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Sample records for identifying candidate colon

  1. Candidal colonization, strain diversity, and antifungal susceptibility among adult diabetic patients.

    Science.gov (United States)

    Al-Attas, Safia A; Amro, Soliman O

    2010-01-01

    Candidal colonization in diabetics is a matter of debate. The aim of this study is to investigate oral candidal colonization, strain diversity, antifungal susceptibility, and the influence of local and systemic host factors on candidal colonization in adult diabetics. We conducted a case-control study that compared 150 diabetics (49 type 1, 101 type 2) with 50 healthy controls. Two salivary samples were collected, using the oral rinse sampling method: one for salivary flow rate and pH determination, and the other for candidal colonization assessment. The candidal isolates were identified and tested in vitro for antifungal susceptibility using the commercial kit, Candifast. The relationship between specific host factors and candidal colonization was also investigated. Diabetics had a higher candidal carriage rate compared to controls, but not density. Candida albicans was the most frequently isolated species, but diabetics had a variety of other candidal species present. None of the control samples were resistant to any tested antifungal, while the diabetic samples had differing resistances to azole antifungals. Although there was a significant positive correlation between glycemic control and candidal colonization in type 2 diabetics, there was a negative correlation between salivary pH and candidal carriage in the controls versus density in type 2 diabetics. Diabetic patients not only had a higher candidal carriage rate, but also a variety of candidal species that were resistant to azole antifungals. Oral candidal colonization was significantly associated with glycemic control, type of diabetes, and salivary pH.

  2. Gene Signature in Sessile Serrated Polyps Identifies Colon Cancer Subtype

    Science.gov (United States)

    Kanth, Priyanka; Bronner, Mary P.; Boucher, Kenneth M.; Burt, Randall W.; Neklason, Deborah W.; Hagedorn, Curt H.; Delker, Don A.

    2016-01-01

    Sessile serrated colon adenoma/polyps (SSA/Ps) are found during routine screening colonoscopy and may account for 20–30% of colon cancers. However, differentiating SSA/Ps from hyperplastic polyps (HP) with little risk of cancer is challenging and complementary molecular markers are needed. Additionally, the molecular mechanisms of colon cancer development from SSA/Ps are poorly understood. RNA sequencing was performed on 21 SSA/Ps, 10 HPs, 10 adenomas, 21 uninvolved colon and 20 control colon specimens. Differential expression and leave-one-out cross validation methods were used to define a unique gene signature of SSA/Ps. Our SSA/P gene signature was evaluated in colon cancer RNA-Seq data from The Cancer Genome Atlas (TCGA) to identify a subtype of colon cancers that may develop from SSA/Ps. A total of 1422 differentially expressed genes were found in SSA/Ps relative to controls. Serrated polyposis syndrome (n=12) and sporadic SSA/Ps (n=9) exhibited almost complete (96%) gene overlap. A 51-gene panel in SSA/P showed similar expression in a subset of TCGA colon cancers with high microsatellite instability (MSI-H). A smaller seven-gene panel showed high sensitivity and specificity in identifying BRAF mutant, CpG island methylator phenotype high (CIMP-H) and MLH1 silenced colon cancers. We describe a unique gene signature in SSA/Ps that identifies a subset of colon cancers likely to develop through the serrated pathway. These gene panels may be utilized for improved differentiation of SSA/Ps from HPs and provide insights into novel molecular pathways altered in colon cancer arising from the serrated pathway. PMID:27026680

  3. Targeted sequencing of established and candidate colorectal cancer genes in the Colon Cancer Family Registry Cohort.

    Science.gov (United States)

    Raskin, Leon; Guo, Yan; Du, Liping; Clendenning, Mark; Rosty, Christophe; Lindor, Noralane M; Gruber, Stephen B; Buchanan, Daniel D

    2017-11-07

    The underlying genetic cause of colorectal cancer (CRC) can be identified for 5-10% of all cases, while at least 20% of CRC cases are thought to be due to inherited genetic factors. Screening for highly penetrant mutations in genes associated with Mendelian cancer syndromes using next-generation sequencing (NGS) can be prohibitively expensive for studies requiring large samples sizes. The aim of the study was to identify rare single nucleotide variants and small indels in 40 established or candidate CRC susceptibility genes in 1,046 familial CRC cases (including both MSS and MSI-H tumor subtypes) and 1,006 unrelated controls from the Colon Cancer Family Registry Cohort using a robust and cost-effective DNA pooling NGS strategy. We identified 264 variants in 38 genes that were observed only in cases, comprising either very rare (minor allele frequency cancer susceptibility genes BAP1, CDH1, CHEK2, ENG, and MSH3 . For the candidate CRC genes, we identified likely pathogenic variants in the helicase domain of POLQ and in the LRIG1 , SH2B3 , and NOS1 genes and present their clinicopathological characteristics. Using a DNA pooling NGS strategy, we identified novel germline mutations in established CRC susceptibility genes in familial CRC cases. Further studies are required to support the role of POLQ , LRIG1 , SH2B3 and NOS1 as CRC susceptibility genes.

  4. ENU Mutagenesis in Mice Identifies Candidate Genes For Hypogonadism

    Science.gov (United States)

    Weiss, Jeffrey; Hurley, Lisa A.; Harris, Rebecca M.; Finlayson, Courtney; Tong, Minghan; Fisher, Lisa A.; Moran, Jennifer L.; Beier, David R.; Mason, Christopher; Jameson, J. Larry

    2012-01-01

    Genome-wide mutagenesis was performed in mice to identify candidate genes for male infertility, for which the predominant causes remain idiopathic. Mice were mutagenized using N-ethyl-N-nitrosourea (ENU), bred, and screened for phenotypes associated with the male urogenital system. Fifteen heritable lines were isolated and chromosomal loci were assigned using low density genome-wide SNP arrays. Ten of the fifteen lines were pursued further using higher resolution SNP analysis to narrow the candidate gene regions. Exon sequencing of candidate genes identified mutations in mice with cystic kidneys (Bicc1), cryptorchidism (Rxfp2), restricted germ cell deficiency (Plk4), and severe germ cell deficiency (Prdm9). In two other lines with severe hypogonadism candidate sequencing failed to identify mutations, suggesting defects in genes with previously undocumented roles in gonadal function. These genomic intervals were sequenced in their entirety and a candidate mutation was identified in SnrpE in one of the two lines. The line harboring the SnrpE variant retains substantial spermatogenesis despite small testis size, an unusual phenotype. In addition to the reproductive defects, heritable phenotypes were observed in mice with ataxia (Myo5a), tremors (Pmp22), growth retardation (unknown gene), and hydrocephalus (unknown gene). These results demonstrate that the ENU screen is an effective tool for identifying potential causes of male infertility. PMID:22258617

  5. Identifying and Assessing Dispositions of Educational Leadership Candidates

    Science.gov (United States)

    Melton, Teri; Mallory, Barbara J.; Green, James

    2010-01-01

    The purpose of this study was to identify educational leadership programs' procedures for the identification and assessment of leadership dispositions. The findings of this cross sectional survey indicated that there is little consistency in practice in defining and assessing dispositions of leadership candidates. While findings indicated that the…

  6. 'Omics' approaches in tomato aimed at identifying candidate genes ...

    African Journals Online (AJOL)

    adriana

    2013-12-04

    Dec 4, 2013 ... approaches could be combined in order to identify candidate genes for the genetic control of ascorbic ..... applied to other traits under the complex control of many ... Engineering increased vitamin C levels in ... Chem. Biol. 13:532–538. Giovannucci E, Rimm EB, Liu Y, Stampfer MJ, Willett WC (2002). A.

  7. Identifying molecular targets of lifestyle modifications in colon cancer prevention

    Directory of Open Access Journals (Sweden)

    Molly Marie Derry

    2013-05-01

    Full Text Available One in four deaths in the United States is cancer-related, and colorectal cancer (CRC is the second leading cause of cancer-associated deaths. Screening strategies are utilized but have not reduced disease incidence or mortality. In this regard, there is an interest in cancer preventive strategies focusing on lifestyle intervention, where specific etiologic factors involved in cancer initiation, promotion, and progression could be targeted. For example, exposure to dietary carcinogens, such as nitrosamines and polycyclic aromatic hydrocarbons influences colon carcinogenesis. Furthermore, dietary deficiencies could alter sensitivity to genetic damage and influence carcinogen metabolism contributing to CRC. High alcohol consumption increases the risk of mutations including the fact that acetaldehyde, an ethanol metabolite, is classified as a group 1 carcinogen. Tobacco smoke exposure is also a risk factor for cancer development; ~20% of CRCs are associated with smoking. Additionally, obese patients have a higher risk of cancer development, which is further supported by the fact that physical activity decreases CRC risk by 55%. Similarly, chronic inflammatory conditions also increase the risk of CRC development. Moreover, the circadian clock alters digestion and regulates other biochemical, physiological and behavioral processes that could positively influence CRC. Taken together, colon carcinogenesis involves a number of etiological factors, and therefore, to create effective preventive strategies, molecular targets need to be identified and beleaguered prior to disease progression. With this in mind, the following is a comprehensive review identifying downstream target proteins of the above lifestyle risk factors, which are modulated during colon carcinogenesis and could be targeted for CRC prevention by novel agents including phytochemicals.

  8. Novel approaches to identify protective malaria vaccine candidates

    Directory of Open Access Journals (Sweden)

    Wan Ni eChia

    2014-11-01

    Full Text Available Efforts to develop vaccines against malaria have been the focus of substantial research activities for decades. Several categories of candidate vaccines are currently being developed for protection against malaria, based on antigens corresponding to the pre-erythrocytic, blood-stage or sexual stages of the parasite. Long lasting sterile protection from Plasmodium falciparum sporozoite challenge has been observed in human following vaccination with whole parasite formulations, clearly demonstrating that a protective immune response targeting predominantly the pre-erythrocytic stages can develop against malaria. However, most of vaccine candidates currently being investigated, which are mostly subunits vaccines, have not been able to induce substantial (>50% protection thus far. This is due to the fact that the antigens responsible for protection against the different parasite stages are still yet to be known and relevant correlates of protection have remained elusive. For a vaccine to be developed in a timely manner, novel approaches are required. In this article, we review the novel approaches that have been developed to identify the antigens for the development of an effective malaria vaccine.

  9. Clinicopathologic factors identify sporadic mismatch repair-defective colon cancers

    DEFF Research Database (Denmark)

    Halvarsson, Britta; Anderson, Harald; Domanska, Katarina

    2008-01-01

    Identification of sporadic mismatch repair (MMR)-defective colon cancers is increasingly demanded for decisions on adjuvant therapies. We evaluated clinicopathologic factors for the identification of these prognostically favorable tumors. Histopathologic features in 238 consecutive colon cancers...

  10. Identifying candidate driver genes by integrative ovarian cancer genomics data

    Science.gov (United States)

    Lu, Xinguo; Lu, Jibo

    2017-08-01

    Integrative analysis of molecular mechanics underlying cancer can distinguish interactions that cannot be revealed based on one kind of data for the appropriate diagnosis and treatment of cancer patients. Tumor samples exhibit heterogeneity in omics data, such as somatic mutations, Copy Number Variations CNVs), gene expression profiles and so on. In this paper we combined gene co-expression modules and mutation modulators separately in tumor patients to obtain the candidate driver genes for resistant and sensitive tumor from the heterogeneous data. The final list of modulators identified are well known in biological processes associated with ovarian cancer, such as CCL17, CACTIN, CCL16, CCL22, APOB, KDF1, CCL11, HNF1B, LRG1, MED1 and so on, which can help to facilitate the discovery of biomarkers, molecular diagnostics, and drug discovery.

  11. Clinicopathologic factors identify sporadic mismatch repair-defective colon cancers

    DEFF Research Database (Denmark)

    Halvarsson, Britta; Anderson, Harald; Domanska, Katarina

    2008-01-01

    Identification of sporadic mismatch repair (MMR)-defective colon cancers is increasingly demanded for decisions on adjuvant therapies. We evaluated clinicopathologic factors for the identification of these prognostically favorable tumors. Histopathologic features in 238 consecutive colon cancers...... and excluded 61.5% of the tumors from MMR testing. This clinicopathologic index thus successfully selects MMR-defective colon cancers. Udgivelsesdato: 2008-Feb...

  12. Identifying Candidate Reprogramming Genes in Mouse Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Gao, Fang; Li, Jingyu; Zhang, Heng; Yang, Xu; An, Tiezhu

    2017-08-01

    Factor-based induced reprogramming approaches have tremendous potential for human regenerative medicine, but the efficiencies of these approaches are still low. In this study, we analyzed the global transcriptional profiles of mouse induced pluripotent stem cells (miPSCs) and mouse embryonic stem cells (mESCs) from seven different labs and present here the first successful clustering according to cell type, not by lab of origin. We identified 2131 different expression genes (DEs) as candidate pluripotency-associated genes by comparing mESCs/miPSCs with somatic cells and 720 DEs between miPSCs and mESCs. Interestingly, there was a significant overlap between the two DE sets. Therefore, we defined the overlap DEs as "consensus DEs" including 313 miPSC-specific genes expressed at a higher level in miPSCs versus mESCs and 184 mESC-specific genes in total and reasoned that these may contribute to the differences in pluripotency between mESCs and miPSCs. A classification of "consensus DEs" according to their different expression levels between somatic cells and mESCs/miPSCs shows that 86% of the miPSC-specific genes are more highly expressed in somatic cells, while 73% of mESC-specific genes are highly expressed in mESCs/miPSCs, indicating that the miPSCs have not efficiently silenced the expression pattern of the somatic cells from which they are derived and failed to completely induce the genes with high expression levels in mESCs. We further revealed a strong correlation between oocyte-enriched factors and insufficiently induced mESC-specific genes and identified 11 hub genes via network analysis. In light of these findings, we postulated that these key hub genes might not only drive somatic cell nuclear transfer (SCNT) reprogramming but also augment the efficiency and quality of miPSC reprogramming.

  13. Colonoscopy can miss diverticula of the left colon identified by barium enema.

    Science.gov (United States)

    Niikura, Ryota; Nagata, Naoyoshi; Shimbo, Takuro; Akiyama, Junichi; Uemura, Naomi

    2013-04-21

    To identify the diagnostic value of colonoscopy for diverticulosis as determined by barium enema. A total of 65 patients with hematochezia who underwent colonoscopy and barium enema were analyzed, and the diagnostic value of colonoscopy for diverticula was assessed. The receiver operating characteristic area under the curve was compared in relation to age (barium enema. Colonoscopy had a sensitivity of 91% and specificity of 90%. No significant differences were found in the receiver operating characteristic area under the curve (ROC-AUC) for age group or sex. The ROC-AUC of the left colon was significantly lower than that of the right colon (0.81 vs 0.96, P = 0.02). Colonoscopy identified 486 colonic diverticula, while barium enema identified 1186. The detection ratio for the entire colon was therefore 0.41 (486/1186). The detection ratio in the left colon (0.32, 189/588) was significantly lower than that of the right colon (0.50, 297/598) (P barium enema, only half the number of colonic diverticula can be detected by colonoscopy in the entire colon and even less in the left colon.

  14. A statistical approach to identify candidate cues for nestmate recognition

    DEFF Research Database (Denmark)

    van Zweden, Jelle; Pontieri, Luigi; Pedersen, Jes Søe

    2014-01-01

    normalization, centroid,and distance calculation is most diagnostic to discriminate between NMR cues andother compounds. We find that using a “global centroid” instead of a “colony centroid”significantly improves the analysis. One reason may be that this new approach, unlikeprevious ones, provides...... than forF. exsecta, possibly due to less than ideal datasets. Nonetheless, some compound setsperformed better than others, showing that this approach can be used to identify candidatecompounds to be tested in bio-assays, and eventually crack the sophisticated code thatgoverns nestmate recognition....

  15. NDE of PWR fuel: Identifying candidates for hot cell examination

    International Nuclear Information System (INIS)

    Moon, J.E.; Bury, J.G.; Correal, O.A.; Kunishi, H.; Wilson, H.W.

    1992-05-01

    On-site examinations were performed at the Indian Point 3 and Callaway reactors to attempt to identify the leakage mechanism of several leaking fuel rods. The exams consisted of removing the leaking fuel rods from the assembly and performing a visual examination. These results, combined with other available on-site data on leaking fuel rods, were used to select fuel rods for shipment to a hot cell for detailed root cause examination. Three fuel rods from the Indian Point 3 reactor were found to be leaking due to debris-induced fretting. The examinations at Callaway were terminated prior to completion due to utility scheduler conflicts. Rods from the Callaway reactor were selected for shipment to the hot cell along with the rods from the Byron 1 and 2 and V.C. Summer reactors. The data presented in the report summarize the coolant activity history, the UT examination results, and a summary of the review of the fabrication records. The basis for the selection of the rods to be sent to the hot cells is also summarized

  16. Reverse Vaccinology: An Approach for Identifying Leptospiral Vaccine Candidates

    Directory of Open Access Journals (Sweden)

    Odir A. Dellagostin

    2017-01-01

    Full Text Available Leptospirosis is a major public health problem with an incidence of over one million human cases each year. It is a globally distributed, zoonotic disease and is associated with significant economic losses in farm animals. Leptospirosis is caused by pathogenic Leptospira spp. that can infect a wide range of domestic and wild animals. Given the inability to control the cycle of transmission among animals and humans, there is an urgent demand for a new vaccine. Inactivated whole-cell vaccines (bacterins are routinely used in livestock and domestic animals, however, protection is serovar-restricted and short-term only. To overcome these limitations, efforts have focused on the development of recombinant vaccines, with partial success. Reverse vaccinology (RV has been successfully applied to many infectious diseases. A growing number of leptospiral genome sequences are now available in public databases, providing an opportunity to search for prospective vaccine antigens using RV. Several promising leptospiral antigens were identified using this approach, although only a few have been characterized and evaluated in animal models. In this review, we summarize the use of RV for leptospirosis and discuss the need for potential improvements for the successful development of a new vaccine towards reducing the burden of human and animal leptospirosis.

  17. Pilot study on the use of data mining to identify cochlear implant candidates.

    Science.gov (United States)

    Grisel, Jedidiah J; Schafer, Erin; Lam, Anne; Griffin, Terry

    2018-05-01

    The goal of this pilot study was to determine the clinical utility of data-mining software that screens for cochlear implant (CI) candidacy. The Auditory Implant Initiative developed a software module that screens for CI candidates via integration with a software system (Noah 4) that serves as a depository for hearing test data. To identify candidates, patient audiograms from one practice were exported into the screening module. Candidates were tracked to determine if any eventually underwent implantation. After loading 4836 audiograms from the Noah 4 system, the screening module identified 558 potential CI candidates. After reviewing the data for the potential candidates, 117 were targeted and invited to an educational event. Following the event, a total of six candidates were evaluated, and two were implanted. This objective approach to identifying candidates has the potential to address the gross underutilization of CIs by removing any bias or lack of knowledge regarding the management of severe to profound sensorineural hearing loss with CIs. The screening module was an effective tool for identifying potential CI candidates at one ENT practice. On a larger scale, the screening module has the potential to impact thousands of CI candidates worldwide.

  18. Identifying molecular subtypes in human colon cancer using gene expression and DNA methylation microarray data

    OpenAIRE

    REN, ZHONGLU; WANG, WENHUI; LI, JINMING

    2015-01-01

    Identifying colon cancer subtypes based on molecular signatures may allow for a more rational, patient-specific approach to therapy in the future. Classifications using gene expression data have been attempted before with little concordance between the different studies carried out. In this study we aimed to uncover subtypes of colon cancer that have distinct biological characteristics and identify a set of novel biomarkers which could best reflect the clinical and/or biological characteristi...

  19. Identifying Canadian Teacher Candidates' Needs for Training in the Use of Inclusive Classroom Assessment

    Science.gov (United States)

    Lin, Pei-Ying; Lin, Yu-Cheng

    2015-01-01

    To identify teacher candidates' needs for training in inclusive classroom assessment, the present study investigated teacher candidates' beliefs about inclusive classroom assessments for all students educated in regular classrooms, including those with special needs and English language learners. An innovative theoretical assessment model,…

  20. A Generally Applicable Translational Strategy Identifies S100A4 as a Candidate Gene in Allergy

    DEFF Research Database (Denmark)

    Bruhn, Sören; Fang, Yu; Barrenäs, Fredrik

    2014-01-01

    The identification of diagnostic markers and therapeutic candidate genes in common diseases is complicated by the involvement of thousands of genes. We hypothesized that genes co-regulated with a key gene in allergy, IL13, would form a module that could help to identify candidate genes. We identi...

  1. CVExplorer: identifying candidate developers by mining and exploring their open source contributions.

    CSIR Research Space (South Africa)

    Greene, GJ

    2016-09-01

    Full Text Available Open source code contributions contain a large amount of technical skill information about developers, which can help to identify suitable candidates for a particular development job and therefore impact the success of a development team. We develop...

  2. Metabolomics analysis identifies intestinal microbiota-derived biomarkers of colonization resistance in clindamycin-treated mice.

    Directory of Open Access Journals (Sweden)

    Robin L P Jump

    Full Text Available The intestinal microbiota protect the host against enteric pathogens through a defense mechanism termed colonization resistance. Antibiotics excreted into the intestinal tract may disrupt colonization resistance and alter normal metabolic functions of the microbiota. We used a mouse model to test the hypothesis that alterations in levels of bacterial metabolites in fecal specimens could provide useful biomarkers indicating disrupted or intact colonization resistance after antibiotic treatment.To assess in vivo colonization resistance, mice were challenged with oral vancomycin-resistant Enterococcus or Clostridium difficile spores at varying time points after treatment with the lincosamide antibiotic clindamycin. For concurrent groups of antibiotic-treated mice, stool samples were analyzed using quantitative real-time polymerase chain reaction to assess changes in the microbiota and using non-targeted metabolic profiling. To assess whether the findings were applicable to another antibiotic class that suppresses intestinal anaerobes, similar experiments were conducted with piperacillin/tazobactam.Colonization resistance began to recover within 5 days and was intact by 12 days after clindamycin treatment, coinciding with the recovery bacteria from the families Lachnospiraceae and Ruminococcaceae, both part of the phylum Firmicutes. Clindamycin treatment caused marked changes in metabolites present in fecal specimens. Of 484 compounds analyzed, 146 (30% exhibited a significant increase or decrease in concentration during clindamycin treatment followed by recovery to baseline that coincided with restoration of in vivo colonization resistance. Identified as potential biomarkers of colonization resistance, these compounds included intermediates in carbohydrate or protein metabolism that increased (pentitols, gamma-glutamyl amino acids and inositol metabolites or decreased (pentoses, dipeptides with clindamycin treatment. Piperacillin

  3. Identifying colon cancer risk modules with better classification performance based on human signaling network.

    Science.gov (United States)

    Qu, Xiaoli; Xie, Ruiqiang; Chen, Lina; Feng, Chenchen; Zhou, Yanyan; Li, Wan; Huang, Hao; Jia, Xu; Lv, Junjie; He, Yuehan; Du, Youwen; Li, Weiguo; Shi, Yuchen; He, Weiming

    2014-10-01

    Identifying differences between normal and tumor samples from a modular perspective may help to improve our understanding of the mechanisms responsible for colon cancer. Many cancer studies have shown that signaling transduction and biological pathways are disturbed in disease states, and expression profiles can distinguish variations in diseases. In this study, we integrated a weighted human signaling network and gene expression profiles to select risk modules associated with tumor conditions. Risk modules as classification features by our method had a better classification performance than other methods, and one risk module for colon cancer had a good classification performance for distinguishing between normal/tumor samples and between tumor stages. All genes in the module were annotated to the biological process of positive regulation of cell proliferation, and were highly associated with colon cancer. These results suggested that these genes might be the potential risk genes for colon cancer. Copyright © 2013. Published by Elsevier Inc.

  4. Identifying molecular subtypes in human colon cancer using gene expression and DNA methylation microarray data.

    Science.gov (United States)

    Ren, Zhonglu; Wang, Wenhui; Li, Jinming

    2016-02-01

    Identifying colon cancer subtypes based on molecular signatures may allow for a more rational, patient-specific approach to therapy in the future. Classifications using gene expression data have been attempted before with little concordance between the different studies carried out. In this study we aimed to uncover subtypes of colon cancer that have distinct biological characteristics and identify a set of novel biomarkers which could best reflect the clinical and/or biological characteristics of each subtype. Clustering analysis and discriminant analysis were utilized to discover the subtypes in two different molecular levels on 153 colon cancer samples from The Cancer Genome Atlas (TCGA) Data Portal. At gene expression level, we identified two major subtypes, ECL1 (expression cluster 1) and ECL2 (expression cluster 2) and a list of signature genes. Due to the heterogeneity of colon cancer, the subtype ECL1 can be further subdivided into three nested subclasses, and HOTAIR were found upregulated in subclass 2. At DNA methylation level, we uncovered three major subtypes, MCL1 (methylation cluster 1), MCL2 (methylation cluster 2) and MCL3 (methylation cluster 3). We found only three subtypes of CpG island methylator phenotype (CIMP) in colon cancer instead of the four subtypes in the previous reports, and we found no sufficient evidence to subdivide MCL3 into two distinct subgroups.

  5. Three surgical planes identified in laparoscopic complete mesocolic excision for right-sided colon cancer.

    Science.gov (United States)

    Zhu, Da-Jian; Chen, Xiao-Wu; OuYang, Man-Zhao; Lu, Yan

    2016-01-12

    Complete mesocolic excision provides a correct anatomical plane for colon cancer surgery. However, manifestation of the surgical plane during laparoscopic complete mesocolic excision versus in computed tomography images remains to be examined. Patients who underwent laparoscopic complete mesocolic excision for right-sided colon cancer underwent an abdominal computed tomography scan. The spatial relationship of the intraoperative surgical planes were examined, and then computed tomography reconstruction methods were applied. The resulting images were analyzed. In 44 right-sided colon cancer patients, the surgical plane for laparoscopic complete mesocolic excision was found to be composed of three surgical planes that were identified by computed tomography imaging with cross-sectional multiplanar reconstruction, maximum intensity projection, and volume reconstruction. For the operations performed, the mean bleeding volume was 73±32.3 ml and the mean number of harvested lymph nodes was 22±9.7. The follow-up period ranged from 6-40 months (mean 21.2), and only two patients had distant metastases. The laparoscopic complete mesocolic excision surgical plane for right-sided colon cancer is composed of three surgical planes. When these surgical planes were identified, laparoscopic complete mesocolic excision was a safe and effective procedure for the resection of colon cancer.

  6. Eliciting, Identifying, Interpreting, and Responding to Students' Ideas: Teacher Candidates' Growth in Formative Assessment Practices

    Science.gov (United States)

    Gotwals, Amelia Wenk; Birmingham, Daniel

    2016-06-01

    With the goal of helping teacher candidates become well-started beginners, it is important that methods courses in teacher education programs focus on high-leverage practices. Using responsive teaching practices, specifically eliciting, identifying, interpreting, and responding to students' science ideas (i.e., formative assessment), can be used to support all students in learning science successfully. This study follows seven secondary science teacher candidates in a yearlong practice-based methods course. Course assignments (i.e., plans for and reflections on teaching) as well as teaching videos were analyzed using a recursive qualitative approach. In this paper, we present themes and patterns in teacher candidates' abilities to elicit, identify, interpret, and respond to students' ideas. Specifically, we found that those teacher candidates who grew in the ways in which they elicited students' ideas from fall to spring were also those who were able to adopt a more balanced reflection approach (considering both teacher and student moves). However, we found that even the teacher candidates who grew in these practices did not move toward seeing students' ideas as nuanced; rather, they saw students' ideas in a dichotomous fashion: right or wrong. We discuss implications for teacher preparation, specifically for how to promote productive reflection and tools for better understanding students' ideas.

  7. Candidate gene linkage approach to identify DNA variants that predispose to preterm birth

    DEFF Research Database (Denmark)

    Bream, Elise N A; Leppellere, Cara R; Cooper, Margaret E

    2013-01-01

    Background:The aim of this study was to identify genetic variants contributing to preterm birth (PTB) using a linkage candidate gene approach.Methods:We studied 99 single-nucleotide polymorphisms (SNPs) for 33 genes in 257 families with PTBs segregating. Nonparametric and parametric analyses were...... through the infant and/or the mother in the etiology of PTB....

  8. A cross-species genetic analysis identifies candidate genes for mouse anxiety and human bipolar disorder

    Directory of Open Access Journals (Sweden)

    David G Ashbrook

    2015-07-01

    Full Text Available Bipolar disorder (BD is a significant neuropsychiatric disorder with a lifetime prevalence of ~1%. To identify genetic variants underlying BD genome-wide association studies (GWAS have been carried out. While many variants of small effect associated with BD have been identified few have yet been confirmed, partly because of the low power of GWAS due to multiple comparisons being made. Complementary mapping studies using murine models have identified genetic variants for behavioral traits linked to BD, often with high power, but these identified regions often contain too many genes for clear identification of candidate genes. In the current study we have aligned human BD GWAS results and mouse linkage studies to help define and evaluate candidate genes linked to BD, seeking to use the power of the mouse mapping with the precision of GWAS. We use quantitative trait mapping for open field test and elevated zero maze data in the largest mammalian model system, the BXD recombinant inbred mouse population, to identify genomic regions associated with these BD-like phenotypes. We then investigate these regions in whole genome data from the Psychiatric Genomics Consortium’s bipolar disorder GWAS to identify candidate genes associated with BD. Finally we establish the biological relevance and pathways of these genes in a comprehensive systems genetics analysis.We identify four genes associated with both mouse anxiety and human BD. While TNR is a novel candidate for BD, we can confirm previously suggested associations with CMYA5, MCTP1 and RXRG. A cross-species, systems genetics analysis shows that MCTP1, RXRG and TNR coexpress with genes linked to psychiatric disorders and identify the striatum as a potential site of action. CMYA5, MCTP1, RXRG and TNR are associated with mouse anxiety and human BD. We hypothesize that MCTP1, RXRG and TNR influence intercellular signaling in the striatum.

  9. BAYESIAN ANALYSIS TO IDENTIFY NEW STAR CANDIDATES IN NEARBY YOUNG STELLAR KINEMATIC GROUPS

    International Nuclear Information System (INIS)

    Malo, Lison; Doyon, René; Lafrenière, David; Artigau, Étienne; Gagné, Jonathan; Baron, Frédérique; Riedel, Adric

    2013-01-01

    We present a new method based on a Bayesian analysis to identify new members of nearby young kinematic groups. The analysis minimally takes into account the position, proper motion, magnitude, and color of a star, but other observables can be readily added (e.g., radial velocity, distance). We use this method to find new young low-mass stars in the β Pictoris and AB Doradus moving groups and in the TW Hydrae, Tucana-Horologium, Columba, Carina, and Argus associations. Starting from a sample of 758 mid-K to mid-M (K5V-M5V) stars showing youth indicators such as Hα and X-ray emission, our analysis yields 214 new highly probable low-mass members of the kinematic groups analyzed. One is in TW Hydrae, 37 in β Pictoris, 17 in Tucana-Horologium, 20 in Columba, 6 in Carina, 50 in Argus, 32 in AB Doradus, and the remaining 51 candidates are likely young but have an ambiguous membership to more than one association. The false alarm rate for new candidates is estimated to be 5% for β Pictoris and TW Hydrae, 10% for Tucana-Horologium, Columba, Carina, and Argus, and 14% for AB Doradus. Our analysis confirms the membership of 58 stars proposed in the literature. Firm membership confirmation of our new candidates will require measurement of their radial velocity (predicted by our analysis), parallax, and lithium 6708 Å equivalent width. We have initiated these follow-up observations for a number of candidates, and we have identified two stars (2MASSJ01112542+1526214, 2MASSJ05241914-1601153) as very strong candidate members of the β Pictoris moving group and one strong candidate member (2MASSJ05332558-5117131) of the Tucana-Horologium association; these three stars have radial velocity measurements confirming their membership and lithium detections consistent with young age.

  10. Phosphoproteomic Analysis Identifies Signaling Pathways Regulated by Curcumin in Human Colon Cancer Cells.

    Science.gov (United States)

    Sato, Tatsuhiro; Higuchi, Yutaka; Shibagaki, Yoshio; Hattori, Seisuke

    2017-09-01

    Curcumin, a major polyphenol of the spice turmeric, acts as a potent chemopreventive and chemotherapeutic agent in several cancer types, including colon cancer. Although various proteins have been shown to be affected by curcumin, how curcumin exerts its anticancer activity is not fully understood. Phosphoproteomic analyses were performed using SW480 and SW620 human colon cancer cells to identify curcumin-affected signaling pathways. Curcumin inhibited the growth of the two cell lines in a dose-dependent manner. Thirty-nine curcumin-regulated phosphoproteins were identified, five of which are involved in cancer signaling pathways. Detailed analyses revealed that the mTORC1 and p53 signaling pathways are main targets of curcumin. Our results provide insight into the molecular mechanisms of the anticancer activities of curcumin and future molecular targets for its clinical application. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  11. An Approach to Identify and Characterize a Subunit Candidate Shigella Vaccine Antigen.

    Science.gov (United States)

    Pore, Debasis; Chakrabarti, Manoj K

    2016-01-01

    Shigellosis remains a serious issue throughout the developing countries, particularly in children under the age of 5. Numerous strategies have been tested to develop vaccines targeting shigellosis; unfortunately despite several years of extensive research, no safe, effective, and inexpensive vaccine against shigellosis is available so far. Here, we illustrate in detail an approach to identify and establish immunogenic outer membrane proteins from Shigella flexneri 2a as subunit vaccine candidates.

  12. Exome sequencing of a large family identifies potential candidate genes contributing risk to bipolar disorder.

    Science.gov (United States)

    Zhang, Tianxiao; Hou, Liping; Chen, David T; McMahon, Francis J; Wang, Jen-Chyong; Rice, John P

    2018-03-01

    Bipolar disorder is a mental illness with lifetime prevalence of about 1%. Previous genetic studies have identified multiple chromosomal linkage regions and candidate genes that might be associated with bipolar disorder. The present study aimed to identify potential susceptibility variants for bipolar disorder using 6 related case samples from a four-generation family. A combination of exome sequencing and linkage analysis was performed to identify potential susceptibility variants for bipolar disorder. Our study identified a list of five potential candidate genes for bipolar disorder. Among these five genes, GRID1(Glutamate Receptor Delta-1 Subunit), which was previously reported to be associated with several psychiatric disorders and brain related traits, is particularly interesting. Variants with functional significance in this gene were identified from two cousins in our bipolar disorder pedigree. Our findings suggest a potential role for these genes and the related rare variants in the onset and development of bipolar disorder in this one family. Additional research is needed to replicate these findings and evaluate their patho-biological significance. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Genome-wide association study identifies candidate genes for starch content regulation in maize kernels

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    Na Liu

    2016-07-01

    Full Text Available Kernel starch content is an important trait in maize (Zea mays L. as it accounts for 65% to 75% of the dry kernel weight and positively correlates with seed yield. A number of starch synthesis-related genes have been identified in maize in recent years. However, many loci underlying variation in starch content among maize inbred lines still remain to be identified. The current study is a genome-wide association study that used a set of 263 maize inbred lines. In this panel, the average kernel starch content was 66.99%, ranging from 60.60% to 71.58% over the three study years. These inbred lines were genotyped with the SNP50 BeadChip maize array, which is comprised of 56,110 evenly spaced, random SNPs. Population structure was controlled by a mixed linear model (MLM as implemented in the software package TASSEL. After the statistical analyses, four SNPs were identified as significantly associated with starch content (P ≤ 0.0001, among which one each are located on chromosomes 1 and 5 and two are on chromosome 2. Furthermore, 77 candidate genes associated with starch synthesis were found within the 100-kb intervals containing these four QTLs, and four highly associated genes were within 20-kb intervals of the associated SNPs. Among the four genes, Glucose-1-phosphate adenylyltransferase (APS1; Gene ID GRMZM2G163437 is known as an important regulator of kernel starch content. The identified SNPs, QTLs, and candidate genes may not only be readily used for germplasm improvement by marker-assisted selection in breeding, but can also elucidate the genetic basis of starch content. Further studies on these identified candidate genes may help determine the molecular mechanisms regulating kernel starch content in maize and other important cereal crops.

  14. Identifying Novel Candidate Genes Related to Apoptosis from a Protein-Protein Interaction Network

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    Baoman Wang

    2015-01-01

    Full Text Available Apoptosis is the process of programmed cell death (PCD that occurs in multicellular organisms. This process of normal cell death is required to maintain the balance of homeostasis. In addition, some diseases, such as obesity, cancer, and neurodegenerative diseases, can be cured through apoptosis, which produces few side effects. An effective comprehension of the mechanisms underlying apoptosis will be helpful to prevent and treat some diseases. The identification of genes related to apoptosis is essential to uncover its underlying mechanisms. In this study, a computational method was proposed to identify novel candidate genes related to apoptosis. First, protein-protein interaction information was used to construct a weighted graph. Second, a shortest path algorithm was applied to the graph to search for new candidate genes. Finally, the obtained genes were filtered by a permutation test. As a result, 26 genes were obtained, and we discuss their likelihood of being novel apoptosis-related genes by collecting evidence from published literature.

  15. Transcriptomic Analysis Using Olive Varieties and Breeding Progenies Identifies Candidate Genes Involved in Plant Architecture.

    Science.gov (United States)

    González-Plaza, Juan J; Ortiz-Martín, Inmaculada; Muñoz-Mérida, Antonio; García-López, Carmen; Sánchez-Sevilla, José F; Luque, Francisco; Trelles, Oswaldo; Bejarano, Eduardo R; De La Rosa, Raúl; Valpuesta, Victoriano; Beuzón, Carmen R

    2016-01-01

    Plant architecture is a critical trait in fruit crops that can significantly influence yield, pruning, planting density and harvesting. Little is known about how plant architecture is genetically determined in olive, were most of the existing varieties are traditional with an architecture poorly suited for modern growing and harvesting systems. In the present study, we have carried out microarray analysis of meristematic tissue to compare expression profiles of olive varieties displaying differences in architecture, as well as seedlings from their cross pooled on the basis of their sharing architecture-related phenotypes. The microarray used, previously developed by our group has already been applied to identify candidates genes involved in regulating juvenile to adult transition in the shoot apex of seedlings. Varieties with distinct architecture phenotypes and individuals from segregating progenies displaying opposite architecture features were used to link phenotype to expression. Here, we identify 2252 differentially expressed genes (DEGs) associated to differences in plant architecture. Microarray results were validated by quantitative RT-PCR carried out on genes with functional annotation likely related to plant architecture. Twelve of these genes were further analyzed in individual seedlings of the corresponding pool. We also examined Arabidopsis mutants in putative orthologs of these targeted candidate genes, finding altered architecture for most of them. This supports a functional conservation between species and potential biological relevance of the candidate genes identified. This study is the first to identify genes associated to plant architecture in olive, and the results obtained could be of great help in future programs aimed at selecting phenotypes adapted to modern cultivation practices in this species.

  16. Auto-Vetting Transiting Planet Candidates Identified by the Kepler Pipeline

    Science.gov (United States)

    Jenkins, Jon M.; McCauliff, Sean; Burke, Christopher; Seader, Shawn; Twicken, Joseph; Klaus, Todd; Sanderfer, Dwight; Srivastava, Ashok; Haas, Michael R.

    2014-04-01

    The Kepler Mission simultaneously measures the brightness of more than 150,000 stars every 29.4 minutes primarily for the purpose of transit photometry. Over the course of its 3.5-year primary mission Kepler has observed over 190,000 distinct stars, announcing 2,321 planet candidates, 2,165 eclipsing binaries, and 105 confirmed planets. As Kepler moves into its 4-year extended mission, the total number of transit-like features identified in the light curves has increased to as many as ~18,000. This number of signals has become intractable for human beings to inspect by eye in a thorough and timely fashion. To mitigate this problem we are developing machine learning approaches to perform the task of reviewing the diagnostics for each transit signal candidate to establish a preliminary list of planetary candidates ranked from most credible to least credible. Our preliminary results indicate that random forests can classify potential transiting planet signatures with an accuracy of more than 98.6% as measured by the area under a receiver-operating curve.

  17. Exome Sequencing and Linkage Analysis Identified Novel Candidate Genes in Recessive Intellectual Disability Associated with Ataxia.

    Science.gov (United States)

    Jazayeri, Roshanak; Hu, Hao; Fattahi, Zohreh; Musante, Luciana; Abedini, Seyedeh Sedigheh; Hosseini, Masoumeh; Wienker, Thomas F; Ropers, Hans Hilger; Najmabadi, Hossein; Kahrizi, Kimia

    2015-10-01

    Intellectual disability (ID) is a neuro-developmental disorder which causes considerable socio-economic problems. Some ID individuals are also affected by ataxia, and the condition includes different mutations affecting several genes. We used whole exome sequencing (WES) in combination with homozygosity mapping (HM) to identify the genetic defects in five consanguineous families among our cohort study, with two affected children with ID and ataxia as major clinical symptoms. We identified three novel candidate genes, RIPPLY1, MRPL10, SNX14, and a new mutation in known gene SURF1. All are autosomal genes, except RIPPLY1, which is located on the X chromosome. Two are housekeeping genes, implicated in transcription and translation regulation and intracellular trafficking, and two encode mitochondrial proteins. The pathogenesis of these variants was evaluated by mutation classification, bioinformatic methods, review of medical and biological relevance, co-segregation studies in the particular family, and a normal population study. Linkage analysis and exome sequencing of a small number of affected family members is a powerful new technique which can be used to decrease the number of candidate genes in heterogenic disorders such as ID, and may even identify the responsible gene(s).

  18. Epidermal growth factor gene is a newly identified candidate gene for gout

    OpenAIRE

    Lin Han; Chunwei Cao; Zhaotong Jia; Shiguo Liu; Zhen Liu; Ruosai Xin; Can Wang; Xinde Li; Wei Ren; Xuefeng Wang; Changgui Li

    2016-01-01

    Chromosome 4q25 has been identified as a genomic region associated with gout. However, the associations of gout with the genes in this region have not yet been confirmed. Here, we performed two-stage analysis to determine whether variations in candidate genes in the 4q25 region are associated with gout in a male Chinese Han population. We first evaluated 96 tag single nucleotide polymorphisms (SNPs) in eight inflammatory/immune pathway- or glucose/lipid metabolism-related genes in the 4q25 re...

  19. Structural identifiability analyses of candidate models for in vitro Pitavastatin hepatic uptake.

    Science.gov (United States)

    Grandjean, Thomas R B; Chappell, Michael J; Yates, James W T; Evans, Neil D

    2014-05-01

    In this paper a review of the application of four different techniques (a version of the similarity transformation approach for autonomous uncontrolled systems, a non-differential input/output observable normal form approach, the characteristic set differential algebra and a recent algebraic input/output relationship approach) to determine the structural identifiability of certain in vitro nonlinear pharmacokinetic models is provided. The Organic Anion Transporting Polypeptide (OATP) substrate, Pitavastatin, is used as a probe on freshly isolated animal and human hepatocytes. Candidate pharmacokinetic non-linear compartmental models have been derived to characterise the uptake process of Pitavastatin. As a prerequisite to parameter estimation, structural identifiability analyses are performed to establish that all unknown parameters can be identified from the experimental observations available. Copyright © 2013. Published by Elsevier Ireland Ltd.

  20. Selection on plant male function genes identifies candidates for reproductive isolation of yellow monkeyflowers.

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    Jan E Aagaard

    Full Text Available Understanding the genetic basis of reproductive isolation promises insight into speciation and the origins of biological diversity. While progress has been made in identifying genes underlying barriers to reproduction that function after fertilization (post-zygotic isolation, we know much less about earlier acting pre-zygotic barriers. Of particular interest are barriers involved in mating and fertilization that can evolve extremely rapidly under sexual selection, suggesting they may play a prominent role in the initial stages of reproductive isolation. A significant challenge to the field of speciation genetics is developing new approaches for identification of candidate genes underlying these barriers, particularly among non-traditional model systems. We employ powerful proteomic and genomic strategies to study the genetic basis of conspecific pollen precedence, an important component of pre-zygotic reproductive isolation among yellow monkeyflowers (Mimulus spp. resulting from male pollen competition. We use isotopic labeling in combination with shotgun proteomics to identify more than 2,000 male function (pollen tube proteins within maternal reproductive structures (styles of M. guttatus flowers where pollen competition occurs. We then sequence array-captured pollen tube exomes from a large outcrossing population of M. guttatus, and identify those genes with evidence of selective sweeps or balancing selection consistent with their role in pollen competition. We also test for evidence of positive selection on these genes more broadly across yellow monkeyflowers, because a signal of adaptive divergence is a common feature of genes causing reproductive isolation. Together the molecular evolution studies identify 159 pollen tube proteins that are candidate genes for conspecific pollen precedence. Our work demonstrates how powerful proteomic and genomic tools can be readily adapted to non-traditional model systems, allowing for genome-wide screens

  1. Novel candidate genes and regions for childhood apraxia of speech identified by array comparative genomic hybridization.

    Science.gov (United States)

    Laffin, Jennifer J S; Raca, Gordana; Jackson, Craig A; Strand, Edythe A; Jakielski, Kathy J; Shriberg, Lawrence D

    2012-11-01

    The goal of this study was to identify new candidate genes and genomic copy-number variations associated with a rare, severe, and persistent speech disorder termed childhood apraxia of speech. Childhood apraxia of speech is the speech disorder segregating with a mutation in FOXP2 in a multigenerational London pedigree widely studied for its role in the development of speech-language in humans. A total of 24 participants who were suspected to have childhood apraxia of speech were assessed using a comprehensive protocol that samples speech in challenging contexts. All participants met clinical-research criteria for childhood apraxia of speech. Array comparative genomic hybridization analyses were completed using a customized 385K Nimblegen array (Roche Nimblegen, Madison, WI) with increased coverage of genes and regions previously associated with childhood apraxia of speech. A total of 16 copy-number variations with potential consequences for speech-language development were detected in 12 or half of the 24 participants. The copy-number variations occurred on 10 chromosomes, 3 of which had two to four candidate regions. Several participants were identified with copy-number variations in two to three regions. In addition, one participant had a heterozygous FOXP2 mutation and a copy-number variation on chromosome 2, and one participant had a 16p11.2 microdeletion and copy-number variations on chromosomes 13 and 14. Findings support the likelihood of heterogeneous genomic pathways associated with childhood apraxia of speech.

  2. Association Analysis Suggests SOD2 as a Newly Identified Candidate Gene Associated With Leprosy Susceptibility.

    Science.gov (United States)

    Ramos, Geovana Brotto; Salomão, Heloisa; Francio, Angela Schneider; Fava, Vinícius Medeiros; Werneck, Renata Iani; Mira, Marcelo Távora

    2016-08-01

    Genetic studies have identified several genes and genomic regions contributing to the control of host susceptibility to leprosy. Here, we test variants of the positional and functional candidate gene SOD2 for association with leprosy in 2 independent population samples. Family-based analysis revealed an association between leprosy and allele G of marker rs295340 (P = .042) and borderline evidence of an association between leprosy and alleles C and A of markers rs4880 (P = .077) and rs5746136 (P = .071), respectively. Findings were validated in an independent case-control sample for markers rs295340 (P = .049) and rs4880 (P = .038). These results suggest SOD2 as a newly identified gene conferring susceptibility to leprosy. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  3. Identifying candidate agents for lung adenocarcinoma by walking the human interactome

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    Sun Y

    2016-09-01

    Full Text Available Yajiao Sun,1 Ranran Zhang,2 Zhe Jiang,1 Rongyao Xia,1 Jingwen Zhang,1 Jing Liu,1 Fuhui Chen1 1Department of Respiratory, The Second Affiliated Hospital of Harbin Medical University, 2Department of Respiratory, Harbin First Hospital, Harbin, People’s Republic of China Abstract: Despite recent advances in therapeutic strategies for lung cancer, mortality is still increasing. Therefore, there is an urgent need to identify effective novel drugs. In the present study, we implement drug repositioning for lung adenocarcinoma (LUAD by a bioinformatics method followed by experimental validation. We first identified differentially expressed genes between LUAD tissues and nontumor tissues from RNA sequencing data obtained from The Cancer Genome Atlas database. Then, candidate small molecular drugs were ranked according to the effect of their targets on differentially expressed genes of LUAD by a random walk with restart algorithm in protein–protein interaction networks. Our method identified some potentially novel agents for LUAD besides those that had been previously reported (eg, hesperidin. Finally, we experimentally verified that atracurium, one of the potential agents, could induce A549 cells death in non-small-cell lung cancer-derived A549 cells by an MTT assay, acridine orange and ethidium bromide staining, and electron microscopy. Furthermore, Western blot assays demonstrated that atracurium upregulated the proapoptotic Bad and Bax proteins, downregulated the antiapoptotic p-Bad and Bcl-2 proteins, and enhanced caspase-3 activity. It could also reduce the expression of p53 and p21Cip1/Waf1 in A549 cells. In brief, the candidate agents identified by our approach may provide greater insights into improving the therapeutic status of LUAD. Keywords: lung adenocarcinoma, drug repositioning, bioinformatics, protein–protein interaction network, atracurium

  4. Exome sequencing of Pakistani consanguineous families identifies 30 novel candidate genes for recessive intellectual disability.

