals at three different intestinal regeneration stages (3-, 7- and 14-days post evisceration) against the profile from normal (uneviscerated) intestines. The number of differentially expressed probes ranged from 70% at p < 0.05 to 39% at p < 0.001. Clustering analyses show specific profiles of expression for early (first week) and late (second week) regeneration stages. We used semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) to validate the expression profile of fifteen microarray detected differentially expressed genes which resulted in over 86% concordance between both techniques. Most of the differentially expressed ESTs showed no clear similarity to sequences in the databases and might represent novel genes associated with regeneration. However, other ESTs were similar to genes known to be involved in regeneration-related processes, wound healing, cell proliferation, differentiation, morphological plasticity, cell survival, stress response, immune challenge, and neoplastic transformation. Among those that have been validated, cytoskeletal genes, such as actins, and developmental genes, such as Wnt and Hox genes, show interesting expression profiles during regeneration. Conclusion Our findings set the base for future studies into the molecular basis of intestinal regeneration. Moreover, it advances the use of echinoderms in regenerative biology, animals that because of their amazing properties and their key evolutionary position, might provide important clues to the genetic basis of regenerative processes. PMID:19505337

Two different protein expression profiles of oral squamous cell carcinoma analyzed by immunoprecipitation high-performance liquid chromatography.

PubMed

Kim, Soung Min; Jeong, Dasul; Kim, Min Keun; Lee, Sang Shin; Lee, Suk Keun

2017-08-08

Oral squamous cell carcinoma (OSCC) is one of the most dangerous cancers in the body, producing serious complications with individual behaviors. Many different pathogenetic factors are involved in the carcinogenesis of OSCC. Cancer cells derived from oral keratinocytes can produce different carcinogenic signaling pathways through differences in protein expression, but their protein expression profiles cannot be easily explored with ordinary detection methods. The present study compared the protein expression profiles between two different types of OSCCs, which were analyzed through immunoprecipitation high-performance liquid chromatography (IP-HPLC). Two types of squamous cell carcinoma (SCC) occurred in a mandibular (SCC-1) and maxillary gingiva (SCC-2), but their clinical features and progression were quite different from each other. SCC-1 showed a large gingival ulceration with severe halitosis and extensive bony destruction, while SCC-2 showed a relatively small papillary gingival swelling but rapidly grew to form a large submucosal mass, followed by early cervical lymph node metastasis. In the histological observation, SCC-1 was relatively well differentiated with a severe inflammatory reaction, while SCC-2 showed severely infiltrative growth of each cancer islets accompanied with a mild inflammatory reaction. IP-HPLC analysis revealed contrary protein expression profiles analyzed by 72 different oncogenic proteins. SCC-1 showed more cellular apoptosis and invasive growth than SCC-2 through increased expression of caspases, MMPs, p53 signaling, FAS signaling, TGF-β1 signaling, and angiogenesis factors, while SCC-2 showed more cellular growth and survival than SCC-1 through the increased expression of proliferating factors, RAS signaling, eIF5A signaling, WNT signaling, and survivin. The increased trends of cellular apoptosis and invasiveness in the protein expression profiles of SCC-1 were implicative of its extensive gingival ulceration and bony destruction, while the increased trends of cellular proliferation and survival in the protein profile of SCC-2 were implicative of its rapid growing tumor mass and early lymph node metastasis. These analyses of the essential oncogenic protein expression profiles in OSCC provide important information for genetic counseling or customized gene therapy in cancer treatment. Therefore, protein expression profile analysis through IP-HPLC is helpful not only for the molecular genetic diagnosis of cancer but also in identifying target molecules for customized gene therapy in near future.

Local Context Finder (LCF) reveals multidimensional relationships among mRNA expression profiles of Arabidopsis responding to pathogen infection

PubMed Central

Katagiri, Fumiaki; Glazebrook, Jane

2003-01-01

A major task in computational analysis of mRNA expression profiles is definition of relationships among profiles on the basis of similarities among them. This is generally achieved by pattern recognition in the distribution of data points representing each profile in a high-dimensional space. Some drawbacks of commonly used pattern recognition algorithms stem from their use of a globally linear space and/or limited degrees of freedom. A pattern recognition method called Local Context Finder (LCF) is described here. LCF uses nonlinear dimensionality reduction for pattern recognition. Then it builds a network of profiles based on the nonlinear dimensionality reduction results. LCF was used to analyze mRNA expression profiles of the plant host Arabidopsis interacting with the bacterial pathogen Pseudomonas syringae. In one case, LCF revealed two dimensions essential to explain the effects of the NahG transgene and the ndr1 mutation on resistant and susceptible responses. In another case, plant mutants deficient in responses to pathogen infection were classified on the basis of LCF analysis of their profiles. The classification by LCF was consistent with the results of biological characterization of the mutants. Thus, LCF is a powerful method for extracting information from expression profile data. PMID:12960373

Occupational Competency Profile for Health Occupations Education Program: Health Agency Assessment. Information Series: Report No. 10.

ERIC Educational Resources Information Center

Walters, Norma J.

This assessment instrument is intended to provide health occupations teachers and state departments of education with information needed to revise and improve the curriculum used in training prospective health occupations teachers and in updating certification requirements for practicing health care professionals. The profile lists the…

Analyzing gene expression time-courses based on multi-resolution shape mixture model.

PubMed

Li, Ying; He, Ye; Zhang, Yu

2016-11-01

Biological processes actually are a dynamic molecular process over time. Time course gene expression experiments provide opportunities to explore patterns of gene expression change over a time and understand the dynamic behavior of gene expression, which is crucial for study on development and progression of biology and disease. Analysis of the gene expression time-course profiles has not been fully exploited so far. It is still a challenge problem. We propose a novel shape-based mixture model clustering method for gene expression time-course profiles to explore the significant gene groups. Based on multi-resolution fractal features and mixture clustering model, we proposed a multi-resolution shape mixture model algorithm. Multi-resolution fractal features is computed by wavelet decomposition, which explore patterns of change over time of gene expression at different resolution. Our proposed multi-resolution shape mixture model algorithm is a probabilistic framework which offers a more natural and robust way of clustering time-course gene expression. We assessed the performance of our proposed algorithm using yeast time-course gene expression profiles compared with several popular clustering methods for gene expression profiles. The grouped genes identified by different methods are evaluated by enrichment analysis of biological pathways and known protein-protein interactions from experiment evidence. The grouped genes identified by our proposed algorithm have more strong biological significance. A novel multi-resolution shape mixture model algorithm based on multi-resolution fractal features is proposed. Our proposed model provides a novel horizons and an alternative tool for visualization and analysis of time-course gene expression profiles. The R and Matlab program is available upon the request. Copyright © 2016 Elsevier Inc. All rights reserved.

Gene set differential analysis of time course expression profiles via sparse estimation in functional logistic model with application to time-dependent biomarker detection.

PubMed

Kayano, Mitsunori; Matsui, Hidetoshi; Yamaguchi, Rui; Imoto, Seiya; Miyano, Satoru

2016-04-01

High-throughput time course expression profiles have been available in the last decade due to developments in measurement techniques and devices. Functional data analysis, which treats smoothed curves instead of originally observed discrete data, is effective for the time course expression profiles in terms of dimension reduction, robustness, and applicability to data measured at small and irregularly spaced time points. However, the statistical method of differential analysis for time course expression profiles has not been well established. We propose a functional logistic model based on elastic net regularization (F-Logistic) in order to identify the genes with dynamic alterations in case/control study. We employ a mixed model as a smoothing method to obtain functional data; then F-Logistic is applied to time course profiles measured at small and irregularly spaced time points. We evaluate the performance of F-Logistic in comparison with another functional data approach, i.e. functional ANOVA test (F-ANOVA), by applying the methods to real and synthetic time course data sets. The real data sets consist of the time course gene expression profiles for long-term effects of recombinant interferon β on disease progression in multiple sclerosis. F-Logistic distinguishes dynamic alterations, which cannot be found by competitive approaches such as F-ANOVA, in case/control study based on time course expression profiles. F-Logistic is effective for time-dependent biomarker detection, diagnosis, and therapy. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

21 CFR 862.1163 - Cardiac allograft gene expression profiling test system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1163 Cardiac allograft gene expression profiling test system. (a...

21 CFR 862.1163 - Cardiac allograft gene expression profiling test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1163 Cardiac allograft gene expression profiling test system. (a...

21 CFR 862.1163 - Cardiac allograft gene expression profiling test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1163 Cardiac allograft gene expression profiling test system. (a...

21 CFR 862.1163 - Cardiac allograft gene expression profiling test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems § 862.1163 Cardiac allograft gene expression profiling test system. (a...

Expression and secretory profile of buffalo fetal fibroblasts and Wharton's jelly feeder layers.

PubMed

Parmar, Mehtab S; Mishra, Smruti Ranjan; Somal, Anjali; Pandey, Sriti; Kumar, G Sai; Sarkar, Mihir; Chandra, Vikash; Sharma, G Taru

2017-05-01

The present study examined the comparative expression and secretory profile of vital signaling molecules in buffalo fetal fibroblasts (BFF) and Wharton's jelly (BWJ) feeder layers at different passages. Both feeder layers were expanded up to 8th passage. Signaling molecules viz. bone morphogenetic protein 4 (BMP4), fibroblast growth factor 2 (FGF2), leukemia inhibitory factor (LIF) and transforming growth factor beta 1 (TGFB1) and pluripotency-associated transcriptional factors (POU5F1, SOX2, NANOG, KLF4, MYC and FOXD3) were immunolocalized in the both feeder types. A clear variation in the expression pattern of key signaling molecules with passaging was registered in both feeders compared to primary culture (0 passage). The conditioned media (CM) was collected from different passages (2, 4, 6, 8) of both the feeder layers and was quantified using enzyme-linked immunosorbent assay (ELISA). Concomitant to expression profile, protein quantification also revealed differences in the concentration of signaling molecules at different time points. Conjointly, expression and secretory profile revealed that 2nd passage of BFF and 6th passage of BWJ exhibit optimal levels of key signaling molecules thus may be selected as best passages for embryonic stem cells (ESCs) propagation. Further, the effect of mitomycin-C (MMC) treatment on the expression profile of signaling molecules in the selected passages of BFF and BWJ revealed that MMC modulates the expression profile of these molecules. In conclusion, the results indicate that feeder layers vary in expression and secretory pattern of vital signaling molecules with passaging. Based on these findings, the appropriate feeder passages may be selected for the quality propagation of buffalo ESCs. Copyright © 2017 Elsevier B.V. All rights reserved.

Gene expression profiling via LongSAGE in a non-model plant species: a case study in seeds of Brassica napus

PubMed Central

Obermeier, Christian; Hosseini, Bashir; Friedt, Wolfgang; Snowdon, Rod

2009-01-01

Background Serial analysis of gene expression (LongSAGE) was applied for gene expression profiling in seeds of oilseed rape (Brassica napus ssp. napus). The usefulness of this technique for detailed expression profiling in a non-model organism was demonstrated for the highly complex, neither fully sequenced nor annotated genome of B. napus by applying a tag-to-gene matching strategy based on Brassica ESTs and the annotated proteome of the closely related model crucifer A. thaliana. Results Transcripts from 3,094 genes were detected at two time-points of seed development, 23 days and 35 days after pollination (DAP). Differential expression showed a shift from gene expression involved in diverse developmental processes including cell proliferation and seed coat formation at 23 DAP to more focussed metabolic processes including storage protein accumulation and lipid deposition at 35 DAP. The most abundant transcripts at 23 DAP were coding for diverse protease inhibitor proteins and proteases, including cysteine proteases involved in seed coat formation and a number of lipid transfer proteins involved in embryo pattern formation. At 35 DAP, transcripts encoding napin, cruciferin and oleosin storage proteins were most abundant. Over both time-points, 18.6% of the detected genes were matched by Brassica ESTs identified by LongSAGE tags in antisense orientation. This suggests a strong involvement of antisense transcript expression in regulatory processes during B. napus seed development. Conclusion This study underlines the potential of transcript tagging approaches for gene expression profiling in Brassica crop species via EST matching to annotated A. thaliana genes. Limits of tag detection for low-abundance transcripts can today be overcome by ultra-high throughput sequencing approaches, so that tag-based gene expression profiling may soon become the method of choice for global expression profiling in non-model species. PMID:19575793

Gene Expression Profiles of Chlamydophila pneumoniae during the Developmental Cycle and Iron Depletion–Mediated Persistence

PubMed Central

Mäurer, André P; Mehlitz, Adrian; Mollenkopf, Hans J; Meyer, Thomas F

2007-01-01

The obligate intracellular, gram-negative bacterium Chlamydophila pneumoniae (Cpn) has impact as a human pathogen. Little is known about changes in the Cpn transcriptome during its biphasic developmental cycle (the acute infection) and persistence. The latter stage has been linked to chronic diseases. To analyze Cpn CWL029 gene expression, we designed a pathogen-specific oligo microarray and optimized the extraction method for pathogen RNA. Throughout the acute infection, ratio expression profiles for each gene were generated using 48 h post infection as a reference. Based on these profiles, significantly expressed genes were separated into 12 expression clusters using self-organizing map clustering and manual sorting into the “early”, “mid”, “late”, and “tardy” cluster classes. The latter two were differentiated because the “tardy” class showed steadily increasing expression at the end of the cycle. The transcriptome of the Cpn elementary body (EB) and published EB proteomics data were compared to the cluster profile of the acute infection. We found an intriguing association between “late” genes and genes coding for EB proteins, whereas “tardy” genes were mainly associated with genes coding for EB mRNA. It has been published that iron depletion leads to Cpn persistence. We compared the gene expression profiles during iron depletion–mediated persistence with the expression clusters of the acute infection. This led to the finding that establishment of iron depletion–mediated persistence is more likely a mid-cycle arrest in development rather than a completely distinct gene expression pattern. Here, we describe the Cpn transcriptome during the acute infection, differentiating “late” genes, which correlate to EB proteins, and “tardy” genes, which lead to EB mRNA. Expression profiles during iron mediated–persistence led us to propose the hypothesis that the transcriptomic “clock” is arrested during acute mid-cycle. PMID:17590080

A Gene Expression Profile of BRCAness That Predicts for Responsiveness to Platinum and PARP Inhibitors

DTIC Science & Technology

2015-10-01

1 Award Number: W81XWH-10-1-0585 TITLE: A Gene Expression Profile of BRCAness That Predicts for Responsiveness to Platinum and PARP Inhibitors...TITLE AND SUBTITLE A Gene Expression Profile of BRCAness That Predicts for Responsiveness to Platinum and PARP Inhibitors 5a. CONTRACT NUMBER W81XWH...BRCAlike, i.e. not HR deficient and are resistant to PARPis but are sensitive to platinum . These tumors exhibit alterations in another DNA repair

Adoption of Gene Expression Profile Testing and Association With Use of Chemotherapy Among Women With Breast Cancer

PubMed Central

Hassett, Michael J.; Silver, Samuel M.; Hughes, Melissa E.; Blayney, Douglas W.; Edge, Stephen B.; Herman, James G.; Hudis, Clifford A.; Marcom, P. Kelly; Pettinga, Jane E.; Share, David; Theriault, Richard; Wong, Yu-Ning; Vandergrift, Jonathan L.; Niland, Joyce C.; Weeks, Jane C.

2012-01-01

Purpose Gene expression profile (GEP) testing is a relatively new technology that offers the potential of personalized medicine to patients, yet little is known about its adoption into routine practice. One of the first commercially available GEP tests, a 21-gene profile, was developed to estimate the benefit of adjuvant chemotherapy for hormone receptor–positive breast cancer (HR-positive BC). Patients and Methods By using a prospective registry data set outlining the routine care provided to women diagnosed from 2006 to 2008 with HR-positive BC at 17 comprehensive and community-based cancer centers, we assessed GEP test adoption and the association between testing and chemotherapy use. Results Of 7,375 women, 20.4% had GEP testing and 50.2% received chemotherapy. Over time, testing increased (14.7% in 2006 to 27.5% in 2008; P < .01) and use of chemotherapy decreased (53.9% in 2006 to 47.0% in 2008; P < .01). Characteristics independently associated with lower odds of testing included African American versus white race (odds ratio [OR], 0.70; 95% CI, 0.54 to 0.92) and high school or less versus more than high school education (OR, 0.63; 95% CI, 0.52 to 0.76). Overall, testing was associated with lower odds of chemotherapy use (OR, 0.70; 95% CI, 0.62 to 0.80). Stratified analyses demonstrated that for small, node-negative cancers, testing was associated with higher odds of chemotherapy use (OR, 11.13; 95% CI, 5.39 to 22.99), whereas for node-positive and large node-negative cancers, testing was associated with lower odds of chemotherapy use (OR, 0.11; 95% CI, 0.07 to 0.17). Conclusion There has been a progressive increase in use of this GEP test and an associated shift in the characteristics of and overall reduction in the proportion of women with HR-positive BC receiving adjuvant chemotherapy. PMID:22585699

Identification and handling of artifactual gene expression profiles emerging in microarray hybridization experiments

PubMed Central

Brodsky, Leonid; Leontovich, Andrei; Shtutman, Michael; Feinstein, Elena

2004-01-01

Mathematical methods of analysis of microarray hybridizations deal with gene expression profiles as elementary units. However, some of these profiles do not reflect a biologically relevant transcriptional response, but rather stem from technical artifacts. Here, we describe two technically independent but rationally interconnected methods for identification of such artifactual profiles. Our diagnostics are based on detection of deviations from uniformity, which is assumed as the main underlying principle of microarray design. Method 1 is based on detection of non-uniformity of microarray distribution of printed genes that are clustered based on the similarity of their expression profiles. Method 2 is based on evaluation of the presence of gene-specific microarray spots within the slides’ areas characterized by an abnormal concentration of low/high differential expression values, which we define as ‘patterns of differentials’. Applying two novel algorithms, for nested clustering (method 1) and for pattern detection (method 2), we can make a dual estimation of the profile’s quality for almost every printed gene. Genes with artifactual profiles detected by method 1 may then be removed from further analysis. Suspicious differential expression values detected by method 2 may be either removed or weighted according to the probabilities of patterns that cover them, thus diminishing their input in any further data analysis. PMID:14999086

RON is not a prognostic marker for resectable pancreatic cancer.

PubMed

Tactacan, Carole M; Chang, David K; Cowley, Mark J; Humphrey, Emily S; Wu, Jianmin; Gill, Anthony J; Chou, Angela; Nones, Katia; Grimmond, Sean M; Sutherland, Robert L; Biankin, Andrew V; Daly, Roger J

2012-09-07

The receptor tyrosine kinase RON exhibits increased expression during pancreatic cancer progression and promotes migration, invasion and gemcitabine resistance of pancreatic cancer cells in experimental models. However, the prognostic significance of RON expression in pancreatic cancer is unknown. RON expression was characterized in several large cohorts, including a prospective study, totaling 492 pancreatic cancer patients and relationships with patient outcome and clinico-pathologic variables were assessed. RON expression was associated with outcome in a training set, but this was not recapitulated in the validation set, nor was there any association with therapeutic responsiveness in the validation set or the prospective study. Although RON is implicated in pancreatic cancer progression in experimental models, and may constitute a therapeutic target, RON expression is not associated with prognosis or therapeutic responsiveness in resected pancreatic cancer.

Prospective Surface Marker-Based Isolation and Expansion of Fetal Endothelial Colony-Forming Cells From Human Term Placenta

PubMed Central

Patel, Jatin; Seppanen, Elke; Chong, Mark S.K.; Yeo, Julie S.L.; Teo, Erin Y.L.; Chan, Jerry K.Y.; Fisk, Nicholas M.

2013-01-01

The term placenta is a highly vascularized tissue and is usually discarded upon birth. Our objective was to isolate clinically relevant quantities of fetal endothelial colony-forming cells (ECFCs) from human term placenta and to compare them to the well-established donor-matched umbilical cord blood (UCB)-derived ECFCs. A sorting strategy was devised to enrich for CD45−CD34+CD31Lo cells prior to primary plating to obtain pure placental ECFCs (PL-ECFCs) upon culture. UCB-ECFCs were derived using a well-described assay. PL-ECFCs were fetal in origin and expressed the same cell surface markers as UCB-ECFCs. Most importantly, a single term placenta could yield as many ECFCs as 27 UCB donors. PL-ECFCs and UCB-ECFCs had similar in vitro and in vivo vessel forming capacities and restored mouse hind limb ischemia in similar proportions. Gene expression profiles were only minimally divergent between PL-ECFCs and UCB-ECFCs, probably reflecting a vascular source versus a circulating source. Finally, PL-ECFCs and UCB-ECFCs displayed similar hierarchies between high and low proliferative colonies. We report a robust strategy to isolate ECFCs from human term placentas based on their cell surface expression. This yielded much larger quantities of ECFCs than UCB, but the cells were comparable in immunophenotype, gene expression, and in vivo functional ability. We conclude that PL-ECFCs have significant bio-banking and clinical translatability potential. PMID:24106336

Effect of risperidone versus haloperidol on emotional responding in schizophrenic patients.

PubMed

Fakra, E; Khalfa, S; Da Fonseca, D; Besnier, N; Delaveau, P; Azorin, J M; Blin, O

2008-10-01

Studies on emotional processing report that schizophrenic patients present a specific pattern of emotional responding that usually includes deficits in emotional expressiveness, increased feelings of unpleasant emotion but decreased feelings of pleasant emotion, and increased physiological reactivity. However, studies have rarely controlled the nature of antipsychotic medication. Yet, the influence of these drugs on emotional response is uncertain and could vary depending on their pharmacological profile. This prospective and randomized study aimed to compare the effects of an atypical antipsychotic, risperidone, to a typical one, haloperidol, on patients' emotional responding during an emotional induction task. Twenty-five schizophrenic patients underwent two emotional and clinical evaluations: one before treatment initiation and a second 4 weeks after. Emotional states of fear, sadness, anger, joy, and disgust were induced, as well as a neutral baseline state. Video recordings of patients during the induction task allowed for assessment of emotional expressiveness. Self-reports and measures of skin conductance and heart rate were performed to determine both subjective and physiological reactions to emotional experience. Compared to haloperidol, risperidone did not reduce patients' facial expressiveness, decreased physiological reactivity, and decreased experience of unpleasant emotion but maintained experience of pleasant emotion. Emotional expressiveness was negatively correlated to parkisonism. Our preliminary results suggest that atypical antipsychotics allow for better-adapted patterns of emotional responding than typical ones do. We suggest that this effect is due to reduced striatal D2 blockade, therefore, attenuating akinesia, coupled with increased 5HT and DA levels in prefrontal cortex, which improves emotional regulation.

Electrical resistivity surveys in Prospect Gulch, San Juan County, Colorado

USGS Publications Warehouse

McDougal, Robert R.

2006-01-01

Prospect Gulch is a major source of naturally occurring and mining related metals to Cement Creek, a tributary of the upper Animas River in southwestern Colorado. Efforts to improve water quality in the watershed have focused on Prospect Gulch because many of its abandoned mines and are located on federal lands. Information on sources and pathways of metals, and related ground-water flow, will be useful to help prioritize and develop remediation strategies. It has been shown that the occurrence of sulfate, aluminum, iron, zinc and other metals associated with historical mining and the natural weathering of pyritic rock is substantial. In this study, direct current resistivity surveys were conducted to determine the subsurface resistivity distribution and to identify faults and fractures that may act as ground-water conduits or barriers to flow. Five lines of resistivity data were collected in the vicinity of Prospect Gulch, and cross-section profiles were constructed from the field data using a two-dimensional inversion algorithm. The conductive anomalies in the profiles are most likely caused by wet or saturated rocks and sediments, clay rich deposits, or high TDS ground water. Resistive anomalies are likely bedrock, dry surficial and sub-surface deposits, or deposits of ferricrete.

Dynamic transcriptomic analysis in hircine longissimus dorsi muscle from fetal to neonatal development stages.

PubMed

Zhan, Siyuan; Zhao, Wei; Song, Tianzeng; Dong, Yao; Guo, Jiazhong; Cao, Jiaxue; Zhong, Tao; Wang, Linjie; Li, Li; Zhang, Hongping

2018-01-01

Muscle growth and development from fetal to neonatal stages consist of a series of delicately regulated and orchestrated changes in expression of genes. In this study, we performed whole transcriptome profiling based on RNA-Seq of caprine longissimus dorsi muscle tissue obtained from prenatal stages (days 45, 60, and 105 of gestation) and neonatal stage (the 3-day-old newborn) to identify genes that are differentially expressed and investigate their temporal expression profiles. A total of 3276 differentially expressed genes (DEGs) were identified (Q value < 0.01). Time-series expression profile clustering analysis indicated that DEGs were significantly clustered into eight clusters which can be divided into two classes (Q value < 0.05), class I profiles with downregulated patterns and class II profiles with upregulated patterns. Based on cluster analysis, GO enrichment analysis found that 75, 25, and 8 terms to be significantly enriched in biological process (BP), cellular component (CC), and molecular function (MF) categories in class I profiles, while 35, 21, and 8 terms to be significantly enriched in BP, CC, and MF in class II profiles. KEGG pathway analysis revealed that DEGs from class I profiles were significantly enriched in 22 pathways and the most enriched pathway was Rap1 signaling pathway. DEGs from class II profiles were significantly enriched in 17 pathways and the mainly enriched pathway was AMPK signaling pathway. Finally, six selected DEGs from our sequencing results were confirmed by qPCR. Our study provides a comprehensive understanding of the molecular mechanisms during goat skeletal muscle development from fetal to neonatal stages and valuable information for future studies of muscle development in goats.

Advanced colorectal adenoma related gene expression signature may predict prognostic for colorectal cancer patients with adenoma-carcinoma sequence.

PubMed

Li, Bing; Shi, Xiao-Yu; Liao, Dai-Xiang; Cao, Bang-Rong; Luo, Cheng-Hua; Cheng, Shu-Jun

2015-01-01

There are still no absolute parameters predicting progression of adenoma into cancer. The present study aimed to characterize functional differences on the multistep carcinogenetic process from the adenoma-carcinoma sequence. All samples were collected and mRNA expression profiling was performed by using Agilent Microarray high-throughput gene-chip technology. Then, the characteristics of mRNA expression profiles of adenoma-carcinoma sequence were described with bioinformatics software, and we analyzed the relationship between gene expression profiles of adenoma-adenocarcinoma sequence and clinical prognosis of colorectal cancer. The mRNA expressions of adenoma-carcinoma sequence were significantly different between high-grade intraepithelial neoplasia group and adenocarcinoma group. The biological process of gene ontology function enrichment analysis on differentially expressed genes between high-grade intraepithelial neoplasia group and adenocarcinoma group showed that genes enriched in the extracellular structure organization, skeletal system development, biological adhesion and itself regulated growth regulation, with the P value after FDR correction of less than 0.05. In addition, IPR-related protein mainly focused on the insulin-like growth factor binding proteins. The variable trends of gene expression profiles for adenoma-carcinoma sequence were mainly concentrated in high-grade intraepithelial neoplasia and adenocarcinoma. The differentially expressed genes are significantly correlated between high-grade intraepithelial neoplasia group and adenocarcinoma group. Bioinformatics analysis is an effective way to study the gene expression profiles in the adenoma-carcinoma sequence, and may provide an effective tool to involve colorectal cancer research strategy into colorectal adenoma or advanced adenoma.

Social Anxiety and Positive Emotions: A Prospective Examination of a Self-Regulatory Model with Tendencies to Suppress or Express Emotions as a Moderating Variable

ERIC Educational Resources Information Center

Kashdan, Todd B.; Breen, William E.

2008-01-01

The purpose of the present study was to examine social anxiety as a predictor of positive emotions using a short-term prospective design. We examined whether the effects of social anxiety on positive emotions are moderated by tendencies to openly express or suppress emotions. Over the course of a 3-month interval, people with excessive social…

Adolescents with gender identity disorder who were accepted or rejected for sex reassignment surgery: a prospective follow-up study.

PubMed

Smith, Y L; van Goozen, S H; Cohen-Kettenis, P T

2001-04-01

To conduct a prospective follow-up study with 20 treated adolescent transsexuals to evaluate early sex reassignment, and with 21 nontreated and 6 delayed-treatment adolescents to evaluate the decisions not to allow them to start sex reassignment at all or at an early age. Subjects were tested on their psychological, social, and sexual functioning. Follow-up interviews were conducted from March 1995 until July 1999. Treated patients had undergone surgery 1 to 4 years before follow-up; nontreated patients were tested 1 to 7 years after application. Within the treated and the nontreated group, pre- and posttreatment data were compared. Results between the groups were also compared. Postoperatively the treated group was no longer gender-dysphoric and was psychologically and socially functioning quite well. Nobody expressed regrets concerning the decision to undergo sex reassignment. Without sex reassignment, the nontreated group showed some improvement, but they also showed a more dysfunctional psychological profile. Careful diagnosis and strict criteria are necessary and sufficient to justify hormone treatment in adolescent transsexuals. Even though some of the nontreated patients may actually have gender identity disorder, the high levels of psychopathology found in this group justify the decision to not start hormone treatment too soon or too easily.

Bioorthogonal Metabolic Labeling of Nascent RNA in Neurons Improves the Sensitivity of Transcriptome-Wide Profiling.

PubMed

Zajaczkowski, Esmi L; Zhao, Qiong-Yi; Zhang, Zong Hong; Li, Xiang; Wei, Wei; Marshall, Paul R; Leighton, Laura J; Nainar, Sarah; Feng, Chao; Spitale, Robert C; Bredy, Timothy W

2018-06-15

Transcriptome-wide expression profiling of neurons has provided important insights into the underlying molecular mechanisms and gene expression patterns that transpire during learning and memory formation. However, there is a paucity of tools for profiling stimulus-induced RNA within specific neuronal cell populations. A bioorthogonal method to chemically label nascent (i.e., newly transcribed) RNA in a cell-type-specific and temporally controlled manner, which is also amenable to bioconjugation via click chemistry, was recently developed and optimized within conventional immortalized cell lines. However, its value within a more fragile and complicated cellular system such as neurons, as well as for transcriptome-wide expression profiling, has yet to be demonstrated. Here, we report the visualization and sequencing of activity-dependent nascent RNA derived from neurons using this labeling method. This work has important implications for improving transcriptome-wide expression profiling and visualization of nascent RNA in neurons, which has the potential to provide valuable insights into the mechanisms underlying neural plasticity, learning, and memory.

MicroRNA expression in melanocytic nevi: the usefulness of formalin-fixed, paraffin-embedded material for miRNA microarray profiling.

PubMed

Glud, Martin; Klausen, Mikkel; Gniadecki, Robert; Rossing, Maria; Hastrup, Nina; Nielsen, Finn C; Drzewiecki, Krzysztof T

2009-05-01

MicroRNAs (miRNAs) are small, noncoding RNA molecules that regulate cellular differentiation, proliferation, and apoptosis. MiRNAs are expressed in a developmentally regulated and tissue-specific manner. Aberrant expression may contribute to pathological processes such as cancer, and miRNA may therefore serve as biomarkers that may be useful in a clinical environment for diagnosis of various diseases. Most miRNA profiling studies have used fresh tissue samples. However, in some types of cancer, including malignant melanoma, fresh material is difficult to obtain from primary tumors, and most surgical specimens are formalin fixed and paraffin embedded (FFPE). To explore whether FFPE material would be suitable for miRNA profiling in melanocytic lesions, we compared miRNA expression patterns in FFPE versus fresh frozen samples, obtained from 15 human melanocytic nevi. Out of microarray data, we identified 84 miRNAs that were expressed in both types of samples and represented an miRNA profile of melanocytic nevi. Our results showed a high correlation in miRNA expression (Spearman r-value of 0.80) between paired FFPE and fresh frozen material. The data were further validated by quantitative RT-PCR. In conclusion, FFPE specimens of melanocytic lesions are suitable as a source for miRNA microarray profiling.

MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype.

PubMed

Blenkiron, Cherie; Goldstein, Leonard D; Thorne, Natalie P; Spiteri, Inmaculada; Chin, Suet-Feung; Dunning, Mark J; Barbosa-Morais, Nuno L; Teschendorff, Andrew E; Green, Andrew R; Ellis, Ian O; Tavaré, Simon; Caldas, Carlos; Miska, Eric A

2007-01-01

MicroRNAs (miRNAs), a class of short non-coding RNAs found in many plants and animals, often act post-transcriptionally to inhibit gene expression. Here we report the analysis of miRNA expression in 93 primary human breast tumors, using a bead-based flow cytometric miRNA expression profiling method. Of 309 human miRNAs assayed, we identify 133 miRNAs expressed in human breast and breast tumors. We used mRNA expression profiling to classify the breast tumors as luminal A, luminal B, basal-like, HER2+ and normal-like. A number of miRNAs are differentially expressed between these molecular tumor subtypes and individual miRNAs are associated with clinicopathological factors. Furthermore, we find that miRNAs could classify basal versus luminal tumor subtypes in an independent data set. In some cases, changes in miRNA expression correlate with genomic loss or gain; in others, changes in miRNA expression are likely due to changes in primary transcription and or miRNA biogenesis. Finally, the expression of DICER1 and AGO2 is correlated with tumor subtype and may explain some of the changes in miRNA expression observed. This study represents the first integrated analysis of miRNA expression, mRNA expression and genomic changes in human breast cancer and may serve as a basis for functional studies of the role of miRNAs in the etiology of breast cancer. Furthermore, we demonstrate that bead-based flow cytometric miRNA expression profiling might be a suitable platform to classify breast cancer into prognostic molecular subtypes.

Gene Expression Profiling of Peripheral Blood From Kidney Transplant Recipients for the Early Detection of Digestive System Cancer.

PubMed

Kusaka, M; Okamoto, M; Takenaka, M; Sasaki, H; Fukami, N; Kataoka, K; Ito, T; Kenmochi, T; Hoshinaga, K; Shiroki, R

2017-06-01

Kidney transplant recipients are at increased risk of developing cancer in comparison with the general population. To effectively manage post-transplantation malignancies, it is essential to proactively monitor patients. A long-term intensive screening program was associated with a reduced incidence of cancer after transplantation. This study evaluated the usefulness of the gene expression profiling of peripheral blood samples obtained from kidney transplant patients and adopted a screening test for detecting cancer of the digestive system (gastric, colon, pancreas, and biliary tract). Nineteen patients were included in this study and a total of 53 gene expression screening tests were performed. The gene expression profiles of blood-delivered total RNA and whole genome human gene expression profiles were obtained. We investigated the expression levels of 2665 genes associated with digestive cancers and counted the number of genes in which expression was altered. A hierarchical clustering analysis was also performed. The final prediction of the cancer possibility was determined according to an algorithm. The number of genes in which expression was altered was significantly increased in the kidney transplant recipients in comparison with the general population (1091 ± 63 vs 823 ± 94; P = .0024). The number of genes with altered expression decreased after the induction of mechanistic target of rapamycin (mTOR) inhibitor (1484 ± 227 vs 883 ± 154; P = .0439). No cases of possible digestive cancer were detected in this study period. The gene expression profiling of peripheral blood samples may be a useful and noninvasive diagnostic tool that allows for the early detection of cancer of the digestive system. Copyright © 2017 Elsevier Inc. All rights reserved.

Differences in cortisol profiles and circadian adjustment time between nurses working night shifts and regular day shifts: A prospective longitudinal study.

PubMed

Niu, Shu-Fen; Chung, Min-Huey; Chu, Hsin; Tsai, Jui-Chen; Lin, Chun-Chieh; Liao, Yuan-Mei; Ou, Keng-Liang; O'Brien, Anthony Paul; Chou, Kuei-Ru

2015-07-01

This study explored the differences in the circadian salivary cortisol profiles between nurses working night shifts and regular day shifts following a slow rotating shift schedule to assess the number of days required for adjusting the circadian rhythm of salivary cortisol levels in nurses working consecutive night shifts and the number of days off required to restore the diurnal circadian rhythm of salivary cortisol levels. This was a prospective, longitudinal, parallel-group comparative study. The participants were randomly assigned to night and day-shift groups, and saliva samples were collected to measure their cortisol levels and circadian secretion patterns. Significant differences were observed in the overall salivary cortisol pattern parameters (cortisol awakening response, changes in cortisol profiles between 6 and 12h after awakening, and changes in cortisol profiles between 30 min and 12 h after awakening) from Days 2 to 4 of the workdays between both groups. However, on Day 2 of the days off, both groups exhibited similar cortisol profiles and the cortisol profiles in the night-shift group were restored. Nurses working night shifts require at least 4 days to adjust their circadian rhythms of cortisol secretions. Moreover, on changing from night shift to other shifts, nurses must be allowed more than 2 days off work. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ability of prospective assessment of personality profiles to predict the practice specialty of medical students

PubMed Central

Maron, Bradley A.; Fein, Steven; Hillel, Alexander T.; El Baghdadi, Mariam M.; Rodenhauser, Paul

2007-01-01

Medical practice encompasses a diverse spectrum of specialties. Factors that impact selection of clinical disciplines by young physicians may have recently evolved associated with changes in medical school demographics. We assessed whether physicians gravitate to certain practice specialties due to preexisting personality traits. The Neuroticism-Extraversion-Openness Personality Inventory Revised Test was administered prospectively to 130 first-year students the week before they began medical school. Scores for five traits (neuroticism, extraversion, openness, agreeableness, conscientiousness) were compared with the selection among nine medical residencies at the conclusion of medical school. Personality scores for medical students selecting psychiatry residencies showed greater degrees of neuroticism (P < 0.01) and openness (P < 0.03). Students electing family practice also deviated from other specialties, showing a lower degree of neuroticism (P < 0.03). Unexpectedly, personality traits in prospective surgical residents did not differ from those of students choosing nonsurgical residencies. Personality profiles present before medical school appear to predict the selection of some residencies and clinical specialties but not others. PMID:17256038

Recent advances in T-cell immunotherapy for haematological malignancies.

PubMed

Rouce, Rayne H; Sharma, Sandhya; Huynh, Mai; Heslop, Helen E

2017-03-01

In vitro discoveries have paved the way for bench-to-bedside translation in adoptive T cell immunotherapy, resulting in remarkable clinical responses in a variety of haematological malignancies. Adoptively transferred T cells genetically modified to express CD19 CARs have shown great promise, although many unanswered questions regarding how to optimize T-cell therapies for both safety and efficacy remain. Similarly, T cells that recognize viral or tumour antigens though their native receptors have produced encouraging clinical responses. Honing manufacturing processes will increase the availability of T-cell products, while combining T-cell therapies has the ability to increase complete response rates. Lastly, innovative mechanisms to control these therapies may improve safety profiles while genome editing offers the prospect of modulating T-cell function. This review will focus on recent advances in T-cell immunotherapy, highlighting both clinical and pre-clinical advances, as well as exploring what the future holds. © 2016 John Wiley & Sons Ltd.

Characterization of stem cells and cancer cells on the basis of gene expression profile stability, plasticity, and robustness: dynamical systems theory of gene expressions under cell-cell interaction explains mutational robustness of differentiated cells and suggests how cancer cells emerge.

PubMed

Kaneko, Kunihiko

2011-06-01

Here I present and discuss a model that, among other things, appears able to describe the dynamics of cancer cell origin from the perspective of stable and unstable gene expression profiles. In identifying such aberrant gene expression profiles as lying outside the normal stable states attracted through development and normal cell differentiation, the hypothesis explains why cancer cells accumulate mutations, to which they are not robust, and why these mutations create a new stable state far from the normal gene expression profile space. Such cells are in strong contrast with normal cell types that appeared as an attractor state in the gene expression dynamical system under cell-cell interaction and achieved robustness to noise through evolution, which in turn also conferred robustness to mutation. In complex gene regulation networks, other aberrant cellular states lacking such high robustness are expected to remain, which would correspond to cancer cells. Copyright © 2011 WILEY Periodicals, Inc.

Gene expression profiling of single cells on large-scale oligonucleotide arrays

PubMed Central

Hartmann, Claudia H.; Klein, Christoph A.

2006-01-01

Over the last decade, important insights into the regulation of cellular responses to various stimuli were gained by global gene expression analyses of cell populations. More recently, specific cell functions and underlying regulatory networks of rare cells isolated from their natural environment moved to the center of attention. However, low cell numbers still hinder gene expression profiling of rare ex vivo material in biomedical research. Therefore, we developed a robust method for gene expression profiling of single cells on high-density oligonucleotide arrays with excellent coverage of low abundance transcripts. The protocol was extensively tested with freshly isolated single cells of very low mRNA content including single epithelial, mature and immature dendritic cells and hematopoietic stem cells. Quantitative PCR confirmed that the PCR-based global amplification method did not change the relative ratios of transcript abundance and unsupervised hierarchical cluster analysis revealed that the histogenetic origin of an individual cell is correctly reflected by the gene expression profile. Moreover, the gene expression data from dendritic cells demonstrate that cellular differentiation and pathway activation can be monitored in individual cells. PMID:17071717

Evaluation of the Location and Recency of Faulting Near Prospective Surface Facilities in Midway Valley, Nye County, Nevada

USGS Publications Warehouse

Swan, F.H.; Wesling, J.R.; Angell, M.M.; Thomas, A.P.; Whitney, J.W.; Gibson, J.D.

2001-01-01

Evaluation of surface faulting that may pose a hazard to prospective surface facilities is an important element of the tectonic studies for the potential Yucca Mountain high-level radioactive waste repository in southwestern Nevada. For this purpose, a program of detailed geologic mapping and trenching was done to obtain surface and near-surface geologic data that are essential for determining the location and recency of faults at a prospective surface-facilities site located east of Exile Hill in Midway Valley, near the eastern base of Yucca Mountain. The dominant tectonic features in the Midway Valley area are the north- to northeast-trending, west-dipping normal faults that bound the Midway Valley structural block-the Bow Ridge fault on the west side of Exile Hill and the Paint-brush Canyon fault on the east side of the valley. Trenching of Quaternary sediments has exposed evidence of displacements, which demonstrate that these block-bounding faults repeatedly ruptured the surface during the middle to late Quaternary. Geologic mapping, subsurface borehole and geophysical data, and the results of trenching activities indicate the presence of north- to northeast-trending faults and northwest-trending faults in Tertiary volcanic rocks beneath alluvial and colluvial sediments near the prospective surface-facilities site. North to northeast-trending faults include the Exile Hill fault along the eastern base of Exile Hill and faults to the east beneath the surficial deposits of Midway Valley. These faults have no geomorphic expression, but two north- to northeast-trending zones of fractures exposed in excavated profiles of middle to late Pleistocene deposits at the prospective surface-facilities site appear to be associated with these faults. Northwest-trending faults include the West Portal and East Portal faults, but no disruption of Quaternary deposits by these faults is evident. The western zone of fractures is associated with the Exile Hill fault. The eastern zone of fractures is within Quaternary alluvial sediments, but no bedrock was encountered in trenches and soil pits in this part of the prospective surface facilities site; thus, the direct association of this zone with one or more bedrock faults is uncertain. No displacement of lithologic contacts and soil horizons could be detected in the fractured Quaternary deposits. The results of these investigations imply the absence of any appreciable late Quaternary faulting activity at the prospective surface-facilities site.

RNA transcriptional biosignature analysis for identifying febrile infants with serious bacterial infections in the emergency department: a feasibility study.

PubMed

Mahajan, Prashant; Kuppermann, Nathan; Suarez, Nicolas; Mejias, Asuncion; Casper, Charlie; Dean, J Michael; Ramilo, Octavio

2015-01-01

To develop the infrastructure and demonstrate the feasibility of conducting microarray-based RNA transcriptional profile analyses for the diagnosis of serious bacterial infections in febrile infants 60 days and younger in a multicenter pediatric emergency research network. We designed a prospective multicenter cohort study with the aim of enrolling more than 4000 febrile infants 60 days and younger. To ensure success of conducting complex genomic studies in emergency department (ED) settings, we established an infrastructure within the Pediatric Emergency Care Applied Research Network, including 21 sites, to evaluate RNA transcriptional profiles in young febrile infants. We developed a comprehensive manual of operations and trained site investigators to obtain and process blood samples for RNA extraction and genomic analyses. We created standard operating procedures for blood sample collection, processing, storage, shipping, and analyses. We planned to prospectively identify, enroll, and collect 1 mL blood samples for genomic analyses from eligible patients to identify logistical issues with study procedures. Finally, we planned to batch blood samples and determined RNA quantity and quality at the central microarray laboratory and organized data analysis with the Pediatric Emergency Care Applied Research Network data coordinating center. Below we report on establishment of the infrastructure and the feasibility success in the first year based on the enrollment of a limited number of patients. We successfully established the infrastructure at 21 EDs. Over the first 5 months we enrolled 79% (74 of 94) of eligible febrile infants. We were able to obtain and ship 1 mL of blood from 74% (55 of 74) of enrolled participants, with at least 1 sample per participating ED. The 55 samples were shipped and evaluated at the microarray laboratory, and 95% (52 of 55) of blood samples were of adequate quality and contained sufficient RNA for expression analysis. It is possible to create a robust infrastructure to conduct genomic studies in young febrile infants in the context of a multicenter pediatric ED research setting. The sufficient quantity and high quality of RNA obtained suggests that whole blood transcriptional profile analysis for the diagnostic evaluation of young febrile infants can be successfully performed in this setting.

Expression Profile of Cytokines and Enzymes mRNA in Blood Leukocytes of Dogs with Leptospirosis and Its Associated Pulmonary Hemorrhage Syndrome.

PubMed

Maissen-Villiger, Carla A; Schweighauser, Ariane; van Dorland, H Anette; Morel, Claudine; Bruckmaier, Rupert M; Zurbriggen, Andreas; Francey, Thierry

2016-01-01

Dogs with leptospirosis show similar organ manifestations and disease course as human patients, including acute kidney injury and pulmonary hemorrhage, making this naturally-occurring infection a good animal model for human leptospirosis. Expression patterns of cytokines and enzymes have been correlated with disease manifestations and clinical outcome in humans and animals. The aim of this study was to describe mRNA expression of pro- and anti-inflammatory mediators in canine leptospirosis and to compare it with other renal diseases to identify patterns characterizing the disease and especially its pulmonary form. The mRNA abundance of cytokines (IL-1α, IL-1β, IL-8, IL-10, TNF-α, TGF-β) and enzymes (5-LO, iNOS) was measured prospectively in blood leukocytes from 34 dogs with severe leptospirosis and acute kidney injury, including 22 dogs with leptospirosis-associated pulmonary hemorrhages. Dogs with leptospirosis were compared to 14 dogs with acute kidney injury of other origin than leptospirosis, 8 dogs with chronic kidney disease, and 10 healthy control dogs. Canine leptospirosis was characterized by high 5-LO and low TNF-α expression compared to other causes of acute kidney injury, although the decreased TNF-α expression was also seen in chronic kidney disease. Leptospirosis-associated pulmonary hemorrhage was not characterized by a specific pattern, with only mild changes noted, including increased IL-10 and decreased 5-LO expression on some days in affected dogs. Fatal outcome from pulmonary hemorrhages was associated with low TNF-α, high IL-1β, and high iNOS expression, a pattern possibly expressed also in dogs with other forms of acute kidney injury. The patterns of cytokine and enzyme expression observed in the present study indicate a complex pro- and anti-inflammatory response to the infection with leptospires. The recognition of these signatures may be of diagnostic and prognostic relevance for affected individuals and they may indicate options for newer therapies targeting the identified pathways.

Prospective technical validation and assessment of intra-tumour heterogeneity of a low density array hypoxia gene profile in head and neck squamous cell carcinoma.

PubMed

Betts, Guy N J; Eustace, Amanda; Patiar, Shalini; Valentine, Helen R; Irlam, Joely; Ramachandran, Anassuya; Merve, Ashirwad; Homer, Jarrod J; Möller-Levet, Carla; Buffa, Francesca M; Hall, Gillian; Miller, Crispin J; Harris, Adrian L; West, Catharine M L

2013-01-01

Tumour hypoxia is associated with a poor prognosis in head and neck squamous cell carcinoma (HNSCC), however there is no accepted method for assessing hypoxia clinically. We aimed to conduct a technical validation of a hypoxia gene expression signature using the TaqMan Low Density Array (TLDA) platform to investigate if this approach reliably identified hypoxic tumours. Tumour samples (n=201) from 80 HNSCC patients were collected prospectively from two centres. Fifty-three patients received pimonidazole prior to surgery. TaqMan Low Density Array-Hypoxia Scores (TLDA-HS) were obtained by quantitative real-time PCR (qPCR) using a 25-gene signature and customised TLDA cards. Assay performance was assessed as coefficient of variation (CoV). The assay was sensitive with linear reaction efficiencies across a 4 log(10) range of inputted cDNA (0.001-10 ng/μl). Intra- (CoV=6.9%) and inter- (CoV=2.0%) assay reproducibility were excellent. Intra-tumour heterogeneity was lower for TLDA-HS (23.2%) than for pimonidazole (67.2%) or single gene measurements of CA9 (62.2%), VEGFA (45.0%) or HIG2 (39.4%). TLDA-HS in HNSCC cell lines increased with decreasing pO(2). TLDA-HS correlated with Affymetrix U133 Plus 2.0 microarray HS (p<0.01) and positive pimonidazole scores (p=0.005). Gene expression measurements of hypoxia using a 25-gene signature and TLDA cards are sensitive, reproducible and associated with lower intra-tumour heterogeneity than assaying individual genes or pimonidazole binding. The approach is suitable for further assessment of prognostic and predictive capability in clinical trial material. Copyright © 2012 Elsevier Ltd. All rights reserved.

Circulating RNA transcripts identify therapeutic response in cystic fibrosis lung disease.

PubMed

Saavedra, Milene T; Hughes, Grant J; Sanders, Linda A; Carr, Michelle; Rodman, David M; Coldren, Christopher D; Geraci, Mark W; Sagel, Scott D; Accurso, Frank J; West, James; Nick, Jerry A

2008-11-01

Circulating leukocyte RNA transcripts are systemic markers of inflammation, which have not been studied in cystic fibrosis (CF) lung disease. Although the standard assessment of pulmonary treatment response is FEV(1), a measure of airflow limitation, the lack of systemic markers to reflect changes in lung inflammation critically limits the testing of proposed therapeutics. We sought to prospectively identify and validate peripheral blood leukocyte genes that could mark resolution of pulmonary infection and inflammation using a model by which RNA transcripts could increase the predictive value of spirometry. Peripheral blood mononuclear cells were isolated from 10 patients with CF and acute pulmonary exacerbations before and after therapy. RNA expression profiling revealed that 10 genes significantly changed with treatment when compared with matched non-CF and control subjects with stable CF to establish baseline transcript abundance. Peripheral blood mononuclear cell RNA transcripts were prospectively validated, using real-time polymerase chain reaction amplification, in an independent cohort of acutely ill patients with CF (n = 14). Patients who responded to therapy were analyzed using general estimating equations and multiple logistic regression, such that changes in FEV(1)% predicted were regressed with transcript changes. Three genes, CD64, ADAM9, and CD36, were significant and independent predictors of a therapeutic response beyond that of FEV(1) alone (P < 0.05). In both cohorts, receiver operating characteristic analysis revealed greater accuracy when genes were combined with FEV(1). Circulating mononuclear cell transcripts characterize a response to the treatment of pulmonary exacerbations. Even in small patient cohorts, changes in gene expression in conjunction with FEV(1) may enhance current outcomes measures for treatment response.

Expression profiling of the mouse early embryo: Reflections and Perspectives

PubMed Central

Ko, Minoru S. H.

2008-01-01

Laboratory mouse plays important role in our understanding of early mammalian development and provides invaluable model for human early embryos, which are difficult to study for ethical and technical reasons. Comprehensive collection of cDNA clones, their sequences, and complete genome sequence information, which have been accumulated over last two decades, have provided even more advantages to mouse models. Here the progress in global gene expression profiling in early mouse embryos and, to some extent, stem cells are reviewed and the future directions and challenges are discussed. The discussions include the restatement of global gene expression profiles as snapshot of cellular status, and subsequent distinction between the differentiation state and physiological state of the cells. The discussions then extend to the biological problems that can be addressed only through global expression profiling, which include: bird’s-eye view of global gene expression changes, molecular index for developmental potency, cell lineage trajectory, microarray-guided cell manipulation, and the possibility of delineating gene regulatory cascades and networks. PMID:16739220

2012 mba.com Prospective Students Survey. Survey Report. The GMAC[R] Survey Series

ERIC Educational Resources Information Center

Schoenfeld, Gregg

2012-01-01

This 2012 mba.com Prospective Students Survey Report explores the motivations, behaviors, program choices, and intended career outcomes of individuals who expressed a desire to further their education in a graduate business program. More than 16,000 prospective business school students who registered on mba.com shared their opinions, preferences,…

Expression signature as a biomarker for prenatal diagnosis of trisomy 21.

PubMed

Volk, Marija; Maver, Aleš; Lovrečić, Luca; Juvan, Peter; Peterlin, Borut

2013-01-01

A universal biomarker panel with the potential to predict high-risk pregnancies or adverse pregnancy outcome does not exist. Transcriptome analysis is a powerful tool to capture differentially expressed genes (DEG), which can be used as biomarker-diagnostic-predictive tool for various conditions in prenatal setting. In search of biomarker set for predicting high-risk pregnancies, we performed global expression profiling to find DEG in Ts21. Subsequently, we performed targeted validation and diagnostic performance evaluation on a larger group of case and control samples. Initially, transcriptomic profiles of 10 cultivated amniocyte samples with Ts21 and 9 with normal euploid constitution were determined using expression microarrays. Datasets from Ts21 transcriptomic studies from GEO repository were incorporated. DEG were discovered using linear regression modelling and validated using RT-PCR quantification on an independent sample of 16 cases with Ts21 and 32 controls. The classification performance of Ts21 status based on expression profiling was performed using supervised machine learning algorithm and evaluated using a leave-one-out cross validation approach. Global gene expression profiling has revealed significant expression changes between normal and Ts21 samples, which in combination with data from previously performed Ts21 transcriptomic studies, were used to generate a multi-gene biomarker for Ts21, comprising of 9 gene expression profiles. In addition to biomarker's high performance in discriminating samples from global expression profiling, we were also able to show its discriminatory performance on a larger sample set 2, validated using RT-PCR experiment (AUC=0.97), while its performance on data from previously published studies reached discriminatory AUC values of 1.00. Our results show that transcriptomic changes might potentially be used to discriminate trisomy of chromosome 21 in the prenatal setting. As expressional alterations reflect both, causal and reactive cellular mechanisms, transcriptomic changes may thus have future potential in the diagnosis of a wide array of heterogeneous diseases that result from genetic disturbances.

mRNA expression profiling of laser microbeam microdissected cells from slender embryonic structures.

PubMed

Scheidl, Stefan J; Nilsson, Sven; Kalén, Mattias; Hellström, Mats; Takemoto, Minoru; Håkansson, Joakim; Lindahl, Per

2002-03-01

Microarray hybridization has rapidly evolved as an important tool for genomic studies and studies of gene regulation at the transcriptome level. Expression profiles from homogenous samples such as yeast and mammalian cell cultures are currently extending our understanding of biology, whereas analyses of multicellular organisms are more difficult because of tissue complexity. The combination of laser microdissection, RNA amplification, and microarray hybridization has the potential to provide expression profiles from selected populations of cells in vivo. In this article, we present and evaluate an experimental procedure for global gene expression analysis of slender embryonic structures using laser microbeam microdissection and laser pressure catapulting. As a proof of principle, expression profiles from 1000 cells in the mouse embryonic (E9.5) dorsal aorta were generated and compared with profiles for captured mesenchymal cells located one cell diameter further away from the aortic lumen. A number of genes were overexpressed in the aorta, including 11 previously known markers for blood vessels. Among the blood vessel markers were endoglin, tie-2, PDGFB, and integrin-beta1, that are important regulators of blood vessel formation. This demonstrates that microarray analysis of laser microbeam micro-dissected cells is sufficiently sensitive for identifying genes with regulative functions.

ABC gene expression profiles have clinical importance and possibly form a new hallmark of cancer.

PubMed

Dvorak, Pavel; Pesta, Martin; Soucek, Pavel

2017-05-01

Adenosine triphosphate-binding cassette proteins constitute a large family of active transporters through extracellular and intracellular membranes. Increased drug efflux based on adenosine triphosphate-binding cassette protein activity is related to the development of cancer cell chemoresistance. Several articles have focused on adenosine triphosphate-binding cassette gene expression profiles (signatures), based on the expression of all 49 human adenosine triphosphate-binding cassette genes, in individual tumor types and reported connections to established clinicopathological features. The aim of this study was to test our theory about the existence of adenosine triphosphate-binding cassette gene expression profiles common to multiple types of tumors, which may modify tumor progression and provide clinically relevant information. Such general adenosine triphosphate-binding cassette profiles could constitute a new attribute of carcinogenesis. Our combined cohort consisted of tissues from 151 cancer patients-breast, colorectal, and pancreatic carcinomas. Standard protocols for RNA isolation and quantitative real-time polymerase chain reaction were followed. Gene expression data from individual tumor types as well as a merged tumor dataset were analyzed by bioinformatics tools. Several general adenosine triphosphate-binding cassette profiles, with differences in gene functions, were established and shown to have significant relations to clinicopathological features such as tumor size, histological grade, or clinical stage. Genes ABCC7, A3, A8, A12, and C8 prevailed among the most upregulated or downregulated ones. In conclusion, the results supported our theory about general adenosine triphosphate-binding cassette gene expression profiles and their importance for cancer on clinical as well as research levels. The presence of ABCC7 (official symbol CFTR) among the genes with key roles in the profiles supports the emerging evidence about its crucial role in various cancers. Graphical abstract.

In-Vivo Expression Profiling of Pseudomonas aeruginosa Infections Reveals Niche-Specific and Strain-Independent Transcriptional Programs

PubMed Central

Bielecki, Piotr; Puchałka, Jacek; Wos-Oxley, Melissa L.; Loessner, Holger; Glik, Justyna; Kawecki, Marek; Nowak, Mariusz; Tümmler, Burkhard; Weiss, Siegfried; dos Santos, Vítor A. P. Martins

2011-01-01

Pseudomonas aeruginosa is a threatening, opportunistic pathogen causing disease in immunocompromised individuals. The hallmark of P. aeruginosa virulence is its multi-factorial and combinatorial nature. It renders such bacteria infectious for many organisms and it is often resistant to antibiotics. To gain insights into the physiology of P. aeruginosa during infection, we assessed the transcriptional programs of three different P. aeruginosa strains directly after isolation from burn wounds of humans. We compared the programs to those of the same strains using two infection models: a plant model, which consisted of the infection of the midrib of lettuce leaves, and a murine tumor model, which was obtained by infection of mice with an induced tumor in the abdomen. All control conditions of P. aeruginosa cells growing in suspension and as a biofilm were added to the analysis. We found that these different P. aeruginosa strains express a pool of distinct genetic traits that are activated under particular infection conditions regardless of their genetic variability. The knowledge herein generated will advance our understanding of P. aeruginosa virulence and provide valuable cues for the definition of prospective targets to develop novel intervention strategies. PMID:21931663

IGFBP1 increases β-cell regeneration by promoting α- to β-cell transdifferentiation.

PubMed

Lu, Jing; Liu, Ka-Cheuk; Schulz, Nadja; Karampelias, Christos; Charbord, Jérémie; Hilding, Agneta; Rautio, Linn; Bertolino, Philippe; Östenson, Claes-Göran; Brismar, Kerstin; Andersson, Olov

2016-09-15

There is great interest in therapeutically harnessing endogenous regenerative mechanisms to increase the number of β cells in people with diabetes. By performing whole-genome expression profiling of zebrafish islets, we identified 11 secreted proteins that are upregulated during β-cell regeneration. We then tested the proteins' ability to potentiate β-cell regeneration in zebrafish at supraphysiological levels. One protein, insulin-like growth factor (Igf) binding-protein 1 (Igfbp1), potently promoted β-cell regeneration by potentiating α- to β-cell transdifferentiation. Using various inhibitors and activators of the Igf pathway, we show that Igfbp1 exerts its regenerative effect, at least partly, by inhibiting Igf signaling. Igfbp1's effect on transdifferentiation appears conserved across species: Treating mouse and human islets with recombinant IGFBP1 in vitro increased the number of cells co-expressing insulin and glucagon threefold. Moreover, a prospective human study showed that having high IGFBP1 levels reduces the risk of developing type-2 diabetes by more than 85%. Thus, we identify IGFBP1 as an endogenous promoter of β-cell regeneration and highlight its clinical importance in diabetes. © 2016 The Authors. Published under the terms of the CC BY NC ND 4.0 license.

In-vivo expression profiling of Pseudomonas aeruginosa infections reveals niche-specific and strain-independent transcriptional programs.

PubMed

Bielecki, Piotr; Puchałka, Jacek; Wos-Oxley, Melissa L; Loessner, Holger; Glik, Justyna; Kawecki, Marek; Nowak, Mariusz; Tümmler, Burkhard; Weiss, Siegfried; dos Santos, Vítor A P Martins

2011-01-01

Pseudomonas aeruginosa is a threatening, opportunistic pathogen causing disease in immunocompromised individuals. The hallmark of P. aeruginosa virulence is its multi-factorial and combinatorial nature. It renders such bacteria infectious for many organisms and it is often resistant to antibiotics. To gain insights into the physiology of P. aeruginosa during infection, we assessed the transcriptional programs of three different P. aeruginosa strains directly after isolation from burn wounds of humans. We compared the programs to those of the same strains using two infection models: a plant model, which consisted of the infection of the midrib of lettuce leaves, and a murine tumor model, which was obtained by infection of mice with an induced tumor in the abdomen. All control conditions of P. aeruginosa cells growing in suspension and as a biofilm were added to the analysis. We found that these different P. aeruginosa strains express a pool of distinct genetic traits that are activated under particular infection conditions regardless of their genetic variability. The knowledge herein generated will advance our understanding of P. aeruginosa virulence and provide valuable cues for the definition of prospective targets to develop novel intervention strategies.

Novel surgical procedures in glaucoma: advances in penetrating glaucoma surgery.

PubMed

Filippopoulos, Theodoros; Rhee, Douglas J

2008-03-01

Despite late modifications and enhancements, traditional penetrating glaucoma surgery is not without complications and is reserved for patients in whom pharmacologic treatment and/or laser trabeculoplasty do not suffice to control the intraocular pressure. This article critically reviews recent advances in penetrating glaucoma surgery with particular attention paid to two novel surgical approaches: ab interno trabeculectomy with the Trabectome and implantation of the Ex-PRESS shunt. Ab interno trabeculectomy (Trabectome) achieves a sustained 30% reduction in intraocular pressure by focally ablating and cauterizing the trabecular meshwork/inner wall of Schlemm's canal. It has a remarkable safety profile with respect to early hypotonous or infectious complications as it does not generate a bleb, but it can be associated with early postoperative intraocular pressure spikes that may necessitate additional glaucoma surgery. The Ex-PRESS shunt is more commonly implanted under a partial thickness scleral flap, and appears to have similar efficacy to standard trabeculectomy offering some advantages with respect to the rate of early complications related to hypotony. Penetrating glaucoma surgery will continue to evolve. As prospective randomized clinical trials become available, we will determine the exact role of these surgical techniques in the glaucoma surgical armamentarium.

Cell-specific prediction and application of drug-induced gene expression profiles.

PubMed

Hodos, Rachel; Zhang, Ping; Lee, Hao-Chih; Duan, Qiaonan; Wang, Zichen; Clark, Neil R; Ma'ayan, Avi; Wang, Fei; Kidd, Brian; Hu, Jianying; Sontag, David; Dudley, Joel

2018-01-01

Gene expression profiling of in vitro drug perturbations is useful for many biomedical discovery applications including drug repurposing and elucidation of drug mechanisms. However, limited data availability across cell types has hindered our capacity to leverage or explore the cell-specificity of these perturbations. While recent efforts have generated a large number of drug perturbation profiles across a variety of human cell types, many gaps remain in this combinatorial drug-cell space. Hence, we asked whether it is possible to fill these gaps by predicting cell-specific drug perturbation profiles using available expression data from related conditions--i.e. from other drugs and cell types. We developed a computational framework that first arranges existing profiles into a three-dimensional array (or tensor) indexed by drugs, genes, and cell types, and then uses either local (nearest-neighbors) or global (tensor completion) information to predict unmeasured profiles. We evaluate prediction accuracy using a variety of metrics, and find that the two methods have complementary performance, each superior in different regions in the drug-cell space. Predictions achieve correlations of 0.68 with true values, and maintain accurate differentially expressed genes (AUC 0.81). Finally, we demonstrate that the predicted profiles add value for making downstream associations with drug targets and therapeutic classes.

Cell-specific prediction and application of drug-induced gene expression profiles

PubMed Central

Hodos, Rachel; Zhang, Ping; Lee, Hao-Chih; Duan, Qiaonan; Wang, Zichen; Clark, Neil R.; Ma'ayan, Avi; Wang, Fei; Kidd, Brian; Hu, Jianying; Sontag, David

2017-01-01

Gene expression profiling of in vitro drug perturbations is useful for many biomedical discovery applications including drug repurposing and elucidation of drug mechanisms. However, limited data availability across cell types has hindered our capacity to leverage or explore the cell-specificity of these perturbations. While recent efforts have generated a large number of drug perturbation profiles across a variety of human cell types, many gaps remain in this combinatorial drug-cell space. Hence, we asked whether it is possible to fill these gaps by predicting cell-specific drug perturbation profiles using available expression data from related conditions--i.e. from other drugs and cell types. We developed a computational framework that first arranges existing profiles into a three-dimensional array (or tensor) indexed by drugs, genes, and cell types, and then uses either local (nearest-neighbors) or global (tensor completion) information to predict unmeasured profiles. We evaluate prediction accuracy using a variety of metrics, and find that the two methods have complementary performance, each superior in different regions in the drug-cell space. Predictions achieve correlations of 0.68 with true values, and maintain accurate differentially expressed genes (AUC 0.81). Finally, we demonstrate that the predicted profiles add value for making downstream associations with drug targets and therapeutic classes. PMID:29218867

microRNA-342, microRNA-191 and microRNA-510 are differentially expressed in T regulatory cells of type 1 diabetic patients.

PubMed

Hezova, Renata; Slaby, Ondrej; Faltejskova, Petra; Mikulkova, Zuzana; Buresova, Ivana; Raja, K R Muthu; Hodek, Jan; Ovesna, Jaroslava; Michalek, Jaroslav

2010-01-01

Regulatory T cells (Tregs) are critical regulators of autoimmune diseases, including type 1 diabetes mellitus. It is hypothesised that Tregs' function can be influenced by changes in the expression of specific microRNAs (miRNAs). Thus, we performed miRNAs profiling in a population of Tregs separated from peripheral blood of five type 1 diabetic patients and six healthy donors. For more detailed molecular characterisation of Tregs, we additionally compared miRNAs expression profiles of Tregs and conventional T cells. Tregs were isolated according to CD3+, CD4+, CD25(hi)+ and CD127- by flow cytometry, and miRNA expression profiling was performed using TaqMan Array Human MicroRNA Panel-1 (384-well low density array). In Tregs of diabetic patients we found significantly increased expression of miRNA-510 (p=0.05) and decreased expression of both miRNA-342 (p<0.0001) and miRNA-191 (p=0.0079). When comparing Tregs and T cells, we revealed that Tregs had significant higher expression of miRNA-146a and lower expression of eight specific miRNAs (20b, 31, 99a, 100, 125b, 151, 335, and 365). To our knowledge, this is the first study demonstrating changes in miRNA expression profiles occurring in Tregs of T1D patients and a miRNAs signature of adult Tregs.

Stress amplifies sex differences in primate prefrontal profiles of gene expression.

PubMed

Lee, Alex G; Hagenauer, Megan; Absher, Devin; Morrison, Kathleen E; Bale, Tracy L; Myers, Richard M; Watson, Stanley J; Akil, Huda; Schatzberg, Alan F; Lyons, David M

2017-11-02

Stress is a recognized risk factor for mood and anxiety disorders that occur more often in women than men. Prefrontal brain regions mediate stress coping, cognitive control, and emotion. Here, we investigate sex differences and stress effects on prefrontal cortical profiles of gene expression in squirrel monkey adults. Dorsolateral, ventrolateral, and ventromedial prefrontal cortical regions from 18 females and 12 males were collected after stress or no-stress treatment conditions. Gene expression profiles were acquired using HumanHT-12v4.0 Expression BeadChip arrays adapted for squirrel monkeys. Extensive variation between prefrontal cortical regions was discerned in the expression of numerous autosomal and sex chromosome genes. Robust sex differences were also identified across prefrontal cortical regions in the expression of mostly autosomal genes. Genes with increased expression in females compared to males were overrepresented in mitogen-activated protein kinase and neurotrophin signaling pathways. Many fewer genes with increased expression in males compared to females were discerned, and no molecular pathways were identified. Effect sizes for sex differences were greater in stress compared to no-stress conditions for ventromedial and ventrolateral prefrontal cortical regions but not dorsolateral prefrontal cortex. Stress amplifies sex differences in gene expression profiles for prefrontal cortical regions involved in stress coping and emotion regulation. Results suggest molecular targets for new treatments of stress disorders in human mental health.

RNA Expression Profiles from Blood for the Diagnosis of Stroke and its Causes

PubMed Central

Sharp, Frank R; Jickling, Glen C; Stamova, Boryana; Tian, Yingfang; Zhan, Xinhua; Ander, Bradley P; Cox, Christopher; Kuczynski, Beth; Liu, DaZhi

2013-01-01

A blood test to detect stroke and its causes would be particularly useful in babies, young children, and patients in intensive care units, and for emergencies when imaging is difficult to obtain or unavailable. Using whole genome microarrays, we first showed specific gene expression profiles in rats 24 hours after ischemic and hemorrhagic stroke, hypoxia, and hypoglycemia. These proof-of-principle studies revealed that groups of genes (called gene profiles) can distinguish ischemic stroke patients from controls 3 hours to 24 hours after the strokes. In addition, gene expression profiles have been developed that distinguish stroke due to large-vessel atherosclerosis from cardioembolic stroke. These profiles will be useful for predicting the causes of cryptogenic stroke. Our results in adults suggest similar diagnostic tools could be developed for children. PMID:21636778

Autism Spectrum Disorder Symptoms in Infants with Fragile X Syndrome: A Prospective Case Series

ERIC Educational Resources Information Center

Hogan, Abigail L.; Caravella, Kelly E.; Ezell, Jordan; Rague, Lisa; Hills, Kimberly; Roberts, Jane E.

2017-01-01

No studies to date have prospectively examined early autism spectrum disorder (ASD) markers in infants with fragile X syndrome (FXS), who are at elevated risk for ASD. This paper describes the developmental profiles of eight infants with FXS from 9 to 24 months of age. Four meet diagnostic criteria for ASD at 24 months of age, and four do not.…

Electrocardiographic Changes in Children and Adolescents Treated with Ziprasidone: A Prospective Study.

ERIC Educational Resources Information Center

McElfresh, Adeline; Scahill, Lawrence; State, Matthew; Martin, Andres

2005-01-01

Objective: To assess the electrocardiographic safety profile of low-dose ziprasidone ([less than or equal to]40 mg/day) among pediatric outpatients treated for up to 6 months. Method: This was a prospective, open-label trial involving 20 subjects with a mean age of 13.2 [+ or -] 3.0 years. Subjects received a mean ziprasidone dose of 30 [+ or -]…

Gene-expression profiling for rejection surveillance after cardiac transplantation.

PubMed

Pham, Michael X; Teuteberg, Jeffrey J; Kfoury, Abdallah G; Starling, Randall C; Deng, Mario C; Cappola, Thomas P; Kao, Andrew; Anderson, Allen S; Cotts, William G; Ewald, Gregory A; Baran, David A; Bogaev, Roberta C; Elashoff, Barbara; Baron, Helen; Yee, James; Valantine, Hannah A

2010-05-20

Endomyocardial biopsy is the standard method of monitoring for rejection in recipients of a cardiac transplant. However, this procedure is uncomfortable, and there are risks associated with it. Gene-expression profiling of peripheral-blood specimens has been shown to correlate with the results of an endomyocardial biopsy. We randomly assigned 602 patients who had undergone cardiac transplantation 6 months to 5 years previously to be monitored for rejection with the use of gene-expression profiling or with the use of routine endomyocardial biopsies, in addition to clinical and echocardiographic assessment of graft function. We performed a noninferiority comparison of the two approaches with respect to the composite primary outcome of rejection with hemodynamic compromise, graft dysfunction due to other causes, death, or retransplantation. During a median follow-up period of 19 months, patients who were monitored with gene-expression profiling and those who underwent routine biopsies had similar 2-year cumulative rates of the composite primary outcome (14.5% and 15.3%, respectively; hazard ratio with gene-expression profiling, 1.04; 95% confidence interval, 0.67 to 1.68). The 2-year rates of death from any cause were also similar in the two groups (6.3% and 5.5%, respectively; P=0.82). Patients who were monitored with the use of gene-expression profiling underwent fewer biopsies per person-year of follow-up than did patients who were monitored with the use of endomyocardial biopsies (0.5 vs. 3.0, P<0.001). Among selected patients who had received a cardiac transplant more than 6 months previously and who were at a low risk for rejection, a strategy of monitoring for rejection that involved gene-expression profiling, as compared with routine biopsies, was not associated with an increased risk of serious adverse outcomes and resulted in the performance of significantly fewer biopsies. (ClinicalTrials.gov number, NCT00351559.) 2010 Massachusetts Medical Society

Investigating the Receptive-Expressive Vocabulary Profile in Children with Idiopathic ASD and Comorbid ASD and Fragile X Syndrome

ERIC Educational Resources Information Center

Haebig, Eileen; Sterling, Audra

2017-01-01

Previous work has noted that some children with autism spectrum disorder (ASD) display weaknesses in receptive vocabulary relative to expressive vocabulary abilities. The current study extended previous work by examining the receptive-expressive vocabulary profile in boys with idiopathic ASD and boys with concomitant ASD and fragile X syndrome…

Characterization of the transcriptome profiles related to globin gene switching during in vitro erythroid maturation

PubMed Central

2012-01-01

Background The fetal and adult globin genes in the human β-globin cluster on chromosome 11 are sequentially expressed to achieve normal hemoglobin switching during human development. The pharmacological induction of fetal γ-globin (HBG) to replace abnormal adult sickle βS-globin is a successful strategy to treat sickle cell disease; however the molecular mechanism of γ-gene silencing after birth is not fully understood. Therefore, we performed global gene expression profiling using primary erythroid progenitors grown from human peripheral blood mononuclear cells to characterize gene expression patterns during the γ-globin to β-globin (γ/β) switch observed throughout in vitro erythroid differentiation. Results We confirmed erythroid maturation in our culture system using cell morphologic features defined by Giemsa staining and the γ/β-globin switch by reverse transcription-quantitative PCR (RT-qPCR) analysis. We observed maximal γ-globin expression at day 7 with a switch to a predominance of β-globin expression by day 28 and the γ/β-globin switch occurred around day 21. Expression patterns for transcription factors including GATA1, GATA2, KLF1 and NFE2 confirmed our system produced the expected pattern of expression based on the known function of these factors in globin gene regulation. Subsequent gene expression profiling was performed with RNA isolated from progenitors harvested at day 7, 14, 21, and 28 in culture. Three major gene profiles were generated by Principal Component Analysis (PCA). For profile-1 genes, where expression decreased from day 7 to day 28, we identified 2,102 genes down-regulated > 1.5-fold. Ingenuity pathway analysis (IPA) for profile-1 genes demonstrated involvement of the Cdc42, phospholipase C, NF-Kβ, Interleukin-4, and p38 mitogen activated protein kinase (MAPK) signaling pathways. Transcription factors known to be involved in γ-and β-globin regulation were identified. The same approach was used to generate profile-2 genes where expression was up-regulated over 28 days in culture. IPA for the 2,437 genes with > 1.5-fold induction identified the mitotic roles of polo-like kinase, aryl hydrocarbon receptor, cell cycle control, and ATM (Ataxia Telangiectasia Mutated Protein) signaling pathways; transcription factors identified included KLF1, GATA1 and NFE2 among others. Finally, profile-3 was generated from 1,579 genes with maximal expression at day 21, around the time of the γ/β-globin switch. IPA identified associations with cell cycle control, ATM, and aryl hydrocarbon receptor signaling pathways. Conclusions The transcriptome analysis completed with erythroid progenitors grown in vitro identified groups of genes with distinct expression profiles, which function in metabolic pathways associated with cell survival, hematopoiesis, blood cells activation, and inflammatory responses. This study represents the first report of a transcriptome analysis in human primary erythroid progenitors to identify transcription factors involved in hemoglobin switching. Our results also demonstrate that the in vitro liquid culture system is an excellent model to define mechanisms of global gene expression and the DNA-binding protein and signaling pathways involved in globin gene regulation. PMID:22537182

MicroRNA expression profiling during the life cycle of the silkworm (Bombyx mori)

PubMed Central

Liu, Shiping; Zhang, Liang; Li, Qibin; Zhao, Ping; Duan, Jun; Cheng, Daojun; Xiang, Zhonghuai; Xia, Qingyou

2009-01-01

Background MicroRNAs (miRNAs) are expressed by a wide range of eukaryotic organisms, and function in diverse biological processes. Numerous miRNAs have been identified in Bombyx mori, but the temporal expression profiles of miRNAs corresponding to each stage transition over the entire life cycle of the silkworm remain to be established. To obtain a comprehensive overview of the correlation between miRNA expression and stage transitions, we performed a whole-life test and subsequent stage-by-stage examinations on nearly one hundred miRNAs in the silkworm. Results Our results show that miRNAs display a wide variety of expression profiles over the whole life of the silkworm, including continuous expression from embryo to adult (miR-184), up-regulation over the entire life cycle (let-7 and miR-100), down-regulation over the entire life cycle (miR-124), expression associated with embryogenesis (miR-29 and miR-92), up-regulation from early 3rd instar to pupa (miR-275), and complementary pulses in expression between miR-34b and miR-275. Stage-by-stage examinations revealed further expression patterns, such as emergence at specific time-points during embryogenesis and up-regulation of miRNA groups in late embryos (miR-1 and bantam), expression associated with stage transition between instar and molt larval stages (miR-34b), expression associated with silk gland growth and spinning activity (miR-274), continuous high expression from the spinning larval to pupal and adult stages (miR-252 and miR-31a), a coordinate expression trough in day 3 pupae of both sexes (miR-10b and miR-281), up-regulation in pupal metamorphosis of both sexes (miR-29b), and down-regulation in pupal metamorphosis of both sexes (miR-275). Conclusion We present the full-scale expression profiles of miRNAs throughout the life cycle of Bombyx mori. The whole-life expression profile was further investigated via stage-by-stage analysis. Our data provide an important resource for more detailed functional analysis of miRNAs in this animal. PMID:19785751

MicroRNA expression profiling during the life cycle of the silkworm (Bombyx mori).

PubMed

Liu, Shiping; Zhang, Liang; Li, Qibin; Zhao, Ping; Duan, Jun; Cheng, Daojun; Xiang, Zhonghuai; Xia, Qingyou

2009-09-28

MicroRNAs (miRNAs) are expressed by a wide range of eukaryotic organisms, and function in diverse biological processes. Numerous miRNAs have been identified in Bombyx mori, but the temporal expression profiles of miRNAs corresponding to each stage transition over the entire life cycle of the silkworm remain to be established. To obtain a comprehensive overview of the correlation between miRNA expression and stage transitions, we performed a whole-life test and subsequent stage-by-stage examinations on nearly one hundred miRNAs in the silkworm. Our results show that miRNAs display a wide variety of expression profiles over the whole life of the silkworm, including continuous expression from embryo to adult (miR-184), up-regulation over the entire life cycle (let-7 and miR-100), down-regulation over the entire life cycle (miR-124), expression associated with embryogenesis (miR-29 and miR-92), up-regulation from early 3rd instar to pupa (miR-275), and complementary pulses in expression between miR-34b and miR-275. Stage-by-stage examinations revealed further expression patterns, such as emergence at specific time-points during embryogenesis and up-regulation of miRNA groups in late embryos (miR-1 and bantam), expression associated with stage transition between instar and molt larval stages (miR-34b), expression associated with silk gland growth and spinning activity (miR-274), continuous high expression from the spinning larval to pupal and adult stages (miR-252 and miR-31a), a coordinate expression trough in day 3 pupae of both sexes (miR-10b and miR-281), up-regulation in pupal metamorphosis of both sexes (miR-29b), and down-regulation in pupal metamorphosis of both sexes (miR-275). We present the full-scale expression profiles of miRNAs throughout the life cycle of Bombyx mori. The whole-life expression profile was further investigated via stage-by-stage analysis. Our data provide an important resource for more detailed functional analysis of miRNAs in this animal.

Distinct profiles of expressed sequence tags during intestinal regeneration in the sea cucumber Holothuria glaberrima

PubMed Central

Rojas-Cartagena, Carmencita; Ortíz-Pineda, Pablo; Ramírez-Gómez, Francisco; Suárez-Castillo, Edna C.; Matos-Cruz, Vanessa; Rodríguez, Carlos; Ortíz-Zuazaga, Humberto; García-Arrarás, José E.

2010-01-01

Repair and regeneration are key processes for tissue maintenance, and their disruption may lead to disease states. Little is known about the molecular mechanisms that underline the repair and regeneration of the digestive tract. The sea cucumber Holothuria glaberrima represents an excellent model to dissect and characterize the molecular events during intestinal regeneration. To study the gene expression profile, cDNA libraries were constructed from normal, 3-day, and 7-day regenerating intestines of H. glaberrima. Clones were randomly sequenced and queried against the nonredundant protein database at the National Center for Biotechnology Information. RT-PCR analyses were made of several genes to determine their expression profile during intestinal regeneration. A total of 5,173 sequences from three cDNA libraries were obtained. About 46.2, 35.6, and 26.2% of the sequences for the normal, 3-days, and 7-days cDNA libraries, respectively, shared significant similarity with known sequences in the protein database of GenBank but only present 10% of similarity among them. Analysis of the libraries in terms of functional processes, protein domains, and most common sequences suggests that a differential expression profile is taking place during the regeneration process. Further examination of the expressed sequence tag dataset revealed that 12 putative genes are differentially expressed at significant level (R > 6). Experimental validation by RT-PCR analysis reveals that at least three genes (unknown C-4677-1, melanotransferrin, and centaurin) present a differential expression during regeneration. These findings strongly suggest that the gene expression profile varies among regeneration stages and provide evidence for the existence of differential gene expression. PMID:17579180

Behaviorally activated mRNA expression profiles produce signatures of learning and enhanced inhibition in aged rats with preserved memory.

PubMed

Haberman, Rebecca P; Colantuoni, Carlo; Koh, Ming Teng; Gallagher, Michela

2013-01-01

Aging is often associated with cognitive decline, but many elderly individuals maintain a high level of function throughout life. Here we studied outbred rats, which also exhibit individual differences across a spectrum of outcomes that includes both preserved and impaired spatial memory. Previous work in this model identified the CA3 subfield of the hippocampus as a region critically affected by age and integral to differing cognitive outcomes. Earlier microarray profiling revealed distinct gene expression profiles in the CA3 region, under basal conditions, for aged rats with intact memory and those with impairment. Because prominent age-related deficits within the CA3 occur during neural encoding of new information, here we used microarray analysis to gain a broad perspective of the aged CA3 transcriptome under activated conditions. Behaviorally-induced CA3 expression profiles differentiated aged rats with intact memory from those with impaired memory. In the activated profile, we observed substantial numbers of genes (greater than 1000) exhibiting increased expression in aged unimpaired rats relative to aged impaired, including many involved in synaptic plasticity and memory mechanisms. This unimpaired aged profile also overlapped significantly with a learning induced gene profile previously acquired in young adults. Alongside the increased transcripts common to both young learning and aged rats with preserved memory, many transcripts behaviorally-activated in the current study had previously been identified as repressed in the aged unimpaired phenotype in basal expression. A further distinct feature of the activated profile of aged rats with intact memory is the increased expression of an ensemble of genes involved in inhibitory synapse function, which could control the phenotype of neural hyperexcitability found in the CA3 region of aged impaired rats. These data support the conclusion that aged subjects with preserved memory recruit adaptive mechanisms to retain tight control over excitability under both basal and activated conditions.

Gene Expression Profiling of Monkeypox Virus-Infected Cells Reveals Novel Interfaces for Host-Virus Interactions

DTIC Science & Technology

2010-07-28

expression is plotted on Y -axis after normalization to mock-treated samples. Results plotted to compare calculated fold change in expression of each gene ...RESEARCH Open Access Gene expression profiling of monkeypox virus-infected cells reveals novel interfaces for host-virus interactions Abdulnaser...suppress antiviral cell defenses, exploit host cell machinery, and delay infection-induced cell death. However, a comprehensive study of all host genes

Network-Induced Classification Kernels for Gene Expression Profile Analysis

PubMed Central

Dror, Gideon; Shamir, Ron

2012-01-01

Abstract Computational classification of gene expression profiles into distinct disease phenotypes has been highly successful to date. Still, robustness, accuracy, and biological interpretation of the results have been limited, and it was suggested that use of protein interaction information jointly with the expression profiles can improve the results. Here, we study three aspects of this problem. First, we show that interactions are indeed relevant by showing that co-expressed genes tend to be closer in the network of interactions. Second, we show that the improved performance of one extant method utilizing expression and interactions is not really due to the biological information in the network, while in another method this is not the case. Finally, we develop a new kernel method—called NICK—that integrates network and expression data for SVM classification, and demonstrate that overall it achieves better results than extant methods while running two orders of magnitude faster. PMID:22697242

Integrated analysis of numerous heterogeneous gene expression profiles for detecting robust disease-specific biomarkers and proposing drug targets.

PubMed

Amar, David; Hait, Tom; Izraeli, Shai; Shamir, Ron

2015-09-18

Genome-wide expression profiling has revolutionized biomedical research; vast amounts of expression data from numerous studies of many diseases are now available. Making the best use of this resource in order to better understand disease processes and treatment remains an open challenge. In particular, disease biomarkers detected in case-control studies suffer from low reliability and are only weakly reproducible. Here, we present a systematic integrative analysis methodology to overcome these shortcomings. We assembled and manually curated more than 14,000 expression profiles spanning 48 diseases and 18 expression platforms. We show that when studying a particular disease, judicious utilization of profiles from other diseases and information on disease hierarchy improves classification quality, avoids overoptimistic evaluation of that quality, and enhances disease-specific biomarker discovery. This approach yielded specific biomarkers for 24 of the analyzed diseases. We demonstrate how to combine these biomarkers with large-scale interaction, mutation and drug target data, forming a highly valuable disease summary that suggests novel directions in disease understanding and drug repurposing. Our analysis also estimates the number of samples required to reach a desired level of biomarker stability. This methodology can greatly improve the exploitation of the mountain of expression profiles for better disease analysis. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Modelling gene expression profiles related to prostate tumor progression using binary states

PubMed Central

2013-01-01

Background Cancer is a complex disease commonly characterized by the disrupted activity of several cancer-related genes such as oncogenes and tumor-suppressor genes. Previous studies suggest that the process of tumor progression to malignancy is dynamic and can be traced by changes in gene expression. Despite the enormous efforts made for differential expression detection and biomarker discovery, few methods have been designed to model the gene expression level to tumor stage during malignancy progression. Such models could help us understand the dynamics and simplify or reveal the complexity of tumor progression. Methods We have modeled an on-off state of gene activation per sample then per stage to select gene expression profiles associated to tumor progression. The selection is guided by statistical significance of profiles based on random permutated datasets. Results We show that our method identifies expected profiles corresponding to oncogenes and tumor suppressor genes in a prostate tumor progression dataset. Comparisons with other methods support our findings and indicate that a considerable proportion of significant profiles is not found by other statistical tests commonly used to detect differential expression between tumor stages nor found by other tailored methods. Ontology and pathway analysis concurred with these findings. Conclusions Results suggest that our methodology may be a valuable tool to study tumor malignancy progression, which might reveal novel cancer therapies. PMID:23721350

Chemical water shutoff profile research status and development trends

NASA Astrophysics Data System (ADS)

Xu, L. T.

2017-08-01

Excess water production is now a common problem encountered in almost every water flooding mature oilfield. The exploitation of oil field is faced with great challenge because of the decrease of oil field production. For the development of high water cut rare the status quo chemical water shutoff profile control technology is an important solution to solve this problem. Oilfield chemical water shutoff has important application prospects. This paper analyzes the water shutoff profile control and water shutoff profile control agent currently oilfield applications, moreover the use and development of blocking agent profile technology is to improve reservoir recovery and propose solutions. With the constant increase in water cut, profile technology should be simple, efficient, practical and profile control agent of development should be economic, environmental, and long period

Lex-SVM: exploring the potential of exon expression profiling for disease classification.

PubMed

Yuan, Xiongying; Zhao, Yi; Liu, Changning; Bu, Dongbo

2011-04-01

Exon expression profiling technologies, including exon arrays and RNA-Seq, measure the abundance of every exon in a gene. Compared with gene expression profiling technologies like 3' array, exon expression profiling technologies could detect alterations in both transcription and alternative splicing, therefore they are expected to be more sensitive in diagnosis. However, exon expression profiling also brings higher dimension, more redundancy, and significant correlation among features. Ignoring the correlation structure among exons of a gene, a popular classification method like L1-SVM selects exons individually from each gene and thus is vulnerable to noise. To overcome this limitation, we present in this paper a new variant of SVM named Lex-SVM to incorporate correlation structure among exons and known splicing patterns to promote classification performance. Specifically, we construct a new norm, ex-norm, including our prior knowledge on exon correlation structure to regularize the coefficients of a linear SVM. Lex-SVM can be solved efficiently using standard linear programming techniques. The advantage of Lex-SVM is that it can select features group-wisely, force features in a subgroup to take equal weihts and exclude the features that contradict the majority in the subgroup. Experimental results suggest that on exon expression profile, Lex-SVM is more accurate than existing methods. Lex-SVM also generates a more compact model and selects genes more consistently in cross-validation. Unlike L1-SVM selecting only one exon in a gene, Lex-SVM assigns equal weights to as many exons in a gene as possible, lending itself easier for further interpretation.

Regulation and Gene Expression Profiling of NKG2D Positive Human Cytomegalovirus-Primed CD4+ T-Cells

PubMed Central

Jensen, Helle; Folkersen, Lasse; Skov, Søren

2012-01-01

NKG2D is a stimulatory receptor expressed by natural killer (NK) cells, CD8+ T-cells, and γδ T-cells. NKG2D expression is normally absent from CD4+ T-cells, however recently a subset of NKG2D+ CD4+ T-cells has been found, which is specific for human cytomegalovirus (HCMV). This particular subset of HCMV-specific NKG2D+ CD4+ T-cells possesses effector-like functions, thus resembling the subsets of NKG2D+ CD4+ T-cells found in other chronic inflammations. However, the precise mechanism leading to NKG2D expression on HCMV-specific CD4+ T-cells is currently not known. In this study we used genome-wide analysis of individual genes and gene set enrichment analysis (GSEA) to investigate the gene expression profile of NKG2D+ CD4+ T-cells, generated from HCMV-primed CD4+ T-cells. We show that the HCMV-primed NKG2D+ CD4+ T-cells possess a higher differentiated phenotype than the NKG2D– CD4+ T-cells, both at the gene expression profile and cytokine profile. The ability to express NKG2D at the cell surface was primarily determined by the activation or differentiation status of the CD4+ T-cells and not by the antigen presenting cells. We observed a correlation between CD94 and NKG2D expression in the CD4+ T-cells following HCMV stimulation. However, knock-down of CD94 did not affect NKG2D cell surface expression or signaling. In addition, we show that NKG2D is recycled at the cell surface of activated CD4+ T-cells, whereas it is produced de novo in resting CD4+ T-cells. These findings provide novel information about the gene expression profile of HCMV-primed NKG2D+ CD4+ T-cells, as well as the mechanisms regulating NKG2D cell surface expression. PMID:22870231

Regulation and gene expression profiling of NKG2D positive human cytomegalovirus-primed CD4+ T-cells.

PubMed

Jensen, Helle; Folkersen, Lasse; Skov, Søren

2012-01-01

NKG2D is a stimulatory receptor expressed by natural killer (NK) cells, CD8(+) T-cells, and γδ T-cells. NKG2D expression is normally absent from CD4(+) T-cells, however recently a subset of NKG2D(+) CD4(+) T-cells has been found, which is specific for human cytomegalovirus (HCMV). This particular subset of HCMV-specific NKG2D(+) CD4(+) T-cells possesses effector-like functions, thus resembling the subsets of NKG2D(+) CD4(+) T-cells found in other chronic inflammations. However, the precise mechanism leading to NKG2D expression on HCMV-specific CD4(+) T-cells is currently not known. In this study we used genome-wide analysis of individual genes and gene set enrichment analysis (GSEA) to investigate the gene expression profile of NKG2D(+) CD4(+) T-cells, generated from HCMV-primed CD4(+) T-cells. We show that the HCMV-primed NKG2D(+) CD4(+) T-cells possess a higher differentiated phenotype than the NKG2D(-) CD4(+) T-cells, both at the gene expression profile and cytokine profile. The ability to express NKG2D at the cell surface was primarily determined by the activation or differentiation status of the CD4(+) T-cells and not by the antigen presenting cells. We observed a correlation between CD94 and NKG2D expression in the CD4(+) T-cells following HCMV stimulation. However, knock-down of CD94 did not affect NKG2D cell surface expression or signaling. In addition, we show that NKG2D is recycled at the cell surface of activated CD4(+) T-cells, whereas it is produced de novo in resting CD4(+) T-cells. These findings provide novel information about the gene expression profile of HCMV-primed NKG2D(+) CD4(+) T-cells, as well as the mechanisms regulating NKG2D cell surface expression.

Microarray Meta-Analysis Identifies Acute Lung Injury Biomarkers in Donor Lungs That Predict Development of Primary Graft Failure in Recipients

PubMed Central

Haitsma, Jack J.; Furmli, Suleiman; Masoom, Hussain; Liu, Mingyao; Imai, Yumiko; Slutsky, Arthur S.; Beyene, Joseph; Greenwood, Celia M. T.; dos Santos, Claudia

2012-01-01

Objectives To perform a meta-analysis of gene expression microarray data from animal studies of lung injury, and to identify an injury-specific gene expression signature capable of predicting the development of lung injury in humans. Methods We performed a microarray meta-analysis using 77 microarray chips across six platforms, two species and different animal lung injury models exposed to lung injury with or/and without mechanical ventilation. Individual gene chips were classified and grouped based on the strategy used to induce lung injury. Effect size (change in gene expression) was calculated between non-injurious and injurious conditions comparing two main strategies to pool chips: (1) one-hit and (2) two-hit lung injury models. A random effects model was used to integrate individual effect sizes calculated from each experiment. Classification models were built using the gene expression signatures generated by the meta-analysis to predict the development of lung injury in human lung transplant recipients. Results Two injury-specific lists of differentially expressed genes generated from our meta-analysis of lung injury models were validated using external data sets and prospective data from animal models of ventilator-induced lung injury (VILI). Pathway analysis of gene sets revealed that both new and previously implicated VILI-related pathways are enriched with differentially regulated genes. Classification model based on gene expression signatures identified in animal models of lung injury predicted development of primary graft failure (PGF) in lung transplant recipients with larger than 80% accuracy based upon injury profiles from transplant donors. We also found that better classifier performance can be achieved by using meta-analysis to identify differentially-expressed genes than using single study-based differential analysis. Conclusion Taken together, our data suggests that microarray analysis of gene expression data allows for the detection of “injury" gene predictors that can classify lung injury samples and identify patients at risk for clinically relevant lung injury complications. PMID:23071521

Microarray‑based bioinformatics analysis of the prospective target gene network of key miRNAs influenced by long non‑coding RNA PVT1 in HCC.

PubMed

Zhang, Yu; Mo, Wei-Jia; Wang, Xiao; Zhang, Tong-Tong; Qin, Yuan; Wang, Han-Lin; Chen, Gang; Wei, Dan-Ming; Dang, Yi-Wu

2018-05-02

The long non‑coding RNA (lncRNA) PVT1 plays vital roles in the tumorigenesis and development of various types of cancer. However, the potential expression profiling, functions and pathways of PVT1 in HCC remain unknown. PVT1 was knocked down in SMMC‑7721 cells, and a miRNA microarray analysis was performed to detect the differentially expressed miRNAs. Twelve target prediction algorithms were used to predict the underlying targets of these differentially expressed miRNAs. Bioinformatics analysis was performed to explore the underlying functions, pathways and networks of the targeted genes. Furthermore, the relationship between PVT1 and the clinical parameters in HCC was confirmed based on the original data in the TCGA database. Among the differentially expressed miRNAs, the top two upregulated and downregulated miRNAs were selected for further analysis based on the false discovery rate (FDR), fold‑change (FC) and P‑values. Based on the TCGA database, PVT1 was obviously highly expressed in HCC, and a statistically higher PVT1 expression was found for sex (male), ethnicity (Asian) and pathological grade (G3+G4) compared to the control groups (P<0.05). Furthermore, Gene Ontology (GO) analysis revealed that the target genes were involved in complex cellular pathways, such as the macromolecule biosynthetic process, compound metabolic process, and transcription. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the MAPK and Wnt signaling pathways may be correlated with the regulation of the four candidate miRNAs. The results therefore provide significant information on the differentially expressed miRNAs associated with PVT1 in HCC, and we hypothesized that PVT1 may play vital roles in HCC by regulating different miRNAs or target gene expression (particularly MAPK8) via the MAPK or Wnt signaling pathways. Thus, further investigation of the molecular mechanism of PVT1 in HCC is needed.

Multicenter prospective evaluation of the express view reading mode for small-bowel capsule endoscopy studies.

PubMed

Saurin, Jean-Christophe; Jacob, Philippe; Heyries, Laurent; Pesanti, Christian; Cholet, Franck; Fassler, Isaac; Boulant, James; Bramli, Slim; De Leusse, Antoin; Rahmi, Gabriel

2018-05-01

 Reducing the reading time of capsule endoscopy films is of high priority for gastroenterologists. We report a prospective multicenter evaluation of an "express view" reading mode (Intromedic capsule system).  Eighty-three patients with obscure gastrointestinal bleeding were prospectively included in 10 centers. All patients underwent small-bowel capsule endoscopy (Intromedic, Seoul, Republic of Korea). Films were read in standard mode, then a second reading was performed in express view mode at a second center. For each lesion, the precise location, nature, and relevance were collected. A consensus reading and review were done by three experts, and considered to be the gold standard.  The mean reading time of capsule films was 39.7 minutes (11 - 180 minutes) and 19.7 minutes (4 - 40 minutes) by standard and express view mode, respectively ( P  < 1 × 10  - 4 ). The consensus review identified a significant lesion in 44/83 patients (53.0 %). Standard reading and express view reading had a 93.3 % and 82.2 % sensitivity, respectively (NS). Consensus review identified 70 significant images from which standard reading and express view reading detected 58 (82.9 %) and 55 (78.6 %), respectively. The informatics algorithm detected 66/70 images (94.3 %) thus missing four small-bowel angiodysplasia.  The express view algorithm allows an important shortening of Intromedic capsule film reading time with a high sensitivity.

CHANGES IN GENE EXPRESSION PROFILE FOLLOWING SHORT-TERM EXPOSURE TO AN ENVIRONMENTALLY RELEVANT MIXTURE OF PHAHS

EPA Science Inventory

Changes in gene expression profile following short-term exposure to an environmentally relevant mixture of PHAHs
Polyhalogenated aromatic hydrocarbons (PHAH) including, polychlorinated biphenyls (PCBs), polychlorinated dibenzodioxins (PCDDS) and polychlorinated dibenzofurans...

The changes of gene expression profiling between segmental vitiligo, generalized vitiligo and healthy individual.

PubMed

Wang, Ping; Li, Yong; Nie, Huiqiong; Zhang, Xiaoyan; Shao, Qiongyan; Hou, Xiuli; Xu, Wen; Hong, Weisong; Xu, Aie

2016-10-01

Vitiligo is a common acquired depigmentation skin disease characterized by loss or dysfunction of melanocytes within the skin lesion, but its pathologenesis is far from lucid. The gene expression profiling of segmental vitiligo (SV) and generalized vitiligo (GV) need further investigation. To better understanding the common and distinct factors, especially in the view of gene expression profile, which were involved in the diseases development and maintenance of segmental vitiligo (SV) and generalized vitiligo (GV). Peripheral bloods were collected from SV, GV and healthy individual (HI), followed by leukocytes separation and total RNA extraction. The high-throughput whole genome expression microarrays were used to assay the gene expression profiles between HI, SV and GV. Bioinformatics tools were employed to annotated the biological function of differently expressed genes. Quantitative PCR assay was used to validate the gene expression of array. Compared to HI, 239 over-expressed genes and 175 down-expressed genes detected in SV, 688 over-expressed genes and 560 down-expressed genes were found in GV, following the criteria of log2 (fold change)≥0.585 and P value<0.05. In these differently expressed genes, 60 over-expressed genes and 60 down-expressed genes had similar tendency in SV and GV. Compared to SV, 223 genes were up regulated and 129 genes were down regulated in GV. In the SV with HI as control, the differently expressed genes were mainly involved in the adaptive immune response, cytokine-cytokine receptor interaction, chemokine signaling, focal adhesion and sphingolipid metabolism. The differently expressed genes between GV and HI were mainly involved in the innate immune, autophagy, apoptosis, melanocyte biology, ubiquitin mediated proteolysis and tyrosine metabolism, which was different from SV. While the differently expressed genes between SV and GV were mainly involved in the metabolism pathway of purine, pyrimidine, glycolysis and sphingolipid. Above results suggested that they not only shared part bio-process and signal pathway, but more important, they utilized different biological mechanism in their pathogenesis and maintenance. Our results provide a comprehensive view on the gene expression profiling change between SV and GV especially in the side of leukocytes, and may facilitate the future study on their molecular mechanism and theraputic targets. Copyright © 2016 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Diversity in the carotenoid profiles and the expression of genes related to carotenoid accumulation among citrus genotypes

PubMed Central

Ikoma, Yoshinori; Matsumoto, Hikaru; Kato, Masaya

2016-01-01

Carotenoids are not only important to the plants themselves but also are beneficial to human health. Since citrus fruit is a good source of carotenoids for the human diet, it is important to study carotenoid profiles and the accumulation mechanism in citrus fruit. Thus, in the present paper, we describe the diversity in the carotenoid profiles of fruit among citrus genotypes. In regard to carotenoids, such as β-cryptoxanthin, violaxanthin, lycopene, and β-citraurin, the relationship between the carotenoid profile and the expression of carotenoid-biosynthetic genes is discussed. Finally, recent results of quantitative trait locus (QTL) analyses of carotenoid contents and expression levels of carotenoid-biosynthetic genes in citrus fruit are shown. PMID:27069398

Performance Assessment of Kernel Density Clustering for Gene Expression Profile Data

PubMed Central

Zeng, Beiyan; Chen, Yiping P.; Smith, Oscar H.

2003-01-01

Kernel density smoothing techniques have been used in classification or supervised learning of gene expression profile (GEP) data, but their applications to clustering or unsupervised learning of those data have not been explored and assessed. Here we report a kernel density clustering method for analysing GEP data and compare its performance with the three most widely-used clustering methods: hierarchical clustering, K-means clustering, and multivariate mixture model-based clustering. Using several methods to measure agreement, between-cluster isolation, and withincluster coherence, such as the Adjusted Rand Index, the Pseudo F test, the r2 test, and the profile plot, we have assessed the effectiveness of kernel density clustering for recovering clusters, and its robustness against noise on clustering both simulated and real GEP data. Our results show that the kernel density clustering method has excellent performance in recovering clusters from simulated data and in grouping large real expression profile data sets into compact and well-isolated clusters, and that it is the most robust clustering method for analysing noisy expression profile data compared to the other three methods assessed. PMID:18629292

Integrative Analysis of Longitudinal Metabolomics Data from a Personal Multi-Omics Profile

PubMed Central

Stanberry, Larissa; Mias, George I.; Haynes, Winston; Higdon, Roger; Snyder, Michael; Kolker, Eugene

2013-01-01

The integrative personal omics profile (iPOP) is a pioneering study that combines genomics, transcriptomics, proteomics, metabolomics and autoantibody profiles from a single individual over a 14-month period. The observation period includes two episodes of viral infection: a human rhinovirus and a respiratory syncytial virus. The profile studies give an informative snapshot into the biological functioning of an organism. We hypothesize that pathway expression levels are associated with disease status. To test this hypothesis, we use biological pathways to integrate metabolomics and proteomics iPOP data. The approach computes the pathways’ differential expression levels at each time point, while taking into account the pathway structure and the longitudinal design. The resulting pathway levels show strong association with the disease status. Further, we identify temporal patterns in metabolite expression levels. The changes in metabolite expression levels also appear to be consistent with the disease status. The results of the integrative analysis suggest that changes in biological pathways may be used to predict and monitor the disease. The iPOP experimental design, data acquisition and analysis issues are discussed within the broader context of personal profiling. PMID:24958148

Decoherence in yeast cell populations and its implications for genome-wide expression noise.

PubMed

Briones, M R S; Bosco, F

2009-01-20

Gene expression "noise" is commonly defined as the stochastic variation of gene expression levels in different cells of the same population under identical growth conditions. Here, we tested whether this "noise" is amplified with time, as a consequence of decoherence in global gene expression profiles (genome-wide microarrays) of synchronized cells. The stochastic component of transcription causes fluctuations that tend to be amplified as time progresses, leading to a decay of correlations of expression profiles, in perfect analogy with elementary relaxation processes. Measuring decoherence, defined here as a decay in the auto-correlation function of yeast genome-wide expression profiles, we found a slowdown in the decay of correlations, opposite to what would be expected if, as in mixing systems, correlations decay exponentially as the equilibrium state is reached. Our results indicate that the populational variation in gene expression (noise) is a consequence of temporal decoherence, in which the slow decay of correlations is a signature of strong interdependence of the transcription dynamics of different genes.

Microarray evaluation of gene expression profiles in inflamed and healthy human dental pulp: the role of IL1beta and CD40 in pulp inflammation.

PubMed

Gatta, V; Zizzari, V L; Dd ' Amico, V; Salini, L; D' Aurora, M; Franchi, S; Antonucci, I; Sberna, M T; Gherlone, E; Stuppia, L; Tetè, S

2012-01-01

Dental pulp undergoes a number of changes passing from healthy status to inflammation due to deep decay. These changes are regulated by several genes resulting differently expressed in inflamed and healthy dental pulp, and the knowledge of the processes underlying this differential expression is of great relevance in the identification of the pathogenesis of the disease. In this study, the gene expression profile of inflamed and healthy dental pulps were compared by microarray analysis, and data obtained were analyzed by Ingenuity Pathway Analysis (IPA) software. This analysis allows to focus on a variety of genes, typically expressed in inflamed tissues. The comparison analysis showed an increased expression of several genes in inflamed pulp, among which IL1β and CD40 resulted of particular interest. These results indicate that gene expression profile of human dental pulp in different physiological and pathological conditions may become an useful tool for improving our knowledge about processes regulating pulp inflammation.

Neighboring Genes Show Correlated Evolution in Gene Expression

PubMed Central

Ghanbarian, Avazeh T.; Hurst, Laurence D.

2015-01-01

When considering the evolution of a gene’s expression profile, we commonly assume that this is unaffected by its genomic neighborhood. This is, however, in contrast to what we know about the lack of autonomy between neighboring genes in gene expression profiles in extant taxa. Indeed, in all eukaryotic genomes genes of similar expression-profile tend to cluster, reflecting chromatin level dynamics. Does it follow that if a gene increases expression in a particular lineage then the genomic neighbors will also increase in their expression or is gene expression evolution autonomous? To address this here we consider evolution of human gene expression since the human-chimp common ancestor, allowing for both variation in estimation of current expression level and error in Bayesian estimation of the ancestral state. We find that in all tissues and both sexes, the change in gene expression of a focal gene on average predicts the change in gene expression of neighbors. The effect is highly pronounced in the immediate vicinity (<100 kb) but extends much further. Sex-specific expression change is also genomically clustered. As genes increasing their expression in humans tend to avoid nuclear lamina domains and be enriched for the gene activator 5-hydroxymethylcytosine, we conclude that, most probably owing to chromatin level control of gene expression, a change in gene expression of one gene likely affects the expression evolution of neighbors, what we term expression piggybacking, an analog of hitchhiking. PMID:25743543

Alteration of the gene expression profile of T-cell receptor αβ-modified T-cells with diffuse large B-cell lymphoma specificity.

PubMed

Zha, Xianfeng; Yin, Qingsong; Tan, Huo; Wang, Chunyan; Chen, Shaohua; Yang, Lijian; Li, Bo; Wu, Xiuli; Li, Yangqiu

2013-05-01

Antigen-specific, T-cell receptor (TCR)-modified cytotoxic T lymphocytes (CTLs) that target tumors are an attractive strategy for specific adoptive immunotherapy. Little is known about whether there are any alterations in the gene expression profile after TCR gene transduction in T cells. We constructed TCR gene-redirected CTLs with specificity for diffuse large B-cell lymphoma (DLBCL)-associated antigens to elucidate the gene expression profiles of TCR gene-redirected T-cells, and we further analyzed the gene expression profile pattern of these redirected T-cells by Affymetrix microarrays. The resulting data were analyzed using Bioconductor software, a two-fold cut-off expression change was applied together with anti-correlation of the profile ratios to render the microarray analysis set. The fold change of all genes was calculated by comparing the three TCR gene-modified T-cells and a negative control counterpart. The gene pathways were analyzed using Bioconductor and Kyoto Encyclopedia of Genes and Genomes. Identical genes whose fold change was greater than or equal to 2.0 in all three TCR gene-redirected T-cell groups in comparison with the negative control were identified as the differentially expressed genes. The differentially expressed genes were comprised of 33 up-regulated genes and 1 down-regulated gene including JUNB, FOS, TNF, INF-γ, DUSP2, IL-1B, CXCL1, CXCL2, CXCL9, CCL2, CCL4, and CCL8. These genes are mainly involved in the TCR signaling, mitogen-activated protein kinase signaling, and cytokine-cytokine receptor interaction pathways. In conclusion, we characterized the gene expression profile of DLBCL-specific TCR gene-redirected T-cells. The changes corresponded to an up-regulation in the differentiation and proliferation of the T-cells. These data may help to explain some of the characteristics of the redirected T-cells.

Global Gene Expression Profiling of the Asymptomatic Bacteriuria Escherichia coli Strain 83972 in the Human Urinary Tract†

PubMed Central

Roos, Viktoria; Klemm, Per

2006-01-01

Urinary tract infections (UTIs) are an important health problem worldwide, with many million cases each year. Escherichia coli is the most common organism causing UTIs in humans. The asymptomatic bacteriuria E. coli strain 83972 is an excellent colonizer of the human urinary tract, where it causes long-term bladder colonization. The strain has been used for prophylactic purposes in patients prone to more severe and recurrent UTIs. For this study, we used DNA microarrays to monitor the expression profile of strain 83972 in the human urinary tract. Significant differences in expression levels were seen between the in vivo expression profiles of strain 83972 in three patients and the corresponding in vitro expression profiles in lab medium and human urine. The data revealed an in vivo lifestyle of microaerobic growth with respiration of nitrate coupled to degradation of sugar acids and amino acids, with no signs of attachment to host tissues. Interestingly, genes involved in NO protection and metabolism showed significant up-regulation in the patients. This is one of the first studies to address bacterial whole-genome expression in humans and the first study to investigate global gene expression of an E. coli strain in the human urinary tract. PMID:16714589

Comparing cancer vs normal gene expression profiles identifies new disease entities and common transcriptional programs in AML patients.

PubMed

Rapin, Nicolas; Bagger, Frederik Otzen; Jendholm, Johan; Mora-Jensen, Helena; Krogh, Anders; Kohlmann, Alexander; Thiede, Christian; Borregaard, Niels; Bullinger, Lars; Winther, Ole; Theilgaard-Mönch, Kim; Porse, Bo T

2014-02-06

Gene expression profiling has been used extensively to characterize cancer, identify novel subtypes, and improve patient stratification. However, it has largely failed to identify transcriptional programs that differ between cancer and corresponding normal cells and has not been efficient in identifying expression changes fundamental to disease etiology. Here we present a method that facilitates the comparison of any cancer sample to its nearest normal cellular counterpart, using acute myeloid leukemia (AML) as a model. We first generated a gene expression-based landscape of the normal hematopoietic hierarchy, using expression profiles from normal stem/progenitor cells, and next mapped the AML patient samples to this landscape. This allowed us to identify the closest normal counterpart of individual AML samples and determine gene expression changes between cancer and normal. We find the cancer vs normal method (CvN method) to be superior to conventional methods in stratifying AML patients with aberrant karyotype and in identifying common aberrant transcriptional programs with potential importance for AML etiology. Moreover, the CvN method uncovered a novel poor-outcome subtype of normal-karyotype AML, which allowed for the generation of a highly prognostic survival signature. Collectively, our CvN method holds great potential as a tool for the analysis of gene expression profiles of cancer patients.