    Science.gov (United States)

    Riazuddin, S; Hussain, M; Razzaq, A; Iqbal, Z; Shahzad, M; Polla, D L; Song, Y; van Beusekom, E; Khan, A A; Tomas-Roca, L; Rashid, M; Zahoor, M Y; Wissink-Lindhout, W M; Basra, M A R; Ansar, M; Agha, Z; van Heeswijk, K; Rasheed, F; Van de Vorst, M; Veltman, J A; Gilissen, C; Akram, J; Kleefstra, T; Assir, M Z; Grozeva, D; Carss, K; Raymond, F L; O'Connor, T D; Riazuddin, S A; Khan, S N; Ahmed, Z M; de Brouwer, A P M; van Bokhoven, H; Riazuddin, S

    2017-11-01

    Intellectual disability (ID) is a clinically and genetically heterogeneous disorder, affecting 1-3% of the general population. Although research into the genetic causes of ID has recently gained momentum, identification of pathogenic mutations that cause autosomal recessive ID (ARID) has lagged behind, predominantly due to non-availability of sizeable families. Here we present the results of exome sequencing in 121 large consanguineous Pakistani ID families. In 60 families, we identified homozygous or compound heterozygous DNA variants in a single gene, 30 affecting reported ID genes and 30 affecting novel candidate ID genes. Potential pathogenicity of these alleles was supported by co-segregation with the phenotype, low frequency in control populations and the application of stringent bioinformatics analyses. In another eight families segregation of multiple pathogenic variants was observed, affecting 19 genes that were either known or are novel candidates for ID. Transcriptome profiles of normal human brain tissues showed that the novel candidate ID genes formed a network significantly enriched for transcriptional co-expression (P<0.0001) in the frontal cortex during fetal development and in the temporal-parietal and sub-cortex during infancy through adulthood. In addition, proteins encoded by 12 novel ID genes directly interact with previously reported ID proteins in six known pathways essential for cognitive function (P<0.0001). These results suggest that disruptions of temporal parietal and sub-cortical neurogenesis during infancy are critical to the pathophysiology of ID. These findings further expand the existing repertoire of genes involved in ARID, and provide new insights into the molecular mechanisms and the transcriptome map of ID.

  5. Candidate genes involved in the biosynthesis of triterpenoid saponins in Platycodon grandiflorum identified by transcriptome analysis

    Directory of Open Access Journals (Sweden)

    Chunhua eMa

    2016-05-01

    Full Text Available Background: Platycodon grandiflorum is the only species in the genus Platycodon of the family Campanulaceae, which has been traditionally used as a medicinal plant for its lung-heat-clearing, antitussive, and expectorant properties in China, Japanese and Korean. Oleanane-type triterpenoid saponins were the main chemical components of P. grandiflorum and platycodin D was the abundant and main bioactive component, but little is known about their biosynthesis in plants. Hence, P. grandiflorum is an ideal medicinal plant for studying the biosynthesis of Oleanane-type saponins. In addition, the genomic information of this important herbal plant is unavailable.Principal Findings:A total of 58,580,566 clean reads were obtained, which were assembled into 34,053 unigenes, with an average length of 936 bp and N50 of 1,661 bp by analyzing the transcriptome data of P. grandiflorum. Among these 34,053 unigenes, 22,409 unigenes (65.80% were annotated based on the information available from public databases, including Nr, NCBI, Swiss-Prot, KOG and KEGG. Furthermore, 21 candidate cytochrome P450 genes and 17 candidate UDP-glycosyltransferase genes most likely involved in triterpenoid saponins biosynthesis pathway were discovered from the transcriptome sequencing of P. grandiflorum. In addition, 10,626 SSRs were identified based on the transcriptome data, which would provide abundant candidates of molecular markers for genetic diversity and genetic map for this medicinal plant.Conclusion:The genomic data obtained from P. grandiflorum, especially the identification of putative genes involved in triterpenoid saponins biosynthesis pathway, will facilitate our understanding of the biosynthesis of triterpenoid saponins at molecular level.

  6. Experimental infections with Mycoplasma agalactiae identify key factors involved in host-colonization.

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    Eric Baranowski

    Full Text Available Mechanisms underlying pathogenic processes in mycoplasma infections are poorly understood, mainly because of limited sequence similarities with classical, bacterial virulence factors. Recently, large-scale transposon mutagenesis in the ruminant pathogen Mycoplasma agalactiae identified the NIF locus, including nifS and nifU, as essential for mycoplasma growth in cell culture, while dispensable in axenic media. To evaluate the importance of this locus in vivo, the infectivity of two knock-out mutants was tested upon experimental infection in the natural host. In this model, the parental PG2 strain was able to establish a systemic infection in lactating ewes, colonizing various body sites such as lymph nodes and the mammary gland, even when inoculated at low doses. In these PG2-infected ewes, we observed over the course of infection (i the development of a specific antibody response and (ii dynamic changes in expression of M. agalactiae surface variable proteins (Vpma, with multiple Vpma profiles co-existing in the same animal. In contrast and despite a sensitive model, none of the knock-out mutants were able to survive and colonize the host. The extreme avirulent phenotype of the two mutants was further supported by the absence of an IgG response in inoculated animals. The exact role of the NIF locus remains to be elucidated but these data demonstrate that it plays a key role in the infectious process of M. agalactiae and most likely of other pathogenic mycoplasma species as many carry closely related homologs.

  7. Identifying the Relationship of Teacher Candidates' Humor Styles with Anxiety and Self-Compassion Levels

    Science.gov (United States)

    Aydin, Aydan

    2015-01-01

    Problem Statement: Teacher candidates who will soon be responsible for educating the future generations should possess certain characteristics. Specific teacher candidates should have specific characteristics taken into consideration: pre-school and primary teacher candidates should be seen as role models by younger students; psychological…

  8. Extended tracts of homozygosity identify novel candidate genes associated with late onset Alzheimer’s Disease

    Science.gov (United States)

    Nalls, M. A.; Guerreiro, R. J.; Simon-Sanchez, J.; Bras, J. T.; Traynor, B. J.; Gibbs, J. R.; Launer, L.; Hardy, J.; Singleton, A. B.

    2010-01-01

    Large tracts of extended homozygosity are more prevalent in outbred populations than previously thought. With the advent of high-density genotyping platforms, regions of extended homozygosity can be accurately located allowing for the identification of rare recessive risk variants contributing to disease. We compared measures of extended homozygosity (greater than 1 megabase in length) in a population of 837 late onset Alzheimer’s disease (LOAD) cases and 550 controls. In our analyses, we identify one homozygous region on chromosome 8 that is significantly associated with LOAD after adjusting for multiple testing. This region contains seven genes from which the most biologically plausible candidates are STAR, EIF4EBP1 and ADRB3. We also compared the total numbers of homozygous runs and the total length of these runs between cases and controls, showing a suggestive difference in these measures (p-values 0.052-0.062). This research suggests a recessive component to the etiology of LOAD. PMID:19271249

  9. Sequence-Based Introgression Mapping Identifies Candidate White Mold Tolerance Genes in Common Bean

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    Sujan Mamidi

    2016-07-01

    Full Text Available White mold, caused by the necrotrophic fungus (Lib. de Bary, is a major disease of common bean ( L.. WM7.1 and WM8.3 are two quantitative trait loci (QTL with major effects on tolerance to the pathogen. Advanced backcross populations segregating individually for either of the two QTL, and a recombinant inbred (RI population segregating for both QTL were used to fine map and confirm the genetic location of the QTL. The QTL intervals were physically mapped using the reference common bean genome sequence, and the physical intervals for each QTL were further confirmed by sequence-based introgression mapping. Using whole-genome sequence data from susceptible and tolerant DNA pools, introgressed regions were identified as those with significantly higher numbers of single-nucleotide polymorphisms (SNPs relative to the whole genome. By combining the QTL and SNP data, WM7.1 was located to a 660-kb region that contained 41 gene models on the proximal end of chromosome Pv07, while the WM8.3 introgression was narrowed to a 1.36-Mb region containing 70 gene models. The most polymorphic candidate gene in the WM7.1 region encodes a BEACH-domain protein associated with apoptosis. Within the WM8.3 interval, a receptor-like protein with the potential to recognize pathogen effectors was the most polymorphic gene. The use of gene and sequence-based mapping identified two candidate genes whose putative functions are consistent with the current model of pathogenicity.

  10. A Proteomic Approach Identifies Candidate Early Biomarkers to Predict Severe Dengue in Children.

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    Dang My Nhi

    2016-02-01

    Full Text Available Severe dengue with severe plasma leakage (SD-SPL is the most frequent of dengue severe form. Plasma biomarkers for early predictive diagnosis of SD-SPL are required in the primary clinics for the prevention of dengue death.Among 63 confirmed dengue pediatric patients recruited, hospital based longitudinal study detected six SD-SPL and ten dengue with warning sign (DWS. To identify the specific proteins increased or decreased in the SD-SPL plasma obtained 6-48 hours before the shock compared with the DWS, the isobaric tags for relative and absolute quantification (iTRAQ technology was performed using four patients each group. Validation was undertaken in 6 SD-SPL and 10 DWS patients.Nineteen plasma proteins exhibited significantly different relative concentrations (p<0.05, with five over-expressed and fourteen under-expressed in SD-SPL compared with DWS. The individual protein was classified to either blood coagulation, vascular regulation, cellular transport-related processes or immune response. The immunoblot quantification showed angiotensinogen and antithrombin III significantly increased in SD-SPL whole plasma of early stage compared with DWS subjects. Even using this small number of samples, antithrombin III predicted SD-SPL before shock occurrence with accuracy.Proteins identified here may serve as candidate predictive markers to diagnose SD-SPL for timely clinical management. Since the number of subjects are small, so further studies are needed to confirm all these biomarkers.

  11. Exome sequencing in 53 sporadic cases of schizophrenia identifies 18 putative candidate genes.

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    Michel Guipponi

    Full Text Available Schizophrenia (SCZ is a severe, debilitating mental illness which has a significant genetic component. The identification of genetic factors related to SCZ has been challenging and these factors remain largely unknown. To evaluate the contribution of de novo variants (DNVs to SCZ, we sequenced the exomes of 53 individuals with sporadic SCZ and of their non-affected parents. We identified 49 DNVs, 18 of which were predicted to alter gene function, including 13 damaging missense mutations, 2 conserved splice site mutations, 2 nonsense mutations, and 1 frameshift deletion. The average number of exonic DNV per proband was 0.88, which corresponds to an exonic point mutation rate of 1.7×10(-8 per nucleotide per generation. The non-synonymous-to-synonymous mutation ratio of 2.06 did not differ from neutral expectations. Overall, this study provides a list of 18 putative candidate genes for sporadic SCZ, and when combined with the results of similar reports, identifies a second proband carrying a non-synonymous DNV in the RGS12 gene.

  12. Genomic profiling identifies GATA6 as a candidate oncogene amplified in pancreatobiliary cancer.

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    Kevin A Kwei

    2008-05-01

    Full Text Available Pancreatobiliary cancers have among the highest mortality rates of any cancer type. Discovering the full spectrum of molecular genetic alterations may suggest new avenues for therapy. To catalogue genomic alterations, we carried out array-based genomic profiling of 31 exocrine pancreatic cancers and 6 distal bile duct cancers, expanded as xenografts to enrich the tumor cell fraction. We identified numerous focal DNA amplifications and deletions, including in 19% of pancreatobiliary cases gain at cytoband 18q11.2, a locus uncommonly amplified in other tumor types. The smallest shared amplification at 18q11.2 included GATA6, a transcriptional regulator previously linked to normal pancreas development. When amplified, GATA6 was overexpressed at both the mRNA and protein levels, and strong immunostaining was observed in 25 of 54 (46% primary pancreatic cancers compared to 0 of 33 normal pancreas specimens surveyed. GATA6 expression in xenografts was associated with specific microarray gene-expression patterns, enriched for GATA binding sites and mitochondrial oxidative phosphorylation activity. siRNA mediated knockdown of GATA6 in pancreatic cancer cell lines with amplification led to reduced cell proliferation, cell cycle progression, and colony formation. Our findings indicate that GATA6 amplification and overexpression contribute to the oncogenic phenotypes of pancreatic cancer cells, and identify GATA6 as a candidate lineage-specific oncogene in pancreatobiliary cancer, with implications for novel treatment strategies.

  13. Gene expression signature analysis identifies vorinostat as a candidate therapy for gastric cancer.

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    Sofie Claerhout

    Full Text Available Gastric cancer continues to be one of the deadliest cancers in the world and therefore identification of new drugs targeting this type of cancer is thus of significant importance. The purpose of this study was to identify and validate a therapeutic agent which might improve the outcomes for gastric cancer patients in the future.Using microarray technology, we generated a gene expression profile of human gastric cancer-specific genes from human gastric cancer tissue samples. We used this profile in the Broad Institute's Connectivity Map analysis to identify candidate therapeutic compounds for gastric cancer. We found the histone deacetylase inhibitor vorinostat as the lead compound and thus a potential therapeutic drug for gastric cancer. Vorinostat induced both apoptosis and autophagy in gastric cancer cell lines. Pharmacological and genetic inhibition of autophagy however, increased the therapeutic efficacy of vorinostat, indicating that a combination of vorinostat with autophagy inhibitors may therapeutically be more beneficial. Moreover, gene expression analysis of gastric cancer identified a collection of genes (ITGB5, TYMS, MYB, APOC1, CBX5, PLA2G2A, and KIF20A whose expression was elevated in gastric tumor tissue and downregulated more than 2-fold by vorinostat treatment in gastric cancer cell lines. In contrast, SCGB2A1, TCN1, CFD, APLP1, and NQO1 manifested a reversed pattern.We showed that analysis of gene expression signature may represent an emerging approach to discover therapeutic agents for gastric cancer, such as vorinostat. The observation of altered gene expression after vorinostat treatment may provide the clue to identify the molecular mechanism of vorinostat and those patients likely to benefit from vorinostat treatment.

  14. Gene Expression Signature Analysis Identifies Vorinostat as a Candidate Therapy for Gastric Cancer

    Science.gov (United States)

    Choi, Woonyoung; Park, Yun-Yong; Kim, KyoungHyun; Kim, Sang-Bae; Lee, Ju-Seog; Mills, Gordon B.; Cho, Jae Yong

    2011-01-01

    Background Gastric cancer continues to be one of the deadliest cancers in the world and therefore identification of new drugs targeting this type of cancer is thus of significant importance. The purpose of this study was to identify and validate a therapeutic agent which might improve the outcomes for gastric cancer patients in the future. Methodology/Principal Findings Using microarray technology, we generated a gene expression profile of human gastric cancer–specific genes from human gastric cancer tissue samples. We used this profile in the Broad Institute's Connectivity Map analysis to identify candidate therapeutic compounds for gastric cancer. We found the histone deacetylase inhibitor vorinostat as the lead compound and thus a potential therapeutic drug for gastric cancer. Vorinostat induced both apoptosis and autophagy in gastric cancer cell lines. Pharmacological and genetic inhibition of autophagy however, increased the therapeutic efficacy of vorinostat, indicating that a combination of vorinostat with autophagy inhibitors may therapeutically be more beneficial. Moreover, gene expression analysis of gastric cancer identified a collection of genes (ITGB5, TYMS, MYB, APOC1, CBX5, PLA2G2A, and KIF20A) whose expression was elevated in gastric tumor tissue and downregulated more than 2-fold by vorinostat treatment in gastric cancer cell lines. In contrast, SCGB2A1, TCN1, CFD, APLP1, and NQO1 manifested a reversed pattern. Conclusions/Significance We showed that analysis of gene expression signature may represent an emerging approach to discover therapeutic agents for gastric cancer, such as vorinostat. The observation of altered gene expression after vorinostat treatment may provide the clue to identify the molecular mechanism of vorinostat and those patients likely to benefit from vorinostat treatment. PMID:21931799

  15. Large-scale evaluation of candidate genes identifies associations between VEGF polymorphisms and bladder cancer risk.

    Directory of Open Access Journals (Sweden)

    Montserrat García-Closas

    2007-02-01

    Full Text Available Common genetic variation could alter the risk for developing bladder cancer. We conducted a large-scale evaluation of single nucleotide polymorphisms (SNPs in candidate genes for cancer to identify common variants that influence bladder cancer risk. An Illumina GoldenGate assay was used to genotype 1,433 SNPs within or near 386 genes in 1,086 cases and 1,033 controls in Spain. The most significant finding was in the 5' UTR of VEGF (rs25648, p for likelihood ratio test, 2 degrees of freedom = 1 x 10(-5. To further investigate the region, we analyzed 29 additional SNPs in VEGF, selected to saturate the promoter and 5' UTR and to tag common genetic variation in this gene. Three additional SNPs in the promoter region (rs833052, rs1109324, and rs1547651 were associated with increased risk for bladder cancer: odds ratio (95% confidence interval: 2.52 (1.06-5.97, 2.74 (1.26-5.98, and 3.02 (1.36-6.63, respectively; and a polymorphism in intron 2 (rs3024994 was associated with reduced risk: 0.65 (0.46-0.91. Two of the promoter SNPs and the intron 2 SNP showed linkage disequilibrium with rs25648. Haplotype analyses revealed three blocks of linkage disequilibrium with significant associations for two blocks including the promoter and 5' UTR (global p = 0.02 and 0.009, respectively. These findings are biologically plausible since VEGF is critical in angiogenesis, which is important for tumor growth, its elevated expression in bladder tumors correlates with tumor progression, and specific 5' UTR haplotypes have been shown to influence promoter activity. Associations between bladder cancer risk and other genes in this report were not robust based on false discovery rate calculations. In conclusion, this large-scale evaluation of candidate cancer genes has identified common genetic variants in the regulatory regions of VEGF that could be associated with bladder cancer risk.

  16. Prediction potential of candidate biomarker sets identified and validated on gene expression data from multiple datasets

    Directory of Open Access Journals (Sweden)

    Karacali Bilge

    2007-10-01

    Full Text Available Abstract Background Independently derived expression profiles of the same biological condition often have few genes in common. In this study, we created populations of expression profiles from publicly available microarray datasets of cancer (breast, lymphoma and renal samples linked to clinical information with an iterative machine learning algorithm. ROC curves were used to assess the prediction error of each profile for classification. We compared the prediction error of profiles correlated with molecular phenotype against profiles correlated with relapse-free status. Prediction error of profiles identified with supervised univariate feature selection algorithms were compared to profiles selected randomly from a all genes on the microarray platform and b a list of known disease-related genes (a priori selection. We also determined the relevance of expression profiles on test arrays from independent datasets, measured on either the same or different microarray platforms. Results Highly discriminative expression profiles were produced on both simulated gene expression data and expression data from breast cancer and lymphoma datasets on the basis of ER and BCL-6 expression, respectively. Use of relapse-free status to identify profiles for prognosis prediction resulted in poorly discriminative decision rules. Supervised feature selection resulted in more accurate classifications than random or a priori selection, however, the difference in prediction error decreased as the number of features increased. These results held when decision rules were applied across-datasets to samples profiled on the same microarray platform. Conclusion Our results show that many gene sets predict molecular phenotypes accurately. Given this, expression profiles identified using different training datasets should be expected to show little agreement. In addition, we demonstrate the difficulty in predicting relapse directly from microarray data using supervised machine

  17. Identifying the Administrative Dispositions Most Preferred by Urban School Leaders and School Leadership Candidates

    Science.gov (United States)

    Pregot, Michael

    2016-01-01

    This research study delves into the newly crafted ISSLC national school leadership standards asking current school leaders and school leadership candidates to prioritize their perceived level of importance of 20 administrative dispositions. 128 school principals and 165 school leadership candidates in the NYC schools responded to an electronic…

  18. Candidíase vulvovaginal: sintomatologia, fatores de risco e colonização anal concomitante Vulvovaginal candidiasis: symptomatology, risk factors and concomitant anal colonization

    Directory of Open Access Journals (Sweden)

    Antônio Arildo Reginaldo de Holanda

    2007-01-01

    and results of anal culture, to identify the frequency of species of Candida albicans and non-C. albicans, and to correlate anal and vaginal colonization. METHODS: a total of 99 patients were included with suspected vulvovaginal candidiasis, from Natal, Brazil, between May 2003 and May 2005, totalling 294 collections. The clinical material, obtained by vaginal and anal swabs, was seeded on CHROMagar Candida®. The yeasts were identified using the classic method, in addition to the growth test at 42º and 45ºC and the Hypertonic Saboraud broth test. Symptomatology, risk factors and anal colonization were assessed according to positive or negative culture for Candida spp. The cultures positive for C. albicans at the two sites were compared with other results encountered. Yates’ chi2 test and Fisher’s exact test were used for statistical analysis. RESULTS: the most frequent was C. albicans in 69% of the cases. Wearing tight and/or synthetic underclothing, the presence of allergic diseases, the occurrence of itching, leukorrhea and hyperemia showed a significant association with positive culture for Candida spp in the vagina. The chance of a patient with positive anal colonization to present with concomitant positive vaginal colonization was 2.8 and 4.9 times greater for Candida spp and C. albicans, respectively. The risk of a patient with anal culture positive for C. albicans to present with positive vaginal colonization was 3.7 times greater when compared to non-C. albicans species. CONCLUSIONS: the most common species was C. albicans, and a relevant association between vaginal cultures positive for Candida spp and the use of tight and/or synthetic underclothing, allergic diseases, the occurrence of pruritus, leukorrhea and erythema was observed (p<0.05. Positive anal colonization concomitant with vaginal colonization was significant, suggesting possible vaginal contamination from the anus.

  19. Back to the sea twice: identifying candidate plant genes for molecular evolution to marine life

    Directory of Open Access Journals (Sweden)

    Reusch Thorsten BH

    2011-01-01

    Full Text Available Abstract Background Seagrasses are a polyphyletic group of monocotyledonous angiosperms that have adapted to a completely submerged lifestyle in marine waters. Here, we exploit two collections of expressed sequence tags (ESTs of two wide-spread and ecologically important seagrass species, the Mediterranean seagrass Posidonia oceanica (L. Delile and the eelgrass Zostera marina L., which have independently evolved from aquatic ancestors. This replicated, yet independent evolutionary history facilitates the identification of traits that may have evolved in parallel and are possible instrumental candidates for adaptation to a marine habitat. Results In our study, we provide the first quantitative perspective on molecular adaptations in two seagrass species. By constructing orthologous gene clusters shared between two seagrasses (Z. marina and P. oceanica and eight distantly related terrestrial angiosperm species, 51 genes could be identified with detection of positive selection along the seagrass branches of the phylogenetic tree. Characterization of these positively selected genes using KEGG pathways and the Gene Ontology uncovered that these genes are mostly involved in translation, metabolism, and photosynthesis. Conclusions These results provide first insights into which seagrass genes have diverged from their terrestrial counterparts via an initial aquatic stage characteristic of the order and to the derived fully-marine stage characteristic of seagrasses. We discuss how adaptive changes in these processes may have contributed to the evolution towards an aquatic and marine existence.

  20. Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder

    Science.gov (United States)

    Yuen, Ryan KC; Merico, Daniele; Bookman, Matt; Howe, Jennifer L; Thiruvahindrapuram, Bhooma; Patel, Rohan V; Whitney, Joe; Deflaux, Nicole; Bingham, Jonathan; Wang, Zhuozhi; Pellecchia, Giovanna; Buchanan, Janet A; Walker, Susan; Marshall, Christian R; Uddin, Mohammed; Zarrei, Mehdi; Deneault, Eric; D’Abate, Lia; Chan, Ada JS; Koyanagi, Stephanie; Paton, Tara; Pereira, Sergio L; Hoang, Ny; Engchuan, Worrawat; Higginbotham, Edward J; Ho, Karen; Lamoureux, Sylvia; Li, Weili; MacDonald, Jeffrey R; Nalpathamkalam, Thomas; Sung, Wilson WL; Tsoi, Fiona J; Wei, John; Xu, Lizhen; Tasse, Anne-Marie; Kirby, Emily; Van Etten, William; Twigger, Simon; Roberts, Wendy; Drmic, Irene; Jilderda, Sanne; Modi, Bonnie MacKinnon; Kellam, Barbara; Szego, Michael; Cytrynbaum, Cheryl; Weksberg, Rosanna; Zwaigenbaum, Lonnie; Woodbury-Smith, Marc; Brian, Jessica; Senman, Lili; Iaboni, Alana; Doyle-Thomas, Krissy; Thompson, Ann; Chrysler, Christina; Leef, Jonathan; Savion-Lemieux, Tal; Smith, Isabel M; Liu, Xudong; Nicolson, Rob; Seifer, Vicki; Fedele, Angie; Cook, Edwin H; Dager, Stephen; Estes, Annette; Gallagher, Louise; Malow, Beth A; Parr, Jeremy R; Spence, Sarah J; Vorstman, Jacob; Frey, Brendan J; Robinson, James T; Strug, Lisa J; Fernandez, Bridget A; Elsabbagh, Mayada; Carter, Melissa T; Hallmayer, Joachim; Knoppers, Bartha M; Anagnostou, Evdokia; Szatmari, Peter; Ring, Robert H; Glazer, David; Pletcher, Mathew T; Scherer, Stephen W

    2017-01-01

    We are performing whole genome sequencing (WGS) of families with Autism Spectrum Disorder (ASD) to build a resource, named MSSNG, to enable the sub-categorization of phenotypes and underlying genetic factors involved. Here, we report WGS of 5,205 samples from families with ASD, accompanied by clinical information, creating a database accessible in a cloud platform, and through an internet portal with controlled access. We found an average of 73.8 de novo single nucleotide variants and 12.6 de novo insertion/deletions (indels) or copy number variations (CNVs) per ASD subject. We identified 18 new candidate ASD-risk genes such as MED13 and PHF3, and found that participants bearing mutations in susceptibility genes had significantly lower adaptive ability (p=6×10−4). In 294/2,620 (11.2%) of ASD cases, a molecular basis could be determined and 7.2% of these carried CNV/chromosomal abnormalities, emphasizing the importance of detecting all forms of genetic variation as diagnostic and therapeutic targets in ASD. PMID:28263302

  1. Epidermal growth factor gene is a newly identified candidate gene for gout

    Science.gov (United States)

    Han, Lin; Cao, Chunwei; Jia, Zhaotong; Liu, Shiguo; Liu, Zhen; Xin, Ruosai; Wang, Can; Li, Xinde; Ren, Wei; Wang, Xuefeng; Li, Changgui

    2016-01-01

    Chromosome 4q25 has been identified as a genomic region associated with gout. However, the associations of gout with the genes in this region have not yet been confirmed. Here, we performed two-stage analysis to determine whether variations in candidate genes in the 4q25 region are associated with gout in a male Chinese Han population. We first evaluated 96 tag single nucleotide polymorphisms (SNPs) in eight inflammatory/immune pathway- or glucose/lipid metabolism-related genes in the 4q25 region in 480 male gout patients and 480 controls. The SNP rs12504538, located in the elongation of very-long-chain-fatty-acid-like family member 6 gene (Elovl6), was found to be associated with gout susceptibility (Padjusted = 0.00595). In the second stage of analysis, we performed fine mapping analysis of 93 tag SNPs in Elovl6 and in the epidermal growth factor gene (EGF) and its flanking regions in 1017 male patients gout and 1897 healthy male controls. We observed a significant association between the T allele of EGF rs2298999 and gout (odds ratio = 0.77, 95% confidence interval = 0.67–0.88, Padjusted = 6.42 × 10−3). These results provide the first evidence for an association between the EGF rs2298999 C/T polymorphism and gout. Our findings should be validated in additional populations. PMID:27506295

  2. Epidermal growth factor gene is a newly identified candidate gene for gout.

    Science.gov (United States)

    Han, Lin; Cao, Chunwei; Jia, Zhaotong; Liu, Shiguo; Liu, Zhen; Xin, Ruosai; Wang, Can; Li, Xinde; Ren, Wei; Wang, Xuefeng; Li, Changgui

    2016-08-10

    Chromosome 4q25 has been identified as a genomic region associated with gout. However, the associations of gout with the genes in this region have not yet been confirmed. Here, we performed two-stage analysis to determine whether variations in candidate genes in the 4q25 region are associated with gout in a male Chinese Han population. We first evaluated 96 tag single nucleotide polymorphisms (SNPs) in eight inflammatory/immune pathway- or glucose/lipid metabolism-related genes in the 4q25 region in 480 male gout patients and 480 controls. The SNP rs12504538, located in the elongation of very-long-chain-fatty-acid-like family member 6 gene (Elovl6), was found to be associated with gout susceptibility (Padjusted = 0.00595). In the second stage of analysis, we performed fine mapping analysis of 93 tag SNPs in Elovl6 and in the epidermal growth factor gene (EGF) and its flanking regions in 1017 male patients gout and 1897 healthy male controls. We observed a significant association between the T allele of EGF rs2298999 and gout (odds ratio = 0.77, 95% confidence interval = 0.67-0.88, Padjusted = 6.42 × 10(-3)). These results provide the first evidence for an association between the EGF rs2298999 C/T polymorphism and gout. Our findings should be validated in additional populations.

  3. Whole-exome sequencing identifies novel candidate predisposition genes for familial polycythemia vera.

    Science.gov (United States)

    Hirvonen, Elina A M; Pitkänen, Esa; Hemminki, Kari; Aaltonen, Lauri A; Kilpivaara, Outi

    2017-04-20

    Polycythemia vera (PV), characterized by massive production of erythrocytes, is one of the myeloproliferative neoplasms. Most patients carry a somatic gain-of-function mutation in JAK2, c.1849G > T (p.Val617Phe), leading to constitutive activation of JAK-STAT signaling pathway. Familial clustering is also observed occasionally, but high-penetrance predisposition genes to PV have remained unidentified. We studied the predisposition to PV by exome sequencing (three cases) in a Finnish PV family with four patients. The 12 shared variants (maximum allowed minor allele frequency  G (p.Phe418Leu) in ZXDC, c.1931C > G (p.Pro644Arg) in ATN1, and c.701G > A (p.Arg234Gln) in LRRC3. We also observed a rare, predicted benign germline variant c.2912C > G (p.Ala971Gly) in BCORL1 in all four patients. Somatic mutations in BCORL1 have been reported in myeloid malignancies. We further screened the variants in eight PV patients in six other Finnish families, but no other carriers were found. Exome sequencing provides a powerful tool for the identification of novel variants, and understanding the familial predisposition of diseases. This is the first report on Finnish familial PV cases, and we identified three novel candidate variants that may predispose to the disease.

  4. Back to the sea twice: identifying candidate plant genes for molecular evolution to marine life.

    Science.gov (United States)

    Wissler, Lothar; Codoñer, Francisco M; Gu, Jenny; Reusch, Thorsten B H; Olsen, Jeanine L; Procaccini, Gabriele; Bornberg-Bauer, Erich

    2011-01-12

    Seagrasses are a polyphyletic group of monocotyledonous angiosperms that have adapted to a completely submerged lifestyle in marine waters. Here, we exploit two collections of expressed sequence tags (ESTs) of two wide-spread and ecologically important seagrass species, the Mediterranean seagrass Posidonia oceanica (L.) Delile and the eelgrass Zostera marina L., which have independently evolved from aquatic ancestors. This replicated, yet independent evolutionary history facilitates the identification of traits that may have evolved in parallel and are possible instrumental candidates for adaptation to a marine habitat. In our study, we provide the first quantitative perspective on molecular adaptations in two seagrass species. By constructing orthologous gene clusters shared between two seagrasses (Z. marina and P. oceanica) and eight distantly related terrestrial angiosperm species, 51 genes could be identified with detection of positive selection along the seagrass branches of the phylogenetic tree. Characterization of these positively selected genes using KEGG pathways and the Gene Ontology uncovered that these genes are mostly involved in translation, metabolism, and photosynthesis. These results provide first insights into which seagrass genes have diverged from their terrestrial counterparts via an initial aquatic stage characteristic of the order and to the derived fully-marine stage characteristic of seagrasses. We discuss how adaptive changes in these processes may have contributed to the evolution towards an aquatic and marine existence.

  5. Integrated database for identifying candidate genes for Aspergillus flavus resistance in maize.

    Science.gov (United States)

    Kelley, Rowena Y; Gresham, Cathy; Harper, Jonathan; Bridges, Susan M; Warburton, Marilyn L; Hawkins, Leigh K; Pechanova, Olga; Peethambaran, Bela; Pechan, Tibor; Luthe, Dawn S; Mylroie, J E; Ankala, Arunkanth; Ozkan, Seval; Henry, W B; Williams, W P

    2010-10-07

    Aspergillus flavus Link:Fr, an opportunistic fungus that produces aflatoxin, is pathogenic to maize and other oilseed crops. Aflatoxin is a potent carcinogen, and its presence markedly reduces the value of grain. Understanding and enhancing host resistance to A. flavus infection and/or subsequent aflatoxin accumulation is generally considered an efficient means of reducing grain losses to aflatoxin. Different proteomic, genomic and genetic studies of maize (Zea mays L.) have generated large data sets with the goal of identifying genes responsible for conferring resistance to A. flavus, or aflatoxin. In order to maximize the usage of different data sets in new studies, including association mapping, we have constructed a relational database with web interface integrating the results of gene expression, proteomic (both gel-based and shotgun), Quantitative Trait Loci (QTL) genetic mapping studies, and sequence data from the literature to facilitate selection of candidate genes for continued investigation. The Corn Fungal Resistance Associated Sequences Database (CFRAS-DB) (http://agbase.msstate.edu/) was created with the main goal of identifying genes important to aflatoxin resistance. CFRAS-DB is implemented using MySQL as the relational database management system running on a Linux server, using an Apache web server, and Perl CGI scripts as the web interface. The database and the associated web-based interface allow researchers to examine many lines of evidence (e.g. microarray, proteomics, QTL studies, SNP data) to assess the potential role of a gene or group of genes in the response of different maize lines to A. flavus infection and subsequent production of aflatoxin by the fungus. CFRAS-DB provides the first opportunity to integrate data pertaining to the problem of A. flavus and aflatoxin resistance in maize in one resource and to support queries across different datasets. The web-based interface gives researchers different query options for mining the database

  6. Use of a combination of CEA and tumor budding to identify high-risk patients with stage II colon cancer.

    Science.gov (United States)

    Du, Changzheng; Xue, Weicheng; Dou, Fangyuan; Peng, Yifan; Yao, Yunfeng; Zhao, Jun; Gu, Jin

    2017-07-24

    High-risk patients with stage II colon cancer may benefit from adjuvant chemotherapy, but identifying this patient population can be difficult. We assessed the prognosis value for predicting tumor progression in patients with stage II colon cancer, of a panel of 2 biomarkers for colon cancer: tumor budding and preoperative carcinoembryonic antigen (CEA). Consecutive patients (N = 134) with stage II colon cancer who underwent curative surgery from 2000 to 2007 were included. Multivariate analysis was used to evaluate the association of CEA and tumor budding grade with 5-year disease-free survival (DFS). The prognostic accuracy of CEA, tumor budding grade and the combination of both (CEA-budding panel) was determined. The study found that both CEA and tumor budding grade were associated with 5-year DFS. The prognostic accuracy for disease progression was higher for the CEA-budding panel (82.1%) than either CEA (70.9%) or tumor budding grade (72.4%) alone. The findings indicate that the combination of CEA levels and tumor budding grade has greater prognostic value for identifying patients with stage II colon cancer who are at high-risk for disease progression, than either marker alone.

  7. Contig Maps and Genomic Sequencing Identify Candidate Genes in the Usher 1C Locus

    Science.gov (United States)

    Higgins, Michael J.; Day, Colleen D.; Smilinich, Nancy J.; Ni, L.; Cooper, Paul R.; Nowak, Norma J.; Davies, Chris; de Jong, Pieter J.; Hejtmancik, Fielding; Evans, Glen A.; Smith, Richard J.H.; Shows, Thomas B.

    1998-01-01

    Usher syndrome 1C (USH1C) is a congenital condition manifesting profound hearing loss, the absence of vestibular function, and eventual retinal degeneration. The USH1C locus has been mapped genetically to a 2- to 3-cM interval in 11p14–15.1 between D11S899 and D11S861. In an effort to identify the USH1C disease gene we have isolated the region between these markers in yeast artificial chromosomes (YACs) using a combination of STS content mapping and Alu–PCR hybridization. The YAC contig is ∼3.5 Mb and has located several other loci within this interval, resulting in the order CEN-LDHA-SAA1-TPH-D11S1310-(D11S1888/KCNC1)-MYOD1-D11S902D11S921-D11S1890-TEL. Subsequent haplotyping and homozygosity analysis refined the location of the disease gene to a 400-kb interval between D11S902 and D11S1890 with all affected individuals being homozygous for the internal marker D11S921. To facilitate gene identification, the critical region has been converted into P1 artificial chromosome (PAC) clones using sequence-tagged sites (STSs) mapped to the YAC contig, Alu–PCR products generated from the YACs, and PAC end probes. A contig of >50 PAC clones has been assembled between D11S1310 and D11S1890, confirming the order of markers used in haplotyping. Three PAC clones representing nearly two-thirds of the USH1C critical region have been sequenced. PowerBLAST analysis identified six clusters of expressed sequence tags (ESTs), two known genes (BIR,SUR1) mapped previously to this region, and a previously characterized but unmapped gene NEFA (DNA binding/EF hand/acidic amino-acid-rich). GRAIL analysis identified 11 CpG islands and 73 exons of excellent quality. These data allowed the construction of a transcription map for the USH1C critical region, consisting of three known genes and six or more novel transcripts. Based on their map location, these loci represent candidate disease loci for USH1C. The NEFA gene was assessed as the USH1C locus by the sequencing of an amplified NEFA

  8. Algorithms to identify colonic ischemia, complications of constipation and irritable bowel syndrome in medical claims data: development and validation.

    Science.gov (United States)

    Sands, Bruce E; Duh, Mei-Sheng; Cali, Clorinda; Ajene, Anuli; Bohn, Rhonda L; Miller, David; Cole, J Alexander; Cook, Suzanne F; Walker, Alexander M

    2006-01-01

    A challenge in the use of insurance claims databases for epidemiologic research is accurate identification and verification of medical conditions. This report describes the development and validation of claims-based algorithms to identify colonic ischemia, hospitalized complications of constipation, and irritable bowel syndrome (IBS). From the research claims databases of a large healthcare company, we selected at random 120 potential cases of IBS and 59 potential cases each of colonic ischemia and hospitalized complications of constipation. We sought the written medical records and were able to abstract 107, 57, and 51 records, respectively. We established a 'true' case status for each subject by applying standard clinical criteria to the available chart data. Comparing the insurance claims histories to the assigned case status, we iteratively developed, tested, and refined claims-based algorithms that would capture the diagnoses obtained from the medical records. We set goals of high specificity for colonic ischemia and hospitalized complications of constipation, and high sensitivity for IBS. The resulting algorithms substantially improved on the accuracy achievable from a naïve acceptance of the diagnostic codes attached to insurance claims. The specificities for colonic ischemia and serious complications of constipation were 87.2 and 92.7%, respectively, and the sensitivity for IBS was 98.9%. U.S. commercial insurance claims data appear to be usable for the study of colonic ischemia, IBS, and serious complications of constipation. (c) 2005 John Wiley & Sons, Ltd.

  9. A Systematic Approach to Identify Candidate Transcription Factors that Control Cell Identity

    Directory of Open Access Journals (Sweden)

    Ana C. D’Alessio

    2015-11-01

    Full Text Available Hundreds of transcription factors (TFs are expressed in each cell type, but cell identity can be induced through the activity of just a small number of core TFs. Systematic identification of these core TFs for a wide variety of cell types is currently lacking and would establish a foundation for understanding the transcriptional control of cell identity in development, disease, and cell-based therapy. Here, we describe a computational approach that generates an atlas of candidate core TFs for a broad spectrum of human cells. The potential impact of the atlas was demonstrated via cellular reprogramming efforts where candidate core TFs proved capable of converting human fibroblasts to retinal pigment epithelial-like cells. These results suggest that candidate core TFs from the atlas will prove a useful starting point for studying transcriptional control of cell identity and reprogramming in many human cell types.

  10. Positional RNA-Seq identifies candidate genes for phenotypic engineering of sexual traits

    NARCIS (Netherlands)

    Arbore, Roberto; Sekii, Kiyono; Beisel, Christian; Ladurner, Peter; Berezikov, Eugene; Schaerer, Lukas

    2015-01-01

    Introduction: RNA interference (RNAi) of trait-specific genes permits the manipulation of specific phenotypic traits ("phenotypic engineering") and thus represents a powerful tool to test trait function in evolutionary studies. The identification of suitable candidate genes, however, often relies on

  11. Oral administration of live Shigella vaccine candidates in rhesus monkeys show no evidence of competition for colonization and immunogenicity between different serotypes.

    Science.gov (United States)

    Ranallo, R T; Kaminski, R; Baqar, S; Dutta, M; Lugo-Roman, L A; Boren, T; Barnoy, S; Venkatesan, M M

    2014-03-26

    Live oral monovalent Shigella flexneri 2a vaccine candidates as well as bivalent formulations with Shigella sonnei were evaluated in a rhesus monkey model for colonization and immunogenicity. Freshly harvested suspensions of S. flexneri 2a vaccine candidates WRSf2G12 and WRSf2G15 as well as S. sonnei vaccine candidate WRSs3 were nasogastrically administered to groups of rhesus monkeys, Macaca mulatta, either in a monovalent form or when combined with each other. The animals were monitored daily for physical well-being, stools were subjected to quantitative colony immunoblot assays for bacterial excretion and blood and stools were evaluated for humoral and mucosal immune responses. No clinical symptoms were noted in any group of animals and the vaccine candidates were excreted robustly for 48-72h without significant changes in either the magnitude or duration of excretion when given as a monovalent or as bivalent mixtures. Similarly, immunological interferences were not apparent in the magnitude of humoral and mucosal immune responses observed toward Shigella-specific antigens when monkeys were fed monovalent or bivalent formulations. These results predict that a multivalent live oral vaccine of more than one serotype can have a favorable outcome for protection against shigellosis. Published by Elsevier Ltd.

  12. Can suitable candidates for levodopa/carbidopa intestinal gel therapy be identified using current evidence?

    Directory of Open Access Journals (Sweden)

    Maria José Catalán

    2017-09-01

    In recent years, strong evidence has supported the use of LCIG in treating motor fluctuations associated with APD, and several clinical studies provide emerging evidence for additional benefits of LCIG treatment in certain patients. This article provides an overview of the published literature on the benefits, limitations, and drawbacks of LCIG in relation to PD symptoms, the psychosocial impact of the disease, and the quality of life of patients, with the aim of determining candidates for whom treatment with LCIG would be beneficial. According to current evidence, patients with APD (defined as inability to achieve optimal control of the disease with conventional oral treatment, a relatively well-preserved cognitive-behavioral status, and good family/caregiver would count as suitable candidates for LCIG treatment. Contraindications in the opinion of the authors are severe dementia and active psychosis.

  13. Candidate luminal B breast cancer genes identified by genome, gene expression and DNA methylation profiling.

    Directory of Open Access Journals (Sweden)

    Stéphanie Cornen

    Full Text Available Breast cancers (BCs of the luminal B subtype are estrogen receptor-positive (ER+, highly proliferative, resistant to standard therapies and have a poor prognosis. To better understand this subtype we compared DNA copy number aberrations (CNAs, DNA promoter methylation, gene expression profiles, and somatic mutations in nine selected genes, in 32 luminal B tumors with those observed in 156 BCs of the other molecular subtypes. Frequent CNAs included 8p11-p12 and 11q13.1-q13.2 amplifications, 7q11.22-q34, 8q21.12-q24.23, 12p12.3-p13.1, 12q13.11-q24.11, 14q21.1-q23.1, 17q11.1-q25.1, 20q11.23-q13.33 gains and 6q14.1-q24.2, 9p21.3-p24,3, 9q21.2, 18p11.31-p11.32 losses. A total of 237 and 101 luminal B-specific candidate oncogenes and tumor suppressor genes (TSGs presented a deregulated expression in relation with their CNAs, including 11 genes previously reported associated with endocrine resistance. Interestingly, 88% of the potential TSGs are located within chromosome arm 6q, and seven candidate oncogenes are potential therapeutic targets. A total of 100 candidate oncogenes were validated in a public series of 5,765 BCs and the overexpression of 67 of these was associated with poor survival in luminal tumors. Twenty-four genes presented a deregulated expression in relation with a high DNA methylation level. FOXO3, PIK3CA and TP53 were the most frequent mutated genes among the nine tested. In a meta-analysis of next-generation sequencing data in 875 BCs, KCNB2 mutations were associated with luminal B cases while candidate TSGs MDN1 (6q15 and UTRN (6q24, were mutated in this subtype. In conclusion, we have reported luminal B candidate genes that may play a role in the development and/or hormone resistance of this aggressive subtype.

  14. Genome-Wide Association Study with Sequence Variants Identifies Candidate Genes for Mastitis Resistance in Dairy Cattle

    DEFF Research Database (Denmark)

    Sahana, Goutam; Guldbrandtsen, Bernt; Bendixen, Christian

    Six genomic regions affecting clinical mastitis were identified through a GWAS study with imputed BovineHD chip genotype data in the Nordic Holstein cattle population. The association analyses were carried out using a SNP-by-SNP analysis by fitting the regression of allele dosage and a polygenic...... Effect Predictor (VEP) vers. 2.6 using ENSEMBL vers. 67 databases. Candidate polymorphisms affecting clinical mastitis were selected based on their association with the traits and functional annotations. A strong positional candidate gene for mastitis resistance on chromosome-6 is the NPFFR2 which...... Factor Receptor Alpha (LIFR) emerged as a strong candidate gene for mastitis resistance. The LIFR gene is involved in acute phase response and is expressed in saliva and mammary gland....

  15. Cancer in silico drug discovery: a systems biology tool for identifying candidate drugs to target specific molecular tumor subtypes.

    Science.gov (United States)

    San Lucas, F Anthony; Fowler, Jerry; Chang, Kyle; Kopetz, Scott; Vilar, Eduardo; Scheet, Paul

    2014-12-01

    Large-scale cancer datasets such as The Cancer Genome Atlas (TCGA) allow researchers to profile tumors based on a wide range of clinical and molecular characteristics. Subsequently, TCGA-derived gene expression profiles can be analyzed with the Connectivity Map (CMap) to find candidate drugs to target tumors with specific clinical phenotypes or molecular characteristics. This represents a powerful computational approach for candidate drug identification, but due to the complexity of TCGA and technology differences between CMap and TCGA experiments, such analyses are challenging to conduct and reproduce. We present Cancer in silico Drug Discovery (CiDD; scheet.org/software), a computational drug discovery platform that addresses these challenges. CiDD integrates data from TCGA, CMap, and Cancer Cell Line Encyclopedia (CCLE) to perform computational drug discovery experiments, generating hypotheses for the following three general problems: (i) determining whether specific clinical phenotypes or molecular characteristics are associated with unique gene expression signatures; (ii) finding candidate drugs to repress these expression signatures; and (iii) identifying cell lines that resemble the tumors being studied for subsequent in vitro experiments. The primary input to CiDD is a clinical or molecular characteristic. The output is a biologically annotated list of candidate drugs and a list of cell lines for in vitro experimentation. We applied CiDD to identify candidate drugs to treat colorectal cancers harboring mutations in BRAF. CiDD identified EGFR and proteasome inhibitors, while proposing five cell lines for in vitro testing. CiDD facilitates phenotype-driven, systematic drug discovery based on clinical and molecular data from TCGA. ©2014 American Association for Cancer Research.

  16. ICSNPathway: identify candidate causal SNPs and pathways from genome-wide association study by one analytical framework.

    Science.gov (United States)

    Zhang, Kunlin; Chang, Suhua; Cui, Sijia; Guo, Liyuan; Zhang, Liuyan; Wang, Jing

    2011-07-01

    Genome-wide association study (GWAS) is widely utilized to identify genes involved in human complex disease or some other trait. One key challenge for GWAS data interpretation is to identify causal SNPs and provide profound evidence on how they affect the trait. Currently, researches are focusing on identification of candidate causal variants from the most significant SNPs of GWAS, while there is lack of support on biological mechanisms as represented by pathways. Although pathway-based analysis (PBA) has been designed to identify disease-related pathways by analyzing the full list of SNPs from GWAS, it does not emphasize on interpreting causal SNPs. To our knowledge, so far there is no web server available to solve the challenge for GWAS data interpretation within one analytical framework. ICSNPathway is developed to identify candidate causal SNPs and their corresponding candidate causal pathways from GWAS by integrating linkage disequilibrium (LD) analysis, functional SNP annotation and PBA. ICSNPathway provides a feasible solution to bridge the gap between GWAS and disease mechanism study by generating hypothesis of SNP → gene → pathway(s). The ICSNPathway server is freely available at http://icsnpathway.psych.ac.cn/.

  17. Next generation sequencing identifies abnormal Y chromosome and candidate causal variants in premature ovarian failure patients.

    Science.gov (United States)

    Lee, Yujung; Kim, Changshin; Park, YoungJoon; Pyun, Jung-A; Kwack, KyuBum

    2016-12-01

    Premature ovarian failure (POF) is characterized by heterogeneous genetic causes such as chromosomal abnormalities and variants in causal genes. Recently, development of techniques made next generation sequencing (NGS) possible to detect genome wide variants including chromosomal abnormalities. Among 37 Korean POF patients, XY karyotype with distal part deletions of Y chromosome, Yp11.32-31 and Yp12 end part, was observed in two patients through NGS. Six deleterious variants in POF genes were also detected which might explain the pathogenesis of POF with abnormalities in the sex chromosomes. Additionally, the two POF patients had no mutation in SRY but three non-synonymous variants were detected in genes regarding sex reversal. These findings suggest candidate causes of POF and sex reversal and show the propriety of NGS to approach the heterogeneous pathogenesis of POF. Copyright © 2016 Elsevier Inc. All rights reserved.

  18. A stratified transcriptomics analysis of polygenic fat and lean mouse adipose tissues identifies novel candidate obesity genes.

    Directory of Open Access Journals (Sweden)

    Nicholas M Morton

    Full Text Available Obesity and metabolic syndrome results from a complex interaction between genetic and environmental factors. In addition to brain-regulated processes, recent genome wide association studies have indicated that genes highly expressed in adipose tissue affect the distribution and function of fat and thus contribute to obesity. Using a stratified transcriptome gene enrichment approach we attempted to identify adipose tissue-specific obesity genes in the unique polygenic Fat (F mouse strain generated by selective breeding over 60 generations for divergent adiposity from a comparator Lean (L strain.To enrich for adipose tissue obesity genes a 'snap-shot' pooled-sample transcriptome comparison of key fat depots and non adipose tissues (muscle, liver, kidney was performed. Known obesity quantitative trait loci (QTL information for the model allowed us to further filter genes for increased likelihood of being causal or secondary for obesity. This successfully identified several genes previously linked to obesity (C1qr1, and Np3r as positional QTL candidate genes elevated specifically in F line adipose tissue. A number of novel obesity candidate genes were also identified (Thbs1, Ppp1r3d, Tmepai, Trp53inp2, Ttc7b, Tuba1a, Fgf13, Fmr that have inferred roles in fat cell function. Quantitative microarray analysis was then applied to the most phenotypically divergent adipose depot after exaggerating F and L strain differences with chronic high fat feeding which revealed a distinct gene expression profile of line, fat depot and diet-responsive inflammatory, angiogenic and metabolic pathways. Selected candidate genes Npr3 and Thbs1, as well as Gys2, a non-QTL gene that otherwise passed our enrichment criteria were characterised, revealing novel functional effects consistent with a contribution to obesity.A focussed candidate gene enrichment strategy in the unique F and L model has identified novel adipose tissue-enriched genes contributing to obesity.

  19. Multiplex flow cytometry barcoding and antibody arrays identify surface antigen profiles of primary and metastatic colon cancer cell lines.

    Directory of Open Access Journals (Sweden)

    Kumar Sukhdeo

    Full Text Available Colon cancer is a deadly disease affecting millions of people worldwide. Current treatment challenges include management of disease burden as well as improvements in detection and targeting of tumor cells. To identify disease state-specific surface antigen signatures, we combined fluorescent cell barcoding with high-throughput flow cytometric profiling of primary and metastatic colon cancer lines (SW480, SW620, and HCT116. Our multiplexed technique offers improvements over conventional methods by permitting the simultaneous and rapid screening of cancer cells with reduced effort and cost. The method uses a protein-level analysis with commercially available antibodies on live cells with intact epitopes to detect potential tumor-specific targets that can be further investigated for their clinical utility. Multiplexed antibody arrays can easily be applied to other tumor types or pathologies for discovery-based approaches to target identification.

  20. A comprehensive candidate gene approach identifies genetic variation associated with osteosarcoma

    International Nuclear Information System (INIS)

    Mirabello, Lisa; Grotmol, Tom; Douglass, Chester; Hayes, Richard B; Hoover, Robert N; Savage, Sharon A; Yu, Kai; Berndt, Sonja I; Burdett, Laurie; Wang, Zhaoming; Chowdhury, Salma; Teshome, Kedest; Uzoka, Arinze; Hutchinson, Amy

    2011-01-01

    Osteosarcoma (OS) is a bone malignancy which occurs primarily in adolescents. Since it occurs during a period of rapid growth, genes important in bone formation and growth are plausible modifiers of risk. Genes involved in DNA repair and ribosomal function may contribute to OS pathogenesis, because they maintain the integrity of critical cellular processes. We evaluated these hypotheses in an OS association study of genes from growth/hormone, bone formation, DNA repair, and ribosomal pathways. We evaluated 4836 tag-SNPs across 255 candidate genes in 96 OS cases and 1426 controls. Logistic regression models were used to estimate the odds ratios (OR) and 95% confidence intervals (CI). Twelve SNPs in growth or DNA repair genes were significantly associated with OS after Bonferroni correction. Four SNPs in the DNA repair gene FANCM (ORs 1.9-2.0, P = 0.003-0.004) and 2 SNPs downstream of the growth hormone gene GH1 (OR 1.6, P = 0.002; OR 0.5, P = 0.0009) were significantly associated with OS. One SNP in the region of each of the following genes was significant: MDM2, MPG, FGF2, FGFR3, GNRH2, and IGF1. Our results suggest that several SNPs in biologically plausible pathways are associated with OS. Larger studies are required to confirm our findings

  1. Gene expression differences between Noccaea caerulescens ecotypes help to identify candidate genes for metal phytoremediation.

    Science.gov (United States)

    Halimaa, Pauliina; Lin, Ya-Fen; Ahonen, Viivi H; Blande, Daniel; Clemens, Stephan; Gyenesei, Attila; Häikiö, Elina; Kärenlampi, Sirpa O; Laiho, Asta; Aarts, Mark G M; Pursiheimo, Juha-Pekka; Schat, Henk; Schmidt, Holger; Tuomainen, Marjo H; Tervahauta, Arja I

    2014-03-18

    Populations of Noccaea caerulescens show tremendous differences in their capacity to hyperaccumulate and hypertolerate metals. To explore the differences that could contribute to these traits, we undertook SOLiD high-throughput sequencing of the root transcriptomes of three phenotypically well-characterized N. caerulescens accessions, i.e., Ganges, La Calamine, and Monte Prinzera. Genes with possible contribution to zinc, cadmium, and nickel hyperaccumulation and hypertolerance were predicted. The most significant differences between the accessions were related to metal ion (di-, trivalent inorganic cation) transmembrane transporter activity, iron and calcium ion binding, (inorganic) anion transmembrane transporter activity, and antioxidant activity. Analysis of correlation between the expression profile of each gene and the metal-related characteristics of the accessions disclosed both previously characterized (HMA4, HMA3) and new candidate genes (e.g., for nickel IRT1, ZIP10, and PDF2.3) as possible contributors to the hyperaccumulation/tolerance phenotype. A number of unknown Noccaea-specific transcripts also showed correlation with Zn(2+), Cd(2+), or Ni(2+) hyperaccumulation/tolerance. This study shows that N. caerulescens populations have evolved great diversity in the expression of metal-related genes, facilitating adaptation to various metalliferous soils. The information will be helpful in the development of improved plants for metal phytoremediation.

  2. In silico analysis to identify vaccine candidates common to multiple serotypes of Shigella and evaluation of their immunogenicity

    KAUST Repository

    Pahil, Sapna

    2017-08-02

    Shigellosis or bacillary dysentery is an important cause of diarrhea, with the majority of the cases occurring in developing countries. Considering the high disease burden, increasing antibiotic resistance, serotype-specific immunity and the post-infectious sequelae associated with shigellosis, there is a pressing need of an effective vaccine against multiple serotypes of the pathogen. In the present study, we used bio-informatics approach to identify antigens shared among multiple serotypes of Shigella spp. This approach led to the identification of many immunogenic peptides. The five most promising peptides based on MHC binding efficiency were a putative lipoprotein (EL PGI I), a putative heat shock protein (EL PGI II), Spa32 (EL PGI III), IcsB (EL PGI IV) and a hypothetical protein (EL PGI V). These peptides were synthesized and the immunogenicity was evaluated in BALB/c mice by ELISA and cytokine assays. The putative heat shock protein (HSP) and the hypothetical protein elicited good humoral response, whereas putative lipoprotein, Spa32 and IcsB elicited good T-cell response as revealed by increased IFN-γ and TNF-α cytokine levels. The patient sera from confirmed cases of shigellosis were also evaluated for the presence of peptide specific antibodies with significant IgG and IgA antibodies against the HSP and the hypothetical protein, bestowing them as potential future vaccine candidates. The antigens reported in this study are novel and have not been tested as vaccine candidates against Shigella. This study offers time and cost-effective way of identifying unprecedented immunogenic antigens to be used as potential vaccine candidates. Moreover, this approach should easily be extendable to find new potential vaccine candidates for other pathogenic bacteria.

  3. In silico analysis to identify vaccine candidates common to multiple serotypes of Shigella and evaluation of their immunogenicity

    KAUST Repository

    Pahil, Sapna; Taneja, Neelam; Ansari, Hifzur Rahman; Raghava, G. P. S.

    2017-01-01

    Shigellosis or bacillary dysentery is an important cause of diarrhea, with the majority of the cases occurring in developing countries. Considering the high disease burden, increasing antibiotic resistance, serotype-specific immunity and the post-infectious sequelae associated with shigellosis, there is a pressing need of an effective vaccine against multiple serotypes of the pathogen. In the present study, we used bio-informatics approach to identify antigens shared among multiple serotypes of Shigella spp. This approach led to the identification of many immunogenic peptides. The five most promising peptides based on MHC binding efficiency were a putative lipoprotein (EL PGI I), a putative heat shock protein (EL PGI II), Spa32 (EL PGI III), IcsB (EL PGI IV) and a hypothetical protein (EL PGI V). These peptides were synthesized and the immunogenicity was evaluated in BALB/c mice by ELISA and cytokine assays. The putative heat shock protein (HSP) and the hypothetical protein elicited good humoral response, whereas putative lipoprotein, Spa32 and IcsB elicited good T-cell response as revealed by increased IFN-γ and TNF-α cytokine levels. The patient sera from confirmed cases of shigellosis were also evaluated for the presence of peptide specific antibodies with significant IgG and IgA antibodies against the HSP and the hypothetical protein, bestowing them as potential future vaccine candidates. The antigens reported in this study are novel and have not been tested as vaccine candidates against Shigella. This study offers time and cost-effective way of identifying unprecedented immunogenic antigens to be used as potential vaccine candidates. Moreover, this approach should easily be extendable to find new potential vaccine candidates for other pathogenic bacteria.

  4. In silico analysis to identify vaccine candidates common to multiple serotypes of Shigella and evaluation of their immunogenicity.

    Science.gov (United States)

    Pahil, Sapna; Taneja, Neelam; Ansari, Hifzur Rahman; Raghava, G P S

    2017-01-01

    Shigellosis or bacillary dysentery is an important cause of diarrhea, with the majority of the cases occurring in developing countries. Considering the high disease burden, increasing antibiotic resistance, serotype-specific immunity and the post-infectious sequelae associated with shigellosis, there is a pressing need of an effective vaccine against multiple serotypes of the pathogen. In the present study, we used bio-informatics approach to identify antigens shared among multiple serotypes of Shigella spp. This approach led to the identification of many immunogenic peptides. The five most promising peptides based on MHC binding efficiency were a putative lipoprotein (EL PGI I), a putative heat shock protein (EL PGI II), Spa32 (EL PGI III), IcsB (EL PGI IV) and a hypothetical protein (EL PGI V). These peptides were synthesized and the immunogenicity was evaluated in BALB/c mice by ELISA and cytokine assays. The putative heat shock protein (HSP) and the hypothetical protein elicited good humoral response, whereas putative lipoprotein, Spa32 and IcsB elicited good T-cell response as revealed by increased IFN-γ and TNF-α cytokine levels. The patient sera from confirmed cases of shigellosis were also evaluated for the presence of peptide specific antibodies with significant IgG and IgA antibodies against the HSP and the hypothetical protein, bestowing them as potential future vaccine candidates. The antigens reported in this study are novel and have not been tested as vaccine candidates against Shigella. This study offers time and cost-effective way of identifying unprecedented immunogenic antigens to be used as potential vaccine candidates. Moreover, this approach should easily be extendable to find new potential vaccine candidates for other pathogenic bacteria.

  5. In silico analysis to identify vaccine candidates common to multiple serotypes of Shigella and evaluation of their immunogenicity.

    Directory of Open Access Journals (Sweden)

    Sapna Pahil

    Full Text Available Shigellosis or bacillary dysentery is an important cause of diarrhea, with the majority of the cases occurring in developing countries. Considering the high disease burden, increasing antibiotic resistance, serotype-specific immunity and the post-infectious sequelae associated with shigellosis, there is a pressing need of an effective vaccine against multiple serotypes of the pathogen. In the present study, we used bio-informatics approach to identify antigens shared among multiple serotypes of Shigella spp. This approach led to the identification of many immunogenic peptides. The five most promising peptides based on MHC binding efficiency were a putative lipoprotein (EL PGI I, a putative heat shock protein (EL PGI II, Spa32 (EL PGI III, IcsB (EL PGI IV and a hypothetical protein (EL PGI V. These peptides were synthesized and the immunogenicity was evaluated in BALB/c mice by ELISA and cytokine assays. The putative heat shock protein (HSP and the hypothetical protein elicited good humoral response, whereas putative lipoprotein, Spa32 and IcsB elicited good T-cell response as revealed by increased IFN-γ and TNF-α cytokine levels. The patient sera from confirmed cases of shigellosis were also evaluated for the presence of peptide specific antibodies with significant IgG and IgA antibodies against the HSP and the hypothetical protein, bestowing them as potential future vaccine candidates. The antigens reported in this study are novel and have not been tested as vaccine candidates against Shigella. This study offers time and cost-effective way of identifying unprecedented immunogenic antigens to be used as potential vaccine candidates. Moreover, this approach should easily be extendable to find new potential vaccine candidates for other pathogenic bacteria.

  6. Proteomics strategy for identifying candidate bioactive proteins in complex mixtures: application to the platelet releasate.

    LENUS (Irish Health Repository)

    O'Connor, Roisin

    2010-01-01

    Proteomic approaches have proven powerful at identifying large numbers of proteins, but there are fewer reports of functional characterization of proteins in biological tissues. Here, we describe an experimental approach that fractionates proteins released from human platelets, linking bioassay activity to identity. We used consecutive orthogonal separation platforms to ensure sensitive detection: (a) ion-exchange of intact proteins, (b) SDS-PAGE separation of ion-exchange fractions and (c) HPLC separation of tryptic digests coupled to electrospray tandem mass spectrometry. Migration of THP-1 monocytes in response to complete or fractionated platelet releasate was assessed and located to just one of the forty-nine ion-exchange fractions. Over 300 proteins were identified in the releasate, with a wide range of annotated biophysical and biochemical properties, in particular platelet activation, adhesion, and wound healing. The presence of PEDF and involucrin, two proteins not previously reported in platelet releasate, was confirmed by western blotting. Proteins identified within the fraction with monocyte promigratory activity and not in other inactive fractions included vimentin, PEDF, and TIMP-1. We conclude that this analytical platform is effective for the characterization of complex bioactive samples.

  7. Exome sequencing identifies three novel candidate genes implicated in intellectual disability.

    Directory of Open Access Journals (Sweden)

    Zehra Agha

    Full Text Available Intellectual disability (ID is a major health problem mostly with an unknown etiology. Recently exome sequencing of individuals with ID identified novel genes implicated in the disease. Therefore the purpose of the present study was to identify the genetic cause of ID in one syndromic and two non-syndromic Pakistani families. Whole exome of three ID probands was sequenced. Missense variations in two plausible novel genes implicated in autosomal recessive ID were identified: lysine (K-specific methyltransferase 2B (KMT2B, zinc finger protein 589 (ZNF589, as well as hedgehog acyltransferase (HHAT with a de novo mutation with autosomal dominant mode of inheritance. The KMT2B recessive variant is the first report of recessive Kleefstra syndrome-like phenotype. Identification of plausible causative mutations for two recessive and a dominant type of ID, in genes not previously implicated in disease, underscores the large genetic heterogeneity of ID. These results also support the viewpoint that large number of ID genes converge on limited number of common networks i.e. ZNF589 belongs to KRAB-domain zinc-finger proteins previously implicated in ID, HHAT is predicted to affect sonic hedgehog, which is involved in several disorders with ID, KMT2B associated with syndromic ID fits the epigenetic module underlying the Kleefstra syndromic spectrum. The association of these novel genes in three different Pakistani ID families highlights the importance of screening these genes in more families with similar phenotypes from different populations to confirm the involvement of these genes in pathogenesis of ID.

  8. Accurately identifying patients who are excellent candidates or unsuitable for a medication: a novel approach

    Directory of Open Access Journals (Sweden)

    South C

    2017-12-01

    Full Text Available Charles South,1–3 A John Rush,4,* Thomas J Carmody,1–3 Manish K Jha,1,2 Madhukar H Trivedi1,2,*1Center for Depression Research and Clinical Care, 2Department of Psychiatry, 3Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas, TX, USA; 4Department of Psychiatry and Behavioral Sciences, Duke-National University of Singapore, Singapore; Duke Medical School, Durham, NC, USA*These authors contributed equally to this work Objective: The objective of the study was to determine whether a unique analytic approach – as a proof of concept – could identify individual depressed outpatients (using 30 baseline clinical and demographic variables who are very likely (75% certain to not benefit (NB or to remit (R, accepting that without sufficient certainty, no prediction (NP would be made.Methods: Patients from the Combining Medications to Enhance Depression Outcomes trial treated with escitalopram (S-CIT + placebo (n=212 or S-CIT + bupropion-SR (n=206 were analyzed separately to assess replicability. For each treatment, the elastic net was used to identify subsets of predictive baseline measures for R and NB, separately. Two different equations that estimate the likelihood of remission and no benefit were developed for each patient. The ratio of these two numbers characterized likely outcomes for each patient.Results: The two treatment cells had comparable rates of remission (40% and no benefit (22%. In S-CIT + bupropion-SR, 11 were predicted NB of which 82% were correct; 26 were predicted R – 85% correct (169 had NP. For S-CIT + placebo, 13 were predicted NB – 69% correct; 44 were predicted R – 75% correct (155 were NP. Overall, 94/418 (22% patients were identified with a meaningful degree of certainty (69%–85% correct. Different variable sets with some overlap were predictive of remission and no benefit within and across treatments, despite comparable outcomes.Conclusion: In two separate analyses with two

  9. Candidate Essential Genes in Burkholderia cenocepacia J2315 Identified by Genome-Wide TraDIS

    KAUST Repository

    Wong, Yee-Chin

    2016-08-22

    Burkholderia cenocepacia infection often leads to fatal cepacia syndrome in cystic fibrosis patients. However, antibiotic therapy rarely results in complete eradication of the pathogen due to its intrinsic resistance to many clinically available antibiotics. Recent attention has turned to the identification of essential genes as the proteins encoded by these genes may serve as potential targets for development of novel antimicrobials. In this study, we utilized TraDIS (Transposon Directed Insertion-site Sequencing) as a genome-wide screening tool to facilitate the identification of B. cenocepacia genes essential for its growth and viability. A transposon mutant pool consisting of approximately 500,000 mutants was successfully constructed, with more than 400,000 unique transposon insertion sites identified by computational analysis of TraDIS datasets. The saturated library allowed for the identification of 383 genes that were predicted to be essential in B. cenocepacia. We extended the application of TraDIS to identify conditionally essential genes required for in vitro growth and revealed an additional repertoire of 439 genes to be crucial for B. cenocepacia growth under nutrient-depleted conditions. The library of B. cenocepacia mutants can subsequently be subjected to various biologically related conditions to facilitate the discovery of genes involved in niche adaptation as well as pathogenicity and virulence.

  10. Candidate Essential Genes in Burkholderia cenocepacia J2315 Identified by Genome-Wide TraDIS

    KAUST Repository

    Wong, Yee-Chin; Abd El Ghany, Moataz; Naeem, Raeece; Lee, Kok-Wei; Tan, Yung-Chie; Pain, Arnab; Nathan, Sheila

    2016-01-01

    Burkholderia cenocepacia infection often leads to fatal cepacia syndrome in cystic fibrosis patients. However, antibiotic therapy rarely results in complete eradication of the pathogen due to its intrinsic resistance to many clinically available antibiotics. Recent attention has turned to the identification of essential genes as the proteins encoded by these genes may serve as potential targets for development of novel antimicrobials. In this study, we utilized TraDIS (Transposon Directed Insertion-site Sequencing) as a genome-wide screening tool to facilitate the identification of B. cenocepacia genes essential for its growth and viability. A transposon mutant pool consisting of approximately 500,000 mutants was successfully constructed, with more than 400,000 unique transposon insertion sites identified by computational analysis of TraDIS datasets. The saturated library allowed for the identification of 383 genes that were predicted to be essential in B. cenocepacia. We extended the application of TraDIS to identify conditionally essential genes required for in vitro growth and revealed an additional repertoire of 439 genes to be crucial for B. cenocepacia growth under nutrient-depleted conditions. The library of B. cenocepacia mutants can subsequently be subjected to various biologically related conditions to facilitate the discovery of genes involved in niche adaptation as well as pathogenicity and virulence.

  11. Candidate essential genes in Burkholderia cenocepacia J2315 identified by genome-wide TraDIS

    Directory of Open Access Journals (Sweden)

    Yee-Chin Wong

    2016-08-01

    Full Text Available Burkholderia cenocepacia infection often leads to fatal cepacia syndrome in cystic fibrosis patients. However, antibiotic therapy rarely results in complete eradication of the pathogen due to its intrinsic resistance to many clinically available antibiotics. Recent attention has turned to the identification of essential genes as the proteins encoded by these genes may serve as potential targets for development of novel antimicrobials. In this study, we utilized TraDIS (Transposon Directed Insertion-site Sequencing as a genome-wide screening tool to facilitate the identification of B. cenocepacia genes essential for its growth and viability. A transposon mutant pool consisting of approximately 500,000 mutants was successfully constructed, with more than 400,000 unique transposon insertion sites identified by computational analysis of TraDIS datasets. The saturated library allowed for the identification of 383 genes that were predicted to be essential in B. cenocepacia. We extended the application of TraDIS to identify conditionally essential genes required for in vitro growth and revealed an additional repertoire of 439 genes to be crucial for B. cenocepacia growth under nutrient-depleted conditions. The library of B. cenocepacia mutants can subsequently be subjected to various biologically related conditions to facilitate the discovery of genes involved in niche adaptation as well as pathogenicity and virulence.

  12. Genome-Wide Association Studies Identify Candidate Genes for Coat Color and Mohair Traits in the Iranian Markhoz Goat.

    Science.gov (United States)

    Nazari-Ghadikolaei, Anahit; Mehrabani-Yeganeh, Hassan; Miarei-Aashtiani, Seyed R; Staiger, Elizabeth A; Rashidi, Amir; Huson, Heather J

    2018-01-01

    The Markhoz goat provides an opportunity to study the genetics underlying coat color and mohair traits of an Angora type goat using genome-wide association studies (GWAS). This indigenous Iranian breed is valued for its quality mohair used in ceremonial garments and has the distinction of exhibiting an array of coat colors including black, brown, and white. Here, we performed 16 GWAS for different fleece (mohair) traits and coat color in 228 Markhoz goats sampled from the Markhoz Goat Research Station in Sanandaj, Kurdistan province, located in western Iran using the Illumina Caprine 50K beadchip. The Efficient Mixed Model Linear analysis was used to identify genomic regions with potential candidate genes contributing to coat color and mohair characteristics while correcting for population structure. Significant associations to coat color were found within or near the ASIP, ITCH, AHCY , and RALY genes on chromosome 13 for black and brown coat color and the KIT and PDGFRA genes on chromosome 6 for white coat color. Individual mohair traits were analyzed for genetic association along with principal components that allowed for a broader perspective of combined traits reflecting overall mohair quality and volume. A multitude of markers demonstrated significant association to mohair traits highlighting potential candidate genes of POU1F1 on chromosome 1 for mohair quality, MREG on chromosome 2 for mohair volume, DUOX1 on chromosome 10 for yearling fleece weight, and ADGRV1 on chromosome 7 for grease percentage. Variation in allele frequencies and haplotypes were identified for coat color and differentiated common markers associated with both brown and black coat color. This demonstrates the potential for genetic markers to be used in future breeding programs to improve selection for coat color and mohair traits. Putative candidate genes, both novel and previously identified in other species or breeds, require further investigation to confirm phenotypic causality and

  13. Genome-Wide Association Studies Identify Candidate Genes for Coat Color and Mohair Traits in the Iranian Markhoz Goat

    Directory of Open Access Journals (Sweden)

    Anahit Nazari-Ghadikolaei

    2018-04-01

    Full Text Available The Markhoz goat provides an opportunity to study the genetics underlying coat color and mohair traits of an Angora type goat using genome-wide association studies (GWAS. This indigenous Iranian breed is valued for its quality mohair used in ceremonial garments and has the distinction of exhibiting an array of coat colors including black, brown, and white. Here, we performed 16 GWAS for different fleece (mohair traits and coat color in 228 Markhoz goats sampled from the Markhoz Goat Research Station in Sanandaj, Kurdistan province, located in western Iran using the Illumina Caprine 50K beadchip. The Efficient Mixed Model Linear analysis was used to identify genomic regions with potential candidate genes contributing to coat color and mohair characteristics while correcting for population structure. Significant associations to coat color were found within or near the ASIP, ITCH, AHCY, and RALY genes on chromosome 13 for black and brown coat color and the KIT and PDGFRA genes on chromosome 6 for white coat color. Individual mohair traits were analyzed for genetic association along with principal components that allowed for a broader perspective of combined traits reflecting overall mohair quality and volume. A multitude of markers demonstrated significant association to mohair traits highlighting potential candidate genes of POU1F1 on chromosome 1 for mohair quality, MREG on chromosome 2 for mohair volume, DUOX1 on chromosome 10 for yearling fleece weight, and ADGRV1 on chromosome 7 for grease percentage. Variation in allele frequencies and haplotypes were identified for coat color and differentiated common markers associated with both brown and black coat color. This demonstrates the potential for genetic markers to be used in future breeding programs to improve selection for coat color and mohair traits. Putative candidate genes, both novel and previously identified in other species or breeds, require further investigation to confirm phenotypic

  14. Genome-wide association study identified genetic variations and candidate genes for plant architecture component traits in Chinese upland cotton.

    Science.gov (United States)

    Su, Junji; Li, Libei; Zhang, Chi; Wang, Caixiang; Gu, Lijiao; Wang, Hantao; Wei, Hengling; Liu, Qibao; Huang, Long; Yu, Shuxun

    2018-06-01

    Thirty significant associations between 22 SNPs and five plant architecture component traits in Chinese upland cotton were identified via GWAS. Four peak SNP loci located on chromosome D03 were simultaneously associated with more plant architecture component traits. A candidate gene, Gh_D03G0922, might be responsible for plant height in upland cotton. A compact plant architecture is increasingly required for mechanized harvesting processes in China. Therefore, cotton plant architecture is an important trait, and its components, such as plant height, fruit branch length and fruit branch angle, affect the suitability of a cultivar for mechanized harvesting. To determine the genetic basis of cotton plant architecture, a genome-wide association study (GWAS) was performed using a panel composed of 355 accessions and 93,250 single nucleotide polymorphisms (SNPs) identified using the specific-locus amplified fragment sequencing method. Thirty significant associations between 22 SNPs and five plant architecture component traits were identified via GWAS. Most importantly, four peak SNP loci located on chromosome D03 were simultaneously associated with more plant architecture component traits, and these SNPs were harbored in one linkage disequilibrium block. Furthermore, 21 candidate genes for plant architecture were predicted in a 0.95-Mb region including the four peak SNPs. One of these genes (Gh_D03G0922) was near the significant SNP D03_31584163 (8.40 kb), and its Arabidopsis homologs contain MADS-box domains that might be involved in plant growth and development. qRT-PCR showed that the expression of Gh_D03G0922 was upregulated in the apical buds and young leaves of the short and compact cotton varieties, and virus-induced gene silencing (VIGS) proved that the silenced plants exhibited increased PH. These results indicate that Gh_D03G0922 is likely the candidate gene for PH in cotton. The genetic variations and candidate genes identified in this study lay a foundation

  15. Candidate gene resequencing to identify rare, pedigree-specific variants influencing healthy aging phenotypes in the long life family study

    DEFF Research Database (Denmark)

    Druley, Todd E; Wang, Lihua; Lin, Shiow J

    2016-01-01

    from six pedigrees. OBFC1 (chromosome 10) is involved in telomere maintenance, and falls within a linkage peak recently reported from an analysis of telomere length in LLFS families. Two different algorithms for single gene associations identified three genes with an enrichment of variation......BACKGROUND: The Long Life Family Study (LLFS) is an international study to identify the genetic components of various healthy aging phenotypes. We hypothesized that pedigree-specific rare variants at longevity-associated genes could have a similar functional impact on healthy phenotypes. METHODS......: We performed custom hybridization capture sequencing to identify the functional variants in 464 candidate genes for longevity or the major diseases of aging in 615 pedigrees (4,953 individuals) from the LLFS, using a multiplexed, custom hybridization capture. Variants were analyzed individually...

  16. Coalitional game theory as a promising approach to identify candidate autism genes.

    Science.gov (United States)

    Gupta, Anika; Sun, Min Woo; Paskov, Kelley Marie; Stockham, Nate Tyler; Jung, Jae-Yoon; Wall, Dennis Paul

    2018-01-01

    Despite mounting evidence for the strong role of genetics in the phenotypic manifestation of Autism Spectrum Disorder (ASD), the specific genes responsible for the variable forms of ASD remain undefined. ASD may be best explained by a combinatorial genetic model with varying epistatic interactions across many small effect mutations. Coalitional or cooperative game theory is a technique that studies the combined effects of groups of players, known as coalitions, seeking to identify players who tend to improve the performance--the relationship to a specific disease phenotype--of any coalition they join. This method has been previously shown to boost biologically informative signal in gene expression data but to-date has not been applied to the search for cooperative mutations among putative ASD genes. We describe our approach to highlight genes relevant to ASD using coalitional game theory on alteration data of 1,965 fully sequenced genomes from 756 multiplex families. Alterations were encoded into binary matrices for ASD (case) and unaffected (control) samples, indicating likely gene-disrupting, inherited mutations in altered genes. To determine individual gene contributions given an ASD phenotype, a "player" metric, referred to as the Shapley value, was calculated for each gene in the case and control cohorts. Sixty seven genes were found to have significantly elevated player scores and likely represent significant contributors to the genetic coordination underlying ASD. Using network and cross-study analysis, we found that these genes are involved in biological pathways known to be affected in the autism cases and that a subset directly interact with several genes known to have strong associations to autism. These findings suggest that coalitional game theory can be applied to large-scale genomic data to identify hidden yet influential players in complex polygenic disorders such as autism.

  17. Comparative Transcriptome Analysis Identifies Candidate Genes Related to Skin Color Differentiation in Red Tilapia.

    Science.gov (United States)

    Zhu, Wenbin; Wang, Lanmei; Dong, Zaijie; Chen, Xingting; Song, Feibiao; Liu, Nian; Yang, Hui; Fu, Jianjun

    2016-08-11

    Red tilapia is becoming more popular for aquaculture production in China in recent years. However, the pigmentation differentiation in genetic breeding is the main problem limiting its development of commercial red tilapia culture and the genetic basis of skin color variation is still unknown. In this study, we conducted Illumina sequencing of transcriptome on three color variety red tilapia. A total of 224,895,758 reads were generated, resulting in 160,762 assembled contigs that were used as reference contigs. The contigs of red tilapia transcriptome had hits in the range of 53.4% to 86.7% of the unique proteins of zebrafish, fugu, medaka, three-spined stickleback and tilapia. And 44,723 contigs containing 77,423 simple sequence repeats (SSRs) were identified, with 16,646 contigs containing more than one SSR. Three skin transcriptomes were compared pairwise and the results revealed that there were 148 common significantly differentially expressed unigenes and several key genes related to pigment synthesis, i.e. tyr, tyrp1, silv, sox10, slc24a5, cbs and slc7a11, were included. The results will facilitate understanding the molecular mechanisms of skin pigmentation differentiation in red tilapia and accelerate the molecular selection of the specific strain with consistent skin colors.

  18. Candidate chemosensory genes identified in the endoparasitoid Meteorus pulchricornis (Hymenoptera: Braconidae) by antennal transcriptome analysis.

    Science.gov (United States)

    Sheng, Sheng; Liao, Cheng-Wu; Zheng, Yu; Zhou, Yu; Xu, Yan; Song, Wen-Miao; He, Peng; Zhang, Jian; Wu, Fu-An

    2017-06-01

    Meteorus pulchricornis is an endoparasitoid wasp which attacks the larvae of various lepidopteran pests. We present the first antennal transcriptome dataset for M. pulchricornis. A total of 48,845,072 clean reads were obtained and 34,967 unigenes were assembled. Of these, 15,458 unigenes showed a significant similarity (E-value <10 -5 ) to known proteins in the NCBI non-redundant protein database. Gene ontology (GO) and cluster of orthologous groups (COG) analyses were used to classify the functions of M. pulchricornis antennae genes. We identified 16 putative odorant-binding protein (OBP) genes, eight chemosensory protein (CSP) genes, 99 olfactory receptor (OR) genes, 19 ionotropic receptor (IR) genes and one sensory neuron membrane protein (SNMP) gene. BLASTx best hit results and phylogenetic analysis both indicated that these chemosensory genes were most closely related to those found in other hymenopteran species. Real-time quantitative PCR assays showed that 14 MpulOBP genes were antennae-specific. Of these, MpulOBP6, MpulOBP9, MpulOBP10, MpulOBP12, MpulOBP15 and MpulOBP16 were found to have greater expression in the antennae than in other body parts, while MpulOBP2 and MpulOBP3 were expressed predominately in the legs and abdomens, respectively. These results might provide a foundation for future studies of olfactory genes and chemoreception in M. pulchricornis. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Comparison of Expression Profiles in Ovarian Epithelium In Vivo and Ovarian Cancer Identifies Novel Candidate Genes Involved in Disease Pathogenesis

    Science.gov (United States)

    Emmanuel, Catherine; Gava, Natalie; Kennedy, Catherine; Balleine, Rosemary L.; Sharma, Raghwa; Wain, Gerard; Brand, Alison; Hogg, Russell; Etemadmoghadam, Dariush; George, Joshy; Birrer, Michael J.; Clarke, Christine L.; Chenevix-Trench, Georgia; Bowtell, David D. L.; Harnett, Paul R.; deFazio, Anna

    2011-01-01

    Molecular events leading to epithelial ovarian cancer are poorly understood but ovulatory hormones and a high number of life-time ovulations with concomitant proliferation, apoptosis, and inflammation, increases risk. We identified genes that are regulated during the estrous cycle in murine ovarian surface epithelium and analysed these profiles to identify genes dysregulated in human ovarian cancer, using publically available datasets. We identified 338 genes that are regulated in murine ovarian surface epithelium during the estrous cycle and dysregulated in ovarian cancer. Six of seven candidates selected for immunohistochemical validation were expressed in serous ovarian cancer, inclusion cysts, ovarian surface epithelium and in fallopian tube epithelium. Most were overexpressed in ovarian cancer compared with ovarian surface epithelium and/or inclusion cysts (EpCAM, EZH2, BIRC5) although BIRC5 and EZH2 were expressed as highly in fallopian tube epithelium as in ovarian cancer. We prioritised the 338 genes for those likely to be important for ovarian cancer development by in silico analyses of copy number aberration and mutation using publically available datasets and identified genes with established roles in ovarian cancer as well as novel genes for which we have evidence for involvement in ovarian cancer. Chromosome segregation emerged as an important process in which genes from our list of 338 were over-represented including two (BUB1, NCAPD2) for which there is evidence of amplification and mutation. NUAK2, upregulated in ovarian surface epithelium in proestrus and predicted to have a driver mutation in ovarian cancer, was examined in a larger cohort of serous ovarian cancer where patients with lower NUAK2 expression had shorter overall survival. In conclusion, defining genes that are activated in normal epithelium in the course of ovulation that are also dysregulated in cancer has identified a number of pathways and novel candidate genes that may contribute

  20. Proteomic analysis of cerebrospinal fluid from children with central nervous system tumors identifies candidate proteins relating to tumor metastatic spread.

    Science.gov (United States)

    Spreafico, Filippo; Bongarzone, Italia; Pizzamiglio, Sara; Magni, Ruben; Taverna, Elena; De Bortoli, Maida; Ciniselli, Chiara M; Barzanò, Elena; Biassoni, Veronica; Luchini, Alessandra; Liotta, Lance A; Zhou, Weidong; Signore, Michele; Verderio, Paolo; Massimino, Maura

    2017-07-11

    Central nervous system (CNS) tumors are the most common solid tumors in childhood. Since the sensitivity of combined cerebrospinal fluid (CSF) cytology and radiological neuroimaging in detecting meningeal metastases remains relatively low, we sought to characterize the CSF proteome of patients with CSF tumors to identify biomarkers predictive of metastatic spread. CSF samples from 27 children with brain tumors and 13 controls (extra-CNS non-Hodgkin lymphoma) were processed using core-shell hydrogel nanoparticles, and analyzed with reverse-phase liquid chromatography/electrospray tandem mass spectrometry (LC-MS/MS). Candidate proteins were identified with Fisher's exact test and/or a univariate logistic regression model. Reverse phase protein array (RPPA), Western blot (WB), and ELISA were used in the training set and in an independent set of CFS samples (60 cases, 14 controls) to validate our discovery findings. Among the 558 non-redundant proteins identified by LC-MS/MS, 147 were missing from the CSF database at http://www.biosino.org. Fourteen of the 26 final top-candidate proteins were chosen for validation with WB, RPPA and ELISA methods. Six proteins (type 1 collagen, insulin-like growth factor binding protein 4, procollagen C-endopeptidase enhancer 1, glial cell-line derived neurotrophic factor receptor α2, inter-alpha-trypsin inhibitor heavy chain 4, neural proliferation and differentiation control protein-1) revealed the ability to discriminate metastatic cases from controls. Combining a unique dataset of CSFs from pediatric CNS tumors with a novel enabling nanotechnology led us to identify CSF proteins potentially related to metastatic status.

  1. The genome sequence of the most widely cultivated cacao type and its use to identify candidate genes regulating pod color.

    Science.gov (United States)

    Motamayor, Juan C; Mockaitis, Keithanne; Schmutz, Jeremy; Haiminen, Niina; Livingstone, Donald; Cornejo, Omar; Findley, Seth D; Zheng, Ping; Utro, Filippo; Royaert, Stefan; Saski, Christopher; Jenkins, Jerry; Podicheti, Ram; Zhao, Meixia; Scheffler, Brian E; Stack, Joseph C; Feltus, Frank A; Mustiga, Guiliana M; Amores, Freddy; Phillips, Wilbert; Marelli, Jean Philippe; May, Gregory D; Shapiro, Howard; Ma, Jianxin; Bustamante, Carlos D; Schnell, Raymond J; Main, Dorrie; Gilbert, Don; Parida, Laxmi; Kuhn, David N

    2013-06-03

    Theobroma cacao L. cultivar Matina 1-6 belongs to the most cultivated cacao type. The availability of its genome sequence and methods for identifying genes responsible for important cacao traits will aid cacao researchers and breeders. We describe the sequencing and assembly of the genome of Theobroma cacao L. cultivar Matina 1-6. The genome of the Matina 1-6 cultivar is 445 Mbp, which is significantly larger than a sequenced Criollo cultivar, and more typical of other cultivars. The chromosome-scale assembly, version 1.1, contains 711 scaffolds covering 346.0 Mbp, with a contig N50 of 84.4 kbp, a scaffold N50 of 34.4 Mbp, and an evidence-based gene set of 29,408 loci. Version 1.1 has 10x the scaffold N50 and 4x the contig N50 as Criollo, and includes 111 Mb more anchored sequence. The version 1.1 assembly has 4.4% gap sequence, while Criollo has 10.9%. Through a combination of haplotype, association mapping and gene expression analyses, we leverage this robust reference genome to identify a promising candidate gene responsible for pod color variation. We demonstrate that green/red pod color in cacao is likely regulated by the R2R3 MYB transcription factor TcMYB113, homologs of which determine pigmentation in Rosaceae, Solanaceae, and Brassicaceae. One SNP within the target site for a highly conserved trans-acting siRNA in dicots, found within TcMYB113, seems to affect transcript levels of this gene and therefore pod color variation. We report a high-quality sequence and annotation of Theobroma cacao L. and demonstrate its utility in identifying candidate genes regulating traits.

  2. The genome sequence of the most widely cultivated cacao type and its use to identify candidate genes regulating pod color

    Science.gov (United States)

    2013-01-01

    Background Theobroma cacao L. cultivar Matina 1-6 belongs to the most cultivated cacao type. The availability of its genome sequence and methods for identifying genes responsible for important cacao traits will aid cacao researchers and breeders. Results We describe the sequencing and assembly of the genome of Theobroma cacao L. cultivar Matina 1-6. The genome of the Matina 1-6 cultivar is 445 Mbp, which is significantly larger than a sequenced Criollo cultivar, and more typical of other cultivars. The chromosome-scale assembly, version 1.1, contains 711 scaffolds covering 346.0 Mbp, with a contig N50 of 84.4 kbp, a scaffold N50 of 34.4 Mbp, and an evidence-based gene set of 29,408 loci. Version 1.1 has 10x the scaffold N50 and 4x the contig N50 as Criollo, and includes 111 Mb more anchored sequence. The version 1.1 assembly has 4.4% gap sequence, while Criollo has 10.9%. Through a combination of haplotype, association mapping and gene expression analyses, we leverage this robust reference genome to identify a promising candidate gene responsible for pod color variation. We demonstrate that green/red pod color in cacao is likely regulated by the R2R3 MYB transcription factor TcMYB113, homologs of which determine pigmentation in Rosaceae, Solanaceae, and Brassicaceae. One SNP within the target site for a highly conserved trans-acting siRNA in dicots, found within TcMYB113, seems to affect transcript levels of this gene and therefore pod color variation. Conclusions We report a high-quality sequence and annotation of Theobroma cacao L. and demonstrate its utility in identifying candidate genes regulating traits. PMID:23731509

  3. Genome-wide association study to identify candidate loci and genes for Mn toxicity tolerance in rice.

    Directory of Open Access Journals (Sweden)

    Asis Shrestha

    Full Text Available Manganese (Mn is an essential micro-nutrient for plants, but flooded rice fields can accumulate high levels of Mn2+ leading to Mn toxicity. Here, we present a genome-wide association study (GWAS to identify candidate loci conferring Mn toxicity tolerance in rice (Oryza sativa L.. A diversity panel of 288 genotypes was grown in hydroponic solutions in a greenhouse under optimal and toxic Mn concentrations. We applied a Mn toxicity treatment (5 ppm Mn2+, 3 weeks at twelve days after transplanting. Mn toxicity caused moderate damage in rice in terms of biomass loss and symptom formation despite extremely high shoot Mn concentrations ranging from 2.4 to 17.4 mg g-1. The tropical japonica subpopulation was more sensitive to Mn toxicity than other subpopulations. Leaf damage symptoms were significantly correlated with Mn uptake into shoots. Association mapping was conducted for seven traits using 416741 single nucleotide polymorphism (SNP markers using a mixed linear model, and detected six significant associations for the traits shoot manganese concentration and relative shoot length. Candidate regions contained genes coding for a heavy metal transporter, peroxidase precursor and Mn2+ ion binding proteins. The significant marker SNP-2.22465867 caused an amino acid change in a gene (LOC_Os02g37170 with unknown function. This study demonstrated significant natural variation in rice for Mn toxicity tolerance and the possibility of using GWAS to unravel genetic factors responsible for such complex traits.

  4. Identifying the candidate genes involved in the calyx abscission process of 'Kuerlexiangli' (Pyrus sinkiangensis Yu) by digital transcript abundance measurements.

    Science.gov (United States)

    Qi, Xiaoxiao; Wu, Jun; Wang, Lifen; Li, Leiting; Cao, Yufen; Tian, Luming; Dong, Xingguang; Zhang, Shaoling

    2013-10-23

    'Kuerlexiangli' (Pyrus sinkiangensis Yu), a native pear of Xinjiang, China, is an important agricultural fruit and primary export to the international market. However, fruit with persistent calyxes affect fruit shape and quality. Although several studies have looked into the physiological aspects of the calyx abscission process, the underlying molecular mechanisms remain unknown. In order to better understand the molecular basis of the process of calyx abscission, materials at three critical stages of regulation, with 6000 × Flusilazole plus 300 × PBO treatment (calyx abscising treatment) and 50 mg.L-1GA3 treatment (calyx persisting treatment), were collected and cDNA fragments were sequenced using digital transcript abundance measurements to identify candidate genes. Digital transcript abundance measurements was performed using high-throughput Illumina GAII sequencing on seven samples that were collected at three important stages of the calyx abscission process with chemical agent treatments promoting calyx abscission and persistence. Altogether more than 251,123,845 high quality reads were obtained with approximately 8.0 M raw data for each library. The values of 69.85%-71.90% of clean data in the digital transcript abundance measurements could be mapped to the pear genome database. There were 12,054 differentially expressed genes having Gene Ontology (GO) terms and associating with 251 Kyoto Encyclopedia of Genes and Genomes (KEGG) defined pathways. The differentially expressed genes correlated with calyx abscission were mainly involved in photosynthesis, plant hormone signal transduction, cell wall modification, transcriptional regulation, and carbohydrate metabolism. Furthermore, candidate calyx abscission-specific genes, e.g. Inflorescence deficient in abscission gene, were identified. Quantitative real-time PCR was used to confirm the digital transcript abundance measurements results. We identified candidate genes that showed highly dynamic changes in

  5. Expression and functional assessment of candidate type 2 diabetes susceptibility genes identify four new genes contributing to human insulin secretion

    Directory of Open Access Journals (Sweden)

    Fatou K. Ndiaye

    2017-06-01

    Full Text Available Objectives: Genome-wide association studies (GWAS have identified >100 loci independently contributing to type 2 diabetes (T2D risk. However, translational implications for precision medicine and for the development of novel treatments have been disappointing, due to poor knowledge of how these loci impact T2D pathophysiology. Here, we aimed to measure the expression of genes located nearby T2D associated signals and to assess their effect on insulin secretion from pancreatic beta cells. Methods: The expression of 104 candidate T2D susceptibility genes was measured in a human multi-tissue panel, through PCR-free expression assay. The effects of the knockdown of beta-cell enriched genes were next investigated on insulin secretion from the human EndoC-βH1 beta-cell line. Finally, we performed RNA-sequencing (RNA-seq so as to assess the pathways affected by the knockdown of the new genes impacting insulin secretion from EndoC-βH1, and we analyzed the expression of the new genes in mouse models with altered pancreatic beta-cell function. Results: We found that the candidate T2D susceptibility genes' expression is significantly enriched in pancreatic beta cells obtained by laser capture microdissection or sorted by flow cytometry and in EndoC-βH1 cells, but not in insulin sensitive tissues. Furthermore, the knockdown of seven T2D-susceptibility genes (CDKN2A, GCK, HNF4A, KCNK16, SLC30A8, TBC1D4, and TCF19 with already known expression and/or function in beta cells changed insulin secretion, supporting our functional approach. We showed first evidence for a role in insulin secretion of four candidate T2D-susceptibility genes (PRC1, SRR, ZFAND3, and ZFAND6 with no previous knowledge of presence and function in beta cells. RNA-seq in EndoC-βH1 cells with decreased expression of PRC1, SRR, ZFAND6, or ZFAND3 identified specific gene networks related to T2D pathophysiology. Finally, a positive correlation between the expression of Ins2 and the

  6. Candidate exome capture identifies mutation of SDCCAG8 as the cause of a retinal-renal ciliopathy.

    NARCIS (Netherlands)

    Otto, E.A.; Hurd, T.W.; Airik, R.; Chaki, M.; Zhou, W.; Stoetzel, C.; Patil, S.B.; Levy, S.; Ghosh, A.K.; Murga-Zamalloa, C.A.; Reeuwijk, J. van; Letteboer, S.J.F.; Sang, L.; Giles, R.H.; Liu, Q.; Coene, K.L.M.; Estrada-Cuzcano, A.; Collin, R.W.J.; McLaughlin, H.M.; Held, S.; Kasanuki, J.M.; Ramaswami, G.; Conte, J.; Lopez, I.; Washburn, J.; Macdonald, J.; Hu, J.; Yamashita, Y.; Maher, E.R.; Guay-Woodford, L.M.; Neumann, H.P.; Obermuller, N.; Koenekoop, R.K.; Bergmann, C.; Bei, X.; Lewis, R.A.; Katsanis, N.; Lopes, V.; Williams, D.S.; Lyons, R.H.; Dang, C.V.; Brito, D.A.; Dias, M.B.; Zhang, X.; Cavalcoli, J.D.; Nurnberg, G.; Nurnberg, P.; Pierce, E.A.; Jackson, P.K.; Antignac, C.; Saunier, S.; Roepman, R.; Dollfus, H.; Khanna, H.; Hildebrandt, F.

    2010-01-01

    Nephronophthisis-related ciliopathies (NPHP-RC) are recessive disorders that feature dysplasia or degeneration occurring preferentially in the kidney, retina and cerebellum. Here we combined homozygosity mapping with candidate gene analysis by performing 'ciliopathy candidate exome capture' followed

  7. Global analysis of WRKY transcription factor superfamily in Setaria identifies potential candidates involved in abiotic stress signalling

    Directory of Open Access Journals (Sweden)

    Mehanathan eMuthamilarasan

    2015-10-01

    Full Text Available Transcription factors (TFs are major players in stress signalling and constitute an integral part of signalling networks. Among the major TFs, WRKY proteins play pivotal roles in regulation of transcriptional reprogramming associated with stress responses. In view of this, genome- and transcriptome-wide identification of WRKY TF family was performed in the C4 model plants, Setaria italica (SiWRKY and S. viridis (SvWRKY, respectively. The study identified 105 SiWRKY and 44 SvWRKY proteins that were computationally analysed for their physicochemical properties. Sequence alignment and phylogenetic analysis classified these proteins into three major groups, namely I, II and III with majority of WRKY proteins belonging to group II (53 SiWRKY and 23 SvWRKY, followed by group III (39 SiWRKY and 11 SvWRKY and group I (10 SiWRKY and 6 SvWRKY. Group II proteins were further classified into 5 subgroups (IIa to IIe based on their phylogeny. Domain analysis showed the presence of WRKY motif and zinc finger-like structures in these proteins along with additional domains in a few proteins. All SiWRKY genes were physically mapped on the S. italica genome and their duplication analysis revealed that 10 and 8 gene pairs underwent tandem and segmental duplications, respectively. Comparative mapping of SiWRKY and SvWRKY genes in related C4 panicoid genomes demonstrated the orthologous relationships between these genomes. In silico expression analysis of SiWRKY and SvWRKY genes showed their differential expression patterns in different tissues and stress conditions. Expression profiling of candidate SiWRKY genes in response to stress (dehydration and salinity and hormone treatments (abscisic acid, salicylic acid and methyl jasmonate suggested the putative involvement of SiWRKY066 and SiWRKY082 in stress and hormone signalling. These genes could be potential candidates for further characterization to delineate their functional roles in abiotic stress signalling.