Mesothelium expression of vascular cell adhesion molecule-1 (VCAM-1) is associated with an unfavorable prognosis in epithelial ovarian cancer (EOC).

PubMed

Scalici, Jennifer M; Arapovic, Sanja; Saks, Erin J; Atkins, Kristen A; Petroni, Gina; Duska, Linda R; Slack-Davis, Jill K

2017-05-15

Mesothelium vascular cell adhesion molecule-1 (VCAM-1) expression in the metastatic epithelial ovarian cancer (EOC) microenvironment is induced by tumor and mediates tumor cell invasion. VCAM-1 imaging suggests expression during treatment is an indicator of platinum resistance. Here, we assess the potential prognostic significance of mesothelium VCAM-1 expression and prospectively evaluate whether soluble VCAM-1 (sVCAM-1) is a surrogate for mesothelium expression. A retrospective review of EOC patients was performed to evaluate outcomes with mesothelium VCAM-1 expression determined by immunohistochemistry of peritoneum or omentum specimens. A prospective cohort of EOC patients was identified and followed through primary treatment. Serum for sVCAM-1 evaluation, which was performed via enzyme-linked immunosorbent assay, was collected before surgery or neoadjuvant chemotherapy and at each treatment cycle. Peritoneal specimens were obtained during debulking to assess mesothelial VCAM-1 expression. A retrospective review identified 54 advanced-stage EOC patients. Patients expressing mesothelium VCAM-1 had shortened overall survival (44 vs 79 months, P = 0.035) and progression-free survival (18 vs 67 months, P = 0.010); the median time to platinum resistance was 36 months for VCAM-1-expressing patients and not yet determined for the VCAM-1-negative group. In our prospective observational cohort, 18 EOC patients completed primary treatment; 3 were negative for mesothelium VCAM-1 expression, and sVCAM-1 did not vary between groups. Mesothelium VCAM-1 expression is negatively associated with progression-free and overall survival in EOC. This is especially compelling in light of previous data suggesting that persistent VCAM-1 expression during treatment is an indicator of platinum resistance. Our pilot study had insufficient cases to determine whether sVCAM-1 would substitute for mesothelium expression. Cancer 2017;123:977-84. © 2016 American Cancer Society. © 2016 American Cancer Society.

A Prognostic Gene Expression Profile That Predicts Circulating Tumor Cell Presence in Breast Cancer Patients

PubMed Central

Molloy, Timothy J.; Roepman, Paul; Naume, Bjørn; van't Veer, Laura J.

2012-01-01

The detection of circulating tumor cells (CTCs) in the peripheral blood and microarray gene expression profiling of the primary tumor are two promising new technologies able to provide valuable prognostic data for patients with breast cancer. Meta-analyses of several established prognostic breast cancer gene expression profiles in large patient cohorts have demonstrated that despite sharing few genes, their delineation of patients into “good prognosis” or “poor prognosis” are frequently very highly correlated, and combining prognostic profiles does not increase prognostic power. In the current study, we aimed to develop a novel profile which provided independent prognostic data by building a signature predictive of CTC status rather than outcome. Microarray gene expression data from an initial training cohort of 72 breast cancer patients for which CTC status had been determined in a previous study using a multimarker QPCR-based assay was used to develop a CTC-predictive profile. The generated profile was validated in two independent datasets of 49 and 123 patients and confirmed to be both predictive of CTC status, and independently prognostic. Importantly, the “CTC profile” also provided prognostic information independent of the well-established and powerful ‘70-gene’ prognostic breast cancer signature. This profile therefore has the potential to not only add prognostic information to currently-available microarray tests but in some circumstances even replace blood-based prognostic CTC tests at time of diagnosis for those patients already undergoing testing by multigene assays. PMID:22384245

Microarray profiling of gene expression in human adipocytes in response to anthocyanins.

PubMed

Tsuda, Takanori; Ueno, Yuki; Yoshikawa, Toshikazu; Kojo, Hitoshi; Osawa, Toshihiko

2006-04-14

Adipocyte dysfunction is strongly associated with the development of obesity and insulin resistance. It is accepted that the regulation of adipocytokine secretion or the adipocyte specific gene expression is one of the most important targets for the prevention of obesity and amelioration of insulin sensitivity. Recently, we demonstrated that anthocyanins, which are pigments widespread in the plant kingdom, have the potency of anti-obesity in mice and the enhancement adipocytokine secretion and its gene expression in adipocytes. In this study, we have shown the gene expression profile in human adipocytes treated with anthocyanins (cyanidin 3-glucoside; C3G or cyanidin; Cy). The human adipocytes were treated with 100 microM C3G, Cy or vehicle for 24 h. The total RNA from the adipocytes was isolated and carried out GeneChip microarray analysis. Based on the gene expression profile, we demonstrated the significant changes of adipocytokine expression (up-regulation of adiponectin and down-regulation of plasminogen activator inhibitor-1 and interleukin-6). Some of lipid metabolism related genes (uncoupling protein2, acylCoA oxidase1 and perilipin) also significantly induced in both common the C3G or Cy treatment groups. These studies have provided an overview of the gene expression profiles in human adipocytes treated with anthocyanins and demonstrated that anthocyanins can regulate adipocytokine gene expression to ameliorate adipocyte function related with obesity and diabetes that merit further investigation.

Developmental transcriptional profiling reveals key insights into Triticeae reproductive development.

PubMed

Tran, Frances; Penniket, Carolyn; Patel, Rohan V; Provart, Nicholas J; Laroche, André; Rowland, Owen; Robert, Laurian S

2013-06-01

Despite their importance, there remains a paucity of large-scale gene expression-based studies of reproductive development in species belonging to the Triticeae. As a first step to address this deficiency, a gene expression atlas of triticale reproductive development was generated using the 55K Affymetrix GeneChip(®) wheat genome array. The global transcriptional profiles of the anther/pollen, ovary and stigma were analyzed at concurrent developmental stages, and co-expressed as well as preferentially expressed genes were identified. Data analysis revealed both novel and conserved regulatory factors underlying Triticeae floral development and function. This comprehensive resource rests upon detailed gene annotations, and the expression profiles are readily accessible via a web browser. © 2013 Her Majesty the Queen in Right of Canada as represented by the Minister of Agriculture and Agri-Food Canada.

Impact of Profiling Technologies in the Understanding of Recombinant Protein Production

NASA Astrophysics Data System (ADS)

Vijayendran, Chandran; Flaschel, Erwin

Since expression profiling methods have been available in a high throughput fashion, the implication of these technologies in the field of biotechnology has increased dramatically. Microarray technology is one such unique and efficient methodology for simultaneous exploration of expression levels of numerous genes. Likewise, two-dimensional gel electrophoresis or multidimensional liquid chromatography coupled with mass spectrometry are extensively utilised for studying expression levels of numerous proteins. In the field of biotechnology these highly parallel analytical methods have paved the way to study and understand various biological phenomena depending on expression patterns. The next phenomenological level is represented by the metabolome and the (metabolic) fluxome. However, this chapter reviews gene and protein profiling and their impact on understanding recombinant protein production. We focus on the computational methods utilised for the analyses of data obtained from these profiling technologies as well as prominent results focusing on recombinant protein expression with Escherichia coli. Owing to the knowledge accumulated with respect to cellular signals triggered during recombinant protein production, this field is on the way to design strategies for developing improved processes. Both gene and protein profiling have exhibited a handful of functional categories to concentrate on in order to identify target genes and proteins, respectively, involved in the signalling network with major impact on recombinant protein production.

Lung tumor diagnosis and subtype discovery by gene expression profiling.

PubMed

Wang, Lu-yong; Tu, Zhuowen

2006-01-01

The optimal treatment of patients with complex diseases, such as cancers, depends on the accurate diagnosis by using a combination of clinical and histopathological data. In many scenarios, it becomes tremendously difficult because of the limitations in clinical presentation and histopathology. To accurate diagnose complex diseases, the molecular classification based on gene or protein expression profiles are indispensable for modern medicine. Moreover, many heterogeneous diseases consist of various potential subtypes in molecular basis and differ remarkably in their response to therapies. It is critical to accurate predict subgroup on disease gene expression profiles. More fundamental knowledge of the molecular basis and classification of disease could aid in the prediction of patient outcome, the informed selection of therapies, and identification of novel molecular targets for therapy. In this paper, we propose a new disease diagnostic method, probabilistic boosting tree (PB tree) method, on gene expression profiles of lung tumors. It enables accurate disease classification and subtype discovery in disease. It automatically constructs a tree in which each node combines a number of weak classifiers into a strong classifier. Also, subtype discovery is naturally embedded in the learning process. Our algorithm achieves excellent diagnostic performance, and meanwhile it is capable of detecting the disease subtype based on gene expression profile.

mRNA Expression Profiling of Laser Microbeam Microdissected Cells from Slender Embryonic Structures

PubMed Central

Scheidl, Stefan J.; Nilsson, Sven; Kalén, Mattias; Hellström, Mats; Takemoto, Minoru; Håkansson, Joakim; Lindahl, Per

2002-01-01

Microarray hybridization has rapidly evolved as an important tool for genomic studies and studies of gene regulation at the transcriptome level. Expression profiles from homogenous samples such as yeast and mammalian cell cultures are currently extending our understanding of biology, whereas analyses of multicellular organisms are more difficult because of tissue complexity. The combination of laser microdissection, RNA amplification, and microarray hybridization has the potential to provide expression profiles from selected populations of cells in vivo. In this article, we present and evaluate an experimental procedure for global gene expression analysis of slender embryonic structures using laser microbeam microdissection and laser pressure catapulting. As a proof of principle, expression profiles from 1000 cells in the mouse embryonic (E9.5) dorsal aorta were generated and compared with profiles for captured mesenchymal cells located one cell diameter further away from the aortic lumen. A number of genes were overexpressed in the aorta, including 11 previously known markers for blood vessels. Among the blood vessel markers were endoglin, tie-2, PDGFB, and integrin-β1, that are important regulators of blood vessel formation. This demonstrates that microarray analysis of laser microbeam micro-dissected cells is sufficiently sensitive for identifying genes with regulative functions. PMID:11891179

Mechanistic and Structural Analysis of Drosophila melanogaster Arylalkylamine N-Acetyltransferases

PubMed Central

2015-01-01

Arylalkylamine N-acetyltransferase (AANAT) catalyzes the penultimate step in the biosynthesis of melatonin and other N-acetylarylalkylamides from the corresponding arylalkylamine and acetyl-CoA. The N-acetylation of arylalkylamines is a critical step in Drosophila melanogaster for the inactivation of the bioactive amines and the sclerotization of the cuticle. Two AANAT variants (AANATA and AANATB) have been identified in D. melanogaster, in which AANATA differs from AANATB by the truncation of 35 amino acids from the N-terminus. We have expressed and purified both D. melanogaster AANAT variants (AANATA and AANATB) in Escherichia coli and used the purified enzymes to demonstrate that this N-terminal truncation does not affect the activity of the enzyme. Subsequent characterization of the kinetic and chemical mechanism of AANATA identified an ordered sequential mechanism, with acetyl-CoA binding first, followed by tyramine. We used a combination of pH–activity profiling and site-directed mutagenesis to study prospective residues believed to function in AANATA catalysis. These data led to an assignment of Glu-47 as the general base in catalysis with an apparent pKa of 7.0. Using the data generated for the kinetic mechanism, structure–function relationships, pH–rate profiles, and site-directed mutagenesis, we propose a chemical mechanism for AANATA. PMID:25406072

Personalized RNA Medicine for Pancreatic Cancer.

PubMed

Gilles, Maud-Emmanuelle; Hao, Liangliang; Huang, Ling; Rupaimoole, Rajesha; Lopez-Casas, Pedro P; Pulver, Emilia; Jeong, Jong Cheol; Muthuswamy, Senthil K; Hidalgo, Manuel; Bhatia, Sangeeta N; Slack, Frank J

2018-04-01

Purpose: Since drug responses vary between patients, it is crucial to develop pre-clinical or co-clinical strategies that forecast patient response. In this study, we tested whether RNA-based therapeutics were suitable for personalized medicine by using patient-derived-organoid (PDO) and patient-derived-xenograft (PDX) models. Experimental Design: We performed microRNA (miRNA) profiling of PDX samples to determine the status of miRNA deregulation in individual pancreatic ductal adenocarcinoma (PDAC) patients. To deliver personalized RNA-based-therapy targeting oncogenic miRNAs that form part of this common PDAC miRNA over-expression signature, we packaged antimiR oligonucleotides against one of these miRNAs in tumor-penetrating nanocomplexes (TPN) targeting cell surface proteins on PDAC tumors. Results: As a validation for our pre-clinical strategy, the therapeutic potential of one of our nano-drugs, TPN-21, was first shown to decrease tumor cell growth and survival in PDO avatars for individual patients, then in their PDX avatars. Conclusions: This general approach appears suitable for co-clinical validation of personalized RNA medicine and paves the way to prospectively identify patients with eligible miRNA profiles for personalized RNA-based therapy. Clin Cancer Res; 24(7); 1734-47. ©2018 AACR . ©2018 American Association for Cancer Research.

Comparative expression profile of NOD1/2 and certain acute inflammatory cytokines in thermal-stressed cell culture model of native and crossbred cattle

NASA Astrophysics Data System (ADS)

Bhanuprakash, V.; Singh, Umesh; Sengar, Gyanendra Singh; Raja, T. V.; Sajjanar, Basavraj; Alex, Rani; Kumar, Sushil; Alyethodi, R. R.; Kumar, Ashish; Sharma, Ankur; Kumar, Suresh; Bhusan, Bharat; Deb, Rajib

2017-05-01

Thermotolerance depends mainly on the health and immune status of the animals. The variation in the immune status of the animals may alter the level of tolerance of animals exposed to heat or cold stress. The present study was conducted to investigate the expression profile of two important nucleotide binding and oligomerization domain receptors (NLRs) (NOD1 and NOD2) and their central signalling molecule RIP2 gene during in vitro thermal-stressed bovine peripheral blood mononuclear cells (PBMCs) of native (Sahiwal) and crossbred (Sahiwal X HF) cattle. We also examined the differential expression profile of certain acute inflammatory cytokines in in vitro thermal-stressed PBMC culture among native and its crossbred counterparts. Results revealed that the expression profile of NOD1/2 positively correlates with the thermal stress, signalling molecule and cytokines. Present findings also highlighted that the expression patterns during thermal stress were comparatively superior among indigenous compared to crossbred cattle which may add references regarding the better immune adaptability of Zebu cattle.

Genomics of NSCLC patients both affirm PD-L1 expression and predict their clinical responses to anti-PD-1 immunotherapy.

PubMed

Brogden, Kim A; Parashar, Deepak; Hallier, Andrea R; Braun, Terry; Qian, Fang; Rizvi, Naiyer A; Bossler, Aaron D; Milhem, Mohammed M; Chan, Timothy A; Abbasi, Taher; Vali, Shireen

2018-02-27

Programmed Death Ligand 1 (PD-L1) is a co-stimulatory and immune checkpoint protein. PD-L1 expression in non-small cell lung cancers (NSCLC) is a hallmark of adaptive resistance and its expression is often used to predict the outcome of Programmed Death 1 (PD-1) and PD-L1 immunotherapy treatments. However, clinical benefits do not occur in all patients and new approaches are needed to assist in selecting patients for PD-1 or PD-L1 immunotherapies. Here, we hypothesized that patient tumor cell genomics influenced cell signaling and expression of PD-L1, chemokines, and immunosuppressive molecules and these profiles could be used to predict patient clinical responses. We used a recent dataset from NSCLC patients treated with pembrolizumab. Deleterious gene mutational profiles in patient exomes were identified and annotated into a cancer network to create NSCLC patient-specific predictive computational simulation models. Validation checks were performed on the cancer network, simulation model predictions, and PD-1 match rates between patient-specific predicted and clinical responses. Expression profiles of these 24 chemokines and immunosuppressive molecules were used to identify patients who would or would not respond to PD-1 immunotherapy. PD-L1 expression alone was not sufficient to predict which patients would or would not respond to PD-1 immunotherapy. Adding chemokine and immunosuppressive molecule expression profiles allowed patient models to achieve a greater than 85.0% predictive correlation among predicted and reported patient clinical responses. Our results suggested that chemokine and immunosuppressive molecule expression profiles can be used to accurately predict clinical responses thus differentiating among patients who would and would not benefit from PD-1 or PD-L1 immunotherapies.

Differential chemokine, chemokine receptor and cytokine expression in Epstein-Barr virus-associated lymphoproliferative diseases.

PubMed

Ohshima, Koichi; Karube, Kennosuke; Hamasaki, Makoto; Tutiya, Takeshi; Yamaguchi, Takahiro; Suefuji, Hiroaki; Suzuki, Keiko; Suzumiya, Junji; Ohga, Shouichi; Kikuchi, Masahiro

2003-08-01

T cell immunity plays an important role in the clinicopathology of Epstein-Barr virus (EBV)-associated diseases. Acute EBV-induced infectious mononucleosis (IM) is a common self-limiting disease, however, other EBV-associated diseases, including chronic active EBV infection (CAEBV), NK cell lymphoma (NKL), and Hodgkin's lymphoma (HL), exhibit distinct clinical features. Chemokines are members of a family of small-secreted proteins. The relationships between chemokines and the chemokine receptor (R) are thought to be important for selectivity of local immunity. Some chemokines, chemokine R and cytokines closely associate with the T cell subtypes, Th1 and Th2 T cells and cytotoxic cells. To clarify the role of T cell immunity in EBV-associated diseases, we conducted gene expression profiling, using chemokine, chemokine R and cytokine DNA chips. Compared to EBV negative non-specific lymphadenitis, CAEBV and NKL exhibited diffuse down- and up-regulation, respectively, of these gene profiles. IM had a predominantly Th1-type profile, whereas HL had a mixed Th1/Th2-type profile. Reduction of the Th1-type cytokine interferon gamma (IFN-gamma) in CAEBV was confirmed by Reverse transcriptase-polymerase chain reaction, whereas IFN-gamma expression was markedly enhanced in NKL, and moderately enhanced in IM. Compared to IM, CAEBV showed slight elevation of "regulated upon activation, normal T expressed and secreted" (RANTES), but almost all other genes assayed were down-regulated. NKL exhibited elevated expression of numerous genes, particularly IFN-gamma-inducible-10 (IP-10) and monokine induced by IFN-gamma (MIG). HL showed variable elevated and reduced expression of various genes, with increased expression of IL-13 receptor and MIG. Our study demonstrated the enormous potential of gene expression profiling for clarifying the pathogenesis of EBV-associated diseases.

Gene expression profiling in liver and testis of rats to characterize the toxicity of triazole fungicides.

PubMed

Tully, Douglas B; Bao, Wenjun; Goetz, Amber K; Blystone, Chad R; Ren, Hongzu; Schmid, Judith E; Strader, Lillian F; Wood, Carmen R; Best, Deborah S; Narotsky, Michael G; Wolf, Douglas C; Rockett, John C; Dix, David J

2006-09-15

Four triazole fungicides were studied using toxicogenomic techniques to identify potential mechanisms of action. Adult male Sprague-Dawley rats were dosed for 14 days by gavage with fluconazole, myclobutanil, propiconazole, or triadimefon. Following exposure, serum was collected for hormone measurements, and liver and testes were collected for histology, enzyme biochemistry, or gene expression profiling. Body and testis weights were unaffected, but liver weights were significantly increased by all four triazoles, and hepatocytes exhibited centrilobular hypertrophy. Myclobutanil exposure increased serum testosterone and decreased sperm motility, but no treatment-related testis histopathology was observed. We hypothesized that gene expression profiles would identify potential mechanisms of toxicity and used DNA microarrays and quantitative real-time PCR (qPCR) to generate profiles. Triazole fungicides are designed to inhibit fungal cytochrome P450 (CYP) 51 enzyme but can also modulate the expression and function of mammalian CYP genes and enzymes. Triazoles affected the expression of numerous CYP genes in rat liver and testis, including multiple Cyp2c and Cyp3a isoforms as well as other xenobiotic metabolizing enzyme (XME) and transporter genes. For some genes, such as Ces2 and Udpgtr2, all four triazoles had similar effects on expression, suggesting possible common mechanisms of action. Many of these CYP, XME and transporter genes are regulated by xeno-sensing nuclear receptors, and hierarchical clustering of CAR/PXR-regulated genes demonstrated the similarities of toxicogenomic responses in liver between all four triazoles and in testis between myclobutanil and triadimefon. Triazoles also affected expression of multiple genes involved in steroid hormone metabolism in the two tissues. Thus, gene expression profiles helped identify possible toxicological mechanisms of the triazole fungicides.

Alteration in gene expression profile and oncogenicity of esophageal squamous cell carcinoma by RIZ1 upregulation.

PubMed

Dong, Shang-Wen; Li, Dong; Xu, Cong; Sun, Pei; Wang, Yuan-Guo; Zhang, Peng

2013-10-07

To investigate the effect of retinoblastoma protein-interacting zinc finger gene 1 (RIZ1) upregulation in gene expression profile and oncogenicity of human esophageal squamous cell carcinoma (ESCC) cell line TE13. TE13 cells were transfected with pcDNA3.1(+)/RIZ1 and pcDNA3.1(+). Changes in gene expression profile were screened and the microarray results were confirmed by reverse transcription-polymerase chain reaction (RT-PCR). Nude mice were inoculated with TE13 cells to establish ESCC xenografts. After two weeks, the inoculated mice were randomly divided into three groups. Tumors were injected with normal saline, transfection reagent pcDNA3.1(+) and transfection reagent pcDNA3.1(+)/RIZ1, respectively. Tumor development was quantified, and changes in gene expression of RIZ1 transfected tumors were detected by RT-PCR and Western blotting. DNA microarray data showed that RIZ1 transfection induced widespread changes in gene expression profile of cell line TE13, with 960 genes upregulated and 1163 downregulated. Treatment of tumor xenografts with RIZ1 recombinant plasmid significantly inhibited tumor growth, decreased tumor size, and increased expression of RIZ1 mRNA compared to control groups. The changes in gene expression profile were also observed in vivo after RIZ1 transfection. Most of the differentially expressed genes were associated with cell development, supervision of viral replication, lymphocyte costimulatory and immune system development in esophageal cells. RIZ1 gene may be involved in multiple cancer pathways, such as cytokine receptor interaction and transforming growth factor beta signaling. The development and progression of esophageal cancer are related to the inactivation of RIZ1. Virus infection may also be an important factor.

Understanding of Prospective Physics Teachers Students Toward Pedagogical Content Knowledge on Optical Geometry Materials

NASA Astrophysics Data System (ADS)

Erwin, E.; Rustaman, N. Y.

2017-09-01

This article discusses about Pedagogical content knowledge (PCK) profile of prospective physics teachers on optical geometry materials. Data collected using interview and questionnaire, and the data were analyzed descriptively. The results showed that PCK is an unfamiliar term to students. The extreme findings in this study is the lack of understanding of PCK by prospective physics teachers relating to the importance of recognizing the characteristics of students and how to manage questions from students, which teacher has to directly answer questions from students, and how to respond to the students’ incorrect answer, mostly prospective physics teachers assume that in case of the students answer incorrectly, the students should be directly blamed. Prospective physics teachers have not yet integrated the pedagogical knowledge with the content knowledge in their possess learning it he optical geometry material.

[Preliminary analysis of retinal gene expression profile of diabetic rat].

PubMed

Mei, Yan; Zhou, Hong-ying; Xiang, Tao; Lu, You-guang; Li, Ai-dong; Tang, En-jie; Yang, Hui-jun

2005-10-01

Establishing the retinal gene expression profiles of non-diabetic rat and diabetic rat and comparing the profiles in order to analyze the possible genes related with diabetic retinopathy. The whole retinal transcriptional fragments of non-diabetic rat and 8-week diabetic rat were obtained by restriction fragments differential display-PCR (RFDD-PCR). Bioinformatic analysis of retinal gene expression was performed using soft wares, including Fragment Analysis. After comparison of the expression profiles, the related gene fragments of diabetic retinopathy were initially selected as the target gene of further approach. A total of 3639 significant fragments were obtained. By means of more than 3-fold contrast of fluorescent intensity as the differential expression standard, the authors got 840 differential fragments, accounting for 23.08% of the expressed numbers and including 5 visual related genes, 13 excitatory neruotransmitter genes and 3 inhibitory neurotransmitter genes. At the 8th week, the expression of Rhodopsin kinase, beta-arrestin, Phosducinìrod photoreceptor cGMP-gated channel and Rpe65 as well as iGlu R1-4 were down-regulated. mGluRs and GABA-Rs were all up-regulated, whereas the expression of GlyR was unchanged. These results prompt again that the changes in retinal nervous layer of rat have occurred at an early stage of diabetes. The genes expression pattern of visual related genes and excitatory and inhibitory neurotransmitters in rat diabetic retina have been involved in neuro-dysfunctions of diabetic retina.

Changes in gene expression associated with response to neoadjuvant chemotherapy in breast cancer.

PubMed

Hannemann, Juliane; Oosterkamp, Hendrika M; Bosch, Cathy A J; Velds, Arno; Wessels, Lodewyk F A; Loo, Claudette; Rutgers, Emiel J; Rodenhuis, Sjoerd; van de Vijver, Marc J

2005-05-20

At present, clinically useful markers predicting response of primary breast carcinomas to either doxorubicin-cyclophosphamide (AC) or doxorubicin-docetaxel (AD) are lacking. We investigated whether gene expression profiles of the primary tumor could be used to predict treatment response to either of those chemotherapy regimens. Within a single-institution, randomized, phase II trial, patients with locally advanced breast cancer received six courses of either AC (n = 24) or AD (n = 24) neoadjuvant chemotherapy. Gene expression profiles were generated from core-needle biopsies obtained before treatment and correlated with the response of the primary tumor to the chemotherapy administered. Additionally, pretreatment gene expression profiles were compared with those in tumors remaining after chemotherapy. Ten (20%) of 48 patients showed a (near) pathologic complete remission of the primary tumor after treatment. No gene expression pattern correlating with response could be identified for all patients or for the AC or AD groups separately. The comparison of the pretreatment biopsy and the tumor excised after chemotherapy revealed differences in gene expression in tumors that showed a partial remission but not in tumors that did not respond to chemotherapy. No gene expression profile predicting the response of primary breast carcinomas to AC- or AD-based neoadjuvant chemotherapy could be detected in this interim analysis. More subtle differences in gene expression are likely to be present but can only be reliably identified by studying a larger group of patients. Response of a breast tumor to neoadjuvant chemotherapy results in alterations in gene expression.

Clinical Application of Prognostic Gene Expression Signature in Fusion Gene-Negative Rhabdomyosarcoma: A Report from the Children's Oncology Group.

PubMed

Hingorani, Pooja; Missiaglia, Edoardo; Shipley, Janet; Anderson, James R; Triche, Timothy J; Delorenzi, Mauro; Gastier-Foster, Julie; Wing, Michele; Hawkins, Douglas S; Skapek, Stephen X

2015-10-15

Pediatric rhabdomyosarcoma (RMS) has two common histologic subtypes: embryonal (ERMS) and alveolar (ARMS). PAX-FOXO1 fusion gene status is a more reliable prognostic marker than alveolar histology, whereas fusion gene-negative (FN) ARMS patients are clinically similar to ERMS patients. A five-gene expression signature (MG5) previously identified two diverse risk groups within the fusion gene-negative RMS (FN-RMS) patients, but this has not been independently validated. The goal of this study was to test whether expression of the MG5 metagene, measured using a technical platform that can be applied to routine pathology material, would correlate with outcome in a new cohort of patients with FN-RMS. Cases were taken from the Children's Oncology Group (COG) D9803 study of children with intermediate-risk RMS, and gene expression profiling for the MG5 genes was performed using the nCounter assay. The MG5 score was correlated with clinical and pathologic characteristics as well as overall and event-free survival. MG5 standardized score showed no significant association with any of the available clinicopathologic variables. The MG5 signature score showed a significant correlation with overall (N = 57; HR, 7.3; 95% CI, 1.9-27.0; P = 0.003) and failure-free survival (N = 57; HR, 6.1; 95% CI, 1.9-19.7; P = 0.002). This represents the first, validated molecular prognostic signature for children with FN-RMS who otherwise have intermediate-risk disease. The capacity to measure the expression of a small number of genes in routine pathology material and apply a simple mathematical formula to calculate the MG5 metagene score provides a clear path toward better risk stratification in future prospective clinical trials. ©2015 American Association for Cancer Research.

Metastatic canine mammary carcinomas can be identified by a gene expression profile that partly overlaps with human breast cancer profiles

PubMed Central

2010-01-01

Background Similar to human breast cancer mammary tumors of the female dog are commonly associated with a fatal outcome due to the development of distant metastases. However, the molecular defects leading to metastasis are largely unknown and the value of canine mammary carcinoma as a model for human breast cancer is unclear. In this study, we analyzed the gene expression signatures associated with mammary tumor metastasis and asked for parallels with the human equivalent. Methods Messenger RNA expression profiles of twenty-seven lymph node metastasis positive or negative canine mammary carcinomas were established by microarray analysis. Differentially expressed genes were functionally characterized and associated with molecular pathways. The findings were also correlated with published data on human breast cancer. Results Metastatic canine mammary carcinomas had 1,011 significantly differentially expressed genes when compared to non-metastatic carcinomas. Metastatic carcinomas had a significant up-regulation of genes associated with cell cycle regulation, matrix modulation, protein folding and proteasomal degradation whereas cell differentiation genes, growth factor pathway genes and regulators of actin organization were significantly down-regulated. Interestingly, 265 of the 1,011 differentially expressed canine genes are also related to human breast cancer and, vice versa, parts of a human prognostic gene signature were identified in the expression profiles of the metastatic canine tumors. Conclusions Metastatic canine mammary carcinomas can be discriminated from non-metastatic carcinomas by their gene expression profiles. More than one third of the differentially expressed genes are also described of relevance for human breast cancer. Many of the differentially expressed genes are linked to functions and pathways which appear to be relevant for the induction and maintenance of metastatic progression and may represent new therapeutic targets. Furthermore, dogs are in some aspects suitable as a translational model for human breast tumors in order to identify prognostic molecular signatures and potential therapeutic targets. PMID:21062462

Sister grouping of chimpanzees and humans as revealed by genome-wide phylogenetic analysis of brain gene expression profiles

PubMed Central

Uddin, Monica; Wildman, Derek E.; Liu, Guozhen; Xu, Wenbo; Johnson, Robert M.; Hof, Patrick R.; Kapatos, Gregory; Grossman, Lawrence I.; Goodman, Morris

2004-01-01

Gene expression profiles from the anterior cingulate cortex (ACC) of human, chimpanzee, gorilla, and macaque samples provide clues about genetic regulatory changes in human and other catarrhine primate brains. The ACC, a cerebral neocortical region, has human-specific histological features. Physiologically, an individual's ACC displays increased activity during that individual's performance of cognitive tasks. Of ≈45,000 probe sets on microarray chips representing transcripts of all or most human genes, ≈16,000 were commonly detected in human ACC samples and comparable numbers, 14,000–15,000, in gorilla and chimpanzee ACC samples. Phylogenetic results obtained from gene expression profiles contradict the traditional expectation that the non-human African apes (i.e., chimpanzee and gorilla) should be more like each other than either should be like humans. Instead, the chimpanzee ACC profiles are more like the human than like the gorilla; these profiles demonstrate that chimpanzees are the sister group of humans. Moreover, for those unambiguous expression changes mapping to important biological processes and molecular functions that statistically are significantly represented in the data, the chimpanzee clade shows at least as much apparent regulatory evolution as does the human clade. Among important changes in the ancestry of both humans and chimpanzees, but to a greater extent in humans, are the up-regulated expression profiles of aerobic energy metabolism genes and neuronal function-related genes, suggesting that increased neuronal activity required increased supplies of energy. PMID:14976249

Developmental heterogeneity of cardiac fibroblasts does not predict pathological proliferation and activation.

PubMed

Ali, Shah R; Ranjbarvaziri, Sara; Talkhabi, Mahmood; Zhao, Peng; Subat, Ali; Hojjat, Armin; Kamran, Paniz; Müller, Antonia M S; Volz, Katharina S; Tang, Zhaoyi; Red-Horse, Kristy; Ardehali, Reza

2014-09-12

Fibrosis is mediated partly by extracellular matrix-depositing fibroblasts in the heart. Although these mesenchymal cells are reported to have multiple embryonic origins, the functional consequence of this heterogeneity is unknown. We sought to validate a panel of surface markers to prospectively identify cardiac fibroblasts. We elucidated the developmental origins of cardiac fibroblasts and characterized their corresponding phenotypes. We also determined proliferation rates of each developmental subset of fibroblasts after pressure overload injury. We showed that Thy1(+)CD45(-)CD31(-)CD11b(-)Ter119(-) cells constitute the majority of cardiac fibroblasts. We characterized these cells using flow cytometry, epifluorescence and confocal microscopy, and transcriptional profiling (using reverse transcription polymerase chain reaction and RNA-seq). We used lineage tracing, transplantation studies, and parabiosis to show that most adult cardiac fibroblasts derive from the epicardium, a minority arises from endothelial cells, and a small fraction from Pax3-expressing cells. We did not detect generation of cardiac fibroblasts by bone marrow or circulating cells. Interestingly, proliferation rates of fibroblast subsets on injury were identical, and the relative abundance of each lineage remained the same after injury. The anatomic distribution of fibroblast lineages also remained unchanged after pressure overload. Furthermore, RNA-seq analysis demonstrated that Tie2-derived and Tbx18-derived fibroblasts within each operation group exhibit similar gene expression profiles. The cellular expansion of cardiac fibroblasts after transaortic constriction surgery was not restricted to any single developmental subset. The parallel proliferation and activation of a heterogeneous population of fibroblasts on pressure overload could suggest that common signaling mechanisms stimulate their pathological response. © 2014 American Heart Association, Inc.

TH1/TH2 cytokine profile, metalloprotease-9 activity and hormonal status in pregnant rheumatoid arthritis and systemic lupus erythematosus patients

PubMed Central

MUÑOZ-VALLE, J F; VÁZQUEZ-DEL MERCADO, M; GARCÍA-IGLESIAS, T; OROZCO-BAROCIO, G; BERNARD-MEDINA, G; MARTÍNEZ-BONILLA, G; BASTIDAS-RAMÍREZ, B E; NAVARRO, A D; BUENO, M; MARTÍNEZ-LÓPEZ, E; BEST-AGUILERA, C R; KAMACHI, M; ARMENDÁRIZ-BORUNDA, J

2003-01-01

During the course of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), several immune and neuroendocrine changes associated with pregnancy may exert positive (amelioration) or negative (exacerbation) effects on the clinical outcome. In order to shed light on the mechanisms underlying these responses, we performed a prospective longitudinal study in RA and SLE pregnant women, including healthy pregnant women as a control group. Cytokine messenger RNA (mRNA) expression assessed by quantitative competitive polymerase chain reaction (PCR) in peripheral blood mononuclear cells (PBMC), cytokine levels and lymphocyte proliferation responses (LPR) following phytohaemagglutinin (PHA) stimulation of PBMC, plasma metalloprotease-9 activity (MMP-9) and hormonal status during pregnancy were determined. TNFa was the most abundant cytokine mRNA expressed in PBMC in all groups studied (healthy pregnant women, RA and SLE pregnant patients). However, a general TH2 response reflected by high IL-10 levels was found in RA, as well as SLE, patients. A significant change in IFN-γ was observed in RA patients but only during the first trimester of pregnancy. This compared with a major TH1 response in healthy pregnant women. Interestingly, our study showed a homogeneous hormonal pattern in RA and SLE patients. Although decreased cortisol levels were observed in all patients studied, this is possibly related to the remission of disease activity status brought about by steroid treatment before and during pregnancy. In summary, we suggest that complex immune and hormonal networks are involved in pregnancy and that rheumatic diseases are very dynamic immune processes that cannot be described with a clear-cut cytokine profile. Furthermore, the observations in this study may reflect treatment-related immune effects more than those associated with disease. PMID:12562402

Conditional clustering of temporal expression profiles

PubMed Central

Wang, Ling; Montano, Monty; Rarick, Matt; Sebastiani, Paola

2008-01-01

Background Many microarray experiments produce temporal profiles in different biological conditions but common cluster techniques are not able to analyze the data conditional on the biological conditions. Results This article presents a novel technique to cluster data from time course microarray experiments performed across several experimental conditions. Our algorithm uses polynomial models to describe the gene expression patterns over time, a full Bayesian approach with proper conjugate priors to make the algorithm invariant to linear transformations, and an iterative procedure to identify genes that have a common temporal expression profile across two or more experimental conditions, and genes that have a unique temporal profile in a specific condition. Conclusion We use simulated data to evaluate the effectiveness of this new algorithm in finding the correct number of clusters and in identifying genes with common and unique profiles. We also use the algorithm to characterize the response of human T cells to stimulations of antigen-receptor signaling gene expression temporal profiles measured in six different biological conditions and we identify common and unique genes. These studies suggest that the methodology proposed here is useful in identifying and distinguishing uniquely stimulated genes from commonly stimulated genes in response to variable stimuli. Software for using this clustering method is available from the project home page. PMID:18334028

Extended Lindhard-Scharf-Schiott Theory for Ion Implantation Profiles Expressed with Pearson Function

NASA Astrophysics Data System (ADS)

Suzuki, Kunihiro

2009-04-01

Ion implantation profiles are expressed by the Pearson function with first, second, third, and fourth moment parameters of Rp, ΔRp, γ, and β. We derived an analytical model for these profile moments by solving a Lindhard-Scharf-Schiott (LSS) integration equation using perturbation approximation. This analytical model reproduces Monte Carlo data that were well calibrated to reproduce a vast experimental database. The extended LSS theory is vital for instantaneously predicting ion implantation profiles with any combination of incident ions and substrate atoms including their energy dependence.

SPERM RNA AMPLIFICATION FOR GENE EXPRESSION PROFILING BY DNA MICROARRAY TECHNOLOGY

EPA Science Inventory

Sperm RNA Amplification for Gene Expression Profiling by DNA Microarray Technology
Hongzu Ren, Kary E. Thompson, Judith E. Schmid and David J. Dix, Reproductive Toxicology Division, NHEERL, Office of Research and Development, US Environmental Protection Agency, Research Triang...

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...

GENE EXPRESSION PROFILING TO IDENTIFY MECHANISMS OF MALE REPRODUCTIVE TOXICITY

EPA Science Inventory

Gene Expression Profiling to Identify Mechanisms of Male Reproductive Toxicity
David J. Dix
National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC, 27711, USA.
Ab...

Metatranscriptomic profiles of Eastern subterranean termites, Reticulitermes flavipes (Kollar) fed on second generation feedstocks.

PubMed

Rajarapu, Swapna Priya; Shreve, Jacob T; Bhide, Ketaki P; Thimmapuram, Jyothi; Scharf, Michael E

2015-04-22

Second generation lignocellulosic feedstocks are being considered as an alternative to first generation biofuels that are derived from grain starches and sugars. However, the current pre-treatment methods for second generation biofuel production are inefficient and expensive due to the recalcitrant nature of lignocellulose. In this study, we used the lower termite Reticulitermes flavipes (Kollar), as a model to identify potential pretreatment genes/enzymes specifically adapted for use against agricultural feedstocks. Metatranscriptomic profiling was performed on worker termite guts after feeding on corn stover (CS), soybean residue (SR), or 98% pure cellulose (paper) to identify (i) microbial community, (ii) pathway level and (iii) gene-level responses. Microbial community profiles after CS and SR feeding were different from the paper feeding profile, and protist symbiont abundance decreased significantly in termites feeding on SR and CS relative to paper. Functional profiles after CS feeding were similar to paper and SR; whereas paper and SR showed different profiles. Amino acid and carbohydrate metabolism pathways were downregulated in termites feeding on SR relative to paper and CS. Gene expression analyses showed more significant down regulation of genes after SR feeding relative to paper and CS. Stereotypical lignocellulase genes/enzymes were not differentially expressed, but rather were among the most abundant/constitutively-expressed genes. These results suggest that the effect of CS and SR feeding on termite gut lignocellulase composition is minimal and thus, the most abundantly expressed enzymes appear to encode the best candidate catalysts for use in saccharification of these and related second-generation feedstocks. Further, based on these findings we hypothesize that the most abundantly expressed lignocellulases, rather than those that are differentially expressed have the best potential as pretreatment enzymes for CS and SR feedstocks.

Eph/Ephrin signalling maintains eye field segregation from adjacent neural plate territories during forebrain morphogenesis

PubMed Central

Cavodeassi, Florencia; Ivanovitch, Kenzo; Wilson, Stephen W.

2013-01-01

During forebrain morphogenesis, there is extensive reorganisation of the cells destined to form the eyes, telencephalon and diencephalon. Little is known about the molecular mechanisms that regulate region-specific behaviours and that maintain the coherence of cell populations undergoing specific morphogenetic processes. In this study, we show that the activity of the Eph/Ephrin signalling pathway maintains segregation between the prospective eyes and adjacent regions of the anterior neural plate during the early stages of forebrain morphogenesis in zebrafish. Several Ephrins and Ephs are expressed in complementary domains in the prospective forebrain and combinatorial abrogation of their activity results in incomplete segregation of the eyes and telencephalon and in defective evagination of the optic vesicles. Conversely, expression of exogenous Ephs or Ephrins in regions of the prospective forebrain where they are not usually expressed changes the adhesion properties of the cells, resulting in segregation to the wrong domain without changing their regional fate. The failure of eye morphogenesis in rx3 mutants is accompanied by a loss of complementary expression of Ephs and Ephrins, suggesting that this pathway is activated downstream of the regional fate specification machinery to establish boundaries between domains undergoing different programmes of morphogenesis. PMID:24026122

Integrative Approach to Pain Genetics Identifies Pain Sensitivity Loci across Diseases

PubMed Central

Ruau, David; Dudley, Joel T.; Chen, Rong; Phillips, Nicholas G.; Swan, Gary E.; Lazzeroni, Laura C.; Clark, J. David

2012-01-01

Identifying human genes relevant for the processing of pain requires difficult-to-conduct and expensive large-scale clinical trials. Here, we examine a novel integrative paradigm for data-driven discovery of pain gene candidates, taking advantage of the vast amount of existing disease-related clinical literature and gene expression microarray data stored in large international repositories. First, thousands of diseases were ranked according to a disease-specific pain index (DSPI), derived from Medical Subject Heading (MESH) annotations in MEDLINE. Second, gene expression profiles of 121 of these human diseases were obtained from public sources. Third, genes with expression variation significantly correlated with DSPI across diseases were selected as candidate pain genes. Finally, selected candidate pain genes were genotyped in an independent human cohort and prospectively evaluated for significant association between variants and measures of pain sensitivity. The strongest signal was with rs4512126 (5q32, ABLIM3, P = 1.3×10−10) for the sensitivity to cold pressor pain in males, but not in females. Significant associations were also observed with rs12548828, rs7826700 and rs1075791 on 8q22.2 within NCALD (P = 1.7×10−4, 1.8×10−4, and 2.2×10−4 respectively). Our results demonstrate the utility of a novel paradigm that integrates publicly available disease-specific gene expression data with clinical data curated from MEDLINE to facilitate the discovery of pain-relevant genes. This data-derived list of pain gene candidates enables additional focused and efficient biological studies validating additional candidates. PMID:22685391

An Integrated Clinico-transcriptomic Approach Identifies a Central Role of the Heme Degradation Pathway for Septic Complications after Trauma.

PubMed

Rittirsch, Daniel; Schoenborn, Veit; Lindig, Sandro; Wanner, Elisabeth; Sprengel, Kai; Günkel, Sebastian; Blaess, Markus; Schaarschmidt, Barbara; Sailer, Patricia; Märsmann, Sonja; Simmen, Hans-Peter; Cinelli, Paolo; Bauer, Michael; Claus, Ralf A; Wanner, Guido A

2016-12-01

The present study was aimed to identify mechanisms linked to complicated courses and adverse events after severe trauma by a systems biology approach. In severe trauma, overwhelming systemic inflammation can result in additional damage and the development of complications, including sepsis. In a prospective, longitudinal single-center study, RNA samples from circulating leukocytes from patients with multiple injury (injury severity score ≥17 points; n = 81) were analyzed for dynamic changes in gene expression over a period of 21 days by whole-genome screening (discovery set; n = 10 patients; 90 samples) and quantitative RT-PCR (validation set; n = 71 patients, 517 samples). Multivariate correlational analysis of transcripts and clinical parameters was used to identify mechanisms related to sepsis. Transcriptome profiling of the discovery set revealed the strongest changes between patients with either systemic inflammation or sepsis in gene expression of the heme degradation pathway. Using quantitative RT-PCR analyses (validation set), the key components haptoglobin (HP), cluster of differentiation (CD) 163, heme oxygenase-1 (HMOX1), and biliverdin reductase A (BLVRA) showed robust changes following trauma. Upregulation of HP was associated with the severity of systemic inflammation and the development of sepsis. Patients who received allogeneic blood transfusions had a higher incidence of nosocomial infections and sepsis, and the amount of blood transfusion as source of free heme correlated with the expression pattern of HP. These findings indicate that the heme degradation pathway is associated with increased susceptibility to septic complications after trauma, which is indicated by HP expression in particular.

Tensor decomposition-based and principal-component-analysis-based unsupervised feature extraction applied to the gene expression and methylation profiles in the brains of social insects with multiple castes.

PubMed

Taguchi, Y-H

2018-05-08

Even though coexistence of multiple phenotypes sharing the same genomic background is interesting, it remains incompletely understood. Epigenomic profiles may represent key factors, with unknown contributions to the development of multiple phenotypes, and social-insect castes are a good model for elucidation of the underlying mechanisms. Nonetheless, previous studies have failed to identify genes associated with aberrant gene expression and methylation profiles because of the lack of suitable methodology that can address this problem properly. A recently proposed principal component analysis (PCA)-based and tensor decomposition (TD)-based unsupervised feature extraction (FE) can solve this problem because these two approaches can deal with gene expression and methylation profiles even when a small number of samples is available. PCA-based and TD-based unsupervised FE methods were applied to the analysis of gene expression and methylation profiles in the brains of two social insects, Polistes canadensis and Dinoponera quadriceps. Genes associated with differential expression and methylation between castes were identified, and analysis of enrichment of Gene Ontology terms confirmed reliability of the obtained sets of genes from the biological standpoint. Biologically relevant genes, shown to be associated with significant differential gene expression and methylation between castes, were identified here for the first time. The identification of these genes may help understand the mechanisms underlying epigenetic control of development of multiple phenotypes under the same genomic conditions.

The Development of Early Profiles of Temperament: Characterization, Continuity, and Etiology

PubMed Central

Beekman, Charles; Neiderhiser, Jenae M.; Buss, Kristin A.; Loken, Eric; Moore, Ginger A.; Leve, Leslie D.; Ganiban, Jody M.; Shaw, Daniel S.; Reiss, David

2015-01-01

This study used a data-driven, person-centered approach to examine the characterization, continuity, and etiology of child temperament from infancy to toddlerhood. Data from 561 families who participated in an ongoing prospective adoption study, the Early Growth and Development Study, were used to estimate latent profiles of temperament at 9, 18, and 27 months. Results indicated that four profiles of temperament best fit the data at all three points of assessment. The characterization of profiles was stable over time while membership in profiles changed across age. Facets of adoptive parent and birth mother personality were predictive of children’s profile membership at each age, providing preliminary evidence for specific environmental and genetic influences on patterns of temperament development from infancy to toddlerhood. PMID:26332208

COnsortium of METabolomics Studies (COMETS)

Cancer.gov

The COnsortium of METabolomics Studies (COMETS) is an extramural-intramural partnership that promotes collaboration among prospective cohort studies that follow participants for a range of outcomes and perform metabolomic profiling of individuals.

Neighboring Genes Show Correlated Evolution in Gene Expression.

PubMed

Ghanbarian, Avazeh T; Hurst, Laurence D

2015-07-01

When considering the evolution of a gene's expression profile, we commonly assume that this is unaffected by its genomic neighborhood. This is, however, in contrast to what we know about the lack of autonomy between neighboring genes in gene expression profiles in extant taxa. Indeed, in all eukaryotic genomes genes of similar expression-profile tend to cluster, reflecting chromatin level dynamics. Does it follow that if a gene increases expression in a particular lineage then the genomic neighbors will also increase in their expression or is gene expression evolution autonomous? To address this here we consider evolution of human gene expression since the human-chimp common ancestor, allowing for both variation in estimation of current expression level and error in Bayesian estimation of the ancestral state. We find that in all tissues and both sexes, the change in gene expression of a focal gene on average predicts the change in gene expression of neighbors. The effect is highly pronounced in the immediate vicinity (<100 kb) but extends much further. Sex-specific expression change is also genomically clustered. As genes increasing their expression in humans tend to avoid nuclear lamina domains and be enriched for the gene activator 5-hydroxymethylcytosine, we conclude that, most probably owing to chromatin level control of gene expression, a change in gene expression of one gene likely affects the expression evolution of neighbors, what we term expression piggybacking, an analog of hitchhiking. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

Validation of Biomarkers Predictive of Recurrence Following Prostatectomy

DTIC Science & Technology

2011-04-14

Bergerheim U, Ekman P, DeMarzo AM, Tibshirani R, Botstein D, Brown PO, Brooks JD, Pollack JR: Gene expression profiling identifies clinically...P, DeMarzo AM, Tibshirani R, Botstein D, Brown PO, Brooks JD, Pollack JR: Gene expression profiling identifies clinically relevant subtypes of

Customizing chemotherapy for colon cancer: the potential of gene expression profiling.

PubMed

Mariadason, John M; Arango, Diego; Augenlicht, Leonard H

2004-06-01

The value of gene expression profiling, or microarray analysis, for the classification and prognosis of multiple forms of cancer is now clearly established. For colon cancer, expression profiling can readily discriminate between normal and tumor tissue, and to some extent between tumors of different histopathological stage and prognosis. While a definitive in vivo study demonstrating the potential of this methodology for predicting response to chemotherapy is presently lacking, the ability of microarrays to distinguish other subtleties of colon cancer phenotype, as well as recent in vitro proof-of-principle experiments utilizing colon cancer cell lines, illustrate the potential of this methodology for predicting the probability of response to specific chemotherapeutic agents. This review discusses some of the recent advances in the use of microarray analysis for understanding and distinguishing colon cancer subtypes, and attempts to identify challenges that need to be overcome in order to achieve the goal of using gene expression profiling for customizing chemotherapy in colon cancer.

Introducing Cytology-Based Theranostics in Oral Squamous Cell Carcinoma: A Pilot Program.

PubMed

Patrikidou, Anna; Valeri, Rosalia Maria; Kitikidou, Kyriaki; Destouni, Charikleia; Vahtsevanos, Konstantinos

2016-04-01

We aimed to evaluate the feasibility and reliability of brush cytology in the biomarker expression profiling of oral squamous cell carcinomas within the concept of theranostics, and to correlate this biomarker profile with patient measurable outcomes. Markers representative of prognostic gene expression changes in oral squamous cell carcinoma was selected. These markers were also selected to involve pathways for which commercially available or investigational agents exist for clinical application. A set of 7 markers were analysed by immunocytochemistry on the archival primary tumour material of 99 oral squamous cell carcinoma patients. We confirmed the feasibility of the technique for the expression profiling of oral squamous cell carcinomas. Furthermore, our results affirm the prognostic significance of the epidermal growth factor receptor (EGFR) family and the angiogenic pathway in oral squamous cell carcinoma, confirming their interest for targeted therapy. Brush cytology appears feasible and applicable for the expression profiling of oral squamous cell carcinoma within the concept of theranostics, according to sample availability.

Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer

PubMed Central

Zhang, Dingxiao; Park, Daechan; Zhong, Yi; Lu, Yue; Rycaj, Kiera; Gong, Shuai; Chen, Xin; Liu, Xin; Chao, Hsueh-Ping; Whitney, Pamela; Calhoun-Davis, Tammy; Takata, Yoko; Shen, Jianjun; Iyer, Vishwanath R.; Tang, Dean G.

2016-01-01

The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features. PMID:26924072

Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer.

PubMed

Zhang, Dingxiao; Park, Daechan; Zhong, Yi; Lu, Yue; Rycaj, Kiera; Gong, Shuai; Chen, Xin; Liu, Xin; Chao, Hsueh-Ping; Whitney, Pamela; Calhoun-Davis, Tammy; Takata, Yoko; Shen, Jianjun; Iyer, Vishwanath R; Tang, Dean G

2016-02-29

The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features.

Glycosyltransferase Gene Expression Profiles Classify Cancer Types and Propose Prognostic Subtypes

NASA Astrophysics Data System (ADS)

Ashkani, Jahanshah; Naidoo, Kevin J.

2016-05-01

Aberrant glycosylation in tumours stem from altered glycosyltransferase (GT) gene expression but can the expression profiles of these signature genes be used to classify cancer types and lead to cancer subtype discovery? The differential structural changes to cellular glycan structures are predominantly regulated by the expression patterns of GT genes and are a hallmark of neoplastic cell metamorphoses. We found that the expression of 210 GT genes taken from 1893 cancer patient samples in The Cancer Genome Atlas (TCGA) microarray data are able to classify six cancers; breast, ovarian, glioblastoma, kidney, colon and lung. The GT gene expression profiles are used to develop cancer classifiers and propose subtypes. The subclassification of breast cancer solid tumour samples illustrates the discovery of subgroups from GT genes that match well against basal-like and HER2-enriched subtypes and correlates to clinical, mutation and survival data. This cancer type glycosyltransferase gene signature finding provides foundational evidence for the centrality of glycosylation in cancer.

Gene expression profiles characterize early graft response in living donor small bowel transplantation: a case report.

PubMed

Bradley, S P; Pahari, M; Uknis, M E; Rastellini, C; Cicalese, L

2006-01-01

The cellular and histological events that occur during the regeneration process in invertebrates have been studied in the field of visceral regeneration. We would like to explore the molecular aspects of the regeneration process in the small intestine. The aim of this study was to characterize the gene expression profiles of the intestinal graft to identify which genes may have a role in regeneration of graft tissue posttransplant. In a patient undergoing living related small bowel transplantation (LRSBTx) in our institution, mucosal biopsies were obtained from the recipient intestine and donor graft at the time of transplant and at weeks 1, 2, 3, and 6 posttransplant. Total RNA was isolated from sample biopsies followed by gene expression profiles determined from the replicate samples (n = 3) for each biopsy using the Affymetrix U133 Plus 2.0 Human GeneChip set. Two profiles were obtained from the data. One profile showed rapid increase of 45 genes immediately after transplant by week 1 with significant changes (P < .05) greater than threefold including the chemokine CXC9 and glutathione-related stress factors, GPX2 and GSTA4. The second profile identified 133 genes that were significantly decreased by threefold or greater immediately after transplant week 1, including UCC1, the human homolog of the Ependymin gene. We have identified two gene expression profiles representing early graft responses to small bowel transplantation. These profiles will serve to identify and study those genes whose products may play a role in accelerating tissue regeneration following segmental LRSBTx.