  8. Global analysis of WRKY transcription factor superfamily in Setaria identifies potential candidates involved in abiotic stress signaling.

    Science.gov (United States)

    Muthamilarasan, Mehanathan; Bonthala, Venkata S; Khandelwal, Rohit; Jaishankar, Jananee; Shweta, Shweta; Nawaz, Kashif; Prasad, Manoj

    2015-01-01

    Transcription factors (TFs) are major players in stress signaling and constitute an integral part of signaling networks. Among the major TFs, WRKY proteins play pivotal roles in regulation of transcriptional reprogramming associated with stress responses. In view of this, genome- and transcriptome-wide identification of WRKY TF family was performed in the C4model plants, Setaria italica (SiWRKY) and S. viridis (SvWRKY), respectively. The study identified 105 SiWRKY and 44 SvWRKY proteins that were computationally analyzed for their physicochemical properties. Sequence alignment and phylogenetic analysis classified these proteins into three major groups, namely I, II, and III with majority of WRKY proteins belonging to group II (53 SiWRKY and 23 SvWRKY), followed by group III (39 SiWRKY and 11 SvWRKY) and group I (10 SiWRKY and 6 SvWRKY). Group II proteins were further classified into 5 subgroups (IIa to IIe) based on their phylogeny. Domain analysis showed the presence of WRKY motif and zinc finger-like structures in these proteins along with additional domains in a few proteins. All SiWRKY genes were physically mapped on the S. italica genome and their duplication analysis revealed that 10 and 8 gene pairs underwent tandem and segmental duplications, respectively. Comparative mapping of SiWRKY and SvWRKY genes in related C4 panicoid genomes demonstrated the orthologous relationships between these genomes. In silico expression analysis of SiWRKY and SvWRKY genes showed their differential expression patterns in different tissues and stress conditions. Expression profiling of candidate SiWRKY genes in response to stress (dehydration and salinity) and hormone treatments (abscisic acid, salicylic acid, and methyl jasmonate) suggested the putative involvement of SiWRKY066 and SiWRKY082 in stress and hormone signaling. These genes could be potential candidates for further characterization to delineate their functional roles in abiotic stress signaling.

  9. A multicopy suppressor screening approach as a means to identify antibiotic resistance determinant candidates in Yersinia pestis

    Directory of Open Access Journals (Sweden)

    Moy Richard L

    2008-07-01

    Full Text Available Abstract Background Yersinia pestis is the causative agent of plague and a potential agent of bioterrorism and biowarfare. The plague biothreat and the emergence of multidrug-resistant plague underscore the need to increase our understanding of the intrinsic potential of Y. pestis for developing antimicrobial resistance and to anticipate the mechanisms of resistance that may emerge in Y. pestis. Identification of Y. pestis genes that, when overexpressed, are capable of reducing antibiotic susceptibility is a useful strategy to expose genes that this pathogen may rely upon to evolve antibiotic resistance via a vertical modality. In this study, we explored the use of a multicopy suppressor, Escherichia coli host-based screening approach as a means to expose antibiotic resistance determinant candidates in Y. pestis. Results We constructed a multicopy plasmid-based, Y. pestis genome-wide expression library of nearly 16,000 clones in E. coli and screened the library for suppressors of the antimicrobial activity of ofloxacin, a fluoroquinolone antibiotic. The screen permitted the identification of a transcriptional regulator-encoding gene (robAYp that increased the MIC99 of ofloxacin by 23-fold when overexpressed from a multicopy plasmid in Y. pestis. Additionally, we found that robAYp overexpression in Y. pestis conferred low-level resistance to many other antibiotics and increased organic solvent tolerance. Overexpression of robAYp also upregulated the expression of several efflux pumps in Y. pestis. Conclusion Our study provides proof of principle for the use of multicopy suppressor screening based on the tractable and easy-to-manipulate E. coli host as a means to identify antibiotic resistance determinant candidates of Y. pestis.

  10. Global analysis of WRKY transcription factor superfamily in Setaria identifies potential candidates involved in abiotic stress signaling

    Science.gov (United States)

    Muthamilarasan, Mehanathan; Bonthala, Venkata S.; Khandelwal, Rohit; Jaishankar, Jananee; Shweta, Shweta; Nawaz, Kashif; Prasad, Manoj

    2015-01-01

    Transcription factors (TFs) are major players in stress signaling and constitute an integral part of signaling networks. Among the major TFs, WRKY proteins play pivotal roles in regulation of transcriptional reprogramming associated with stress responses. In view of this, genome- and transcriptome-wide identification of WRKY TF family was performed in the C4model plants, Setaria italica (SiWRKY) and S. viridis (SvWRKY), respectively. The study identified 105 SiWRKY and 44 SvWRKY proteins that were computationally analyzed for their physicochemical properties. Sequence alignment and phylogenetic analysis classified these proteins into three major groups, namely I, II, and III with majority of WRKY proteins belonging to group II (53 SiWRKY and 23 SvWRKY), followed by group III (39 SiWRKY and 11 SvWRKY) and group I (10 SiWRKY and 6 SvWRKY). Group II proteins were further classified into 5 subgroups (IIa to IIe) based on their phylogeny. Domain analysis showed the presence of WRKY motif and zinc finger-like structures in these proteins along with additional domains in a few proteins. All SiWRKY genes were physically mapped on the S. italica genome and their duplication analysis revealed that 10 and 8 gene pairs underwent tandem and segmental duplications, respectively. Comparative mapping of SiWRKY and SvWRKY genes in related C4 panicoid genomes demonstrated the orthologous relationships between these genomes. In silico expression analysis of SiWRKY and SvWRKY genes showed their differential expression patterns in different tissues and stress conditions. Expression profiling of candidate SiWRKY genes in response to stress (dehydration and salinity) and hormone treatments (abscisic acid, salicylic acid, and methyl jasmonate) suggested the putative involvement of SiWRKY066 and SiWRKY082 in stress and hormone signaling. These genes could be potential candidates for further characterization to delineate their functional roles in abiotic stress signaling. PMID:26635818

  11. Genome‐wide DNA methylation analysis identifies MEGF10 as a novel epigenetically repressed candidate tumor suppressor gene in neuroblastoma

    Science.gov (United States)

    Charlet, Jessica; Tomari, Ayumi; Dallosso, Anthony R.; Szemes, Marianna; Kaselova, Martina; Curry, Thomas J.; Almutairi, Bader; Etchevers, Heather C.; McConville, Carmel; Malik, Karim T. A.

    2016-01-01

    Neuroblastoma is a childhood cancer in which many children still have poor outcomes, emphasising the need to better understand its pathogenesis. Despite recent genome‐wide mutation analyses, many primary neuroblastomas do not contain recognizable driver mutations, implicating alternate molecular pathologies such as epigenetic alterations. To discover genes that become epigenetically deregulated during neuroblastoma tumorigenesis, we took the novel approach of comparing neuroblastomas to neural crest precursor cells, using genome‐wide DNA methylation analysis. We identified 93 genes that were significantly differentially methylated of which 26 (28%) were hypermethylated and 67 (72%) were hypomethylated. Concentrating on hypermethylated genes to identify candidate tumor suppressor loci, we found the cell engulfment and adhesion factor gene MEGF10 to be epigenetically repressed by DNA hypermethylation or by H3K27/K9 methylation in neuroblastoma cell lines. MEGF10 showed significantly down‐regulated expression in neuroblastoma tumor samples; furthermore patients with the lowest‐expressing tumors had reduced relapse‐free survival. Our functional studies showed that knock‐down of MEGF10 expression in neuroblastoma cell lines promoted cell growth, consistent with MEGF10 acting as a clinically relevant, epigenetically deregulated neuroblastoma tumor suppressor gene. © 2016 The Authors. Molecular Carcinogenesis Published by Wiley Periodicals, Inc. PMID:27862318

  12. Genome-Wide Association Study Identifying Candidate Genes Influencing Important Agronomic Traits of Flax (Linum usitatissimum L.) Using SLAF-seq.

    Science.gov (United States)

    Xie, Dongwei; Dai, Zhigang; Yang, Zemao; Sun, Jian; Zhao, Debao; Yang, Xue; Zhang, Liguo; Tang, Qing; Su, Jianguang

    2017-01-01

    Flax ( Linum usitatissimum L.) is an important cash crop, and its agronomic traits directly affect yield and quality. Molecular studies on flax remain inadequate because relatively few flax genes have been associated with agronomic traits or have been identified as having potential applications. To identify markers and candidate genes that can potentially be used for genetic improvement of crucial agronomic traits, we examined 224 specimens of core flax germplasm; specifically, phenotypic data for key traits, including plant height, technical length, number of branches, number of fruits, and 1000-grain weight were investigated under three environmental conditions before specific-locus amplified fragment sequencing (SLAF-seq) was employed to perform a genome-wide association study (GWAS) for these five agronomic traits. Subsequently, the results were used to screen single nucleotide polymorphism (SNP) loci and candidate genes that exhibited a significant correlation with the important agronomic traits. Our analyses identified a total of 42 SNP loci that showed significant correlations with the five important agronomic flax traits. Next, candidate genes were screened in the 10 kb zone of each of the 42 SNP loci. These SNP loci were then analyzed by a more stringent screening via co-identification using both a general linear model (GLM) and a mixed linear model (MLM) as well as co-occurrences in at least two of the three environments, whereby 15 final candidate genes were obtained. Based on these results, we determined that UGT and PL are candidate genes for plant height, GRAS and XTH are candidate genes for the number of branches, Contig1437 and LU0019C12 are candidate genes for the number of fruits, and PHO1 is a candidate gene for the 1000-seed weight. We propose that the identified SNP loci and corresponding candidate genes might serve as a biological basis for improving crucial agronomic flax traits.

  13. Genome-Wide Association Study Identifying Candidate Genes Influencing Important Agronomic Traits of Flax (Linum usitatissimum L. Using SLAF-seq

    Directory of Open Access Journals (Sweden)

    Dongwei Xie

    2018-01-01

    Full Text Available Flax (Linum usitatissimum L. is an important cash crop, and its agronomic traits directly affect yield and quality. Molecular studies on flax remain inadequate because relatively few flax genes have been associated with agronomic traits or have been identified as having potential applications. To identify markers and candidate genes that can potentially be used for genetic improvement of crucial agronomic traits, we examined 224 specimens of core flax germplasm; specifically, phenotypic data for key traits, including plant height, technical length, number of branches, number of fruits, and 1000-grain weight were investigated under three environmental conditions before specific-locus amplified fragment sequencing (SLAF-seq was employed to perform a genome-wide association study (GWAS for these five agronomic traits. Subsequently, the results were used to screen single nucleotide polymorphism (SNP loci and candidate genes that exhibited a significant correlation with the important agronomic traits. Our analyses identified a total of 42 SNP loci that showed significant correlations with the five important agronomic flax traits. Next, candidate genes were screened in the 10 kb zone of each of the 42 SNP loci. These SNP loci were then analyzed by a more stringent screening via co-identification using both a general linear model (GLM and a mixed linear model (MLM as well as co-occurrences in at least two of the three environments, whereby 15 final candidate genes were obtained. Based on these results, we determined that UGT and PL are candidate genes for plant height, GRAS and XTH are candidate genes for the number of branches, Contig1437 and LU0019C12 are candidate genes for the number of fruits, and PHO1 is a candidate gene for the 1000-seed weight. We propose that the identified SNP loci and corresponding candidate genes might serve as a biological basis for improving crucial agronomic flax traits.

  14. A proteomic analysis identifies candidate early biomarkers to predict ovarian hyperstimulation syndrome in polycystic ovarian syndrome patients.

    Science.gov (United States)

    Wu, Lan; Sun, Yazhou; Wan, Jun; Luan, Ting; Cheng, Qing; Tan, Yong

    2017-07-01

    Ovarian hyperstimulation syndrome (OHSS) is a potentially life‑threatening, iatrogenic complication that occurs during assisted reproduction. Polycystic ovarian syndrome (PCOS) significantly increases the risk of OHSS during controlled ovarian stimulation. Therefore, a more effective early prediction technique is required in PCOS patients. Quantitative proteomic analysis of serum proteins indicates the potential diagnostic value for disease. In the present study, the authors revealed the differentially expressed proteins in OHSS patients with PCOS as new diagnostic biomarkers. The promising proteins obtained from liquid chromatography‑mass spectrometry were subjected to ELISA and western blotting assay for further confirmation. A total of 57 proteins were identified with significant difference, of which 29 proteins were upregulated and 28 proteins were downregulated in OHSS patients. Haptoglobin, fibrinogen and lipoprotein lipase were selected as candidate biomarkers. Receiver operating characteristic curve analysis demonstrated all three proteins may have potential as biomarkers to discriminate OHSS in PCOS patients. Haptoglobin, fibrinogen and lipoprotein lipase have never been reported as a predictive marker of OHSS in PCOS patients, and their potential roles in OHSS occurrence deserve further studies. The proteomic results reported in the present study may gain deeper insights into the pathophysiology of OHSS.

  15. Low/Negative Expression of PDGFR-α Identifies the Candidate Primary Mesenchymal Stromal Cells in Adult Human Bone Marrow

    Directory of Open Access Journals (Sweden)

    Hongzhe Li

    2014-12-01

    Full Text Available Human bone marrow (BM contains a rare population of nonhematopoietic mesenchymal stromal cells (MSCs, which are of central importance for the hematopoietic microenvironment. However, the precise phenotypic definition of these cells in adult BM has not yet been reported. In this study, we show that low/negative expression of CD140a (PDGFR-α on lin−/CD45−/CD271+ BM cells identified a cell population with very high MSC activity, measured as fibroblastic colony-forming unit frequency and typical in vitro and in vivo stroma formation and differentiation capacities. Furthermore, these cells exhibited high levels of genes associated with mesenchymal lineages and HSC supportive function. Moreover, lin−/CD45−/CD271+/CD140alow/− cells effectively mediated the ex vivo expansion of transplantable CD34+ hematopoietic stem cells. Taken together, these data indicate that CD140a is a key negative selection marker for adult human BM-MSCs, which enables to prospectively isolate a close to pure population of candidate human adult stroma stem/progenitor cells with potent hematopoiesis-supporting capacity.

  16. Gene expression profiling and candidate gene resequencing identifies pathways and mutations important for malignant transformation caused by leukemogenic fusion genes.

    Science.gov (United States)

    Novak, Rachel L; Harper, David P; Caudell, David; Slape, Christopher; Beachy, Sarah H; Aplan, Peter D

    2012-12-01

    NUP98-HOXD13 (NHD13) and CALM-AF10 (CA10) are oncogenic fusion proteins produced by recurrent chromosomal translocations in patients with acute myeloid leukemia (AML). Transgenic mice that express these fusions develop AML with a long latency and incomplete penetrance, suggesting that collaborating genetic events are required for leukemic transformation. We employed genetic techniques to identify both preleukemic abnormalities in healthy transgenic mice as well as collaborating events leading to leukemic transformation. Candidate gene resequencing revealed that 6 of 27 (22%) CA10 AMLs spontaneously acquired a Ras pathway mutation and 8 of 27 (30%) acquired an Flt3 mutation. Two CA10 AMLs acquired an Flt3 internal-tandem duplication, demonstrating that these mutations can be acquired in murine as well as human AML. Gene expression profiles revealed a marked upregulation of Hox genes, particularly Hoxa5, Hoxa9, and Hoxa10 in both NHD13 and CA10 mice. Furthermore, mir196b, which is embedded within the Hoxa locus, was overexpressed in both CA10 and NHD13 samples. In contrast, the Hox cofactors Meis1 and Pbx3 were differentially expressed; Meis1 was increased in CA10 AMLs but not NHD13 AMLs, whereas Pbx3 was consistently increased in NHD13 but not CA10 AMLs. Silencing of Pbx3 in NHD13 cells led to decreased proliferation, increased apoptosis, and decreased colony formation in vitro, suggesting a previously unexpected role for Pbx3 in leukemic transformation. Published by Elsevier Inc.

  17. A family-based association study identified CYP17 as a candidate gene for obesity susceptibility in Caucasians.

    Science.gov (United States)

    Yan, H; Guo, Y; Yang, T-L; Zhao, L-J; Deng, H-W

    2012-08-06

    The cytochrome P450c17α gene (CYP17) encodes a key biosynthesis enzyme of estrogen, which is critical in regulating adipogenesis and adipocyte development in humans. We therefore hypothesized that CYP17 is a candidate gene for predicting obesity. In order to test this hypothesis, we performed a family-based association test to investigate the relationship between the CYP17 gene and obesity phenotypes in a large sample comprising 1873 subjects from 405 Caucasian nuclear families of European origin recruited by the Osteoporosis Research Center of Creighton University, USA. Both single SNPs and haplotypes were tested for associations with obesity-related phenotypes, including body mass index (BMI) and fat mass. We identified three SNPs to be significantly associated with BMI, including rs3740397, rs6163, and rs619824. We further characterized the linkage disequilibrium structure for CYP17 and found that the whole CYP17 gene was located in a single-linkage disequilibrium block. This block was observed to be significantly associated with BMI. A major haplotype in this block was significantly associated with both BMI and fat mass. In conclusion, we suggest that the CYP17 gene has an effect on obesity in the Caucasian population. Further independent studies will be needed to confirm our findings.

  18. Analyses of germline variants associated with ovarian cancer survival identify functional candidates at the 1q22 and 19p12 outcome loci

    DEFF Research Database (Denmark)

    Glubb, Dylan M; Johnatty, Sharon E; Quinn, Michael C J

    2017-01-01

    We previously identified associations with ovarian cancer outcome at five genetic loci. To identify putatively causal genetic variants and target genes, we prioritized two ovarian outcome loci (1q22 and 19p12) for further study. Bioinformatic and functional genetic analyses indicated that MEF2D...... and ZNF100 are targets of candidate outcome variants at 1q22 and 19p12, respectively. At 19p12, the chromatin interaction of a putative regulatory element with the ZNF100 promoter region correlated with candidate outcome variants. At 1q22, putative regulatory elements enhanced MEF2D promoter activity...... and haplotypes containing candidate outcome variants modulated these effects. In a public dataset, MEF2D and ZNF100 expression were both associated with ovarian cancer progression-free or overall survival time. In an extended set of 6,162 epithelial ovarian cancer patients, we found that functional candidates...

  19. Resistance gene candidates identified by PCR with degenerate oligonucleotide primers map to clusters of resistance genes in lettuce.

    Science.gov (United States)

    Shen, K A; Meyers, B C; Islam-Faridi, M N; Chin, D B; Stelly, D M; Michelmore, R W

    1998-08-01

    The recent cloning of genes for resistance against diverse pathogens from a variety of plants has revealed that many share conserved sequence motifs. This provides the possibility of isolating numerous additional resistance genes by polymerase chain reaction (PCR) with degenerate oligonucleotide primers. We amplified resistance gene candidates (RGCs) from lettuce with multiple combinations of primers with low degeneracy designed from motifs in the nucleotide binding sites (NBSs) of RPS2 of Arabidopsis thaliana and N of tobacco. Genomic DNA, cDNA, and bacterial artificial chromosome (BAC) clones were successfully used as templates. Four families of sequences were identified that had the same similarity to each other as to resistance genes from other species. The relationship of the amplified products to resistance genes was evaluated by several sequence and genetic criteria. The amplified products contained open reading frames with additional sequences characteristic of NBSs. Hybridization of RGCs to genomic DNA and to BAC clones revealed large numbers of related sequences. Genetic analysis demonstrated the existence of clustered multigene families for each of the four RGC sequences. This parallels classical genetic data on clustering of disease resistance genes. Two of the four families mapped to known clusters of resistance genes; these two families were therefore studied in greater detail. Additional evidence that these RGCs could be resistance genes was gained by the identification of leucine-rich repeat (LRR) regions in sequences adjoining the NBS similar to those in RPM1 and RPS2 of A. thaliana. Fluorescent in situ hybridization confirmed the clustered genomic distribution of these sequences. The use of PCR with degenerate oligonucleotide primers is therefore an efficient method to identify numerous RGCs in plants.

  20. Utility of in vivo transcription profiling for identifying Pseudomonas aeruginosa genes needed for gastrointestinal colonization and dissemination

    DEFF Research Database (Denmark)

    Koh, Andrew Y; Mikkelsen, Per J; Smith, Roger S

    2010-01-01

    these mutants and WT P. aeruginosa PA14. To evaluate T3SS factors, we tested GI colonization and neutropenia-induced dissemination of both deletional (PAO1 and PAK) and insertional (PA14) mutants in four genes in the P. aeruginosa T3SS, exoS or exoU, exoT, and popB. There were no significant differences in GI......, increased transcription of genes during in vivo murine GI colonization is not predictive of an essential role for the gene product in either colonization or overall survival following induction of neutropenia....

  1. THE CANDIDATE CLUSTER AND PROTOCLUSTER CATALOG (CCPC). II. SPECTROSCOPICALLY IDENTIFIED STRUCTURES SPANNING 2 <  z  < 6.6

    Energy Technology Data Exchange (ETDEWEB)

    Franck, J. R.; McGaugh, S. S. [Case Western Reserve University, 10900 Euclid Ave., Cleveland, OH 44106 (United States)

    2016-12-10

    The Candidate Cluster and Protocluster Catalog (CCPC) is a list of objects at redshifts z  > 2 composed of galaxies with spectroscopically confirmed redshifts that are coincident on the sky and in redshift. These protoclusters are identified by searching for groups in volumes corresponding to the expected size of the most massive protoclusters at these redshifts. In CCPC1 we identified 43 candidate protoclusters among 14,000 galaxies between 2.74 <  z  < 3.71. Here we expand our search to more than 40,000 galaxies with spectroscopic redshifts z  > 2.00, resulting in an additional 173 candidate structures. The most significant of these are 36 protoclusters with overdensities δ {sub gal} > 7. We also identify three large proto-supercluster candidates containing multiple protoclusters at z  = 2.3, 3.5 and z  = 6.56. Eight candidates with N  ≥ 10 galaxies are found at redshifts z  > 4.0. The last system in the catalog is the most distant spectroscopic protocluster candidate known to date at z  = 6.56.

  2. Gene expression analysis identifies new candidate genes associated with the development of black skin spots in Corriedale sheep.

    Science.gov (United States)

    Peñagaricano, Francisco; Zorrilla, Pilar; Naya, Hugo; Robello, Carlos; Urioste, Jorge I

    2012-02-01

    The white coat colour of sheep is an important economic trait. For unknown reasons, some animals are born with, and others develop with time, black skin spots that can also produce pigmented fibres. The presence of pigmented fibres in the white wool significantly decreases the fibre quality. The aim of this work was to study gene expression in black spots (with and without pigmented fibres) and white skin by microarray techniques, in order to identify the possible genes involved in the development of this trait. Five unrelated Corriedale sheep were used and, for each animal, the three possible comparisons (three different hybridisations) between the three samples of interest were performed. Differential gene expression patterns were analysed using different t-test approaches. Most of the major genes with well-known roles in skin pigmentation, e.g. ASIP, MC1R and C-KIT, showed no significant difference in the gene expression between white skin and black spots. On the other hand, many of the differentially expressed genes (raw P-value spots. The gene expression of C-FOS and KLF4, transcription factors involved in the cellular response to external factors such as ultraviolet light, was validated by quantitative polymerase chain reaction (PCR). This exploratory study provides a list of candidate genes that could be associated with the development of black skin spots that should be studied in more detail. Characterisation of these genes will enable us to discern the molecular mechanisms involved in the development of this feature and, hence, increase our understanding of melanocyte biology and skin pigmentation. In sheep, understanding this phenomenon is a first step towards developing molecular tools to assist in the selection against the presence of pigmented fibres in white wool.

  3. Editor's Highlight: High-Throughput Functional Genomics Identifies Modulators of TCE Metabolite Genotoxicity and Candidate Susceptibility Genes.

    Science.gov (United States)

    De La Rosa, Vanessa Y; Asfaha, Jonathan; Fasullo, Michael; Loguinov, Alex; Li, Peng; Moore, Lee E; Rothman, Nathaniel; Nakamura, Jun; Swenberg, James A; Scelo, Ghislaine; Zhang, Luoping; Smith, Martyn T; Vulpe, Chris D

    2017-11-01

    Trichloroethylene (TCE), an industrial chemical and environmental contaminant, is a human carcinogen. Reactive metabolites are implicated in renal carcinogenesis associated with TCE exposure, yet the toxicity mechanisms of these metabolites and their contribution to cancer and other adverse effects remain unclear. We employed an integrated functional genomics approach that combined functional profiling studies in yeast and avian DT40 cell models to provide new insights into the specific mechanisms contributing to toxicity associated with TCE metabolites. Genome-wide profiling studies in yeast identified the error-prone translesion synthesis (TLS) pathway as an import mechanism in response to TCE metabolites. The role of TLS DNA repair was further confirmed by functional profiling in DT40 avian cell lines, but also revealed that TLS and homologous recombination DNA repair likely play competing roles in cellular susceptibility to TCE metabolites in higher eukaryotes. These DNA repair pathways are highly conserved between yeast, DT40, and humans. We propose that in humans, mutagenic TLS is favored over homologous recombination repair in response to TCE metabolites. The results of these studies contribute to the body of evidence supporting a mutagenic mode of action for TCE-induced renal carcinogenesis mediated by reactive metabolites in humans. Our approach illustrates the potential for high-throughput in vitro functional profiling in yeast to elucidate toxicity pathways (molecular initiating events, key events) and candidate susceptibility genes for focused study. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. Prespecified candidate biomarkers identify follicular lymphoma patients who achieved longer progression-free survival with bortezomib-rituximab versus rituximab.

    Science.gov (United States)

    Coiffier, Bertrand; Li, Weimin; Henitz, Erin D; Karkera, Jayaprakash D; Favis, Reyna; Gaffney, Dana; Shapiro, Alice; Theocharous, Panteli; Elsayed, Yusri A; van de Velde, Helgi; Schaffer, Michael E; Osmanov, Evgenii A; Hong, Xiaonan; Scheliga, Adriana; Mayer, Jiri; Offner, Fritz; Rule, Simon; Teixeira, Adriana; Romejko-Jarosinska, Joanna; de Vos, Sven; Crump, Michael; Shpilberg, Ofer; Zinzani, Pier Luigi; Cakana, Andrew; Esseltine, Dixie-Lee; Mulligan, George; Ricci, Deborah

    2013-05-01

    Identify subgroups of patients with relapsed/refractory follicular lymphoma deriving substantial progression-free survival (PFS) benefit with bortezomib-rituximab versus rituximab in the phase III LYM-3001 study. A total of 676 patients were randomized to five 5-week cycles of bortezomib-rituximab or rituximab. The primary end point was PFS; this prespecified analysis of candidate protein biomarkers and genes was an exploratory objective. Archived tumor tissue and whole blood samples were collected at baseline. Immunohistochemistry and genetic analyses were completed for 4 proteins and 8 genes. In initial pairwise analyses, using individual single-nucleotide polymorphism genotypes, one biomarker pair (PSMB1 P11A C/G heterozygote, low CD68 expression) was associated with a significant PFS benefit with bortezomib-rituximab versus rituximab, controlling for multiple comparison corrections. The pair was analyzed under dominant, recessive, and additive genetic models, with significant association with PFS seen under the dominant model (G/G+C/G). In patients carrying this biomarker pair [PSMB1 P11A G allele, low CD68 expression (≤50 CD68-positive cells), population frequency: 43.6%], median PFS was 14.2 months with bortezomib-rituximab versus 9.1 months with rituximab (HR 0.47, P < 0.0001), and there was a significant overall survival benefit (HR 0.49, P = 0.0461). Response rates were higher and time to next antilymphoma therapy was longer in the bortezomib-rituximab group. In biomarker-negative patients, no significant efficacy differences were seen between treatment groups. Similar proportions of patients had high-risk features in the biomarker-positive and biomarker-negative subsets. Patients with PSMB1 P11A (G allele) and low CD68 expression seemed to have significantly longer PFS and greater clinical benefit with bortezomib-rituximab versus rituximab. ©2013 AACR.

  5. Colon cancer

    Science.gov (United States)

    Colorectal cancer; Cancer - colon; Rectal cancer; Cancer - rectum; Adenocarcinoma - colon; Colon - adenocarcinoma; Colon carcinoma ... eat may play a role in getting colon cancer. Colon cancer may be linked to a high-fat, ...

  6. A de novo transcriptome of the Asian tiger mosquito, Aedes albopictus, to identify candidate transcripts for diapause preparation

    Directory of Open Access Journals (Sweden)

    Poelchau Monica F

    2011-12-01

    Full Text Available Abstract Background Many temperate insects survive the harsh conditions of winter by undergoing photoperiodic diapause, a pre-programmed developmental arrest initiated by short day lengths. Despite the well-established ecological significance of photoperiodic diapause, the molecular basis of this crucial adaptation remains largely unresolved. The Asian tiger mosquito, Aedes albopictus (Skuse, represents an outstanding emerging model to investigate the molecular basis of photoperiodic diapause in a well-defined ecological and evolutionary context. Ae. albopictus is a medically significant vector and is currently considered the most invasive mosquito in the world. Traits related to diapause appear to be important factors contributing to the rapid spread of this mosquito. To generate novel sequence information for this species, as well as to discover transcripts involved in diapause preparation, we sequenced the transcriptome of Ae. albopictus oocytes destined to become diapausing or non-diapausing pharate larvae. Results 454 GS-FLX transcriptome sequencing yielded >1.1 million quality-filtered reads, which we assembled into 69,474 contigs (N50 = 1,009 bp. Our contig filtering approach, where we took advantage of strong sequence similarity to the fully sequenced genome of Aedes aegypti, as well as other reference organisms, resulted in 11,561 high-quality, conservative ESTs. Differential expression estimates based on normalized read counts revealed 57 genes with higher expression, and 257 with lower expression under diapause-inducing conditions. Analysis of expression by qPCR for 47 of these genes indicated a high correlation of expression levels between 454 sequence data and qPCR, but congruence of statistically significant differential expression was low. Seven genes identified as differentially expressed based on qPCR have putative functions that are consistent with the insect diapause syndrome; three genes have unknown function and represent

  7. Using empirical models of species colonization under multiple threatening processes to identify complementary threat-mitigation strategies.

    Science.gov (United States)

    Tulloch, Ayesha I T; Mortelliti, Alessio; Kay, Geoffrey M; Florance, Daniel; Lindenmayer, David

    2016-08-01

    Approaches to prioritize conservation actions are gaining popularity. However, limited empirical evidence exists on which species might benefit most from threat mitigation and on what combination of threats, if mitigated simultaneously, would result in the best outcomes for biodiversity. We devised a way to prioritize threat mitigation at a regional scale with empirical evidence based on predicted changes to population dynamics-information that is lacking in most threat-management prioritization frameworks that rely on expert elicitation. We used dynamic occupancy models to investigate the effects of multiple threats (tree cover, grazing, and presence of an hyperaggressive competitor, the Noisy Miner (Manorina melanocephala) on bird-population dynamics in an endangered woodland community in southeastern Australia. The 3 threatening processes had different effects on different species. We used predicted patch-colonization probabilities to estimate the benefit to each species of removing one or more threats. We then determined the complementary set of threat-mitigation strategies that maximized colonization of all species while ensuring that redundant actions with little benefit were avoided. The single action that resulted in the highest colonization was increasing tree cover, which increased patch colonization by 5% and 11% on average across all species and for declining species, respectively. Combining Noisy Miner control with increasing tree cover increased species colonization by 10% and 19% on average for all species and for declining species respectively, and was a higher priority than changing grazing regimes. Guidance for prioritizing threat mitigation is critical in the face of cumulative threatening processes. By incorporating population dynamics in prioritization of threat management, our approach helps ensure funding is not wasted on ineffective management programs that target the wrong threats or species. © 2016 Society for Conservation Biology.

  8. Secretome Characterization and Correlation Analysis Reveal Putative Pathogenicity Mechanisms and Identify Candidate Avirulence Genes in the Wheat Stripe Rust Fungus Puccinia striiformis f. sp. tritici.

    Science.gov (United States)

    Xia, Chongjing; Wang, Meinan; Cornejo, Omar E; Jiwan, Derick A; See, Deven R; Chen, Xianming

    2017-01-01

    Stripe (yellow) rust, caused by Puccinia striiformis f. sp. tritici ( Pst ), is one of the most destructive diseases of wheat worldwide. Planting resistant cultivars is an effective way to control this disease, but race-specific resistance can be overcome quickly due to the rapid evolving Pst population. Studying the pathogenicity mechanisms is critical for understanding how Pst virulence changes and how to develop wheat cultivars with durable resistance to stripe rust. We re-sequenced 7 Pst isolates and included additional 7 previously sequenced isolates to represent balanced virulence/avirulence profiles for several avirulence loci in seretome analyses. We observed an uneven distribution of heterozygosity among the isolates. Secretome comparison of Pst with other rust fungi identified a large portion of species-specific secreted proteins, suggesting that they may have specific roles when interacting with the wheat host. Thirty-two effectors of Pst were identified from its secretome. We identified candidates for Avr genes corresponding to six Yr genes by correlating polymorphisms for effector genes to the virulence/avirulence profiles of the 14 Pst isolates. The putative AvYr76 was present in the avirulent isolates, but absent in the virulent isolates, suggesting that deleting the coding region of the candidate avirulence gene has produced races virulent to resistance gene Yr76 . We conclude that incorporating avirulence/virulence phenotypes into correlation analysis with variations in genomic structure and secretome, particularly presence/absence polymorphisms of effectors, is an efficient way to identify candidate Avr genes in Pst . The candidate effector genes provide a rich resource for further studies to determine the evolutionary history of Pst populations and the co-evolutionary arms race between Pst and wheat. The Avr candidates identified in this study will lead to cloning avirulence genes in Pst , which will enable us to understand molecular mechanisms

  9. Next-generation sequencing to identify candidate genes and develop diagnostic markers for a novel Phytophthora resistance gene, RpsHC18, in soybean.

    Science.gov (United States)

    Zhong, Chao; Sun, Suli; Li, Yinping; Duan, Canxing; Zhu, Zhendong

    2018-03-01

    A novel Phytophthora sojae resistance gene RpsHC18 was identified and finely mapped on soybean chromosome 3. Two NBS-LRR candidate genes were identified and two diagnostic markers of RpsHC18 were developed. Phytophthora root rot caused by Phytophthora sojae is a destructive disease of soybean. The most effective disease-control strategy is to deploy resistant cultivars carrying Phytophthora-resistant Rps genes. The soybean cultivar Huachun 18 has a broad and distinct resistance spectrum to 12 P. sojae isolates. Quantitative trait loci sequencing (QTL-seq), based on the whole-genome resequencing (WGRS) of two extreme resistant and susceptible phenotype bulks from an F 2:3 population, was performed, and one 767-kb genomic region with ΔSNP-index ≥ 0.9 on chromosome 3 was identified as the RpsHC18 candidate region in Huachun 18. The candidate region was reduced to a 146-kb region by fine mapping. Nonsynonymous SNP and haplotype analyses were carried out in the 146-kb region among ten soybean genotypes using WGRS. Four specific nonsynonymous SNPs were identified in two nucleotide-binding sites-leucine-rich repeat (NBS-LRR) genes, RpsHC18-NBL1 and RpsHC18-NBL2, which were considered to be the candidate genes. Finally, one specific SNP marker in each candidate gene was successfully developed using a tetra-primer ARMS-PCR assay, and the two markers were verified to be specific for RpsHC18 and to effectively distinguish other known Rps genes. In this study, we applied an integrated genomic-based strategy combining WGRS with traditional genetic mapping to identify RpsHC18 candidate genes and develop diagnostic markers. These results suggest that next-generation sequencing is a precise, rapid and cost-effective way to identify candidate genes and develop diagnostic markers, and it can accelerate Rps gene cloning and marker-assisted selection for breeding of P. sojae-resistant soybean cultivars.

  10. Constructing disease-specific gene networks using pair-wise relevance metric: Application to colon cancer identifies interleukin 8, desmin and enolase 1 as the central elements

    Directory of Open Access Journals (Sweden)

    Jiang Wei

    2008-08-01

    Full Text Available Abstract Background With the advance of large-scale omics technologies, it is now feasible to reversely engineer the underlying genetic networks that describe the complex interplays of molecular elements that lead to complex diseases. Current networking approaches are mainly focusing on building genetic networks at large without probing the interaction mechanisms specific to a physiological or disease condition. The aim of this study was thus to develop such a novel networking approach based on the relevance concept, which is ideal to reveal integrative effects of multiple genes in the underlying genetic circuit for complex diseases. Results The approach started with identification of multiple disease pathways, called a gene forest, in which the genes extracted from the decision forest constructed by supervised learning of the genome-wide transcriptional profiles for patients and normal samples. Based on the newly identified disease mechanisms, a novel pair-wise relevance metric, adjusted frequency value, was used to define the degree of genetic relationship between two molecular determinants. We applied the proposed method to analyze a publicly available microarray dataset for colon cancer. The results demonstrated that the colon cancer-specific gene network captured the most important genetic interactions in several cellular processes, such as proliferation, apoptosis, differentiation, mitogenesis and immunity, which are known to be pivotal for tumourigenesis. Further analysis of the topological architecture of the network identified three known hub cancer genes [interleukin 8 (IL8 (p ≈ 0, desmin (DES (p = 2.71 × 10-6 and enolase 1 (ENO1 (p = 4.19 × 10-5], while two novel hub genes [RNA binding motif protein 9 (RBM9 (p = 1.50 × 10-4 and ribosomal protein L30 (RPL30 (p = 1.50 × 10-4] may define new central elements in the gene network specific to colon cancer. Gene Ontology (GO based analysis of the colon cancer-specific gene network and

  11. Constructing disease-specific gene networks using pair-wise relevance metric: application to colon cancer identifies interleukin 8, desmin and enolase 1 as the central elements.

    Science.gov (United States)

    Jiang, Wei; Li, Xia; Rao, Shaoqi; Wang, Lihong; Du, Lei; Li, Chuanxing; Wu, Chao; Wang, Hongzhi; Wang, Yadong; Yang, Baofeng

    2008-08-10

    With the advance of large-scale omics technologies, it is now feasible to reversely engineer the underlying genetic networks that describe the complex interplays of molecular elements that lead to complex diseases. Current networking approaches are mainly focusing on building genetic networks at large without probing the interaction mechanisms specific to a physiological or disease condition. The aim of this study was thus to develop such a novel networking approach based on the relevance concept, which is ideal to reveal integrative effects of multiple genes in the underlying genetic circuit for complex diseases. The approach started with identification of multiple disease pathways, called a gene forest, in which the genes extracted from the decision forest constructed by supervised learning of the genome-wide transcriptional profiles for patients and normal samples. Based on the newly identified disease mechanisms, a novel pair-wise relevance metric, adjusted frequency value, was used to define the degree of genetic relationship between two molecular determinants. We applied the proposed method to analyze a publicly available microarray dataset for colon cancer. The results demonstrated that the colon cancer-specific gene network captured the most important genetic interactions in several cellular processes, such as proliferation, apoptosis, differentiation, mitogenesis and immunity, which are known to be pivotal for tumourigenesis. Further analysis of the topological architecture of the network identified three known hub cancer genes [interleukin 8 (IL8) (p approximately 0), desmin (DES) (p = 2.71 x 10(-6)) and enolase 1 (ENO1) (p = 4.19 x 10(-5))], while two novel hub genes [RNA binding motif protein 9 (RBM9) (p = 1.50 x 10(-4)) and ribosomal protein L30 (RPL30) (p = 1.50 x 10(-4))] may define new central elements in the gene network specific to colon cancer. Gene Ontology (GO) based analysis of the colon cancer-specific gene network and the sub-network that

  12. Proteome analysis identifies the Dpr protein of Streptococcus mutans as an important factor in the presence of early streptococcal colonizers of tooth surfaces.

    Directory of Open Access Journals (Sweden)

    Akihiro Yoshida

    Full Text Available Oral streptococci are primary colonizers of tooth surfaces and Streptococcus mutans is the principal causative agent of dental caries in humans. A number of proteins are involved in the formation of monospecies biofilms by S. mutans. This study analyzed the protein expression profiles of S. mutans biofilms formed in the presence or absence of S. gordonii, a pioneer colonizer of the tooth surface, by two-dimensional gel electrophoresis (2-DE. After identifying S. mutans proteins by Mass spectrometric analysis, their expression in the presence of S. gordonii was analyzed. S. mutans was inoculated with or without S. gordonii DL1. The two species were compartmentalized using 0.2-μl Anopore membranes. The biofilms on polystyrene plates were harvested, and the solubilized proteins were separated by 2-DE. When S. mutans biofilms were formed in the presence of S. gordonii, the peroxide resistance protein Dpr of the former showed 4.3-fold increased expression compared to biofilms that developed in the absence of the pioneer colonizer. In addition, we performed a competition assay using S. mutans antioxidant protein mutants together with S. gordonii and other initial colonizers. Growth of the dpr-knockout S. mutans mutant was significantly inhibited by S. gordonii, as well as by S. sanguinis. Furthermore, a cell viability assay revealed that the viability of the dpr-defective mutant was significantly attenuated compared to the wild-type strain when co-cultured with S. gordonii. Therefore, these results suggest that Dpr might be one of the essential proteins for S. mutans survival on teeth in the presence of early colonizing oral streptococci.

  13. Proteome Analysis Identifies the Dpr Protein of Streptococcus mutans as an Important Factor in the Presence of Early Streptococcal Colonizers of Tooth Surfaces

    Science.gov (United States)

    Yoshida, Akihiro; Niki, Mamiko; Yamamoto, Yuji; Yasunaga, Ai; Ansai, Toshihiro

    2015-01-01

    Oral streptococci are primary colonizers of tooth surfaces and Streptococcus mutans is the principal causative agent of dental caries in humans. A number of proteins are involved in the formation of monospecies biofilms by S. mutans. This study analyzed the protein expression profiles of S. mutans biofilms formed in the presence or absence of S. gordonii, a pioneer colonizer of the tooth surface, by two-dimensional gel electrophoresis (2-DE). After identifying S. mutans proteins by Mass spectrometric analysis, their expression in the presence of S. gordonii was analyzed. S. mutans was inoculated with or without S. gordonii DL1. The two species were compartmentalized using 0.2-μl Anopore membranes. The biofilms on polystyrene plates were harvested, and the solubilized proteins were separated by 2-DE. When S. mutans biofilms were formed in the presence of S. gordonii, the peroxide resistance protein Dpr of the former showed 4.3-fold increased expression compared to biofilms that developed in the absence of the pioneer colonizer. In addition, we performed a competition assay using S. mutans antioxidant protein mutants together with S. gordonii and other initial colonizers. Growth of the dpr-knockout S. mutans mutant was significantly inhibited by S. gordonii, as well as by S. sanguinis. Furthermore, a cell viability assay revealed that the viability of the dpr-defective mutant was significantly attenuated compared to the wild-type strain when co-cultured with S. gordonii. Therefore, these results suggest that Dpr might be one of the essential proteins for S. mutans survival on teeth in the presence of early colonizing oral streptococci. PMID:25816242

  14. Derivation and validation of REASON: a risk score identifying candidates to screen for peripheral arterial disease using ankle brachial index.

    Science.gov (United States)

    Ramos, Rafel; Baena-Díez, Jose Miguel; Quesada, Miquel; Solanas, Pascual; Subirana, Isaac; Sala, Joan; Alzamora, Maite; Forès, Rosa; Masiá, Rafel; Elosua, Roberto; Grau, María; Cordón, Ferran; Pera, Guillem; Rigo, Fernando; Martí, Ruth; Ponjoan, Anna; Cerezo, Carlos; Brugada, Ramon; Marrugat, Jaume

    2011-02-01

    The recommendation of screening with ankle brachial index (ABI) in asymptomatic individuals is controversial. The aims of the present study were to develop and validate a pre-screening test to select candidates for ABI measurement in the Spanish population 50-79 years old, and to compare its predictive capacity to current Inter-Society Consensus (ISC) screening criteria. Two population-based cross-sectional studies were used to develop (n = 4046) and validate (n = 3285) a regression model to predict ABI guidelines, and similar sensitivity. This resulted in fewer patients screened per diagnosis of ABI < 0.9 (10.6 vs. 8.75) and a lower proportion of the population aged 50-79 years candidate to ABI screening (63.3% vs. 55.0%). This model provides accurate ABI < 0.9 risk estimates for ages 50-79, with a better predictive capacity than that of ISC criteria. Its use could reduce possible harms and unnecessary work-ups of ABI screening as a risk stratification strategy in primary prevention of peripheral vascular disease. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  15. Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers.

    Directory of Open Access Journals (Sweden)

    Elena Vigorito

    Full Text Available Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases BRCA1 and 8,211 (631 ovarian cancer cases BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA 2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95%CI: 0.68 to 0.79, p-value 2× 10-16. These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95%CI: 0.59 to 0.80, p-value 1.0 × 10-6. The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population.

  16. Proteomic profiling of antibody-inducing immunogens in tumor tissue identifies PSMA1, LAP3, ANXA3, and maspin as colon cancer markers

    Science.gov (United States)

    Yang, Qian; Roehrl, Michael H.; Wang, Julia Y.

    2018-01-01

    We hypothesized that cancer tissue immunogens – antigens capable of inducing specific antibody production in patients – are promising targets for development of precision diagnostics and humoral immunotherapies. We developed an innovative immuno-proteomic strategy and identified new immunogenic markers of colon cancer. Proteins from cancers and matched normal tissues were separated by 2D gel electrophoresis and blotted with serum antibodies from the same patients. Antibody-reactive proteins were sequenced by mass spectrometry and validated by Western blotting and immunohistochemistry. 170 serum antibody-reactive proteins were identified only in cancerous but not matched normal. Among these, proteasome subunit alpha type 1 (PSA1), leucine aminopeptidase 3 (LAP3), annexin A3 (ANXA3), and maspin (serpin B5) were reproducibly found in tissues from three patients. Differential expression patterns were confirmed in samples from eight patients with various stages of colon adenocarcinoma and liver metastases. These tumor-resident proteins and/or their associated serum antibodies may be promising markers for colon cancer screening and early diagnosis. Furthermore, tumor tissue-specific antibodies could potentially be exploited as immunotherapeutic targets against cancer. More generally, proteomic profiling of antibody-inducing cancer-associated immunogens represents a powerful generic method for uncovering the tumor antigen-ome, i.e., the totality of immunogenic tumor-associated proteins. PMID:29423100

  17. Using microarrays to identify positional candidate genes for QTL: the case study of ACTH response in pigs.

    Science.gov (United States)

    Jouffe, Vincent; Rowe, Suzanne; Liaubet, Laurence; Buitenhuis, Bart; Hornshøj, Henrik; SanCristobal, Magali; Mormède, Pierre; de Koning, D J

    2009-07-16

    Microarray studies can supplement QTL studies by suggesting potential candidate genes in the QTL regions, which by themselves are too large to provide a limited selection of candidate genes. Here we provide a case study where we explore ways to integrate QTL data and microarray data for the pig, which has only a partial genome sequence. We outline various procedures to localize differentially expressed genes on the pig genome and link this with information on published QTL. The starting point is a set of 237 differentially expressed cDNA clones in adrenal tissue from two pig breeds, before and after treatment with adrenocorticotropic hormone (ACTH). Different approaches to localize the differentially expressed (DE) genes to the pig genome showed different levels of success and a clear lack of concordance for some genes between the various approaches. For a focused analysis on 12 genes, overlapping QTL from the public domain were presented. Also, differentially expressed genes underlying QTL for ACTH response were described. Using the latest version of the draft sequence, the differentially expressed genes were mapped to the pig genome. This enabled co-location of DE genes and previously studied QTL regions, but the draft genome sequence is still incomplete and will contain many errors. A further step to explore links between DE genes and QTL at the pathway level was largely unsuccessful due to the lack of annotation of the pig genome. This could be improved by further comparative mapping analyses but this would be time consuming. This paper provides a case study for the integration of QTL data and microarray data for a species with limited genome sequence information and annotation. The results illustrate the challenges that must be addressed but also provide a roadmap for future work that is applicable to other non-model species.

  18. Comparing human pancreatic cell secretomes by in vitro aptamer selection identifies cyclophilin B as a candidate pancreatic cancer biomarker.