Comparison of Glomerular and Podocyte mRNA Profiles in Streptozotocin-Induced Diabetes

PubMed Central

Fu, Jia; Wei, Chengguo; Lee, Kyung; Zhang, Weijia; He, Wu; Chuang, Peter

2016-01-01

Evaluating the mRNA profile of podocytes in the diabetic kidney may indicate genes involved in the pathogenesis of diabetic nephropathy. To determine if the podocyte-specific gene information contained in mRNA profiles of the whole glomerulus of the diabetic kidney accurately reflects gene expression in the isolated podocytes, we crossed Nos3−/− IRG mice with podocin-rtTA and TetON-Cre mice for enhanced green fluorescent protein labeling of podocytes before diabetic injury. Diabetes was induced by streptozotocin, and mRNA profiles of isolated glomeruli and sorted podocytes from diabetic and control mice were examined 10 weeks later. Expression of podocyte-specific markers in glomeruli was downregulated in diabetic mice compared with controls. However, expression of these markers was not altered in sorted podocytes from diabetic mice. When mRNA levels of glomeruli were corrected for podocyte number per glomerulus, the differences in podocyte marker expression disappeared. Analysis of the differentially expressed genes in diabetic mice also revealed distinct upregulated pathways in the glomeruli (mitochondrial function, oxidative stress) and in podocytes (actin organization). In conclusion, our data suggest reduced expression of podocyte markers in glomeruli is a secondary effect of reduced podocyte number, thus podocyte-specific gene expression detected in the whole glomerulus may not represent that in podocytes in the diabetic kidney. PMID:26264855

Establishment of a New Quality Control and Vaccine Safety Test for Influenza Vaccines and Adjuvants Using Gene Expression Profiling

PubMed Central

Momose, Haruka; Mizukami, Takuo; Kuramitsu, Madoka; Takizawa, Kazuya; Masumi, Atsuko; Araki, Kumiko; Furuhata, Keiko; Yamaguchi, Kazunari; Hamaguchi, Isao

2015-01-01

We have previously identified 17 biomarker genes which were upregulated by whole virion influenza vaccines, and reported that gene expression profiles of these biomarker genes had a good correlation with conventional animal safety tests checking body weight and leukocyte counts. In this study, we have shown that conventional animal tests showed varied and no dose-dependent results in serially diluted bulk materials of influenza HA vaccines. In contrast, dose dependency was clearly shown in the expression profiles of biomarker genes, demonstrating higher sensitivity of gene expression analysis than the current animal safety tests of influenza vaccines. The introduction of branched DNA based-concurrent expression analysis could simplify the complexity of multiple gene expression approach, and could shorten the test period from 7 days to 3 days. Furthermore, upregulation of 10 genes, Zbp1, Mx2, Irf7, Lgals9, Ifi47, Tapbp, Timp1, Trafd1, Psmb9, and Tap2, was seen upon virosomal-adjuvanted vaccine treatment, indicating that these biomarkers could be useful for the safety control of virosomal-adjuvanted vaccines. In summary, profiling biomarker gene expression could be a useful, rapid, and highly sensitive method of animal safety testing compared with conventional methods, and could be used to evaluate the safety of various types of influenza vaccines, including adjuvanted vaccine. PMID:25909814

Validation of the prognostic gene portfolio, ClinicoMolecular Triad Classification, using an independent prospective breast cancer cohort and external patient populations.

PubMed

Wang, Dong-Yu; Done, Susan J; Mc Cready, David R; Leong, Wey L

2014-07-04

Using genome-wide expression profiles of a prospective training cohort of breast cancer patients, ClinicoMolecular Triad Classification (CMTC) was recently developed to classify breast cancers into three clinically relevant groups to aid treatment decisions. CMTC was found to be both prognostic and predictive in a large external breast cancer cohort in that study. This study serves to validate the reproducibility of CMTC and its prognostic value using independent patient cohorts. An independent internal cohort (n = 284) and a new external cohort (n = 2,181) were used to validate the association of CMTC between clinicopathological factors, 12 known gene signatures, two molecular subtype classifiers, and 19 oncogenic signalling pathway activities, and to reproduce the abilities of CMTC to predict clinical outcomes of breast cancer. In addition, we also updated the outcome data of the original training cohort (n = 147). The original training cohort reached a statistically significant difference (p < 0.05) in disease-free survivals between the three CMTC groups after an additional two years of follow-up (median = 55 months). The prognostic value of the triad classification was reproduced in the second independent internal cohort and the new external validation cohort. CMTC achieved even higher prognostic significance when all available patients were analyzed (n = 4,851). Oncogenic pathways Myc, E2F1, Ras and β-catenin were again implicated in the high-risk groups. Both prospective internal cohorts and the independent external cohorts reproduced the triad classification of CMTC and its prognostic significance. CMTC is an independent prognostic predictor, and it outperformed 12 other known prognostic gene signatures, molecular subtype classifications, and all other standard prognostic clinicopathological factors. Our results support further development of CMTC portfolio into a guide for personalized breast cancer treatments.

Changes in global gene expression profiles induced by HPV 16 E6 oncoprotein variants in cervical carcinoma C33-A cells

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

Zacapala-Gómez, Ana Elvira, E-mail: zak_ana@yahoo.com.mx; Del Moral-Hernández, Oscar, E-mail: odelmoralh@gmail.com; Villegas-Sepúlveda, Nicolás, E-mail: nvillega@cinvestav.mx

We analyzed the effects of the expression of HPV 16 E6 oncoprotein variants (AA-a, AA-c, E-A176/G350, E-C188/G350, E-G350), and the E-Prototype in global gene expression profiles in an in vitro model. E6 gene was cloned into an expression vector fused to GFP and was transfected in C33-A cells. Affymetrix GeneChip Human Transcriptome Array 2.0 platform was used to analyze the expression of over 245,000 coding transcripts. We found that HPV16 E6 variants altered the expression of 387 different genes in comparison with E-Prototype. The altered genes are involved in cellular processes related to the development of cervical carcinoma, such asmore » adhesion, angiogenesis, apoptosis, differentiation, cell cycle, proliferation, transcription and protein translation. Our results show that polymorphic changes in HPV16 E6 natural variants are sufficient to alter the overall gene expression profile in C33-A cells, explaining in part the observed differences in oncogenic potential of HPV16 variants. - Highlights: • Amino acid changes in HPV16 E6 variants modulate the transciption of specific genes. • This is the first comparison of global gene expression profile of HPV 16 E6 variants. • Each HPV 16 E6 variant appears to have its own molecular signature.« less

Diverse correlation patterns between microRNAs and their targets during tomato fruit development indicates different modes of microRNA actions.

PubMed

Lopez-Gomollon, Sara; Mohorianu, Irina; Szittya, Gyorgy; Moulton, Vincent; Dalmay, Tamas

2012-12-01

MicroRNAs negatively regulate the accumulation of mRNAs therefore when they are expressed in the same cells their expression profiles show an inverse correlation. We previously described one positively correlated miRNA/target pair, but it is not known how widespread this phenomenon is. Here, we investigated the correlation between the expression profiles of differentially expressed miRNAs and their targets during tomato fruit development using deep sequencing, Northern blot and RT-qPCR. We found an equal number of positively and negatively correlated miRNA/target pairs indicating that positive correlation is more frequent than previously thought. We also found that the correlation between microRNA and target expression profiles can vary between mRNAs belonging to the same gene family and even for the same target mRNA at different developmental stages. Since microRNAs always negatively regulate their targets, the high number of positively correlated microRNA/target pairs suggests that mutual exclusion could be as widespread as temporal regulation. The change of correlation during development suggests that the type of regulatory circuit directed by a microRNA can change over time and can be different for individual gene family members. Our results also highlight potential problems for expression profiling-based microRNA target identification/validation.

Gene expression profiling of two distinct neuronal populations in the rodent spinal cord.

PubMed

Ryge, Jesper; Westerdahl, Ann-Charlotte; Alstrøm, Preben; Kiehn, Ole

2008-01-01

In the field of neuroscience microarray gene expression profiles on anatomically defined brain structures are being used increasingly to study both normal brain functions as well as pathological states. Fluorescent tracing techniques in brain tissue that identifies distinct neuronal populations can in combination with global gene expression profiling potentially increase the resolution and specificity of such studies to shed new light on neuronal functions at the cellular level. We examine the microarray gene expression profiles of two distinct neuronal populations in the spinal cord of the neonatal rat, the principal motor neurons and specific interneurons involved in motor control. The gene expression profiles of the respective cell populations were obtained from amplified mRNA originating from 50-250 fluorescently identified and laser microdissected cells. In the data analysis we combine a new microarray normalization procedure with a conglomerate measure of significant differential gene expression. Using our methodology we find 32 genes to be more expressed in the interneurons compared to the motor neurons that all except one have not previously been associated with this neuronal population. As a validation of our method we find 17 genes to be more expressed in the motor neurons than in the interneurons and of these only one had not previously been described in this population. We provide an optimized experimental protocol that allows isolation of gene transcripts from fluorescent retrogradely labeled cell populations in fresh tissue, which can be used to generate amplified aRNA for microarray hybridization from as few as 50 laser microdissected cells. Using this optimized experimental protocol in combination with our microarray analysis methodology we find 49 differentially expressed genes between the motor neurons and the interneurons that reflect the functional differences between these two cell populations in generating and transmitting the motor output in the rodent spinal cord.

Gene Expression Profiling of Two Distinct Neuronal Populations in the Rodent Spinal Cord

PubMed Central

Alstrøm, Preben; Kiehn, Ole

2008-01-01

Background In the field of neuroscience microarray gene expression profiles on anatomically defined brain structures are being used increasingly to study both normal brain functions as well as pathological states. Fluorescent tracing techniques in brain tissue that identifies distinct neuronal populations can in combination with global gene expression profiling potentially increase the resolution and specificity of such studies to shed new light on neuronal functions at the cellular level. Methodology/Principal Findings We examine the microarray gene expression profiles of two distinct neuronal populations in the spinal cord of the neonatal rat, the principal motor neurons and specific interneurons involved in motor control. The gene expression profiles of the respective cell populations were obtained from amplified mRNA originating from 50–250 fluorescently identified and laser microdissected cells. In the data analysis we combine a new microarray normalization procedure with a conglomerate measure of significant differential gene expression. Using our methodology we find 32 genes to be more expressed in the interneurons compared to the motor neurons that all except one have not previously been associated with this neuronal population. As a validation of our method we find 17 genes to be more expressed in the motor neurons than in the interneurons and of these only one had not previously been described in this population. Conclusions/Significance We provide an optimized experimental protocol that allows isolation of gene transcripts from fluorescent retrogradely labeled cell populations in fresh tissue, which can be used to generate amplified aRNA for microarray hybridization from as few as 50 laser microdissected cells. Using this optimized experimental protocol in combination with our microarray analysis methodology we find 49 differentially expressed genes between the motor neurons and the interneurons that reflect the functional differences between these two cell populations in generating and transmitting the motor output in the rodent spinal cord. PMID:18923679

Stationary self-focusing of intense laser beam in cold quantum plasma using ramp density profile

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

Habibi, M.; Ghamari, F.

2012-10-15

By using a transient density profile, we have demonstrated stationary self-focusing of an electromagnetic Gaussian beam in cold quantum plasma. The paper is devoted to the prospects of using upward increasing ramp density profile of an inhomogeneous nonlinear medium with quantum effects in self-focusing mechanism of high intense laser beam. We have found that the upward ramp density profile in addition to quantum effects causes much higher oscillation and better focusing of laser beam in cold quantum plasma in comparison to that in the classical relativistic case. Our computational results reveal the importance and influence of formation of electron densitymore » profiles in enhancing laser self-focusing.« less

PULMONARY GENE EXPRESSION PROFILES OF SPONTANEOUSLY HYPERTENSIVE RATS EXPOSED TO ENVIRONMENTAL TOBACCO SMOKE (ETS)

EPA Science Inventory

Global gene expression profile analysis can be utilized to derive molecular footprints to understand biochemical

pathways implicated in the origin and progression of disease. Functional genomics efforts with tissue-specific focused

genearray appears to be the most...

GENE EXPRESSION PROFILING IN THE LIVER OF CD-1 MICE TO CHARACTERIZE THE HEPATOTOXICITY OF TRIAZOLE FUNGICIDES.

EPA Science Inventory

Four triazole fungicides used in agricultural or pharmaceutical applications were examined for hepatotoxic effects in mouse liver. Besides organ weight, histopathology, and cytochrome P450 (CYP) enzyme induction, DNA microarrays were used to generate gene expression profiles and ...

GENE EXPRESSION PROFILING IN THE LIVER OF CD-1 MICE TO CHARACTERIZE THE HEPATOTOXICITY OF TRIAZOLE FUNGICIDES

EPA Science Inventory

Four triazole fungicides used in agricultural or pharmaceutical applications were examined for hepatotoxic effects in mouse liver. Besides organ weight, histopathology, and cytochrome P450 (CYP) enzyme induction, DNA microarrays were used to generate gene expression profiles and ...

CARDIOPULMONARY GENE EXPRESSION PROFILES IN NORMO- AND SPONTANEOUSLY HYPERSENSITIVE (SH) RATS: IMPACT OF PARTICULATE MATTER (PM) EXPOSURE

EPA Science Inventory

CARDIOPULMONARY GENE EXPRESSION PROFILES IN NORMO- AND SPONTANEOUSLY HYPERTENSIVE (SH) RATS: IMPACT OF PARTICULATE MATTER (PM) EXPOSURE. SS Nadadur UP Kodavanti, Pulmonary Toxicology Branch, ETD, ORD, NHEERL, US Environmental Protection Agency, Research Triangle Park, NC 27711.

Expression Profile of Drug and Nutrient Absorption Related Genes in Madin-Darby Canine Kidney (MDCK) Cells Grown under Differentiation Conditions.

PubMed

Quan, Yong; Jin, Yisheng; Faria, Teresa N; Tilford, Charles A; He, Aiqing; Wall, Doris A; Smith, Ronald L; Vig, Balvinder S

2012-06-18

The expression levels of genes involved in drug and nutrient absorption were evaluated in the Madin-Darby Canine Kidney (MDCK) in vitro drug absorption model. MDCK cells were grown on plastic surfaces (for 3 days) or on Transwell® membranes (for 3, 5, 7, and 9 days). The expression profile of genes including ABC transporters, SLC transporters, and cytochrome P450 (CYP) enzymes was determined using the Affymetrix® Canine GeneChip®. Expression of genes whose probe sets passed a stringent confirmation process was examined. Expression of a few transporter (MDR1, PEPT1 and PEPT2) genes in MDCK cells was confirmed by RT-PCR. The overall gene expression profile was strongly influenced by the type of support the cells were grown on. After 3 days of growth, expression of 28% of the genes was statistically different (1.5-fold cutoff, p < 0.05) between the cells grown on plastic and Transwell® membranes. When cells were differentiated on Transwell® membranes, large changes in gene expression profile were observed during the early stages, which then stabilized after 5-7 days. Only a small number of genes encoding drug absorption related SLC, ABC, and CYP were detected in MDCK cells, and most of them exhibited low hybridization signals. Results from this study provide valuable reference information on endogenous gene expression in MDCK cells that could assist in design of drug-transporter and/or drug-enzyme interaction studies, and help interpret the contributions of various transporters and metabolic enzymes in studies with MDCK cells.

Expression Profile of Drug and Nutrient Absorption Related Genes in Madin-Darby Canine Kidney (MDCK) Cells Grown under Differentiation Conditions

PubMed Central

Quan, Yong; Jin, Yisheng; Faria, Teresa N.; Tilford, Charles A.; He, Aiqing; Wall, Doris A.; Smith, Ronald L.; Vig, Balvinder S.

2012-01-01

The expression levels of genes involved in drug and nutrient absorption were evaluated in the Madin-Darby Canine Kidney (MDCK) in vitro drug absorption model. MDCK cells were grown on plastic surfaces (for 3 days) or on Transwell® membranes (for 3, 5, 7, and 9 days). The expression profile of genes including ABC transporters, SLC transporters, and cytochrome P450 (CYP) enzymes was determined using the Affymetrix® Canine GeneChip®. Expression of genes whose probe sets passed a stringent confirmation process was examined. Expression of a few transporter (MDR1, PEPT1 and PEPT2) genes in MDCK cells was confirmed by RT-PCR. The overall gene expression profile was strongly influenced by the type of support the cells were grown on. After 3 days of growth, expression of 28% of the genes was statistically different (1.5-fold cutoff, p < 0.05) between the cells grown on plastic and Transwell® membranes. When cells were differentiated on Transwell® membranes, large changes in gene expression profile were observed during the early stages, which then stabilized after 5–7 days. Only a small number of genes encoding drug absorption related SLC, ABC, and CYP were detected in MDCK cells, and most of them exhibited low hybridization signals. Results from this study provide valuable reference information on endogenous gene expression in MDCK cells that could assist in design of drug-transporter and/or drug-enzyme interaction studies, and help interpret the contributions of various transporters and metabolic enzymes in studies with MDCK cells. PMID:24300234

Infrequent and low expression of cancer-testis antigens located on the X chromosome in colorectal cancer: implications for immunotherapy in South African populations.

PubMed

Dakshinamurthy, Amirtha Ganesh; Ramesar, Rajkumar; Goldberg, Paul; Blackburn, Jonathan M

2008-11-01

Cancer-testis (CT) antigens are a group of tumor antigens that are expressed in the testis and aberrantly in cancerous tissue but not in somatic tissues. The testis is an immune-privileged site because of the presence of a blood-testis barrier; as a result, CT antigens are considered to be essentially tumor specific and are attractive targets for immunotherapy. CT antigens are classified as the CT-X and the non-X CT antigens depending on the chromosomal location to which the genes are mapped. CT-X antigens are typically highly immunogenic and hence the first step towards tailored immunotherapy is to elucidate the expression profile of CT-X antigens in the respective tumors. In this study we investigated the expression profile of 16 CT-X antigen genes in 34 colorectal cancer (CRC) patients using reverse transcription-polymerase chain reaction. We observed that 12 of the 16 CT-X antigen genes studied did not show expression in any of the CRC samples analyzed. The other 4 CT-X antigen genes showed low frequency of expression and exhibited a highly variable expression profile when compared to other populations. Thus, our study forms the first report on the expression profile of CT-X antigen genes among CRC patients in the genetically diverse South African population. The results of our study suggest that genetic and ethnic variations in population might have a role in the expression of the CT-X antigen genes. Thus our results have significant implications for anti-CT antigen-based immunotherapy trials in this population.

Advancing the use of noncoding RNA in regulatory toxicology: Report of an ECETOC workshop.

PubMed

Aigner, Achim; Buesen, Roland; Gant, Tim; Gooderham, Nigel; Greim, Helmut; Hackermüller, Jörg; Hubesch, Bruno; Laffont, Madeleine; Marczylo, Emma; Meister, Gunter; Petrick, Jay S; Rasoulpour, Reza J; Sauer, Ursula G; Schmidt, Kerstin; Seitz, Hervé; Slack, Frank; Sukata, Tokuo; van der Vies, Saskia M; Verhaert, Jan; Witwer, Kenneth W; Poole, Alan

2016-12-01

The European Centre for the Ecotoxicology and Toxicology of Chemicals (ECETOC) organised a workshop to discuss the state-of-the-art research on noncoding RNAs (ncRNAs) as biomarkers in regulatory toxicology and as analytical and therapeutic agents. There was agreement that ncRNA expression profiling data requires careful evaluation to determine the utility of specific ncRNAs as biomarkers. To advance the use of ncRNA in regulatory toxicology, the following research priorities were identified: (1) Conduct comprehensive literature reviews to identify possibly suitable ncRNAs and areas of toxicology where ncRNA expression profiling could address prevailing scientific deficiencies. (2) Develop consensus on how to conduct ncRNA expression profiling in a toxicological context. (3) Conduct experimental projects, including, e.g., rat (90-day) oral toxicity studies, to evaluate the toxicological relevance of the expression profiles of selected ncRNAs. Thereby, physiological ncRNA expression profiles should be established, including the biological variability of healthy individuals. To substantiate the relevance of key ncRNAs for cell homeostasis or pathogenesis, molecular events should be dose-dependently linked with substance-induced apical effects. Applying a holistic approach, knowledge on ncRNAs, 'omics and epigenetics technologies should be integrated into adverse outcome pathways to improve the understanding of the functional roles of ncRNAs within a regulatory context. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

Clustering of time-course gene expression profiles using normal mixture models with autoregressive random effects

PubMed Central

2012-01-01

Background Time-course gene expression data such as yeast cell cycle data may be periodically expressed. To cluster such data, currently used Fourier series approximations of periodic gene expressions have been found not to be sufficiently adequate to model the complexity of the time-course data, partly due to their ignoring the dependence between the expression measurements over time and the correlation among gene expression profiles. We further investigate the advantages and limitations of available models in the literature and propose a new mixture model with autoregressive random effects of the first order for the clustering of time-course gene-expression profiles. Some simulations and real examples are given to demonstrate the usefulness of the proposed models. Results We illustrate the applicability of our new model using synthetic and real time-course datasets. We show that our model outperforms existing models to provide more reliable and robust clustering of time-course data. Our model provides superior results when genetic profiles are correlated. It also gives comparable results when the correlation between the gene profiles is weak. In the applications to real time-course data, relevant clusters of coregulated genes are obtained, which are supported by gene-function annotation databases. Conclusions Our new model under our extension of the EMMIX-WIRE procedure is more reliable and robust for clustering time-course data because it adopts a random effects model that allows for the correlation among observations at different time points. It postulates gene-specific random effects with an autocorrelation variance structure that models coregulation within the clusters. The developed R package is flexible in its specification of the random effects through user-input parameters that enables improved modelling and consequent clustering of time-course data. PMID:23151154

Biological characterization of adult MYC-translocation-positive mature B-cell lymphomas other than molecular Burkitt lymphoma.

PubMed

Aukema, Sietse M; Kreuz, Markus; Kohler, Christian W; Rosolowski, Maciej; Hasenclever, Dirk; Hummel, Michael; Küppers, Ralf; Lenze, Dido; Ott, German; Pott, Christiane; Richter, Julia; Rosenwald, Andreas; Szczepanowski, Monika; Schwaenen, Carsten; Stein, Harald; Trautmann, Heiko; Wessendorf, Swen; Trümper, Lorenz; Loeffler, Markus; Spang, Rainer; Kluin, Philip M; Klapper, Wolfram; Siebert, Reiner

2014-04-01

Chromosomal translocations affecting the MYC oncogene are the biological hallmark of Burkitt lymphomas but also occur in a subset of other mature B-cell lymphomas. If accompanied by a chromosomal break targeting the BCL2 and/or BCL6 oncogene these MYC translocation-positive (MYC(+)) lymphomas are called double-hit lymphomas, otherwise the term single-hit lymphomas is applied. In order to characterize the biological features of these MYC(+) lymphomas other than Burkitt lymphoma we explored, after exclusion of molecular Burkitt lymphoma as defined by gene expression profiling, the molecular, pathological and clinical aspects of 80 MYC-translocation-positive lymphomas (31 single-hit, 46 double-hit and 3 MYC(+)-lymphomas with unknown BCL6 status). Comparison of single-hit and double-hit lymphomas revealed no difference in MYC partner (IG/non-IG), genomic complexity, MYC expression or gene expression profile. Double-hit lymphomas more frequently showed a germinal center B-cell-like gene expression profile and had higher IGH and MYC mutation frequencies. Gene expression profiling revealed 130 differentially expressed genes between BCL6(+)/MYC(+) and BCL2(+)/MYC(+) double-hit lymphomas. BCL2(+)/MYC(+) double-hit lymphomas more frequently showed a germinal center B-like gene expression profile. Analysis of all lymphomas according to MYC partner (IG/non-IG) revealed no substantial differences. In this series of lymphomas, in which immunochemotherapy was administered in only a minority of cases, single-hit and double-hit lymphomas had a similar poor outcome in contrast to the outcome of molecular Burkitt lymphoma and lymphomas without the MYC break. Our data suggest that, after excluding molecular Burkitt lymphoma and pediatric cases, MYC(+) lymphomas are biologically quite homogeneous with single-hit and double-hit lymphomas as well as IG-MYC and non-IG-MYC(+) lymphomas sharing various molecular characteristics.

Integrating Genomic Analysis with the Genetic Basis of Gene Expression: Preliminary Evidence of the Identification of Causal Genes for Cardiovascular and Metabolic Traits Related to Nutrition in Mexicans123

PubMed Central

Bastarrachea, Raúl A.; Gallegos-Cabriales, Esther C.; Nava-González, Edna J.; Haack, Karin; Voruganti, V. Saroja; Charlesworth, Jac; Laviada-Molina, Hugo A.; Veloz-Garza, Rosa A.; Cardenas-Villarreal, Velia Margarita; Valdovinos-Chavez, Salvador B.; Gomez-Aguilar, Patricia; Meléndez, Guillermo; López-Alvarenga, Juan Carlos; Göring, Harald H. H.; Cole, Shelley A.; Blangero, John; Comuzzie, Anthony G.; Kent, Jack W.

2012-01-01

Whole-transcriptome expression profiling provides novel phenotypes for analysis of complex traits. Gene expression measurements reflect quantitative variation in transcript-specific messenger RNA levels and represent phenotypes lying close to the action of genes. Understanding the genetic basis of gene expression will provide insight into the processes that connect genotype to clinically significant traits representing a central tenet of system biology. Synchronous in vivo expression profiles of lymphocytes, muscle, and subcutaneous fat were obtained from healthy Mexican men. Most genes were expressed at detectable levels in multiple tissues, and RNA levels were correlated between tissue types. A subset of transcripts with high reliability of expression across tissues (estimated by intraclass correlation coefficients) was enriched for cis-regulated genes, suggesting that proximal sequence variants may influence expression similarly in different cellular environments. This integrative global gene expression profiling approach is proving extremely useful for identifying genes and pathways that contribute to complex clinical traits. Clearly, the coincidence of clinical trait quantitative trait loci and expression quantitative trait loci can help in the prioritization of positional candidate genes. Such data will be crucial for the formal integration of positional and transcriptomic information characterized as genetical genomics. PMID:22797999

Molecular profiling of the developing avian telencephalon: regional timing and brain subdivision continuities.

PubMed

Chen, Chun-Chun; Winkler, Candace M; Pfenning, Andreas R; Jarvis, Erich D

2013-11-01

In our companion study (Jarvis et al. [2013] J Comp Neurol. doi: 10.1002/cne.23404) we used quantitative brain molecular profiling to discover that distinct subdivisions in the avian pallium above and below the ventricle and the associated mesopallium lamina have similar molecular profiles, leading to a hypothesis that they may form as continuous subdivisions around the lateral ventricle. To explore this hypothesis, here we profiled the expression of 16 genes at eight developmental stages. The genes included those that define brain subdivisions in the adult and some that are also involved in brain development. We found that phyletic hierarchical cluster and linear regression network analyses of gene expression profiles implicated single and mixed ancestry of these brain regions at early embryonic stages. Most gene expression-defined pallial subdivisions began as one ventral or dorsal domain that later formed specific folds around the lateral ventricle. Subsequently a clear ventricle boundary formed, partitioning them into dorsal and ventral pallial subdivisions surrounding the mesopallium lamina. These subdivisions each included two parts of the mesopallium, the nidopallium and hyperpallium, and the arcopallium and hippocampus, respectively. Each subdivision expression profile had a different temporal order of appearance, similar in timing to the order of analogous cell types of the mammalian cortex. Furthermore, like the mammalian pallium, expression in the ventral pallial subdivisions became distinct during prehatch development, whereas the dorsal portions did so during posthatch development. These findings support the continuum hypothesis of avian brain subdivision development around the ventricle and influence hypotheses on homologies of the avian pallium with other vertebrates. Copyright © 2013 Wiley Periodicals, Inc.

Leader personality and crew effectiveness - A full-mission simulation experiment

NASA Technical Reports Server (NTRS)

Chidester, Thomas R.; Foushee, H. Clayton

1989-01-01

A full-mission simulation research study was completed to assess the impact of individual personality on crew performance. Using a selection algorithm described by Chidester (1987), captains were classified as fitting one of three profiles along a battery of personality assessment scales. The performances of 23 crews led by captains fitting each profile were contrasted over a one and one-half day simulated trip. Crews led by captains fitting a positive Instrumental-Expressive profile (high achievement motivation and interpersonal skill) were consistently effective and made fewer errors. Crews led by captains fitting a Negative Expressive profile (below average achievement motivation, negative expressive style, such as complaining) were consistently less effective and made more errors. Crews led by captains fitting a Negative Instrumental profile (high levels of competitiveness, Verbal Aggressiveness, and Impatience and Irritability) were less effective on the first day but equal to the best on the second day. These results underscore the importance of stable personality variables as predictors of team coordination and performance.

Single-cell mRNA profiling reveals transcriptional heterogeneity among pancreatic circulating tumour cells.

PubMed

Lapin, Morten; Tjensvoll, Kjersti; Oltedal, Satu; Javle, Milind; Smaaland, Rune; Gilje, Bjørnar; Nordgård, Oddmund

2017-05-31

Single-cell mRNA profiling of circulating tumour cells may contribute to a better understanding of the biology of these cells and their role in the metastatic process. In addition, such analyses may reveal new knowledge about the mechanisms underlying chemotherapy resistance and tumour progression in patients with cancer. Single circulating tumour cells were isolated from patients with locally advanced or metastatic pancreatic cancer with immuno-magnetic depletion and immuno-fluorescence microscopy. mRNA expression was analysed with single-cell multiplex RT-qPCR. Hierarchical clustering and principal component analysis were performed to identify expression patterns. Circulating tumour cells were detected in 33 of 56 (59%) examined blood samples. Single-cell mRNA profiling of intact isolated circulating tumour cells revealed both epithelial-like and mesenchymal-like subpopulations, which were distinct from leucocytes. The profiled circulating tumour cells also expressed elevated levels of stem cell markers, and the extracellular matrix protein, SPARC. The expression of SPARC might correspond to an epithelial-mesenchymal transition in pancreatic circulating tumour cells. The analysis of single pancreatic circulating tumour cells identified distinct subpopulations and revealed elevated expression of transcripts relevant to the dissemination of circulating tumour cells to distant organ sites.

Fidelity and enhanced sensitivity of differential transcription profiles following linear amplification of nanogram amounts of endothelial mRNA

NASA Technical Reports Server (NTRS)

Polacek, Denise C.; Passerini, Anthony G.; Shi, Congzhu; Francesco, Nadeene M.; Manduchi, Elisabetta; Grant, Gregory R.; Powell, Steven; Bischof, Helen; Winkler, Hans; Stoeckert, Christian J Jr;

Impacts of temperature and lunar day on gene expression profiles during a monthly reproductive cycle in the brooding coral Pocillopora damicornis.

PubMed

Crowder, Camerron M; Meyer, Eli; Fan, Tung-Yung; Weis, Virginia M

2017-08-01

Reproductive timing in brooding corals has been correlated to temperature and lunar irradiance, but the mechanisms by which corals transduce these environmental variables into molecular signals are unknown. To gain insight into these processes, global gene expression profiles in the coral Pocillopora damicornis were examined (via RNA-Seq) across lunar phases and between temperature treatments, during a monthly planulation cycle. The interaction of temperature and lunar day together had the largest influence on gene expression. Mean timing of planulation, which occurred at lunar days 7.4 and 12.5 for 28- and 23°C-treated corals, respectively, was associated with an upregulation of transcripts in individual temperature treatments. Expression profiles of planulation-associated genes were compared between temperature treatments, revealing that elevated temperatures disrupted expression profiles associated with planulation. Gene functions inferred from homologous matches to online databases suggest complex neuropeptide signalling, with calcium as a central mediator, acting through tyrosine kinase and G protein-coupled receptor pathways. This work contributes to our understanding of coral reproductive physiology and the impacts of environmental variables on coral reproductive pathways. © 2017 John Wiley & Sons Ltd.

Generation of novel pharmacogenomic candidates in the response to methotrexate in juvenile idiopathic arthritis: correlation between gene expression and genotype

PubMed Central

Moncrieffe, Halima; Hinks, Anne; Ursu, Simona; Kassoumeri, Laura; Etheridge, Angela; Hubank, Mike; Martin, Paul; Weiler, Tracey; Glass, David N; Thompson, Susan D.; Thomson, Wendy; Wedderburn, Lucy R

2010-01-01

Objectives Little is known about mechanisms of efficacy of methotrexate (MTX) in childhood arthritis, or genetic influences upon response to MTX. The aims of this study were to use gene expression profiling to identify novel pathways/genes altered by MTX and then investigate these genes for genotype associations with response to MTX treatment. Methods Gene expression profiling before and after MTX treatment was performed on 11 children with juvenile idiopathic arthritis (JIA) treated with MTX, in whom response at 6 months of treatment was defined. Genes showing the most differential gene expression after treatment were selected for SNP genotyping. Genotype frequencies were compared between non-responders and responders (ACR-Ped70). An independent cohort was available for validation. Results Gene expression profiling before and after MTX treatment revealed 1222 differentially expressed probes sets (fold change >1.7, p< 0.05) and 1065 when restricted to full responder cases only. Six highly differentially expressed genes were analysed for genetic association to response to MTX. Three SNPs in the SLC16A7 gene showed significant association with MTX response. One SNP showed validated association in an independent cohort. Conclusions This study is the first, to our knowledge, to evaluate gene expression profiles in children with JIA before and after MTX, and to analyse genetic variation in differentially expressed genes. We have identified a gene which may contribute to genetic variability in MTX response in JIA, and established as proof of principle that genes which are differentially expressed at mRNA level after drug administration may also be good candidates for genetic analysis. PMID:20827233

c-kit expression profile and regulatory factors during spermatogonial stem cell differentiation

PubMed Central

2013-01-01

Background It has been proven that c-kit is crucial for proliferation, migration, survival and maturation of spermatogenic cells. A periodic expression of c-kit is observed from primordial germ cells (PGCs) to spermatogenetic stem cells (SSCs), However, the expression profile of c-kit during the entire spermatogenesis process is still unclear. This study aims to reveal and compare c-kit expression profiles in the SSCs before and after the anticipated differentiation, as well as to examine its relationship with retinoic acid (RA) stimulation. Results We have found that there are more than 4 transcripts of c-kit expressed in the cell lines and in the testes. The transcripts can be divided into short and long categories. The long transcripts include the full-length canonical c-kit transcript and the 3′ end short transcript. Short transcripts include the 3.4 kb short transcript and several truncated transcripts (1.9-3.2 kb). In addition, the 3.4 kb transcript (starting from intron 9 and covering exons 10 ~ 21) is discovered to be specifically expressed in the spermatogonia. The extracellular domain of Kit is obtained in the spermatogonia stage, but the intracellular domain (50 kDa) is constantly expressed in both SSCs and spermatogonia. The c-kit expression profiles in the testis and the spermatogonial stem cell lines vary after RA stimulation. The wave-like changes of the quantitative expression pattern of c-kit (increase initially and decrease afterwards) during the induction process are similar to that of the in vivo male germ cell development process. Conclusions There are dynamic transcription and translation changes of c-kit before and after SSCs’ anticipated differentiation and most importantly, RA is a significant upstream regulatory factor for c-kit expression. PMID:24161026

Gene expression profiles in whole blood and associations with metabolic dysregulation in obesity.

PubMed

Cox, Amanda J; Zhang, Ping; Evans, Tiffany J; Scott, Rodney J; Cripps, Allan W; West, Nicholas P

Gene expression data provides one tool to gain further insight into the complex biological interactions linking obesity and metabolic disease. This study examined associations between blood gene expression profiles and metabolic disease in obesity. Whole blood gene expression profiles, performed using the Illumina HT-12v4 Human Expression Beadchip, were compared between (i) individuals with obesity (O) or lean (L) individuals (n=21 each), (ii) individuals with (M) or without (H) Metabolic Syndrome (n=11 each) matched on age and gender. Enrichment of differentially expressed genes (DEG) into biological pathways was assessed using Ingenuity Pathway Analysis. Association between sets of genes from biological pathways considered functionally relevant and Metabolic Syndrome were further assessed using an area under the curve (AUC) and cross-validated classification rate (CR). For OvL, only 50 genes were significantly differentially expressed based on the selected differential expression threshold (1.2-fold, p<0.05). For MvH, 582 genes were significantly differentially expressed (1.2-fold, p<0.05) and pathway analysis revealed enrichment of DEG into a diverse set of pathways including immune/inflammatory control, insulin signalling and mitochondrial function pathways. Gene sets from the mTOR signalling pathways demonstrated the strongest association with Metabolic Syndrome (p=8.1×10 -8 ; AUC: 0.909, CR: 72.7%). These results support the use of expression profiling in whole blood in the absence of more specific tissue types for investigations of metabolic disease. Using a pathway analysis approach it was possible to identify an enrichment of DEG into biological pathways that could be targeted for in vitro follow-up. Copyright © 2017 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

Recrudescence Mechanisms and Gene Expression Profile of the Reproductive Tracts from Chickens during the Molting Period

PubMed Central

Ahn, Suzie E.; Lim, Chul-Hong; Lee, Jin-Young; Bae, Seung-Min; Kim, Jinyoung; Bazer, Fuller W.; Song, Gwonhwa

2013-01-01

The reproductive system of chickens undergoes dynamic morphological and functional tissue remodeling during the molting period. The present study identified global gene expression profiles following oviductal tissue regression and regeneration in laying hens in which molting was induced by feeding high levels of zinc in the diet. During the molting and recrudescence processes, progressive morphological and physiological changes included regression and re-growth of reproductive organs and fluctuations in concentrations of testosterone, progesterone, estradiol and corticosterone in blood. The cDNA microarray analysis of oviductal tissues revealed the biological significance of gene expression-based modulation in oviductal tissue during its remodeling. Based on the gene expression profiles, expression patterns of selected genes such as, TF, ANGPTL3, p20K, PTN, AvBD11 and SERPINB3 exhibited similar patterns in expression with gradual decreases during regression of the oviduct and sequential increases during resurrection of the functional oviduct. Also, miR-1689* inhibited expression of Sp1, while miR-17-3p, miR-22* and miR-1764 inhibited expression of STAT1. Similarly, chicken miR-1562 and miR-138 reduced the expression of ANGPTL3 and p20K, respectively. These results suggest that these differentially regulated genes are closely correlated with the molecular mechanism(s) for development and tissue remodeling of the avian female reproductive tract, and that miRNA-mediated regulation of key genes likely contributes to remodeling of the avian reproductive tract by controlling expression of those genes post-transcriptionally. The discovered global gene profiles provide new molecular candidates responsible for regulating morphological and functional recrudescence of the avian reproductive tract, and provide novel insights into understanding the remodeling process at the genomic and epigenomic levels. PMID:24098561

GENE EXPRESSION PROFILING OF ACCESSIBLE SURROGATE TISSUES TO MONITOR MOLECULAR CHANGES IN INACCESSIBLE TARGET TISSUES FOLLOWING TOXICANT EXPOSURE

EPA Science Inventory

Gene Expression Profiling Of Accessible Surrogate Tissues To Monitor Molecular Changes In Inaccessible Target Tissues Following Toxicant Exposure
John C. Rockett, Chad R. Blystone, Amber K. Goetz, Rachel N. Murrell, Judith E. Schmid and David J. Dix
Reproductive Toxicology ...

21 CFR 866.6040 - Gene expression profiling test system for breast cancer prognosis.

Code of Federal Regulations, 2010 CFR

2010-04-01

... cancer prognosis. 866.6040 Section 866.6040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... cancer prognosis. (a) Identification. A gene expression profiling test system for breast cancer prognosis... previously diagnosed breast cancer. (b) Classification. Class II (special controls). The special control is...

21 CFR 866.6040 - Gene expression profiling test system for breast cancer prognosis.

Code of Federal Regulations, 2011 CFR

2011-04-01

... cancer prognosis. 866.6040 Section 866.6040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... cancer prognosis. (a) Identification. A gene expression profiling test system for breast cancer prognosis... previously diagnosed breast cancer. (b) Classification. Class II (special controls). The special control is...

EXPRESSION PROFILING OF ESTROGENIC COMPOUNDS USING A SHEEPSHEAD MINNOW CDNA MACROARRAY

EPA Science Inventory

Larkin, Patrick, Leroy C. Folmar, Michael J. Hemmer, Arianna J. Poston and Nancy D. Denslow. 2003. Expression Profiling of Estrogenic Compounds Using a Sheepshead Minnow cDNA Macroarray. Environ. Health Perspect. 111(6):839-846. (ERL,GB 1171).

A variety of anthropogenic c...

Use of Microarray to Analyze Gene Expression Profiles of Acute Effects of Prochloraz on Fathead Minnows Pimephales promelas

EPA Science Inventory

Microarray technology is a powerful tool to investigate the gene expression profiles for thousands of genes simultaneously. In recent years, microarrays have been used to characterize environmental pollutants and identify molecular mode(s) of action of chemicals including endocri...

Bioinforrnatics of Gene Expression Profiling Data Provide Mechanistic Understanding of Acute Ozone-Induced Lung injury

EPA Science Inventory

Acute ozone-induced pulmonary injury and inflammation are well characterized. A few studies have used gene expression profiling to determine the types of changes induced by ozone; however the mechanisms or the pathways involved are less well understood. We presumed that robust bi...

Comparison of Non-Human Primate and Human Whole Blood Tissue Gene Expression Profiles

DTIC Science & Technology

2005-03-01

studies have used rhesus, chimpanzee, gorilla, or orangutan RNA, but to date no gene expression profiling studies are available that use AGM or cynomologus...previous work has been published using human genechips to study NHPs, particularly rhesus, chimpanzee, gorilla, and orangutan (Uddin et al., 2004; Kayo

21 CFR 866.6040 - Gene expression profiling test system for breast cancer prognosis.

Code of Federal Regulations, 2013 CFR

2013-04-01

... cancer prognosis. 866.6040 Section 866.6040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... cancer prognosis. (a) Identification. A gene expression profiling test system for breast cancer prognosis... previously diagnosed breast cancer. (b) Classification. Class II (special controls). The special control is...

21 CFR 866.6040 - Gene expression profiling test system for breast cancer prognosis.

Code of Federal Regulations, 2012 CFR

2012-04-01

... cancer prognosis. 866.6040 Section 866.6040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... cancer prognosis. (a) Identification. A gene expression profiling test system for breast cancer prognosis... previously diagnosed breast cancer. (b) Classification. Class II (special controls). The special control is...

21 CFR 866.6040 - Gene expression profiling test system for breast cancer prognosis.

Code of Federal Regulations, 2014 CFR

2014-04-01

... cancer prognosis. 866.6040 Section 866.6040 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF... cancer prognosis. (a) Identification. A gene expression profiling test system for breast cancer prognosis... previously diagnosed breast cancer. (b) Classification. Class II (special controls). The special control is...

RESIDUAL OIL FLY ASH (ROFA) AND VANADIUM-INDUCED GENE EXPRESSION PROFILES IN HUMAN VASCULAR ENDOTHELIAL CELLS

EPA Science Inventory

Residual oil fly ash (ROFA) and vanadium-induced gene expression profiles in human vascular endothelial cells.
Srikanth S. Nadadur, Urmila P. Kodavanti, Mary Jane Selgrade and Daniel L. Costa, Pulmonary Toxicology Branch, ETD, NHEERL, ORD, US EPA, Research Triangle Park, N...

Candidate EDA targets revealed by expression profiling of primary keratinocytes from Tabby mutant mice

PubMed Central

Esibizione, Diana; Cui, Chang-Yi; Schlessinger, David

2009-01-01

EDA, the gene mutated in anhidrotic ectodermal dysplasia, encodes ectodysplasin, a TNF superfamily member that activates NF-kB mediated transcription. To identify EDA target genes, we have earlier used expression profiling to infer genes differentially expressed at various developmental time points in Tabby (Eda-deficient) compared to wild-type mouse skin. To increase the resolution to find genes whose expression may be restricted to epidermal cells, we have now extended studies to primary keratinocyte cultures established from E19 wild-type and Tabby skin. Using microarrays bearing 44,000 gene probes, we found 385 preliminary candidate genes whose expression was significantly affected by Eda loss. By comparing expression profiles to those from Eda-A1 transgenic skin, we restricted the list to 38 “candidate EDA targets”, 14 of which were already known to be expressed in hair follicles or epidermis. We confirmed expression changes for 3 selected genes, Tbx1, Bmp7, and Jag1, both in keratinocytes and in whole skin, by Q-PCR and Western blotting analyses. Thus, by the analysis of keratinocytes, novel candidate pathways downstream of EDA were detected. PMID:18848976

PROSPECT: Profiling of Resistance Patterns & Oncogenic Signaling Pathways in Evaluation of Cancers of the Thorax and Therapeutic Target Identification

DTIC Science & Technology

2012-06-01

neoadjuvant therapies on disease-free, progression-free, and overall survival will vary across prognostically distinct groups. 3. Specific molecular... prognostically distinct subpopulations of patients with resectable NSCLC, and to assess the extent to which these molecular profiles correlate with tumor...overall survival, and will use Cox proportional hazards models and recursive partitioning methods to identify important biomarkers and prognostically

Transcriptional profiling of the early stages of germination in Candida albicans by real-time RT-PCR.

PubMed

Toyoda, Mika; Cho, Tamaki; Kaminishi, Hidenori; Sudoh, Masayuki; Chibana, Hiroji

2004-12-01

By using real-time RT-PCR, we profiled the expression of CGR1, CaMSI3, EFG1, NRG1, and TUP1 in Candida albicans strains JCM9061 and CAI4 under several conditions, including induction of morphological transition, heat shock, and treatment with calcium inhibitors. Expression of CaMSI3 changed under these growth conditions except during heat shock. CGR1 expression increased during the early stages of hyphal growth in JCM9061, while expression was strain-dependent during heat shock. Both EFG1 and NRG1 were similarly expressed under hypha-inducing conditions and heat shock. Expression of TUP1 was slightly different from the expression of EFG1 or NRG1.

AR-V7 in Peripheral Whole Blood of Patients with Castration-resistant Prostate Cancer: Association with Treatment-specific Outcome Under Abiraterone and Enzalutamide.

PubMed

Seitz, Anna Katharina; Thoene, Silvia; Bietenbeck, Andreas; Nawroth, Roman; Tauber, Robert; Thalgott, Mark; Schmid, Sebastian; Secci, Ramona; Retz, Margitta; Gschwend, Jürgen E; Ruland, Jürgen; Winter, Christof; Heck, Matthias M

2017-11-01

It has been demonstrated that androgen receptor splice variant 7 (AR-V7) expression in circulating tumor cells (CTCs) predicts poor treatment response in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone or enzalutamide. To develop a practical and robust liquid profiling approach for direct quantification of AR-V7 in peripheral whole blood without the need for CTC capture and to determine its potential for predicting treatment response in mCRPC patients. Whole blood samples from a prospective biorepository of 85 mCRPC patients before treatment initiation with abiraterone (n=56) or enzalutamide (n=29) were analyzed via droplet digital polymerase chain reaction. The association of AR-V7 status with prostate-specific antigen (PSA) response defined by PSA decline ≥50% and with PSA-progression-free survival (PSA-PFS), clinical PFS, and overall survival (OS) was assessed. High AR-V7 expression levels in whole blood were detectable in 18% (15/85) of patients. No patient with high AR-V7 expression achieved a PSA response, and AR-V7 status was an independent predictor of PSA response in multivariable logistic regression analysis (p=0.03). High AR-V7 expression was associated with shorter PSA-PFS (median 2.4 vs 3.7 mo; p<0.001), shorter clinical PFS (median 2.7 vs 5.5 mo; p<0.001), and shorter OS (median 4.0 vs. 13.9 mo; p<0.001). On multivariable Cox regression analysis, high AR-V7 expression remained an independent predictor of shorter PSA-PFS (hazard ratio [HR] 7.0, 95% confidence interval [CI] 2.3-20.7; p<0.001), shorter clinical PFS (HR 2.3, 95% CI 1.1-4.9; p=0.02), and shorter OS (HR 3.0, 95% CI 1.4-6.3; p=0.005). Testing of AR-V7 mRNA levels in whole blood is a simple and promising approach to predict poor treatment outcome in mCRPC patients receiving abiraterone or enzalutamide. We established a method for determining AR-V7 status in whole blood. This test predicted treatment resistance in patients with metastatic castration-resistant prostate cancer undergoing treatment with abiraterone or enzalutamide. Prospective validation is needed before application to clinical practice. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Genome-wide Gene Expression Profiling of Acute Metal Exposures in Male Zebrafish

DTIC Science & Technology

2014-10-23

Data in Brief Genome-wide gene expression profiling of acute metal exposures in male zebrafish Christine E. Baer a,⁎, Danielle L. Ippolito b, Naissan... Zebrafish Whole organism Nickel Chromium Cobalt Toxicogenomics To capture global responses to metal poisoning and mechanistic insights into metal...toxicity, gene expression changes were evaluated in whole adult male zebrafish following acute 24 h high dose exposure to three metals with known human

A Gene Expression Signature Associated with Overall Survival in Patients with Hepatocellular Carcinoma Suggests a New Treatment Strategy.

PubMed

Gillet, Jean-Pierre; Andersen, Jesper B; Madigan, James P; Varma, Sudhir; Bagni, Rachel K; Powell, Katie; Burgan, William E; Wu, Chung-Pu; Calcagno, Anna Maria; Ambudkar, Suresh V; Thorgeirsson, Snorri S; Gottesman, Michael M

2016-02-01

Despite improvements in the management of liver cancer, the survival rate for patients with hepatocellular carcinoma (HCC) remains dismal. The survival benefit of systemic chemotherapy for the treatment of liver cancer is only marginal. Although the reasons for treatment failure are multifactorial, intrinsic resistance to chemotherapy plays a primary role. Here, we analyzed the expression of 377 multidrug resistance (MDR)-associated genes in two independent cohorts of patients with advanced HCC, with the aim of finding ways to improve survival in this poor-prognosis cancer. Taqman-based quantitative polymerase chain reaction revealed a 45-gene signature that predicts overall survival (OS) in patients with HCC. Using the Connectivity Map Tool, we were able to identify drugs that converted the gene expression profiles of HCC cell lines from ones matching patients with poor OS to profiles associated with good OS. We found three compounds that convert the gene expression profiles of three HCC cell lines to gene expression profiles associated with good OS. These compounds increase histone acetylation, which correlates with the synergistic sensitization of those MDR tumor cells to conventional chemotherapeutic agents, including cisplatin, sorafenib, and 5-fluorouracil. Our results indicate that it is possible to modulate gene expression profiles in HCC cell lines to those associated with better outcome. This approach also increases sensitization of HCC cells toward conventional chemotherapeutic agents. This work suggests new treatment strategies for a disease for which few therapeutic options exist. U.S. Government work not protected by U.S. copyright.

The influence of high glucose on the Cip/Kip family expression profiles in HRECs.

PubMed

Tian, Jingyi; Ma, Hongjie; Luo, Yan; Hu, Andina; Lin, Shaofen; Li, Tao; Guo, Kai; Li, Jing; Cai, Meng; Tang, Shibo

2013-12-01

Neovascularization is the main characteristic of the proliferative stage of diabetic retinopathy. It has been proven that cell cycle regulation is involved in angiogenesis. The cell cycle regulators, Cip/Kip protein family, belong to the cyclin-dependent kinase inhibitors, are versatile proteins, and except for their function in cell cycle regulation, they also participate in transcription, apoptosis and migration. The expression profiles of the Cip/Kip family in human retina microvascular endothelial cells (HRECs) under normal or high glucose conditions has not been described before. This study was undertaken to determine the expression profiles of the Cip/Kip family proteins, e.g., proteins which are influenced by high glucose and in what manner. Western blot and immunofluorescence analyses were used to investigate the protein expression profiles. Only p21(cip1) and p27(kip1) were detected in HRECs, and they were located in the nucleus. P21(cip1) protein abundance was higher than p27(kip1) in HRECs. Incubation of HRECs in medium containing 30 mM D-glucose for 48 h resulted in downregulation of p21(cip1) protein expression, but had no influence on p27(kip1) protein levels or p21(cip1) mRNA abundance. These results were accompanied by cell cycle G1 phase exit and a lower cell survival rate. Our data show for the first time that high glucose changes the Cip/Kip family expression profiles in HRECs, which may be the foundation for the investigation of the role of the Cip/Kip family in the pathogenesis of diabetic retinopathy.

Similar Response Patterns to 5%Topical Minoxidil Foam in Frontal and Vertex Scalp of Men with Androgenetic Alopecia: A Microarray Analysis

PubMed Central

Mirmirani, P.; Consolo, M.; Oyetakin-White, P.; Baron, E.; Leahy, P.; Karnik, P.

2014-01-01

Summary Background There are regional variations in scalp hair miniaturization seen in androgenetic alopecia (AGA). Use of topical minoxidil can lead to reversal of miniaturization in the vertex scalp. However, its effects on other scalp regions are less well studied. Methods A placebo controlled double-blinded prospective pilot study of minoxidil topical foam 5% (MTF) vs placebo was conducted in sixteen healthy men ages 18-49 with Hamilton-Norwood type IV-V thinning. The subjects were asked to apply the treatment (active drug or placebo) to the scalp twice daily for eight weeks. Stereotactic scalp photographs were taken at the baseline and final visits to monitor global hair growth. Scalp biopsies were done at the leading edge of hair loss from the frontal and vertex scalp before and after treatment with MTF and placebo and microarray analysis was done using the Affymetrix GeneChip HG U133 Plus 2.0. Results Global stereotactic photographs showed that MTF induced hair growth in both the frontal and vertex scalp of AGA patients. Regional differences in gene expression profiles were observed before treatment. However, MTF treatment induced the expression of hair keratin associated genes and decreased the expression of epidermal differentiation complex (EDC) and inflammatory genes in both scalp regions. Conclusions These data suggest that MTF is effective in the treatment of both the frontal and vertex scalp of AGA patients. PMID:25204361

Low adherent cancer cell subpopulations are enriched in tumorigenic and metastatic epithelial-to-mesenchymal transition-induced cancer stem-like cells.

PubMed

Morata-Tarifa, Cynthia; Jiménez, Gema; García, María A; Entrena, José M; Griñán-Lisón, Carmen; Aguilera, Margarita; Picon-Ruiz, Manuel; Marchal, Juan A

2016-01-11

Cancer stem cells are responsible for tumor progression, metastasis, therapy resistance and cancer recurrence, doing their identification and isolation of special relevance. Here we show that low adherent breast and colon cancer cells subpopulations have stem-like properties. Our results demonstrate that trypsin-sensitive (TS) breast and colon cancer cells subpopulations show increased ALDH activity, higher ability to exclude Hoechst 33342, enlarged proportion of cells with a cancer stem-like cell phenotype and are enriched in sphere- and colony-forming cells in vitro. Further studies in MDA-MB-231 breast cancer cells reveal that TS subpopulation expresses higher levels of SLUG, SNAIL, VIMENTIN and N-CADHERIN while show a lack of expression of E-CADHERIN and CLAUDIN, being this profile characteristic of the epithelial-to-mesenchymal transition (EMT). The TS subpopulation shows CXCL10, BMI-1 and OCT4 upregulation, differing also in the expression of several miRNAs involved in EMT and/or cell self-renewal such as miR-34a-5p, miR-34c-5p, miR-21-5p, miR-93-5p and miR-100-5p. Furthermore, in vivo studies in immunocompromised mice demonstrate that MDA-MB-231 TS cells form more and bigger xenograft tumors with shorter latency and have higher metastatic potential. In conclusion, this work presents a new, non-aggressive, easy, inexpensive and reproducible methodology to isolate prospectively cancer stem-like cells for subsequent biological and preclinical studies.

The Development of Early Profiles of Temperament: Characterization, Continuity, and Etiology.

PubMed

Beekman, Charles; Neiderhiser, Jenae M; Buss, Kristin A; Loken, Eric; Moore, Ginger A; Leve, Leslie D; Ganiban, Jody M; Shaw, Daniel S; Reiss, David

2015-01-01

This study used a data-driven, person-centered approach to examine the characterization, continuity, and etiology of child temperament from infancy to toddlerhood. Data from 561 families who participated in an ongoing prospective adoption study, the Early Growth and Development Study, were used to estimate latent profiles of temperament at 9, 18, and 27 months. Results indicated that four profiles of temperament best fit the data at all three points of assessment. The characterization of profiles was stable over time, while membership in profiles changed across age. Facets of adoptive parent and birth mother personality were predictive of children's profile membership at each age, providing preliminary evidence for specific environmental and genetic influences on patterns of temperament development from infancy to toddlerhood. © 2015 The Authors. Child Development © 2015 Society for Research in Child Development, Inc.

Evidence for the cytotoxic effects of Mycobacterium tuberculosis phospholipase C towards macrophages.