    Science.gov (United States)

    Ray, Partha; Rialon-Guevara, Kristy L; Veras, Emanuela; Sullenger, Bruce A; White, Rebekah R

    2012-05-01

    Most cases of pancreatic cancer are not diagnosed until they are no longer curable with surgery. Therefore, it is critical to develop a sensitive, preferably noninvasive, method for detecting the disease at an earlier stage. In order to identify biomarkers for pancreatic cancer, we devised an in vitro positive/negative selection strategy to identify RNA ligands (aptamers) that could detect structural differences between the secretomes of pancreatic cancer and non-cancerous cells. Using this molecular recognition approach, we identified an aptamer (M9-5) that differentially bound conditioned media from cancerous and non-cancerous human pancreatic cell lines. This aptamer further discriminated between the sera of pancreatic cancer patients and healthy volunteers with high sensitivity and specificity. We utilized biochemical purification methods and mass-spectrometric analysis to identify the M9-5 target as cyclophilin B (CypB). This molecular recognition-based strategy simultaneously identified CypB as a serum biomarker and generated a new reagent to recognize it in body fluids. Moreover, this approach should be generalizable to other diseases and complementary to traditional approaches that focus on differences in expression level between samples. Finally, we suggest that the aptamer we identified has the potential to serve as a tool for the early detection of pancreatic cancer.

  19. Genome-wide transcriptome study in wheat identified candidate genes related to processing quality, majority of them showing interaction (quality x development) and having temporal and spatial distributions.

    Science.gov (United States)

    Singh, Anuradha; Mantri, Shrikant; Sharma, Monica; Chaudhury, Ashok; Tuli, Rakesh; Roy, Joy

    2014-01-16

    The cultivated bread wheat (Triticum aestivum L.) possesses unique flour quality, which can be processed into many end-use food products such as bread, pasta, chapatti (unleavened flat bread), biscuit, etc. The present wheat varieties require improvement in processing quality to meet the increasing demand of better quality food products. However, processing quality is very complex and controlled by many genes, which have not been completely explored. To identify the candidate genes whose expressions changed due to variation in processing quality and interaction (quality x development), genome-wide transcriptome studies were performed in two sets of diverse Indian wheat varieties differing for chapatti quality. It is also important to understand the temporal and spatial distributions of their expressions for designing tissue and growth specific functional genomics experiments. Gene-specific two-way ANOVA analysis of expression of about 55 K transcripts in two diverse sets of Indian wheat varieties for chapatti quality at three seed developmental stages identified 236 differentially expressed probe sets (10-fold). Out of 236, 110 probe sets were identified for chapatti quality. Many processing quality related key genes such as glutenin and gliadins, puroindolines, grain softness protein, alpha and beta amylases, proteases, were identified, and many other candidate genes related to cellular and molecular functions were also identified. The ANOVA analysis revealed that the expression of 56 of 110 probe sets was involved in interaction (quality x development). Majority of the probe sets showed differential expression at early stage of seed development i.e. temporal expression. Meta-analysis revealed that the majority of the genes expressed in one or a few growth stages indicating spatial distribution of their expressions. The differential expressions of a few candidate genes such as pre-alpha/beta-gliadin and gamma gliadin were validated by RT-PCR. Therefore, this study

  20. Genome-wide transcriptome study in wheat identified candidate genes related to processing quality, majority of them showing interaction (quality x development) and having temporal and spatial distributions

    Science.gov (United States)

    2014-01-01

    Background The cultivated bread wheat (Triticum aestivum L.) possesses unique flour quality, which can be processed into many end-use food products such as bread, pasta, chapatti (unleavened flat bread), biscuit, etc. The present wheat varieties require improvement in processing quality to meet the increasing demand of better quality food products. However, processing quality is very complex and controlled by many genes, which have not been completely explored. To identify the candidate genes whose expressions changed due to variation in processing quality and interaction (quality x development), genome-wide transcriptome studies were performed in two sets of diverse Indian wheat varieties differing for chapatti quality. It is also important to understand the temporal and spatial distributions of their expressions for designing tissue and growth specific functional genomics experiments. Results Gene-specific two-way ANOVA analysis of expression of about 55 K transcripts in two diverse sets of Indian wheat varieties for chapatti quality at three seed developmental stages identified 236 differentially expressed probe sets (10-fold). Out of 236, 110 probe sets were identified for chapatti quality. Many processing quality related key genes such as glutenin and gliadins, puroindolines, grain softness protein, alpha and beta amylases, proteases, were identified, and many other candidate genes related to cellular and molecular functions were also identified. The ANOVA analysis revealed that the expression of 56 of 110 probe sets was involved in interaction (quality x development). Majority of the probe sets showed differential expression at early stage of seed development i.e. temporal expression. Meta-analysis revealed that the majority of the genes expressed in one or a few growth stages indicating spatial distribution of their expressions. The differential expressions of a few candidate genes such as pre-alpha/beta-gliadin and gamma gliadin were validated by RT

  1. Identifying environmental, social, and psychological correlates of meeting the recommended physical activity levels for colon cancer prevention among Japanese adults.

    Science.gov (United States)

    Ishii, Kaori; Shibata, Ai; Oka, Koichiro

    2013-11-01

    Although physical activity reduces the risk of diseases such as cancer, diabetes and cardiovascular disease, a large proportion of the population is not sufficiently physically active. Therefore, the present study examined the environmental, social, and psychological correlates for meeting the 2 recommended physical activity criteria: ≥420 min per week of at least moderate-intensity activity (MPA criterion) and ≥210 min per week of vigorous activity (VPA criterion) for colon cancer prevention among Japanese adults. Cross-sectional study. The sample included 2000 Japanese adults aged 20-79 years. An Internet-based survey was used to assess seven sociodemographic variables (e.g., education level, employment status), environmental variables (home fitness equipment, access to facilities, neighborhood safety, aesthetic sensibilities, and frequency of observing others exercising, residential area), social variables (social support), psychological variables (self-efficacy, perceived positive (pros) and negative (cons) aspects of exercise), and physical activity. The adjusted odds of meeting each physical activity criterion by these variables were calculated. Overall, 22.3% of the study population met the criterion of MPA, and 7.3% met the criterion of VPA. Having high self-efficacy, fewer perceived cons, possessing home fitness equipment, reporting enjoyable scenery, and living in a rural area were significantly associated with meeting the recommended criteria. Participants who met the 2 activity recommendations differed by self-efficacy, cons, possession of home fitness equipment, reporting of enjoyable scenery, and residential area. These findings imply that strategies to promote more intense physical activities specifically in terms of these variables may be necessary for colon cancer prevention. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  2. Genetic mapping in mice identifies DMBT1 as a candidate modifier of mammary tumors and breast cancer risk

    DEFF Research Database (Denmark)

    Blackburn, Anneke C; Hill, Linda Z; Roberts, Amy L

    2007-01-01

    Low-penetrance breast cancer susceptibility alleles seem to play a significant role in breast cancer risk but are difficult to identify in human cohorts. A genetic screen of 176 N2 backcross progeny of two Trp53(+/-) strains, BALB/c and C57BL/6, which differ in their susceptibility to mammary...... tumors, identified a modifier of mammary tumor susceptibility in an approximately 25-Mb interval on mouse chromosome 7 (designated SuprMam1). Relative to heterozygotes, homozygosity for BALB/c alleles of SuprMam1 significantly decreased mammary tumor latency from 70.7 to 61.1 weeks and increased risk...

  3. Development of Human Breast Milk Microbiota-Associated Mice as a Method to Identify Breast Milk Bacteria Capable of Colonizing Gut.

    Science.gov (United States)

    Wang, Xiaoxin; Lu, Huifang; Feng, Zhou; Cao, Jie; Fang, Chao; Xu, Xianming; Zhao, Liping; Shen, Jian

    2017-01-01

    Human breast milk is recognized as one of multiple important sources of commensal bacteria for infant gut. Previous studies searched for the bacterial strains shared between breast milk and infant feces by isolating bacteria and performing strain-level bacterial genotyping, but only limited number of milk bacteria were identified to colonize infant gut, including bacteria from Bifidobacterium , Staphylococcus , Lactobacillus , and Escherichia / Shigella . Here, to identify the breast milk bacteria capable of colonizing gut without the interference of bacteria of origins other than the milk or the necessity to analyze infant feces, normal chow-fed germ-free mice were orally inoculated with the breast milk collected from a mother 2 days after vaginal delivery. According to 16S rRNA gene-based denaturant gradient gel electrophoresis and Illumina sequencing, bacteria at >1% abundance in the milk inoculum were only Streptococcus (56.0%) and Staphylococcus (37.4%), but in the feces of recipient mice were Streptococcus (80.3 ± 2.3%), Corynebacterium (10.0 ± 2.6 %), Staphylococcus (7.6 ± 1.6%), and Propionibacterium (2.1 ± 0.5%) that were previously shown as dominant bacterial genera in the meconium of C-section-delivered human babies; the abundance of anaerobic gut-associated bacteria, Faecalibacterium , Prevotella , Roseburia , Ruminococcus , and Bacteroides , was 0.01-1% in the milk inoculum and 0.003-0.01% in mouse feces; the abundance of Bifidobacterium spp. was below the detection limit of Illumina sequencing in the milk but at 0.003-0.01% in mouse feces. The human breast milk microbiota-associated mouse model may be used to identify additional breast milk bacteria that potentially colonize infant gut.

  4. Novel CTL epitopes identified through a Y. pestis proteome-wide analysis in the search for vaccine candidates against plague.

    Science.gov (United States)

    Zvi, Anat; Rotem, Shahar; Zauberman, Ayelet; Elia, Uri; Aftalion, Moshe; Bar-Haim, Erez; Mamroud, Emanuelle; Cohen, Ofer

    2017-10-20

    The causative agent of Plague, Yersinia pestis, is a highly virulent pathogen and a potential bioweapon. Depending on the route of infection, two prevalent occurrences of the disease are known, bubonic and pneumonic. The latter has a high fatality rate. In the absence of a licensed vaccine, intense efforts to develop a safe and efficacious vaccine have been conducted, and humoral-driven subunit vaccines containing the F1 and LcrV antigens are currently under clinical trials. It is well known that a cellular immune response might have an essential additive value to immunity and protection against Y. pestis infection. Nevertheless, very few documented epitopes eliciting a protective T-cell response have been reported. Here, we present a combined high throughput computational and experimental effort towards identification of CD8 T-cell epitopes. All 4067 proteins of Y. pestis were analyzed with state-of-the-art recently developed prediction algorithms aimed at mapping potential MHC class I binders. A compilation of the results obtained from several prediction methods revealed a total of 238,000 peptide candidates, which necessitated downstream filtering criteria. Our previously established and proven approach for enrichment of true positive CTL epitopes, which relies on mapping clusters rich in tandem or overlapping predicted MHC binders ("hotspots"), was applied, as well as considerations of predicted binding affinity. A total of 1532 peptides were tested for their ability to elicit a specific T-cell response by following the production of IFNγ from splenocytes isolated from vaccinated mice. Altogether, the screen resulted in 178 positive responders (11.8%), all novel Y. pestis CTL epitopes. These epitopes span 113 Y. pestis proteins. Substantial enrichment of membrane-associated proteins was detected for epitopes selected from hotspots of predicted MHC binders. These results considerably expand the repertoire of known CTL epitopes in Y. pestis and pave the way to

  5. Proteomic profiling of pretreatment serum from HIV-infected patients identifies candidate markers predictive of lymphoma development

    DEFF Research Database (Denmark)

    Vase, Maja Ølholm; Ludvigsen, Maja; Bendix, Knud

    2016-01-01

    . Differentially expressed proteins were identified by liquid chromatography-tandem mass spectrometry. A tissue microarray, containing diagnostic HIV-lymphoma tissue samples (N = 40), was used to investigate immunohistochemical expression of markers in tumoural lesions. RESULTS: Fourteen differentially expressed...... protein spots were detected. Using principal components analysis, spots containing immunoglobulin J chain, apolipoprotein A-I, procollagen C-endopeptidase enhancer-1 and complement C4-A were associated with lymphoma development (P ... with subsequent lymphoma compared with patients without subsequent lymphoma. In the tissue microarray, amyloid A was widely expressed, and high expression showed a tendency towards inferior outcome (log-rank 0.073). CONCLUSION: We identified several differentially expressed protein spots present already...

  6. Global analysis of WRKY transcription factor superfamily in Setaria identifies potential candidates involved in abiotic stress signaling

    OpenAIRE

    Muthamilarasan, Mehanathan; Bonthala, Venkata S.; Khandelwal, Rohit; Jaishankar, Jananee; Shweta, Shweta; Nawaz, Kashif; Prasad, Manoj

    2015-01-01

    Transcription factors (TFs) are major players in stress signalling and constitute an integral part of signalling networks. Among the major TFs, WRKY proteins play pivotal roles in regulation of transcriptional reprogramming associated with stress responses. In view of this, genome- and transcriptome-wide identification of WRKY TF family was performed in the C4 model plants, Setaria italica (SiWRKY) and S. viridis (SvWRKY), respectively. The study identified 105 SiWRKY and 44 SvWRKY proteins t...

  7. Candidate isolated neutron stars and other optically blank x-ray fields identified from the rosat all-sky and sloan digital sky surveys

    Energy Technology Data Exchange (ETDEWEB)

    Agueros, Marcel A.; Anderson, Scott F.; /Washington U., Seattle, Astron. Dept.; Margon, Bruce; /Baltimore, Space Telescope Sci.; Haberl, Frank; Voges, Wolfgang; /Garching,; Annis, James; /Fermilab; Schneider, Donald P.; /Penn State U., Astron. Astrophys.; Brinkmann, Jonathan; /Apache Point Observ.

    2005-11-01

    Only seven radio-quiet isolated neutron stars (INSs) emitting thermal X rays are known, a sample that has yet to definitively address such fundamental issues as the equation of state of degenerate neutron matter. We describe a selection algorithm based on a cross-correlation of the ROSAT All-Sky Survey (RASS) and the Sloan Digital Sky Survey (SDSS) that identifies X-ray error circles devoid of plausible optical counterparts to the SDSS g {approx} 22 magnitudes limit. We quantitatively characterize these error circles as optically blank; they may host INSs or other similarly exotic X-ray sources such as radio-quiet BL Lacs, obscured AGN, etc. Our search is an order of magnitude more selective than previous searches for optically blank RASS error circles, and excludes the 99.9% of error circles that contain more common X-ray-emitting subclasses. We find 11 candidates, nine of which are new. While our search is designed to find the best INS candidates and not to produce a complete list of INSs in the RASS, it is reassuring that our number of candidates is consistent with predictions from INS population models. Further X-ray observations will obtain pinpoint positions and determine whether these sources are entirely optically blank at g {approx} 22, supporting the presence of likely isolated neutron stars and perhaps enabling detailed follow-up studies of neutron star physics.

  8. An in-depth characterization of the major psoriasis susceptibility locus identifies candidate susceptibility alleles within an HLA-C enhancer element.

    Directory of Open Access Journals (Sweden)

    Alex Clop

    Full Text Available Psoriasis is an immune-mediated skin disorder that is inherited as a complex genetic trait. Although genome-wide association scans (GWAS have identified 36 disease susceptibility regions, more than 50% of the genetic variance can be attributed to a single Major Histocompatibility Complex (MHC locus, known as PSORS1. Genetic studies indicate that HLA-C is the strongest PSORS1 candidate gene, since markers tagging HLA-Cw*0602 consistently generate the most significant association signals in GWAS. However, it is unclear whether HLA-Cw*0602 is itself the causal PSORS1 allele, especially as the role of SNPs that may affect its expression has not been investigated. Here, we have undertaken an in-depth molecular characterization of the PSORS1 interval, with a view to identifying regulatory variants that may contribute to disease susceptibility. By analysing high-density SNP data, we refined PSORS1 to a 179 kb region encompassing HLA-C and the neighbouring HCG27 pseudogene. We compared multiple MHC sequences spanning this refined locus and identified 144 candidate susceptibility variants, which are unique to chromosomes bearing HLA-Cw*0602. In parallel, we investigated the epigenetic profile of the critical PSORS1 interval and uncovered three enhancer elements likely to be active in T lymphocytes. Finally we showed that nine candidate susceptibility SNPs map within a HLA-C enhancer and that three of these variants co-localise with binding sites for immune-related transcription factors. These data indicate that SNPs affecting HLA-Cw*0602 expression are likely to contribute to psoriasis susceptibility and highlight the importance of integrating multiple experimental approaches in the investigation of complex genomic regions such as the MHC.

  9. Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

    DEFF Research Database (Denmark)

    Vigorito, Elena; Kuchenbaecker, Karoline B; Beesley, Jonathan

    2016-01-01

    Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2...... mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA 2 mutation carriers respectively...... of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95%CI: 0.59 to 0.80, p-value 1.0 × 10-6). The candidate causal in BRCA1 mutation carriers did not include the strongest...

  10. Label-Free LC-MS/MS Proteomic Analysis of Cerebrospinal Fluid Identifies Protein/Pathway Alterations and Candidate Biomarkers for Amyotrophic Lateral Sclerosis.

    Science.gov (United States)

    Collins, Mahlon A; An, Jiyan; Hood, Brian L; Conrads, Thomas P; Bowser, Robert P

    2015-11-06

    Analysis of the cerebrospinal fluid (CSF) proteome has proven valuable to the study of neurodegenerative disorders. To identify new protein/pathway alterations and candidate biomarkers for amyotrophic lateral sclerosis (ALS), we performed comparative proteomic profiling of CSF from sporadic ALS (sALS), healthy control (HC), and other neurological disease (OND) subjects using label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS). A total of 1712 CSF proteins were detected and relatively quantified by spectral counting. Levels of several proteins with diverse biological functions were significantly altered in sALS samples. Enrichment analysis was used to link these alterations to biological pathways, which were predominantly related to inflammation, neuronal activity, and extracellular matrix regulation. We then used our CSF proteomic profiles to create a support vector machines classifier capable of discriminating training set ALS from non-ALS (HC and OND) samples. Four classifier proteins, WD repeat-containing protein 63, amyloid-like protein 1, SPARC-like protein 1, and cell adhesion molecule 3, were identified by feature selection and externally validated. The resultant classifier distinguished ALS from non-ALS samples with 83% sensitivity and 100% specificity in an independent test set. Collectively, our results illustrate the utility of CSF proteomic profiling for identifying ALS protein/pathway alterations and candidate disease biomarkers.

  11. Low/Negative Expression of PDGFR-α Identifies the Candidate Primary Mesenchymal Stromal Cells in Adult Human Bone Marrow

    DEFF Research Database (Denmark)

    Li, Hongzhe; Ghazanfari, Roshanak; Zacharaki, Dimitra

    2014-01-01

    Human bone marrow (BM) contains a rare population of nonhematopoietic mesenchymal stromal cells (MSCs), which are of central importance for the hematopoietic microenvironment. However, the precise phenotypic definition of these cells in adult BM has not yet been reported. In this study, we show...... exhibited high levels of genes associated with mesenchymal lineages and HSC supportive function. Moreover, lin(-)/CD45(-)/CD271(+)/CD140a(low/-) cells effectively mediated the ex vivo expansion of transplantable CD34(+) hematopoietic stem cells. Taken together, these data indicate that CD140a is a key...... that low/negative expression of CD140a (PDGFR-α) on lin(-)/CD45(-)/CD271(+) BM cells identified a cell population with very high MSC activity, measured as fibroblastic colony-forming unit frequency and typical in vitro and in vivo stroma formation and differentiation capacities. Furthermore, these cells...

  12. The Use of Chemical-Chemical Interaction and Chemical Structure to Identify New Candidate Chemicals Related to Lung Cancer.

    Directory of Open Access Journals (Sweden)

    Lei Chen

    Full Text Available Lung cancer causes over one million deaths every year worldwide. However, prevention and treatment methods for this serious disease are limited. The identification of new chemicals related to lung cancer may aid in disease prevention and the design of more effective treatments. This study employed a weighted network, constructed using chemical-chemical interaction information, to identify new chemicals related to two types of lung cancer: non-small lung cancer and small-cell lung cancer. Then, a randomization test as well as chemical-chemical interaction and chemical structure information were utilized to make further selections. A final analysis of these new chemicals in the context of the current literature indicates that several chemicals are strongly linked to lung cancer.

  13. Metabolite profiling identifies candidate markers reflecting the clinical adaptations associated with Roux-en-Y gastric bypass surgery.

    Directory of Open Access Journals (Sweden)

    David M Mutch

    Full Text Available BACKGROUND: Roux-en-Y gastric bypass (RYGB surgery is associated with weight loss, improved insulin sensitivity and glucose homeostasis, and a reduction in co-morbidities such as diabetes and coronary heart disease. To generate further insight into the numerous metabolic adaptations associated with RYGB surgery, we profiled serum metabolites before and after gastric bypass surgery and integrated metabolite changes with clinical data. METHODOLOGY AND PRINCIPAL FINDINGS: Serum metabolites were detected by gas and liquid chromatography-coupled mass spectrometry before, and 3 and 6 months after RYGB in morbidly obese female subjects (n = 14; BMI = 46.2+/-1.7. Subjects showed decreases in weight-related parameters and improvements in insulin sensitivity post surgery. The abundance of 48% (83 of 172 of the measured metabolites changed significantly within the first 3 months post RYGB (p<0.05, including sphingosines, unsaturated fatty acids, and branched chain amino acids. Dividing subjects into obese (n = 9 and obese/diabetic (n = 5 groups identified 8 metabolites that differed consistently at all time points and whose serum levels changed following RYGB: asparagine, lysophosphatidylcholine (C18:2, nervonic (C24:1 acid, p-Cresol sulfate, lactate, lycopene, glucose, and mannose. Changes in the aforementioned metabolites were integrated with clinical data for body mass index (BMI and estimates for insulin resistance (HOMA-IR. Of these, nervonic acid was significantly and negatively correlated with HOMA-IR (p = 0.001, R = -0.55. CONCLUSIONS: Global metabolite profiling in morbidly obese subjects after RYGB has provided new information regarding the considerable metabolic alterations associated with this surgical procedure. Integrating clinical measurements with metabolomics data is capable of identifying markers that reflect the metabolic adaptations following RYGB.

  14. Inhibition of Thrombopoietin/Mpl Signaling in Adult Hematopoiesis Identifies New Candidates for Hematopoietic Stem Cell Maintenance.

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    Kohlscheen, Saskia; Wintterle, Sabine; Schwarzer, Adrian; Kamp, Christel; Brugman, Martijn H; Breuer, Daniel C; Büsche, Guntram; Baum, Christopher; Modlich, Ute

    2015-01-01

    Thrombopoietin (Thpo) signals via its receptor Mpl and regulates megakaryopoiesis, hematopoietic stem cell (HSC) maintenance and post-transplant expansion. Mpl expression is tightly controlled and deregulation of Thpo/Mpl-signaling is linked to hematological disorders. Here, we constructed an intracellular-truncated, signaling-deficient Mpl protein which is presented on the cell surface (dnMpl). The transplantation of bone marrow cells retrovirally transduced to express dnMpl into wildtype mice induced thrombocytopenia, and a progressive loss of HSC. The aplastic BM allowed the engraftment of a second BM transplant without further conditioning. Functional analysis of the truncated Mpl in vitro and in vivo demonstrated no internalization after Thpo binding and the inhibition of Thpo/Mpl-signaling in wildtype cells due to dominant-negative (dn) effects by receptor competition with wildtype Mpl for Thpo binding. Intracellular inhibition of Mpl could be excluded as the major mechanism by the use of a constitutive-dimerized dnMpl. To further elucidate the molecular changes induced by Thpo/Mpl-inhibition on the HSC-enriched cell population in the BM, we performed gene expression analysis of Lin-Sca1+cKit+ (LSK) cells isolated from mice transplanted with dnMpl transduced BM cells. The gene expression profile supported the exhaustion of HSC due to increased cell cycle progression and identified new and known downstream effectors of Thpo/Mpl-signaling in HSC (namely TIE2, ESAM1 and EPCR detected on the HSC-enriched LSK cell population). We further compared gene expression profiles in LSK cells of dnMpl mice with human CD34+ cells of aplastic anemia patients and identified similar deregulations of important stemness genes in both cell populations. In summary, we established a novel way of Thpo/Mpl inhibition in the adult mouse and performed in depth analysis of the phenotype including gene expression profiling.

  15. A follow-up study for left ventricular mass on chromosome 12p11 identifies potential candidate genes

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    Slifer Susan

    2011-07-01

    Full Text Available Abstract Background Left ventricular mass (LVM is an important risk factor for cardiovascular disease. Previously we found evidence for linkage to chromosome 12p11 in Dominican families, with a significant increase in a subset of families with high average waist circumference (WC. In the present study, we use association analysis to further study the genetic effect on LVM. Methods Association analysis with LVM was done in the one LOD critical region of the linkage peak in an independent sample of 897 Caribbean Hispanics. Genotype data were available on 7085 SNPs from 23 to 53 MB on chromosome 12p11. Adjustment was made for vascular risk factors and population substructure using an additive genetic model. Subset analysis by WC was performed to test for a difference in genetic effects between the high and low WC subsets. Results In the overall analysis, the most significant association was found to rs10743465, downstream of the SOX5 gene (p = 1.27E-05. Also, 19 additional SNPs had nominal p TMTC1. Twelve additional SNPs in or near 6 genes had p Conclusions The current study supports previously identified evidence by linkage for a genetic effect on LVM on chromosome 12p11 using association analysis in population-based Caribbean Hispanic cohort. SOX5 may play an important role in the regulation of LVM. An interaction of TMTC1 with abdominal obesity may contribute to phenotypic variation of LVM.

  16. Molecular profiling of aged neural progenitors identifies Dbx2 as a candidate regulator of age-associated neurogenic decline.

    Science.gov (United States)

    Lupo, Giuseppe; Nisi, Paola S; Esteve, Pilar; Paul, Yu-Lee; Novo, Clara Lopes; Sidders, Ben; Khan, Muhammad A; Biagioni, Stefano; Liu, Hai-Kun; Bovolenta, Paola; Cacci, Emanuele; Rugg-Gunn, Peter J

    2018-06-01

    Adult neurogenesis declines with aging due to the depletion and functional impairment of neural stem/progenitor cells (NSPCs). An improved understanding of the underlying mechanisms that drive age-associated neurogenic deficiency could lead to the development of strategies to alleviate cognitive impairment and facilitate neuroregeneration. An essential step towards this aim is to investigate the molecular changes that occur in NSPC aging on a genomewide scale. In this study, we compare the transcriptional, histone methylation and DNA methylation signatures of NSPCs derived from the subventricular zone (SVZ) of young adult (3 months old) and aged (18 months old) mice. Surprisingly, the transcriptional and epigenomic profiles of SVZ-derived NSPCs are largely unchanged in aged cells. Despite the global similarities, we detect robust age-dependent changes at several hundred genes and regulatory elements, thereby identifying putative regulators of neurogenic decline. Within this list, the homeobox gene Dbx2 is upregulated in vitro and in vivo, and its promoter region has altered histone and DNA methylation levels, in aged NSPCs. Using functional in vitro assays, we show that elevated Dbx2 expression in young adult NSPCs promotes age-related phenotypes, including the reduced proliferation of NSPC cultures and the altered transcript levels of age-associated regulators of NSPC proliferation and differentiation. Depleting Dbx2 in aged NSPCs caused the reverse gene expression changes. Taken together, these results provide new insights into the molecular programmes that are affected during mouse NSPC aging, and uncover a new functional role for Dbx2 in promoting age-related neurogenic decline. © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  17. Candidate nematicidal proteins in a new Pseudomonas veronii isolate identified by its antagonistic properties against Xiphinema index.

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    Canchignia, Hayron; Altimira, Fabiola; Montes, Christian; Sánchez, Evelyn; Tapia, Eduardo; Miccono, María; Espinoza, Daniel; Aguirre, Carlos; Seeger, Michael; Prieto, Humberto

    2017-03-17

    The nematode Xiphinema index affects grape vines and transmits important viruses associated with fanleaf degeneration. Pseudomonas spp. are an extensive bacterial group in which important biodegradation and/or biocontrol properties can occur for several strains in the group. The aim of this study was to identify new Pseudomonas isolates with antagonist activity against X. index. Forty bacterial isolates were obtained from soil and root samples from Chilean vineyards. Thirteen new fluorescent pseudomonads were found and assessed for their antagonistic capability. The nematicide Pseudomonas protegens CHA0 was used as a control. Challenges of nematode individuals in King's B semi-solid agar Petri dishes facilitated the identification of the Pseudomonas veronii isolate R4, as determined by a 16S rRNA sequence comparison. This isolate was as effective as CHA0 as an antagonist of X. index, although it had a different lethality kinetic. Milk-induced R4 cultures exhibited protease and lipase activities in cell supernatants using both gelatin/tributyrin Petri dish assays and zymograms. Three proteins with these activities were isolated and subjected to mass spectrometry. Amino acid partial sequences enabled the identification of a 49-kDa protease similar to metalloprotease AprA and two lipases of 50 kDa and 69 kDa similar to LipA and ExoU, respectively. Electron microscopy analyses of challenged nematodes revealed degraded cuticle after R4 supernatant treatment. These results represent a new and unexplored property in this species associated with the presence of secretable lipases and protease, similar to characterized enzymes present in biocontrol pseudomonads.

  18. A Bayesian Framework for Generalized Linear Mixed Modeling Identifies New Candidate Loci for Late-Onset Alzheimer's Disease.

    Science.gov (United States)

    Wang, Xulong; Philip, Vivek M; Ananda, Guruprasad; White, Charles C; Malhotra, Ankit; Michalski, Paul J; Karuturi, Krishna R Murthy; Chintalapudi, Sumana R; Acklin, Casey; Sasner, Michael; Bennett, David A; De Jager, Philip L; Howell, Gareth R; Carter, Gregory W

    2018-03-05

    Recent technical and methodological advances have greatly enhanced genome-wide association studies (GWAS). The advent of low-cost whole-genome sequencing facilitates high-resolution variant identification, and the development of linear mixed models (LMM) allows improved identification of putatively causal variants. While essential for correcting false positive associations due to sample relatedness and population stratification, LMMs have commonly been restricted to quantitative variables. However, phenotypic traits in association studies are often categorical, coded as binary case-control or ordered variables describing disease stages. To address these issues, we have devised a method for genomic association studies that implements a generalized linear mixed model (GLMM) in a Bayesian framework, called Bayes-GLMM Bayes-GLMM has four major features: (1) support of categorical, binary and quantitative variables; (2) cohesive integration of previous GWAS results for related traits; (3) correction for sample relatedness by mixed modeling; and (4) model estimation by both Markov chain Monte Carlo (MCMC) sampling and maximal likelihood estimation. We applied Bayes-GLMM to the whole-genome sequencing cohort of the Alzheimer's Disease Sequencing Project (ADSP). This study contains 570 individuals from 111 families, each with Alzheimer's disease diagnosed at one of four confidence levels. With Bayes-GLMM we identified four variants in three loci significantly associated with Alzheimer's disease. Two variants, rs140233081 and rs149372995 lie between PRKAR1B and PDGFA The coded proteins are localized to the glial-vascular unit, and PDGFA transcript levels are associated with AD-related neuropathology. In summary, this work provides implementation of a flexible, generalized mixed model approach in a Bayesian framework for association studies. Copyright © 2018, Genetics.

  19. Microarray profiling of mononuclear peripheral blood cells identifies novel candidate genes related to chemoradiation response in rectal cancer.

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    Pablo Palma

    Full Text Available Preoperative chemoradiation significantly improves oncological outcome in locally advanced rectal cancer. However there is no effective method of predicting tumor response to chemoradiation in these patients. Peripheral blood mononuclear cells have emerged recently as pathology markers of cancer and other diseases, making possible their use as therapy predictors. Furthermore, the importance of the immune response in radiosensivity of solid organs led us to hypothesized that microarray gene expression profiling of peripheral blood mononuclear cells could identify patients with response to chemoradiation in rectal cancer. Thirty five 35 patients with locally advanced rectal cancer were recruited initially to perform the study. Peripheral blood samples were obtained before neaodjuvant treatment. RNA was extracted and purified to obtain cDNA and cRNA for hybridization of microarrays included in Human WG CodeLink bioarrays. Quantitative real time PCR was used to validate microarray experiment data. Results were correlated with pathological response, according to Mandard´s criteria and final UICC Stage (patients with tumor regression grade 1-2 and downstaging being defined as responders and patients with grade 3-5 and no downstaging as non-responders. Twenty seven out of 35 patients were finally included in the study. We performed a multiple t-test using Significance Analysis of Microarrays, to find those genes differing significantly in expression, between responders (n = 11 and non-responders (n = 16 to CRT. The differently expressed genes were: BC 035656.1, CIR, PRDM2, CAPG, FALZ, HLA-DPB2, NUPL2, and ZFP36. The measurement of FALZ (p = 0.029 gene expression level determined by qRT-PCR, showed statistically significant differences between the two groups. Gene expression profiling reveals novel genes in peripheral blood samples of mononuclear cells that could predict responders and non-responders to chemoradiation in patients with

  20. Colonic lymphoid follicles associated with colonic neoplasms

    International Nuclear Information System (INIS)

    Glick, S.N.; Teplick, S.K.; Ross, W.M.

    1986-01-01

    The authors prospectively evaluated 62 patients over 40 years old in whom lymphoid follicles were demonstrated on double-contrast enema examinations. Eighteen patients (29%) had no current radiographic evidence of, or history of, colonic neoplasms. Forty-four patients (71%) had an associated neoplasm. Fourteen patients had associated colonic carcinoma, and ten patients had a history of a previously resected colon cancer. One patient had previously undergone resection for ''polyps.'' Twenty-two patients had an associated ''polyp.'' There were no clinical or radiographic features that could reliably distinguish the neoplastic from the nonneoplastic groups. However, lymphoid follicles in the left colon or diffusely involving the colon were more likely to be associated with a colonic neoplasm. Lymphoid follicles were almost always identified near a malignant lesion

  1. Tensor decomposition-based unsupervised feature extraction identifies candidate genes that induce post-traumatic stress disorder-mediated heart diseases.

    Science.gov (United States)

    Taguchi, Y-H

    2017-12-21

    Although post-traumatic stress disorder (PTSD) is primarily a mental disorder, it can cause additional symptoms that do not seem to be directly related to the central nervous system, which PTSD is assumed to directly affect. PTSD-mediated heart diseases are some of such secondary disorders. In spite of the significant correlations between PTSD and heart diseases, spatial separation between the heart and brain (where PTSD is primarily active) prevents researchers from elucidating the mechanisms that bridge the two disorders. Our purpose was to identify genes linking PTSD and heart diseases. In this study, gene expression profiles of various murine tissues observed under various types of stress or without stress were analyzed in an integrated manner using tensor decomposition (TD). Based upon the obtained features, ∼ 400 genes were identified as candidate genes that may mediate heart diseases associated with PTSD. Various gene enrichment analyses supported biological reliability of the identified genes. Ten genes encoding protein-, DNA-, or mRNA-interacting proteins-ILF2, ILF3, ESR1, ESR2, RAD21, HTT, ATF2, NR3C1, TP53, and TP63-were found to be likely to regulate expression of most of these ∼ 400 genes and therefore are candidate primary genes that cause PTSD-mediated heart diseases. Approximately 400 genes in the heart were also found to be strongly affected by various drugs whose known adverse effects are related to heart diseases and/or fear memory conditioning; these data support the reliability of our findings. TD-based unsupervised feature extraction turned out to be a useful method for gene selection and successfully identified possible genes causing PTSD-mediated heart diseases.

  2. Genomewide high-density SNP linkage analysis of non-BRCA1/2 breast cancer families identifies various candidate regions and has greater power than microsatellite studies

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    Gonzalez-Neira Anna

    2007-08-01

    Full Text Available Abstract Background The recent development of new high-throughput technologies for SNP genotyping has opened the possibility of taking a genome-wide linkage approach to the search for new candidate genes involved in heredity diseases. The two major breast cancer susceptibility genes BRCA1 and BRCA2 are involved in 30% of hereditary breast cancer cases, but the discovery of additional breast cancer predisposition genes for the non-BRCA1/2 breast cancer families has so far been unsuccessful. Results In order to evaluate the power improvement provided by using SNP markers in a real situation, we have performed a whole genome screen of 19 non-BRCA1/2 breast cancer families using 4720 genomewide SNPs with Illumina technology (Illumina's Linkage III Panel, with an average distance of 615 Kb/SNP. We identified six regions on chromosomes 2, 3, 4, 7, 11 and 14 as candidates to contain genes involved in breast cancer susceptibility, and additional fine mapping genotyping using microsatellite markers around linkage peaks confirmed five of them, excluding the region on chromosome 3. These results were consistent in analyses that excluded SNPs in high linkage disequilibrium. The results were compared with those obtained previously using a 10 cM microsatellite scan (STR-GWS and we found lower or not significant linkage signals with STR-GWS data compared to SNP data in all cases. Conclusion Our results show the power increase that SNPs can supply in linkage studies.

  3. Transcriptome analysis of the fungal pathogen Fusarium oxysporum f. sp. medicaginis during colonisation of resistant and susceptible Medicago truncatula hosts identifies differential pathogenicity profiles and novel candidate effectors.

    Science.gov (United States)

    Thatcher, Louise F; Williams, Angela H; Garg, Gagan; Buck, Sally-Anne G; Singh, Karam B

    2016-11-03

    Pathogenic members of the Fusarium oxysporum species complex are responsible for vascular wilt disease on many important crops including legumes, where they can be one of the most destructive disease causing necrotrophic fungi. We previously developed a model legume-infecting pathosystem based on the reference legume Medicago truncatula and a pathogenic F. oxysporum forma specialis (f. sp.) medicaginis (Fom). To dissect the molecular pathogenicity arsenal used by this root-infecting pathogen, we sequenced its transcriptome during infection of a susceptible and resistant host accession. High coverage RNA-Seq of Fom infected root samples harvested from susceptible (DZA315) or resistant (A17) M. truncatula seedlings at early or later stages of infection (2 or 7 days post infection (dpi)) and from vegetative (in vitro) samples facilitated the identification of unique and overlapping sets of in planta differentially expressed genes. This included enrichment, particularly in DZA315 in planta up-regulated datasets, for proteins associated with sugar, protein and plant cell wall metabolism, membrane transport, nutrient uptake and oxidative processes. Genes encoding effector-like proteins were identified, including homologues of the F. oxysporum f. sp. lycopersici Secreted In Xylem (SIX) proteins, and several novel candidate effectors based on predicted secretion, small protein size and high in-planta induced expression. The majority of the effector candidates contain no known protein domains but do share high similarity to predicted proteins predominantly from other F. oxysporum ff. spp. as well as other Fusaria (F. solani, F. fujikori, F. verticilloides, F. graminearum and F. pseudograminearum), and from another wilt pathogen of the same class, a Verticillium species. Overall, this suggests these novel effector candidates may play important roles in Fusaria and wilt pathogen virulence. Combining high coverage in planta RNA-Seq with knowledge of fungal pathogenicity

  4. Leaf morphology in Cowpea [Vigna unguiculata (L.) Walp]: QTL analysis, physical mapping and identifying a candidate gene using synteny with model legume species.

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    Pottorff, Marti; Ehlers, Jeffrey D; Fatokun, Christian; Roberts, Philip A; Close, Timothy J

    2012-06-12

    Cowpea [Vigna unguiculata (L.) Walp] exhibits a considerable variation in leaf shape. Although cowpea is mostly utilized as a dry grain and animal fodder crop, cowpea leaves are also used as a high-protein pot herb in many countries of Africa. Leaf morphology was studied in the cowpea RIL population, Sanzi (sub-globose leaf shape) x Vita 7 (hastate leaf shape). A QTL for leaf shape, Hls (hastate leaf shape), was identified on the Sanzi x Vita 7 genetic map spanning from 56.54 cM to 67.54 cM distance on linkage group 15. SNP marker 1_0910 was the most significant over the two experiments, accounting for 74.7% phenotypic variance (LOD 33.82) in a greenhouse experiment and 71.5% phenotypic variance (LOD 30.89) in a field experiment. The corresponding Hls locus was positioned on the cowpea consensus genetic map on linkage group 4, spanning from 25.57 to 35.96 cM. A marker-trait association of the Hls region identified SNP marker 1_0349 alleles co-segregating with either the hastate or sub-globose leaf phenotype. High co-linearity was observed for the syntenic Hls region in Medicago truncatula and Glycine max. One syntenic locus for Hls was identified on Medicago chromosome 7 while syntenic regions for Hls were identified on two soybean chromosomes, 3 and 19. In all three syntenic loci, an ortholog for the EZA1/SWINGER (AT4G02020.1) gene was observed and is the candidate gene for the Hls locus. The Hls locus was identified on the cowpea physical map via SNP markers 1_0910, 1_1013 and 1_0992 which were identified in three BAC contigs; contig926, contig821 and contig25. This study has demonstrated how integrated genomic resources can be utilized for a candidate gene approach. Identification of genes which control leaf morphology may be utilized to improve the quality of cowpea leaves for vegetable and or forage markets as well as contribute to more fundamental research understanding the control of leaf shape in legumes.

  5. A comprehensive approach to identify reliable reference gene candidates to investigate the link between alcoholism and endocrinology in Sprague-Dawley rats.

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    Faten A Taki

    Full Text Available Gender and hormonal differences are often correlated with alcohol dependence and related complications like addiction and breast cancer. Estrogen (E2 is an important sex hormone because it serves as a key protein involved in organism level signaling pathways. Alcoholism has been reported to affect estrogen receptor signaling; however, identifying the players involved in such multi-faceted syndrome is complex and requires an interdisciplinary approach. In many situations, preliminary investigations included a straight forward, yet informative biotechniques such as gene expression analyses using quantitative real time PCR (qRT-PCR. The validity of qRT-PCR-based conclusions is affected by the choice of reliable internal controls. With this in mind, we compiled a list of 15 commonly used housekeeping genes (HKGs as potential reference gene candidates in rat biological models. A comprehensive comparison among 5 statistical approaches (geNorm, dCt method, NormFinder, BestKeeper, and RefFinder was performed to identify the minimal number as well the most stable reference genes required for reliable normalization in experimental rat groups that comprised sham operated (SO, ovariectomized rats in the absence (OVX or presence of E2 (OVXE2. These rat groups were subdivided into subgroups that received alcohol in liquid diet or isocalroic control liquid diet for 12 weeks. Our results showed that U87, 5S rRNA, GAPDH, and U5a were the most reliable gene candidates for reference genes in heart and brain tissue. However, different gene stability ranking was specific for each tissue input combination. The present preliminary findings highlight the variability in reference gene rankings across different experimental conditions and analytic methods and constitute a fundamental step for gene expression assays.

  6. Distinct high resolution genome profiles of early onset and late onset colorectal cancer integrated with gene expression data identify candidate susceptibility loci

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    Merok Marianne A

    2010-05-01

    Full Text Available Abstract Background Estimates suggest that up to 30% of colorectal cancers (CRC may develop due to an increased genetic risk. The mean age at diagnosis for CRC is about 70 years. Time of disease onset 20 years younger than the mean age is assumed to be indicative of genetic susceptibility. We have compared high resolution tumor genome copy number variation (CNV (Roche NimbleGen, 385 000 oligo CGH array in microsatellite stable (MSS tumors from two age groups, including 23 young at onset patients without known hereditary syndromes and with a median age of 44 years (range: 28-53 and 17 elderly patients with median age 79 years (range: 69-87. Our aim was to identify differences in the tumor genomes between these groups and pinpoint potential susceptibility loci. Integration analysis of CNV and genome wide mRNA expression data, available for the same tumors, was performed to identify a restricted candidate gene list. Results The total fraction of the genome with aberrant copy number, the overall genomic profile and the TP53 mutation spectrum were similar between the two age groups. However, both the number of chromosomal aberrations and the number of breakpoints differed significantly between the groups. Gains of 2q35, 10q21.3-22.1, 10q22.3 and 19q13.2-13.31 and losses from 1p31.3, 1q21.1, 2q21.2, 4p16.1-q28.3, 10p11.1 and 19p12, positions that in total contain more than 500 genes, were found significantly more often in the early onset group as compared to the late onset group. Integration analysis revealed a covariation of DNA copy number at these sites and mRNA expression for 107 of the genes. Seven of these genes, CLC, EIF4E, LTBP4, PLA2G12A, PPAT, RG9MTD2, and ZNF574, had significantly different mRNA expression comparing median expression levels across the transcriptome between the two groups. Conclusions Ten genomic loci, containing more than 500 protein coding genes, are identified as more often altered in tumors from early onset versus late

  7. The Use of High-Density SNP Array to Map Homozygosity in Consanguineous Families to Efficiently Identify Candidate Genes: Application to Woodhouse-Sakati Syndrome

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    Molly B. Sheridan

    2015-01-01

    Full Text Available Two consanguineous Qatari siblings presented for evaluation: a 17-4/12-year-old male with hypogonadotropic hypogonadism, alopecia, intellectual disability, and microcephaly and his 19-year-old sister with primary amenorrhea, alopecia, and normal cognition. Both required hormone treatment to produce secondary sex characteristics and pubertal development beyond Tanner 1. SNP array analysis of both probands was performed to detect shared regions of homozygosity which may harbor homozygous mutations in a gene causing their common features of abnormal pubertal development, alopecia, and variable cognitive delay. Our patients shared multiple homozygous genomic regions; ten shared regions were >1 Mb in length and constituted 0.99% of the genome. DCAF17, encoding a transmembrane nuclear protein of uncertain function, was the only gene identified in a homozygous region known to cause hypogonadotropic hypogonadism. DCAF17 mutations are associated with Woodhouse-Sakati syndrome, a rare disorder characterized by alopecia, hypogonadotropic hypogonadism, sensorineural hearing loss, diabetes mellitus, and extrapyramidal movements. Sequencing of the coding exons and flanking intronic regions of DCAF17 in the proband revealed homozygosity for a previously described founder mutation (c.436delC. Targeted DCAF17 sequencing of his affected sibling revealed the same homozygous mutation. This family illustrates the utility of SNP array testing in consanguineous families to efficiently and inexpensively identify regions of genomic homozygosity in which genetic candidates for recessive conditions can be identified.

  8. Cross-species multiple environmental stress responses: An integrated approach to identify candidate genes for multiple stress tolerance in sorghum (Sorghum bicolor (L. Moench and related model species.

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    Adugna Abdi Woldesemayat

    Full Text Available Crop response to the changing climate and unpredictable effects of global warming with adverse conditions such as drought stress has brought concerns about food security to the fore; crop yield loss is a major cause of concern in this regard. Identification of genes with multiple responses across environmental stresses is the genetic foundation that leads to crop adaptation to environmental perturbations.In this paper, we introduce an integrated approach to assess candidate genes for multiple stress responses across-species. The approach combines ontology based semantic data integration with expression profiling, comparative genomics, phylogenomics, functional gene enrichment and gene enrichment network analysis to identify genes associated with plant stress phenotypes. Five different ontologies, viz., Gene Ontology (GO, Trait Ontology (TO, Plant Ontology (PO, Growth Ontology (GRO and Environment Ontology (EO were used to semantically integrate drought related information.Target genes linked to Quantitative Trait Loci (QTLs controlling yield and stress tolerance in sorghum (Sorghum bicolor (L. Moench and closely related species were identified. Based on the enriched GO terms of the biological processes, 1116 sorghum genes with potential responses to 5 different stresses, such as drought (18%, salt (32%, cold (20%, heat (8% and oxidative stress (25% were identified to be over-expressed. Out of 169 sorghum drought responsive QTLs associated genes that were identified based on expression datasets, 56% were shown to have multiple stress responses. On the other hand, out of 168 additional genes that have been evaluated for orthologous pairs, 90% were conserved across species for drought tolerance. Over 50% of identified maize and rice genes were responsive to drought and salt stresses and were co-located within multifunctional QTLs. Among the total identified multi-stress responsive genes, 272 targets were shown to be co-localized within QTLs

  9. Deep sequencing analysis of the transcriptomes of peanut aerial and subterranean young pods identifies candidate genes related to early embryo abortion.

    Science.gov (United States)

    Chen, Xiaoping; Zhu, Wei; Azam, Sarwar; Li, Heying; Zhu, Fanghe; Li, Haifen; Hong, Yanbin; Liu, Haiyan; Zhang, Erhua; Wu, Hong; Yu, Shanlin; Zhou, Guiyuan; Li, Shaoxiong; Zhong, Ni; Wen, Shijie; Li, Xingyu; Knapp, Steve J; Ozias-Akins, Peggy; Varshney, Rajeev K; Liang, Xuanqiang

    2013-01-01

    The failure of peg penetration into the soil leads to seed abortion in peanut. Knowledge of genes involved in these processes is comparatively deficient. Here, we used RNA-seq to gain insights into transcriptomes of aerial and subterranean pods. More than 2 million transcript reads with an average length of 396 bp were generated from one aerial (AP) and two subterranean (SP1 and SP2) pod libraries using pyrosequencing technology. After assembly, sets of 49 632, 49 952 and 50 494 from a total of 74 974 transcript assembly contigs (TACs) were identified in AP, SP1 and SP2, respectively. A clear linear relationship in the gene expression level was observed between these data sets. In brief, 2194 differentially expressed TACs with a 99.0% true-positive rate were identified, among which 859 and 1068 TACs were up-regulated in aerial and subterranean pods, respectively. Functional analysis showed that putative function based on similarity with proteins catalogued in UniProt and gene ontology term classification could be determined for 59 342 (79.2%) and 42 955 (57.3%) TACs, respectively. A total of 2968 TACs were mapped to 174 KEGG pathways, of which 168 were shared by aerial and subterranean transcriptomes. TACs involved in photosynthesis were significantly up-regulated and enriched in the aerial pod. In addition, two senescence-associated genes were identified as significantly up-regulated in the aerial pod, which potentially contribute to embryo abortion in aerial pods, and in turn, to cessation of swelling. The data set generated in this study provides evidence for some functional genes as robust candidates underlying aerial and subterranean pod development and contributes to an elucidation of the evolutionary implications resulting from fruit development under light and dark conditions. © 2012 The Authors Plant Biotechnology Journal © 2012 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

  10. Integration of sequence data from a Consanguineous family with genetic data from an outbred population identifies PLB1 as a candidate rheumatoid arthritis risk gene.

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    Yukinori Okada

    Full Text Available Integrating genetic data from families with highly penetrant forms of disease together with genetic data from outbred populations represents a promising strategy to uncover the complete frequency spectrum of risk alleles for complex traits such as rheumatoid arthritis (RA. Here, we demonstrate that rare, low-frequency and common alleles at one gene locus, phospholipase B1 (PLB1, might contribute to risk of RA in a 4-generation consanguineous pedigree (Middle Eastern ancestry and also in unrelated individuals from the general population (European ancestry. Through identity-by-descent (IBD mapping and whole-exome sequencing, we identified a non-synonymous c.2263G>C (p.G755R mutation at the PLB1 gene on 2q23, which significantly co-segregated with RA in family members with a dominant mode of inheritance (P = 0.009. We further evaluated PLB1 variants and risk of RA using a GWAS meta-analysis of 8,875 RA cases and 29,367 controls of European ancestry. We identified significant contributions of two independent non-coding variants near PLB1 with risk of RA (rs116018341 [MAF = 0.042] and rs116541814 [MAF = 0.021], combined P = 3.2 × 10(-6. Finally, we performed deep exon sequencing of PLB1 in 1,088 RA cases and 1,088 controls (European ancestry, and identified suggestive dispersion of rare protein-coding variant frequencies between cases and controls (P = 0.049 for C-alpha test and P = 0.055 for SKAT. Together, these data suggest that PLB1 is a candidate risk gene for RA. Future studies to characterize the full spectrum of genetic risk in the PLB1 genetic locus are warranted.

  11. Gene Network Construction from Microarray Data Identifies a Key Network Module and Several Candidate Hub Genes in Age-Associated Spatial Learning Impairment.

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    Uddin, Raihan; Singh, Shiva M

    2017-01-01

    As humans age many suffer from a decrease in normal brain functions including spatial learning impairments. This study aimed to better understand the molecular mechanisms in age-associated spatial learning impairment (ASLI). We used a mathematical modeling approach implemented in Weighted Gene Co-expression Network Analysis (WGCNA) to create and compare gene network models of young (learning unimpaired) and aged (predominantly learning impaired) brains from a set of exploratory datasets in rats in the context of ASLI. The major goal was to overcome some of the limitations previously observed in the traditional meta- and pathway analysis using these data, and identify novel ASLI related genes and their networks based on co-expression relationship of genes. This analysis identified a set of network modules in the young, each of which is highly enriched with genes functioning in broad but distinct GO functional categories or biological pathways. Interestingly, the analysis pointed to a single module that was highly enriched with genes functioning in "learning and memory" related functions and pathways. Subsequent differential network analysis of this "learning and memory" module in the aged (predominantly learning impaired) rats compared to the young learning unimpaired rats allowed us to identify a set of novel ASLI candidate hub genes. Some of these genes show significant repeatability in networks generated from independent young and aged validation datasets. These hub genes are highly co-expressed with other genes in the network, which not only show differential expression but also differential co-expression and differential connectivity across age and learning impairment. The known function of these hub genes indicate that they play key roles in critical pathways, including kinase and phosphatase signaling, in functions related to various ion channels, and in maintaining neuronal integrity relating to synaptic plasticity and memory formation. Taken together, they

  12. High-Content Screening in hPSC-Neural Progenitors Identifies Drug Candidates that Inhibit Zika Virus Infection in Fetal-like Organoids and Adult Brain.

    Science.gov (United States)

    Zhou, Ting; Tan, Lei; Cederquist, Gustav Y; Fan, Yujie; Hartley, Brigham J; Mukherjee, Suranjit; Tomishima, Mark; Brennand, Kristen J; Zhang, Qisheng; Schwartz, Robert E; Evans, Todd; Studer, Lorenz; Chen, Shuibing

    2017-08-03

    Zika virus (ZIKV) infects fetal and adult human brain and is associated with serious neurological complications. To date, no therapeutic treatment is available to treat ZIKV-infected patients. We performed a high-content chemical screen using human pluripotent stem cell-derived cortical neural progenitor cells (hNPCs) and found that hippeastrine hydrobromide (HH) and amodiaquine dihydrochloride dihydrate (AQ) can inhibit ZIKV infection in hNPCs. Further validation showed that HH also rescues ZIKV-induced growth and differentiation defects in hNPCs and human fetal-like forebrain organoids. Finally, HH and AQ inhibit ZIKV infection in adult mouse brain in vivo. Strikingly, HH suppresses viral propagation when administered to adult mice with active ZIKV infection, highlighting its therapeutic potential. Our approach highlights the power of stem cell-based screens and validation in human forebrain organoids and mouse models in identifying drug candidates for treating ZIKV infection and related neurological complications in fetal and adult patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Genome-Wide Transcriptome Analysis of Cotton (Gossypium hirsutum L. Identifies Candidate Gene Signatures in Response to Aflatoxin Producing Fungus Aspergillus flavus.

    Directory of Open Access Journals (Sweden)

    Renesh Bedre

    Full Text Available Aflatoxins are toxic and potent carcinogenic metabolites produced from the fungi Aspergillus flavus and A. parasiticus. Aflatoxins can contaminate cottonseed under conducive preharvest and postharvest conditions. United States federal regulations restrict the use of aflatoxin contaminated cottonseed at >20 ppb for animal feed. Several strategies have been proposed for controlling aflatoxin contamination, and much success has been achieved by the application of an atoxigenic strain of A. flavus in cotton, peanut and maize fields. Development of cultivars resistant to aflatoxin through overexpression of resistance associated genes and/or knocking down aflatoxin biosynthesis of A. flavus will be an effective strategy for controlling aflatoxin contamination in cotton. In this study, genome-wide transcriptome profiling was performed to identify differentially expressed genes in response to infection with both toxigenic and atoxigenic strains of A. flavus on cotton (Gossypium hirsutum L. pericarp and seed. The genes involved in antifungal response, oxidative burst, transcription factors, defense signaling pathways and stress response were highly differentially expressed in pericarp and seed tissues in response to A. flavus infection. The cell-wall modifying genes and genes involved in the production of antimicrobial substances were more active in pericarp as compared to seed. The genes involved in auxin and cytokinin signaling were also induced. Most of the genes involved in defense response in cotton were highly induced in pericarp than in seed. The global gene expression analysis in response to fungal invasion in cotton will serve as a source for identifying biomarkers for breeding, potential candidate genes for transgenic manipulation, and will help in understanding complex plant-fungal interaction for future downstream research.

  14. Transcriptomic Analysis Identifies Candidate Genes Related to Intramuscular Fat Deposition and Fatty Acid Composition in the Breast Muscle of Squabs (Columba

    Directory of Open Access Journals (Sweden)

    Manhong Ye

    2016-07-01

    Full Text Available Despite the fact that squab is consumed throughout the world because of its high nutritional value and appreciated sensory attributes, aspects related to its characterization, and in particular genetic issues, have rarely been studied. In this study, meat traits in terms of pH, water-holding capacity, intramuscular fat content, and fatty acid profile of the breast muscle of squabs from two meat pigeon breeds were determined. Breed-specific differences were detected in fat-related traits of intramuscular fat content and fatty acid composition. RNA-Sequencing was applied to compare the transcriptomes of muscle and liver tissues between squabs of two breeds to identify candidate genes associated with the differences in the capacity of fat deposition. A total of 27 differentially expressed genes assigned to pathways of lipid metabolism were identified, of which, six genes belonged to the peroxisome proliferator-activated receptor signaling pathway along with four other genes. Our results confirmed in part previous reports in livestock and provided also a number of genes which had not been related to fat deposition so far. These genes can serve as a basis for further investigations to screen markers closely associated with intramuscular fat content and fatty acid composition in squabs. The data from this study were deposited in the National Center for Biotechnology Information (NCBI’s Sequence Read Archive under the accession numbers SRX1680021 and SRX1680022. This is the first transcriptome analysis of the muscle and liver tissue in Columba using next generation sequencing technology. Data provided here are of potential value to dissect functional genes influencing fat deposition in squabs.

  15. Genome-wide analysis of the CCCH zinc finger family identifies tissue specific and stress responsive candidates in chickpea (Cicer arietinum L.).

    Science.gov (United States)

    Pradhan, Seema; Kant, Chandra; Verma, Subodh; Bhatia, Sabhyata

    2017-01-01

    The CCCH zinc finger is a group of proteins characterised by a typical motif consisting of three cysteine residues and one histidine residue. These proteins have been reported to play important roles in regulation of plant growth, developmental processes and environmental responses. In the present study, genome wide analysis of the CCCH zinc finger gene family was carried out in the available chickpea genome. Various bioinformatics tools were employed to predict 58 CCCH zinc finger genes in chickpea (designated CarC3H1-58), which were analysed for their physio-chemical properties. Phylogenetic analysis classified the proteins into 12 groups in which members of a particular group had similar structural organization. Further, the numbers as well as the types of CCCH motifs present in the CarC3H proteins were compared with those from Arabidopsis and Medicago truncatula. Synteny analysis revealed valuable information regarding the evolution of this gene family. Tandem and segmental duplication events were identified and their Ka/Ks values revealed that the CarC3H gene family in chickpea had undergone purifying selection. Digital, as well as real time qRT-PCR expression analysis was performed which helped in identification of several CarC3H members that expressed preferentially in specific chickpea tissues as well as during abiotic stresses (desiccation, cold, salinity). Moreover, molecular characterization of an important member CarC3H45 was carried out. This study provides comprehensive genomic information about the important CCCH zinc finger gene family in chickpea. The identified tissue specific and abiotic stress specific CCCH genes could be potential candidates for further characterization to delineate their functional roles in development and stress.

  16. Identifying miRNA and gene modules of colon cancer associated with pathological stage by weighted gene co-expression network analysis

    Directory of Open Access Journals (Sweden)

    Zhou X

    2018-05-01

    characterize the results of WGCNA.Results: Two gene modules (Gmagenta and Ggreen and one miRNA module were associated with the pathological stage. Six hub genes (COL1A2, THBS2, BGN, COL1A1, TAGLN and DACT3 were related to prognosis and validated to be associated with the pathological stage. Five hub miRNAs were identified to be related to prognosis (hsa-miR-125b-5p, hsa-miR-145-5p, hsa-let-7c-5p, hsa-miR-218-5p and hsa-miR-125b-2-3p. A total of 18 hub genes and seven hub miRNAs were predominantly expressed in tumor stroma. Proteoglycans in cancer, focal adhesion, extracellular matrix (ECM–receptor interaction and so on were common pathways of the three modules. Hsa-let-7c-5p was located at the core of miRNA–gene network.Conclusion: These findings help to advance the understanding of tumor stroma in the progression of CAC and provide prognostic biomarkers as well as therapeutic targets. Keywords: colon adenocarcinoma, weighted gene co-expression network analysis, differentially expressed genes, differentially expressed miRNA, tumor stroma

  17. A genome-wide association study identifies candidate loci associated to syringomyelia secondary to Chiari-like malformation in Cavalier King Charles Spaniels.

    Science.gov (United States)

    Ancot, Frédéric; Lemay, Philippe; Knowler, Susan P; Kennedy, Karen; Griffiths, Sandra; Cherubini, Giunio Bruto; Sykes, Jane; Mandigers, Paul J J; Rouleau, Guy A; Rusbridge, Clare; Kibar, Zoha

    2018-03-22

    Syringomyelia (SM) is a common condition affecting brachycephalic toy breed dogs and is characterized by the development of fluid-filled cavities within the spinal cord. It is often concurrent with a complex developmental malformation of the skull and craniocervical vertebrae called Chiari-like malformation (CM) characterized by a conformational change and overcrowding of the brain and cervical spinal cord particularly at the craniocervical junction. CM and SM have a polygenic mode of inheritance with variable penetrance. We identified six cranial T1-weighted sagittal MRI measurements that were associated to maximum transverse diameter of the syrinx cavity. Increased syrinx transverse diameter has been correlated previously with increased likelihood of behavioral signs of pain. We next conducted a whole genome association study of these traits in 65 Cavalier King Charles Spaniel (CKCS) dogs (33 controls, 32 with extreme phenotypes). Two loci on CFA22 and CFA26 were found to be significantly associated to two traits associated with a reduced volume and altered orientation of the caudal cranial fossa. Their reconstructed haplotypes defined two associated regions that harbor only two genes: PCDH17 on CFA22 and ZWINT on CFA26. PCDH17 codes for a cell adhesion molecule expressed specifically in the brain and spinal cord. ZWINT plays a role in chromosome segregation and its expression is increased with the onset of neuropathic pain. Targeted genomic sequencing of these regions identified respectively 37 and 339 SNPs with significantly associated P values. Genotyping of tagSNPs selected from these 2 candidate loci in an extended cohort of 461 CKCS (187 unaffected, 274 SM affected) identified 2 SNPs on CFA22 that were significantly associated to SM strengthening the candidacy of this locus in SM development. We identified 2 loci on CFA22 and CFA26 that contained only 2 genes, PCDH17 and ZWINT, significantly associated to two traits associated with syrinx transverse

  18. Induction of KIAA1199/CEMIP is associated with colon cancer phenotype and poor patient survival.

    Science.gov (United States)

    Fink, Stephen P; Myeroff, Lois L; Kariv, Revital; Platzer, Petra; Xin, Baozhong; Mikkola, Debra; Lawrence, Earl; Morris, Nathan; Nosrati, Arman; Willson, James K V; Willis, Joseph; Veigl, Martina; Barnholtz-Sloan, Jill S; Wang, Zhenghe; Markowitz, Sanford D

    2015-10-13

    Genes induced in colon cancer provide novel candidate biomarkers of tumor phenotype and aggressiveness. We originally identified KIAA1199 (now officially called CEMIP) as a transcript highly induced in colon cancer: initially designating the transcript as Colon Cancer Secreted Protein 1. We molecularly characterized CEMIP expression both at the mRNA and protein level and found it is a secreted protein induced an average of 54-fold in colon cancer. Knockout of CEMIPreduced the ability of human colon cancer cells to form xenograft tumors in athymic mice. Tumors that did grow had increased deposition of hyaluronan, linking CEMIP participation in hyaluronan degradation to the modulation of tumor phenotype. We find CEMIP mRNA overexpression correlates with poorer patient survival. In stage III only (n = 31) or in combined stage II plus stage III colon cancer cases (n = 73), 5-year overall survival was significantly better (p = 0.004 and p = 0.0003, respectively) among patients with low CEMIP expressing tumors than those with high CEMIP expressing tumors. These results demonstrate that CEMIP directly facilitates colon tumor growth, and high CEMIP expression correlates with poor outcome in stage III and in stages II+III combined cohorts. We present CEMIP as a candidate prognostic marker for colon cancer and a potential therapeutic target.

  19. Intermediate phenotype analysis of patients, unaffected siblings, and healthy controls identifies VMAT2 as a candidate gene for psychotic disorder and neurocognition

    NARCIS (Netherlands)

    Simons, C.J.; van Winkel, R.; Bruggeman, R.; Cahn, W.; de Haan, L.; Kahn, R.S.; Krabbendam, L.; Linzen, D.; Myin-Germeys, I.; van Os, J; Wiersma, D.

    2013-01-01

    Psychotic disorders are associated with neurocognitive alterations that aggregate in unaffected family members, suggesting that genetic vulnerability to psychotic disorder impacts neurocognition. The aim of the present study was to investigate whether selected schizophrenia candidate single

  20. Comparative transcriptome analysis of stylar canal cells identifies novel candidate genes implicated in the self-incompatibility response of Citrus clementina

    Directory of Open Access Journals (Sweden)

    Caruso Marco

    2012-02-01

    Full Text Available Abstract Background Reproductive biology in citrus is still poorly understood. Although in recent years several efforts have been made to study pollen-pistil interaction and self-incompatibility, little information is available about the molecular mechanisms regulating these processes. Here we report the identification of candidate genes involved in pollen-pistil interaction and self-incompatibility in clementine (Citrus clementina Hort. ex Tan.. These genes have been identified comparing the transcriptomes of laser-microdissected stylar canal cells (SCC isolated from two genotypes differing for self-incompatibility response ('Comune', a self-incompatible cultivar and 'Monreal', a self- compatible mutation of 'Comune'. Results The transcriptome profiling of SCC indicated that the differential regulation of few specific, mostly uncharacterized transcripts is associated with the breakdown of self-incompatibility in 'Monreal'. Among them, a novel F-box gene showed a drastic up-regulation both in laser microdissected stylar canal cells and in self-pollinated whole styles with stigmas of 'Comune' in concomitance with the arrest of pollen tube growth. Moreover, we identify a non-characterized gene family as closely associated to the self-incompatibility genetic program activated in 'Comune'. Three different aspartic-acid rich (Asp-rich protein genes, located in tandem in the clementine genome, were over-represented in the transcriptome of 'Comune'. These genes are tightly linked to a DELLA gene, previously found to be up-regulated in the self-incompatible genotype during pollen-pistil interaction. Conclusion The highly specific transcriptome survey of the stylar canal cells identified novel genes which have not been previously associated with self-pollen rejection in citrus and in other plant species. Bioinformatic and transcriptional analyses suggested that the mutation leading to self-compatibility in 'Monreal' affected the expression of non

  1. Igf1r+/CD34+ immature ICC are putative adult progenitor cells, identified ultrastructurally as fibroblast-like ICC in Ws/Ws rat colon

    DEFF Research Database (Denmark)

    Wang, X Y; Albertí, E; White, E J

    2009-01-01

    by ICC in the wild-type rat colon, suggesting them to be immature ICC. In addition, a marked increase in immunoreactivity for insulin-like growth factor 1 receptor (Igf1r) occurred, co-localized with CD34 but not with c-Kit. A significantly higher number of Igf1r(+)/CD34(+) cells were found in Ws....../Ws compared to wild-type rat colons. These CD34(+)/Igf1r(+) cells in the Ws/Ws colon occupied the same space as FL-ICC. Hence we propose that a subset of immature ICC (FL-ICC) consists of adult progenitor cells. Immunohistochemistry revealed a reduction of neurons positive for neuronal nitric oxide synthase...

  2. Genome-wide scan for visceral leishmaniasis in mixed-breed dogs identifies candidate genes involved in T helper cells and macrophage signaling

    Science.gov (United States)

    We conducted a genome-wide scan for visceral leishmaniasis in mixed-breed dogs from a highly endemic area in Brazil using 149,648 single nucleotide polymorphism (SNP) markers genotyped in 20 cases and 28 controls. Using a mixed model approach, we found two candidate loci on canine autosomes 1 and 2....

  3. Genomewide high-density SNP linkage analysis of non-BRCA1/2 breast cancer families identifies various candidate regions and has greater power than microsatellite studies

    NARCIS (Netherlands)

    A. González-Neira (Anna); J.M. Rosa-Rosa; A. Osorio (Ana); E. Gonzalez (Emilio); M.C. Southey (Melissa); O. Sinilnikova (Olga); H. Lynch (Henry); R.A. Oldenburg (Rogier); C.J. van Asperen (Christi); N. Hoogerbrugge (Nicoline); G. Pita (Guillermo); P. Devilee (Peter); D. Goldgar (David); J. Benítez (Javier)

    2007-01-01

    textabstractBackground: The recent development of new high-throughput technologies for SNP genotyping has opened the possibility of taking a genome-wide linkage approach to the search for new candidate genes involved in heredity diseases. The two major breast cancer susceptibility genes BRCA1 and

  4. Systematic characterisation of disease associated balanced chromosome rearrangements by FISH: cytogenetically and genetically anchored YACs identify microdeletions and candidate regions for mental retardation genes

    DEFF Research Database (Denmark)

    Wirth, J; Nothwang, H G; van der Maarel, S

    1999-01-01

    the Mendelian Cytogenetics Network (MCN), a collaborative effort of, at present, 270 cytogenetic laboratories throughout the world. In this pilot study, we have characterised 10 different MR associated chromosome regions delineating candidate regions for MR. Five of these regions are narrowed to breakpoint...

  5. Different waves of effector genes with contrasted genomic location are expressed by Leptosphaeria maculans during cotyledon and stem colonization of oilseed rape.

    Science.gov (United States)

    Gervais, Julie; Plissonneau, Clémence; Linglin, Juliette; Meyer, Michel; Labadie, Karine; Cruaud, Corinne; Fudal, Isabelle; Rouxel, Thierry; Balesdent, Marie-Hélène

    2017-10-01

    Leptosphaeria maculans, the causal agent of stem canker disease, colonizes oilseed rape (Brassica napus) in two stages: a short and early colonization stage corresponding to cotyledon or leaf colonization, and a late colonization stage during which the fungus colonizes systemically and symptomlessly the plant during several months before stem canker appears. To date, the determinants of the late colonization stage are poorly understood; L. maculans may either successfully escape plant defences, leading to stem canker development, or the plant may develop an 'adult-stage' resistance reducing canker incidence. To obtain an insight into these determinants, we performed an RNA-sequencing (RNA-seq) pilot project comparing fungal gene expression in infected cotyledons and in symptomless or necrotic stems. Despite the low fraction of fungal material in infected stems, sufficient fungal transcripts were detected and a large number of fungal genes were expressed, thus validating the feasibility of the approach. Our analysis showed that all avirulence genes previously identified are under-expressed during stem colonization compared with cotyledon colonization. A validation RNA-seq experiment was then performed to investigate the expression of candidate effector genes during systemic colonization. Three hundred and seven 'late' effector candidates, under-expressed in the early colonization stage and over-expressed in the infected stems, were identified. Finally, our analysis revealed a link between the regulation of expression of effectors and their genomic location: the 'late' effector candidates, putatively involved in systemic colonization, are located in gene-rich genomic regions, whereas the 'early' effector genes, over-expressed in the early colonization stage, are located in gene-poor regions of the genome. © 2016 BSPP AND JOHN WILEY & SONS LTD.

  6. Colon interposition

    International Nuclear Information System (INIS)

    Isolauri, J.; Tampere Univ. Central Hospital; Paakkala, T.; Arajaervi, P.; Markkula, H.

    1987-01-01

    Colon interposition was carried out in 12 patients with oesophageal carcinoma and on 38 patients with benign oesophageal disease an average of 71 months before the radiographic examination. Various ischaemic changes including 'jejunization', loss of haustration and stricture formation were observed in 15 cases. In 12 patients one or several diverticula were seen in the colon graft. Reflux was observed in 17 cases in supine position. Double contrast technique in the examination of interposed colon is recommended. (orig.)

  7. Optical observations of the nearby galaxy IC342 with narrow band [SII] and hα filters. II - detection of 16 optically-identified supernova remnant candidates

    Directory of Open Access Journals (Sweden)

    Vučetić M.M.

    2015-01-01

    Full Text Available We present the detection of 16 optical supernova remnant (SNR candidates in the nearby spiral galaxy IC342. The candidates were detected by applying the [Sii]/Hα ratio criterion on observations made with the 2 m RCC telescope at Rozhen National Astronomical Observatory in Bulgaria. In this paper, we report the coordinates, diameters, Hα and [S ii] fluxes for 16 SNRs detected in two fields of view in the IC342 galaxy. Also, we estimate the contamination of total Hα flux from SNRs in the observed portion of IC342 to be 1.4%. This would represent the fractional error when the star formation rate (SFR for this galaxy is derived from the total galaxy’s Hα emission.

  8. Colonic lipoma

    International Nuclear Information System (INIS)

    Siddiqui, M.S.; Khatri, A.R.; Quraishy, M.S.; Fatima, L.; Muzaffar, S.

    2003-01-01

    Lipoma of the colon is rare and may lead to intestinal obstruct. We have presented two cases of colonic lipoma. Both were elderly females, one presented with diarrhea and the other with sub-acute intestinal obstruction. After colonoscopy surgical removal was done. Histopathology revealed lipoma. (author)

  9. Colonic angiodysplasia

    International Nuclear Information System (INIS)

    Vallee, C.; Legmann, P.; Garnier, T.; Levesque, M.

    1984-01-01

    The main clinical, endoscopic and radiographic findings in thirty documented cases of colonic angiodysplasia or vacular ectasia are described. We emphasise the association with colonic diverticulosis and cardiovascular pathology, describe the histological changes, summarize the present physiopathological hypothesis, and consider the various therapeutic approaches. (orig.)

  10. Colonic locomotion

    NARCIS (Netherlands)

    Dodou, D.

    2006-01-01

    The most effective screening method for colonic cancer is colonoscopy. However, colonoscopy cannot be easily embraced by the population because of the related pain intensity. Robotic devices that pull themselves forward through the colon are a possible alternative. The main challenge for such

  11. Integrative ChIP-seq/microarray analysis identifies a CTNNB1 target signature enriched in intestinal stem cells and colon cancer.

    Science.gov (United States)

    Watanabe, Kazuhide; Biesinger, Jacob; Salmans, Michael L; Roberts, Brian S; Arthur, William T; Cleary, Michele; Andersen, Bogi; Xie, Xiaohui; Dai, Xing

    2014-01-01

    Deregulation of canonical Wnt/CTNNB1 (beta-catenin) pathway is one of the earliest events in the pathogenesis of colon cancer. Mutations in APC or CTNNB1 are highly frequent in colon cancer and cause aberrant stabilization of CTNNB1, which activates the transcription of Wnt target genes by binding to chromatin via the TCF/LEF transcription factors. Here we report an integrative analysis of genome-wide chromatin occupancy of CTNNB1 by chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) and gene expression profiling by microarray analysis upon RNAi-mediated knockdown of CTNNB1 in colon cancer cells. We observed 3629 CTNNB1 binding peaks across the genome and a significant correlation between CTNNB1 binding and knockdown-induced gene expression change. Our integrative analysis led to the discovery of a direct Wnt target signature composed of 162 genes. Gene ontology analysis of this signature revealed a significant enrichment of Wnt pathway genes, suggesting multiple feedback regulations of the pathway. We provide evidence that this gene signature partially overlaps with the Lgr5+ intestinal stem cell signature, and is significantly enriched in normal intestinal stem cells as well as in clinical colorectal cancer samples. Interestingly, while the expression of the CTNNB1 target gene set does not correlate with survival, elevated expression of negative feedback regulators within the signature predicts better prognosis. Our data provide a genome-wide view of chromatin occupancy and gene regulation of Wnt/CTNNB1 signaling in colon cancer cells.

  12. Integrative ChIP-seq/microarray analysis identifies a CTNNB1 target signature enriched in intestinal stem cells and colon cancer.

    Directory of Open Access Journals (Sweden)

    Kazuhide Watanabe

    Full Text Available Deregulation of canonical Wnt/CTNNB1 (beta-catenin pathway is one of the earliest events in the pathogenesis of colon cancer. Mutations in APC or CTNNB1 are highly frequent in colon cancer and cause aberrant stabilization of CTNNB1, which activates the transcription of Wnt target genes by binding to chromatin via the TCF/LEF transcription factors. Here we report an integrative analysis of genome-wide chromatin occupancy of CTNNB1 by chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq and gene expression profiling by microarray analysis upon RNAi-mediated knockdown of CTNNB1 in colon cancer cells.We observed 3629 CTNNB1 binding peaks across the genome and a significant correlation between CTNNB1 binding and knockdown-induced gene expression change. Our integrative analysis led to the discovery of a direct Wnt target signature composed of 162 genes. Gene ontology analysis of this signature revealed a significant enrichment of Wnt pathway genes, suggesting multiple feedback regulations of the pathway. We provide evidence that this gene signature partially overlaps with the Lgr5+ intestinal stem cell signature, and is significantly enriched in normal intestinal stem cells as well as in clinical colorectal cancer samples. Interestingly, while the expression of the CTNNB1 target gene set does not correlate with survival, elevated expression of negative feedback regulators within the signature predicts better prognosis.Our data provide a genome-wide view of chromatin occupancy and gene regulation of Wnt/CTNNB1 signaling in colon cancer cells.

  13. Combined serial analysis of gene expression and transcription factor binding site prediction identifies novel-candidate-target genes of Nr2e1 in neocortex development.

    Science.gov (United States)

    Schmouth, Jean-François; Arenillas, David; Corso-Díaz, Ximena; Xie, Yuan-Yun; Bohacec, Slavita; Banks, Kathleen G; Bonaguro, Russell J; Wong, Siaw H; Jones, Steven J M; Marra, Marco A; Simpson, Elizabeth M; Wasserman, Wyeth W

    2015-07-24

    Nr2e1 (nuclear receptor subfamily 2, group e, member 1) encodes a transcription factor important in neocortex development. Previous work has shown that nuclear receptors can have hundreds of target genes, and bind more than 300 co-interacting proteins. However, recognition of the critical role of Nr2e1 in neural stem cells and neocortex development is relatively recent, thus the molecular mechanisms involved for this nuclear receptor are only beginning to be understood. Serial analysis of gene expression (SAGE), has given researchers both qualitative and quantitative information pertaining to biological processes. Thus, in this work, six LongSAGE mouse libraries were generated from laser microdissected tissue samples of dorsal VZ/SVZ (ventricular zone and subventricular zone) from the telencephalon of wild-type (Wt) and Nr2e1-null embryos at the critical development ages E13.5, E15.5, and E17.5. We then used a novel approach, implementing multiple computational methods followed by biological validation to further our understanding of Nr2e1 in neocortex development. In this work, we have generated a list of 1279 genes that are differentially expressed in response to altered Nr2e1 expression during in vivo neocortex development. We have refined this list to 64 candidate direct-targets of NR2E1. Our data suggested distinct roles for Nr2e1 during different neocortex developmental stages. Most importantly, our results suggest a possible novel pathway by which Nr2e1 regulates neurogenesis, which includes Lhx2 as one of the candidate direct-target genes, and SOX9 as a co-interactor. In conclusion, we have provided new candidate interacting partners and numerous well-developed testable hypotheses for understanding the pathways by which Nr2e1 functions to regulate neocortex development.

  14. Evaluation of the Morpho-physiology characteristics of maize inbred lines introduced from CIMMYT to identify the best candidates for planting in acidic soil in Jasinga, Indonesia

    Science.gov (United States)

    Lubis, K.; Sutjahjo, S. H.; Syukur, M.; Trikoesoemaningtyas

    2016-08-01

    Technological developments and climate change have affected crop planting strategies. For example, maize production has expanded to sub-optimal lands, including acidic soil common in areas like Indonesia. Breeding programs have created inbred lines of maize introduced from CIMMYT; they were tested locally in acidic soils to determine their adaptability and tolerance mechanisms. Breeds CLA 46 and NEI 9008 were found to be excellent candidates for acidic soil due to their ASI, high number of grains per year, and suitable dry seed weight.

  15. Outcomes of colon resection in patients with metastatic colon cancer.

    Science.gov (United States)

    Moghadamyeghaneh, Zhobin; Hanna, Mark H; Hwang, Grace; Mills, Steven; Pigazzi, Alessio; Stamos, Michael J; Carmichael, Joseph C

    2016-08-01

    Patients with advanced colorectal cancer have a high incidence of postoperative complications. We sought to identify outcomes of patients who underwent resection for colon cancer by cancer stage. The National Surgical Quality Improvement Program database was used to evaluate all patients who underwent colon resection with a diagnosis of colon cancer from 2012 to 2014. Multivariate logistic regression analysis was performed to investigate patient outcomes by cancer stage. A total of 7,786 colon cancer patients who underwent colon resection were identified. Of these, 10.8% had metastasis at the time of operation. Patients with metastatic disease had significantly increased risks of perioperative morbidity (adjusted odds ratio [AOR]: 1.44, P = .01) and mortality (AOR: 3.72, P = .01). Patients with metastatic disease were significantly younger (AOR: .99, P colon cancer have metastatic disease. Postoperative morbidity and mortality are significantly higher than in patients with localized disease. Published by Elsevier Inc.

  16. Colon neoplasm

    International Nuclear Information System (INIS)

    Kimura F, K.

    1991-01-01

    The main aspects of colon neoplasms are described, including several factors that predispose the disease, the occurrence, the main biomedical radiography and the evaluation after the surgery. (C.G.C.)

  17. Conservative management of colonic injury during percutaneous ...

    African Journals Online (AJOL)

    M. Elghoneimy

    2016-02-22

    Feb 22, 2016 ... Patients' records were searched for the occurrence of colonic injury. Records were ... tion to opacify the system and the percutaneous renal access was .... identify the presence of a retrorenal colon, yet the rarity of such a.

  18. The EndoC-βH1 cell line is a valid model of human beta cells and applicable for screenings to identify novel drug target candidates.

    Science.gov (United States)

    Tsonkova, Violeta Georgieva; Sand, Fredrik Wolfhagen; Wolf, Xenia Asbæk; Grunnet, Lars Groth; Kirstine Ringgaard, Anna; Ingvorsen, Camilla; Winkel, Louise; Kalisz, Mark; Dalgaard, Kevin; Bruun, Christine; Fels, Johannes Josef; Helgstrand, Charlotte; Hastrup, Sven; Öberg, Fredrik Kryh; Vernet, Erik; Sandrini, Michael Paolo Bastner; Shaw, Allan Christian; Jessen, Carsten; Grønborg, Mads; Hald, Jacob; Willenbrock, Hanni; Madsen, Dennis; Wernersson, Rasmus; Hansson, Lena; Jensen, Jan Nygaard; Plesner, Annette; Alanentalo, Tomas; Petersen, Maja Borup Kjær; Grapin-Botton, Anne; Honoré, Christian; Ahnfelt-Rønne, Jonas; Hecksher-Sørensen, Jacob; Ravassard, Philippe; Madsen, Ole D; Rescan, Claude; Frogne, Thomas

    2018-02-01

    To characterize the EndoC-βH1 cell line as a model for human beta cells and evaluate its beta cell functionality, focusing on insulin secretion, proliferation, apoptosis and ER stress, with the objective to assess its potential as a screening platform for identification of novel anti-diabetic drug candidates. EndoC-βH1 was transplanted into mice for validation of in vivo functionality. Insulin secretion was evaluated in cells cultured as monolayer and as pseudoislets, as well as in diabetic mice. Cytokine induced apoptosis, glucolipotoxicity, and ER stress responses were assessed. Beta cell relevant mRNA and protein expression were investigated by qPCR and antibody staining. Hundreds of proteins or peptides were tested for their effect on insulin secretion and proliferation. Transplantation of EndoC-βH1 cells restored normoglycemia in streptozotocin induced diabetic mice. Both in vitro and in vivo, we observed a clear insulin response to glucose, and, in vitro, we found a significant increase in insulin secretion from EndoC-βH1 pseudoislets compared to monolayer cultures for both glucose and incretins. Apoptosis and ER stress were inducible in the cells and caspase 3/7 activity was elevated in response to cytokines, but not affected by the saturated fatty acid palmitate. By screening of various proteins and peptides, we found Bombesin (BB) receptor agonists and Pituitary Adenylate Cyclase-Activating Polypeptides (PACAP) to significantly induce insulin secretion and the proteins SerpinA6, STC1, and APOH to significantly stimulate proliferation. ER stress was readily induced by Tunicamycin and resulted in a reduction of insulin mRNA. Somatostatin (SST) was found to be expressed by 1% of the cells and manipulation of the SST receptors was found to significantly affect insulin secretion. Overall, the EndoC-βH1 cells strongly resemble human islet beta cells in terms of glucose and incretin stimulated insulin secretion capabilities. The cell line has an active

  19. The EndoC-βH1 cell line is a valid model of human beta cells and applicable for screenings to identify novel drug target candidates

    Directory of Open Access Journals (Sweden)

    Violeta Georgieva Tsonkova

    2018-02-01

    Full Text Available Objective: To characterize the EndoC-βH1 cell line as a model for human beta cells and evaluate its beta cell functionality, focusing on insulin secretion, proliferation, apoptosis and ER stress, with the objective to assess its potential as a screening platform for identification of novel anti-diabetic drug candidates. Methods: EndoC-βH1 was transplanted into mice for validation of in vivo functionality. Insulin secretion was evaluated in cells cultured as monolayer and as pseudoislets, as well as in diabetic mice. Cytokine induced apoptosis, glucolipotoxicity, and ER stress responses were assessed. Beta cell relevant mRNA and protein expression were investigated by qPCR and antibody staining. Hundreds of proteins or peptides were tested for their effect on insulin secretion and proliferation. Results: Transplantation of EndoC-βH1 cells restored normoglycemia in streptozotocin induced diabetic mice. Both in vitro and in vivo, we observed a clear insulin response to glucose, and, in vitro, we found a significant increase in insulin secretion from EndoC-βH1 pseudoislets compared to monolayer cultures for both glucose and incretins.Apoptosis and ER stress were inducible in the cells and caspase 3/7 activity was elevated in response to cytokines, but not affected by the saturated fatty acid palmitate.By screening of various proteins and peptides, we found Bombesin (BB receptor agonists and Pituitary Adenylate Cyclase-Activating Polypeptides (PACAP to significantly induce insulin secretion and the proteins SerpinA6, STC1, and APOH to significantly stimulate proliferation.ER stress was readily induced by Tunicamycin and resulted in a reduction of insulin mRNA. Somatostatin (SST was found to be expressed by 1% of the cells and manipulation of the SST receptors was found to significantly affect insulin secretion. Conclusions: Overall, the EndoC-βH1 cells strongly resemble human islet beta cells in terms of glucose and incretin stimulated

  20. Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

    NARCIS (Netherlands)

    Vigorito, E.; Kuchenbaecker, K.B.; Beesley, J.; Adlard, J.; Agnarsson, B.A.; Andrulis, I.L.; Arun, B.K.; Barjhoux, L.; Belotti, M.; Benitez, J.; Berger, A.; Bojesen, A.; Bonanni, B.; Brewer, C.; Caldes, T.; Caligo, M.A.; Campbell, I.; Chan, S.B.; Claes, K.B.; Cohn, D.E.; Cook, J.; Daly, M.B.; Damiola, F.; Davidson, R.; Pauw, A. de; Delnatte, C.; Diez, O.; Domchek, S.M.; Dumont, M.; Durda, K.; Dworniczak, B.; Easton, D.F.; Eccles, D.; Edwinsdotter Ardnor, C.; Eeles, R.; Ejlertsen, B.; Ellis, S.; Evans, D.G.; Feliubadalo, L.; Fostira, F.; Foulkes, W.D.; Friedman, E.; Frost, D.; Gaddam, P.; Ganz, P.A.; Garber, J.; Garcia-Barberan, V.; Gauthier-Villars, M.; Gehrig, A.; Gerdes, A.M.; Giraud, S.; Godwin, A.K.; Goldgar, D.E.; Hake, C.R.; Hansen, T.V.; Healey, S.; Hodgson, S.; Hogervorst, F.B.; Houdayer, C.; Hulick, P.J.; Imyanitov, E.N.; Isaacs, C.; Izatt, L.; Izquierdo, A.; Jacobs, L; Jakubowska, A.; Janavicius, R.; Jaworska-Bieniek, K.; Jensen, U.B.; John, E.M.; Vijai, J.; Karlan, B.Y.; Kast, K.; Khan, S.; Kwong, A.; Laitman, Y.; Lester, J.; Lesueur, F.; Liljegren, A.; Lubinski, J.; Mai, P.L.; Manoukian, S.; Mazoyer, S.; Meindl, A.; Mensenkamp, A.R.; Montagna, M.; Nathanson, K.L.; Neuhausen, S.L.; Nevanlinna, H.; Niederacher, D.; Olah, E.; Olopade, O.I.; Ong, K.R.; Osorio, A.; Park, S.K.; Paulsson-Karlsson, Y.; Pedersen, I.S.; Peissel, B.; Peterlongo, P.; et al.,

    2016-01-01

    Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2

  1. Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

    DEFF Research Database (Denmark)

    Vigorito, Elena; Kuchenbaecker, Karoline B; Beesley, Jonathan

    2016-01-01

    Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 ...

  2. Diffuse hemangioma of the colon

    International Nuclear Information System (INIS)

    Reis, J.; Caseiro-Alves, F.; Cruz, L.; Moreira, A.; Rebelo, O.

    1995-01-01

    We report two cases of diffuse hemangioma of the colon in adolescent patients. One patient had multiple phleboliths at the lower pelvis identified with plain radiographs of the abdomen. Several aspects were seen on double-contrast enema: luminal narrowing, colonic-wall thickening and submucosal colonic masses that changed in appearance with the degree of colonic distension. Angiography was inconclusive in one case. Use of CT and MR provided relevant information regarding the true extent of the disease, but MR was superior in demonstrating unequivocally the vascular nature of the lesions. (orig.)

  3. Frequency of Somatic TP53 Mutations in Combination with Known Pathogenic Mutations in Colon Adenocarcinoma, Non–Small Cell Lung Carcinoma, and Gliomas as Identified by Next-Generation Sequencing

    Directory of Open Access Journals (Sweden)

    Zahra Shajani-Yi

    2018-03-01

    Full Text Available The tumor suppressor gene TP53 is the most frequently mutated gene in human cancer. It encodes p53, a DNA-binding transcription factor that regulates multiple genes involved in DNA repair, metabolism, cell cycle arrest, apoptosis, and senescence. TP53 is associated with human cancer by mutations that lead to a loss of wild-type p53 function as well as mutations that confer alternate oncogenic functions that enable them to promote invasion, metastasis, proliferation, and cell survival. Identifying the discrete TP53 mutations in tumor cells may help direct therapies that are more effective. In this study, we identified the frequency of individual TP53 mutations in patients with colon adenocarcinoma (48%, non–small cell lung carcinoma (NSCLC (36%, and glioma/glioblastoma (28% at our institution using next-generation sequencing. We also identified the occurrence of somatic mutations in numerous actionable genes including BRAF, EGFR, KRAS, IDH1, and PIK3CA that occurred concurrently with these TP53 mutations. Of the 480 tumors examined that contained one or more mutations in the TP53 gene, 219 were colon adenocarcinomas, 215 were NSCLCs, and 46 were gliomas/glioblastomas. Among the patients positive for TP53 mutations diagnosed with colon adenocarcinoma, 50% also showed at least one mutation in pathogenic genes of which 14% were BRAF, 33% were KRAS, and 3% were NRAS. Forty-seven percent of NSCLC patients harboring TP53 mutations also had a mutation in at least one actionable pathogenic variant with the following frequencies: BRAF: 4%, EGFR: 10%, KRAS: 28%, and PIK3CA: 4%. Fifty-two percent of patients diagnosed with glioma/glioblastoma with a positive TP53 mutation had at least one concurrent mutation in a known pathogenic gene of which 9% were CDKN2A, 41% were IDH1, and 11% were PIK3CA.

  4. Microarray analysis and scale-free gene networks identify candidate regulators in drought-stressed roots of loblolly pine (P. taeda L.

    Directory of Open Access Journals (Sweden)

    Bordeaux John M

    2011-05-01

    Full Text Available Abstract Background Global transcriptional analysis of loblolly pine (Pinus taeda L. is challenging due to limited molecular tools. PtGen2, a 26,496 feature cDNA microarray, was fabricated and used to assess drought-induced gene expression in loblolly pine propagule roots. Statistical analysis of differential expression and weighted gene correlation network analysis were used to identify drought-responsive genes and further characterize the molecular basis of drought tolerance in loblolly pine. Results Microarrays were used to interrogate root cDNA populations obtained from 12 genotype × treatment combinations (four genotypes, three watering regimes. Comparison of drought-stressed roots with roots from the control treatment identified 2445 genes displaying at least a 1.5-fold expression difference (false discovery rate = 0.01. Genes commonly associated with drought response in pine and other plant species, as well as a number of abiotic and biotic stress-related genes, were up-regulated in drought-stressed roots. Only 76 genes were identified as differentially expressed in drought-recovered roots, indicating that the transcript population can return to the pre-drought state within 48 hours. Gene correlation analysis predicts a scale-free network topology and identifies eleven co-expression modules that ranged in size from 34 to 938 members. Network topological parameters identified a number of central nodes (hubs including those with significant homology (E-values ≤ 2 × 10-30 to 9-cis-epoxycarotenoid dioxygenase, zeatin O-glucosyltransferase, and ABA-responsive protein. Identified hubs also include genes that have been associated previously with osmotic stress, phytohormones, enzymes that detoxify reactive oxygen species, and several genes of unknown function. Conclusion PtGen2 was used to evaluate transcriptome responses in loblolly pine and was leveraged to identify 2445 differentially expressed genes responding to severe drought stress in

  5. Microarray analysis and scale-free gene networks identify candidate regulators in drought-stressed roots of loblolly pine (P. taeda L.)

    Science.gov (United States)

    2011-01-01

    Background Global transcriptional analysis of loblolly pine (Pinus taeda L.) is challenging due to limited molecular tools. PtGen2, a 26,496 feature cDNA microarray, was fabricated and used to assess drought-induced gene expression in loblolly pine propagule roots. Statistical analysis of differential expression and weighted gene correlation network analysis were used to identify drought-responsive genes and further characterize the molecular basis of drought tolerance in loblolly pine. Results Microarrays were used to interrogate root cDNA populations obtained from 12 genotype × treatment combinations (four genotypes, three watering regimes). Comparison of drought-stressed roots with roots from the control treatment identified 2445 genes displaying at least a 1.5-fold expression difference (false discovery rate = 0.01). Genes commonly associated with drought response in pine and other plant species, as well as a number of abiotic and biotic stress-related genes, were up-regulated in drought-stressed roots. Only 76 genes were identified as differentially expressed in drought-recovered roots, indicating that the transcript population can return to the pre-drought state within 48 hours. Gene correlation analysis predicts a scale-free network topology and identifies eleven co-expression modules that ranged in size from 34 to 938 members. Network topological parameters identified a number of central nodes (hubs) including those with significant homology (E-values ≤ 2 × 10-30) to 9-cis-epoxycarotenoid dioxygenase, zeatin O-glucosyltransferase, and ABA-responsive protein. Identified hubs also include genes that have been associated previously with osmotic stress, phytohormones, enzymes that detoxify reactive oxygen species, and several genes of unknown function. Conclusion PtGen2 was used to evaluate transcriptome responses in loblolly pine and was leveraged to identify 2445 differentially expressed genes responding to severe drought stress in roots. Many of the

  6. Prognostic and predictive potential molecular biomarkers in colon cancer.

    Science.gov (United States)

    Nastase, A; Pâslaru, L; Niculescu, A M; Ionescu, M; Dumitraşcu, T; Herlea, V; Dima, S; Gheorghe, C; Lazar, V; Popescu, I

    2011-01-01

    An important objective in nowadays research is the discovery of new biomarkers that can detect colon tumours in early stages and indicate with accuracy the status of the disease. The aim of our study was to identify potential biomarkers for colon cancer onset and progression. We assessed gene expression profiles of a list of 10 candidate genes (MMP-1, MMP-3, MMP-7, DEFA 1, DEFA-5, DEFA-6, IL-8, CXCL-1, SPP-1, CTHRC-1) by quantitative real time PCR in triplets of colonic mucosa (normal, adenoma, tumoral tissue) collected from the same patient during surgery for a group of 20 patients. Additionally we performed immunohistochemistry for DEFA1-3 and SPP1. We remarked that DEFA5 and DEFA6 are key factors in adenoma formation (p<0.05). MMP7 is important in the transition from a benign to a malignant status (p <0.01) and further in metastasis being a prognostic indicator for tumor transformation and for the metastatic potential of cancer cells. IL8, irrespective of tumor stage, has a high mRNA level in adenocarcinoma (p< 0.05). The level of expression for SPP1 is correlated with tumor level. We suggest that high levels of DEFAS, DEFA6 (key elements in adenoma formation), MMP7 (marker of colon cancer onset and progression to metastasis), SPP1 (marker of progression) and IL8 could be used to diagnose an early stage colon cancer and to evaluate the prognostic of progression for colon tumors. Further, if DEFA5 and DEFA6 level of expression are low but MMP7, SPP1 and IL8 level are high we could point out that the transition from adenoma to adenocarcinoma had already occurred. Thus, DEFA5, DEFA6, MMP7, IL8 and SPP1 consist in a valuable panel of biomarkers, whose detection can be used in early detection and progressive disease and also in prognostic of colon cancer.

  7. RNA-Seq analysis and annotation of a draft blueberry genome assembly identifies candidate genes involved in fruit ripening, biosynthesis of bioactive compounds, and stage-specific alternative splicing.

    Science.gov (United States)

    Gupta, Vikas; Estrada, April D; Blakley, Ivory; Reid, Rob; Patel, Ketan; Meyer, Mason D; Andersen, Stig Uggerhøj; Brown, Allan F; Lila, Mary Ann; Loraine, Ann E

    2015-01-01

    Blueberries are a rich source of antioxidants and other beneficial compounds that can protect against disease. Identifying genes involved in synthesis of bioactive compounds could enable the breeding of berry varieties with enhanced health benefits. Toward this end, we annotated a previously sequenced draft blueberry genome assembly using RNA-Seq data from five stages of berry fruit development and ripening. Genome-guided assembly of RNA-Seq read alignments combined with output from ab initio gene finders produced around 60,000 gene models, of which more than half were similar to proteins from other species, typically the grape Vitis vinifera. Comparison of gene models to the PlantCyc database of metabolic pathway enzymes identified candidate genes involved in synthesis of bioactive compounds, including bixin, an apocarotenoid with potential disease-fighting properties, and defense-related cyanogenic glycosides, which are toxic. Cyanogenic glycoside (CG) biosynthetic enzymes were highly expressed in green fruit, and a candidate CG detoxification enzyme was up-regulated during fruit ripening. Candidate genes for ethylene, anthocyanin, and 400 other biosynthetic pathways were also identified. Homology-based annotation using Blast2GO and InterPro assigned Gene Ontology terms to around 15,000 genes. RNA-Seq expression profiling showed that blueberry growth, maturation, and ripening involve dynamic gene expression changes, including coordinated up- and down-regulation of metabolic pathway enzymes and transcriptional regulators. Analysis of RNA-seq alignments identified developmentally regulated alternative splicing, promoter use, and 3' end formation. We report genome sequence, gene models, functional annotations, and RNA-Seq expression data that provide an important new resource enabling high throughput studies in blueberry.