PubMed

Bakala N'goma, J C; Schué, M; Carrière, F; Geerlof, A; Canaan, S

2010-12-01

Phospholipase Cs (PLCs) contribute importantly to the virulence and pathogenicity of several bacteria. It has been reported in previous studies that mutations in the four predicted plc genes of Mycobacterium tuberculosis inhibit the growth of these bacteria during the late phase of infection in mice. These enzymes have not yet been fully characterised, mainly because they are not easy to produce in large quantities. With a view to elucidating the role of all Mycobacterium tuberculosis phospholipase Cs (PLC-A, PLC-B, PLC-C and PLC-D), a large amount of active, soluble recombinant PLCs, were expressed and purified using Mycobacterium smegmatis as expression system. These enzymes showed different pH activity profiles. PLC-C was found to be the most active of the four recombinant PLCs under acidic conditions. All the enzymes tested induced cytotoxic effects on mouse macrophage RAW 264.7 cell lines, via direct or indirect enzymatic hydrolysis of cell membrane phospholipids. These results open new prospects for characterising biochemical and structural features of Mycobacterium tuberculosis PLCs, which might lead to the identification of novel anti-tuberculosis drug targets. All mycobacterial phospholipase Cs can now be studied in order to determine their role in the virulence and pathogenicity of bacteria of this kind. 2010 Elsevier B.V. All rights reserved.

Asymmetric segregation and self-renewal of hematopoietic stem and progenitor cells with endocytic Ap2a2.

PubMed

Ting, Stephen B; Deneault, Eric; Hope, Kristin; Cellot, Sonia; Chagraoui, Jalila; Mayotte, Nadine; Dorn, Jonas F; Laverdure, Jean-Philippe; Harvey, Michael; Hawkins, Edwin D; Russell, Sarah M; Maddox, Paul S; Iscove, Norman N; Sauvageau, Guy

2012-03-15

The stem cell-intrinsic model of self-renewal via asymmetric cell division (ACD) posits that fate determinants be partitioned unequally between daughter cells to either activate or suppress the stemness state. ACD is a purported mechanism by which hematopoietic stem cells (HSCs) self-renew, but definitive evidence for this cellular process remains open to conjecture. To address this issue, we chose 73 candidate genes that function within the cell polarity network to identify potential determinants that may concomitantly alter HSC fate while also exhibiting asymmetric segregation at cell division. Initial gene-expression profiles of polarity candidates showed high and differential expression in both HSCs and leukemia stem cells. Altered HSC fate was assessed by our established in vitro to in vivo screen on a subcohort of candidate polarity genes, which revealed 6 novel positive regulators of HSC function: Ap2a2, Gpsm2, Tmod1, Kif3a, Racgap1, and Ccnb1. Interestingly, live-cell videomicroscopy of the endocytic protein AP2A2 shows instances of asymmetric segregation during HSC/progenitor cell cytokinesis. These results contribute further evidence that ACD is functional in HSC self-renewal, suggest a role for Ap2a2 in HSC activity, and provide a unique opportunity to prospectively analyze progeny from HSC asymmetric divisions.

PAMAM (generation 4) incorporated gelatin 3D matrix as an improved dermal substitute for skin tissue engineering.

PubMed

Maji, Somnath; Agarwal, Tarun; Maiti, Tapas Kumar

2017-07-01

The study explored the prospects of PAMAM (generation 4) applicability in gelatin based scaffolds for skin tissue engineering. The effect of PAMAM on physico-chemical and biological characteristics of gelatin scaffolds was evaluated. Gelatin scaffolds (with/without PAMAM) were prepared by lyophilization, chemically crosslinked by glutaraldehyde and characterized for their morphology (pore size), chemical features (bond nature), water adsorption, biodegradation and biological compatibility. The study demonstrated that addition of PAMAM did not significantly alter the pore size distribution or porosity of the scaffolds. However, water adsorption potential and collagenase mediated degradation significantly enhanced over period of the study. Both the scaffolds (with/without PAMAM) were highly biocompatible and hemocompatible. PAMAM (G4) blended scaffolds showed relatively higher cellular adhesion and proliferation of both keratinocytes and fibroblasts with an improved gene expression profile of native collagen type I of fibroblasts. Moreover, expression of angiogenesis inducing genes, HIF1α and VEGF were also higher in PAMAM blended gelatin matrix. Also, PAMAM incorporated gelatin matrix showed a slower rate of drug release which confirms its suitability for therapeutic delivery during wound healing. These results clearly suggest that blending PAMAM (G4) into the matrix could provide an additional support to scaffold assisted wound healing. Copyright © 2017 Elsevier B.V. All rights reserved.

Gene expression profiling in the early phases of DMD: a constant molecular signature characterizes DMD muscle from early postnatal life throughout disease progression.

PubMed

Pescatori, Mario; Broccolini, Aldobrando; Minetti, Carlo; Bertini, Enrico; Bruno, Claudio; D'amico, Adele; Bernardini, Camilla; Mirabella, Massimiliano; Silvestri, Gabriella; Giglio, Vincenzo; Modoni, Anna; Pedemonte, Marina; Tasca, Giorgio; Galluzzi, Giuliana; Mercuri, Eugenio; Tonali, Pietro A; Ricci, Enzo

2007-04-01

Genome-wide gene expression profiling of skeletal muscle from Duchenne muscular dystrophy (DMD) patients has been used to describe muscle tissue alterations in DMD children older than 5 years. By studying the expression profile of 19 patients younger than 2 years, we describe with high resolution the gene expression signature that characterizes DMD muscle during the initial or "presymptomatic" phase of the disease. We show that in the first 2 years of the disease, DMD muscle is already set to express a distinctive gene expression pattern considerably different from the one expressed by normal, age-matched muscle. This "dystrophic" molecular signature is characterized by a coordinate induction of genes involved in the inflammatory response, extracellular matrix (ECM) remodeling and muscle regeneration, and the reduced transcription of those involved in energy metabolism. Despite the lower degree of muscle dysfunction experienced, our younger patients showed abnormal expression of most of the genes reported as differentially expressed in more advanced stages of the disease. By analyzing our patients as a time series, we provide evidence that some genes, including members of three pathways involved in morphogenetic signaling-Wnt, Notch, and BMP-are progressively induced or repressed in the natural history of DMD.

Dynamics of wound healing signaling as a potential therapeutic target for radiation-induced tissue damage.

PubMed

Chung, Yih-Lin; Pui, Newman N M

2015-01-01

We hypothesized the histone deacetylase inhibitor phenylbutyrate (PB) has beneficial effects on radiation-induced injury by modulating the expression of DNA repair and wound healing genes. Hamsters received a radiosurgical dose of radiation (40 Gy) to the cheek and were treated with varying PB dosing regimens. Gross alteration of the irradiated cheeks, eating function, histological changes, and gene expression during the course of wound healing were compared between treatment groups. Pathological analysis showed decreased radiation-induced mucositis, facilitated epithelial cell growth, and preventing ulcerative wound formation, after short-term PB treatment, but not after vehicle or sustained PB. The radiation-induced wound healing gene expression profile exhibited a sequential transition from the inflammatory and DNA repair phases to the tissue remodeling phase in the vehicle group. Sustained PB treatment resulted in a prolonged wound healing gene expression profile and delayed the wound healing process. Short-term PB shortened the duration of inflammatory cytokine expression, triggered repeated pulsed expression of cell cycle and DNA repair-regulating genes, and promoted earlier oscillatory expression of tissue remodeling genes. Distinct gene expression patterns between sustained and short-term treatment suggest dynamic profiling of wound healing gene expression can be an important part of a biological therapeutic strategy to mitigate radiation-related tissue injury. © 2015 by the Wound Healing Society.

Personal Metaphors of Prospective Secondary Economics and Science Teachers

ERIC Educational Resources Information Center

Mellado, Lucia; Bermejo, Maria Luisa; Mellado, Vicente

2012-01-01

Using the responses to open questions, this qualitative study examines the personal metaphors expressed by prospective secondary education teachers, 46 science graduates and 41 economics graduates. The metaphors are classified into the four categories of Leavy, McSorley, and Bote: the behaviourist/transmissive, the cognitivist/constructivist, the…

MicroRNA and mesial temporal lobe epilepsy with hippocampal sclerosis: Whole miRNome profiling of human hippocampus.

PubMed

Bencurova, Petra; Baloun, Jiri; Musilova, Katerina; Radova, Lenka; Tichy, Boris; Pail, Martin; Zeman, Martin; Brichtova, Eva; Hermanova, Marketa; Pospisilova, Sarka; Mraz, Marek; Brazdil, Milan

2017-10-01

Mesial temporal lobe epilepsy (mTLE) is a severe neurological disorder characterized by recurrent seizures. mTLE is frequently accompanied by neurodegeneration in the hippocampus resulting in hippocampal sclerosis (HS), the most common morphological correlate of drug resistance in mTLE patients. Incomplete knowledge of pathological changes in mTLE+HS complicates its therapy. The pathological mechanism underlying mTLE+HS may involve abnormal gene expression regulation, including posttranscriptional networks involving microRNAs (miRNAs). miRNA expression deregulation has been reported in various disorders, including epilepsy. However, the miRNA profile of mTLE+HS is not completely known and needs to be addressed. Here, we have focused on hippocampal miRNA profiling in 33 mTLE+HS patients and nine postmortem controls to reveal abnormally expressed miRNAs. In this study, we significantly reduced technology-related bias (the most common source of false positivity in miRNA profiling data) by combining two different miRNA profiling methods, namely next generation sequencing and miRNA-specific quantitative real-time polymerase chain reaction. These methods combined have identified and validated 20 miRNAs with altered expression in the human epileptic hippocampus; 19 miRNAs were up-regulated and one down-regulated in mTLE+HS patients. Nine of these miRNAs have not been previously associated with epilepsy, and 19 aberrantly expressed miRNAs potentially regulate the targets and pathways linked with epilepsy (such as potassium channels, γ-aminobutyric acid, neurotrophin signaling, and axon guidance). This study extends current knowledge of miRNA-mediated gene expression regulation in mTLE+HS by identifying miRNAs with altered expression in mTLE+HS, including nine novel abnormally expressed miRNAs and their putative targets. These observations further encourage the potential of microRNA-based biomarkers or therapies. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

microRNA expression profiling in fetal single ventricle malformation identified by deep sequencing.

PubMed

Yu, Zhang-Bin; Han, Shu-Ping; Bai, Yun-Fei; Zhu, Chun; Pan, Ya; Guo, Xi-Rong

2012-01-01

microRNAs (miRNAs) have emerged as key regulators in many biological processes, particularly cardiac growth and development, although the specific miRNA expression profile associated with this process remains to be elucidated. This study aimed to characterize the cellular microRNA profile involved in the development of congenital heart malformation, through the investigation of single ventricle (SV) defects. Comprehensive miRNA profiling in human fetal SV cardiac tissue was performed by deep sequencing. Differential expression of 48 miRNAs was revealed by sequencing by oligonucleotide ligation and detection (SOLiD) analysis. Of these, 38 were down-regulated and 10 were up-regulated in differentiated SV cardiac tissue, compared to control cardiac tissue. This was confirmed by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis. Predicted target genes of the 48 differentially expressed miRNAs were analyzed by gene ontology and categorized according to cellular process, regulation of biological process and metabolic process. Pathway-Express analysis identified the WNT and mTOR signaling pathways as the most significant processes putatively affected by the differential expression of these miRNAs. The candidate genes involved in cardiac development were identified as potential targets for these differentially expressed microRNAs and the collaborative network of microRNAs and cardiac development related-mRNAs was constructed. These data provide the basis for future investigation of the mechanism of the occurrence and development of fetal SV malformations.

Gene expression profiles in peripheral blood mononuclear cells of Chinese nickel refinery workers with high exposures to nickel and control subjects

PubMed Central

Arita, Adriana; Muñoz, Alexandra; Chervona, Yana; Niu, Jingping; Qu, Qingshan; Zhao, Najuan; Ruan, Ye; Kiok, Kathrin; Kluz, Thomas; Sun, Hong; Clancy, Hailey A.; Shamy, Magdy; Costa, Max

2012-01-01

Background Occupational exposure to nickel (Ni) is associated with an increased risk of lung and nasal cancers. Ni compounds exhibit weak mutagenic activity, alter the cell’s epigenetic homeostasis, and activate signaling pathways. However, changes in gene expression associated with Ni exposure have only been investigated in vitro. This study was conducted in a Chinese population to determine whether occupational exposure to Ni was associated with differential gene expression profiles in the peripheral blood mononuclear cells (PBMCs) of Ni-refinery workers when compared to referents. Methods Eight Ni-refinery workers and ten referents were selected. PBMC RNA was extracted and gene expression profiling was performed using Affymetrix exon arrays. Differentially expressed genes between both groups were identified in a global analysis. Results There were a total of 2756 differentially expressed genes (DEG) in the Ni-refinery workers relative to the control subjects (FDR adjusted p<0.05) with 770 up-regulated genes and 1986 down-regulated genes. DNA repair and epigenetic genes were significantly overrepresented (p< 0.0002) among the DEG. Of 31 DNA repair genes, 29 were repressed in the high exposure group and two were overexpressed. Of the 16 epigenetic genes 12 were repressed in the high exposure group and 4 were overexpressed. Conclusions The results of this study indicate that occupational exposure to Ni is associated with alterations in gene expression profiles in PBMCs of subjects. Impact Gene expression may be useful in identifying patterns of deregulation that precede clinical identification of Ni-induced cancers. PMID:23195993

A combined analysis of genome-wide expression profiling of bipolar disorder in human prefrontal cortex.

PubMed

Wang, Jinglu; Qu, Susu; Wang, Weixiao; Guo, Liyuan; Zhang, Kunlin; Chang, Suhua; Wang, Jing

2016-11-01

Numbers of gene expression profiling studies of bipolar disorder have been published. Besides different array chips and tissues, variety of the data processes in different cohorts aggravated the inconsistency of results of these genome-wide gene expression profiling studies. By searching the gene expression databases, we obtained six data sets for prefrontal cortex (PFC) of bipolar disorder with raw data and combinable platforms. We used standardized pre-processing and quality control procedures to analyze each data set separately and then combined them into a large gene expression matrix with 101 bipolar disorder subjects and 106 controls. A standard linear mixed-effects model was used to calculate the differentially expressed genes (DEGs). Multiple levels of sensitivity analyses and cross validation with genetic data were conducted. Functional and network analyses were carried out on basis of the DEGs. In the result, we identified 198 unique differentially expressed genes in the PFC of bipolar disorder and control. Among them, 115 DEGs were robust to at least three leave-one-out tests or different pre-processing methods; 51 DEGs were validated with genetic association signals. Pathway enrichment analysis showed these DEGs were related with regulation of neurological system, cell death and apoptosis, and several basic binding processes. Protein-protein interaction network further identified one key hub gene. We have contributed the most comprehensive integrated analysis of bipolar disorder expression profiling studies in PFC to date. The DEGs, especially those with multiple validations, may denote a common signature of bipolar disorder and contribute to the pathogenesis of disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

Adult cystic nephroma and mixed epithelial and stromal tumor of the kidney are the same disease entity: molecular and histologic evidence.

PubMed

Zhou, Ming; Kort, Eric; Hoekstra, Philip; Westphal, Michael; Magi-Galluzzi, Cristina; Sercia, Linda; Lane, Brian; Rini, Brian; Bukowski, Ronald; Teh, Bin T

2009-01-01

Adult cystic nephroma (CN) and mixed epithelial and stromal tumor of the kidney (MEST) are considered as separate entities in the 2004 World Health Organization classification of renal neoplasms. Recent studies suggested that the two share clinicopathologic features and may represent the same disease process of varying morphology. However, definitive genetic evidence is lacking. We examined their relationship using gene expression profiling and histologic analysis. Gene expression profiles of 3 CN and 3 MEST were analyzed using HGU133 Plus 2.0 microarrays (Affymetrix) and were compared with each other and also with 48 other renal tumors and 13 normal kidneys. Histologic examination of 26 CN and 13 MEST focused on the cystic septal thickness, cyst-to-stroma ratio, stromal cellularity and composition, types of epithelial cells lining cysts and glands, and estrogen and progesterone receptors expression. Patients' age, sex distribution, and tumor size were similar between the two. They also shared many histologic features, including lining epithelium of cysts and glands, stromal cellularity and composition. Unsupervised clustering of mRNA expression profiles demonstrated that they had very similar expression profiles that were distinct from other renal tumors. By microarray analysis, progesterone receptor expression was significantly higher in CN and MEST relative to both normal and other renal tumors, while estrogen receptor expression was not. By immunohistochemistry, expression of both receptors was similar between CN and MEST. This study provides the most convincing molecular evidence that CN and MEST represent different parts of the morphologic spectrum of the same disease.

Stage-specific differential gene expression profiling and functional network analysis during morphogenesis of diphyodont dentition in miniature pigs, Sus Scrofa

PubMed Central

2014-01-01

Background Our current knowledge of tooth development derives mainly from studies in mice, which have only one set of non-replaced teeth, compared with the diphyodont dentition in humans. The miniature pig is also diphyodont, making it a valuable alternative model for understanding human tooth development and replacement. However, little is known about gene expression and function during swine odontogenesis. The goal of this study is to undertake the survey of differential gene expression profiling and functional network analysis during morphogenesis of diphyodont dentition in miniature pigs. The identification of genes related to diphyodont development should lead to a better understanding of morphogenetic patterns and the mechanisms of diphyodont replacement in large animal models and humans. Results The temporal gene expression profiles during early diphyodont development in miniature pigs were detected with the Affymetrix Porcine GeneChip. The gene expression data were further evaluated by ANOVA as well as pathway and STC analyses. A total of 2,053 genes were detected with differential expression. Several signal pathways and 151 genes were then identified through the construction of pathway and signal networks. Conclusions The gene expression profiles indicated that spatio-temporal down-regulation patterns of gene expression were predominant; while, both dynamic activation and inhibition of pathways occurred during the morphogenesis of diphyodont dentition. Our study offers a mechanistic framework for understanding dynamic gene regulation of early diphyodont development and provides a molecular basis for studying teeth development, replacement, and regeneration in miniature pigs. PMID:24498892

Seasonal alteration in amounts of lignans and their glucosides and gene expression of the relevant biosynthetic enzymes in the Forsythia suspense leaf.

PubMed

Morimoto, Kinuyo; Satake, Honoo

2013-01-01

Lignans of Forsythia spp. are essential components of various Chinese medicines and health diets. However, the seasonal alteration in lignan amounts and the gene expression profile of lignan-biosynthetic enzymes has yet to be investigated. In this study, we have assessed seasonal alteration in amounts of major lignans, such as pinoresinol, matairesinol, and arctigenin, and examined the gene expression profile of pinoresinol/lariciresinol reductase (PLR), pinoresinol-glucosylating enzyme (UGT71A18), and secoisolariciresinol dehydrogenase (SIRD) in the leaf of Forsythia suspense from April to November. All of the lignans in the leaf continuously increased from April to June, reached the maximal level in June, and then decreased. Ninety percent of pinoresinol and matairesinol was converted into glucosides, while approximately 50% of arctigenin was aglycone. PLR was stably expressed from April to August, whereas the PLR expression was not detected from September to November. In contrast, the UGT71A18 expression was found from August to November, but not from April to July. The SIRD expression was prominent from April to May, not detected in June to July, and then increased again from September to November. These expression profiles of the lignan-synthetic enzymes are largely compatible with the alteration in lignan contents. Furthermore, such seasonal lignan profiles are in good agreement with the fact that the Forsythia leaves for Chinese medicinal tea are harvested in June. This is the first report on seasonal alteration in lignans and the relevant biosynthetic enzyme genes in the leaf of Forsythia species.

EFFECTS OF STORAGE, RNA EXTRACTION, GENECHIP TYPE, AND DONOR SEX ON GENE EXPRESSION PROFILING OF HUMAN WHOLE BLOOD

EPA Science Inventory

Background: Gene expression profiling of whole blood may be useful for monitoring toxicological exposure and for diagnosis and monitoring of various diseases. Several methods are available that can be used to transport, store, and extract RNA from whole blood, but it is not clear...

Global gene expression profiling in infants with acute respiratory syncytial virus broncholitis demonstrates systemic activation of interferon signaling networks

USDA-ARS?s Scientific Manuscript database

Respiratory syncytial virus (RSV) is a leading cause of pediatric lower respiratory tract infections and has a high impact on pediatric emergency department utilization. Variation in host response may influence the pathogenesis and disease severity. We evaluated global gene expression profiles to be...

HEPATIC GENE EXPRESSION PROFILES OF RATS EXPOSED TO PERFLUOROOCTANE SULFONATE (PFOS) IN UTERO

EPA Science Inventory

Hepatic Gene Expression Profiles of Rats Exposed to Perfluorooctanesulfonate (PFOS) in utero.
J.A. Bjork1, J.M. Berthiaume1, C. Lau2, J. L. Butenhoff3, and K.B. Wallace1

1Department of Biochemistry & Molecular Biology, University of Minnesota School of Medicine, Dulut...

Cognitive Profiles of Finnish Preschool Children with Expressive and Receptive Language Impairment

ERIC Educational Resources Information Center

Saar, Virpi; Levänen, Sari; Komulainen, Erkki

2018-01-01

Purpose: The aim of this study was to compare the verbal and nonverbal cognitive profiles of children with specific language impairment (SLI) with problems predominantly in expressive (SLI-E) or receptive (SLI-R) language skills. These diagnostic subgroups have not been compared before in psychological studies. Method: Participants were…

DOES RESPONSE EVALUATION OF GENE EXPRESSION PROFILES IN THE SKIN OF K6/ODC MICE EXPOSED TO SODIUM ARSENITE

EPA Science Inventory

Abstract - Chronic drinking water exposure to inorganic arsenic and its metabolites increases tumor frequency in the skin of K6/ODC transgenic mice. To identify potential biomarkers and modes of action for this skin tumorigenicity, gene expression profiles were characterized fro...

Transcriptional response of peripheral lymphocytes to early fibrosarcoma: a model system for cancer detection based on hybridization signatures.

PubMed

Marques, Márcia M C; Junta, Cristina M; Zárate-Blades, Carlos R; Sakamoto-Hojo, Elza Tiemi; Donadi, Eduardo A; Passos, Geraldo A S

2009-07-01

Since circulating leukocytes, mainly B and T cells, continuously maintain vigilant and comprehensive immune surveillance, these cells could be used as reporters for signs of infection or other pathologies, including cancer. Activated lymphocyte clones trigger a sensitive transcriptional response, which could be identified by gene expression profiling. To assess this hypothesis, we conducted microarray analysis of the gene expression profile of lymphocytes isolated from immunocompetent BALB/c mice subcutaneously injected with different numbers of tumorigenic B61 fibrosarcoma cells. Flow cytometry demonstrated that the number of circulating T (CD3(+)CD4(+) or CD3(+)CD8(+)) or B (CD19(+)) cells did not change. However, the lymphocytes isolated from tumor cell-injected animals expressed a unique transcriptional profile that was identifiable before the development of a palpable tumor mass. This finding demonstrates that the transcriptional response appears before alterations in the main lymphocyte subsets and that the gene expression profile of peripheral lymphocytes can serve as a sensitive and accurate method for the early detection of cancer.

MicroRNA Expression Profile Selection for Cancer Staging Classification Using Backpropagation

NASA Astrophysics Data System (ADS)

Anjarwati; Wibowo, Adi; Adhy, Satriyo; Kusumaningrum, Retno

2018-05-01

Ovarian cancer, breast cancer, and lung cancer are deadly diseases and require serious treatment. The cancers are among the fifth most common causes of cancer-induced deaths especially for woman. The high mortality rate of cancer is caused by the lack of effective strategies for early detection of the cancer, whereas if its detected in the early stages, the life survival of cancer patients will be 90%, otherwise the survival rate only 30% when the cancers detected on metastasis stages or cancer cells have spread from a primary site of cancer. MicroRNAs can be used as potential biomarkers for cancer due to their profile expression on the cancers. In this paper, we proposed the feature selection of microRNA expression profiles for classification of the cancers stages using Backpropagation Neural Network. The Cancer stages are classified into before metastasis and after metastasis. Several combinations of the microRNA expression profiles from medical references are compared to find the best features for the classification. The accuracy and the mean square errors are used as basis testing the comparison.

Evaluation of an Innovative Fixation System for Chevron Bunionectomy.

PubMed

Bennett, Gordon L; Sabetta, James A

2016-02-01

Distal chevron metatarsal osteotomy bunionectomy is a commonly performed procedure for the treatment of mild to moderate hallux valgus deformity. There are several different methods to stabilize this osteotomy. We evaluated a new intramedullary plate system. We prospectively evaluated 57 consecutive patients who underwent distal chevron metatarsal osteotomy bunionectomy utilizing the intramedullary plate system. All operative procedures were performed by the senior author. Patients were evaluated preoperatively, postoperatively, and at a final follow-up utilizing the American Orthopaedic Foot & Ankle Society (AOFAS) forefoot scoring system. Sixty-three surgically corrected feet went on to heal the osteotomy site. There were no hardware failures. We had one patient that expressed mild discomfort over the plate. All patients significantly improved their AOFAS scores compared with preoperative values. We concluded that the distal chevron metatarsal osteotomy bunionectomy resulted in excellent function and pain relief. The new plate system was a reliable and stable implant with a low profile, good strength, and ease of use. Level IV, retrospective case series. © The Author(s) 2015.

Reconstituting development of pancreatic intraepithelial neoplasia from primary human pancreas duct cells

PubMed Central

Lee, Jonghyeob; Snyder, Emily R.; Liu, Yinghua; Gu, Xueying; Wang, Jing; Flowers, Brittany M.; Kim, Yoo Jung; Park, Sangbin; Szot, Gregory L.; Hruban, Ralph H.; Longacre, Teri A.; Kim, Seung K.

2017-01-01

Development of systems that reconstitute hallmark features of human pancreatic intraepithelial neoplasia (PanINs), the precursor to pancreatic ductal adenocarcinoma, could generate new strategies for early diagnosis and intervention. However, human cell-based PanIN models with defined mutations are unavailable. Here, we report that genetic modification of primary human pancreatic cells leads to development of lesions resembling native human PanINs. Primary human pancreas duct cells harbouring oncogenic KRAS and induced mutations in CDKN2A, SMAD4 and TP53 expand in vitro as epithelial spheres. After pancreatic transplantation, mutant clones form lesions histologically similar to native PanINs, including prominent stromal responses. Gene expression profiling reveals molecular similarities of mutant clones with native PanINs, and identifies potential PanIN biomarker candidates including Neuromedin U, a circulating peptide hormone. Prospective reconstitution of human PanIN development from primary cells provides experimental opportunities to investigate pancreas cancer development, progression and early-stage detection. PMID:28272465

Energy boost in laser wakefield accelerators using sharp density transitions

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

Döpp, A.; Guillaume, E.; Thaury, C.

The energy gain in laser wakefield accelerators is limited by dephasing between the driving laser pulse and the highly relativistic electrons in its wake. Since this phase depends on both the driver and the cavity length, the effects of dephasing can be mitigated with appropriate tailoring of the plasma density along propagation. Preceding studies have discussed the prospects of continuous phase-locking in the linear wakefield regime. However, most experiments are performed in the highly non-linear regime and rely on self-guiding of the laser pulse. Due to the complexity of the driver evolution in this regime, it is much more difficultmore » to achieve phase locking. As an alternative, we study the scenario of rapid rephasing in sharp density transitions, as was recently demonstrated experimentally. Starting from a phenomenological model, we deduce expressions for the electron energy gain in such density profiles. The results are in accordance with particle-in-cell simulations, and we present gain estimations for single and multiple stages of rephasing.« less

Combat Wound Initiative program.

PubMed

Stojadinovic, Alexander; Elster, Eric; Potter, Benjamin K; Davis, Thomas A; Tadaki, Doug K; Brown, Trevor S; Ahlers, Stephen; Attinger, Christopher E; Andersen, Romney C; Burris, David; Centeno, Jose; Champion, Hunter; Crumbley, David R; Denobile, John; Duga, Michael; Dunne, James R; Eberhardt, John; Ennis, William J; Forsberg, Jonathan A; Hawksworth, Jason; Helling, Thomas S; Lazarus, Gerald S; Milner, Stephen M; Mullick, Florabel G; Owner, Christopher R; Pasquina, Paul F; Patel, Chirag R; Peoples, George E; Nissan, Aviram; Ring, Michael; Sandberg, Glenn D; Schaden, Wolfgang; Schultz, Gregory S; Scofield, Tom; Shawen, Scott B; Sheppard, Forest R; Stannard, James P; Weina, Peter J; Zenilman, Jonathan M

2010-07-01

The Combat Wound Initiative (CWI) program is a collaborative, multidisciplinary, and interservice public-private partnership that provides personalized, state-of-the-art, and complex wound care via targeted clinical and translational research. The CWI uses a bench-to-bedside approach to translational research, including the rapid development of a human extracorporeal shock wave therapy (ESWT) study in complex wounds after establishing the potential efficacy, biologic mechanisms, and safety of this treatment modality in a murine model. Additional clinical trials include the prospective use of clinical data, serum and wound biomarkers, and wound gene expression profiles to predict wound healing/failure and additional clinical patient outcomes following combat-related trauma. These clinical research data are analyzed using machine-based learning algorithms to develop predictive treatment models to guide clinical decision-making. Future CWI directions include additional clinical trials and study centers and the refinement and deployment of our genetically driven, personalized medicine initiative to provide patient-specific care across multiple medical disciplines, with an emphasis on combat casualty care.

Genome-wide DNA methylation profiling integrated with gene expression profiling identifies PAX9 as a novel prognostic marker in chronic lymphocytic leukemia.

PubMed

Rani, Lata; Mathur, Nitin; Gupta, Ritu; Gogia, Ajay; Kaur, Gurvinder; Dhanjal, Jaspreet Kaur; Sundar, Durai; Kumar, Lalit; Sharma, Atul

2017-01-01

In chronic lymphocytic leukemia (CLL), epigenomic and genomic studies have expanded the existing knowledge about the disease biology and led to the identification of potential biomarkers relevant for implementation of personalized medicine. In this study, an attempt has been made to examine and integrate the global DNA methylation changes with gene expression profile and their impact on clinical outcome in early stage CLL patients. The integration of DNA methylation profile ( n  = 14) with the gene expression profile ( n  = 21) revealed 142 genes as hypermethylated-downregulated and; 62 genes as hypomethylated-upregulated in early stage CLL patients compared to CD19+ B-cells from healthy individuals. The mRNA expression levels of 17 genes identified to be differentially methylated and/or differentially expressed was further examined in early stage CLL patients ( n  = 93) by quantitative real time PCR (RQ-PCR). Significant differences were observed in the mRNA expression of MEIS1 , PMEPA1 , SOX7 , SPRY1 , CDK6 , TBX2 , and SPRY2 genes in CLL cells as compared to B-cells from healthy individuals. The analysis in the IGHV mutation based categories (Unmutated = 39, Mutated = 54) revealed significantly higher mRNA expression of CRY1 and PAX9 genes in the IGHV unmutated subgroup ( p  < 0.001). The relative risk of treatment initiation was significantly higher among patients with high expression of CRY1 (RR = 1.91, p  = 0.005) or PAX9 (RR = 1.87, p  = 0.001). High expression of CRY1 (HR: 3.53, p  < 0.001) or PAX9 (HR: 3.14, p  < 0.001) gene was significantly associated with shorter time to first treatment. The high expression of PAX9 gene (HR: 3.29, 95% CI 1.172-9.272, p  = 0.016) was also predictive of shorter overall survival in CLL. The DNA methylation changes associated with mRNA expression of CRY1 and PAX9 genes allow risk stratification of early stage CLL patients. This comprehensive analysis supports the concept that the epigenetic changes along with the altered expression of genes have the potential to predict clinical outcome in early stage CLL patients.

Dysregulation of hepatic microRNA expression profiles with Clonorchis sinensis infection.

PubMed

Han, Su; Tang, Qiaoran; Lu, Xi; Chen, Rui; Li, Yihong; Shu, Jing; Zhang, Xiaoli; Cao, Jianping

2016-11-30

Clonorchiasis remains an important zoonotic parasitic disease worldwide. The molecular mechanisms of host-parasite interaction are not fully understood. Non-coding microRNAs (miRNAs) are considered to be key regulators in parasitic diseases. The regulation of miRNAs and host micro-environment may be involved in clonorchiasis, and require further investigation. MiRNA microarray technology and bioinformatic analysis were used to investigate the regulatory mechanisms of host miRNA and to compare miRNA expression profiles in the liver tissues of control and Clonorchis sinensis (C. sinensis)-infected rats. A total of eight miRNAs were downregulated and two were upregulated, which showed differentially altered expression profiles in the liver tissue of C. sinensis-infected rats. Further analysis of the differentially expressed miRNAs revealed that many important signal pathways were triggered after infection with C. sinensis, which were related to clonorchiasis pathogenesis, such as cell apoptosis and inflammation, as well as genes involved in signal transduction mechanisms, such as pathways in cancer and the Wnt and Mitogen-activated protein kinases (MAPK) signaling pathways. The present study revealed that the miRNA expression profiles of the host were changed by C. sinensis infection. This dysregulation in miRNA expression may contribute to the etiology and pathophysiology of clonorchiasis. These results also provide new insights into the regulatory mechanisms of miRNAs in clonorchiasis, which may present potential targets for future C. sinensis control strategies.

Biochemical characteristics and gene expression profiles of two paralogous luciferases from the Japanese firefly Pyrocoelia atripennis (Coleoptera, Lampyridae, Lampyrinae): insight into the evolution of firefly luciferase genes.

PubMed

Bessho-Uehara, Manabu; Konishi, Kaori; Oba, Yuichi

2017-08-09

Two paralogous genes of firefly luciferase, Luc1 and Luc2, have been isolated from the species in two subfamilies, Luciolinae and Photurinae, of the family Lampyridae. The gene expression profiles have previously been examined only in the species of Luciolinae. Here we isolated Luc1 and Luc2 genes from the Japanese firefly Pyrocoelia atripennis. This is the first report of the presence of both Luc1 and Luc2 genes in the species of the subfamily Lampyrinae and of the exon-intron structure of Luc2 in the family Lampyridae. The luminescence of both gene products peaked at 547 nm under neutral buffer conditions, and the spectrum of Luc1, but not Luc2, was red-shifted under acidic conditions, as observed for Luc2 in the Luciolinae species. The semi-quantitative reverse transcription-polymerase chain reaction suggested that Luc1 was expressed in lanterns of all the stages except eggs, while Luc2 was expressed in the non-lantern bodies of eggs, prepupae, pupae, and female adults. These expression profiles are consistent with those in the Luciolinae species. Considering the distant phylogenetic relationship between Lampyrinae and Luciolinae in Lampyridae, we propose that fireflies generally possess two different luciferase genes and the biochemical properties and gene expression profiles for each paralog are conserved among lampyrid species.

Dose-response relationships in gene expression profiles in rainbow trout, Oncorhyncus mykiss, exposed to ethynylestradiol.

PubMed

Hook, Sharon E; Skillman, Ann D; Small, Jack A; Schultz, Irvin R

2006-07-01

Determining how gene expression profiles change with toxicant dose will improve the utility of arrays in identifying biomarkers and modes of toxic action. Isogenic rainbow trout, Oncorhyncus mykiss,were exposed to 10, 50 or 100 ng/L ethynylestradiol (a xeno-estrogen) for 7 days. Following exposure hepatic RNA was extracted. Fluorescently labeled cDNA were generated and hybridized against a commercially available Atlantic Salmon/Trout array (GRASP project, University of Victoria) spotted with 16,000 cDNAs. Transcript expression in treated vs control fish was analyzed via Genespring (Silicon Genetics) to identify genes with altered expression, as well as to determine gene clustering patterns that can be used as "expression signatures". Array results were confirmed via qRT PCR. Our analysis indicates that gene expression profiles varied somewhat with dose. Established biomarkers of exposure to estrogenic chemicals, such as vitellogenin, vitelline envelope proteins, and the estrogen receptor alpha, were induced at every dose. Other genes were dose specific, suggesting that different doses induce distinct physiological responses. These findings demonstrate that cDNA microarrays could be used to identify both toxicant class and relative dose.

Determination of absolute expression profiles using multiplexed miRNA analysis

PubMed Central

Song, Jee Hoon; Cheng, Yulan; Saeui, Christopher T.; Cheung, Douglas G.; Croce, Carlo M.; Yarema, Kevin J.; Meltzer, Stephen J.; Liu, Kelvin J.; Wang, Tza-Huei

2017-01-01

Accurate measurement of miRNA expression is critical to understanding their role in gene expression as well as their application as disease biomarkers. Correct identification of changes in miRNA expression rests on reliable normalization to account for biological and technological variance between samples. Ligo-miR is a multiplex assay designed to rapidly measure absolute miRNA copy numbers, thus reducing dependence on biological controls. It uses a simple 2-step ligation process to generate length coded products that can be quantified using a variety of DNA sizing methods. We demonstrate Ligo-miR’s ability to quantify miRNA expression down to 20 copies per cell sensitivity, accurately discriminate between closely related miRNA, and reliably measure differential changes as small as 1.2-fold. Then, benchmarking studies were performed to show the high correlation between Ligo-miR, microarray, and TaqMan qRT-PCR. Finally, Ligo-miR was used to determine copy number profiles in a number of breast, esophageal, and pancreatic cell lines and to demonstrate the utility of copy number analysis for providing layered insight into expression profile changes. PMID:28704432

A Gata2-Dependent Transcription Network Regulates Uterine Progesterone Responsiveness and Endometrial Function.

PubMed

Rubel, Cory A; Wu, San-Pin; Lin, Lin; Wang, Tianyuan; Lanz, Rainer B; Li, Xilong; Kommagani, Ramakrishna; Franco, Heather L; Camper, Sally A; Tong, Qiang; Jeong, Jae-Wook; Lydon, John P; DeMayo, Francesco J

2016-10-25

Altered progesterone responsiveness leads to female infertility and cancer, but underlying mechanisms remain unclear. Mice with uterine-specific ablation of GATA binding protein 2 (Gata2) are infertile, showing failures in embryo implantation, endometrial decidualization, and uninhibited estrogen signaling. Gata2 deficiency results in reduced progesterone receptor (PGR) expression and attenuated progesterone signaling, as evidenced by genome-wide expression profiling and chromatin immunoprecipitation. GATA2 not only occupies at and promotes expression of the Pgr gene but also regulates downstream progesterone responsive genes in conjunction with the PGR. Additionally, Gata2 knockout uteri exhibit abnormal luminal epithelia with ectopic TRP63 expressing squamous cells and a cancer-related molecular profile in a progesterone-independent manner. Lastly, we found a conserved GATA2-PGR regulatory network in both human and mice based on gene signature and path analyses using gene expression profiles of human endometrial tissues. In conclusion, uterine Gata2 regulates a key regulatory network of gene expression for progesterone signaling at the early pregnancy stage. Published by Elsevier Inc.

Pregnancy-induced gene expression changes in vivo among women with rheumatoid arthritis: a pilot study.

PubMed

Goin, Dana E; Smed, Mette Kiel; Pachter, Lior; Purdom, Elizabeth; Nelson, J Lee; Kjærgaard, Hanne; Olsen, Jørn; Hetland, Merete Lund; Zoffmann, Vibeke; Ottesen, Bent; Jawaheer, Damini

2017-05-25

Little is known about gene expression changes induced by pregnancy in women with rheumatoid arthritis (RA) and healthy women because the few studies previously conducted did not have pre-pregnancy samples available as baseline. We have established a cohort of women with RA and healthy women followed prospectively from a pre-pregnancy baseline. In this study, we tested the hypothesis that pregnancy-induced changes in gene expression among women with RA who improve during pregnancy (pregDAS improved ) overlap substantially with changes observed among healthy women and differ from changes observed among women with RA who worsen during pregnancy (pregDAS worse ). Global gene expression profiles were generated by RNA sequencing (RNA-seq) from 11 women with RA and 5 healthy women before pregnancy (T0) and at the third trimester (T3). Among the women with RA, eight showed an improvement in disease activity by T3, whereas three worsened. Differential expression analysis was used to identify genes demonstrating significant changes in expression within each of the RA and healthy groups (T3 vs T0), as well as between the groups at each time point. Gene set enrichment was assessed in terms of Gene Ontology processes and protein networks. A total of 1296 genes were differentially expressed between T3 and T0 among the 8 pregDAS improved women, with 161 genes showing at least two-fold change (FC) in expression by T3. The majority (108 of 161 genes) were also differentially expressed among healthy women (q<0.05, FC≥2). Additionally, a small cluster of genes demonstrated contrasting changes in expression between the pregDAS improved and pregDAS worse groups, all of which were inducible by type I interferon (IFN). These IFN-inducible genes were over-expressed at T3 compared to the T0 baseline among the pregDAS improved women. In our pilot RNA-seq dataset, increased pregnancy-induced expression of type I IFN-inducible genes was observed among women with RA who improved during pregnancy, but not among women who worsened. These findings warrant further investigation into expression of these genes in RA pregnancy and their potential role in modulation of disease activity. These results are nevertheless preliminary and should be interpreted with caution until replicated in a larger sample.

Cycle spokes and chain related injuries in children--emerging injuries in Malaysia.

PubMed

Nazri, M Y; Hafiz, A; Yusof, A; Khalid, K A; Aminudin, C A

2005-07-01

A descriptive prospective study of 16 children with injuries inflicted by bicycle spokes and chain was undertaken to identify the demographic profiles of such injuries. Aspects of preventive measures are proposed.

Hypoxia reduces the E-cadherin expression and increases OSCC cell migration regardless of the E-cadherin methylation profile.

PubMed

Domingos, Patrícia Luciana Batista; Souza, Marcela Gonçalves; Guimarães, Talita Antunes; Santos, Eliane Sobrinho; Farias, Lucyana Conceição; de Carvalho Fraga, Carlos Alberto; Jones, Kimberly Marie; Santos, Sérgio Henrique Souza; de Paula, Alfredo Maurício Batista; Guimarães, André Luiz Sena

2017-05-01

The purpose of the current study is to investigate the association between E-cadherin methylation status, hypoxia and OSCC. HaCat and SCC9 cell lines were submitted to hypoxic treatment, followed by methylation profile analysis (MS-PCR) and analysis of the expression of mRNA gene E-cadherin (RT-PCR). Study group samples comprise individuals affected by potentially malignant lesions Potential Malignant Oral Lesion (PMOL, n=18) and oral squamous cell carcinoma (OSCC, n=28). The control group oral mucosa (OM, n=15) of patients with an oral mucocele. Cell migration ability was evaluated a scratch wound assay in SCC9 and HaCat cell lines RESULTS: E-cadherin mRNA expression in the cell lines SCC9 and HaCat was significantly reduced under hypoxia, regardless of the methylation profile, when compared to the control group. No differences in methylation profile of the E-cadherin were observed among the groups OM, PMOL and OSCC. HaCat and SCC9 presented increases in cell migration rates under hypoxia. The current study demonstrates that hypoxia reduces E-cadherin expression and increase cell migration, regardless of the methylation profile. Additionally, no differences in E-cadherin methylation patterns were observed among OM, PMOL and OSCC. Copyright © 2017 Elsevier GmbH. All rights reserved.

Gene Expression Dynamics Inspector (GEDI): for integrative analysis of expression profiles

NASA Technical Reports Server (NTRS)

Eichler, Gabriel S.; Huang, Sui; Ingber, Donald E.

2003-01-01

Genome-wide expression profiles contain global patterns that evade visual detection in current gene clustering analysis. Here, a Gene Expression Dynamics Inspector (GEDI) is described that uses self-organizing maps to translate high-dimensional expression profiles of time courses or sample classes into animated, coherent and robust mosaics images. GEDI facilitates identification of interesting patterns of molecular activity simultaneously across gene, time and sample space without prior assumption of any structure in the data, and then permits the user to retrieve genes of interest. Important changes in genome-wide activities may be quickly identified based on 'Gestalt' recognition and hence, GEDI may be especially useful for non-specialist end users, such as physicians. AVAILABILITY: GEDI v1.0 is written in Matlab, and binary Matlab.dll files which require Matlab to run can be downloaded for free by academic institutions at http://www.chip.org/ge/gedihome.html Supplementary information: http://www.chip.org/ge/gedihome.html.

From reads to genes to pathways: differential expression analysis of RNA-Seq experiments using Rsubread and the edgeR quasi-likelihood pipeline.

PubMed

Chen, Yunshun; Lun, Aaron T L; Smyth, Gordon K

2016-01-01

In recent years, RNA sequencing (RNA-seq) has become a very widely used technology for profiling gene expression. One of the most common aims of RNA-seq profiling is to identify genes or molecular pathways that are differentially expressed (DE) between two or more biological conditions. This article demonstrates a computational workflow for the detection of DE genes and pathways from RNA-seq data by providing a complete analysis of an RNA-seq experiment profiling epithelial cell subsets in the mouse mammary gland. The workflow uses R software packages from the open-source Bioconductor project and covers all steps of the analysis pipeline, including alignment of read sequences, data exploration, differential expression analysis, visualization and pathway analysis. Read alignment and count quantification is conducted using the Rsubread package and the statistical analyses are performed using the edgeR package. The differential expression analysis uses the quasi-likelihood functionality of edgeR.

Activity-based protein profiling for biochemical pathway discovery in cancer

PubMed Central

Nomura, Daniel K.; Dix, Melissa M.; Cravatt, Benjamin F.

2011-01-01

Large-scale profiling methods have uncovered numerous gene and protein expression changes that correlate with tumorigenesis. However, determining the relevance of these expression changes and which biochemical pathways they affect has been hindered by our incomplete understanding of the proteome and its myriad functions and modes of regulation. Activity-based profiling platforms enable both the discovery of cancer-relevant enzymes and selective pharmacological probes to perturb and characterize these proteins in tumour cells. When integrated with other large-scale profiling methods, activity-based proteomics can provide insight into the metabolic and signalling pathways that support cancer pathogenesis and illuminate new strategies for disease diagnosis and treatment. PMID:20703252

Identifying antimalarial compounds targeting dihydrofolate reductase-thymidylate synthase (DHFR-TS) by chemogenomic profiling.

PubMed

Aroonsri, Aiyada; Akinola, Olugbenga; Posayapisit, Navaporn; Songsungthong, Warangkhana; Uthaipibull, Chairat; Kamchonwongpaisan, Sumalee; Gbotosho, Grace O; Yuthavong, Yongyuth; Shaw, Philip J

2016-07-01

The mode of action of many antimalarial drugs is unknown. Chemogenomic profiling is a powerful method to address this issue. This experimental approach entails disruption of gene function and phenotypic screening for changes in sensitivity to bioactive compounds. Here, we describe the application of reverse genetics for chemogenomic profiling in Plasmodium. Plasmodium falciparum parasites harbouring a transgenic insertion of the glmS ribozyme downstream of the dihydrofolate reductase-thymidylate synthase (DHFR-TS) gene were used for chemogenomic profiling of antimalarial compounds to identify those which target DHFR-TS. DHFR-TS expression can be attenuated by exposing parasites to glucosamine. Parasites with attenuated DHFR-TS expression were significantly more sensitive to antifolate drugs known to target DHFR-TS. In contrast, no change in sensitivity to other antimalarial drugs with different modes of action was observed. Chemogenomic profiling was performed using the Medicines for Malaria Venture (Switzerland) Malaria Box compound library, and two compounds were identified as novel DHFR-TS inhibitors. We also tested the glmS ribozyme in Plasmodium berghei, a rodent malaria parasite. The expression of reporter genes with downstream glmS ribozyme could be attenuated in transgenic parasites comparable with that obtained in P. falciparum. The chemogenomic profiling method was applied in a P. berghei line expressing a pyrimethamine-resistant Toxoplasma gondii DHFR-TS reporter gene under glmS ribozyme control. Parasites with attenuated expression of this gene were significantly sensitised to antifolates targeting DHFR-TS, but not other drugs with different modes of action. In conclusion, these data show that the glmS ribozyme reverse genetic tool can be applied for identifying primary targets of antimalarial compounds in human and rodent malaria parasites. Copyright © 2016 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

Circulating Long Noncoding RNAs as Potential Biomarkers of Sepsis: A Preliminary Study.

PubMed

Dai, Yu; Liang, Zhixin; Li, Yulin; Li, Chunsun; Chen, Liangan

2017-11-01

Long noncoding RNAs (lncRNAs) are becoming promising biomarker candidates in various diseases as assessed via sequencing technologies. Sepsis is a life-threatening disease without ideal biomarkers. The aim of this study was to investigate the expression profile of lncRNAs in the peripheral blood of sepsis patients and to find potential biomarkers of sepsis. A lncRNA expression profile was performed using peripheral blood from three sepsis patients and three healthy volunteers using microarray screening. The differentially expressed lncRNAs were validated by real-time quantitative polymerase chain reaction (qRT-PCR) in a further set of 22 sepsis patients and 22 healthy volunteers. Among 1316 differentially expressed lncRNAs, 771 were downregulated and 545 were upregulated. Results of the qRT-PCR were consistent with the microarray data. lncRNA ENST00000452391.1, uc001vji.1, and uc021zxw.1 were significantly differentially expressed between sepsis patients and healthy volunteers. Moreover, lncRNA ENST00000504301.1 and ENST00000452391.1 were significantly differentially expressed between sepsis survivors and nonsurvivors. The lncRNA expression profile in the peripheral blood of sepsis patients significantly differed from that of healthy volunteers. Circulating lncRNAs may be good candidates for sepsis biomarkers.

Identification and substrate prediction of new Fragaria x ananassa aquaporins and expression in different tissues and during strawberry fruit development.

PubMed

Merlaen, Britt; De Keyser, Ellen; Van Labeke, Marie-Christine

2018-01-01

The newly identified aquaporin coding sequences presented here pave the way for further insights into the plant-water relations in the commercial strawberry ( Fragaria x ananassa ). Aquaporins are water channel proteins that allow water to cross (intra)cellular membranes. In Fragaria x ananassa , few of them have been identified hitherto, hampering the exploration of the water transport regulation at cellular level. Here, we present new aquaporin coding sequences belonging to different subclasses: plasma membrane intrinsic proteins subtype 1 and subtype 2 (PIP1 and PIP2) and tonoplast intrinsic proteins (TIP). The classification is based on phylogenetic analysis and is confirmed by the presence of conserved residues. Substrate-specific signature sequences (SSSSs) and specificity-determining positions (SDPs) predict the substrate specificity of each new aquaporin. Expression profiling in leaves, petioles and developing fruits reveals distinct patterns, even within the same (sub)class. Expression profiles range from leaf-specific expression over constitutive expression to fruit-specific expression. Both upregulation and downregulation during fruit ripening occur. Substrate specificity and expression profiles suggest that functional specialization exists among aquaporins belonging to a different but also to the same (sub)class.

PmiRExAt: plant miRNA expression atlas database and web applications

PubMed Central

Gurjar, Anoop Kishor Singh; Panwar, Abhijeet Singh; Gupta, Rajinder; Mantri, Shrikant S.

2016-01-01

High-throughput small RNA (sRNA) sequencing technology enables an entirely new perspective for plant microRNA (miRNA) research and has immense potential to unravel regulatory networks. Novel insights gained through data mining in publically available rich resource of sRNA data will help in designing biotechnology-based approaches for crop improvement to enhance plant yield and nutritional value. Bioinformatics resources enabling meta-analysis of miRNA expression across multiple plant species are still evolving. Here, we report PmiRExAt, a new online database resource that caters plant miRNA expression atlas. The web-based repository comprises of miRNA expression profile and query tool for 1859 wheat, 2330 rice and 283 maize miRNA. The database interface offers open and easy access to miRNA expression profile and helps in identifying tissue preferential, differential and constitutively expressing miRNAs. A feature enabling expression study of conserved miRNA across multiple species is also implemented. Custom expression analysis feature enables expression analysis of novel miRNA in total 117 datasets. New sRNA dataset can also be uploaded for analysing miRNA expression profiles for 73 plant species. PmiRExAt application program interface, a simple object access protocol web service allows other programmers to remotely invoke the methods written for doing programmatic search operations on PmiRExAt database. Database URL: http://pmirexat.nabi.res.in. PMID:27081157

Comparison of gene expression and fatty acid profiles in concentrate and forage finished beef.

PubMed

Buchanan, J W; Garmyn, A J; Hilton, G G; VanOverbeke, D L; Duan, Q; Beitz, D C; Mateescu, R G

2013-01-01

Fatty acid profiles and intramuscular expression of genes involved in fatty acid metabolism were characterized in concentrate- (CO) and forage- (FO) based finishing systems. Intramuscular samples from the adductor were taken at slaughter from 99 heifers finished on a CO diet and 58 heifers finished on a FO diet. Strip loins were obtained at fabrication to evaluate fatty acid profiles of LM muscle for all 157 heifers by using gas chromatography fatty acid methyl ester analysis. Composition was analyzed for differences by using the General Linear Model (GLM) procedure in SAS. Differences in fatty acid profile included a greater atherogenic index, greater percentage total MUFA, decreased omega-3 to omega-6 ratio, decreased percentage total PUFA, and decreased percentage omega-3 fatty acids in CO- compared with FO-finished heifers (P<0.05). Fatty acid profiles from intramuscular samples were ranked by the atherogenic index, and 20 heifers with either a high (HAI; n=10) or low (LAI; n=10) atherogenic index were selected for gene expression analysis using real-time PCR (RT-PCR). Gene expression data for the 20 individuals were analyzed as a 2 by 2 factorial arrangement of treatments using the GLM procedure in SAS. There was no significant diet × atherogenic index interaction identified for any gene (P>0.05). Upregulation was observed for PPARγ, fatty acid synthase (FASN), and fatty acid binding protein 4 (FABP4) in FO-finished compared with CO-finished heifers in both atherogenic index categories (P<0.05). Upregulation of diglyceride acyl transferase 2 (DGAT2) was observed in FO-finished heifers with a HAI (P<0.05). Expression of steroyl Co-A desaturase (SCD) was upregulated in CO-finished heifers with a LAI, and downregulated in FO-finished heifers with a HAI (P<0.05). Expression of adiponectin (ADIPOQ) was significantly downregulated in CO-finished heifers with a HAI compared with all other categories (P<0.05). The genes identified in this study which exhibit differential regulation in response to diet or in animals with extreme fatty acid profiles may provide genetic markers for selecting desirable fatty acid profiles in future selection programs.

Prospects for engineering dynamic CRISPR-Cas transcriptional circuits to improve bioproduction.

PubMed

Fontana, Jason; Voje, William E; Zalatan, Jesse G; Carothers, James M

2018-05-08

Dynamic control of gene expression is emerging as an important strategy for controlling flux in metabolic pathways and improving bioproduction of valuable compounds. Integrating dynamic genetic control tools with CRISPR-Cas transcriptional regulation could significantly improve our ability to fine-tune the expression of multiple endogenous and heterologous genes according to the state of the cell. In this mini-review, we combine an analysis of recent literature with examples from our own work to discuss the prospects and challenges of developing dynamically regulated CRISPR-Cas transcriptional control systems for applications in synthetic biology and metabolic engineering.

Gene expression profiling in the hippocampus of learned helpless and nonhelpless rats.

PubMed

Kohen, R; Kirov, S; Navaja, G P; Happe, H Kevin; Hamblin, M W; Snoddy, J R; Neumaier, J F; Petty, F

2005-01-01

In the learned helplessness (LH) animal model of depression, failure to attempt escape from avoidable environmental stress, LH, indicates behavioral despair, whereas nonhelpless (NH) behavior reflects behavioral resilience to the effects of environmental stress. Comparing hippocampal gene expression with large-scale oligonucleotide microarrays, we found that stress-resilient (NH) rats, although behaviorally indistinguishable from controls, showed a distinct gene expression profile compared to LH, sham stressed, and naïve control animals. Genes that were confirmed as differentially expressed in the NH group by quantitative PCR strongly correlated in their levels of expression across all four animal groups. Differential expression could not be confirmed at the protein level. We identified several shared degenerate sequence motifs in the 3' untranslated region (3'UTR) of differentially expressed genes that could be a factor in this tight correlation of expression levels among differentially expressed genes.

Gene expression variability in human hepatic drug metabolizing enzymes and transporters.

PubMed

Yang, Lun; Price, Elvin T; Chang, Ching-Wei; Li, Yan; Huang, Ying; Guo, Li-Wu; Guo, Yongli; Kaput, Jim; Shi, Leming; Ning, Baitang

2013-01-01

Interindividual variability in the expression of drug-metabolizing enzymes and transporters (DMETs) in human liver may contribute to interindividual differences in drug efficacy and adverse reactions. Published studies that analyzed variability in the expression of DMET genes were limited by sample sizes and the number of genes profiled. We systematically analyzed the expression of 374 DMETs from a microarray data set consisting of gene expression profiles derived from 427 human liver samples. The standard deviation of interindividual expression for DMET genes was much higher than that for non-DMET genes. The 20 DMET genes with the largest variability in the expression provided examples of the interindividual variation. Gene expression data were also analyzed using network analysis methods, which delineates the similarities of biological functionalities and regulation mechanisms for these highly variable DMET genes. Expression variability of human hepatic DMET genes may affect drug-gene interactions and disease susceptibility, with concomitant clinical implications.