  8. Colonic potassium handling

    DEFF Research Database (Denmark)

    Sørensen, Mads Vaarby; Matos, Joana E.; Prætorius, Helle

    2010-01-01

    , intestinal K+ losses caused by activated ion secretion may become life threatening. This topical review provides an update of the molecular mechanisms and the regulation of mammalian colonic K+ absorption and secretion. It is motivated by recent results, which have identified the K+ secretory ion channel...... regulated by hormones and adapts readily to changes in dietary K+ intake, aldosterone and multiple local paracrine agonists. In chronic renal insufficiency, colonic K+ secretion is greatly enhanced and becomes an important accessory K+ excretory pathway. During severe diarrheal diseases of different causes...

  9. CGMIM: Automated text-mining of Online Mendelian Inheritance in Man (OMIM to identify genetically-associated cancers and candidate genes

    Directory of Open Access Journals (Sweden)

    Jones Steven

    2005-03-01

    Full Text Available Abstract Background Online Mendelian Inheritance in Man (OMIM is a computerized database of information about genes and heritable traits in human populations, based on information reported in the scientific literature. Our objective was to establish an automated text-mining system for OMIM that will identify genetically-related cancers and cancer-related genes. We developed the computer program CGMIM to search for entries in OMIM that are related to one or more cancer types. We performed manual searches of OMIM to verify the program results. Results In the OMIM database on September 30, 2004, CGMIM identified 1943 genes related to cancer. BRCA2 (OMIM *164757, BRAF (OMIM *164757 and CDKN2A (OMIM *600160 were each related to 14 types of cancer. There were 45 genes related to cancer of the esophagus, 121 genes related to cancer of the stomach, and 21 genes related to both. Analysis of CGMIM results indicate that fewer than three gene entries in OMIM should mention both, and the more than seven-fold discrepancy suggests cancers of the esophagus and stomach are more genetically related than current literature suggests. Conclusion CGMIM identifies genetically-related cancers and cancer-related genes. In several ways, cancers with shared genetic etiology are anticipated to lead to further etiologic hypotheses and advances regarding environmental agents. CGMIM results are posted monthly and the source code can be obtained free of charge from the BC Cancer Research Centre website http://www.bccrc.ca/ccr/CGMIM.

  10. LC-QTOF-MS identification of porcine-specific peptide in heat treated pork identifies candidate markers for meat species determination.

    Science.gov (United States)

    Sarah, S A; Faradalila, W N; Salwani, M S; Amin, I; Karsani, S A; Sazili, A Q

    2016-05-15

    The purpose of this study was to identify porcine-specific peptide markers from thermally processed meat that could differentiate pork from beef, chevon and chicken meat. In the initial stage, markers from tryptic digested protein of chilled, boiled and autoclaved pork were identified using LC-QTOF-MS. An MRM method was then established for verification. A thorough investigation of LC-QTOF-MS data showed that only seven porcine-specific peptides were consistently detected. Among these peptides, two were derived from lactate dehydrogenase, one from creatine kinase, and four from serum albumin protein. However, MRM could only detect four peptides (EVTEFAK, LVVITAGAR, FVIER and TVLGNFAAFVQK) that were consistently present in pork samples. In conclusion, meat species determination through a tandem mass spectrometry platform shows high potential in providing scientifically valid and reliable results even at peptide level. Besides, the specificity and selectivity offered by the proteomics approach also provide a robust platform for Halal authentication. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Global MicroRNA Profiling in Human Bone Marrow Skeletal—Stromal or Mesenchymal–Stem Cells Identified Candidates for Bone Regeneration

    DEFF Research Database (Denmark)

    Chang, Chi Chih; Venø, Morten T.; Chen, Li

    2018-01-01

    Bone remodeling and regeneration are highly regulated multistep processes involving posttranscriptional regulation by microRNAs (miRNAs). Here, we performed a global profiling of differentially expressed miRNAs in bone-marrow-derived skeletal cells (BMSCs; also known as stromal or mesenchymal stem......RNAs for enhancing bone tissue regeneration. Scaffolds functionalized with miRNA nano-carriers enhanced osteoblastogenesis in 3D culture and retained this ability at least 2 weeks after storage. Additionally, anti-miR-222 enhanced in vivo ectopic bone formation through targeting the cell-cycle inhibitor CDKN1B...... cells) during in vitro osteoblast differentiation. We functionally validated the regulatory effects of several miRNAs on osteoblast differentiation and identified 15 miRNAs, most significantly miR-222 and miR-423, as regulators of osteoblastogenesis. In addition, we tested the possible targeting of mi...

  12. miR-155, identified as anti-metastatic by global miRNA profiling of a metastasis model, inhibits cancer cell extravasation and colonization in vivo and causes significant signaling alterations

    DEFF Research Database (Denmark)

    Gravgaard, Karina Hedelund; Terp, Mikkel G; Lund, Rikke R

    2015-01-01

    To gain insight into miRNA regulation in metastasis formation, we used a metastasis cell line model that allows investigation of extravasation and colonization of circulating cancer cells to lungs in mice. Using global miRNA profiling, 28 miRNAs were found to exhibit significantly altered...... proliferation or apoptosis in established lung tumors. To identify proteins regulated by miR-155 and thus delineate its function in our cell model, we compared the proteome of xenograft tumors derived from miR-155-overexpressing CL16 cells and CL16 control cells using mass spectrometry-based proteomics. >4......,000 proteins were identified, of which 92 were consistently differentially expressed. Network analysis revealed that the altered proteins were associated with cellular functions such as movement, growth and survival as well as cell-to-cell signaling and interaction. Downregulation of the three metastasis...

  13. Exploration of 19 serotoninergic candidate genes in adults and children with attention-deficit/hyperactivity disorder identifies association for 5HT2A, DDC and MAOB.

    Science.gov (United States)

    Ribasés, M; Ramos-Quiroga, J A; Hervás, A; Bosch, R; Bielsa, A; Gastaminza, X; Artigas, J; Rodriguez-Ben, S; Estivill, X; Casas, M; Cormand, B; Bayés, M

    2009-01-01

    Attention-deficit/hyperactivity disorder (ADHD) is a common psychiatric disorder in which different genetic and environmental susceptibility factors are involved. Several lines of evidence support the view that at least 30% of ADHD patients diagnosed in childhood continue to suffer the disorder during adulthood and that genetic risk factors may play an essential role in the persistence of the disorder throughout lifespan. Genetic, biochemical and pharmacological studies support the idea that the serotonin system participates in the etiology of ADHD. Based on these data, we aimed to analyze single nucleotide polymorphisms across 19 genes involved in the serotoninergic neurotransmission in a clinical sample of 451 ADHD patients (188 adults and 263 children) and 400 controls using a population-based association study. Several significant associations were found after correcting for multiple testing: (1) the DDC gene was strongly associated with both adulthood (P=0.00053; odds ratio (OR)=2.17) and childhood ADHD (P=0.0017; OR=1.90); (2) the MAOB gene was found specifically associated in the adult ADHD sample (P=0.0029; OR=1.90) and (3) the 5HT2A gene showed evidence of association only with the combined ADHD subtype both in adults (P=0.0036; OR=1.63) and children (P=0.0084; OR=1.49). Our data support the contribution of the serotoninergic system in the genetic predisposition to ADHD, identifying common childhood and adulthood ADHD susceptibility factors, associations that are specific to ADHD subtypes and one variant potentially involved in the continuity of the disorder throughout lifespan.

  14. Proteogenomic characterization of human colon and rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Bing; Wang, Jing; Wang, Xiaojing; Zhu, Jing; Liu, Qi; Shi, Zhiao; Chambers, Matthew C.; Zimmerman, Lisa J.; Shaddox, Kent F.; Kim, Sangtae; Davies, Sherri; Wang, Sean; Wang, Pei; Kinsinger, Christopher; Rivers, Robert; Rodriguez, Henry; Townsend, Reid; Ellis, Matthew; Carr, Steven A.; Tabb, David L.; Coffey, Robert J.; Slebos, Robbert; Liebler, Daniel

    2014-09-18

    We analyzed proteomes of colon and rectal tumors previously characterized by the Cancer Genome Atlas (TCGA) and performed integrated proteogenomic analyses. Protein sequence variants encoded by somatic genomic variations displayed reduced expression compared to protein variants encoded by germline variations. mRNA transcript abundance did not reliably predict protein expression differences between tumors. Proteomics identified five protein expression subtypes, two of which were associated with the TCGA "MSI/CIMP" transcriptional subtype, but had distinct mutation and methylation patterns and associated with different clinical outcomes. Although CNAs showed strong cis- and trans-effects on mRNA expression, relatively few of these extend to the protein level. Thus, proteomics data enabled prioritization of candidate driver genes. Our analyses identified HNF4A, a novel candidate driver gene in tumors with chromosome 20q amplifications. Integrated proteogenomic analysis provides functional context to interpret genomic abnormalities and affords novel insights into cancer biology.

  15. Laparoscopic colectomy for transverse colon carcinoma.

    Science.gov (United States)

    Zmora, O; Bar-Dayan, A; Khaikin, M; Lebeydev, A; Shabtai, M; Ayalon, A; Rosin, D

    2010-03-01

    Laparoscopic resection of transverse colon carcinoma is technically demanding and was excluded from most of the large trials of laparoscopic colectomy. The aim of this study was to assess the safety, feasibility, and outcome of laparoscopic resection of carcinoma of the transverse colon. A retrospective review was performed to identify patients who underwent laparoscopic resection of transverse colon carcinoma. These patients were compared to patients who had laparoscopic resection for right and sigmoid colon carcinoma. In addition, they were compared to a historical series of patients who underwent open resection for transverse colon cancer. A total of 22 patients underwent laparoscopic resection for transverse colon carcinoma. Sixty-eight patients operated for right colon cancer and 64 operated for sigmoid colon cancer served as comparison groups. Twenty-four patients were identified for the historical open group. Intraoperative complications occurred in 4.5% of patients with transverse colon cancer compared to 5.9% (P = 1.0) and 7.8% (P = 1.0) of patients with right and sigmoid colon cancer, respectively. The early postoperative complication rate was 45, 50 (P = 1.0), and 37.5% (P = 0.22) in the three groups, respectively. Conversion was required in 1 (5%) patient in the laparoscopic transverse colon group. The conversion rate and late complications were not significantly different in the three groups. There was no significant difference in the number of lymph nodes harvested in the laparoscopic and open groups. Operative time was significantly longer in the laparoscopic transverse colectomy group when compared to all other groups (P = 0.001, 0.008, and transverse colectomy, respectively). The results of laparoscopic colon resection for transverse colon carcinoma are comparable to the results of laparoscopic resection of right or sigmoid colon cancer and open resection of transverse colon carcinoma. These results suggest that laparoscopic resection of transverse

  16. Evaluation of colonic lesions and pitfalls in CT colonography: A systematic approach based on morphology, attenuation and mobility

    International Nuclear Information System (INIS)

    Mang, Thomas; Gryspeerdt, Stefaan; Schima, Wolfgang; Lefere, Philippe

    2013-01-01

    Computed tomographic colonography is a reliable technique for the detection and classification of neoplastic and non-neoplastic lesions of the colon. It is based on a thin-section CT dataset of the cleansed and air-distended colon, acquired in prone and supine position. Two-dimensional and 3D projections are used in combination for image interpretation. The evaluation of CT colonography datasets is based on two steps, lesion perception to detect a polyp candidate and image interpretation to correctly characterize colonic filling defects. A thorough knowledge of the morphologic and attenuation characteristics of common colonic lesions and artifacts facilitates characterization of the findings. The purpose of this review article is to give an overview of the key CT colonographic imaging criteria to correctly characterize common colorectal lesions and to identify typical pitfalls and pseudolesions

  17. Schwannoma of the Colon

    Directory of Open Access Journals (Sweden)

    Ronaldo Nonose

    2009-09-01

    Full Text Available Schwannomas are neoplasms originating from Schwann cells, which are the cells forming nerve sheaths. These neoplasms generally involve peripheral nerves. They rarely affect the gastrointestinal tract and primary colon involvement is extremely rare. The objective of the present paper was to present a case of primary schwannoma of the sigmoid colon, unassociated with von Recklinghausen disease, that was histopathologically confirmed by means of an immunohistochemical panel. The patient was a 71-year-old woman who had had rectal bleeding when evacuating, with pain and tenesmus, for 4 months. She underwent colonoscopy, which identified a raised submucous lesion of 2.8 cm in diameter, located in the sigmoid colon, 30 cm from the anal margin. During examination, loop polypectomy with lesion excision was performed. Histopathological evaluation showed that this was a tumor of stromal origin. Its resection margins were compromised by neoplasia, and colon resection by means of videolaparoscopy was indicated. Conventional histopathological examination using the hematoxylin-eosin technique suggested that the neoplasm was of mesenchymal origin. An immunohistochemical panel was run for etiological confirmation, using anti-CD34 antibodies, desmin, cytokeratins (AE1/AE3, cKit, chromogranin and S-100 protein. The panel showed intense immunoexpression of S-100 protein. Investigation of the proliferative activity rate using Ki-67 antibodies showed that there was a low rate of mitotic activity, thus confirming the diagnosis of primary benign schwannoma of the colon. The patient’s postoperative evolution was uneventful and she remains in good health, without signs of tumor recurrence, 15 months after surgical excision.

  18. High-throughput typing method to identify a non-outbreak-involved Legionella pneumophila strain colonizing the entire water supply system in the town of Rennes, France.

    Science.gov (United States)

    Sobral, D; Le Cann, P; Gerard, A; Jarraud, S; Lebeau, B; Loisy-Hamon, F; Vergnaud, G; Pourcel, C

    2011-10-01

    Two legionellosis outbreaks occurred in the city of Rennes, France, during the past decade, requiring in-depth monitoring of Legionella pneumophila in the water network and the cooling towers in the city. In order to characterize the resulting large collection of isolates, an automated low-cost typing method was developed. The multiplex capillary-based variable-number tandem repeat (VNTR) (multiple-locus VNTR analysis [MLVA]) assay requiring only one PCR amplification per isolate ensures a high level of discrimination and reduces hands-on and time requirements. In less than 2 days and using one 4-capillary apparatus, 217 environmental isolates collected between 2000 and 2009 and 5 clinical isolates obtained during outbreaks in 2000 and 2006 in Rennes were analyzed, and 15 different genotypes were identified. A large cluster of isolates with closely related genotypes and representing 77% of the population was composed exclusively of environmental isolates extracted from hot water supply systems. It was not responsible for the known Rennes epidemic cases, although strains showing a similar MLVA profile have regularly been involved in European outbreaks. The clinical isolates in Rennes had the same genotype as isolates contaminating a mall's cooling tower. This study further demonstrates that unknown environmental or genetic factors contribute to the pathogenicity of some strains. This work illustrates the potential of the high-throughput MLVA typing method to investigate the origin of legionellosis cases by allowing the systematic typing of any new isolate and inclusion of data in shared databases.

  19. Synthesis of 2',4-dihydroxy-3-methoxychalcone and 2',4',4-trihydroxy-3-methoxychalcone as a candidate anticancer against cervical (WiDr), colon (HeLa), and breast (T47d) cancer cell lines in vitro

    Science.gov (United States)

    Matsjeh, Sabirin; Swasono, Respati Tri; Anwar, Chairil; Solikhah, Eti Nurwening; Lestari, Endang

    2017-03-01

    The compound 2',4-dihydroxy-3-methoxychalcone and 2',4',4-trihydroxy-3-methoxychalcone have been synthesized through Claisen-Schmidt reaction from 2-hydroxyacetophenone and 2,4-dihydroxyacetophenone with 4-hydroxy-3-methoxy benzaldehida (vanillin) in aqueous KOH 40% and KSF montmorillonite as catalyst in methanol. All these products were characterized by FT-IR, TLC Scanner, GC-MS, MS-Direct, and 1H-NMR and 13C-NMR spectrometer. Both of these compounds were tested citotoxycity activity as an anticancer against cervical, colon, and breast cancer cells (Hela, WiDr, and T47D cell lines) using MTT assay in vitro. Dose series given test solution concentration on Hela, WiDr, and T47D cells started from 6,25; 25; 50 and 100 µg/mL with incubation treatment for 24 hours. The result of study showed that the 2',4-dihydroxy-3-methoxychalcone as bright yellow crystal with the melting point of 114-115 °C and the yield of 13.77% and the 2',4',4-trihydroxy-3-methoxychalcone as bright yellow crystals with the melting point of 195-197 °C and the yield of 6%. Other 2',4-dihydroxy-3-methoxychalcone and 2',4',4-trihydroxy-3-methoxychalcone also exhibited cytotoxic activity against the cancer cell lines, with the 2',4',4-trihydroxy-3-methoxychalcone showed greater activities than the 2',4-dihydroxy-3-methoxychalcone in WiDr cell lines. The 2',4-dihydroxy-3-methoxychalcone and 2',4',4-trihydroxy-3-methoxychalcone exhibited strong anticancer activities with IC50 value below 20 µg/mL. The activity of 2',4',4-trihydroxy-3-methoxychalcone showed the most active against Hela and WiDr cell lines with IC50 value 8.53 and 2.66 µg/mL respectively, than T47D cell lines with IC50 value 24.61 µg/mL. The test results cytotoxic of 2',4-dihydroxy-3-methoxychalcone showed the most active against Hela and WiDr cell lines with IC50 value 12.80, 19.57 µg/mL than T47D cell lines with IC50 value of 20.73 µg/mL. IC50 value indicated that 2',4-dihydroxy-3-methoxychalcone and 2',4',4-trihydroxy-3

  20. Synthesis of 7-hydroxy-4'-methoxyflavanone and 7-hydroxy-4'-methoxyflavone as a candidate anticancer against cervical (HeLa) cancer cell and colon (WiDr) cancer cell by in vitro

    Science.gov (United States)

    Matsjeh, Sabirin; Anwar, Chairil; Solikhah, Eti Nurwening; Farah, Harra Ismi; Nurfitria, Kurnia

    2017-03-01

    The compound 7-hydroxy-4'-methoxyflavanone and 7-hydroxy-4'-methoxyflavone have been synthesized through cyclization reaction of 2 ', 4'-dihydroxy-4-methoxychalcone (1,3-diphenyl-2-propene-1-one). The 2 ', 4'-dihydroxy-4-methoxychalcone were synthesized through Claisen-Schmidt condensation from 2,4-dihydroxyacetophenone and 4-methoxybenzaldehyde (anisaldehyde) in aqueous KOH as a catalyst in ethanol. The 7-hydroxy-4'-methoxyflavanone has been synthesized through cyclization reaction of 2 ', 4'-dihydroxy-4-methoxychalcone by Oxa-Michael addition reaction with sulfuric acid as a catalyst in ethanol. The 7-hydroxy-4'-methoxyflavone has been synthesized through oxidative cyclization reaction of 2 ', 4'-dihydroxy-4-methoxychalcone using I2 in DMSO as a catalyst with a mole ratio (1: 1) mol. All these producets were characterized by FT-IR, GC-MS, and 1H-NMR and 13C-NMR spectrometer. Both of these compounds were tested citotoxycity activity as an anticancer against cervical and colon cancer cells (HeLa and WiDr cell lines) using MTT assay in vitro. Dose series given test solution concentration on HeLa and WiDr cells starting from 0,78; 1,56; 3,12; 6,25; 12,50; 25; 50 and 100 µg/mL with a long incubation treatment for 24 hours. The results study showed that the 7-hydroxy-4'-methoxyflavanone as bright yellow crystals with a melting point 172-174 ° C and a yield of 56.67% and the 7-hydroxy-4'-methoxyflavone as bright yellow crystals with a yield of 88, 31%, and a melting point of 263-265 ° C. The test results cytotoxic 7-hydroxy-4-methoxyflavone showed active against HeLa cells with IC50 value of 25.73 µg/mL and was quite active in the WiDr cells with IC50 value of 83.75 µg/mL. The result of the activity of 7-hydroxy-4-methoxyflavanone show active cytotoxic activity against HeLa and WiDr cell growth with IC50 value of 40.13 µg/mL and 37.85 µg/mL. IC50 value indicated that 7-hydroxy-4'-methoxyflavone and 7-hydroxy-4'-methoxyflavanone potential as inhibitors in HeLa and

  1. QTLs and potential candidate genes for heat stress tolerance identified from the mapping populations specifically segregating for Fv/Fm in wheat

    DEFF Research Database (Denmark)

    Sharma, Dew Kumari; Torp, Anna Maria; Rosenqvist, Eva

    2017-01-01

    Despite the fact that F-v/F-m (maximum quantum efficiency of photosystem II) is the most widely used parameter for a rapid non-destructive measure of stress detection in plants, there are barely any studies on the genetic understanding of this trait under heat stress. Our aim was to identify...... quantitative trait locus (QTL) and the potential candidate genes linked to F-v/F-m for improved photosynthesis under heat stress in wheat (Triticum aestivum L.). Three bi-parental F-2 mapping populations were generated by crossing three heat tolerant male parents (origin: Afghanistan and Pakistan) selected...... for high F-v/F-m with a common heat susceptible female parent (origin: Germany) selected for lowest F-v/F-m out of a pool of 1274 wheat cultivars of diverse geographic origin. Parents together with 140 F-2 individuals in each population were phenotyped by F-v/F-m under heat stress (40 degrees C for 3 days...

  2. A prognostic analysis of 895 cases of stage III colon cancer in different colon subsites.

    Science.gov (United States)

    Zhang, Yan; Ma, Junli; Zhang, Sai; Deng, Ganlu; Wu, Xiaoling; He, Jingxuan; Pei, Haiping; Shen, Hong; Zeng, Shan

    2015-09-01

    Stage III colon cancer is currently treated as an entity with a unified therapeutic principle. The aim of the retrospective study is to explore the clinicopathological characteristics and outcomes of site-specific stage III colon cancers and the influences of tumor location on prognosis. Eight hundred ninety-five patients with stage III colon cancer treated with radical operation and subsequent adjuvant chemotherapy (5-fluorouracil/oxaliplatin) were divided into seven groups according to colon segment (cecum, ascending colon, hepatic flexure, transverse colon, splenic flexure, descending colon, and sigmoid colon). Expression of excision repair cross-complementing group 1 (ERCC1) and thymidylate synthase (TS) was examined by immunohistochemistry. We assessed if differences exist in patient characteristics and clinic outcomes between the seven groups. There were significant differences in tumor differentiation (P Cancer (AJCC) tumor-node-metastasis (TNM) stage (P colon. Cox regression analyses identified that tumor location was an independent prognostic factor for RFS and OS. Stage III colon cancer located proximally carried a poorer survival than that located distally. Different efficacies of FOLFOX adjuvant chemotherapy may be an important factor affecting survival of site-specific stage III colon cancers.

  3. Incidence of Candida species colonization in neonatal intensive care unit at Riyadh Hospital, Saudi Arabia

    Directory of Open Access Journals (Sweden)

    Mohammed S. Alhussaini

    2016-10-01

    Full Text Available Background: Candida species are important hospital-acquired pathogens in infants admitted to the neonatal intensive care unit (NICU. This study was performed in the NICU of Saudi Arabian Hospital, Riyadh region, KSA to analyze patterns of neonatal Candida colonization as well as to determine the potential risk factors.Methods: Weekly surveillance fungal cultures of anal area, oral cavity, umbilicus and ear canal of neonates were performed from birth until their discharge from the hospital. Colonization was analyzed for timing, site, species, birth weight and gestational age. Potential environmental reservoirs and hands of health care workers (HCWs were also cultured monthly for fungi. Antifungal susceptibility of the identified isolates was also determined.Results: One hundred subjects have been recruited in this study. The overall colonization rate was 51%. Early colonization was found in 27 (27% neonates whereas 24 (24% neonates were lately colonized during their stay in NICU. Colonization was more in preterm neonates than in full and post term. Perianal area and oral cavity were the most frequent colonized sites. C. albicans was the main spp. (58.8% isolated from the neonates followed by C. tropicalis (17.6%, C. glabrata (15.6%, and C. krusei (2%. Of the 51 isolated Candida spp., 68.6% were sensitive to fluconazole, 80% to itraconazole and 64.7% to ketoconazole, while only 33% were sensitive to amphotericin B.Conclusion: Candida has emerged as a common cause of infections in infants admitted to NICU, and C. albicans is the most commonly isolated candidal species. Neonatal infections caused by non- albicans species occur at a later age during their stay in NICU.

  4. A Genome Wide Study of Copy Number Variation Associated with Nasopharyngeal Carcinoma in Malaysian Chinese Identifies CNVs at 11q14.3 and 6p21.3 as Candidate Loci

    Science.gov (United States)

    Low, Joyce Siew Yong; Chin, Yoon Ming; Mushiroda, Taisei; Kubo, Michiaki; Govindasamy, Gopala Krishnan; Pua, Kin Choo; Yap, Yoke Yeow; Yap, Lee Fah; Subramaniam, Selva Kumar; Ong, Cheng Ai; Tan, Tee Yong; Khoo, Alan Soo Beng; Ng, Ching Ching

    2016-01-01

    Background Nasopharyngeal carcinoma (NPC) is a neoplasm of the epithelial lining of the nasopharynx. Despite various reports linking genomic variants to NPC predisposition, very few reports were done on copy number variations (CNV). CNV is an inherent structural variation that has been found to be involved in cancer predisposition. Methods A discovery cohort of Malaysian Chinese descent (NPC patients, n = 140; Healthy controls, n = 256) were genotyped using Illumina® HumanOmniExpress BeadChip. PennCNV and cnvPartition calling algorithms were applied for CNV calling. Taqman CNV assays and digital PCR were used to validate CNV calls and replicate candidate copy number variant region (CNVR) associations in a follow-up Malaysian Chinese (NPC cases, n = 465; and Healthy controls, n = 677) and Malay cohort (NPC cases, n = 114; Healthy controls, n = 124). Results Six putative CNVRs overlapping GRM5, MICA/HCP5/HCG26, LILRB3/LILRA6, DPY19L2, RNase3/RNase2 and GOLPH3 genes were jointly identified by PennCNV and cnvPartition. CNVs overlapping GRM5 and MICA/HCP5/HCG26 were subjected to further validation by Taqman CNV assays and digital PCR. Combined analysis in Malaysian Chinese cohort revealed a strong association at CNVR on chromosome 11q14.3 (Pcombined = 1.54x10-5; odds ratio (OR) = 7.27; 95% CI = 2.96–17.88) overlapping GRM5 and a suggestive association at CNVR on chromosome 6p21.3 (Pcombined = 1.29x10-3; OR = 4.21; 95% CI = 1.75–10.11) overlapping MICA/HCP5/HCG26 genes. Conclusion Our results demonstrated the association of CNVs towards NPC susceptibility, implicating a possible role of CNVs in NPC development. PMID:26730743

  5. A Genome Wide Study of Copy Number Variation Associated with Nasopharyngeal Carcinoma in Malaysian Chinese Identifies CNVs at 11q14.3 and 6p21.3 as Candidate Loci.

    Directory of Open Access Journals (Sweden)

    Joyce Siew Yong Low

    Full Text Available Nasopharyngeal carcinoma (NPC is a neoplasm of the epithelial lining of the nasopharynx. Despite various reports linking genomic variants to NPC predisposition, very few reports were done on copy number variations (CNV. CNV is an inherent structural variation that has been found to be involved in cancer predisposition.A discovery cohort of Malaysian Chinese descent (NPC patients, n = 140; Healthy controls, n = 256 were genotyped using Illumina® HumanOmniExpress BeadChip. PennCNV and cnvPartition calling algorithms were applied for CNV calling. Taqman CNV assays and digital PCR were used to validate CNV calls and replicate candidate copy number variant region (CNVR associations in a follow-up Malaysian Chinese (NPC cases, n = 465; and Healthy controls, n = 677 and Malay cohort (NPC cases, n = 114; Healthy controls, n = 124.Six putative CNVRs overlapping GRM5, MICA/HCP5/HCG26, LILRB3/LILRA6, DPY19L2, RNase3/RNase2 and GOLPH3 genes were jointly identified by PennCNV and cnvPartition. CNVs overlapping GRM5 and MICA/HCP5/HCG26 were subjected to further validation by Taqman CNV assays and digital PCR. Combined analysis in Malaysian Chinese cohort revealed a strong association at CNVR on chromosome 11q14.3 (Pcombined = 1.54x10-5; odds ratio (OR = 7.27; 95% CI = 2.96-17.88 overlapping GRM5 and a suggestive association at CNVR on chromosome 6p21.3 (Pcombined = 1.29x10-3; OR = 4.21; 95% CI = 1.75-10.11 overlapping MICA/HCP5/HCG26 genes.Our results demonstrated the association of CNVs towards NPC susceptibility, implicating a possible role of CNVs in NPC development.

  6. Antegrade Colonic Lavage in Acute Colonic Obstruction

    OpenAIRE

    Foster, Michael E.; Johnson, Colin D.

    1986-01-01

    Conventional management of acute left sided colonic obstruction employs some form of proximal colostomy. Intraoperative antegrade colonic irrigation relieves proximal faecal loading and may permit safer primary resection and anastomosis. The results of a pilot study are presented, and are shown to be favourable.

  7. Colon and rectal cancer survival by tumor location and microsatellite instability: the Colon Cancer Family Registry.

    Science.gov (United States)

    Phipps, Amanda I; Lindor, Noralane M; Jenkins, Mark A; Baron, John A; Win, Aung Ko; Gallinger, Steven; Gryfe, Robert; Newcomb, Polly A

    2013-08-01

    Cancers in the proximal colon, distal colon, and rectum are frequently studied together; however, there are biological differences in cancers across these sites, particularly in the prevalence of microsatellite instability. We assessed the differences in survival by colon or rectal cancer site, considering the contribution of microsatellite instability to such differences. This is a population-based prospective cohort study for cancer survival. This study was conducted within the Colon Cancer Family Registry, an international consortium. Participants were identified from population-based cancer registries in the United States, Canada, and Australia. Information on tumor site, microsatellite instability, and survival after diagnosis was available for 3284 men and women diagnosed with incident invasive colon or rectal cancer between 1997 and 2002, with ages at diagnosis ranging from 18 to 74. Cox regression was used to calculate hazard ratios for the association between all-cause mortality and tumor location, overall and by microsatellite instability status. Distal colon (HR, 0.59; 95% CI, 0.49-0.71) and rectal cancers (HR, 0.68; 95% CI, 0.57-0.81) were associated with lower mortality than proximal colon cancer overall. Compared specifically with patients with proximal colon cancer exhibiting no/low microsatellite instability, patients with distal colon and rectal cancers experienced lower mortality, regardless of microsatellite instability status; patients with proximal colon cancer exhibiting high microsatellite instability had the lowest mortality. Study limitations include the absence of stage at diagnosis and cause-of-death information for all but a subset of study participants. Some patient groups defined jointly by tumor site and microsatellite instability status are subject to small numbers. Proximal colon cancer survival differs from survival for distal colon and rectal cancer in a manner apparently dependent on microsatellite instability status. These

  8. Combining heterogeneous features for colonic polyp detection in CTC based on semi-definite programming

    Science.gov (United States)

    Wang, Shijun; Yao, Jianhua; Petrick, Nicholas A.; Summers, Ronald M.

    2009-02-01

    Colon cancer is the second leading cause of cancer-related deaths in the United States. Computed tomographic colonography (CTC) combined with a computer aided detection system provides a feasible combination for improving colonic polyps detection and increasing the use of CTC for colon cancer screening. To distinguish true polyps from false positives, various features extracted from polyp candidates have been proposed. Most of these features try to capture the shape information of polyp candidates or neighborhood knowledge about the surrounding structures (fold, colon wall, etc.). In this paper, we propose a new set of shape descriptors for polyp candidates based on statistical curvature information. These features, called histogram of curvature features, are rotation, translation and scale invariant and can be treated as complementing our existing feature set. Then in order to make full use of the traditional features (defined as group A) and the new features (group B) which are highly heterogeneous, we employed a multiple kernel learning method based on semi-definite programming to identify an optimized classification kernel based on the combined set of features. We did leave-one-patient-out test on a CTC dataset which contained scans from 50 patients (with 90 6-9mm polyp detections). Experimental results show that a support vector machine (SVM) based on the combined feature set and the semi-definite optimization kernel achieved higher FROC performance compared to SVMs using the two groups of features separately. At a false positive per patient rate of 7, the sensitivity on 6-9mm polyps using the combined features improved from 0.78 (Group A) and 0.73 (Group B) to 0.82 (p<=0.01).

  9. Citizen Candidates Under Uncertainty

    OpenAIRE

    Eguia, Jon X.

    2005-01-01

    In this paper we make two contributions to the growing literature on "citizen-candidate" models of representative democracy. First, we add uncertainty about the total vote count. We show that in a society with a large electorate, where the outcome of the election is uncertain and where winning candidates receive a large reward from holding office, there will be a two-candidate equilibrium and no equilibria with a single candidate. Second, we introduce a new concept of equilibrium, which we te...

  10. Management of Colonic Volvulus

    Science.gov (United States)

    Gingold, Daniel; Murrell, Zuri

    2012-01-01

    Colonic volvulus is a common cause of large bowel obstruction worldwide. It can affect all parts of the colon, but most commonly occurs in the sigmoid and cecal areas. This disease has been described for centuries, and was studied by Hippocrates himself. Currently, colonic volvulus is the third most common cause of large bowel obstruction worldwide, and is responsible for ∼15% of large bowel obstructions in the United States. This article will discuss the history of colonic volvulus, and the predisposing factors that lead to this disease. Moreover, the epidemiology and diagnosis of each type of colonic volvulus, along with the various treatment options will be reviewed. PMID:24294126

  11. Duplication Cyst of the Sigmoid Colon

    Directory of Open Access Journals (Sweden)

    Bastian Domajnko

    2009-01-01

    Full Text Available A 21-year-old male with developmental delay presented with abdominal pain of two days' duration. He was afebrile and his abdomen was soft with mild diffuse tenderness. There were no peritoneal signs. Plain x-ray demonstrated a large air-filled structure in the right upper quadrant. Computed tomography of the abdomen revealed a 9×8 cm structure adjacent to the hepatic flexure containing an air-fluid level. It did not contain oral contrast and had no apparent communication with the colon. At operation, the cystic lesion was identified as a duplication cyst of the sigmoid colon that was adherent to the right upper quadrant. The cyst was excised with a segment of the sigmoid colon and a stapled colo-colostomy was performed. Recovery was uneventful. Final pathology was consistent with a duplication cyst of the sigmoid colon. The cyst was attached to the colon but did not communicate with the lumen.

  12. CT staging of colon cancer

    Energy Technology Data Exchange (ETDEWEB)

    Dighe, S. [Department of Radiology, Royal Marsden Hospital, Sutton SM5 2TT (United Kingdom); Swift, I. [Department of Surgery, Mayday University Hospital, Croydon CR7 7YE (United Kingdom); Brown, G. [Department of Radiology, Royal Marsden Hospital, Sutton SM5 2TT (United Kingdom)], E-mail: gina.brown@rmh.nhs.uk

    2008-12-15

    Computer tomography (CT) has been the principal investigation in the staging of colon cancers. The information obtained with routine CT has been limited to identifying the site of the tumour, size of the tumour, infiltration into surrounding structures and metastatic spread. The Foxtrot trial National Cancer Research Institute (NCRI) has been specifically designed to evaluate the efficacy of neoadjuvant treatment in colon cancers by using preoperative chemotherapy with or without an anti-Epidermal Growth Factor Receptor (EGFR) monoclonal antibody to improve outcome in high-risk operable colon cancer. Patients are selected based on their staging CT examination. The criteria for poor prognosis are T4 and T3 tumours with more than 5 mm extramural depth. Thus the success of the trial would depend upon the confidence of the radiologist to identify the patients that would receive the neoadjuvant treatment. The aim of this review is to explain the process of identifying high-risk features seen on the staging CT images. This will help to identify a cohort of patients that could truly benefit from neoadjuvant strategies.

  13. CT staging of colon cancer

    International Nuclear Information System (INIS)

    Dighe, S.; Swift, I.; Brown, G.

    2008-01-01

    Computer tomography (CT) has been the principal investigation in the staging of colon cancers. The information obtained with routine CT has been limited to identifying the site of the tumour, size of the tumour, infiltration into surrounding structures and metastatic spread. The Foxtrot trial National Cancer Research Institute (NCRI) has been specifically designed to evaluate the efficacy of neoadjuvant treatment in colon cancers by using preoperative chemotherapy with or without an anti-Epidermal Growth Factor Receptor (EGFR) monoclonal antibody to improve outcome in high-risk operable colon cancer. Patients are selected based on their staging CT examination. The criteria for poor prognosis are T4 and T3 tumours with more than 5 mm extramural depth. Thus the success of the trial would depend upon the confidence of the radiologist to identify the patients that would receive the neoadjuvant treatment. The aim of this review is to explain the process of identifying high-risk features seen on the staging CT images. This will help to identify a cohort of patients that could truly benefit from neoadjuvant strategies

  14. CT in colon cancer

    International Nuclear Information System (INIS)

    Fujita, Nobuyuki; Hasegawa, Takashi; Kubo, Kozo; Ogawa, Hajime; Sato, Yukihiko; Tomita, Masayoshi; Hanawa, Makoto; Matsuzawa, Tohru; Nishioka, Ken

    1990-01-01

    CT pictures from 59 lesions of advanced colon cancer including rectal cancer were reviewed to evaluate a role of CT in preoperative staging diagnosis. CT findings were recorded following general rules for clinical and pathological studies on cancer of colon rectum and anus, proposed by Japanese society for cancer of colon and rectum. Tumors were detected in 90% of advanced colon cancers. Sensitivity in local extension (S factor) was 58.0%. Sensitivity in lymphonode involvement (N factor) was 50.0%. Sensitivity in final staging diagnosis, dividing colon cancer into two groups below st II and above st III, was 63.3%. Further study should be necessitated to provide useful information for preoperative staging diagnosis of colon cancer. (author)

  15. An Act of Colonization

    DEFF Research Database (Denmark)

    Rasmussen, Anders Bo

    When Gideon Welles, U.S. Secretary of the Navy, sat down to write his diary entry on September 26, 1862, his thoughts turned once more to colonization. President Lincoln was an ardent proponent of colonization, “the government-promoted settlement of black Americans in Africa or some other location....... Croix. Thus, when the Lincoln administration seriously considered colonization plans in 1862, Danish Charge d’Affaires Waldemar Raasløff offered free transport for freedmen to the Caribbean island, where there was a “distinct lack of laborers.” As a small first step towards colonization, Denmark...

  16. Colon cancer screening

    Science.gov (United States)

    Screening for colon cancer; Colonoscopy - screening; Sigmoidoscopy - screening; Virtual colonoscopy - screening; Fecal immunochemical test; Stool DNA test; sDNA test; Colorectal cancer - screening; Rectal ...

  17. Validation of methylation biomarkers that distinguish normal colon mucosa from cancer patients from normal colon mucosa of patients without cancer

    Science.gov (United States)

    Cesaroni, Matteo; Powell, Jasmine; Sapienza, Carmen

    2014-01-01

    We have validated differences in DNA methylation levels of candidate genes previously reported to discriminate between normal colon mucosa of colon cancer patients and normal colon mucosa of individuals without cancer. Here, we report that CpG sites in 16 of the 30 candidate genes selected show significant differences in mean methylation level in normal colon mucosa of 24 cancer patients and 24 controls. A support vector machine trained on these data and data for an additional 66 CpGs yielded an 18-gene signature, composed of 10 of the validated candidate genes plus eight additional candidates. This model exhibited 96% sensitivity and 100% specificity in a 40-sample training set and classified all eight samples in the test set correctly. Moreover, we found a moderate-strong correlation (Pearson coefficients r=0.253-0.722) between methylation levels in colon mucosa and methylation levels in peripheral blood for seven of the 18 genes in the support vector model. These seven genes, alone, classified 44 of the 48 patients in the validation set correctly and five CpGs selected from only two of the seven genes classified 41 of the 48 patients in the discovery set correctly. These results suggest that methylation biomarkers may be developed that will, at minimum, serve as useful objective and quantitative diagnostic complements to colonoscopy as a cancer-screening tool. These data also suggest that it may be possible to monitor biomarker methylation levels in tissues collected much less invasively than by colonoscopy. PMID:24806665

  18. Chemical synthesis, docking studies and biological effects of functionalized 1,3-diaryl-2-propen-1-ones on human colon cancer cells

    Directory of Open Access Journals (Sweden)

    Guo-Min Zhu

    2015-03-01

    Full Text Available A series of 1, 3-diaryl-2-propen-1-ones was synthesised in order to obtain a new type of anticancer drug, designed with hybrid features to inhibit colon cancer activated receptor. Based on computational modelling and docking studies, potential inhibitors were synthesised and their biological activity evaluated. The structures of newly synthesized compounds were confirmed by 1HNMR, 13CNMR and Mass spectrometry. All analogues were evaluated for in vitro cytotoxicity against human colon (caco-2 cancer cell lines. Compounds 1b, 1f-1h, and 2i showed significant cytotoxicity. Chalcones 1b, 1f and 1g were identified as the most potent and selective anticancer agents with IC50 values <1 µg/mL and 1.5 µg/mL, against caco-2 cell line, respectively. In conclusion, this finding confirms the suitability of indolyl chalcone analogues as candidates for further investigation towards the management of colon cancer related diseases.

  19. CT Findings of Colonic Complications Associated with Colon Cancer

    International Nuclear Information System (INIS)

    Kim, Sang Won; Shin, Hyeong Cheol; Kim, Il Young; Kim, Young Tong; Kim, Chang Jin

    2010-01-01

    A broad spectrum of colonic complications can occur in patients with colon cancer. Clinically, some of these complications can obscure the presence of underlying malignancies in the colon and these complications may require emergency surgical management. The complications of the colon that can be associated with colon cancer include obstruction, perforation, abscess formation, acute appendicitis, ischemic colitis and intussusception. Although the majority of these complications only rarely occur, familiarity with the various manifestations of colon cancer complications will facilitate making an accurate diagnosis and administering prompt management in these situations. The purpose of this pictorial essay is to review the CT appearance of the colonic complications associated with colon cancer

  20. CT Findings of Colonic Complications Associated with Colon Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang Won; Shin, Hyeong Cheol; Kim, Il Young; Kim, Young Tong; Kim, Chang Jin [Cheonan Hospital, Soonchunhyang University, Cheonan (Korea, Republic of)

    2010-04-15

    A broad spectrum of colonic complications can occur in patients with colon cancer. Clinically, some of these complications can obscure the presence of underlying malignancies in the colon and these complications may require emergency surgical management. The complications of the colon that can be associated with colon cancer include obstruction, perforation, abscess formation, acute appendicitis, ischemic colitis and intussusception. Although the majority of these complications only rarely occur, familiarity with the various manifestations of colon cancer complications will facilitate making an accurate diagnosis and administering prompt management in these situations. The purpose of this pictorial essay is to review the CT appearance of the colonic complications associated with colon cancer.

  1. Colon and rectal cancer

    International Nuclear Information System (INIS)

    Saldombide, L.; Cordoba, A.

    2010-01-01

    This study is about the diagnosis, therapy and monitoring of colon cancer. The techniques used are the endoscopy with biopsy in the pre and post operative colon surgery, abdominal ultrasound, chest X-ray studies of hemogram as well as liver and renal function

  2. Colon of the rat

    International Nuclear Information System (INIS)

    Lindstroem, C.G.; Rosengren, J.-E.; Fork, F.-T.

    1979-01-01

    The anatomy and radiologic appearance of the colon in rats are described on the basis of 300 animals treated with carcinogenic agents and 40 normal rats. The macroscopic and microscopic appearance of the mucosa varies in the different parts of the colon. Lymphoid plaques are normal structures. The results justify a new anatomic nomenclature. (Auth.)

  3. Echoendoscopic characterization of the human colon

    Directory of Open Access Journals (Sweden)

    Fernando M. Castro-Poças

    Full Text Available Purpose: To characterize colon and rectum walls, pericolic and perirectal spaces, using endoscopic ultrasonography miniprobes. Methods: Sixty individuals (50% males, aged 18-80, were included. Using 12 and 20 MHz endoscopic ultrasonography miniprobes, all different colon segments (ascending, transverse, descending, sigmoid and rectum were evaluated according to the number and thickness of the different layers in intestinal wall, to the presence and (largest diameter of vessels in the submucosa and of peri-intestinal nodes. Results: The 20 MHz miniprobe identified a higher number of layers than the 12 MHz miniprobe, with medians of 7 and 5 respectively (p < 0.001. The rectal wall (p = 0.001, its muscularis propria (p < 0.001 and mucosa (p = 0.01 were significantly thicker than the different segments of the colon, which had no significant differences between them. Patients aged 41-60 presented thicker colonic wall and muscularis propria in descending (p = 0.001 and p = 0.004 and rectum (p=0.01 and p=0.01. Submucosal vessels were identified in 30% of individuals in descending and rectum, and in 12% in ascending. Adenopathies were observed in 9% of the colon segments and 5% in rectum. Conclusions: A higher frequency enabled the identification of a higher number of layers. Rectal wall is thicker than the one from all the segments of the colon and there are no differences between these, namely in the ascending colon. Moreover, peri-intestinal adenopathies were rarely identified but present in asymptomatic individuals. All together, these results describe for the first time features which are relevant during staging and therapeutic management of colonic lesions.

  4. Analysis of Polymorphic Membrane Protein Expression in Cultured Cells Identifies PmpA and PmpH of Chlamydia psittaci as Candidate Factors in Pathogenesis and Immunity to Infection.

    Science.gov (United States)

    Van Lent, Sarah; De Vos, Winnok H; Huot Creasy, Heather; Marques, Patricia X; Ravel, Jacques; Vanrompay, Daisy; Bavoil, Patrik; Hsia, Ru-Ching

    2016-01-01

    The polymorphic membrane protein (Pmp) paralogous families of Chlamydia trachomatis, Chlamydia pneumoniae and Chlamydia abortus are putative targets for Chlamydia vaccine development. To determine whether this is also the case for Pmp family members of C. psittaci, we analyzed transcription levels, protein production and localization of several Pmps of C. psittaci. Pmp expression profiles were characterized using quantitative real-time PCR (RT-qPCR), immunofluorescence (IF) and immuno-electron microscopy (IEM) under normal and stress conditions. We found that PmpA was highly produced in all inclusions as early as 12 hpi in all biological replicates. In addition, PmpA and PmpH appeared to be unusually accessible to antibody as determined by both immunofluorescence and immuno-electron microscopy. Our results suggest an important role for these Pmps in the pathogenesis of C. psittaci, and make them promising candidates in vaccine development.

  5. Candidate cave entrances on Mars

    Science.gov (United States)

    Cushing, Glen E.

    2012-01-01

    This paper presents newly discovered candidate cave entrances into Martian near-surface lava tubes, volcano-tectonic fracture systems, and pit craters and describes their characteristics and exploration possibilities. These candidates are all collapse features that occur either intermittently along laterally continuous trench-like depressions or in the floors of sheer-walled atypical pit craters. As viewed from orbit, locations of most candidates are visibly consistent with known terrestrial features such as tube-fed lava flows, volcano-tectonic fractures, and pit craters, each of which forms by mechanisms that can produce caves. Although we cannot determine subsurface extents of the Martian features discussed here, some may continue unimpeded for many kilometers if terrestrial examples are indeed analogous. The features presented here were identified in images acquired by the Mars Odyssey's Thermal Emission Imaging System visible-wavelength camera, and by the Mars Reconnaissance Orbiter's Context Camera. Select candidates have since been targeted by the High-Resolution Imaging Science Experiment. Martian caves are promising potential sites for future human habitation and astrobiology investigations; understanding their characteristics is critical for long-term mission planning and for developing the necessary exploration technologies.

  6. Identification of Novel Vaccine Candidates against Campylobacter through Reverse Vaccinology

    Directory of Open Access Journals (Sweden)

    Marine Meunier

    2016-01-01

    Full Text Available Campylobacteriosis is the most prevalent bacterial foodborne gastroenteritis affecting humans in the European Union. Human cases are mainly due to Campylobacter jejuni or Campylobacter coli, and contamination is associated with the handling and/or consumption of poultry meat. In fact, poultry constitutes the bacteria’s main reservoir. A promising way of decreasing the incidence of campylobacteriosis in humans would be to decrease avian colonization. Poultry vaccination is of potential for this purpose. However, despite many studies, there is currently no vaccine available on the market to reduce the intestinal Campylobacter load in chickens. It is essential to identify and characterize new vaccine antigens. This study applied the reverse vaccinology approach to detect new vaccine candidates. The main criteria used to select immune proteins were localization, antigenicity, and number of B-epitopes. Fourteen proteins were identified as potential vaccine antigens. In vitro and in vivo experiments now need to be performed to validate the immune and protective power of these newly identified antigens.

  7. A Case of Sigmoid Colon Tuberculosis Mimicking Colon Cancer

    OpenAIRE

    Yu, Seong-Min; Park, Jong-Hwan; Kim, Min-Dae; Lee, Hee-Ryong; Jung, Peel; Ryu, Tae-Hyun; Choi, Seung-Ho; Lee, Il-Seon

    2012-01-01

    Tuberculosis of the sigmoid colon is a rare disorder. An 80-year-old man visited Bongseng Memorial Hospital for medical examination. A colonoscopy was performed, and a lesion in the sigmoid colon that was suspected to be colon cancer was found. A biopsy was performed, and tuberculous enteritis with chronic granulomatous inflammation was diagnosed. Intestinal tuberculosis is most frequent in the ileocecal area, followed by the ascending colon, transverse colon, duodenum, stomach, and sigmoid c...