Diffusion Profiling via a Histogram Approach Distinguishes Low-grade from High-grade Meningiomas, Can Reflect the Respective Proliferative Potential and Progesterone Receptor Status.

PubMed

Gihr, Georg Alexander; Horvath-Rizea, Diana; Garnov, Nikita; Kohlhof-Meinecke, Patricia; Ganslandt, Oliver; Henkes, Hans; Meyer, Hans Jonas; Hoffmann, Karl-Titus; Surov, Alexey; Schob, Stefan

2018-02-01

Presurgical grading, estimation of growth kinetics, and other prognostic factors are becoming increasingly important for selecting the best therapeutic approach for meningioma patients. Diffusion-weighted imaging (DWI) provides microstructural information and reflects tumor biology. A novel DWI approach, histogram profiling of apparent diffusion coefficient (ADC) volumes, provides more distinct information than conventional DWI. Therefore, our study investigated whether ADC histogram profiling distinguishes low-grade from high-grade lesions and reflects Ki-67 expression and progesterone receptor status. Pretreatment ADC volumes of 37 meningioma patients (28 low-grade, 9 high-grade) were used for histogram profiling. WHO grade, Ki-67 expression, and progesterone receptor status were evaluated. Comparative and correlative statistics investigating the association between histogram profiling and neuropathology were performed. The entire ADC profile (p10, p25, p75, p90, mean, median) was significantly lower in high-grade versus low-grade meningiomas. The lower percentiles, mean, and modus showed significant correlations with Ki-67 expression. Skewness and entropy of the ADC volumes were significantly associated with progesterone receptor status and Ki-67 expression. ROC analysis revealed entropy to be the most accurate parameter distinguishing low-grade from high-grade meningiomas. ADC histogram profiling provides a distinct set of parameters, which help differentiate low-grade versus high-grade meningiomas. Also, histogram metrics correlate significantly with histological surrogates of the respective proliferative potential. More specifically, entropy revealed to be the most promising imaging biomarker for presurgical grading. Both, entropy and skewness were significantly associated with progesterone receptor status and Ki-67 expression and therefore should be investigated further as predictors for prognostically relevant tumor biological features. Since absolute ADC values vary between MRI scanners of different vendors and field strengths, their use is more limited in the presurgical setting.

[Differential gene expression profile in ischemic myocardium of Wistar rats with acute myocardial infarction: the study on gene construction, identification and function].

PubMed

Guo, Chun Yu; Yin, Hui Jun; Jiang, Yue Rong; Xue, Mei; Zhang, Lu; Shi, Da Zhuo

2008-06-18

To construct the differential genes expressed profile in the ischemic myocardium tissue reduced from acute myocardial infarction(AMI), and determine the biological functions of target genes. AMI model was generated by ligation of the left anterior descending coronary artery in Wistar rats. Total RNA was extracted from the normal and the ischemic heart tissues under the ligation point 7 days after the operation. Differential gene expression profiles of the two samples were constructed using Long Serial Analysis of Gene Expression(LongSAGE). Real time fluorescence quantitative PCR was used to verify gene expression profile and to identify the expression of 2 functional genes. The activities of enzymes from functional genes were determined by histochemistry. A total of 15,966 tags were screened from the normal and the ischemic LongSAGE maps. The similarities of the sequences were compared using the BLAST algebra in NCBI and 7,665 novel tags were found. In the ischemic tissue 142 genes were significantly changed compared with those in the normal tissue (P<0.05). These differentially expressed genes represented the proteins which might play important roles in the pathways of oxidation and phosphorylation, ATP synthesis and glycolysis. The partial genes identified by LongSAGE were confirmed using real time fluorescence quantitative PCR. Two genes related to energy metabolism, COX5a and ATP5e, were screened and quantified. Expression of two functional genes down-regulated at their mRNA levels and the activities of correlative functional enzymes decreased compared with those in the normal tissue. AMI causes a series of changes in gene expression, in which the abnormal expression of genes related to energy metabolism could be one of the molecular mechanisms of AMI. The intervention of the expressions of COX5a and ATP5e may be a new target for AMI therapy.

In silico identification and comparative analysis of differentially expressed genes in human and mouse tissues

PubMed Central

Pao, Sheng-Ying; Lin, Win-Li; Hwang, Ming-Jing

2006-01-01

Background Screening for differentially expressed genes on the genomic scale and comparative analysis of the expression profiles of orthologous genes between species to study gene function and regulation are becoming increasingly feasible. Expressed sequence tags (ESTs) are an excellent source of data for such studies using bioinformatic approaches because of the rich libraries and tremendous amount of data now available in the public domain. However, any large-scale EST-based bioinformatics analysis must deal with the heterogeneous, and often ambiguous, tissue and organ terms used to describe EST libraries. Results To deal with the issue of tissue source, in this work, we carefully screened and organized more than 8 million human and mouse ESTs into 157 human and 108 mouse tissue/organ categories, to which we applied an established statistic test using different thresholds of the p value to identify genes differentially expressed in different tissues. Further analysis of the tissue distribution and level of expression of human and mouse orthologous genes showed that tissue-specific orthologs tended to have more similar expression patterns than those lacking significant tissue specificity. On the other hand, a number of orthologs were found to have significant disparity in their expression profiles, hinting at novel functions, divergent regulation, or new ortholog relationships. Conclusion Comprehensive statistics on the tissue-specific expression of human and mouse genes were obtained in this very large-scale, EST-based analysis. These statistical results have been organized into a database, freely accessible at our website , for easy searching of human and mouse tissue-specific genes and for investigating gene expression profiles in the context of comparative genomics. Comparative analysis showed that, although highly tissue-specific genes tend to exhibit similar expression profiles in human and mouse, there are significant exceptions, indicating that orthologous genes, while sharing basic genomic properties, could result in distinct phenotypes. PMID:16626500

Molecular evolution and expression profile of the chemerine encoding gene RARRES2 in baboon and chimpanzee.

PubMed

González-Alvarez, Rafael; Garza-Rodríguez, María de Lourdes; Delgado-Enciso, Iván; Treviño-Alvarado, Víctor Manuel; Canales-Del-Castillo, Ricardo; Martínez-De-Villarreal, Laura Elia; Lugo-Trampe, Ángel; Tejero, María Elizabeth; Schlabritz-Loutsevitch, Natalia E; Rocha-Pizaña, María Del Refugio; Cole, Shelley A; Reséndez-Pérez, Diana; Moises-Alvarez, Mario; Comuzzie, Anthony G; Barrera-Saldaña, Hugo Alberto; Garza-Guajardo, Raquel; Barboza-Quintana, Oralia; Rodríguez-Sánchez, Irám Pablo

2015-06-12

Chemerin, encoded by the retinoic acid receptor responder 2 (RARRES2) gene is an adipocytesecreted protein with autocrine/paracrine functions in adipose tissue, metabolism and inflammation with a recently described function in vascular tone regulation, liver, steatosis, etc. This molecule is believed to represent a critical endocrine signal linking obesity to diabetes. There are no data available regarding evolution of RARRES2 in non-human primates and great apes. Expression profile and orthology in RARRES2 genes are unknown aspects in the biology of this multigene family in primates. Thus; we attempt to describe expression profile and phylogenetic relationship as complementary knowledge in the function of this gene in primates. To do that, we performed A RT-PCR from different tissues obtained during necropsies. Also we tested the hypotheses of positive evolution, purifying selection, and neutrality. And finally a phylogenetic analysis was made between primates RARRES2 protein. RARRES2 transcripts were present in liver, lung, adipose tissue, ovary, pancreas, heart, hypothalamus and pituitary tissues. Expression in kidney and leukocytes were not detectable in either species. It was determined that the studied genes are orthologous. RARRES2 evolution fits the hypothesis of purifying selection. Expression profiles of the RARRES2 gene are similar in baboons and chimpanzees and are also phylogenetically related.

Identification of specific gene expression profiles in fibroblasts derived from middle ear cholesteatoma.

PubMed

Yoshikawa, Mamoru; Kojima, Hiromi; Wada, Kota; Tsukidate, Toshiharu; Okada, Naoko; Saito, Hirohisa; Moriyama, Hiroshi

2006-07-01

To investigate the role of fibroblasts in the pathogenesis of cholesteatoma. Tissue specimens were obtained from our patients. Middle ear cholesteatoma-derived fibroblasts (MECFs) and postauricular skin-derived fibroblasts (SFs) as controls were then cultured for a few weeks. These fibroblasts were stimulated with interleukin (IL) 1alpha and/or IL-1beta before gene expression assays. We used the human genome U133A probe array (GeneChip) and real-time polymerase chain reaction to examine and compare the gene expression profiles of the MECFs and SFs. Six patients who had undergone tympanoplasty. The IL-1alpha-regulated genes were classified into 4 distinct clusters on the basis of profiles differentially regulated by SF and MECF using a hierarchical clustering analysis. The messenger RNA expressions of LARC (liver and activation-regulated chemokine), GMCSF (granulocyte-macrophage colony-stimulating factor), epiregulin, ICAM1 (intercellular adhesion molecule 1), and TGFA (transforming growth factor alpha) were more strongly up-regulated by IL-1alpha and/or IL-1beta in MECF than in SF, suggesting that these fibroblasts derived from different tissues retained their typical gene expression profiles. Fibroblasts may play a role in hyperkeratosis of middle ear cholesteatoma by releasing molecules involved in inflammation and epidermal growth. These fibroblasts may retain tissue-specific characteristics presumably controlled by epigenetic mechanisms.

Expression Profiles of TGF-β and TLR Pathways in Porphyromonas gingivalis and Prevotella intermedia Challenged Osteoblasts.

PubMed

Aydin, Kubra; Ekinci, Fatma Yesim; Korachi, May

2015-04-01

The presence of certain oral pathogens at implant sites can hinder the osseointegration process. However, it is unclear how and by what microorganisms it happens. This study investigated whether the presence of oral pathogens of Porphyromonas gingivalis and Prevotella intermedia individually, play a role in the failure of bone formation by determining the expression profiles of Transforming Growth Factor Beta (TGF-β/Bone Morphogenic Protein (BMP) and Toll-Like Receptor (TLR) pathways in challenged osteoblasts. Cell viability of P. gingivalis and P. intermedia challenged osteoblasts were determined by WST assay. Changes in osteoblast morphology and inhibition of mineralization were observed by Scanning Electron Microscopy (SEM) and Von Kossa staining, respectively. Expression of TGF-β and TLR pathway genes on challenged cells were identified by RT profiler array. Both P. gingivalis and P. intermedia challenges resulted in reduced viability and mineralization of osteoblasts. Viability was reduced to 56.8% (P. gingivalis) and 52.75% (P. intermedia) at 1000 multiplicity. Amongst 48 genes examined, expressions of BMPER, SMAD1, IL8 and NFRKB were found to be highly upregulated by both bacterial challenges (Fold Change > 4). P. gingivalis and P. intermedia could play a role in implant failure by changing the expression profiles of genes related to bone formation and resorption.

Defining the Human Macula Transcriptome and Candidate Retinal Disease Genes UsingEyeSAGE

PubMed Central

Rickman, Catherine Bowes; Ebright, Jessica N.; Zavodni, Zachary J.; Yu, Ling; Wang, Tianyuan; Daiger, Stephen P.; Wistow, Graeme; Boon, Kathy; Hauser, Michael A.

2009-01-01

Purpose To develop large-scale, high-throughput annotation of the human macula transcriptome and to identify and prioritize candidate genes for inherited retinal dystrophies, based on ocular-expression profiles using serial analysis of gene expression (SAGE). Methods Two human retina and two retinal pigment epithelium (RPE)/choroid SAGE libraries made from matched macula or midperipheral retina and adjacent RPE/choroid of morphologically normal 28- to 66-year-old donors and a human central retina longSAGE library made from 41- to 66-year-old donors were generated. Their transcription profiles were entered into a relational database, EyeSAGE, including microarray expression profiles of retina and publicly available normal human tissue SAGE libraries. EyeSAGE was used to identify retina- and RPE-specific and -associated genes, and candidate genes for retina and RPE disease loci. Differential and/or cell-type specific expression was validated by quantitative and single-cell RT-PCR. Results Cone photoreceptor-associated gene expression was elevated in the macula transcription profiles. Analysis of the longSAGE retina tags enhanced tag-to-gene mapping and revealed alternatively spliced genes. Analysis of candidate gene expression tables for the identified Bardet-Biedl syndrome disease gene (BBS5) in the BBS5 disease region table yielded BBS5 as the top candidate. Compelling candidates for inherited retina diseases were identified. Conclusions The EyeSAGE database, combining three different gene-profiling platforms including the authors’ multidonor-derived retina/RPE SAGE libraries and existing single-donor retina/RPE libraries, is a powerful resource for definition of the retina and RPE transcriptomes. It can be used to identify retina-specific genes, including alternatively spliced transcripts and to prioritize candidate genes within mapped retinal disease regions. PMID:16723438

Defining the human macula transcriptome and candidate retinal disease genes using EyeSAGE.

PubMed

Bowes Rickman, Catherine; Ebright, Jessica N; Zavodni, Zachary J; Yu, Ling; Wang, Tianyuan; Daiger, Stephen P; Wistow, Graeme; Boon, Kathy; Hauser, Michael A

2006-06-01

To develop large-scale, high-throughput annotation of the human macula transcriptome and to identify and prioritize candidate genes for inherited retinal dystrophies, based on ocular-expression profiles using serial analysis of gene expression (SAGE). Two human retina and two retinal pigment epithelium (RPE)/choroid SAGE libraries made from matched macula or midperipheral retina and adjacent RPE/choroid of morphologically normal 28- to 66-year-old donors and a human central retina longSAGE library made from 41- to 66-year-old donors were generated. Their transcription profiles were entered into a relational database, EyeSAGE, including microarray expression profiles of retina and publicly available normal human tissue SAGE libraries. EyeSAGE was used to identify retina- and RPE-specific and -associated genes, and candidate genes for retina and RPE disease loci. Differential and/or cell-type specific expression was validated by quantitative and single-cell RT-PCR. Cone photoreceptor-associated gene expression was elevated in the macula transcription profiles. Analysis of the longSAGE retina tags enhanced tag-to-gene mapping and revealed alternatively spliced genes. Analysis of candidate gene expression tables for the identified Bardet-Biedl syndrome disease gene (BBS5) in the BBS5 disease region table yielded BBS5 as the top candidate. Compelling candidates for inherited retina diseases were identified. The EyeSAGE database, combining three different gene-profiling platforms including the authors' multidonor-derived retina/RPE SAGE libraries and existing single-donor retina/RPE libraries, is a powerful resource for definition of the retina and RPE transcriptomes. It can be used to identify retina-specific genes, including alternatively spliced transcripts and to prioritize candidate genes within mapped retinal disease regions.

Gene Expression Profiling of Bronchoalveolar Lavage Cells During Aspergillus Colonization of the Lung Allograft.

PubMed

Weigt, S Samuel; Wang, Xiaoyan; Palchevskiy, Vyacheslav; Patel, Naman; Derhovanessian, Ariss; Shino, Michael Y; Sayah, David M; Lynch, Joseph P; Saggar, Rajan; Ross, David J; Kubak, Bernie M; Ardehali, Abbas; Palmer, Scott; Husain, Shahid; Belperio, John A

2018-06-01

Aspergillus colonization after lung transplant is associated with an increased risk of chronic lung allograft dysfunction (CLAD). We hypothesized that gene expression during Aspergillus colonization could provide clues to CLAD pathogenesis. We examined transcriptional profiles in 3- or 6-month surveillance bronchoalveolar lavage fluid cell pellets from recipients with Aspergillus fumigatus colonization (n = 12) and without colonization (n = 10). Among the Aspergillus colonized, we also explored profiles in those who developed CLAD (n = 6) or remained CLAD-free (n = 6). Transcription profiles were assayed with the HG-U133 Plus 2.0 microarray (Affymetrix). Differential gene expression was based on an absolute fold difference of 2.0 or greater and unadjusted P value less than 0.05. We used NIH Database for Annotation, Visualization and Integrated Discovery for functional analyses, with false discovery rates less than 5% considered significant. Aspergillus colonization was associated with differential expression of 489 probe sets, representing 404 unique genes. "Defense response" genes and genes in the "cytokine-cytokine receptor" Kyoto Encyclopedia of Genes and Genomes pathway were notably enriched in this list. Among Aspergillus colonized patients, CLAD development was associated with differential expression of 69 probe sets, representing 64 unique genes. This list was enriched for genes involved in "immune response" and "response to wounding", among others. Notably, both chitinase 3-like-1 and chitotriosidase were associated with progression to CLAD. Aspergillus colonization is associated with gene expression profiles related to defense responses including cytokine signaling. Epithelial wounding, as well as the innate immune response to chitin that is present in the fungal cell wall, may be key in the link between Aspergillus colonization and CLAD.

Identification of gene expression profiling associated with erlotinib-related skin toxicity in pancreatic adenocarcinoma patients

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

Caba, Octavio, E-mail: ocaba@ujaen.es

Erlotinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor that showed activity against pancreatic ductal adenocarcinoma (PDAC). The drug's most frequently reported side effect as a result of EGFR inhibition is skin rash (SR), a symptom which has been associated with a better therapeutic response to the drug. Gene expression profiling can be used as a tool to predict which patients will develop this important cutaneous manifestation. The aim of the present study was to identify which genes may influence the appearance of SR in PDAC patients. The study included 34 PDAC patients treated with erlotinib: 21 patientsmore » developed any grade of SR, while 13 patients did not (controls). Before administering any chemotherapy regimen and the development of SR, we collected RNA from peripheral blood samples of all patients and studied the differential gene expression pattern using the Illumina microarray platform HumanHT-12 v4 Expression BeadChip. Seven genes (FAM46C, IFITM3, GMPR, DENND6B, SELENBP1, NOL10, and SIAH2), involved in different pathways including regulatory, migratory, and signalling processes, were downregulated in PDAC patients with SR. Our results suggest the existence of a gene expression profiling significantly correlated with erlotinib-induced SR in PDAC that could be used as prognostic indicator in this patients. - Highlights: • Skin rash (SR) is the most characteristic side effect of erlotinib in PDAC patients. • Erlotinib-induced SR has been associated with a better clinical outcome. • Gene expression profiling was used to determine who will develop this manifestation. • 7 genes involved in different pathways were downregulated in PDAC patients with SR. • Our profile correlated with erlotinib-induced SR in PDAC could be used for prognosis.« less

Histological staining methods preparatory to laser capture microdissection significantly affect the integrity of the cellular RNA.

PubMed

Wang, Hongyang; Owens, James D; Shih, Joanna H; Li, Ming-Chung; Bonner, Robert F; Mushinski, J Frederic

2006-04-27

Gene expression profiling by microarray analysis of cells enriched by laser capture microdissection (LCM) faces several technical challenges. Frozen sections yield higher quality RNA than paraffin-imbedded sections, but even with frozen sections, the staining methods used for histological identification of cells of interest could still damage the mRNA in the cells. To study the contribution of staining methods to degradation of results from gene expression profiling of LCM samples, we subjected pellets of the mouse plasma cell tumor cell line TEPC 1165 to direct RNA extraction and to parallel frozen sectioning for LCM and subsequent RNA extraction. We used microarray hybridization analysis to compare gene expression profiles of RNA from cell pellets with gene expression profiles of RNA from frozen sections that had been stained with hematoxylin and eosin (H&E), Nissl Stain (NS), and for immunofluorescence (IF) as well as with the plasma cell-revealing methyl green pyronin (MGP) stain. All RNAs were amplified with two rounds of T7-based in vitro transcription and analyzed by two-color expression analysis on 10-K cDNA microarrays. The MGP-stained samples showed the least introduction of mRNA loss, followed by H&E and immunofluorescence. Nissl staining was significantly more detrimental to gene expression profiles, presumably owing to an aqueous step in which RNA may have been damaged by endogenous or exogenous RNAases. RNA damage can occur during the staining steps preparatory to laser capture microdissection, with the consequence of loss of representation of certain genes in microarray hybridization analysis. Inclusion of RNAase inhibitor in aqueous staining solutions appears to be important in protecting RNA from loss of gene transcripts.

Histological staining methods preparatory to laser capture microdissection significantly affect the integrity of the cellular RNA

PubMed Central

Wang, Hongyang; Owens, James D; Shih, Joanna H; Li, Ming-Chung; Bonner, Robert F; Mushinski, J Frederic

2006-01-01

Background Gene expression profiling by microarray analysis of cells enriched by laser capture microdissection (LCM) faces several technical challenges. Frozen sections yield higher quality RNA than paraffin-imbedded sections, but even with frozen sections, the staining methods used for histological identification of cells of interest could still damage the mRNA in the cells. To study the contribution of staining methods to degradation of results from gene expression profiling of LCM samples, we subjected pellets of the mouse plasma cell tumor cell line TEPC 1165 to direct RNA extraction and to parallel frozen sectioning for LCM and subsequent RNA extraction. We used microarray hybridization analysis to compare gene expression profiles of RNA from cell pellets with gene expression profiles of RNA from frozen sections that had been stained with hematoxylin and eosin (H&E), Nissl Stain (NS), and for immunofluorescence (IF) as well as with the plasma cell-revealing methyl green pyronin (MGP) stain. All RNAs were amplified with two rounds of T7-based in vitro transcription and analyzed by two-color expression analysis on 10-K cDNA microarrays. Results The MGP-stained samples showed the least introduction of mRNA loss, followed by H&E and immunofluorescence. Nissl staining was significantly more detrimental to gene expression profiles, presumably owing to an aqueous step in which RNA may have been damaged by endogenous or exogenous RNAases. Conclusion RNA damage can occur during the staining steps preparatory to laser capture microdissection, with the consequence of loss of representation of certain genes in microarray hybridization analysis. Inclusion of RNAase inhibitor in aqueous staining solutions appears to be important in protecting RNA from loss of gene transcripts. PMID:16643667

Gene expression profiling in respond to TBT exposure in small abalone Haliotis diversicolor.

PubMed

Jia, Xiwei; Zou, Zhihua; Wang, Guodong; Wang, Shuhong; Wang, Yilei; Zhang, Ziping

2011-10-01

In this study, we investigated the gene expression profiling of small abalone, Haliotis diversicolor by tributyltin (TBT) exposure using a cDNA microarray containing 2473 unique transcripts. Totally, 107 up-regulated genes and 41 down-regulated genes were found. For further investigation of candidate genes from microarray data and EST analysis, quantitative real-time PCR was performed at 6 h, 24 h, 48 h, 96 h and 192 h TBT exposure. 26 genes were found to be significantly differentially expressed in different time course, 3 of them were unknown. Some gene homologues like cellulose, endo-beta-1,4-glucanase, ferritin subunit 1 and thiolester containing protein II CG7052-PB might be the good biomarker candidate for TBT monitor. The identification of stress response genes and their expression profiles will permit detailed investigation of the defense responses of small abalone genes. Published by Elsevier Ltd.

Abnormal gene expression profiles in human ovaries from polycystic ovary syndrome patients.

PubMed

Jansen, Erik; Laven, Joop S E; Dommerholt, Henri B R; Polman, Jan; van Rijt, Cindy; van den Hurk, Caroline; Westland, Jolanda; Mosselman, Sietse; Fauser, Bart C J M

2004-12-01

Polycystic ovary syndrome (PCOS) represents the most common cause of anovulatory infertility and affects 5-10% of women of reproductive age. The etiology of PCOS is still unknown. The current study is the first to describe consistent differences in gene expression profiles in human ovaries comparing PCOS patients vs. healthy normoovulatory individuals. The microarray analysis of PCOS vs. normal ovaries identifies dysregulated expression of genes encoding components of several biological pathways or systems such as Wnt signaling, extracellular matrix components, and immunological factors. Resulting data may provide novel clues for ovarian dysfunction in PCOS. Intriguingly, the gene expression profiles of ovaries from (long-term) androgen-treated female-to-male transsexuals (TSX) show considerable overlap with PCOS. This observation provides supportive evidence that androgens play a key role in the pathogenesis of PCOS. Presented data may contribute to a better understanding of dysregulated pathways in PCOS, which might ultimately reveal novel leads for therapeutic intervention.

Expression of MIF and TNFA in psoriatic arthritis: relationship with Th1/Th2/Th17 cytokine profiles and clinical variables.

PubMed

Bautista-Herrera, L A; De la Cruz-Mosso, U; Morales-Zambrano, R; Villanueva-Quintero, G D; Hernández-Bello, J; Ramírez-Dueñas, M G; Martínez-López, E; Brennan-Bourdon, L M; Baños-Hernández, C J; Muñoz-Valle, J F

2018-05-01

Psoriatic arthritis (PsA) is an autoimmune inflammatory disease associated with psoriasis. The cause of this pathology is still unknown, but research suggests the diseases are caused by a deregulated cytokine production. MIF is a cytokine associated with immunomodulation of Th1, Th2, and Th17 cytokine profiles in inflammatory diseases. Based on this knowledge, the aim of this study was to determine the association of MIF and TNFA expression with Th1, Th2, and Th17 cytokine profiles in serum levels of PsA patients. A cross-sectional study was performed in 50 PsA patients and 30 control subjects (CS). The cytokine profiles were quantified by BioPlex MagPix system and the mRNA expression levels by real-time PCR. TNFA mRNA expression was 138.81-folds higher in PsA patients than CS (p < 0.001). Regarding MIF mRNA expression, no significant differences were observed; however, a positive correlation was identified between MIF mRNA expression and PsA time of evolution (r = - 0.53, p = 0.009). An increase of Th1 (IFNγ: PsA = 37.1 pg/mL vs. CS = 17 pg/mL, p < 0.05; TNFα: PsA = 24.6 pg/mL vs. CS = 9.8 pg/mL, p < 0.0001) and Th17 cytokine profiles (IL-17: PsA = 6.4 pg/mL vs. CS = 2.7 pg/mL, p < 0.05; IL-22: PsA = 8.4 pg/mL vs. CS = 1.8 pg/mL, p < 0.001), were found in PsA patients. Th2 cytokines were not significantly different in both groups. In conclusion, a high expression of TNFA mRNA, as well as an increase of Th1 and Th17 cytokine profiles evaluated by IFNγ, TNFα, IL-17, and IL-22 cytokines, was observed in PsA patients.

Arabidopsis Gene Family Profiler (aGFP)--user-oriented transcriptomic database with easy-to-use graphic interface.

PubMed

Dupl'áková, Nikoleta; Renák, David; Hovanec, Patrik; Honysová, Barbora; Twell, David; Honys, David

2007-07-23

Microarray technologies now belong to the standard functional genomics toolbox and have undergone massive development leading to increased genome coverage, accuracy and reliability. The number of experiments exploiting microarray technology has markedly increased in recent years. In parallel with the rapid accumulation of transcriptomic data, on-line analysis tools are being introduced to simplify their use. Global statistical data analysis methods contribute to the development of overall concepts about gene expression patterns and to query and compose working hypotheses. More recently, these applications are being supplemented with more specialized products offering visualization and specific data mining tools. We present a curated gene family-oriented gene expression database, Arabidopsis Gene Family Profiler (aGFP; http://agfp.ueb.cas.cz), which gives the user access to a large collection of normalised Affymetrix ATH1 microarray datasets. The database currently contains NASC Array and AtGenExpress transcriptomic datasets for various tissues at different developmental stages of wild type plants gathered from nearly 350 gene chips. The Arabidopsis GFP database has been designed as an easy-to-use tool for users needing an easily accessible resource for expression data of single genes, pre-defined gene families or custom gene sets, with the further possibility of keyword search. Arabidopsis Gene Family Profiler presents a user-friendly web interface using both graphic and text output. Data are stored at the MySQL server and individual queries are created in PHP script. The most distinguishable features of Arabidopsis Gene Family Profiler database are: 1) the presentation of normalized datasets (Affymetrix MAS algorithm and calculation of model-based gene-expression values based on the Perfect Match-only model); 2) the choice between two different normalization algorithms (Affymetrix MAS4 or MAS5 algorithms); 3) an intuitive interface; 4) an interactive "virtual plant" visualizing the spatial and developmental expression profiles of both gene families and individual genes. Arabidopsis GFP gives users the possibility to analyze current Arabidopsis developmental transcriptomic data starting with simple global queries that can be expanded and further refined to visualize comparative and highly selective gene expression profiles.

Exposure to metals mixtures: Genomic alterations of infectious ...

EPA Pesticide Factsheets

Exposure to toxic metals can have harmful health effects, particularly in children. Although studies have investigated the individual effects toxic metals have on gene expression and health outcomes, there are no studies assessing the effect of metal mixtures on gene expression profiles. Here, we assessed the mixture effect of six toxic metals (arsenic, beryllium, cadmium, chromium, mercury, and lead) on gene expression profiles in children in Detroit, Michigan. As part of the Mechanistic Indicators of Childhood Asthma (MICA) cross sectional study, we assessed metal exposure in 131 children in Detroit using fingernail metals levels. A metals mixture score was calculated and compared to gene expression profiles across the population adjusting for age and race. There were 145 unique genes that were significantly differentially expressed when comparing children exposed to low and high levels of the metals mixture. Of the genes differentially expressed, 107 (74%) had increased expression while 38 (26%) had decreased expression. The main biological function associated with multiple metals was infectious disease. Within that group, genes were associated with infection of respiratory tract (P < 10-6) severe acute respiratory syndrome (P < 10-5), and sepsis (P < 10-3). Taken together, these data demonstrate that exposure to metals mixtures may activate gene networks related to infectious disease response. This abstract does not necessarily reflect the views or policie

Embryonic stem cell-like features of testicular carcinoma in situ revealed by genome-wide gene expression profiling.

PubMed

Almstrup, Kristian; Hoei-Hansen, Christina E; Wirkner, Ute; Blake, Jonathon; Schwager, Christian; Ansorge, Wilhelm; Nielsen, John E; Skakkebaek, Niels E; Rajpert-De Meyts, Ewa; Leffers, Henrik

2004-07-15

Carcinoma in situ (CIS) is the common precursor of histologically heterogeneous testicular germ cell tumors (TGCTs), which in recent decades have markedly increased and now are the most common malignancy of young men. Using genome-wide gene expression profiling, we identified >200 genes highly expressed in testicular CIS, including many never reported in testicular neoplasms. Expression was further verified by semiquantitative reverse transcription-PCR and in situ hybridization. Among the highest expressed genes were NANOG and POU5F1, and reverse transcription-PCR revealed possible changes in their stoichiometry on progression into embryonic carcinoma. We compared the CIS expression profile with patterns reported in embryonic stem cells (ESCs), which revealed a substantial overlap that may be as high as 50%. We also demonstrated an over-representation of expressed genes in regions of 17q and 12, reported as unstable in cultured ESCs. The close similarity between CIS and ESCs explains the pluripotency of CIS. Moreover, the findings are consistent with an early prenatal origin of TGCTs and thus suggest that etiologic factors operating in utero are of primary importance for the incidence trends of TGCTs. Finally, some of the highly expressed genes identified in this study are promising candidates for new diagnostic markers for CIS and/or TGCTs.

Stem Cell-Associated Marker Expression in Canine Hair Follicles

PubMed Central

Gerhards, Nora M.; Sayar, Beyza S.; Origgi, Francesco C.; Galichet, Arnaud; Müller, Eliane J.; Welle, Monika M.; Wiener, Dominique J.

2016-01-01

Functional hair follicle (HF) stem cells (SCs) are crucial to maintain the constant recurring growth of hair. In mice and humans, SC subpopulations with different biomarker expression profiles have been identified in discrete anatomic compartments of the HF. The rare studies investigating canine HF SCs have shown similarities in biomarker expression profiles to that of mouse and human SCs. The aim of our study was to broaden the current repertoire of SC-associated markers and their expression patterns in the dog. We combined analyses on the expression levels of CD34, K15, Sox9, CD200, Nestin, LGR5 and LGR6 in canine skin using RT-qPCR, the corresponding proteins in dog skin lysates, and their expression patterns in canine HFs using immunohistochemistry. Using validated antibodies, we were able to define the location of CD34, Sox9, Keratin15, LGR5 and Nestin in canine HFs and confirm that all tested biomarkers are expressed in canine skin. Our results show similarities between the expression profile of canine, human and mouse HF SC markers. This repertoire of biomarkers will allow us to conduct functional studies and investigate alterations in the canine SC compartment of different diseases, like alopecia or skin cancer with the possibility to extend relevant findings to human patients. PMID:26739040

Stem Cell-Associated Marker Expression in Canine Hair Follicles.

PubMed

Gerhards, Nora M; Sayar, Beyza S; Origgi, Francesco C; Galichet, Arnaud; Müller, Eliane J; Welle, Monika M; Wiener, Dominique J

2016-03-01

Functional hair follicle (HF) stem cells (SCs) are crucial to maintain the constant recurring growth of hair. In mice and humans, SC subpopulations with different biomarker expression profiles have been identified in discrete anatomic compartments of the HF. The rare studies investigating canine HF SCs have shown similarities in biomarker expression profiles to that of mouse and human SCs. The aim of our study was to broaden the current repertoire of SC-associated markers and their expression patterns in the dog. We combined analyses on the expression levels of CD34, K15, Sox9, CD200, Nestin, LGR5 and LGR6 in canine skin using RT-qPCR, the corresponding proteins in dog skin lysates, and their expression patterns in canine HFs using immunohistochemistry. Using validated antibodies, we were able to define the location of CD34, Sox9, Keratin15, LGR5 and Nestin in canine HFs and confirm that all tested biomarkers are expressed in canine skin. Our results show similarities between the expression profile of canine, human and mouse HF SC markers. This repertoire of biomarkers will allow us to conduct functional studies and investigate alterations in the canine SC compartment of different diseases, like alopecia or skin cancer with the possibility to extend relevant findings to human patients. © 2016 The Histochemical Society.

Similar response patterns to topical minoxidil foam 5% in frontal and vertex scalp of men with androgenetic alopecia: a microarray analysis.

PubMed

Mirmirani, P; Consolo, M; Oyetakin-White, P; Baron, E; Leahy, P; Karnik, P

2015-06-01

There are regional variations in the scalp hair miniaturization seen in androgenetic alopecia (AGA). Use of topical minoxidil can lead to reversal of miniaturization in the vertex scalp. However, its effects on other scalp regions have been less well studied. To determine whether scalp biopsies from men with AGA show variable gene expression before and after 8 weeks of treatment with minoxidil topical foam 5% (MTF) vs. placebo. A placebo-controlled double-blinded prospective pilot study of MTF vs. placebo was conducted in 16 healthy men aged 18-49 years with Hamilton-Norwood type IV-V thinning. The subjects were asked to apply the treatment (active drug or placebo) to the scalp twice daily for 8 weeks. Stereotactic scalp photographs were taken at the baseline and final visits, to monitor global hair growth. Scalp biopsies were taken at the leading edge of hair loss from the frontal and vertex scalp before and after treatment with MTF and placebo, and microarray analysis was performed using the Affymetrix GeneChip HG U133 Plus 2.0. Global stereotactic photographs showed that MTF induced hair growth in both the frontal and vertex scalp of patients with AGA. Regional differences in gene expression profiles were observed before treatment. However, MTF treatment induced the expression of hair keratin-associated genes and decreased the expression of epidermal differentiation complex and inflammatory genes in both scalp regions. These data suggest that MTF is effective in the treatment of both the frontal and vertex scalp of patients with AGA. © 2014 British Association of Dermatologists.

Aberrant expression of epithelial leucine-rich repeat containing G protein-coupled receptor 5-positive cells in the eutopic endometrium in endometriosis and implications in deep-infiltrating endometriosis.

PubMed

Vallvé-Juanico, Júlia; Suárez-Salvador, Elena; Castellví, Josep; Ballesteros, Agustín; Taylor, Hugh S; Gil-Moreno, Antonio; Santamaria, Xavier

2017-11-01

To characterize leucine-rich repeat containing G protein-coupled receptor 5-positive (LGR5 + ) cells from the endometrium of women with endometriosis. Prospective experimental study. University hospital/fertility clinic. Twenty-seven women with endometriosis who underwent surgery and 12 healthy egg donors, together comprising 39 endometrial samples. Obtaining of uterine aspirates by using a Cornier Pipelle. Immunofluorescence in formalin-fixed paraffin-embedded tissue from mice and healthy and pathologic human endometrium using antibodies against LGR5, E-cadherin, and cytokeratin, and epithelial and stromal LGR5 + cells isolated from healthy and pathologic human eutopic endometrium by fluorescence-activated cell sorting and transcriptomic characterization by RNA high sequencing. Immunofluorescence showed that LGR5 + cells colocalized with epithelial markers in the stroma of the endometrium only in endometriotic patients. The results from RNA high sequencing of LGR5 + cells from epithelium and stroma did not show any statistically significant differences between them. The LGR5 + versus LGR5 - cells in pathologic endometrium showed 394 differentially expressed genes. The LGR5 + cells in deep-infiltrating endometriosis expressed inflammatory markers not present in the other types of the disease. Our results revealed the presence of aberrantly located LGR5 + cells coexpressing epithelial markers in the stromal compartment of women with endometriosis. These cells have a statistically significantly different expression profile in deep-infiltrating endometriosis in comparison with other types of endometriosis, independent of the menstrual cycle phase. Further studies are needed to elucidate their role and influence in reproductive outcomes. Copyright © 2017. Published by Elsevier Inc.

DNA Microarray Analysis Identifies CKS2 and LEPR as Potential Markers of Meningioma Recurrence

PubMed Central

Menghi, Francesca; Orzan, Francesca N.; Eoli, Marica; Farinotti, Mariangela; Maderna, Emanuela; Pisati, Federica; Bianchessi, Donatella; Valletta, Lorella; Lodrini, Sandro; Galli, Giuseppe; Anghileri, Elena; Pellegatta, Serena; Pollo, Bianca

2011-01-01

Meningiomas are the most frequent intracranial tumors. Surgery can be curative, but recurrences are possible. We performed gene expression analyses and loss of heterozygosity (LOH) studies looking for new markers predicting the recurrence risk. We analyzed expression profiles of 23 meningiomas (10 grade I, 10 grade II, and 3 grade III) and validated the data using quantitative polymerase chain reaction (qPCR). We performed LOH analysis on 40 meningiomas, investigating chromosomal regions on 1p, 9p, 10q, 14q, and 22q. We found 233 and 268 probe sets to be significantly down- and upregulated, respectively, in grade II or III meningiomas. Genes downregulated in high-grade meningiomas were overrepresented on chromosomes 1, 6, 9, 10, and 14. Based on functional enrichment analysis, we selected LIM domain and actin binding 1 (LIMA1), tissue inhibitor of metalloproteinases 3 (TIMP3), cyclin-dependent kinases regulatory subunit 2 (CKS2), leptin receptor (LEPR), and baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) for validation using qPCR and confirmed their differential expression in the two groups of tumors. We calculated ΔCt values of CKS2 and LEPR and found that their differential expression (C-L index) was significantly higher in grade I than in grade II or III meningiomas (p < .0001). Interestingly, the C-L index of nine grade I meningiomas from patients who relapsed in <5 years was significantly lower than in grade I meningiomas from patients who did not relapse. These findings indicate that the C-L index may be relevant to define the progression risk in meningioma patients, helping guide their clinical management. A prospective analysis on a larger number of cases is warranted. PMID:21948653

DNA microarray analysis identifies CKS2 and LEPR as potential markers of meningioma recurrence.

PubMed

Menghi, Francesca; Orzan, Francesca N; Eoli, Marica; Farinotti, Mariangela; Maderna, Emanuela; Pisati, Federica; Bianchessi, Donatella; Valletta, Lorella; Lodrini, Sandro; Galli, Giuseppe; Anghileri, Elena; Pellegatta, Serena; Pollo, Bianca; Finocchiaro, Gaetano

2011-01-01

Meningiomas are the most frequent intracranial tumors. Surgery can be curative, but recurrences are possible. We performed gene expression analyses and loss of heterozygosity (LOH) studies looking for new markers predicting the recurrence risk. We analyzed expression profiles of 23 meningiomas (10 grade I, 10 grade II, and 3 grade III) and validated the data using quantitative polymerase chain reaction (qPCR). We performed LOH analysis on 40 meningiomas, investigating chromosomal regions on 1p, 9p, 10q, 14q, and 22q. We found 233 and 268 probe sets to be significantly down- and upregulated, respectively, in grade II or III meningiomas. Genes downregulated in high-grade meningiomas were overrepresented on chromosomes 1, 6, 9, 10, and 14. Based on functional enrichment analysis, we selected LIM domain and actin binding 1 (LIMA1), tissue inhibitor of metalloproteinases 3 (TIMP3), cyclin-dependent kinases regulatory subunit 2 (CKS2), leptin receptor (LEPR), and baculoviral inhibitor of apoptosis repeat-containing 5 (BIRC5) for validation using qPCR and confirmed their differential expression in the two groups of tumors. We calculated ΔCt values of CKS2 and LEPR and found that their differential expression (C-L index) was significantly higher in grade I than in grade II or III meningiomas (p < .0001). Interestingly, the C-L index of nine grade I meningiomas from patients who relapsed in <5 years was significantly lower than in grade I meningiomas from patients who did not relapse. These findings indicate that the C-L index may be relevant to define the progression risk in meningioma patients, helping guide their clinical management. A prospective analysis on a larger number of cases is warranted.

Human cancer tissues exhibit reduced A-to-I editing of miRNAs coupled with elevated editing of their targets

PubMed Central

Pinto, Yishay; Buchumenski, Ilana

2018-01-01

Abstract A-to-I RNA editing is an important post-transcriptional modification, known to be altered in tumors. It targets dozens of sites within miRNAs, some of which impact miRNA biogenesis and function, as well as many miRNA recognition sites. However, the full extent of the effect of editing on regulation by miRNAs and its behavior in human cancers is still unknown. Here we systematically characterized miRNA editing in 10 593 human samples across 32 cancer types and normal controls. We find that the majority of previously reported sites show little to no evidence for editing in this dataset, compile a list of 58 reliable miRNA editing sites, and study them across normal and cancer samples. Edited miRNA versions tend to suppress expression of known oncogenes, and, consistently, we observe a clear global tendency for hypo-editing in tumors, in strike contrast to the behavior for mRNA editing, allowing an accurate classification of normal/tumor samples based on their miRNA editing profile. In many cancers this profile correlates with patients' survival. Finally, thousands of miRNA binding sites are differentially edited in cancer. Our study thus establishes the important effect of RNA editing on miRNA-regulation in the tumor cell, with prospects for diagnostic and prognostic applications. PMID:29165639

Socioeconomic characteristics of patients with oropharyngeal carcinoma according to tumor HPV status, patient smoking status, and sexual behavior.

PubMed

Dahlstrom, Kristina R; Bell, Diana; Hanby, Duncan; Li, Guojun; Wang, Li-E; Wei, Qingyi; Williams, Michelle D; Sturgis, Erich M

2015-09-01

Patients with oropharyngeal cancer (OPC) have distinct risk factor profiles reflected in the human papillomavirus (HPV) status of their tumor, and these profiles may also be influenced by factors related to socioeconomic status (SES). The goal of this study was to describe the socioeconomic characteristics of a large cohort of patients with OPC according to HPV status, smoking status, and sexual behavior. Patients with OPC prospectively provided information about their smoking and alcohol use, socioeconomic characteristics, and sexual behaviors. HPV status was determined by a composite of immunohistochemistry for p16 expression, HPV in situ hybridization, and PCR assay in 356 patients. Standard descriptive statistics and logistic regression were used to compare socioeconomic characteristics between patient subgroups. Patients with HPV-positive OPC had higher levels of education, income, and overall SES. Among patients with HPV-positive OPC, never/light smokers had more than 5 times the odds of having at least a bachelor's degree and being in the highest level of SES compared with smokers. Patients with HPV-positive OPC and those with higher levels of education and SES had higher numbers of lifetime any and oral sex partners, although not all of these differences were significant. Socioeconomic differences among subgroups of OPC patients have implications for OPC prevention efforts, including tobacco cessation, behavior modification, and vaccination programs. Copyright © 2015 Elsevier Ltd. All rights reserved.

Selection and Validation of Reference Genes for qRT-PCR Expression Analysis of Candidate Genes Involved in Olfactory Communication in the Butterfly Bicyclus anynana

PubMed Central

Arun, Alok; Baumlé, Véronique; Amelot, Gaël; Nieberding, Caroline M.

2015-01-01

Real-time quantitative reverse transcription PCR (qRT-PCR) is a technique widely used to quantify the transcriptional expression level of candidate genes. qRT-PCR requires the selection of one or several suitable reference genes, whose expression profiles remain stable across conditions, to normalize the qRT-PCR expression profiles of candidate genes. Although several butterfly species (Lepidoptera) have become important models in molecular evolutionary ecology, so far no study aimed at identifying reference genes for accurate data normalization for any butterfly is available. The African bush brown butterfly Bicyclus anynana has drawn considerable attention owing to its suitability as a model for evolutionary ecology, and we here provide a maiden extensive study to identify suitable reference gene in this species. We monitored the expression profile of twelve reference genes: eEF-1α, FK506, UBQL40, RpS8, RpS18, HSP, GAPDH, VATPase, ACT3, TBP, eIF2 and G6PD. We tested the stability of their expression profiles in three different tissues (wings, brains, antennae), two developmental stages (pupal and adult) and two sexes (male and female), all of which were subjected to two food treatments (food stress and control feeding ad libitum). The expression stability and ranking of twelve reference genes was assessed using two algorithm-based methods, NormFinder and geNorm. Both methods identified RpS8 as the best suitable reference gene for expression data normalization. We also showed that the use of two reference genes is sufficient to effectively normalize the qRT-PCR data under varying tissues and experimental conditions that we used in B. anynana. Finally, we tested the effect of choosing reference genes with different stability on the normalization of the transcript abundance of a candidate gene involved in olfactory communication in B. anynana, the Fatty Acyl Reductase 2, and we confirmed that using an unstable reference gene can drastically alter the expression profile of the target candidate genes. PMID:25793735

Selection and validation of reference genes for qRT-PCR expression analysis of candidate genes involved in olfactory communication in the butterfly Bicyclus anynana.

PubMed

Arun, Alok; Baumlé, Véronique; Amelot, Gaël; Nieberding, Caroline M

2015-01-01

Real-time quantitative reverse transcription PCR (qRT-PCR) is a technique widely used to quantify the transcriptional expression level of candidate genes. qRT-PCR requires the selection of one or several suitable reference genes, whose expression profiles remain stable across conditions, to normalize the qRT-PCR expression profiles of candidate genes. Although several butterfly species (Lepidoptera) have become important models in molecular evolutionary ecology, so far no study aimed at identifying reference genes for accurate data normalization for any butterfly is available. The African bush brown butterfly Bicyclus anynana has drawn considerable attention owing to its suitability as a model for evolutionary ecology, and we here provide a maiden extensive study to identify suitable reference gene in this species. We monitored the expression profile of twelve reference genes: eEF-1α, FK506, UBQL40, RpS8, RpS18, HSP, GAPDH, VATPase, ACT3, TBP, eIF2 and G6PD. We tested the stability of their expression profiles in three different tissues (wings, brains, antennae), two developmental stages (pupal and adult) and two sexes (male and female), all of which were subjected to two food treatments (food stress and control feeding ad libitum). The expression stability and ranking of twelve reference genes was assessed using two algorithm-based methods, NormFinder and geNorm. Both methods identified RpS8 as the best suitable reference gene for expression data normalization. We also showed that the use of two reference genes is sufficient to effectively normalize the qRT-PCR data under varying tissues and experimental conditions that we used in B. anynana. Finally, we tested the effect of choosing reference genes with different stability on the normalization of the transcript abundance of a candidate gene involved in olfactory communication in B. anynana, the Fatty Acyl Reductase 2, and we confirmed that using an unstable reference gene can drastically alter the expression profile of the target candidate genes.

The resemblance and disparity of gene expression in dormant and non-dormant seeds and crown buds of leafy spurge (Euphorbia esula)

USDA-ARS?s Scientific Manuscript database

Overlaps in transcriptome profiles between different phases of bud and seed dormancy have not been determined. Thus, we compared various phases of dormancy between seeds and buds to identify common genes and molecular processes. Cluster analysis of expression profiles for 201 selected genes indicate...

GENE EXPRESSION CHANGES IN ARABIDOPSIS THALIANA SEEDLING ROOTS EXPOSED TO THE MUNITION HEXAHYDRO-1,3,5-TRINITRO-1,3,5-TRIAZINE

EPA Science Inventory

Arabidopsis thaliana root transcriptome responses to the munition, hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), were assessed using serial analysis of gene expression (SAGE). Comparison of the transcriptional profile for the RDX response to a profile previously described for Ar...

MicroRNA expression profiles from eggs of different qualities associated with post-ovulatory ageing in rainbow trout (Oncorhynchus mykiss)

USDA-ARS?s Scientific Manuscript database

Background: Egg quality is an important aspect in rainbow trout farming. Post-ovulatory aging is one of the most important factors affecting egg quality. MicroRNAs (miRNAs) are the major regulators in various biological processes and their expression profiles could serve as reliable biomarkers for v...

WISC-IV Intellectual Profiles in Italian Children with Specific Learning Disorder and Related Impairments in Reading, Written Expression, and Mathematics

ERIC Educational Resources Information Center

Poletti, Michele

2016-01-01

The fifth edition of the "Diagnostic and Statistical Manual of Mental Disorders" grouped specific learning disabilities in the single diagnostic category of specific learning disorder (SLD), with specifiers for impairments in reading, written expression, and mathematics. This study aimed at investigating the intellectual profile,…

DIFFERENTIAL TRANSCRIPTION FACTOR ACTIVATION AD GENE EXPRESSION PROFILES IN HUMAN VASCULAR ENDOTHELIAL CELLS ON EXPOSURE TO RESIDUAL OIL FLY ASH (ROFA) AND VANADIUM

EPA Science Inventory

Differential transcription factor activation and gene expression profiles in human vascular endothelial cells on exposure to residual oil fly ash (ROFA) and vanadium.
Srikanth S. Nadadur and Daniel L. Costa, US EPA, ORD, NHEERL (ETD, Pulmonary Toxicology Branch), Research ...

Gene expression profiling of bovine ovarian follicular and luteal cells provides insight into cellular identities and functions

USDA-ARS?s Scientific Manuscript database

After ovulation, somatic cells of the ovarian follicle (theca and granulosa cells) become the small and large luteal cells of the corpus luteum. Aside from known cell type-specific receptors and steroidogenic enzymes, little is known about the differences in the gene expression profiles of these fou...

Characterization and expression analysis of two cDNAs encoding Xa1 and oxysterol binding proteins in sorghum (Sorghum bicolor)

USDA-ARS?s Scientific Manuscript database

Using suppression subtractive hybridization (SSH) and subsequent microarray analysis, expression profiles of sorghum genes responsive to greenbug phloem-feeding were obtained and identified. Among the profiles, two cDNAs designated to MM73 and MM95 were identified to encode Xa1 (Xa1) and oxysterol ...

Discriminating Down Syndrome and Fragile X Syndrome Based on Language Ability

ERIC Educational Resources Information Center

Finestack, Lizbeth H.; Sterling, Audra M.; Abbeduto, Leonard

2013-01-01

This study compared the receptive and expressive language profiles of verbally expressive children and adolescents with Down Syndrome (DS) and those with Fragile X syndrome (FXS) and examined the extent to which these profiles reliably differentiate the diagnostic groups. A total of twenty-four verbal participants with DS (mean age: 12 years),…

GENE EXPRESSION PROFILING OF THE RAT KIDNEY FOLLOWING CHRONIC EXPOSURE (100 WKS) TO THE WATER DISINFECTANT BYPRODUCT AND RENAL CARCINOGEN, POTASSIUM BROMATE.

EPA Science Inventory

Gene expression profiling of the rat kidney following chronic exposure (100 wks) to the water
disinfectant byproduct and renal carcinogen, potassium bromate.

Don Delker, James Allen, Gail Nelson, Tanya Moore, Barbara Roop, Russell Owen, and Anthony DeAngelo. Environment...

GENE EXPRESSION PROFILES IN HUMAN AND RAT VASCULAR ENDOTHELIAL CELLS EXPOSED TO RESIDUAL OIL FLY ASH (ROFA) AND VANADIUM (V)

EPA Science Inventory

Gene expression profiles in human and rat vascular endothelial cells exposed to residual oil fly ash (ROFA) or vanadium (V).
Srikanth S. Nadadur, Darrell W. Winsett and Daniel L. Costa, US EPA, ORD, NHEERL (ETD, Pulmonary Toxicology Branch), Research Triangle Park, NC 27711.

GENE EXPRESSION PROFILING OF MOUSE SKIN AND PAPILLOMAS FOLLOWING CHRONIC EXPOSURE TO MONOMETHYLARSONOUS ACID IN K6/ODC TRANSGENIC MICE

EPA Science Inventory

Methylarsonous acid [MMA(III)], a common metabolite of inorganic arsenic metabolism, increases tumor frequency in the skin of K6/ODC transgenic mice following a chronic exposure. To characterize gene expression profiles predictive of MMA(III) exposure and mode of action of carcin...

Profiles of Receptive and Expressive Language Abilities in Boys with Comorbid Fragile X Syndrome and Autism

ERIC Educational Resources Information Center

McDuffie, Andrea; Kover, Sara; Abbeduto, Leonard; Lewis, Pamela; Brown, Ted

2012-01-01

The authors examined receptive and expressive language profiles for a group of verbal male children and adolescents who had fragile X syndrome along with varying degrees of autism symptoms. A categorical approach for assigning autism diagnostic classification, based on the combined use of the Autism Diagnostic Interview--Revised and the Autism…

Moving Toward Integrating Gene Expression Profiling into High-throughput Testing:A Gene Expression Biomarker Accurately Predicts Estrogen Receptor α Modulation in a Microarray Compendium

EPA Science Inventory

Microarray profiling of chemical-induced effects is being increasingly used in medium and high-throughput formats. In this study, we describe computational methods to identify molecular targets from whole-genome microarray data using as an example the estrogen receptor α (ERα), ...

A proof of the DBRF-MEGN method, an algorithm for deducing minimum equivalent gene networks

PubMed Central

2011-01-01

Background We previously developed the DBRF-MEGN (difference-based regulation finding-minimum equivalent gene network) method, which deduces the most parsimonious signed directed graphs (SDGs) consistent with expression profiles of single-gene deletion mutants. However, until the present study, we have not presented the details of the method's algorithm or a proof of the algorithm. Results We describe in detail the algorithm of the DBRF-MEGN method and prove that the algorithm deduces all of the exact solutions of the most parsimonious SDGs consistent with expression profiles of gene deletion mutants. Conclusions The DBRF-MEGN method provides all of the exact solutions of the most parsimonious SDGs consistent with expression profiles of gene deletion mutants. PMID:21699737

Profiling differential gene expression of corals along a transect of waters adjacent to the Bermuda municipal dump.

PubMed

Morgan, Michael B; Edge, Sara E; Snell, Terry W

2005-01-01

A coral cDNA array containing 32 genes was used to examine the gene expression profiles of coral populations located at four sites that varied with distance from a semi-submerged municipal dump in Castle Harbour, Bermuda (previously identified as a point source of anthropogenic stressors). Genes on the array represent transcripts induced under controlled laboratory conditions to a variety of stressors both natural (temperature, sediment, salinity, darkness) and xenobiotic (heavy metals, pesticides, PAH) in origin. The gene expression profiles produced revealed information about the types of stressors. Consistent with other studies undertaken in Castle Harbour, the coral cDNA array detected responses to heavy metals, sedimentation, as well as oxidative stress.

Prospective Teachers' Awareness and Expression of Emotions: Associations with Proposed Strategies for Behavioral Management in the Classroom

ERIC Educational Resources Information Center

Garner, Pamela W.; Moses, Laurence K.; Waajid, Badiyyah

2013-01-01

This research examined whether prospective teachers' emotion regulation styles, dispositional empathy, and conceptions of competent student emotion and behavior were predictive of their attitudes about bullying and proposed responses to peer conflict. Overall, participants perceived physical bullying as more serious than verbal and relational…

Impact of Sonic Hedgehog Pathway Expression on Outcome in HPV Negative Head and Neck Carcinoma Patients after Surgery and Adjuvant Radiotherapy

PubMed Central

Enzenhofer, Elisabeth; Parzefall, Thomas; Haymerle, Georg; Schneider, Sven; Kadletz, Lorenz; Heiduschka, Gregor; Pammer, Johannes; Oberndorfer, Felicitas; Wrba, Fritz; Loader, Benjamin; Grasl, Matthäus Christoph; Perisanidis, Christos; Erovic, Boban M.

2016-01-01

Introduction HPV positive patients suffering from head and neck cancer benefit from intensified radiotherapy when applied as a primary as well as an adjuvant treatment strategy. However, HPV negative patients treated with surgery and adjuvant radiotherapy lack validated prognostic biomarkers. It is therefore important to define prognostic biomarkers in this particular patient population. Especially, ´high-risk groups´ need to be defined in order to adapt treatment protocols. Since dysregulation of the sonic hedgehog pathway plays an important role in carcinogenesis, we aimed to assess whether members of the sonic hedgehog-signaling pathway may act as prognostic factors in patients with HPV negative head and neck squamous cell carcinoma. Materials and Methods In this prospective study, pretreatment tumor biopsies of patients with head and neck squamous cell carcinoma were taken during panendoscopy (2005 to 2008). All patients were treated with surgery and postoperative radiotherapy. After assessment of HPV and p16 status, protein expression profiles of the Sonic hedgehog-signaling pathway were determined by immunohistochemistry and tissue microarray analyses in 36 HPV negative tumor biopsies. Expression profiles of Sonic hedgehog, Indian hedgehog, Patched, Smoothened, Gli-1, Gli-2 and Gli-3 were correlated with patients´ clinical data, local-control rate, disease-free as well as overall survival. Data from The Cancer Genome Atlas databank were used for external validation of our results. Results Gli-1 (p = 0.04) and Gli-2 (p = 0.02) overexpression was significantly linked to improved overall survival of HPV negative patients. Gli-2 (p = 0.04) overexpression correlated significantly with prolonged disease-free survival. Cox-multivariate analysis showed that overexpression of Gli-2 correlated independently (HR 0.40, 95% CI 0.16–0.95, p = 0.03) with increased overall survival. Discussion Gli-1 and Gli-2 overexpression represents a substantial prognostic factor for overall and disease-free survival in patients with locally advanced HPV negative head and neck cancer undergoing surgery and postoperative radiotherapy. PMID:27918595

Exploiting the full power of temporal gene expression profiling through a new statistical test: application to the analysis of muscular dystrophy data.

PubMed

Vinciotti, Veronica; Liu, Xiaohui; Turk, Rolf; de Meijer, Emile J; 't Hoen, Peter A C

2006-04-03

The identification of biologically interesting genes in a temporal expression profiling dataset is challenging and complicated by high levels of experimental noise. Most statistical methods used in the literature do not fully exploit the temporal ordering in the dataset and are not suited to the case where temporal profiles are measured for a number of different biological conditions. We present a statistical test that makes explicit use of the temporal order in the data by fitting polynomial functions to the temporal profile of each gene and for each biological condition. A Hotelling T2-statistic is derived to detect the genes for which the parameters of these polynomials are significantly different from each other. We validate the temporal Hotelling T2-test on muscular gene expression data from four mouse strains which were profiled at different ages: dystrophin-, beta-sarcoglycan and gamma-sarcoglycan deficient mice, and wild-type mice. The first three are animal models for different muscular dystrophies. Extensive biological validation shows that the method is capable of finding genes with temporal profiles significantly different across the four strains, as well as identifying potential biomarkers for each form of the disease. The added value of the temporal test compared to an identical test which does not make use of temporal ordering is demonstrated via a simulation study, and through confirmation of the expression profiles from selected genes by quantitative PCR experiments. The proposed method maximises the detection of the biologically interesting genes, whilst minimising false detections. The temporal Hotelling T2-test is capable of finding relatively small and robust sets of genes that display different temporal profiles between the conditions of interest. The test is simple, it can be used on gene expression data generated from any experimental design and for any number of conditions, and it allows fast interpretation of the temporal behaviour of genes. The R code is available from V.V. The microarray data have been submitted to GEO under series GSE1574 and GSE3523.

Exploiting the full power of temporal gene expression profiling through a new statistical test: Application to the analysis of muscular dystrophy data

PubMed Central

Vinciotti, Veronica; Liu, Xiaohui; Turk, Rolf; de Meijer, Emile J; 't Hoen, Peter AC

2006-01-01

Background The identification of biologically interesting genes in a temporal expression profiling dataset is challenging and complicated by high levels of experimental noise. Most statistical methods used in the literature do not fully exploit the temporal ordering in the dataset and are not suited to the case where temporal profiles are measured for a number of different biological conditions. We present a statistical test that makes explicit use of the temporal order in the data by fitting polynomial functions to the temporal profile of each gene and for each biological condition. A Hotelling T2-statistic is derived to detect the genes for which the parameters of these polynomials are significantly different from each other. Results We validate the temporal Hotelling T2-test on muscular gene expression data from four mouse strains which were profiled at different ages: dystrophin-, beta-sarcoglycan and gamma-sarcoglycan deficient mice, and wild-type mice. The first three are animal models for different muscular dystrophies. Extensive biological validation shows that the method is capable of finding genes with temporal profiles significantly different across the four strains, as well as identifying potential biomarkers for each form of the disease. The added value of the temporal test compared to an identical test which does not make use of temporal ordering is demonstrated via a simulation study, and through confirmation of the expression profiles from selected genes by quantitative PCR experiments. The proposed method maximises the detection of the biologically interesting genes, whilst minimising false detections. Conclusion The temporal Hotelling T2-test is capable of finding relatively small and robust sets of genes that display different temporal profiles between the conditions of interest. The test is simple, it can be used on gene expression data generated from any experimental design and for any number of conditions, and it allows fast interpretation of the temporal behaviour of genes. The R code is available from V.V. The microarray data have been submitted to GEO under series GSE1574 and GSE3523. PMID:16584545

The Nutrient Profile of Foods Consumed Using the British Food Standards Agency Nutrient Profiling System Is Associated with Metabolic Syndrome in the SU.VI.MAX Cohort.

PubMed

Julia, Chantal; Fézeu, Léopold K; Ducrot, Pauline; Méjean, Caroline; Péneau, Sandrine; Touvier, Mathilde; Hercberg, Serge; Kesse-Guyot, Emmanuelle

2015-10-01

Metabolic syndrome (MetS), comprising high waist circumference, blood pressure, glycemia, and triglycerides, and lower HDL cholesterol could in part be prevented by adequate nutrition. Nutrient profiling systems could be useful public health tools to help consumers make healthier food choices. An individual dietary index (DI) based on nutrient profiling of foods consumed could characterize dietary patterns in relation to the onset of MetS. The objective of this study was to prospectively investigate the association between the Food Standards Agency (FSA) Nutrient Profiling System (NPS) DI and the onset of MetS in a middle-aged French cohort. Participants from the SUpplémentation en VItamines et Minéraux AntioXydants cohort (SU.VI.MAX, n = 3741) were included in the present study. The FSA NPS DI was computed by using dietary data from 24 h records at inclusion. MetS was identified at baseline and at year 13 of follow-up with the use of self-reported medication, data from clinical investigations, and biological measurements. A prospective association between the FSA NPS DI (in quartiles and continuous) and the onset of MetS was investigated by using logistic regression. Poorer diets identified with the use of the FSA NPS DI were significantly associated with a higher risk of developing MetS (OR for poorer vs. healthier FSA NPS DI: 1.43; 95% CI: 1.08, 1.89; P-trend across quartiles = 0.02). The FSA NPS DI was significantly associated with the systolic blood pressure (SBP) and diastolic blood pressure (DBP) components of MetS (difference between healthier vs. poorer FSA NPS DI: 2.16 mm Hg for SBP and 1.5 mm Hg for DBP, P-trend across quartiles = 0.02). The FSA NPS DI was prospectively associated with the onset of MetS in a middle-aged French population. The application of NPSs in public health initiatives may help the population make healthier food choices, which might reduce the risk of developing MetS. © 2015 American Society for Nutrition.

Gene Expression Signatures Based on Variability can Robustly Predict Tumor Progression and Prognosis

PubMed Central

Dinalankara, Wikum; Bravo, Héctor Corrada

2015-01-01

Gene expression signatures are commonly used to create cancer prognosis and diagnosis methods, yet only a small number of them are successfully deployed in the clinic since many fail to replicate performance on subsequent validation. A primary reason for this lack of reproducibility is the fact that these signatures attempt to model the highly variable and unstable genomic behavior of cancer. Our group recently introduced gene expression anti-profiles as a robust methodology to derive gene expression signatures based on the observation that while gene expression measurements are highly heterogeneous across tumors of a specific cancer type relative to the normal tissue, their degree of deviation from normal tissue expression in specific genes involved in tissue differentiation is a stable tumor mark that is reproducible across experiments and cancer types. Here we show that constructing gene expression signatures based on variability and the anti-profile approach yields classifiers capable of successfully distinguishing benign growths from cancerous growths based on deviation from normal expression. We then show that this same approach generates stable and reproducible signatures that predict probability of relapse and survival based on tumor gene expression. These results suggest that using the anti-profile framework for the discovery of genomic signatures is an avenue leading to the development of reproducible signatures suitable for adoption in clinical settings. PMID:26078586

Genome-Wide Expression Profiling of Complex Regional Pain Syndrome

PubMed Central

Jin, Eun-Heui; Zhang, Enji; Ko, Youngkwon; Sim, Woo Seog; Moon, Dong Eon; Yoon, Keon Jung; Hong, Jang Hee; Lee, Won Hyung

2013-01-01

Complex regional pain syndrome (CRPS) is a chronic, progressive, and devastating pain syndrome characterized by spontaneous pain, hyperalgesia, allodynia, altered skin temperature, and motor dysfunction. Although previous gene expression profiling studies have been conducted in animal pain models, there genome-wide expression profiling in the whole blood of CRPS patients has not been reported yet. Here, we successfully identified certain pain-related genes through genome-wide expression profiling in the blood from CRPS patients. We found that 80 genes were differentially expressed between 4 CRPS patients (2 CRPS I and 2 CRPS II) and 5 controls (cut-off value: 1.5-fold change and p<0.05). Most of those genes were associated with signal transduction, developmental processes, cell structure and motility, and immunity and defense. The expression levels of major histocompatibility complex class I A subtype (HLA-A29.1), matrix metalloproteinase 9 (MMP9), alanine aminopeptidase N (ANPEP), l-histidine decarboxylase (HDC), granulocyte colony-stimulating factor 3 receptor (G-CSF3R), and signal transducer and activator of transcription 3 (STAT3) genes selected from the microarray were confirmed in 24 CRPS patients and 18 controls by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). We focused on the MMP9 gene that, by qRT-PCR, showed a statistically significant difference in expression in CRPS patients compared to controls with the highest relative fold change (4.0±1.23 times and p = 1.4×10−4). The up-regulation of MMP9 gene in the blood may be related to the pain progression in CRPS patients. Our findings, which offer a valuable contribution to the understanding of the differential gene expression in CRPS may help in the understanding of the pathophysiology of CRPS pain progression. PMID:24244504

Transcriptome Profile Analysis from Different Sex Types of Ginkgo biloba L.

PubMed

Du, Shuhui; Sang, Yalin; Liu, Xiaojing; Xing, Shiyan; Li, Jihong; Tang, Haixia; Sun, Limin

2016-01-01

In plants, sex determination is a comprehensive process of correlated events, which involves genes that are differentially and/or specifically expressed in distinct developmental phases. Exploring gene expression profiles from different sex types will contribute to fully understanding sex determination in plants. In this study, we conducted RNA-sequencing of female and male buds (FB and MB) as well as ovulate strobilus and staminate strobilus (OS and SS) of Ginkgo biloba to gain insights into the genes potentially related to sex determination in this species. Approximately 60 Gb of clean reads were obtained from eight cDNA libraries. De novo assembly of the clean reads generated 108,307 unigenes with an average length of 796 bp. Among these unigenes, 51,953 (47.97%) had at least one significant match with a gene sequence in the public databases searched. A total of 4709 and 9802 differentially expressed genes (DEGs) were identified in MB vs. FB and SS vs. OS, respectively. Genes involved in plant hormone signal and transduction as well as those encoding DNA methyltransferase were found to be differentially expressed between different sex types. Their potential roles in sex determination of G. biloba were discussed. Pistil-related genes were expressed in male buds while anther-specific genes were identified in female buds, suggesting that dioecism in G. biloba was resulted from the selective arrest of reproductive primordia. High correlation of expression level was found between the RNA-Seq and quantitative real-time PCR results. The transcriptome resources that we generated allowed us to characterize gene expression profiles and examine differential expression profiles, which provided foundations for identifying functional genes associated with sex determination in G. biloba.

Two-pass imputation algorithm for missing value estimation in gene expression time series.

PubMed

Tsiporkova, Elena; Boeva, Veselka

2007-10-01

Gene expression microarray experiments frequently generate datasets with multiple values missing. However, most of the analysis, mining, and classification methods for gene expression data require a complete matrix of gene array values. Therefore, the accurate estimation of missing values in such datasets has been recognized as an important issue, and several imputation algorithms have already been proposed to the biological community. Most of these approaches, however, are not particularly suitable for time series expression profiles. In view of this, we propose a novel imputation algorithm, which is specially suited for the estimation of missing values in gene expression time series data. The algorithm utilizes Dynamic Time Warping (DTW) distance in order to measure the similarity between time expression profiles, and subsequently selects for each gene expression profile with missing values a dedicated set of candidate profiles for estimation. Three different DTW-based imputation (DTWimpute) algorithms have been considered: position-wise, neighborhood-wise, and two-pass imputation. These have initially been prototyped in Perl, and their accuracy has been evaluated on yeast expression time series data using several different parameter settings. The experiments have shown that the two-pass algorithm consistently outperforms, in particular for datasets with a higher level of missing entries, the neighborhood-wise and the position-wise algorithms. The performance of the two-pass DTWimpute algorithm has further been benchmarked against the weighted K-Nearest Neighbors algorithm, which is widely used in the biological community; the former algorithm has appeared superior to the latter one. Motivated by these findings, indicating clearly the added value of the DTW techniques for missing value estimation in time series data, we have built an optimized C++ implementation of the two-pass DTWimpute algorithm. The software also provides for a choice between three different initial rough imputation methods.

Blood-Based Gene Expression Profiles Models for Classification of Subsyndromal Symptomatic Depression and Major Depressive Disorder

PubMed Central

Yu, Shunying; Yuan, Chengmei; Hong, Wu; Wang, Zuowei; Cui, Jian; Shi, Tieliu; Fang, Yiru

2012-01-01

Subsyndromal symptomatic depression (SSD) is a subtype of subthreshold depressive and also lead to significant psychosocial functional impairment as same as major depressive disorder (MDD). Several studies have suggested that SSD is a transitory phenomena in the depression spectrum and is thus considered a subtype of depression. However, the pathophysioloy of depression remain largely obscure and studies on SSD are limited. The present study compared the expression profile and made the classification with the leukocytes by using whole-genome cRNA microarrays among drug-free first-episode subjects with SSD, MDD, and matched controls (8 subjects in each group). Support vector machines (SVMs) were utilized for training and testing on candidate signature expression profiles from signature selection step. Firstly, we identified 63 differentially expressed SSD signatures in contrast to control (P< = 5.0E-4) and 30 differentially expressed MDD signatures in contrast to control, respectively. Then, 123 gene signatures were identified with significantly differential expression level between SSD and MDD. Secondly, in order to conduct priority selection for biomarkers for SSD and MDD together, we selected top gene signatures from each group of pair-wise comparison results, and merged the signatures together to generate better profiles used for clearly classify SSD and MDD sets in the same time. In details, we tried different combination of signatures from the three pair-wise compartmental results and finally determined 48 gene expression signatures with 100% accuracy. Our finding suggested that SSD and MDD did not exhibit the same expressed genome signature with peripheral blood leukocyte, and blood cell–derived RNA of these 48 gene models may have significant value for performing diagnostic functions and classifying SSD, MDD, and healthy controls. PMID:22348066

Transcriptome Profile Analysis from Different Sex Types of Ginkgo biloba L.

PubMed Central

Du, Shuhui; Sang, Yalin; Liu, Xiaojing; Xing, Shiyan; Li, Jihong; Tang, Haixia; Sun, Limin

2016-01-01

In plants, sex determination is a comprehensive process of correlated events, which involves genes that are differentially and/or specifically expressed in distinct developmental phases. Exploring gene expression profiles from different sex types will contribute to fully understanding sex determination in plants. In this study, we conducted RNA-sequencing of female and male buds (FB and MB) as well as ovulate strobilus and staminate strobilus (OS and SS) of Ginkgo biloba to gain insights into the genes potentially related to sex determination in this species. Approximately 60 Gb of clean reads were obtained from eight cDNA libraries. De novo assembly of the clean reads generated 108,307 unigenes with an average length of 796 bp. Among these unigenes, 51,953 (47.97%) had at least one significant match with a gene sequence in the public databases searched. A total of 4709 and 9802 differentially expressed genes (DEGs) were identified in MB vs. FB and SS vs. OS, respectively. Genes involved in plant hormone signal and transduction as well as those encoding DNA methyltransferase were found to be differentially expressed between different sex types. Their potential roles in sex determination of G. biloba were discussed. Pistil-related genes were expressed in male buds while anther-specific genes were identified in female buds, suggesting that dioecism in G. biloba was resulted from the selective arrest of reproductive primordia. High correlation of expression level was found between the RNA-Seq and quantitative real-time PCR results. The transcriptome resources that we generated allowed us to characterize gene expression profiles and examine differential expression profiles, which provided foundations for identifying functional genes associated with sex determination in G. biloba. PMID:27379148

RAS oncogene-mediated deregulation of the transcriptome: from molecular signature to function.

PubMed

Schäfer, Reinhold; Sers, Christine

2011-01-01

Transcriptome analysis of cancer cells has developed into a standard procedure to elucidate multiple features of the malignant process and to link gene expression to clinical properties. Gene expression profiling based on microarrays provides essentially correlative information and needs to be transferred to the functional level in order to understand the activity and contribution of individual genes or sets of genes as elements of the gene signature. To date, there exist significant gaps in the functional understanding of gene expression profiles. Moreover, the processes that drive the profound transcriptional alterations that characterize cancer cells remain mainly elusive. We have used pathway-restricted gene expression profiles derived from RAS oncogene-transformed cells and from RAS-expressing cancer cells to identify regulators downstream of the MAPK pathway.We describe the role of epigenetic regulation exemplified by the control of several immune genes in generic cell lines and colorectal cancer cells, particularly the functional interaction between signaling and DNA methylation. Moreover, we assess the role of the architectural transcription factor high mobility AT-hook 2 (HMGA2) as a regulator of the RAS-responsive transcriptome in ovarian epithelial cells. Finally, we describe an integrated approach combining pathway interference in colorectal cancer cells, gene expression profiling and computational analysis of regulatory elements of deregulated target genes. This strategy resulted in the identification of Y-box binding protein 1 (YBX1) as a regulator of MAPK-dependent proliferation and gene expression. The implications for a therapeutic application of HMGA2 gene silencing and the role of YBX1 as a prognostic factor are discussed.

Identification of the Neuromuscular Junction Transcriptome of Extraocular Muscle by Laser Capture Microdissection

PubMed Central

Ketterer, Caroline; Zeiger, Ulrike; Budak, Murat T.; Rubinstein, Neal A.; Khurana, Tejvir S.

2010-01-01

Purpose. To examine and characterize the profile of genes expressed at the synapses or neuromuscular junctions (NMJs) of extraocular muscles (EOMs) compared with those expressed at the tibialis anterior (TA). Methods. Adult rat eyeballs with rectus EOMs attached and TAs were dissected, snap frozen, serially sectioned, and stained for acetylcholinesterase (AChE) to identify the NMJs. Approximately 6000 NMJs for rectus EOM (EOMsyn), 6000 NMJs for TA (TAsyn), equal amounts of NMJ-free fiber regions (EOMfib, TAfib), and underlying myonuclei and RNAs were captured by laser capture microdissection (LCM). RNA was processed for microarray-based expression profiling. Expression profiles and interaction lists were generated for genes differentially expressed at synaptic and nonsynaptic regions of EOM (EOMsyn versus EOMfib) and TA (TAsyn versus TAfib). Profiles were validated by using real-time quantitative polymerase chain reaction (qPCR). Results. The regional transcriptomes associated with NMJs of EOMs and TAs were identified. Two hundred seventy-five genes were preferentially expressed in EOMsyn (compared with EOMfib), 230 in TAsyn (compared with TAfib), and 288 additional transcripts expressed in both synapses. Identified genes included novel genes as well as well-known, evolutionarily conserved synaptic markers (e.g., nicotinic acetylcholine receptor (AChR) alpha (Chrna) and epsilon (Chrne) subunits and nestin (Nes). Conclusions. Transcriptome level differences exist between EOM synaptic regions and TA synaptic regions. The definition of the synaptic transcriptome provides insight into the mechanism of formation and functioning of the unique synapses of EOM and their differential involvement in diseases noted in the EOM allotype. PMID:20393109

Gene expression profiles of metabolic aggressiveness and tumor recurrence in benign meningioma.

PubMed

Serna, Eva; Morales, José Manuel; Mata, Manuel; Gonzalez-Darder, José; San Miguel, Teresa; Gil-Benso, Rosario; Lopez-Gines, Concha; Cerda-Nicolas, Miguel; Monleon, Daniel

2013-01-01

Around 20% of meningiomas histologically benign may be clinically aggressive and recur. This strongly affects management of meningioma patients. There is a need to evaluate the potential aggressiveness of an individual meningioma. Additional criteria for better classification of meningiomas will improve clinical decisions as well as patient follow up strategy after surgery. The aim of this study was to determine the relationship between gene expression profiles and new metabolic subgroups of benign meningioma with potential clinical relevance. Forty benign and fourteen atypical meningioma tissue samples were included in the study. We obtained metabolic profiles by NMR and recurrence after surgery information for all of them. We measured gene expression by oligonucleotide microarray measurements on 19 of them. To our knowledge, this is the first time that distinct gene expression profiles are reported for benign meningioma molecular subgroups with clinical correlation. Our results show that metabolic aggressiveness in otherwise histological benign meningioma proceeds mostly through alterations in the expression of genes involved in the regulation of transcription, mainly the LMO3 gene. Genes involved in tumor metabolism, like IGF1R, are also differentially expressed in those meningioma subgroups with higher rates of membrane turnover, higher energy demand and increased resistance to apoptosis. These new subgroups of benign meningiomas exhibit different rates of recurrence. This work shows that benign meningioma with metabolic aggressiveness constitute a subgroup of potentially recurrent tumors in which alterations in genes regulating critical features of aggressiveness, like increased angiogenesis or cell invasion, are still no predominant. The determination of these gene expression biosignatures may allow the early detection of clinically aggressive tumors.

Identification of a Novel Reference Gene for Apple Transcriptional Profiling under Postharvest Conditions

PubMed Central

Storch, Tatiane Timm; Pegoraro, Camila; Finatto, Taciane; Quecini, Vera; Rombaldi, Cesar Valmor; Girardi, César Luis

2015-01-01

Reverse Transcription quantitative PCR (RT-qPCR) is one of the most important techniques for gene expression profiling due to its high sensibility and reproducibility. However, the reliability of the results is highly dependent on data normalization, performed by comparisons between the expression profiles of the genes of interest against those of constitutively expressed, reference genes. Although the technique is widely used in fruit postharvest experiments, the transcription stability of reference genes has not been thoroughly investigated under these experimental conditions. Thus, we have determined the transcriptional profile, under these conditions, of three genes commonly used as reference—ACTIN (MdACT), PROTEIN DISULPHIDE ISOMERASE (MdPDI) and UBIQUITIN-CONJUGATING ENZYME E2 (MdUBC)—along with two novel candidates—HISTONE 1 (MdH1) and NUCLEOSSOME ASSEMBLY 1 PROTEIN (MdNAP1). The expression profile of the genes was investigated throughout five experiments, with three of them encompassing the postharvest period and the other two, consisting of developmental and spatial phases. The transcriptional stability was comparatively investigated using four distinct software packages: BestKeeper, NormFinder, geNorm and DataAssist. Gene ranking results for transcriptional stability were similar for the investigated software packages, with the exception of BestKeeper. The classic reference gene MdUBC ranked among the most stably transcribed in all investigated experimental conditions. Transcript accumulation profiles for the novel reference candidate gene MdH1 were stable throughout the tested conditions, especially in experiments encompassing the postharvest period. Thus, our results present a novel reference gene for postharvest experiments in apple and reinforce the importance of checking the transcription profile of reference genes under the experimental conditions of interest. PMID:25774904

Identification of a novel reference gene for apple transcriptional profiling under postharvest conditions.

PubMed

Storch, Tatiane Timm; Pegoraro, Camila; Finatto, Taciane; Quecini, Vera; Rombaldi, Cesar Valmor; Girardi, César Luis

2015-01-01

Reverse Transcription quantitative PCR (RT-qPCR) is one of the most important techniques for gene expression profiling due to its high sensibility and reproducibility. However, the reliability of the results is highly dependent on data normalization, performed by comparisons between the expression profiles of the genes of interest against those of constitutively expressed, reference genes. Although the technique is widely used in fruit postharvest experiments, the transcription stability of reference genes has not been thoroughly investigated under these experimental conditions. Thus, we have determined the transcriptional profile, under these conditions, of three genes commonly used as reference--ACTIN (MdACT), PROTEIN DISULPHIDE ISOMERASE (MdPDI) and UBIQUITIN-CONJUGATING ENZYME E2 (MdUBC)--along with two novel candidates--HISTONE 1 (MdH1) and NUCLEOSSOME ASSEMBLY 1 PROTEIN (MdNAP1). The expression profile of the genes was investigated throughout five experiments, with three of them encompassing the postharvest period and the other two, consisting of developmental and spatial phases. The transcriptional stability was comparatively investigated using four distinct software packages: BestKeeper, NormFinder, geNorm and DataAssist. Gene ranking results for transcriptional stability were similar for the investigated software packages, with the exception of BestKeeper. The classic reference gene MdUBC ranked among the most stably transcribed in all investigated experimental conditions. Transcript accumulation profiles for the novel reference candidate gene MdH1 were stable throughout the tested conditions, especially in experiments encompassing the postharvest period. Thus, our results present a novel reference gene for postharvest experiments in apple and reinforce the importance of checking the transcription profile of reference genes under the experimental conditions of interest.

Oligonucleotide Microarray Analysis of Dietary-Induced Hyperlipidemia Gene Expression Profiles in Miniature Pigs

PubMed Central

Takahashi, Junko; Waki, Shiori; Matsumoto, Rena; Odake, Junji; Miyaji, Takayuki; Tottori, Junichi; Iwanaga, Takehiro; Iwahashi, Hitoshi

2012-01-01

Background Hyperlipidemia animal models have been established, but complete gene expression profiles of the transition from normal lipid levels have not been obtained. Miniature pigs are useful model animals for gene expression studies on dietary-induced hyperlipidemia because they have a similar anatomy and digestive physiology to humans, and blood samples can be obtained from them repeatedly. Methodology Two typical dietary treatments were used for dietary-induced hyperlipidemia models, by using specific pathogen-free (SPF) Clawn miniature pigs. One was a high-fat and high-cholesterol diet (HFCD) and the other was a high-fat, high-cholesterol, and high-sucrose diet (HFCSD). Microarray analyses were conducted from whole blood samples during the dietary period and from white blood cells at the end of the dietary period to evaluate the transition of expression profiles of the two dietary models. Principal Findings Variations in whole blood gene expression intensity within the HFCD or the HFCSD group were in the same range as the controls provide with normal diet at all periods. This indicates uniformity of dietary-induced hyperlipidemia for our dietary protocols. Gene ontology- (GO) based functional analyses revealed that characteristics of the common changes between HFCD and HFCSD were involved in inflammatory responses and reproduction. The correlation coefficient between whole blood and white blood cell expression profiles at 27 weeks with the HFCSD diet was significantly lower than that of the control and HFCD diet groups. This may be due to the effects of RNA originating from the tissues and/or organs. Conclusions No statistically significant differences in fasting plasma lipids and glucose levels between the HFCD and HFCSD groups were observed. However, blood RNA analyses revealed different characteristics corresponding to the dietary protocols. In this study, whole blood RNA analyses proved to be a useful tool to evaluate transitions in dietary-induced hyperlipidemia gene expression profiles in miniature pigs. PMID:22662175

Transcriptome Profiling of Bovine Milk Oligosaccharide Metabolism Genes Using RNA-Sequencing

PubMed Central

Wickramasinghe, Saumya; Hua, Serenus; Rincon, Gonzalo; Islas-Trejo, Alma; German, J. Bruce; Lebrilla, Carlito B.; Medrano, Juan F.

2011-01-01

This study examines the genes coding for enzymes involved in bovine milk oligosaccharide metabolism by comparing the oligosaccharide profiles with the expressions of glycosylation-related genes. Fresh milk samples (n = 32) were collected from four Holstein and Jersey cows at days 1, 15, 90 and 250 of lactation and free milk oligosaccharide profiles were analyzed. RNA was extracted from milk somatic cells at days 15 and 250 of lactation (n = 12) and gene expression analysis was conducted by RNA-Sequencing. A list was created of 121 glycosylation-related genes involved in oligosaccharide metabolism pathways in bovine by analyzing the oligosaccharide profiles and performing an extensive literature search. No significant differences were observed in either oligosaccharide profiles or expressions of glycosylation-related genes between Holstein and Jersey cows. The highest concentrations of free oligosaccharides were observed in the colostrum samples and a sharp decrease was observed in the concentration of free oligosaccharides on day 15, followed by progressive decrease on days 90 and 250. Ninety-two glycosylation-related genes were expressed in milk somatic cells. Most of these genes exhibited higher expression in day 250 samples indicating increases in net glycosylation-related metabolism in spite of decreases in free milk oligosaccharides in late lactation milk. Even though fucosylated free oligosaccharides were not identified, gene expression indicated the likely presence of fucosylated oligosaccharides in bovine milk. Fucosidase genes were expressed in milk and a possible explanation for not detecting fucosylated free oligosaccharides is the degradation of large fucosylated free oligosaccharides by the fucosidases. Detailed characterization of enzymes encoded by the 92 glycosylation-related genes identified in this study will provide the basic knowledge for metabolic network analysis of oligosaccharides in mammalian milk. These candidate genes will guide the design of a targeted breeding strategy to optimize the content of beneficial oligosaccharides in bovine milk. PMID:21541029

Study methods, recruitment, socio-demographic findings and demographic representativeness in the OPPERA study

PubMed Central

Slade, Gary D.; Bair, Eric; By, Kunthel; Mulkey, Flora; Baraian, Cristina; Rothwell, Rebecca; Reynolds, Maria; Miller, Vanessa; Gonzalez, Yoly; Gordon, Sharon; Ribeiro-Dasilva, Margarete; Lim, Pei Feng; Greenspan, Joel D; Dubner, Ron; Fillingim, Roger B; Diatchenko, Luda; Maixner, William; Dampier, Dawn; Knott, Charles; Ohrbach, Richard

2011-01-01

This paper describes methods used in the project “Orofacial Pain Prospective Evaluation and Risk Assessment” (OPPERA) and evaluates socio-demographic characteristics associated with temporomandibular disorders (TMD) in the OPPERA case-control study. Representativeness was investigated by comparing socio-demographic profiles of OPPERA participants with population census profiles of counties near study sites and by comparing age- and gender-associations with TMD in OPPERA and the 2007-09 US National Health Interview Survey. Volunteers aged 18-44 years were recruited at four US study sites: 3,263 people without TMD were enrolled into the prospective cohort study; 1,633 of them were selected as controls for the baseline case-control study. Cases were 185 volunteers with examiner-classified TMD. Distributions of some demographic characteristics among OPPERA participants differed from census profiles, although there was less difference in socio-economic profiles. Odds of TMD was associated with greater age in this 18-44 year range; females had three times the odds of TMD as males; and relative to non-Hispanic-Whites, other racial groups had one-fifth the odds of TMD. Age- and gender-associations with chronic TMD were strikingly similar to associations observed in the US population. Assessments of representativeness in this demographically diverse group of community volunteers suggest that OPPERA case-control findings have good internal validity. PMID:22074749

Current health and preferences for life-prolonging treatments: an application of prospect theory to end-of-life decision making.

PubMed

Winter, Laraine; Parker, Barbara

2007-10-01

As a substantial body of research attests, the acceptability of life-prolonging treatment (e.g., tube feeding) tends to be greater among people in worse health than among healthier ones. Because a decision for or against a life-prolonging treatment represents a choice between two prospects-life (usually in poor health) and death-we propose a decision model, Prospect Theory, as a theoretical account of this phenomenon. Prospect Theory postulates that pairs of distant prospects are less distinguishable than pairs of closer ones. Thus, to healthy individuals, the prospects of death and life in poor health would both be remote, and therefore, the distinction between them, small. To less healthy individuals, however, the difference between the same pairs of prospects would appear greater, and therefore, life-prolonging treatment may be more acceptable. In a cross-sectional study of 304 community-dwelling people, aged 60 years and over in the Philadelphia area, USA, preferences for 4 life-prolonging treatments in 9 health scenarios were examined in relation to participants' current health, operationalized as number of deficits in physical functioning. As predicted, less healthy people expressed stronger preferences for all life-prolonging treatments compared with healthier ones, with differences greatest in the worse-health scenarios. Preferences also varied by health scenario, with any treatment preferred in the better health scenarios. Treatment preferences did not differ by type of treatment, depressed mood or any demographic characteristic except race, with African-Americans expressing stronger treatment preferences. Implications for advance care planning are discussed.

Parental Expressivity and Parenting Styles in Chinese Families: Prospective and Unique Relations to Children's Psychological Adjustment.

PubMed

Chen, Stephen H; Zhou, Qing; Eisenberg, Nancy; Valiente, Carlos; Wang, Yun

2011-01-01

OBJECTIVES: Parents from different cultures differ in how frequently they express emotions. However, the generalizability of the relations between parental expressivity and child adjustment in non-Western cultures has not been extensively studied. The goal of the present study was to investigate prospective relations between parental expressivity within the family (positive, negative dominant, and negative submissive expressivity) and Chinese children's psychological adjustment, above and beyond parenting styles. DESIGN: The study used two waves (3.8 years apart) of longitudinal data from a sample (n= 425) of children in Beijing (mean ages = 7.7 years at T1 and 11.6 years at T2). Parental expressivity and parenting styles were self-reported. To reduce the potential measurement overlap, items that tap parental expression of emotions toward the child were removed from the parenting style measure. Children's adjustment was measured with parents', teachers', and peers' or children's reports. RESULTS: Consistent with findings with European American samples, parental negative dominant expressivity uniquely and positively predicted Chinese children's externalizing problems controlling for prior externalizing problems, parenting styles, and family SES. Neither parental expressivity nor parenting styles uniquely predicted social competence. CONCLUSIONS: Despite previously reported cultural differences in the mean levels of parental expressivity, some of the socialization functions of parental expressivity found in Western countries can be generalized to Chinese families. Although parental expressivity and parenting styles are related constructs, their unique relations to child's adjustment suggest that they should be examined as distinct processes.

Biological mechanism analysis of acute renal allograft rejection: integrated of mRNA and microRNA expression profiles.

PubMed

Huang, Shi-Ming; Zhao, Xia; Zhao, Xue-Mei; Wang, Xiao-Ying; Li, Shan-Shan; Zhu, Yu-Hui

2014-01-01

Renal transplantation is the preferred method for most patients with end-stage renal disease, however, acute renal allograft rejection is still a major risk factor for recipients leading to renal injury. To improve the early diagnosis and treatment of acute rejection, study on the molecular mechanism of it is urgent. MicroRNA (miRNA) expression profile and mRNA expression profile of acute renal allograft rejection and well-functioning allograft downloaded from ArrayExpress database were applied to identify differentially expressed (DE) miRNAs and DE mRNAs. DE miRNAs targets were predicted by combining five algorithm. By overlapping the DE mRNAs and DE miRNAs targets, common genes were obtained. Differentially co-expressed genes (DCGs) were identified by differential co-expression profile (DCp) and differential co-expression enrichment (DCe) methods in Differentially Co-expressed Genes and Links (DCGL) package. Then, co-expression network of DCGs and the cluster analysis were performed. Functional enrichment analysis for DCGs was undergone. A total of 1270 miRNA targets were predicted and 698 DE mRNAs were obtained. While overlapping miRNA targets and DE mRNAs, 59 common genes were gained. We obtained 103 DCGs and 5 transcription factors (TFs) based on regulatory impact factors (RIF), then built the regulation network of miRNA targets and DE mRNAs. By clustering the co-expression network, 5 modules were obtained. Thereinto, module 1 had the highest degree and module 2 showed the most number of DCGs and common genes. TF CEBPB and several common genes, such as RXRA, BASP1 and AKAP10, were mapped on the co-expression network. C1R showed the highest degree in the network. These genes might be associated with human acute renal allograft rejection. We conducted biological analysis on integration of DE mRNA and DE miRNA in acute renal allograft rejection, displayed gene expression patterns and screened out genes and TFs that may be related to acute renal allograft rejection.

Biological mechanism analysis of acute renal allograft rejection: integrated of mRNA and microRNA expression profiles

PubMed Central

Huang, Shi-Ming; Zhao, Xia; Zhao, Xue-Mei; Wang, Xiao-Ying; Li, Shan-Shan; Zhu, Yu-Hui

2014-01-01

Objectives: Renal transplantation is the preferred method for most patients with end-stage renal disease, however, acute renal allograft rejection is still a major risk factor for recipients leading to renal injury. To improve the early diagnosis and treatment of acute rejection, study on the molecular mechanism of it is urgent. Methods: MicroRNA (miRNA) expression profile and mRNA expression profile of acute renal allograft rejection and well-functioning allograft downloaded from ArrayExpress database were applied to identify differentially expressed (DE) miRNAs and DE mRNAs. DE miRNAs targets were predicted by combining five algorithm. By overlapping the DE mRNAs and DE miRNAs targets, common genes were obtained. Differentially co-expressed genes (DCGs) were identified by differential co-expression profile (DCp) and differential co-expression enrichment (DCe) methods in Differentially Co-expressed Genes and Links (DCGL) package. Then, co-expression network of DCGs and the cluster analysis were performed. Functional enrichment analysis for DCGs was undergone. Results: A total of 1270 miRNA targets were predicted and 698 DE mRNAs were obtained. While overlapping miRNA targets and DE mRNAs, 59 common genes were gained. We obtained 103 DCGs and 5 transcription factors (TFs) based on regulatory impact factors (RIF), then built the regulation network of miRNA targets and DE mRNAs. By clustering the co-expression network, 5 modules were obtained. Thereinto, module 1 had the highest degree and module 2 showed the most number of DCGs and common genes. TF CEBPB and several common genes, such as RXRA, BASP1 and AKAP10, were mapped on the co-expression network. C1R showed the highest degree in the network. These genes might be associated with human acute renal allograft rejection. Conclusions: We conducted biological analysis on integration of DE mRNA and DE miRNA in acute renal allograft rejection, displayed gene expression patterns and screened out genes and TFs that may be related to acute renal allograft rejection. PMID:25664019

Comparative analysis of gene expression profiles of hip articular cartilage between non-traumatic necrosis and osteoarthritis.

PubMed

Wang, Wenyu; Liu, Yang; Hao, Jingcan; Zheng, Shuyu; Wen, Yan; Xiao, Xiao; He, Awen; Fan, Qianrui; Zhang, Feng; Liu, Ruiyu

2016-10-10

Hip cartilage destruction is consistently observed in the non-traumatic osteonecrosis of femoral head (NOFH) and accelerates its bone necrosis. The molecular mechanism underlying the cartilage damage of NOFH remains elusive. In this study, we conducted a systematically comparative study of gene expression profiles between NOFH and osteoarthritis (OA). Hip articular cartilage specimens were collected from 12 NOFH patients and 12 controls with traumatic femoral neck fracture for microarray (n=4) and quantitative real-time PCR validation experiments (n=8). Gene expression profiling of articular cartilage was performed using Agilent Human 4×44K Microarray chip. The accuracy of microarray experiment was further validated by qRT-PCR. Gene expression results of OA hip cartilage were derived from previously published study. Significance Analysis of Microarrays (SAM) software was applied for identifying differently expressed genes. Gene ontology (GO) and pathway enrichment analysis were conducted by Gene Set Enrichment Analysis software and DAVID tool, respectively. Totally, 27 differently expressed genes were identified for NOFH. Comparing the gene expression profiles of NOFH cartilage and OA cartilage detected 8 common differently expressed genes, including COL5A1, OGN, ANGPTL4, CRIP1, NFIL3, METRNL, ID2 and STEAP1. GO comparative analysis identified 10 common significant GO terms, mainly implicated in apoptosis and development process. Pathway comparative analysis observed that ECM-receptor interaction pathway and focal adhesion pathway were enriched in the differently expressed genes of both NOFH and hip OA. In conclusion, we identified a set of differently expressed genes, GO and pathways for NOFH articular destruction, some of which were also involved in the hip OA. Our study results may help to reveal the pathogenetic similarities and differences of cartilage damage of NOFH and hip OA. Copyright © 2016 Elsevier B.V. All rights reserved.

Seasonal Changes in Bacterial and Archaeal Gene Expression Patterns across Salinity Gradients in the Columbia River Coastal Margin

PubMed Central

Smith, Maria W.; Herfort, Lydie; Tyrol, Kaitlin; Suciu, Dominic; Campbell, Victoria; Crump, Byron C.; Peterson, Tawnya D.; Zuber, Peter; Baptista, Antonio M.; Simon, Holly M.

2010-01-01

Through their metabolic activities, microbial populations mediate the impact of high gradient regions on ecological function and productivity of the highly dynamic Columbia River coastal margin (CRCM). A 2226-probe oligonucleotide DNA microarray was developed to investigate expression patterns for microbial genes involved in nitrogen and carbon metabolism in the CRCM. Initial experiments with the environmental microarrays were directed toward validation of the platform and yielded high reproducibility in multiple tests. Bioinformatic and experimental validation also indicated that >85% of the microarray probes were specific for their corresponding target genes and for a few homologs within the same microbial family. The validated probe set was used to query gene expression responses by microbial assemblages to environmental variability. Sixty-four samples from the river, estuary, plume, and adjacent ocean were collected in different seasons and analyzed to correlate the measured variability in chemical, physical and biological water parameters to differences in global gene expression profiles. The method produced robust seasonal profiles corresponding to pre-freshet spring (April) and late summer (August). Overall relative gene expression was high in both seasons and was consistent with high microbial abundance measured by total RNA, heterotrophic bacterial production, and chlorophyll a. Both seasonal patterns involved large numbers of genes that were highly expressed relative to background, yet each produced very different gene expression profiles. April patterns revealed high differential gene expression in the coastal margin samples (estuary, plume and adjacent ocean) relative to freshwater, while little differential gene expression was observed along the river-to-ocean transition in August. Microbial gene expression profiles appeared to relate, in part, to seasonal differences in nutrient availability and potential resource competition. Furthermore, our results suggest that highly-active particle-attached microbiota in the Columbia River water column may perform dissimilatory nitrate reduction (both dentrification and DNRA) within anoxic particle microniches. PMID:20967204

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

Common patterns and disease-related signatures in tuberculosis and sarcoidosis.

PubMed

Maertzdorf, Jeroen; Weiner, January; Mollenkopf, Hans-Joachim; Bauer, Torsten; Prasse, Antje; Müller-Quernheim, Joachim; Kaufmann, Stefan H E

2012-05-15

In light of the marked global health impact of tuberculosis (TB), strong focus has been on identifying biosignatures. Gene expression profiles in blood cells identified so far are indicative of a persistent activation of the immune system and chronic inflammatory pathology in active TB. Definition of a biosignature with unique specificity for TB demands that identified profiles can differentiate diseases with similar pathology, like sarcoidosis (SARC). Here, we present a detailed comparison between pulmonary TB and SARC, including whole-blood gene expression profiling, microRNA expression, and multiplex serum analytes. Our analysis reveals that previously disclosed gene expression signatures in TB show highly similar patterns in SARC, with a common up-regulation of proinflammatory pathways and IFN signaling and close similarity to TB-related signatures. microRNA expression also presented a highly similar pattern in both diseases, whereas cytokines in the serum of TB patients revealed a slightly elevated proinflammatory pattern compared with SARC and controls. Our results indicate several differences in expression between the two diseases, with increased metabolic activity and significantly higher antimicrobial defense responses in TB. However, matrix metallopeptidase 14 was identified as the most distinctive marker of SARC. Described communalities as well as unique signatures in blood profiles of two distinct inflammatory pulmonary diseases not only have considerable implications for the design of TB biosignatures and future diagnosis, but they also provide insights into biological processes underlying chronic inflammatory disease entities of different etiology.

Transcriptional profile of P. syringae pv. phaseolicola NPS3121 at low temperature: Physiology of phytopathogenic bacteria

PubMed Central

2013-01-01

Background Low temperatures play key roles in the development of most plant diseases, mainly because of their influence on the expression of various virulence factors in phytopathogenic bacteria. Thus far, studies regarding this environmental parameter have focused on specific themes and little is known about phytopathogenic bacteria physiology under these conditions. To obtain a global view regarding phytopathogenic bacteria strategies in response to physiologically relevant temperature changes, we used DNA microarray technology to compare the gene expression profile of the model bacterial pathogen P. syringae pv. phaseolicola NPS3121 grown at 18°C and 28°C. Results A total of 236 differentially regulated genes were identified, of which 133 were up-regulated and 103 were down-regulated at 18°C compared to 28°C. The majority of these genes are involved in pathogenicity and virulence processes. In general, the results of this study suggest that the expression profile obtained may be related to the fact that low temperatures induce oxidative stress in bacterial cells, which in turn influences the expression of iron metabolism genes. The expression also appears to be correlated with the profile expression obtained in genes related to motility, biofilm production, and the type III secretion system. Conclusions From the data obtained in this study, we can begin to understand the strategies used by this phytopathogen during low temperature growth, which can occur in host interactions and disease development. PMID:23587016

Identifying arsenic trioxide (ATO) functions in leukemia cells by using time series gene expression profiles.

PubMed

Yang, Hong; Lin, Shan; Cui, Jingru

2014-02-10

Arsenic trioxide (ATO) is presently the most active single agent in the treatment of acute promyelocytic leukemia (APL). In order to explore the molecular mechanism of ATO in leukemia cells with time series, we adopted bioinformatics strategy to analyze expression changing patterns and changes in transcription regulation modules of time series genes filtered from Gene Expression Omnibus database (GSE24946). We totally screened out 1847 time series genes for subsequent analysis. The KEGG (Kyoto encyclopedia of genes and genomes) pathways enrichment analysis of these genes showed that oxidative phosphorylation and ribosome were the top 2 significantly enriched pathways. STEM software was employed to compare changing patterns of gene expression with assigned 50 expression patterns. We screened out 7 significantly enriched patterns and 4 tendency charts of time series genes. The result of Gene Ontology showed that functions of times series genes mainly distributed in profiles 41, 40, 39 and 38. Seven genes with positive regulation of cell adhesion function were enriched in profile 40, and presented the same first increased model then decreased model as profile 40. The transcription module analysis showed that they mainly involved in oxidative phosphorylation pathway and ribosome pathway. Overall, our data summarized the gene expression changes in ATO treated K562-r cell lines with time and suggested that time series genes mainly regulated cell adhesive. Furthermore, our result may provide theoretical basis of molecular biology in treating acute promyelocytic leukemia. Copyright © 2013 Elsevier B.V. All rights reserved.

Effect of the parental origin of the X-chromosome on the clinical features, associated complications, the two-year-response to growth hormone (rhGH) and the biochemical profile in patients with turner syndrome

PubMed Central

2013-01-01

Background It is possible that genes on the X chromosome are expressed differently depending of its parental origin. The objective of this study was to determine the influence of the parental origin of the X-chromosome on phenotypic variability, response to rhGH and on the biochemical profile of TS patients. Methods This was a cross-sectional multicenter correlational study carried out over three years in six Latin-American university hospitals. Unrelated 45,X TS patients (n =  93; 18.3 ± 8.5 years )) were evaluated. A subgroup (n =  34) of the patients were prospectively treated with rhGH over two years. DNA profiles of patients and their mothers were compared to determine the parental origin of the retained X-chromosome through 10 polymorphic X-chromosome-STRs. The association with clinical features, biochemical profiles and anthropometric data at the beginning and after two years of rhGH treatment was determined. Results Seventy two percent of patients retained the maternal X chromosome (Xm). A trend towards significance between maternal height and patients final height (p ≤ 0.07) in 45,Xm subjects was observed. There was no correlation between paternal height and patient height. No differences were detected between both groups in regard to dysmorphic features, classical malformations or increase in the height-SDS after rhGH. There were higher levels of triglycerides, total and LDL cholesterol in patients >20 years who retained the Xm. Conclusions The parental origin of the retained X chromosome may influence lipid metabolism in TS patients, but its effect on growth seems to be minimal. No parental-origin-effect on the phenotypic features, associated anomalies and on the growth response to rhGH was found in 45,X TS individuals. PMID:23731950

Genome-wide expression profiling of in vivo-derived bloodstream parasite stages and dynamic analysis of mRNA alterations during synchronous differentiation in Trypanosoma brucei

PubMed Central

Kabani, Sarah; Fenn, Katelyn; Ross, Alan; Ivens, Al; Smith, Terry K; Ghazal, Peter; Matthews, Keith

2009-01-01

Background Trypanosomes undergo extensive developmental changes during their complex life cycle. Crucial among these is the transition between slender and stumpy bloodstream forms and, thereafter, the differentiation from stumpy to tsetse-midgut procyclic forms. These developmental events are highly regulated, temporally reproducible and accompanied by expression changes mediated almost exclusively at the post-transcriptional level. Results In this study we have examined, by whole-genome microarray analysis, the mRNA abundance of genes in slender and stumpy forms of T.brucei AnTat1.1 cells, and also during their synchronous differentiation to procyclic forms. In total, five biological replicates representing the differentiation of matched parasite populations derived from five individual mouse infections were assayed, with RNAs being derived at key biological time points during the time course of their synchronous differentiation to procyclic forms. Importantly, the biological context of these mRNA profiles was established by assaying the coincident cellular events in each population (surface antigen exchange, morphological restructuring, cell cycle re-entry), thereby linking the observed gene expression changes to the well-established framework of trypanosome differentiation. Conclusion Using stringent statistical analysis and validation of the derived profiles against experimentally-predicted gene expression and phenotypic changes, we have established the profile of regulated gene expression during these important life-cycle transitions. The highly synchronous nature of differentiation between stumpy and procyclic forms also means that these studies of mRNA profiles are directly relevant to the changes in mRNA abundance within individual cells during this well-characterised developmental transition. PMID:19747379

Molecular Markers in Patients with Chronic Wounds to Guide Surgical Debridement

PubMed Central

Brem, Harold; Stojadinovic, Olivera; Diegelmann, Robert F; Entero, Hyacinth; Lee, Brian; Pastar, Irena; Golinko, Michael; Rosenberg, Harvey; Tomic-Canic, Marjana

2007-01-01

Chronic wounds, such as venous ulcers, are characterized by physiological impairments manifested by delays in healing, resulting in severe morbidity. Surgical debridement is routinely performed on chronic wounds because it stimulates healing. However, procedures are repeated many times on the same patient because, in contrast to tumor excision, there are no objective biological/molecular markers to guide the extent of debridement. To develop bioassays that can potentially guide surgical debridement, we assessed the pathogenesis of the patients’ wound tissue before and after wound debridement. We obtained biopsies from three patients at two locations, the nonhealing edge (prior to debridement) and the adjacent, nonulcerated skin of the venous ulcers (post debridement), and evaluated their histology, biological response to wounding (migration) and gene expression profile. We found that biopsies from the nonhealing edges exhibit distinct pathogenic morphology (hyperproliferative/hyperkeratotic epidermis; dermal fibrosis; increased procollagen synthesis). Fibroblasts deriving from this location exhibit impaired migration in comparison to the cells from adjacent nonulcerated biopsies, which exhibit normalization of morphology and normal migration capacity. The nonhealing edges have a specific, identifiable, and reproducible gene expression profile. The adjacent nonulcerated biopsies have their own distinctive reproducible gene expression profile, signifying that particular wound areas can be identified by gene expression profiling. We conclude that chronic ulcers contain distinct subpopulations of cells with different capacity to heal and that gene expression profiling can be utilized to identify them. In the future, molecular markers will be developed to identify the nonimpaired tissue, thereby making surgical debridement more accurate and more efficacious. PMID:17515955

The role of high-density lipoprotein cholesterol in risk for posttraumatic stress disorder: taking a nutritional approach toward universal prevention.

PubMed

Hamazaki, K; Nishi, D; Yonemoto, N; Noguchi, H; Kim, Y; Matsuoka, Y

2014-09-01

Several cross-sectional studies, but no prospective studies, have reported an association between an abnormal lipid profile and posttraumatic stress disorder (PTSD). We hypothesized that an abnormal lipid profile might predict risk for developing PTSD. In this prospective study, we analyzed data from 237 antidepressant-naïve severely injured patients who participated in the Tachikawa Cohort of Motor Vehicle Accident Study. High-density lipoprotein cholesterol (HDL-C) levels at baseline were significantly lower in patients with PTSD than those without PTSD at 6 months after motor vehicle accident (MVA) and were inversely associated with risk for PTSD. In contrast, triglycerides (TG) at baseline were significantly higher in patients with PTSD than in those without PTSD at 6 months post-MVA and were positively associated with risk for PTSD. There was no clear association between low-density lipoprotein cholesterol or total cholesterol and risk for PTSD. In conclusion, low HDL-C and high TG may be risk factors for PTSD. Determining lipid profiles might help identify those at risk for PTSD after experiencing trauma. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

[Study of testicular cancer gene expression in samples of oral leukoplakia and squamous cell carcinoma of the mouth].

PubMed

Skorodumova, L O; Muraev, A A; Zakharova, E S; Shepelev, M V; Korobko, I V; Zaderenko, I A; Ivanov, S Iu; Gnuchev, N V; Georgiev, G P; Larin, S S

2012-01-01

Cancer-testis (CT) antigens are normally expressed mostly in human germ cells, there is also an aberrant expression in some tumor cells. This expression profile makes them potential tumor growth biomarkers and a promising target for tumor immunotherapy. Specificity of CT genes expression in oral malignant and potentially malignant diseases, e.g. oral leukoplakia, is not yet studied. Data on CT genes expression profile in leukoplakia would allow developing new diagnostic methods with potential value for immunotherapy and prophylaxis of leukoplakia malignization. In our study we compared CT genes expression in normal oral mucosa, oral leukoplakia and oral squamous cell carcinoma. We are the first to describe CT genes expression in oral leukoplakia without dysplasia. This findings make impossible differential diagnosis of oral leukoplakia and squamous cell carcinoma on the basis of CT genes expression. The prognostic value of CT genes expression is still unclear, therefore the longitudinal studies are necessary.

Multiple biomarkers in molecular oncology. II. Molecular diagnostics applications in breast cancer management.

PubMed

Malinowski, Douglas P

2007-05-01

In recent years, the application of genomic and proteomic technologies to the problem of breast cancer prognosis and the prediction of therapy response have begun to yield encouraging results. Independent studies employing transcriptional profiling of primary breast cancer specimens using DNA microarrays have identified gene expression profiles that correlate with clinical outcome in primary breast biopsy specimens. Recent advances in microarray technology have demonstrated reproducibility, making clinical applications more achievable. In this regard, one such DNA microarray device based upon a 70-gene expression signature was recently cleared by the US FDA for application to breast cancer prognosis. These DNA microarrays often employ at least 70 gene targets for transcriptional profiling and prognostic assessment in breast cancer. The use of PCR-based methods utilizing a small subset of genes has recently demonstrated the ability to predict the clinical outcome in early-stage breast cancer. Furthermore, protein-based immunohistochemistry methods have progressed from using gene clusters and gene expression profiling to smaller subsets of expressed proteins to predict prognosis in early-stage breast cancer. Beyond prognostic applications, DNA microarray-based transcriptional profiling has demonstrated the ability to predict response to chemotherapy in early-stage breast cancer patients. In this review, recent advances in the use of multiple markers for prognosis of disease recurrence in early-stage breast cancer and the prediction of therapy response will be discussed.

DIFFERENTIAL GENE EXPRESSION PROFILES IN RAT TRACHAEL EPITHELIAL (RTE) CELLS IN RESPONSE TO COMBUSTION-SOURCE PARTICULATE MATTER (PM) AND VANADIUM (V) A PRIMARY METAL CONSTITUENT

EPA Science Inventory

Differential gene expression profiles in rat tracheal epithelial (RTE) cells in response to combustion-source particulate matter (PM) and vanadium (V) a primary metal constituent
Srikanth S. Nadadur, Janice A. Dye and Daniel L. Costa, US EPA, ORD, NHEERL (ETD, Pulmonary Toxico...

Classification of early-stage non-small cell lung cancer by weighing gene expression profiles with connectivity information.

PubMed

Zhang, Ao; Tian, Suyan

2018-05-01

Pathway-based feature selection algorithms, which utilize biological information contained in pathways to guide which features/genes should be selected, have evolved quickly and become widespread in the field of bioinformatics. Based on how the pathway information is incorporated, we classify pathway-based feature selection algorithms into three major categories-penalty, stepwise forward, and weighting. Compared to the first two categories, the weighting methods have been underutilized even though they are usually the simplest ones. In this article, we constructed three different genes' connectivity information-based weights for each gene and then conducted feature selection upon the resulting weighted gene expression profiles. Using both simulations and a real-world application, we have demonstrated that when the data-driven connectivity information constructed from the data of specific disease under study is considered, the resulting weighted gene expression profiles slightly outperform the original expression profiles. In summary, a big challenge faced by the weighting method is how to estimate pathway knowledge-based weights more accurately and precisely. Only until the issue is conquered successfully will wide utilization of the weighting methods be impossible. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The dark cube: dark and light character profiles.

PubMed

Garcia, Danilo; Rosenberg, Patricia

2016-01-01

Background. Research addressing distinctions and similarities between people's malevolent character traits (i.e., the Dark Triad: Machiavellianism, narcissism, and psychopathy) has detected inconsistent linear associations to temperament traits. Additionally, these dark traits seem to have a common core expressed as uncooperativeness. Hence, some researchers suggest that the dark traits are best represented as one global construct (i.e., the unification argument) rather than as ternary construct (i.e., the uniqueness argument). We put forward the dark cube (cf. Cloninger's character cube) comprising eight dark profiles that can be used to compare individuals who differ in one dark character trait while holding the other two constant. Our aim was to investigate in which circumstances individuals who are high in each one of the dark character traits differ in Cloninger's "light" character traits: self-directedness, cooperativeness, and self-transcendence. We also investigated if people's dark character profiles were associated to their light character profiles. Method. A total of 997 participants recruited from Amazon's Mechanical Turk (MTurk) responded to the Short Dark Triad and the Short Character Inventory. Participants were allocated to eight different dark profiles and eight light profiles based on their scores in each of the traits and any possible combination of high and low scores. We used three-way interaction regression analyses and t-tests to investigate differences in light character traits between individuals with different dark profiles. As a second step, we compared the individuals' dark profile with her/his character profile using an exact cell-wise analysis conducted in the ROPstat software (http://www.ropstat.com). Results. Individuals who expressed high levels of Machiavellianism and those who expressed high levels of psychopathy also expressed low self-directedness and low cooperativeness. Individuals with high levels of narcissism, in contrast, scored high in self-directedness. Moreover, individuals with a profile low in the dark traits were more likely to end up with a profile high in cooperativeness. The opposite was true for those individuals with a profile high in the dark traits. The rest of the cross-comparisons revealed some of the characteristics of human personality as a non-linear complex dynamic system. Conclusions. Our study suggests that individuals who are high in Machiavellianism and psychopathy share a unified non-agentic and uncooperative character (i.e., irresponsible, low in self-control, unempathetic, unhelpful, untolerant), while individuals high in narcissism have a more unique character configuration expressed as high agency and, when the other dark traits are high, highly spiritual but uncooperative. In other words, based on differences in their associations to the light side of character, the Dark Triad seems to be a dyad rather than a triad.

The dark cube: dark and light character profiles

PubMed Central

2016-01-01

Background. Research addressing distinctions and similarities between people’s malevolent character traits (i.e., the Dark Triad: Machiavellianism, narcissism, and psychopathy) has detected inconsistent linear associations to temperament traits. Additionally, these dark traits seem to have a common core expressed as uncooperativeness. Hence, some researchers suggest that the dark traits are best represented as one global construct (i.e., the unification argument) rather than as ternary construct (i.e., the uniqueness argument). We put forward the dark cube (cf. Cloninger’s character cube) comprising eight dark profiles that can be used to compare individuals who differ in one dark character trait while holding the other two constant. Our aim was to investigate in which circumstances individuals who are high in each one of the dark character traits differ in Cloninger’s “light” character traits: self-directedness, cooperativeness, and self-transcendence. We also investigated if people’s dark character profiles were associated to their light character profiles. Method. A total of 997 participants recruited from Amazon’s Mechanical Turk (MTurk) responded to the Short Dark Triad and the Short Character Inventory. Participants were allocated to eight different dark profiles and eight light profiles based on their scores in each of the traits and any possible combination of high and low scores. We used three-way interaction regression analyses and t-tests to investigate differences in light character traits between individuals with different dark profiles. As a second step, we compared the individuals’ dark profile with her/his character profile using an exact cell-wise analysis conducted in the ROPstat software (http://www.ropstat.com). Results. Individuals who expressed high levels of Machiavellianism and those who expressed high levels of psychopathy also expressed low self-directedness and low cooperativeness. Individuals with high levels of narcissism, in contrast, scored high in self-directedness. Moreover, individuals with a profile low in the dark traits were more likely to end up with a profile high in cooperativeness. The opposite was true for those individuals with a profile high in the dark traits. The rest of the cross-comparisons revealed some of the characteristics of human personality as a non-linear complex dynamic system. Conclusions. Our study suggests that individuals who are high in Machiavellianism and psychopathy share a unified non-agentic and uncooperative character (i.e., irresponsible, low in self-control, unempathetic, unhelpful, untolerant), while individuals high in narcissism have a more unique character configuration expressed as high agency and, when the other dark traits are high, highly spiritual but uncooperative. In other words, based on differences in their associations to the light side of character, the Dark Triad seems to be a dyad rather than a triad. PMID:26966650

[Research progress in neuropsychopharmacology updated for the post-genomic era].

PubMed

Nakanishi, Toru

2009-11-01

Neuropsychopharmacological research in the post genomic (genomic sequence) era has been developing rapidly through the use of novel techniques including DNA chips. We have applied these techniques to investigate the anti-tumor effect of NSAIDs, isolate novel genes specifically expressed in rheumatoid arthritis, and analyze gene expression profiles in mesenchymal stem cells. Recently, we have developed a novel system of quantitative PCR for detection of BDNF mRNA isoforms. By using this system, we identified the exon-specific mode of expression in acute and chronic pain. In addition, we have made gene expression profiles of KO mice of beta2 subunits in acetylcholine receptors.

Dose–response relationships in gene expression profiles in rainbow trout, Oncorhyncus mykiss, exposed to ethynylestradiol

PubMed Central

Hook, Sharon E.; Skillman, Ann D.; Small, Jack A.; Schultz, Irvin R.

2008-01-01

Determining how gene expression profiles change with toxicant dose will improve the utility of arrays in identifying biomarkers and modes of toxic action. Isogenic rainbow trout, Oncorhyncus mykiss, were exposed to 10, 50 or 100 ng/L ethynylestradiol (a xeno-estrogen) for 7 days. Following exposure hepatic RNA was extracted. Fluorescently labeled cDNA were generated and hybridized against a commercially available Atlantic Salmon/Trout array (GRASP project, University of Victoria) spotted with 16,000 cDNAs. Transcript expression in treated vs control fish was analyzed via Genespring (Silicon Genetics) to identify genes with altered expression, as well as to determine gene clustering patterns that can be used as “expression signatures”. Array results were confirmed via qRT PCR. Our analysis indicates that gene expression profiles varied somewhat with dose. Established biomarkers of exposure to estrogenic chemicals, such as vitellogenin, vitelline envelope proteins, and the estrogen receptor alpha, were induced at every dose. Other genes were dose specific, suggesting that diffierent doses induce distinct physiological responses. These findings demonstrate that cDNA microarrays could be used to identify both toxicant class and relative dose. PMID:16725192

Single-nucleotide polymorphism-gene intermixed networking reveals co-linkers connected to multiple gene expression phenotypes

PubMed Central

Gong, Bin-Sheng; Zhang, Qing-Pu; Zhang, Guang-Mei; Zhang, Shao-Jun; Zhang, Wei; Lv, Hong-Chao; Zhang, Fan; Lv, Sa-Li; Li, Chuan-Xing; Rao, Shao-Qi; Li, Xia

2007-01-01

Gene expression profiles and single-nucleotide polymorphism (SNP) profiles are modern data for genetic analysis. It is possible to use the two types of information to analyze the relationships among genes by some genetical genomics approaches. In this study, gene expression profiles were used as expression traits. And relationships among the genes, which were co-linked to a common SNP(s), were identified by integrating the two types of information. Further research on the co-expressions among the co-linked genes was carried out after the gene-SNP relationships were established using the Haseman-Elston sib-pair regression. The results showed that the co-expressions among the co-linked genes were significantly higher if the number of connections between the genes and a SNP(s) was more than six. Then, the genes were interconnected via one or more SNP co-linkers to construct a gene-SNP intermixed network. The genes sharing more SNPs tended to have a stronger correlation. Finally, a gene-gene network was constructed with their intensities of relationships (the number of SNP co-linkers shared) as the weights for the edges. PMID:18466544

Peripheral blood gene expression profiles in metabolic syndrome, coronary artery disease and type 2 diabetes.

PubMed

Grayson, B L; Wang, L; Aune, T M

2011-07-01

To determine if individuals with metabolic disorders possess unique gene expression profiles, we compared transcript levels in peripheral blood from patients with coronary artery disease (CAD), type 2 diabetes (T2D) and their precursor state, metabolic syndrome to those of control (CTRL) subjects and subjects with rheumatoid arthritis (RA). The gene expression profile of each metabolic state was distinguishable from CTRLs and correlated with other metabolic states more than with RA. Of note, subjects in the metabolic cohorts overexpressed gene sets that participate in the innate immune response. Genes involved in activation of the pro-inflammatory transcription factor, NF-κB, were overexpressed in CAD whereas genes differentially expressed in T2D have key roles in T-cell activation and signaling. Reverse transcriptase PCR validation confirmed microarray results. Furthermore, several genes differentially expressed in human metabolic disorders have been previously shown to participate in inflammatory responses in murine models of obesity and T2D. Taken together, these data demonstrate that peripheral blood from individuals with metabolic disorders display overlapping and non-overlapping patterns of gene expression indicative of unique, underlying immune processes.

Overexpression of miR-9 in mast cells is associated with invasive behavior and spontaneous metastasis

PubMed Central

2014-01-01

Background While microRNA (miRNA) expression is known to be altered in a variety of human malignancies contributing to cancer development and progression, the potential role of miRNA dysregulation in malignant mast cell disease has not been previously explored. The purpose of this study was to investigate the potential contribution of miRNA dysregulation to the biology of canine mast cell tumors (MCTs), a well-established spontaneous model of malignant mast cell disease. Methods We evaluated the miRNA expression profiles from biologically low-grade and biologically high-grade primary canine MCTs using real-time PCR-based TaqMan Low Density miRNA Arrays and performed real-time PCR to evaluate miR-9 expression in primary canine MCTs, malignant mast cell lines, and normal bone marrow-derived mast cells (BMMCs). Mouse mast cell lines and BMMCs were transduced with empty or pre-miR-9 expressing lentiviral constructs and cell proliferation, caspase 3/7 activity, and invasion were assessed. Transcriptional profiling of cells overexpressing miR-9 was performed using Affymetrix GeneChip Mouse Gene 2.0 ST arrays and real-time PCR was performed to validate changes in mRNA expression. Results Our data demonstrate that unique miRNA expression profiles correlate with the biological behavior of primary canine MCTs and that miR-9 expression is increased in biologically high grade canine MCTs and malignant cell lines compared to biologically low grade tumors and normal canine BMMCs. In transformed mouse malignant mast cell lines expressing either wild-type (C57) or activating (P815) KIT mutations and mouse BMMCs, miR-9 overexpression significantly enhanced invasion but had no effect on cell proliferation or apoptosis. Transcriptional profiling of normal mouse BMMCs and P815 cells possessing enforced miR-9 expression demonstrated dysregulation of several genes, including upregulation of CMA1, a protease involved in activation of matrix metalloproteases and extracellular matrix remodeling. Conclusions Our findings demonstrate that unique miRNA expression profiles correlate with the biological behavior of canine MCTs. Furthermore, dysregulation of miR-9 is associated with MCT metastasis potentially through the induction of an invasive phenotype, identifying a potentially novel pathway for therapeutic intervention. PMID:24517413

SOX2 expression levels distinguish between neural progenitor populations of the developing dorsal telencephalon.

PubMed

Hutton, Scott R; Pevny, Larysa H

2011-04-01

The HMG-Box transcription factor SOX2 is expressed in neural progenitor populations throughout the developing and adult central nervous system and is necessary to maintain their progenitor identity. However, it is unclear whether SOX2 levels are uniformly expressed across all neural progenitor populations. In the developing dorsal telencephalon, two distinct populations of neural progenitors, radial glia and intermediate progenitor cells, are responsible for generating a majority of excitatory neurons found in the adult neocortex. Here we demonstrate, using both cellular and molecular analyses, that SOX2 is differentially expressed between radial glial and intermediate progenitor populations. Moreover, utilizing a SOX2(EGFP) mouse line, we show that this differential expression can be used to prospectively isolate distinct, viable populations of radial glia and intermediate cells for in vitro analysis. Given the limited repertoire of cell-surface markers currently available for neural progenitor cells, this provides an invaluable tool for prospectively identifying and isolating distinct classes of neural progenitor cells from the central nervous system. Copyright © 2011 Elsevier Inc. All rights reserved.

Liver Gene Expression Profiles of Rats Treated with Clofibric Acid

PubMed Central

Michel, Cécile; Desdouets, Chantal; Sacre-Salem, Béatrice; Gautier, Jean-Charles; Roberts, Ruth; Boitier, Eric

2003-01-01

Clofibric acid (CLO) is a peroxisome proliferator (PP) that acts through the peroxisome proliferator activated receptor α, leading to hepatocarcinogenesis in rodents. CLO-induced hepatocarcinogenesis is a multi-step process, first transforming normal liver cells into foci. The combination of laser capture microdissection (LCM) and genomics has the potential to provide expression profiles from such small cell clusters, giving an opportunity to understand the process of cancer development in response to PPs. To our knowledge, this is the first evaluation of the impact of the successive steps of LCM procedure on gene expression profiling by comparing profiles from LCM samples to those obtained with non-microdissected liver samples collected after a 1 month CLO treatment in the rat. We showed that hematoxylin and eosin (H&E) staining and laser microdissection itself do not impact on RNA quality. However, the overall process of the LCM procedure affects the RNA quality, resulting in a bias in the gene profiles. Nonetheless, this bias did not prevent accurate determination of a CLO-specific molecular signature. Thus, gene-profiling analysis of microdissected foci, identified by H&E staining may provide insight into the mechanisms underlying non-genotoxic hepatocarcinogenesis in the rat by allowing identification of specific genes that are regulated by CLO in early pre-neoplastic foci. PMID:14633594

Liver gene expression profiles of rats treated with clofibric acid: comparison of whole liver and laser capture microdissected liver.

PubMed

Michel, Cécile; Desdouets, Chantal; Sacre-Salem, Béatrice; Gautier, Jean-Charles; Roberts, Ruth; Boitier, Eric

2003-12-01

Clofibric acid (CLO) is a peroxisome proliferator (PP) that acts through the peroxisome proliferator activated receptor alpha, leading to hepatocarcinogenesis in rodents. CLO-induced hepatocarcinogenesis is a multi-step process, first transforming normal liver cells into foci. The combination of laser capture microdissection (LCM) and genomics has the potential to provide expression profiles from such small cell clusters, giving an opportunity to understand the process of cancer development in response to PPs. To our knowledge, this is the first evaluation of the impact of the successive steps of LCM procedure on gene expression profiling by comparing profiles from LCM samples to those obtained with non-microdissected liver samples collected after a 1 month CLO treatment in the rat. We showed that hematoxylin and eosin (H&E) staining and laser microdissection itself do not impact on RNA quality. However, the overall process of the LCM procedure affects the RNA quality, resulting in a bias in the gene profiles. Nonetheless, this bias did not prevent accurate determination of a CLO-specific molecular signature. Thus, gene-profiling analysis of microdissected foci, identified by H&E staining may provide insight into the mechanisms underlying non-genotoxic hepatocarcinogenesis in the rat by allowing identification of specific genes that are regulated by CLO in early pre-neoplastic foci.

High Diversity and Variability in the Vaginal Microbiome in Women following Preterm Premature Rupture of Membranes (PPROM): A Prospective Cohort Study

PubMed Central

Paramel Jayaprakash, Teenus; Wagner, Emily C.; van Schalkwyk, Julie; Albert, Arianne Y. K.; Hill, Janet E.; Money, Deborah M.

2016-01-01

Objective To characterize the vaginal microbiota of women following preterm premature rupture of membranes (PPROM), and determine if microbiome composition predicts latency duration and perinatal outcomes. Design A prospective cohort study Setting Canada Population Women with PPROM between 24+0 and 33+6 weeks gestational age (GA). Methods Microbiome profiles, based on pyrosequencing of the cpn60 universal target, were generated from vaginal samples at time of presentation with PPROM, weekly thereafter, and at delivery. Main Outcome Measures Vaginal microbiome composition, latency duration, gestational age at delivery, perinatal outcomes. Results Microbiome profiles were generated from 70 samples from 36 women. Mean GA at PPROM was 28.8 wk (mean latency 2.7 wk). Microbiome profiles were highly diverse but sequences representing Megasphaera type 1 and Prevotella spp. were detected in all vaginal samples. Only 13/70 samples were dominated by Lactobacillus spp. Microbiome profiles at the time of membrane rupture did not cluster by gestational age at PPROM, latency duration, presence of chorioamnionitis or by infant outcomes. Mycoplasma and/or Ureaplasma were detected by PCR in 81% (29/36) of women, and these women had significantly lower GA at delivery and correspondingly lower birth weight infants than Mycoplasma and/or Ureaplasma negative women. Conclusion Women with PPROM had mixed, abnormal vaginal microbiota but the microbiome profile at PPROM did not correlate with latency duration. Prevotella spp. and Megasphaera type I were ubiquitous. The presence of Mollicutes in the vaginal microbiome was associated with lower GA at delivery. The microbiome was remarkably unstable during the latency period. PMID:27861554

Altered Expression of Diabetes-Related Genes in Alzheimer's Disease Brains: The Hisayama Study

PubMed Central

Hokama, Masaaki; Oka, Sugako; Leon, Julio; Ninomiya, Toshiharu; Honda, Hiroyuki; Sasaki, Kensuke; Iwaki, Toru; Ohara, Tomoyuki; Sasaki, Tomio; LaFerla, Frank M.; Kiyohara, Yutaka; Nakabeppu, Yusaku

2014-01-01

Diabetes mellitus (DM) is considered to be a risk factor for dementia including Alzheimer's disease (AD). However, the molecular mechanism underlying this risk is not well understood. We examined gene expression profiles in postmortem human brains donated for the Hisayama study. Three-way analysis of variance of microarray data from frontal cortex, temporal cortex, and hippocampus was performed with the presence/absence of AD and vascular dementia, and sex, as factors. Comparative analyses of expression changes in the brains of AD patients and a mouse model of AD were also performed. Relevant changes in gene expression identified by microarray analysis were validated by quantitative real-time reverse-transcription polymerase chain reaction and western blotting. The hippocampi of AD brains showed the most significant alteration in gene expression profile. Genes involved in noninsulin-dependent DM and obesity were significantly altered in both AD brains and the AD mouse model, as were genes related to psychiatric disorders and AD. The alterations in the expression profiles of DM-related genes in AD brains were independent of peripheral DM-related abnormalities. These results indicate that altered expression of genes related to DM in AD brains is a result of AD pathology, which may thereby be exacerbated by peripheral insulin resistance or DM. PMID:23595620

Serum miRNAs Signature Plays an Important Role in Keloid Disease.

PubMed

Luan, Y; Liu, Y; Liu, C; Lin, Q; He, F; Dong, X; Xiao, Z

2016-01-01

The molecular mechanism underlying the pathogenesis of keloid is largely unknown. MicroRNA (miRNA) is a class of small regulatory RNA that has emerged as a group of posttranscriptional gene repressors, participating in diverse pathophysiological processes of skin diseases. We investigated the expression profiles of miRNAs in the sera of patients to decipher the complicated factors involved in the development of keloid disease. MiRNA expression profiling in the sera from 9 keloid patients and 7 normal controls were characterized using a miRNA microarray containing established human mature and precursor miRNA sequences. Quantitative real-time PCR was performed to confirm the expression of miRNAs. The putative targets of differentially expressed miRNAs were functionally annotated by bioinformatics. MiRNA microarray analysis identified 37 differentially expressed miRNAs (17 upregulated and 20 downregulated) in keloid patients, compared to the healthy controls. Functional annotations revealed that the targets of those differentially expressed miRNAs were enriched in signaling pathways essential for scar formation and wound healing. The expression profiling of miRNAs is altered in the keloid, providing a clue for the molecular mechanisms underlying its initiation and progression. MiRNAs may partly contribute to the etiology of keloids by affecting the critical signaling pathways relevant to keloid pathogenesis.

MicroRNA expression profiling in alveolar macrophages of indigenous Chinese Tongcheng pigs infected with PRRSV in vivo.

PubMed

Zhou, Xiang; Michal, Jennifer J; Jiang, Zhihua; Liu, Bang

2017-11-01

Porcine respiratory and reproductive syndrome (PRRS), caused by PRRS virus (PRRSV), is one of the most serious infectious diseases in the swine industry worldwide. Indigenous Chinese Tongcheng (TC) pigs reportedly show strong resistance to PRRSV infection. The miRNA expression profiles of porcine alveolar macrophages (PAMs) of control TC pigs and those infected with PRRSV in vivo were analyzed by high-throughput sequencing to explore changes induced by infection. A total of 182 known miRNAs including 101 miRNA-5p and 81 miRNA-3p were identified with 23 up-regulated differentially expressed miRNAs (DEmiRNAs) and 25 down-regulated DEmiRNAs. Gene Ontology analysis showed that predicted target genes for the DEmiRNAs were enriched in immune response, transcription regulation, and cell death. The integrative analysis of mRNA and miRNA expression revealed that down-regulated methylation-related genes (DNMT1 and DNMT3b) were targeted by five up-regulated DEmiRNAs. Furthermore, 35 pairs of miRNAs (70 miRNAs) were co-expressed after PRRSV infection and six pairs were co-expressed differently. Our results describe miRNA expression profiles of TC pigs in response to PRRSV infection and lay a strong foundation for developing novel therapies to control PRRS in pigs.

Temporal Changes in Gene Expression in Rainbow Trout Exposed to Ethynyl Estradiol*

PubMed Central

Skillman, Ann D.; Small, Jack A.; Schultz, Irvin R.

2007-01-01

We examined changes in the genomic response during continuous exposure to the xenoestrogen ethynylestradiol. Isogenic rainbow trout Oncorhynchus mykiss were exposed to nominal concentrations of 100 ng/L ethynyl estradiol (EE2) for a period of three weeks. At fixed time points within the exposure, fish were euthanized, livers harvested and RNA extracted. Fluorescently labeled cDNA were generated and hybridized against a commercially available Salmonid array (GRASP project, University of Victoria, Canada) spotted with 16,000 cDNAs. The slides were scanned to measure abundance of a given transcript in each sample relative to controls. Data were analyzed via Genespring (Silicon Genetics) to identify a list of up and down regulated genes, and to determine gene clustering patterns that can be used as “expression signatures”. Gene ontology was determined using the annotation available from the GRASP website. Our analysis indicates each exposure time period generated specific gene expression profiles. Changes in gene expression were best understood by grouping genes by their gene expression profiles rather than examining fold change at a particular time point. Many of the genes commonly used as biomarkers of exposure to xenoestrogens were not induced initially and did not have gene expression profiles typical of the majority of genes with altered expression. PMID:17215170

Temporal changes in gene expression in rainbow trout exposed to ethynyl estradiol.

PubMed

Hook, Sharon E; Skillman, Ann D; Small, Jack A; Schultz, Irvin R

2007-02-01

We examined changes in the genomic response during continuous exposure to the xenoestrogen ethynyl estradiol. Isogenic rainbow trout Oncorhynchus mykiss were exposed to nominal concentrations of 100 ng/L ethynyl estradiol (EE2) for a period of 3 weeks. At fixed time points within the exposure, fish were euthanized, livers harvested and RNA extracted. Fluorescently labeled cDNA were generated and hybridized against a commercially available Salmonid array (GRASP project, University of Victoria, Canada) spotted with 16,000 cDNAs. The slides were scanned to measure abundance of a given transcript in each sample relative to controls. Data were analyzed via Genespring (Silicon Genetics) to identify a list of up and down regulated genes, and to determine gene clustering patterns that can be used as "expression signatures". Gene ontology was determined using the annotation available from the GRASP website. Our analysis indicates each exposure time period generated specific gene expression profiles. Changes in gene expression were best understood by grouping genes by their gene expression profiles rather than examining fold change at a particular time point. Many of the genes commonly used as biomarkers of exposure to xenoestrogens were not induced initially and did not have gene expression profiles typical of the majority of genes with altered expression.

Comprehensive analysis of the transcriptional profile of the Mediator complex across human cancer types.

PubMed

Syring, Isabella; Klümper, Niklas; Offermann, Anne; Braun, Martin; Deng, Mario; Boehm, Diana; Queisser, Angela; von Mässenhausen, Anne; Brägelmann, Johannes; Vogel, Wenzel; Schmidt, Doris; Majores, Michael; Schindler, Anne; Kristiansen, Glen; Müller, Stefan C; Ellinger, Jörg; Shaikhibrahim, Zaki; Perner, Sven

2016-04-26

The Mediator complex is a key regulator of gene transcription and several studies demonstrated altered expressions of particular subunits in diverse human diseases, especially cancer. However a systematic study deciphering the transcriptional expression of the Mediator across different cancer entities is still lacking.We therefore performed a comprehensive in silico cancer vs. benign analysis of the Mediator complex subunits (MEDs) for 20 tumor entities using Oncomine datasets. The transcriptional expression profiles across almost all cancer entities showed differentially expressed MEDs as compared to benign tissue. Differential expression of MED8 in renal cell carcinoma (RCC) and MED12 in lung cancer (LCa) were validated and further investigated by immunohistochemical staining on tissue microarrays containing large numbers of specimen. MED8 in clear cell RCC (ccRCC) associated with shorter survival and advanced TNM stage and showed higher expression in metastatic than primary tumors. In vitro, siRNA mediated MED8 knockdown significantly impaired proliferation and motility in ccRCC cell lines, hinting at a role for MED8 to serve as a novel therapeutic target in ccRCC. Taken together, our Mediator complex transcriptome proved to be a valid tool for identifying cancer-related shifts in Mediator complex composition, revealing that MEDs do exhibit cancer specific transcriptional expression profiles.

Validation of the β-amy1 transcription profiling assay and selection of reference genes suited for a RT-qPCR assay in developing barley caryopsis.

PubMed

Ovesná, Jaroslava; Kučera, Ladislav; Vaculová, Kateřina; Štrymplová, Kamila; Svobodová, Ilona; Milella, Luigi

2012-01-01

Reverse transcription coupled with real-time quantitative PCR (RT-qPCR) is a frequently used method for gene expression profiling. Reference genes (RGs) are commonly employed to normalize gene expression data. A limited information exist on the gene expression and profiling in developing barley caryopsis. Expression stability was assessed by measuring the cycle threshold (Ct) range and applying both the GeNorm (pair-wise comparison of geometric means) and Normfinder (model-based approach) principles for the calculation. Here, we have identified a set of four RGs suitable for studying gene expression in the developing barley caryopsis. These encode the proteins GAPDH, HSP90, HSP70 and ubiquitin. We found a correlation between the frequency of occurrence of a transcript in silico and its suitability as an RG. This set of RGs was tested by comparing the normalized level of β-amylase (β-amy1) transcript with directly measured quantities of the BMY1 gene product in the developing barley caryopsis. This panel of genes could be used for other gene expression studies, as well as to optimize β-amy1 analysis for study of the impact of β-amy1 expression upon barley end-use quality.

Identifying potential maternal genes of Bombyx mori using digital gene expression profiling

PubMed Central

Xu, Pingzhen

2018-01-01

Maternal genes present in mature oocytes play a crucial role in the early development of silkworm. Although maternal genes have been widely studied in many other species, there has been limited research in Bombyx mori. High-throughput next generation sequencing provides a practical method for gene discovery on a genome-wide level. Herein, a transcriptome study was used to identify maternal-related genes from silkworm eggs. Unfertilized eggs from five different stages of early development were used to detect the changing situation of gene expression. The expressed genes showed different patterns over time. Seventy-six maternal genes were annotated according to homology analysis with Drosophila melanogaster. More than half of the differentially expressed maternal genes fell into four expression patterns, while the expression patterns showed a downward trend over time. The functional annotation of these material genes was mainly related to transcription factor activity, growth factor activity, nucleic acid binding, RNA binding, ATP binding, and ion binding. Additionally, twenty-two gene clusters including maternal genes were identified from 18 scaffolds. Altogether, we plotted a profile for the maternal genes of Bombyx mori using a digital gene expression profiling method. This will provide the basis for maternal-specific signature research and improve the understanding of the early development of silkworm. PMID:29462160

Alteration of gene expression profiling including GPR174 and GNG2 is associated with vasovagal syncope.

PubMed

Huang, Yu-Juan; Zhou, Zai-wei; Xu, Miao; Ma, Qing-wen; Yan, Jing-bin; Wang, Jian-yi; Zhang, Quo-qin; Huang, Min; Bao, Liming

2015-03-01

Vasovagal syncope (VVS) causes accidental harm for susceptible patients. However, pathophysiology of this disorder remains largely unknown. In an effort to understanding of molecular mechanism for VVS, genome-wide gene expression profiling analyses were performed on VVS patients at syncope state. A total of 66 Type 1 VVS child patients and the same number healthy controls were enrolled in this study. Peripheral blood RNAs were isolated from all subjects, of which 10 RNA samples were randomly selected from each groups for gene expression profile analysis using Gene ST 1.0 arrays (Affymetrix). The results revealed that 103 genes were differently expressed between the patients and controls. Significantly, two G-proteins related genes, GPR174 and GNG2 that have not been related to VVS were among the differently expressed genes. The microarray results were confirmed by qRT-PCR in all the tested individuals. Ingenuity pathway analysis and gene ontology annotation study showed that the differently expressed genes are associated with stress response and apoptosis, suggesting that the alteration of some gene expression including G-proteins related genes is associated with VVS. This study provides new insight into the molecular mechanism of VVS and would be helpful to further identify new molecular biomarkers for the disease.

Expression profiles of sugarcane under drought conditions: Variation in gene regulation.

PubMed

Andrade, Júlio César Farias de; Terto, Jackeline; Silva, José Vieira; Almeida, Cícero

2015-12-01

Drought is a major factor in decreased sugarcane productivity because of the resulting morphophysiological effects that it causes. Gene expression studies that have examined the influence of water stress in sugarcane have yielded divergent results, indicating the absence of a fixed pattern of changes in gene expression. In this work, we investigated the expression profiles of 12 genes in the leaves of a drought-tolerant genotype (RB72910) of sugarcane and compared the results with those of other studies. The genotype was subjected to 80-100% water availability (control condition) and 0-20% water availability (simulated drought). To analyze the physiological status, the SPAD index, Fv/Fm ratio, net photosynthesis (A), stomatal conductance (gs) and stomatal transpiration (E) were measured. Total RNA was extracted from leaves and the expression of SAMDC, ZmPIP2-1 protein, ZmTIP4-2 protein, WIP protein, LTP protein, histone H3, DNAj, ferredoxin I, β-tubulin, photosystem I, gene 1 and gene 2 was analyzed by quantitative real-time PCR (RT-PCR). Important differences in the expression profiles of these genes were observed when compared with other genotypes, suggesting that complex defense mechanisms are activated in response to water stress. However, there was no recognizable pattern for the changes in expression of the different proteins associated with tolerance to drought stress.

Prospective EFL Teachers' Perceptions of ICT Integration: A Study of Distance Higher Education in Turkey

ERIC Educational Resources Information Center

Hismanoglu, Murat

2012-01-01

This paper aims to investigate the perceptions of prospective EFL teachers in the distance higher education system toward ICT implementation in teaching English as a foreign language. The majority of respondents who expressed negative attitudes to ICT integration found the nature, level and delivery of the training inadequate and accordingly…

Genome-wide analysis and expression profiling of the Solanum tuberosum aquaporins.

PubMed

Venkatesh, Jelli; Yu, Jae-Woong; Park, Se Won

2013-12-01

Aquaporins belongs to the major intrinsic proteins involved in the transcellular membrane transport of water and other small solutes. A comprehensive genome-wide search for the homologues of Solanum tuberosum major intrinsic protein (MIP) revealed 41 full-length potato aquaporin genes. All potato aquaporins are grouped into five subfamilies; plasma membrane intrinsic proteins (PIPs), tonoplast intrinsic proteins (TIPs), NOD26-like intrinsic proteins (NIPs), small basic intrinsic proteins (SIPs) and x-intrinsic proteins (XIPs). Functional predictions based on the aromatic/arginine (ar/R) selectivity filters and Froger's positions showed a remarkable difference in substrate transport specificity among subfamilies. The expression pattern of potato aquaporins, examined by qPCR analysis, showed distinct expression profiles in various organs and tuber developmental stages. Furthermore, qPCR analysis of potato plantlets, subjected to various abiotic stresses revealed the marked effect of stresses on expression levels of aquaporins. Taken together, the expression profiles of aquaporins imply that aquaporins play important roles in plant growth and development, in addition to maintaining water homeostasis in response to environmental stresses. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Non-small cell lung cancer detection using microRNA expression profiling of bronchoalveolar lavage fluid and sputum.

PubMed

Kim, Julian O; Gazala, Sayf; Razzak, Rene; Guo, Linghong; Ghosh, Sunita; Roa, Wilson H; Bédard, Eric L R

2015-04-01

To assess if miRNA expression profiling of bronchoalveolar lavage (BAL) fluid and sputum could be used to detect early-stage non-small cell lung cancer (NSCLC). Hierarchical cluster analysis was performed on the expression levels of 5 miRNAs (miR-21, miR-143, miR-155, miR-210, and miR-372) which were quantified using RNA reverse transcription and quantitative real-time polymerase chain reaction in sputum and BAL samples from NSCLC cases and cancer-free controls. Cluster analysis of the miRNA expression levels in BAL samples from 21 NSCLC cases and sputum samples from 10 cancer-free controls yielded a diagnostic sensitivity of 85.7% and specificity of 100%. Cluster analysis of sputum samples from the same patients yielded a diagnostic sensitivity of 67.8% and specificity of 90%. miRNA expression profiling of sputum and BAL fluids represent a potential means to detect early-stage NSCLC. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Computational Prediction and Validation of BAHD1 as a Novel Molecule for Ulcerative Colitis

NASA Astrophysics Data System (ADS)

Zhu, Huatuo; Wan, Xingyong; Li, Jing; Han, Lu; Bo, Xiaochen; Chen, Wenguo; Lu, Chao; Shen, Zhe; Xu, Chenfu; Chen, Lihua; Yu, Chaohui; Xu, Guoqiang

2015-07-01

Ulcerative colitis (UC) is a common inflammatory bowel disease (IBD) producing intestinal inflammation and tissue damage. The precise aetiology of UC remains unknown. In this study, we applied a rank-based expression profile comparative algorithm, gene set enrichment analysis (GSEA), to evaluate the expression profiles of UC patients and small interfering RNA (siRNA)-perturbed cells to predict proteins that might be essential in UC from publicly available expression profiles. We used quantitative PCR (qPCR) to characterize the expression levels of those genes predicted to be the most important for UC in dextran sodium sulphate (DSS)-induced colitic mice. We found that bromo-adjacent homology domain (BAHD1), a novel heterochromatinization factor in vertebrates, was the most downregulated gene. We further validated a potential role of BAHD1 as a regulatory factor for inflammation through the TNF signalling pathway in vitro. Our findings indicate that computational approaches leveraging public gene expression data can be used to infer potential genes or proteins for diseases, and BAHD1 might act as an indispensable factor in regulating the cellular inflammatory response in UC.

Benzoate-mediated changes on expression profile of soluble proteins in Serratia sp. DS001.

PubMed

Pandeeti, E V P; Chinnaboina, M R; Siddavattam, D

2009-05-01

To assess differences in protein expression profile associated with shift in carbon source from succinate to benzoate in Serratia sp. DS001 using a proteomics approach. A basic proteome map was generated for the soluble proteins extracted from Serratia sp. DS001 grown in succinate and benzoate. The differently and differentially expressed proteins were identified using ImageMaster 2D Platinum software (GE Healthcare). The identity of the proteins was determined by employing MS or MS/MS. Important enzymes such as Catechol 1,2 dioxygenase and transcriptional regulators that belong to the LysR superfamily were identified. Nearly 70 proteins were found to be differentially expressed when benzoate was used as carbon source. Based on the protein identity and degradation products generated from benzoate it is found that ortho pathway is operational in Serratia sp. DS001. Expression profile of the soluble proteins associated with shift in carbon source was mapped. The study also elucidates degradation pathway of benzoate in Serratia sp. DS001 by correlating the proteomics data with the catabolites of benzoate.

[New methods of patient selection for improved anticholinergic therapy].

PubMed

Neuhaus, J; Schwalenberg, T; Schlichting, N; Schulze, M; Horn, L-C; Stolzenburg, J-U

2007-09-01

M3-specific inhibitors are currently preferred for anticholinergic therapy of OAB. However, not all of the patients profit from this regimen. This might reflect a heterogeneity of the patient group. The aim of this work is to define subgroups of patients with specific alterations of receptor expression and to profile the receptor expression individually. These receptor profiles might be used for the development of evidence-based "tailored" therapies. Detrusor probes from bladder carcinoma patients (BCa, n=9 F, n=7 male) and interstitial cystitis patients (IC, n=9 female) were examined using confocal immunofluorescence and PCR. M2, M3, P2X1-3, and H1-3 mRNAs were demonstrated in detrusor tissue. As revealed by immunofluorescence, the M2 receptor expression was significantly higher in female compared to male BCa tissues. In addition, the M2 receptor was further upregulated in IC vs BCa in female detrusor. IC patients showed specific alterations of their receptor profile. Individual receptor profiles might be used to optimize medicinal therapies.

Inclusion criteria provide heterogeneity in baseline profiles of patients with mild cognitive impairment: comparison of two prospective cohort studies

PubMed Central

Kawashima, Shoji; Kato, Takashi

2012-01-01

Background Mild cognitive impairment (MCI) is considered to represent a transitional stage between ageing and Alzheimer's disease (AD). To aim at identifying neuroimaging measures associated with cognitive changes in healthy elderly and MCI patients, longitudinal multicentre studies are ongoing in several countries. The patient profiles of each study are based on unique inclusion criteria. Objectives The purpose of the study is to clarify differences in baseline profiles of MCI patients between Studies on Diagnosis of Early Alzheimer's Disease—Japan (SEAD-J) and Alzheimer's Disease Neuroimaging Initiative (ADNI) and to examine the association between baseline profiles and risk of early conversion to AD. Design Prospective cohort study. Setting and participants SEAD-J recruited 114 patients from nine facilities in Japan. A total of 200 patients in ADNI with fluorodeoxyglucose–positron emission tomography (FDG-PET) were enrolled from the USA. Methods Baseline profiles were statistically analysed. For FDG-PET at a time of inclusion, associations between each profile and cerebral metabolic rate for glucose (CMRgl) were examined using SPM5 software. In each study, the ratio of conversion to AD within the 1-year and 2-year period after inclusion was investigated and differences in baseline profiles between AD converters and non-converters were analysed. Results SEAD-J included MCI patients with more severe verbal memory deficits and extracted patients with higher depressive tendencies. These differences were likely to be associated with criteria. SEAD-J exhibited a higher rate of conversion within 1 year compared with ADNI (24.5% vs 13.5%). In FDG-PET analyses of SEAD-J, AD converters within 1 year showed more severe decrease of FDG uptake in bilateral inferior parietal regions compared with non-converters. Conclusions Different inclusion criteria provided differences in baseline profiles. The severity of memory deficit might cause increase of the AD conversion within 1 year. Clinical outcomes of multicentre studies for early diagnosis of AD should be interpreted carefully considering profiles of patients. PMID:22535791

Effects of Simulated Microgravity on the Expression Profile of Microrna in Human Lymphoblastoid Cells

NASA Astrophysics Data System (ADS)

Zhang, Ye; Wu, Honglu; Ramesh, Govindarajan; Rohde, Larry; Story, Michael; Mangala, Lingegowda

2012-07-01

EFFECTS OF SIMULATED MICROGRAVITY ON THE EXPRESSION PROFILE OF MICRORNA IN HUMAN LYMPHOBLASTOID CELLS Lingegowda S. Mangala1,2, Ye Zhang1,3, Zhenhua He2, Kamal Emami1, Govindarajan T. Ramesh4, Michael Story 5, Larry H. Rohde2, and Honglu Wu1 1 NASA Johnson Space Center, Houston, Texas, USA 2 University of Houston Clear Lake, Houston, Texas, USA 3 Wyle Integrated Science and Engineering Group, Houston, Texas, USA 4 Norfolk State University, Norfolk, VA, USA 5 University of Texas, Southwestern Medical Center, Dallas, Texas, USA This study explores the changes in expression of microRNA (miRNA) and related genes under simulated microgravity conditions. In comparison to static 1g, microgravity has been shown to alter global gene expression patterns and protein levels in cultured cells or animals. miRNA has recently emerged as an important regulator of gene expression, possibly regulating as many as one-third of all human genes. However, very little is known about the effect of altered gravity on miRNA expression. To test the hypothesis that the miRNA expression profile would be altered in zero gravity resulting in altered regulation of gene expression leading to metabolic or functional changes in cells, we cultured TK6 human lymphoblastoid cells in a High Aspect Ratio Vessel (HARV; bioreactor) for 72 h either in the rotating condition to model microgravity in space or in the static condition as a control. Expression of several miRNA was changed significantly in the simulated microgravity condition including miR-150, miR-34a, miR-423-5p, miR-22 and miR-141, miR-618 and miR-222. To confirm whether this altered miRNA expression correlates with gene expression and functional changes of the cells, we performed DNA microarray and validated the related genes using q-RT PCR. Network and pathway analysis of gene and miRNA expression profiles indicates that the regulation of cell communication and catalytic activities, as well as pathways involved in immune response_IL-15 signaling and NGF mediated NF-kB activation were significantly altered under the simulated microgravity condition.

Re-evaluating microglia expression profiles using RiboTag and cell isolation strategies.

PubMed

Haimon, Zhana; Volaski, Alon; Orthgiess, Johannes; Boura-Halfon, Sigalit; Varol, Diana; Shemer, Anat; Yona, Simon; Zuckerman, Binyamin; David, Eyal; Chappell-Maor, Louise; Bechmann, Ingo; Gericke, Martin; Ulitsky, Igor; Jung, Steffen

2018-06-01

Transcriptome profiling is widely used to infer functional states of specific cell types, as well as their responses to stimuli, to define contributions to physiology and pathophysiology. Focusing on microglia, the brain's macrophages, we report here a side-by-side comparison of classical cell-sorting-based transcriptome sequencing and the 'RiboTag' method, which avoids cell retrieval from tissue context and yields translatome sequencing information. Conventional whole-cell microglial transcriptomes were found to be significantly tainted by artifacts introduced by tissue dissociation, cargo contamination and transcripts sequestered from ribosomes. Conversely, our data highlight the added value of RiboTag profiling for assessing the lineage accuracy of Cre recombinase expression in transgenic mice. Collectively, this study indicates method-based biases, reveals observer effects and establishes RiboTag-based translatome profiling as a valuable complement to standard sorting-based profiling strategies.

Gene Expression Profiling of Multiple Leiomyomata Uteri and Matched Normal Tissue from a Single Patient

PubMed Central

Dimitrova, Irina K.; Richer, Jennifer K.; Rudolph, Michael C.; Spoelstra, Nicole S.; Reno, Elaine M.; Medina, Theresa M.; Bradford, Andrew P.

2009-01-01

Objective To identify differentially expressed genes between fibroid and adjacent normal myometrium in an identical hormonal and genetic background. Design Array analysis of 3 leiomyomata and matched adjacent normal myometrium in a single patient. Setting University of Colorado Hospital. Patient(s) A single female undergoing medically indicated hysterectomy for symptomatic fibroids. Interventions(s) mRNA isolation and microarray analysis, reverse-transcriptase polymerase chain reaction, western blotting and immunohistochemistry. Main Outcome Measure(s) Changes in mRNA and protein levels in leiomyomata and matched normal myometrium. Result(s) Expression of 197 genes was increased and 619 decreased, significantly by at least 2 fold, in leiomyomata relative to normal myometrium. Expression profiles between tumors were similar and normal myometrial samples showed minimal variation. Changes in, and variation of, expression of selected genes were confirmed in additional normal and leiomyoma samples from multiple patients. Conclusion(s) Analysis of multiple tumors from a single patient confirmed changes in expression of genes described in previous, apparently disparate, studies and identified novel targets. Gene expression profiles in leiomyomata are consistent with increased activation of mitogenic pathways and inhibition of apoptosis. Down-regulation of genes implicated in invasion and metastasis, of cancers, was observed in fibroids. This expression pattern may underlie the benign nature of uterine leiomyomata and may aid in the differential diagnosis of leiomyosarcoma. PMID:18672237

Maternal Pre-Gravid Obesity Changes Gene Expression Profiles Towards Greater Inflammation and Reduced Insulin Sensitivity in Umbilical Cord

PubMed Central

Thakali, Keshari M.; Saben, Jessica; Faske, Jennifer B.; Lindsey, Forrest; Gomez-Acevedo, Horacio; Lowery, Curtis L.; Badger, Thomas M.; Andres, Aline; Shankar, Kartik

2014-01-01

Background Maternal obesity is associated with unfavorable outcomes, which may be reflected in the as yet undiscovered gene expression profiles of the umbilical cord (UC). Methods UCs from 12 lean (pre-gravid BMI < 24.9) and 10 overweight/obese (OW/OB, pre-gravid BMI ≥25) women without gestational diabetes were collected for gene expression analysis using Human Primeview microarrays (Affymetrix). Metabolic parameters were assayed in mother’s plasma and cord blood. Results Although offspring birth weight and adiposity (at 2-wk) did not differ between groups, expression of 232 transcripts was affected in UC from OW/OB compared to those of lean mothers. GSEA analysis revealed an up-regulation of genes related to metabolism, stimulus and defense response and inhibitory to insulin signaling in the OW/OB group. We confirmed that EGR1, periostin, and FOSB mRNA expression was induced in UCs from OW/OB moms, while endothelin receptor B, KFL10, PEG3 and EGLN3 expression was decreased. Messenger RNA expression of EGR1, FOSB, MEST and SOCS1 were positively correlated (p<0.05) with mother’s first trimester body fat mass (%). Conclusions Our data suggest a positive association between maternal obesity and changes in UC gene expression profiles favoring inflammation and insulin resistance, potentially predisposing infants to develop metabolic dysfunction later on in life. PMID:24819376

Cellular expansion and gene expression in the developing grape (Vitis vinifera L.).

PubMed

Schlosser, J; Olsson, N; Weis, M; Reid, K; Peng, F; Lund, S; Bowen, P

2008-01-01

Expression profiles of genes involved in cell wall metabolism and water transport were compared with changes in grape (Vitis vinifera L.) berry growth, basic chemical composition, and the shape, size, and wall thickness of cells within tissues of the berry pericarp. Expression of cell wall-modifying and aquaporin genes in berry pericarp tissues generally followed a bimodal expression profile with high levels of expression coinciding with the two periods of rapid berry growth, stages I and III, and low levels of expression corresponding to the slow-growth period, stage II. Cellular expansion was observed throughout all tissues during stage I, and only mesocarp cellular expansion was observed during stage III. Expansion of only exocarp cells was evident during transition between stages II and III. Cell wall-modifying and aquaporin gene expression profiles followed similar trends in exocarp and mesocarp tissues throughout berry development, with the exception of the up-regulation of pectin methylesterase, pectate lyase, two aquaporin genes (AQ1 and AQ2), and two expansin genes (EXP3 and EXPL) during stage II, which was delayed in the exocarp tissue compared with mesocarp tissue. Exocarp endo-(1-->3)-beta-glucanase and expansin-like gene expression was concurrent with increases in epidermal and hypodermal cell wall thickness. These results indicate a potential role of the grape berry skin in modulating grape berry growth.

Expression Profiles of TGF-β and TLR Pathways in Porphyromonas gingivalis and Prevotella intermedia Challenged Osteoblasts

PubMed Central

Aydin, Kubra; Ekinci, Fatma Yesim; Korachi, May

2015-01-01

Background: The presence of certain oral pathogens at implant sites can hinder the osseointegration process. However, it is unclear how and by what microorganisms it happens. Objectives: This study investigated whether the presence of oral pathogens of Porphyromonas gingivalis and Prevotella intermedia individually, play a role in the failure of bone formation by determining the expression profiles of Transforming Growth Factor Beta (TGF-β/Bone Morphogenic Protein (BMP) and Toll-Like Receptor (TLR) pathways in challenged osteoblasts. Materials and Methods: Cell viability of P. gingivalis and P. intermedia challenged osteoblasts were determined by WST assay. Changes in osteoblast morphology and inhibition of mineralization were observed by Scanning Electron Microscopy (SEM) and Von Kossa staining, respectively. Expression of TGF-β and TLR pathway genes on challenged cells were identified by RT profiler array. Both P. gingivalis and P. intermedia challenges resulted in reduced viability and mineralization of osteoblasts. Results: Viability was reduced to 56.8% (P. gingivalis) and 52.75% (P. intermedia) at 1000 multiplicity. Amongst 48 genes examined, expressions of BMPER, SMAD1, IL8 and NFRKB were found to be highly upregulated by both bacterial challenges (Fold Change > 4). Conclusions: P. gingivalis and P. intermedia could play a role in implant failure by changing the expression profiles of genes related to bone formation and resorption. PMID:26034550

A Modified ABCDE Model of Flowering in Orchids Based on Gene Expression Profiling Studies of the Moth Orchid Phalaenopsis aphrodite

PubMed Central

Lee, Ann-Ying; Chen, Chun-Yi; Chang, Yao-Chien Alex; Chao, Ya-Ting; Shih, Ming-Che

2013-01-01

Previously we developed genomic resources for orchids, including transcriptomic analyses using next-generation sequencing techniques and construction of a web-based orchid genomic database. Here, we report a modified molecular model of flower development in the Orchidaceae based on functional analysis of gene expression profiles in Phalaenopsis aphrodite (a moth orchid) that revealed novel roles for the transcription factors involved in floral organ pattern formation. Phalaenopsis orchid floral organ-specific genes were identified by microarray analysis. Several critical transcription factors including AP3, PI, AP1 and AGL6, displayed distinct spatial distribution patterns. Phylogenetic analysis of orchid MADS box genes was conducted to infer the evolutionary relationship among floral organ-specific genes. The results suggest that gene duplication MADS box genes in orchid may have resulted in their gaining novel functions during evolution. Based on these analyses, a modified model of orchid flowering was proposed. Comparison of the expression profiles of flowers of a peloric mutant and wild-type Phalaenopsis orchid further identified genes associated with lip morphology and peloric effects. Large scale investigation of gene expression profiles revealed that homeotic genes from the ABCDE model of flower development classes A and B in the Phalaenopsis orchid have novel functions due to evolutionary diversification, and display differential expression patterns. PMID:24265826

Mining the archives: a cross-platform analysis of gene ...

EPA Pesticide Factsheets

Formalin-fixed paraffin-embedded (FFPE) tissue samples represent a potentially invaluable resource for genomic research into the molecular basis of disease. However, use of FFPE samples in gene expression studies has been limited by technical challenges resulting from degradation of nucleic acids. Here we evaluated gene expression profiles derived from fresh-frozen (FRO) and FFPE mouse liver tissues using two DNA microarray protocols and two whole transcriptome sequencing (RNA-seq) library preparation methodologies. The ribo-depletion protocol outperformed the other three methods by having the highest correlations of differentially expressed genes (DEGs) and best overlap of pathways between FRO and FFPE groups. We next tested the effect of sample time in formalin (18 hours or 3 weeks) on gene expression profiles. Hierarchical clustering of the datasets indicated that test article treatment, and not preservation method, was the main driver of gene expression profiles. Meta- and pathway analyses indicated that biological responses were generally consistent for 18-hour and 3-week FFPE samples compared to FRO samples. However, clear erosion of signal intensity with time in formalin was evident, and DEG numbers differed by platform and preservation method. Lastly, we investigated the effect of age in FFPE block on genomic profiles. RNA-seq analysis of 8-, 19-, and 26-year-old control blocks using the ribo-depletion protocol resulted in comparable quality metrics, inc

Genetic validation of whole-transcriptome sequencing for mapping expression affected by cis-regulatory variation.

PubMed

Babak, Tomas; Garrett-Engele, Philip; Armour, Christopher D; Raymond, Christopher K; Keller, Mark P; Chen, Ronghua; Rohl, Carol A; Johnson, Jason M; Attie, Alan D; Fraser, Hunter B; Schadt, Eric E

2010-08-13

Identifying associations between genotypes and gene expression levels using microarrays has enabled systematic interrogation of regulatory variation underlying complex phenotypes. This approach has vast potential for functional characterization of disease states, but its prohibitive cost, given hundreds to thousands of individual samples from populations have to be genotyped and expression profiled, has limited its widespread application. Here we demonstrate that genomic regions with allele-specific expression (ASE) detected by sequencing cDNA are highly enriched for cis-acting expression quantitative trait loci (cis-eQTL) identified by profiling of 500 animals in parallel, with up to 90% agreement on the allele that is preferentially expressed. We also observed widespread noncoding and antisense ASE and identified several allele-specific alternative splicing variants. Monitoring ASE by sequencing cDNA from as little as one sample is a practical alternative to expression genetics for mapping cis-acting variation that regulates RNA transcription and processing.

Payment and Provider Profiling of Episodes of Illness of Clinical Illnesses Involving Rehabilitation.

ERIC Educational Resources Information Center

Goldfield, Norbert; Averill, Richard; Eisenhandler, Jon; Hughes, John S.; Muldoon, John; Steinbeck, Barbara; Bagadia, Farah

2001-01-01

Summarizes the development of a new risk adjustment methodology, the Clinical Risk Grouping System, a prospective capitation risk adjuster, that should be useful for payment and monitoring of episodes of clinical conditions that involve rehabilitation. (SLD)

[Differential expression genes of bone tissues surrounding implants in diabetic rats by gene chip].

PubMed

Wang, Xin-xin; Ma, Yue; Li, Qing; Jiang, Bao-qi; Lan, Jing

2012-10-01

To compare mRNA expression profiles of bone tissues surrounding implants between normal rats and rats with diabetes using microarray technology. Six Wistar rats were randomly selected and divided into normal model group and diabetic group. Diabetic model condition was established by injecting Streptozotocin into peritoneal space. Titanium implants were implanted into the epiphyseal end of the rats' tibia. Bone tissues surrounding implant were harvested and sampled after 3 months to perform comprehensive RNA gene expression profiling, including 17983 for genome-wide association study.GO analysis was used to compare different gene expression and real-time PCR was used to confirm the results on core samples. The results indicated that there were 1084 differential gene expression. In the diabetic model, there were 352 enhanced expression genes, 732 suppressed expression genes. GO analysis involved 1154 different functional type. Osteoblast related gene expressions in bone tissue samples of diabetic rats were decreased, and lipid metabolism pathway related gene expression was increased.