  8. Synchronous colon and gastric advanced carcinomas

    International Nuclear Information System (INIS)

    Giuliani, A.; Demoro, M.; Corona, M.; Di Bari, M.; Ricciardulli, T.; Galati, G.; Ciardi, A.

    2005-01-01

    An unusual case of advanced synchronous colon and gastric carcinoma is described. A 36 year old female was admitted to our Department with a stenosing right colon cancer diagnosed at endoscopy which was performed for lower crampy abdominal pain and gross blood in the stool. Multiple colon polyps, distal to the tumor, were also detected. On preoperative abdominal computed tomography, a stenosing right colon cancer, without evidence of abdominal diffusion, was confirmed. At laparotomy, in addition to colon cancer, an antral gastric cancer was incidentally found. En bloc hemi gastrectomy and subtotal colectomy were performed. Digestive continuity was restored by gastrojejunal and ileosigmoid anastomoses. At histology, a poorly differentiated gastric adenocarcinoma with signet ring-cell component (pT2, pN0; stage IB) and a moderately differentiated colon adenocarcinoma with a tubulovillous component (pT3, pN1; stage III, Stage Dukes C) were revealed. Both tumors showed a low expression of p53 and c-erb2 oncoproteins. No genetic defect was identified in the APC and MMR genes. The patient is alive, without recurrence, two years after the operation

  9. Staphylococcus aureus in the community: colonization versus infection.

    Directory of Open Access Journals (Sweden)

    Maureen Miller

    Full Text Available BACKGROUND: Antibiotic-resistant Staphylococcus aureus infections have increased dramatically in the community, yet S. aureus nasal colonization has remained stable. The objectives of this study were to determine if S. aureus colonization is a useful proxy measure to study disease transmission and infection in community settings, and to identify potential community reservoirs. METHODOLOGY/PRINCIPAL FINDINGS: Randomly selected households in Northern Manhattan, completed a structured social network questionnaire and provided nasal swabs that were typed by pulsed field gel electrophoresis to identify S. aureus colonizing strains. The main outcome measures were: 1 colonization with S. aureus; and 2 recent serious skin infection. Risk factor analyses were conducted at both the individual and the household levels; logistic regression models identified independent risks for household colonization and infection. RESULTS: 321 surveyed households contained 914 members. The S. aureus prevalence was 25% and MRSA was 0.4%. More than 40% of households were colonized. Recent antibiotic use was the only significant correlate for household colonization (p = .002. Seventy-eight (24% households reported serious skin infection. In contrast with colonization, five of the six risk factors that increased the risk of skin infection in the household at the univariate level remained independently significant in multivariable analysis: international travel, sports participation, surgery, antibiotic use and towel sharing. S. aureus colonization was not significantly associated with serious skin infection in any analysis. Among multiperson households with more than one person colonized, 50% carried the same strain. CONCLUSIONS/SIGNIFICANCE: The lack of association between S. aureus nasal colonization and serious skin infection underscores the need to explore alternative venues or body sites that may be crucial to transmission. Moreover, the magnitude of colonization and

  10. Improving Outcomes Following Penetrating Colon Wounds

    Science.gov (United States)

    Miller, Preston R.; Fabian, Timothy C.; Croce, Martin A.; Magnotti, Louis J.; Elizabeth Pritchard, F.; Minard, Gayle; Stewart, Ronald M.

    2002-01-01

    Introduction During World War II, failure to treat penetrating colon injuries with diversion could result in court martial. Based on this wartime experience, colostomy for civilian colon wounds became the standard of care for the next 4 decades. Previous work from our institution demonstrated that primary repair was the optimal management for nondestructive colon wounds. Optimal management of destructive wounds requiring resection remains controversial. To address this issue, we performed a study that demonstrated risk factors (pre or intraoperative transfusion requirement of more than 6 units of packed red blood cells, significant comorbid diseases) that were associated with a suture line failure rate of 14%, and of whom 33% died. Based on these outcomes, a clinical pathway for management of destructive colon wounds was developed. The results of the implementation of this pathway are the focus of this report. Methods Patients with penetrating colon injury were identified from the registry of a level I trauma center over a 5-year period. Records were reviewed for demographics, injury characteristics, and outcome. Patients with nondestructive injuries underwent primary repair. Patients with destructive wounds but no comorbidities or large transfusion requirement underwent resection and anastomosis, while patients with destructive wounds and significant medical illness or transfusion requirements of more than 6 units/blood received end colostomy. The current patients (CP) were compared to the previous study (PS) to determine the impact of the clinical pathway. Outcomes examined included colon related mortality and morbidity (suture line leak and abscess). Results Over a 5.5-year period, 231 patients had penetrating colon wounds. 209 survived more 24 hours and comprise the study population. Primary repair was performed on 153 (73%) patients, and 56 patients had destructive injuries (27%). Of these, 40 (71%) had resection and anastomosis and 16 (29%) had diversion

  11. The frequency of genes encoding three putative group B streptococcal virulence factors among invasive and colonizing isolates

    Directory of Open Access Journals (Sweden)

    Borchardt Stephanie M

    2006-07-01

    Full Text Available Abstract Background Group B Streptococcus (GBS causes severe infections in very young infants and invasive disease in pregnant women and adults with underlying medical conditions. GBS pathogenicity varies between and within serotypes, with considerable variation in genetic content between strains. Three proteins, Rib encoded by rib, and alpha and beta C proteins encoded by bca and bac, respectively, have been suggested as potential vaccine candidates for GBS. It is not known, however, whether these genes occur more frequently in invasive versus colonizing GBS strains. Methods We screened 162 invasive and 338 colonizing GBS strains from different collections using dot blot hybridization to assess the frequency of bca, bac and rib. All strains were defined by serotyping for capsular type, and frequency differences were tested using the Chi square test. Results Genes encoding the beta C protein (bac and Rib (rib occurred at similar frequencies among invasive and colonizing isolates, bac (20% vs. 23%, and rib (28% vs. 20%, while the alpha (bca C protein was more frequently found in colonizing strains (46% vs, invasive (29%. Invasive strains were associated with specific serotype/gene combinations. Conclusion Novel virulence factors must be identified to better understand GBS disease.

  12. Upregulated expression of human neutrophil peptides 1, 2 and 3 (HNP 1-3) in colon cancer serum and tumours

    DEFF Research Database (Denmark)

    Albrethsen, Jakob; Bøgebo, Rikke; Gammeltoft, Steen

    2005-01-01

    of identifying biomarkers for colon cancer. METHODS: By Surface Enhanced Laser Desorption/Ionisation--Time Of Flight/Mass spectrometry (SELDI-TOF/MS) we compare the protein profiles of colon cancer serum with serum from healthy individuals and the protein profiles of colon tumours with normal colon tissue...

  13. Views on Values Education: From Teacher Candidates to Experienced Teachers

    Science.gov (United States)

    Iscan, Canay Demirhan

    2015-01-01

    This study aimed to identify the views of experienced class teachers and class teacher candidates on values education. It conducted standard open-ended interviews with experienced class teachers and teacher candidates. The study group comprised 9 experienced class teachers from different socio-economic levels and 9 teacher candidates with…

  14. Alternative splicing and differential gene expression in colon cancer detected by a whole genome exon array

    Directory of Open Access Journals (Sweden)

    Sugnet Charles

    2006-12-01

    Full Text Available Abstract Background Alternative splicing is a mechanism for increasing protein diversity by excluding or including exons during post-transcriptional processing. Alternatively spliced proteins are particularly relevant in oncology since they may contribute to the etiology of cancer, provide selective drug targets, or serve as a marker set for cancer diagnosis. While conventional identification of splice variants generally targets individual genes, we present here a new exon-centric array (GeneChip Human Exon 1.0 ST that allows genome-wide identification of differential splice variation, and concurrently provides a flexible and inclusive analysis of gene expression. Results We analyzed 20 paired tumor-normal colon cancer samples using a microarray designed to detect over one million putative exons that can be virtually assembled into potential gene-level transcripts according to various levels of prior supporting evidence. Analysis of high confidence (empirically supported transcripts identified 160 differentially expressed genes, with 42 genes occupying a network impacting cell proliferation and another twenty nine genes with unknown functions. A more speculative analysis, including transcripts based solely on computational prediction, produced another 160 differentially expressed genes, three-fourths of which have no previous annotation. We also present a comparison of gene signal estimations from the Exon 1.0 ST and the U133 Plus 2.0 arrays. Novel splicing events were predicted by experimental algorithms that compare the relative contribution of each exon to the cognate transcript intensity in each tissue. The resulting candidate splice variants were validated with RT-PCR. We found nine genes that were differentially spliced between colon tumors and normal colon tissues, several of which have not been previously implicated in cancer. Top scoring candidates from our analysis were also found to substantially overlap with EST-based bioinformatic

  15. Carotenoids and colon cancer.

    Science.gov (United States)

    Slattery, M L; Benson, J; Curtin, K; Ma, K N; Schaeffer, D; Potter, J D

    2000-02-01

    Carotenoids have numerous biological properties that may underpin a role for them as chemopreventive agents. However, except for beta-carotene, little is known about how dietary carotenoids are associated with common cancers, including colon cancer. The objective of this study was to evaluate associations between dietary alpha-carotene, beta-carotene, lycopene, lutein, zeaxanthin, and beta-cryptoxanthin and the risk of colon cancer. Data were collected from 1993 case subjects with first primary incident adenocarcinoma of the colon and from 2410 population-based control subjects. Dietary data were collected from a detailed diet-history questionnaire and nutrient values for dietary carotenoids were obtained from the US Department of Agriculture-Nutrition Coordinating Center carotenoid database (1998 updated version). Lutein was inversely associated with colon cancer in both men and women [odds ratio (OR) for upper quintile of intake relative to lowest quintile of intake: 0.83; 95% CI: 0.66, 1.04; P = 0.04 for linear trend]. The greatest inverse association was observed among subjects in whom colon cancer was diagnosed when they were young (OR: 0.66; 95% CI: 0.48, 0.92; P = 0.02 for linear trend) and among those with tumors located in the proximal segment of the colon (OR: 0.65; 95% CI: 0.51, 0.91; P lettuce, tomatoes, oranges and orange juice, carrots, celery, and greens. These data suggest that incorporating these foods into the diet may help reduce the risk of developing colon cancer.

  16. Describing the Diapause-Preparatory Proteome of the Beetle Colaphellus bowringi and Identifying Candidates Affecting Lipid Accumulation Using Isobaric Tags for Mass Spectrometry-Based Proteome Quantification (iTRAQ

    Directory of Open Access Journals (Sweden)

    Daniel A. Hahn

    2017-04-01

    Full Text Available Prior to entering diapause, insects must prepare themselves physiologically to withstand the stresses of arresting their development for a lengthy period. While studies describing the biochemical and cellular milieu of the maintenance phase of diapause are accumulating, few studies have taken an “omics” approach to describing molecular events during the diapause preparatory phase. We used isobaric tags and mass spectrometry (iTRAQ to quantitatively compare the expression profiles of proteins identified during the onset of diapause preparation phase in the heads of adult female cabbage beetles, Colaphellus bowringi. A total of 3,175 proteins were identified, 297 of which were differentially expressed between diapause-destined and non-diapause-destined female adults and could therefore be involved in diapause preparation in this species. Comparison of identified proteins with protein function databases shows that many of these differentially expressed proteins enhanced in diapause destined beetles are involved in energy production and conversion, carbohydrate metabolism and transport, and lipid metabolism. Further hand annotation of differentially abundant peptides nominates several associated with stress hardiness, including HSPs and antioxidants, as well as neural development. In contrast, non-diapause destined beetles show substantial increases in cuticle proteins, suggesting additional post-emergence growth. Using RNA interference to silence a fatty acid-binding protein (FABP that was highly abundant in the head of diapause-destined females prevented the accumulation of lipids in the fat body, a common product of diapause preparation in this species and others. Surprisingly, RNAi against the FABP also affected the transcript abundance of several heat shock proteins. These results suggest that the identified differentially expressed proteins that play vital roles in lipid metabolism may also contribute somehow to enhanced hardiness to

  17. Endoscopic Localization of Colon Cancer Is Frequently Inaccurate.

    Science.gov (United States)

    Nayor, Jennifer; Rotman, Stephen R; Chan, Walter W; Goldberg, Joel E; Saltzman, John R

    2017-08-01

    Colonoscopic location of a tumor can influence both the surgical procedure choice and overall treatment strategy. To determine the accuracy of colonoscopy in determining the location of colon cancer compared to surgical localization and to elucidate factors that predict discordant colon cancer localization. We conducted a retrospective cross-sectional study of colon cancers diagnosed on colonoscopy at two academic tertiary-care hospitals and two affiliated community hospitals from 2012 to 2014. Colon cancer location was obtained from the endoscopic and surgical pathology reports and characterized by colon segment. We collected data on patient demographics, tumor characteristics, endoscopic procedure characteristics, surgery planned, and surgery performed. Univariate analyses using Chi-squared test and multivariate analysis using forward stepwise logistic regression were performed to determine factors that predict discordant colon cancer localization. There were 110 colon cancer cases identified during the study period. Inaccurate endoscopic colon cancer localization was found in 29% (32/110) of cases. These included 14 cases (12.7%) that were discordant by more than one colonic segment and three cases where the presurgical planned procedure was significantly changed at the time of surgery. On univariate analyses, right-sided colon lesions were associated with increased inaccuracy (43.8 vs 24.4%, p = 0.04). On multivariate analysis, right-sided colon lesions remained independently associated with inaccuracy (OR 1.74, 95% CI 1.03-2.93, p = 0.04). Colon cancer location as determined by colonoscopy is often inaccurate, which can result in intraoperative changes to surgical management, particularly in the right colon.

  18. CT colonography for preoperative examination of the proximal colon using a transanal drainage tube for acute malignant colonic obstruction

    International Nuclear Information System (INIS)

    Sasaki, Kazuaki; Hirano, Yuji; Oono, Keisuke; Sasaki, Kazunori; Someya, Tetsufumi; Harada, Keisuke; Ezoe, Eiri; Furuhata, Tomohisa; Hirata, Koichi

    2011-01-01

    The purpose of this study was to evaluate the feasibility of CT colonography for preoperative examination of the proximal colon using a transanal drainage tube in patients with acute colon obstruction caused by colorectal cancer. Ten patients who received initial treatment for acute malignant colon obstruction at our hospital between June 2004 and December 2008 were studied. In these patients, elective surgery was possible after transanal drainage tube insertion, and the colon on the oral side from the cancer lesion was examined using a drainage tube. Air was injected through the tube into the oral side of the colon, and CT colonography was assessed for the presence or absence of lesions on the oral side. The images of the oral side of the colon were good enough to allow adequate interpretation in 9 of the 10 patients. In the first patient, the visualization of the area near the lesion was somewhat fair, although the right side colon was well visualized. There were no complications associated with this examination. The present preoperative examination using a transanal drainage tube was useful for determining the extent of intestinal resection when patients were not candidates for colonoscopy or barium enema examination. (author)

  19. Identification Of Protein Vaccine Candidates Using Comprehensive Proteomic Analysis Strategies

    National Research Council Canada - National Science Library

    Rohrbough, James G

    2007-01-01

    Presented in this dissertation are proteomic analysis studies focused on identifying proteins to be used as vaccine candidates against Coccidioidomycosis, a potentially fatal human pulmonary disease...

  20. CT findings of colonic diverticulitis

    International Nuclear Information System (INIS)

    Sasaki, Shigeru; Ohba, Satoru; Mizutani, Masaru

    1998-01-01

    Although colonic diverticulitis has no indication for operation, but in some mistaken cases were operated with a diagnosis of acute appendicitis. We evaluated the CT findings of colonic diverticulitis about 19 cases and of asymptomatic colonic diverticula about 15 cases retrospectively. Diagnosis was confirmed of barium enema and operation. CT are complementary methods of examination that can delineated the range of thickening of the colon and the extension of inflammatory changes around the colon. We also believe that CT findings of colonic diverticulitis are useful for differentiating from a diagnosis of appendicitis. (author)

  1. Complicated colonic intussusception

    Directory of Open Access Journals (Sweden)

    Justin James

    2012-01-01

    Full Text Available The manuscript deals with the case of a 53-year-old woman who developed large bowel obstruction. Per-rectal examination revealed a pedunculated lesion in the rectum; rigid sigmoidoscopy revealed a prolapsing pedunculated mass with a necrotic surface. The patient recovered well following anterior resection. Histology confirmed a pedunculated sub mucosal lipoma as the lead point for intussusception. Colonic intussusception is a rare cause of adult large bowel obstruction, and the preoperative clinical diagnosis of this condition can be difficult. Resection of the involved segment of the colon is the most appropriate choice of treatment in most such cases.

  2. Fungal colonization of air-conditioning systems

    Directory of Open Access Journals (Sweden)

    Ljaljević-Grbić Milica

    2008-01-01

    Full Text Available Fungi have been implicated as quantitatively the most important bioaerosol component of indoor air associated with contaminated air-conditioning systems. rarely, indoor fungi may cause human infections, but more commonly allergenic responses ranging from pneumonitis to asthma-like symptoms. From all air conditioner filters analyzed, 16 fungal taxa were isolated and identified. Aspergillus fumigatus causes more lethal infections worldwide than any other mold. Air-conditioning filters that adsorb moisture and volatile organics appear to provide suitable substrates for fungal colonization. It is important to stress that fungal colonization of air-conditioning systems should not be ignored, especially in hospital environments.

  3. Extra colonic Findings on CT Colonography in Symptomatic Patients

    International Nuclear Information System (INIS)

    Drahovska, I.; Nigut, F.; Mach, P.; Lazurova, I.; Gombosova, L.

    2011-01-01

    The paper is an analysis of the consequences of the extra colonic findings identified on CT colonography examination of symptomatic patients and the validity of the intravenous application of contrast medium in this examination. The authors enrolled 252 patients, who underwent CT colonogprahy.128 extra colonic findings was identified in 80 patients (31.74%). The average age was 65.62 years (SD = 12.7, min. age was 29, max. age. 85 years). According the clinical significance the extra colonic findings have been divided into three groups – low, moderate and very important extra colonic findings. Low significant findings were 68 (53.12%), moderate 26 (20.31%) and very important extra colonic findings were 34 (26.56%), of which 30 were malignant nature. (author)

  4. Evolution of the operative management of colon trauma.

    Science.gov (United States)

    Sharpe, John P; Magnotti, Louis J; Fabian, Timothy C; Croce, Martin A

    2017-01-01

    For any trauma surgeon, colon wounds remain a relatively common, yet sometimes challenging, clinical problem. Evolution in operative technique and improvements in antimicrobial therapy during the past two centuries have brought remarkable improvements in both morbidity and mortality after injury to the colon. Much of the early progress in management and patient survival after colon trauma evolved from wartime experience. Multiple evidence-based studies during the last several decades have allowed for more aggressive management, with most wounds undergoing primary repair or resection and anastomosis with an acceptably low suture line failure rate. Despite the abundance of quality evidence regarding management of colon trauma obtained from both military and civilian experience, there remains some debate among institutions regarding management of specific injuries. This is especially true with respect to destructive wounds, injuries to the left colon, blunt colon trauma and those wounds requiring colonic discontinuity during an abbreviated laparotomy. Some programs have developed data-driven protocols that have simplified management of destructive colon wounds, clearly identifying those high-risk patients who should undergo diversion, regardless of mechanism or anatomic location. This update will describe the progression in the approach to colon injuries through history while providing a current review of the literature regarding management of the more controversial wounds.

  5. Microarray-based identification and RT-PCR test screening for epithelial-specific mRNAs in peripheral blood of patients with colon cancer

    Directory of Open Access Journals (Sweden)

    Coppola Domenico

    2006-10-01

    Full Text Available Abstract Background The efficacy of screening for colorectal cancer using a simple blood-based assay for the detection of tumor cells disseminated in the circulation at an early stage of the disease is gaining positive feedback from several lines of research. This method seems able to reduce colorectal cancer mortality and may replace colonoscopy as the most effective means of detecting colonic lesions. Methods In this work, we present a new microarray-based high-throughput screening method to identifying candidate marker mRNAs for the early detection of epithelial cells diluted in peripheral blood cells. This method includes 1. direct comparison of different samples of colonic mucosa and of blood cells to identify consistent epithelial-specific mRNAs from among 20,000 cDNA assayed by microarray slides; 2. identification of candidate marker mRNAs by data analysis, which allowed selection of only 10 putative differentially expressed genes; 3. Selection of some of the most suitable mRNAs (TMEM69, RANBP3 and PRSS22 that were assayed in blood samples from normal subjects and patients with colon cancer as possible markers for the presence of epithelial cells in the blood, using reverse transcription – polymerase chain reaction (RT-PCR. Results Our present results seem to provide an indication, for the first time obtained by genome-scale screening, that a suitable and consistent colon epithelium mRNA marker may be difficult to identify. Conclusion The design of new approaches to identify such markers is warranted.

  6. Dark matter candidates

    International Nuclear Information System (INIS)

    Turner, M.S.

    1989-01-01

    One of the simplest, yet most profound, questions we can ask about the Universe is, how much stuff is in it, and further what is that stuff composed of? Needless to say, the answer to this question has very important implications for the evolution of the Universe, determining both the ultimate fate and the course of structure formation. Remarkably, at this late date in the history of the Universe we still do not have a definitive answer to this simplest of questions---although we have some very intriguing clues. It is known with certainty that most of the material in the Universe is dark, and we have the strong suspicion that the dominant component of material in the Cosmos is not baryons, but rather is exotic relic elementary particles left over from the earliest, very hot epoch of the Universe. If true, the Dark Matter question is a most fundamental one facing both particle physics and cosmology. The leading particle dark matter candidates are: the axion, the neutralino, and a light neutrino species. All three candidates are accessible to experimental tests, and experiments are now in progress. In addition, there are several dark horse, long shot, candidates, including the superheavy magnetic monopole and soliton stars. 13 refs

  7. Colonization, mouse-style

    Directory of Open Access Journals (Sweden)

    Searle Jeremy B

    2010-10-01

    Full Text Available Abstract Several recent papers, including one in BMC Evolutionary Biology, examine the colonization history of house mice. As well as background for the analysis of mouse adaptation, such studies offer a perspective on the history of movements of the humans that accidentally transported the mice. See research article: http://www.biomedcentral.com/1471-2148/10/325

  8. Validation of methylation biomarkers that distinguish normal colon mucosa of cancer patients from normal colon mucosa of patients without cancer.

    Science.gov (United States)

    Cesaroni, Matteo; Powell, Jasmine; Sapienza, Carmen

    2014-07-01

    We have validated differences in DNA methylation levels of candidate genes previously reported to discriminate between normal colon mucosa of patients with colon cancer and normal colon mucosa of individuals without cancer. Here, we report that CpG sites in 16 of the 30 candidate genes selected show significant differences in mean methylation level in normal colon mucosa of 24 patients with cancer and 24 controls. A support vector machine trained on these data and data for an additional 66 CpGs yielded an 18-gene signature, composed of ten of the validated candidate genes plus eight additional candidates. This model exhibited 96% sensitivity and 100% specificity in a 40-sample training set and classified all eight samples in the test set correctly. Moreover, we found a moderate-strong correlation (Pearson coefficients r = 0.253-0.722) between methylation levels in colon mucosa and methylation levels in peripheral blood for seven of the 18 genes in the support vector model. These seven genes, alone, classified 44 of the 48 patients in the validation set correctly and five CpGs selected from only two of the seven genes classified 41 of the 48 patients in the discovery set correctly. These results suggest that methylation biomarkers may be developed that will, at minimum, serve as useful objective and quantitative diagnostic complements to colonoscopy as a cancer-screening tool. These data also suggest that it may be possible to monitor biomarker methylation levels in tissues collected much less invasively than by colonoscopy. ©2014 American Association for Cancer Research.

  9. External coating of colonic anastomoses

    DEFF Research Database (Denmark)

    Pommergaard, Hans-Christian; Achiam, Michael Patrick; Rosenberg, Jacob

    2012-01-01

    Colon anastomotic leakage remains both a frequent and serious complication in gastrointestinal surgery. External coating of colonic anastomoses has been proposed as a means to lower the rate of this complication. The aim of this review was to evaluate existing studies on external coating of colonic...

  10. Colonic microbiota signatures across five northern European countries

    NARCIS (Netherlands)

    Lay, C.; Rigottier-Gois, L.; Holmstrom, K.; Rajilic-Stojanovic, M.; Vaughan, E.E.; Vos, de W.M.; Collins, M.D.; Thiel, R.; Namsolleck, P.; Blaut, M.; Dore, J.

    2005-01-01

    The composition of the colonic microbiota of 91 northern Europeans was characterized by fluorescent in situ hybridization using 18 phylogenetic probes. On average 75% of the bacteria were identified, and large interindividual variations were observed. Clostridium coccoides and Clostridium leptum

  11. Identify drug repurposing candidates by mining the protein data bank.

    Science.gov (United States)

    Moriaud, Fabrice; Richard, Stéphane B; Adcock, Stewart A; Chanas-Martin, Laetitia; Surgand, Jean-Sébastien; Ben Jelloul, Marouane; Delfaud, François

    2011-07-01

    Predicting off-targets by computational methods is gaining increasing interest in early-stage drug discovery. Here, we present a computational method based on full 3D comparisons of 3D structures. When a similar binding site is detected in the Protein Data Bank (PDB) (or any protein structure database), it is possible that the corresponding ligand also binds to that similar site. On one hand, this target hopping case is probably rare because it requires a high similarity between the binding sites. On the other hand, it could be a strong rational evidence to highlight possible off-target reactions and possibly a potential undesired side effect. This target-based drug repurposing can be extended a significant step further with the capability of searching the full surface of all proteins in the PDB, and therefore not relying on pocket detection. Using this approach, we describe how MED-SuMo reproduces the repurposing of tadalafil from PDE5A to PDE4A and a structure of PDE4A with tadalafil. Searching for local protein similarities generates more hits than for whole binding site similarities and therefore fragment repurposing is more likely to occur than for drug-sized compounds. In this work, we illustrate that by mining the PDB for proteins sharing similarities with the hinge region of protein kinases. The experimentally validated examples, biotin carboxylase and synapsin, are retrieved. Further to fragment repurposing, this approach can be applied to the detection of druggable sites from 3D structures. This is illustrated with detection of the protein kinase hinge motif in the HIV-RT non-nucleosidic allosteric site.

  12. 'Omics' approaches in tomato aimed at identifying candidate genes ...

    African Journals Online (AJOL)

    adriana

    2013-12-04

    Dec 4, 2013 ... importance for human health and nutrition. This species has ... function to genes, proteins and metabolites is still a daunting task. Major challenges ... relation of the expression pattern of genes with the accu- mulation pattern of ..... M, Gordon JS, Rose, JKC, Martin G, Tanksley SD, Bouzayen M,. Jahn MM ...

  13. 'Omics' approaches in tomato aimed at identifying candidate genes ...

    African Journals Online (AJOL)

    Tomato (Solanum lycopersicum) is one of the most important vegetables in the world with significant importance for human health and nutrition. This species has long served as model system for plant genetics, development, physiology, pathology, and fleshy fruit ripening, resulting in the accumulation of many genetic and ...

  14. A New Way to Confirm Planet Candidates

    Science.gov (United States)

    Kohler, Susanna

    2016-05-01

    What was the big deal behind the Kepler news conference yesterday? Its not just that the number of confirmed planets found by Kepler has more than doubled (though thats certainly exciting news!). Whats especially interesting is the way in which these new planets were confirmed.Number of planet discoveries by year since 1995, including previous non-Kepler discoveries (blue), previous Kepler discoveries (light blue) and the newly validated Kepler planets (orange). [NASA Ames/W. Stenzel; Princeton University/T. Morton]No Need for Follow-UpBefore Kepler, the way we confirmed planet candidates was with follow-up observations. The candidate could be validated either by directly imaging (which is rare) or obtaining a large number radial-velocity measurements of the wobble of the planets host star due to the planets orbit. But once Kepler started producing planet candidates, these approaches to validation became less feasible. A lot of Kepler candidates are small and orbit faint stars, making follow-up observations difficult or impossible.This problem is what inspired the development of whats known as probabilistic validation, an analysis technique that involves assessing the likelihood that the candidates signal is caused by various false-positive scenarios. Using this technique allows astronomers to estimate the likelihood of a candidate signal being a true planet detection; if that likelihood is high enough, the planet candidate can be confirmed without the need for follow-up observations.A breakdown of the catalog of Kepler Objects of Interest. Just over half had previously been identified as false positives or confirmed as candidates. 1284 are newly validated, and another 455 have FPP of1090%. [Morton et al. 2016]Probabilistic validation has been used in the past to confirm individual planet candidates in Kepler data, but now Timothy Morton (Princeton University) and collaborators have taken this to a new level: they developed the first code thats designed to do fully

  15. Patients with Acromegaly Presenting with Colon Cancer: A Case Series

    Directory of Open Access Journals (Sweden)

    Murray B. Gordon

    2016-01-01

    Full Text Available Introduction. Frequent colonoscopy screenings are critical for early diagnosis of colon cancer in patients with acromegaly. Case Presentations. We performed a retrospective analysis of the incidental diagnoses of colon cancer from the ACCESS trial (ClinicalTrials.gov identifier: NCT01995734. Colon cancer was identified in 2 patients (4.5%. Case  1 patient was a 36-year-old male with acromegaly who underwent transsphenoidal surgery to remove the pituitary adenoma. After surgery, the patient underwent routine colonoscopy screening, which revealed a 40 mm tubular adenoma in the descending colon. A T1N1a carcinoma was surgically removed, and 1 of 22 lymph nodes was positive for metastatic disease, leading to a diagnosis of stage 3 colon cancer. Case  2 patient was a 50-year-old male with acromegaly who underwent transsphenoidal surgery to remove a 2 cm pituitary adenoma. The patient reported severe cramping and lower abdominal pain, and an invasive 8.1 cm3 grade 2 adenocarcinoma with signet rings was identified in the ascending colon and removed. Of the 37 lymph nodes, 34 were positive for the presence of tumor cells, and stage 3c colon cancer was confirmed. Conclusion. Current guidelines for colonoscopy screening at the time of diagnosis of acromegaly and at appropriate follow-up intervals should be followed.

  16. Optimized candidal biofilm microtiter assay

    NARCIS (Netherlands)

    Krom, Bastiaan P.; Cohen, Jesse B.; Feser, Gail E. McElhaney; Cihlar, Ronald L.

    Microtiter based candidal biofilm formation is commonly being used. Here we describe the analysis of factors influencing the development of candidal biofilms such as the coating with serum, growth medium and pH. The data reported here show that optimal candidal biofilm formation is obtained when

  17. JELLYFISH GALAXY CANDIDATES AT LOW REDSHIFT

    Energy Technology Data Exchange (ETDEWEB)

    Poggianti, B. M.; Fasano, G.; Omizzolo, A.; Gullieuszik, M.; Bettoni, D.; Paccagnella, A. [INAF-Astronomical Observatory of Padova (Italy); Moretti, A.; D’Onofrio, M. [Physics and Astronomy Department, University of Padova (Italy); Jaffé, Y. L. [Department of Astronomy, Universidad de Concepción, Concepción (Chile); Vulcani, B. [Kavli Institute for the Physics and Mathematics of the universe (WPI), The University of Tokyo Institutes for Advanced Study (UTIAS), the University of Tokyo, Kashiwa, 277-8582 (Japan); Fritz, J. [Centro de Radioastronomía y Astrofísica, CRyA, UNAM, Michoacán (Mexico); Couch, W. [Australian Astronomical Observatory, North Ryde, NSW 1670 (Australia)

    2016-03-15

    Galaxies that are being stripped of their gas can sometimes be recognized from their optical appearance. Extreme examples of stripped galaxies are the so-called “jellyfish galaxies” that exhibit tentacles of debris material with a characteristic jellyfish morphology. We have conducted the first systematic search for galaxies that are being stripped of their gas at low-z (z = 0.04−0.07) in different environments, selecting galaxies with varying degrees of morphological evidence for stripping. We have visually inspected B- and V-band images and identified 344 candidates in 71 galaxy clusters of the OMEGAWINGS+WINGS sample and 75 candidates in groups and lower mass structures in the PM2GC sample. We present the atlas of stripping candidates and a first analysis of their environment and their basic properties, such as morphologies, star formation rates and galaxy stellar masses. Candidates are found in all clusters and at all clustercentric radii, and their number does not correlate with the cluster velocity dispersion σ or X-ray luminosity L{sub X}. Interestingly, convincing cases of candidates are also found in groups and lower mass halos (10{sup 11}−10{sup 14}M{sub ⊙}), although the physical mechanism at work needs to be securely identified. All the candidates are disky, have stellar masses ranging from log M/M{sub ⊙} < 9 to > 11.5 and the majority of them form stars at a rate that is on average a factor of 2 higher (2.5σ) compared to non-stripped galaxies of similar mass. The few post-starburst and passive candidates have weak stripping evidence. We conclude that disturbed morphologies suggestive of stripping phenomena are ubiquitous in clusters and could be present even in groups and low mass halos. Further studies will reveal the physics of the gas stripping and clarify the mechanisms at work.

  18. Malignant transformation of colonic epithelial cells by a colon-derived long noncoding RNA

    International Nuclear Information System (INIS)

    Franklin, Jeffrey L.; Rankin, Carl R.; Levy, Shawn; Snoddy, Jay R.; Zhang, Bing; Washington, Mary Kay; Thomson, J. Michael; Whitehead, Robert H.; Coffey, Robert J.

    2013-01-01

    Highlights: •Non-coding RNAs are found in the colonic crypt progenitor compartment. •Colonocytes transformed by ncNRFR are highly invasive and metastatic. •ncNRFR has a region similar to the miRNA, let-7 family. •ncNRFR expression alters let-7 activity as measured by reporter construct. •ncNRFR expression upregulates let-7b targets. -- Abstract: Recent progress has been made in the identification of protein-coding genes and miRNAs that are expressed in and alter the behavior of colonic epithelia. However, the role of long non-coding RNAs (lncRNAs) in colonic homeostasis is just beginning to be explored. By gene expression profiling of post-mitotic, differentiated tops and proliferative, progenitor-compartment bottoms of microdissected adult mouse colonic crypts, we identified several lncRNAs more highly expressed in crypt bottoms. One identified lncRNA, designated non-coding Nras functional RNA (ncNRFR), resides within the Nras locus but appears to be independent of the Nras coding transcript. Stable overexpression of ncNRFR in non-transformed, conditionally immortalized mouse colonocytes results in malignant transformation, as determined by growth in soft agar and formation of highly invasive tumors in nude mice. Moreover, ncNRFR appears to inhibit the function of the tumor suppressor let-7. These results suggest precise regulation of ncNRFR is necessary for proper cell growth in the colonic crypt, and its misregulation results in neoplastic transformation

  19. Impact of location on outcome after penetrating colon injuries.

    Science.gov (United States)

    Sharpe, John P; Magnotti, Louis J; Weinberg, Jordan A; Zarzaur, Ben L; Shahan, Charles P; Parks, Nancy A; Fabian, Timothy C; Croce, Martin A

    2012-12-01

    Most studies examining suture line failure after penetrating colon injuries have focused on right- versus left-sided injuries. In our institution, operative decisions (resection plus anastomosis vs. diversion) are based on a defined management algorithm regardless of injury location. The purpose of this study was to evaluate the effect of injury location on outcomes after penetrating colon injuries. Consecutive patients with full thickness penetrating colon injuries for 13 years were stratified by age, injury location and mechanism, and severity of shock. According to the algorithm, patients with nondestructive injuries underwent primary repair. Destructive wounds underwent resection plus anastomosis in the absence of comorbidities or large preoperative or intraoperative transfusion requirements (>6 U of packed red blood cells); otherwise, they were diverted. Injury location was defined as ascending, transverse, descending (including splenic flexure), and sigmoid. Multivariable logistic regression was performed to determine whether injury location was an independent predictor of either morbidity or mortality. Four hundred sixty-nine patients were identified: 314 (67%) underwent primary repair and 155 (33%) underwent resection. Most injuries involved the transverse colon (39%), followed by the ascending colon (26%), the descending colon (21%), and the sigmoid colon (14%). Overall, there were 13 suture line failures (3%) and 72 abscesses (15%). Most suture line failures involved injuries to the descending colon (p = 0.06), whereas most abscesses followed injuries to the ascending colon (p = 0.37). Multivariable logistic regression failed to identify injury location as an independent predictor of either morbidity or mortality after adjusting for 24-hour transfusions, base excess, shock index, injury mechanism, and operative management. Injury location did not affect morbidity or mortality after penetrating colon injuries. Nondestructive injuries should be primarily

  20. Diet, genes, and microbes: complexities of colon cancer prevention.

    Science.gov (United States)

    Birt, Diane F; Phillips, Gregory J

    2014-01-01

    Colorectal cancer is one of the leading causes of cancer-related deaths in the United States, and generally, as countries climb the economic ladder, their rates of colon cancer increase. Colon cancer was an early disease where key genetic mutations were identified as important in disease progression, and there is considerable interest in determining whether specific mutations sensitize the colon to cancer prevention strategies. Epidemiological studies have revealed that fiber- and vegetable-rich diets and physical activity are associated with reduced rates of colon cancer, while consumption of red and processed meat, or alcoholic beverages, and overconsumption as reflected in obesity are associated with increased rates. Animal studies have probed these effects and suggested directions for further refinement of diet in colon cancer prevention. Recently a central role for the microorganisms in the gastrointestinal tract in colon cancer development is being probed, and it is hypothesized that the microbes may integrate diet and host genetics in the etiology of the disease. This review provides background on dietary, genetic, and microbial impacts on colon cancer and describes an ongoing project using rodent models to assess the ability of digestion-resistant starch in the integration of these factors with the goal of furthering colon cancer prevention.

  1. Towards Treating Chemistry Teacher Candidates as Human

    Science.gov (United States)

    Lewthwaite, Brian Ellis

    2008-01-01

    This research inquiry investigates the factors influencing chemistry teacher candidates' development during their extended practica in the second and final year of an After-Degree Bachelor of Education at a university in central Canada. A variety of data sources are used to identify the risk and protective factors impeding and contributing to the…

  2. Diverticular disease of the right colon

    Directory of Open Access Journals (Sweden)

    Boutross-Tadross Odette

    2011-10-01

    Full Text Available Abstract Background The incidence of colonic diverticular disease varies with national origin, cultural background and diet. The frequency of this disease increases with advancing age. Right-sided diverticular disease is uncommon and reported to occur in 1-2% of surgical specimens in European and American series. In contrast the disease is more prevalent and reported in 43-50% of specimens in Asian series. Various lines of evidence suggest this variation may represent hereditary differences. The aim of the study is to report all cases of right sided diverticular disease underwent surgical resection or identified during pathological examination of right hemicoloectomy specimens Methods A retrospective review of all surgical specimens with right sided colonic diverticular disease selected from a larger database of all colonic diverticulosis and diverticulitis surgical specimen reported between January 1993 and December 2010 at the Pathology Department McMaster University Medical Centre Canada. The clinical and pathological features of these cases were reviewed Results The review identified 15 cases of right colon diverticulosis. The clinical diagnoses of these cases were appendicitis, diverticulitis or adenocarcinoma. Eight cases of single congenital perforated diverticuli were identified and seven cases were incidental multiple acquired diverticuli found in specimen resected for right side colonic carcinomas/large adenomas. Laparotomy or laparoscopic assisted haemicolectomies were done for all cases. Pathological examination showed caecal wall thickening with inflammation associated with perforated diverticuli. Histology confirmed true solitary diverticuli that exhibited in two cases thick walled vessels in the submucosa and muscular layer indicating vascular malformation/angiodysplasia. Acquired diverticuli tend to be multiple and are mostly seen in specimens resected for neoplastic right colon diseases. Conclusion Single true diverticular

  3. Diverticular disease of the right colon.

    Science.gov (United States)

    Radhi, Jasim M; Ramsay, Jennifer A; Boutross-Tadross, Odette

    2011-10-06

    The incidence of colonic diverticular disease varies with national origin, cultural background and diet. The frequency of this disease increases with advancing age. Right-sided diverticular disease is uncommon and reported to occur in 1-2% of surgical specimens in European and American series. In contrast the disease is more prevalent and reported in 43-50% of specimens in Asian series. Various lines of evidence suggest this variation may represent hereditary differences. The aim of the study is to report all cases of right sided diverticular disease underwent surgical resection or identified during pathological examination of right hemicoloectomy specimens A retrospective review of all surgical specimens with right sided colonic diverticular disease selected from a larger database of all colonic diverticulosis and diverticulitis surgical specimen reported between January 1993 and December 2010 at the Pathology Department McMaster University Medical Centre Canada. The clinical and pathological features of these cases were reviewed The review identified 15 cases of right colon diverticulosis. The clinical diagnoses of these cases were appendicitis, diverticulitis or adenocarcinoma. Eight cases of single congenital perforated diverticuli were identified and seven cases were incidental multiple acquired diverticuli found in specimen resected for right side colonic carcinomas/large adenomas. Laparotomy or laparoscopic assisted haemicolectomies were done for all cases. Pathological examination showed caecal wall thickening with inflammation associated with perforated diverticuli. Histology confirmed true solitary diverticuli that exhibited in two cases thick walled vessels in the submucosa and muscular layer indicating vascular malformation/angiodysplasia. Acquired diverticuli tend to be multiple and are mostly seen in specimens resected for neoplastic right colon diseases. Single true diverticular disease of the right colon is usually of congenital type and affects

  4. Immunoreactive proteins of Bifidobacterium longum ssp. longum CCM 7952 and Bifidobacterium longum ssp. longum CCDM 372 identified by gnotobiotic mono-colonized mice sera, immune rabbit sera and nonimmune human sera.

    Directory of Open Access Journals (Sweden)

    Sabina Górska

    2016-09-01

    Full Text Available The Bifidobacteria show great diversity in the cell surface architecture which may influence the physicochemical properties of the bacterial cell and strain specific properties. The immunomodulatory role of bifidobacteria has been extensively studied, however studies on the immunoreactivity of their protein molecules are very limited. Here, we compared six different methods of protein isolation and purification and we report identification of immunogenic and immunoreactive protein of two human Bifidobacterium longum ssp. longum strains. We evaluated potential immunoreactive properties of proteins employing polyclonal sera obtained from germ free mouse, rabbit and human. The protein yield was isolation method-dependent and the reactivity of proteins detected by SDS-PAGE and Western blotting was heterogeneous and varied between different serum samples. The proteins with the highest immunoreactivity were isolated, purified and have them sequenced. Among the immunoreactive proteins we identified enolase, aspartokinase, pyruvate kinase, DnaK (B. longum ssp. longum CCM 7952 and sugar ABC transporter ATP-binding protein, phosphoglycerate kinase, peptidoglycan synthethase penicillin-binding protein 3, transaldolase, ribosomal proteins and glyceraldehyde 3-phosphate dehydrogenase (B. longum ssp. longum CCDM 372.

  5. Immunoreactive Proteins of Bifidobacterium longum ssp. longum CCM 7952 and Bifidobacterium longum ssp. longum CCDM 372 Identified by Gnotobiotic Mono-Colonized Mice Sera, Immune Rabbit Sera and Non-immune Human Sera.

    Science.gov (United States)

    Górska, Sabina; Dylus, Ewa; Rudawska, Angelika; Brzozowska, Ewa; Srutkova, Dagmar; Schwarzer, Martin; Razim, Agnieszka; Kozakova, Hana; Gamian, Andrzej

    2016-01-01

    The Bifidobacteria show great diversity in the cell surface architecture which may influence the physicochemical properties of the bacterial cell and strain specific properties. The immunomodulatory role of bifidobacteria has been extensively studied, however studies on the immunoreactivity of their protein molecules are very limited. Here, we compared six different methods of protein isolation and purification and we report identification of immunogenic and immunoreactive protein of two human Bifidobacterium longum ssp. longum strains. We evaluated potential immunoreactive properties of proteins employing polyclonal sera obtained from germ free mouse, rabbit and human. The protein yield was isolation method-dependent and the reactivity of proteins detected by SDS-PAGE and Western blotting was heterogeneous and varied between different serum samples. The proteins with the highest immunoreactivity were isolated, purified and have them sequenced. Among the immunoreactive proteins we identified enolase, aspartokinase, pyruvate kinase, DnaK ( B. longum ssp. longum CCM 7952) and sugar ABC transporter ATP-binding protein, phosphoglycerate kinase, peptidoglycan synthethase penicillin-binding protein 3, transaldolase, ribosomal proteins and glyceraldehyde 3-phosphate dehydrogenase ( B. longum ssp. longum CCDM 372).

  6. Improved survival with early adjuvant chemotherapy after colonic resection for stage III colonic cancer

    DEFF Research Database (Denmark)

    Klein, Mads; Azaquoun, Najah; Jensen, Benny Vittrup

    2015-01-01

    . Data on patients with stage III colonic cancer operated between January 1, 2005 and August 31, 2012 were retrieved. Perioperative variables, surgical modality, and time to adjuvant therapy (8 weeks) were evaluated and Cox regression was performed to identify factors influencing survival...

  7. Accuracy of colonoscopy in localizing colonic cancer.

    Science.gov (United States)

    Stanciu, C; Trifan, Anca; Khder, Saad Alla

    2007-01-01

    It is important to establish the precise localization of colonic cancer preoperatively; while colonoscopy is regarded as the diagnostic gold standard for colorectal cancer, its ability to localize the tumor is less reliable. To define the accuracy of colonoscopy in identifying the location of colonic cancer. All of the patients who had a colorectal cancer diagnosed by colonoscopy at the Institute of Gastroenterology and Hepatology, Iaşi and subsequently received a surgical intervention at three teaching hospitals in Iaşi, between January 2001 and December 2005, were included in this study. Endoscopic records and operative notes were carefully reviewed, and tumor localization was recorded. There were 161 patients (89 men, 72 women, aged 61.3 +/- 12.8 years) who underwent conventional surgery for colon cancer detected by colonoscopy during the study period. Twenty-two patients (13.66%) had erroneous colonoscopic localization of the tumors. The overall accuracy of preoperative colonoscopic localization was 87.58%. Colonoscopy is an accurate, reliable method for locating colon cancer, although additional techniques (i.e., endoscopic tattooing) should be performed at least for small lesions.

  8. Selection of radio pulsar candidates using artificial neural networks

    OpenAIRE

    Eatough, R. P.; Molkenthin, N.; Kramer, M.; Noutsos, A.; Keith, M. J.; Stappers, B. W.; Lyne, A. G.

    2010-01-01

    Radio pulsar surveys are producing many more pulsar candidates than can be inspected by human experts in a practical length of time. Here we present a technique to automatically identify credible pulsar candidates from pulsar surveys using an artificial neural network. The technique has been applied to candidates from a recent re-analysis of the Parkes multi-beam pulsar survey resulting in the discovery of a previously unidentified pulsar.

  9. Colonic motility and enema spreading

    International Nuclear Information System (INIS)

    Hardy, J.G.; Wood, E.; Clark, A.G.; Reynolds, J.R.; Queen's Medical Centre, Nottingham

    1986-01-01

    Radiolabelled enema solution was administered to eight healthy subjects, both in fasted and fed states. Enema spreading was monitored over a 4-h period using gamma scintigraphy and colonic motility was recorded simultaneously using a pressure sensitive radiotelemetry capsule. The rate and extent of enema dispersion were unaffected by eating. Spreading could be correlated with colonic motility and was inhibited by aboral propulsion of the colonic contents. (orig.)

  10. Vasohibin-1 suppresses colon cancer

    OpenAIRE

    Liu, Shuai; Han, Bing; Zhang, Qunyuan; Dou, Jie; Wang, Fang; Lin, Wenli; Sun, Yuping; Peng, Guangyong

    2015-01-01

    Vasohibin-1 (VASH1) is an endogenous angiogenesis inhibitor. However, the clinical relevance of VASH1 in colon cancer and its regulations on cancer angiogenesis and cancer cell biological characteristics are still unknown. Here we showed that stromal VASH1 levels were negatively correlated with tumor size, advanced clinical stage and distant metastases in colon cancer patients. Overexpression of VASH1 in colon cancer cells induced apoptosis and senescence, inhibiting cancer cell growth and co...

  11. Scalar tetraquark candidates on the lattice

    International Nuclear Information System (INIS)

    Berlin, Joshua

    2017-01-01

    The topic of this thesis is the investigation of scalar tetraquark candidates from lattice QCD. It is motivated by a previous study originating in the twisted mass collaboration. The initial tetraquark candidate of choice is the a 0 (980), an isovector in the nonet of light scalars (J P =0 + ). This channel is still poorly understood. It displays an inverted mass hierarchy to what is expected from the conventional quark model and the a 0 (980) and f 0 (980) feature a surprising mass degeneracy. For this reasons the a 0 (980) is a long assumed tetraquark candidate in the literature. We follow a methodological approach by studying the sensitivity of the scalar spectrum with fully dynamical quarks to a large basis of two-quark and four-quark creation operators. Ultimately, the candidate has to be identified in the direct vicinity of two two-particles states, which is understandably inevitable for a tetraquark candidate. To succeed in this difficult task two-meson creation operators are essential to employ in this channel. By localized four-quark operators we intend to probe the Hamiltonian on eigenstates with a closely bound four-quark structure.

  12. Scalar tetraquark candidates on the lattice

    Energy Technology Data Exchange (ETDEWEB)

    Berlin, Joshua

    2017-07-01

    The topic of this thesis is the investigation of scalar tetraquark candidates from lattice QCD. It is motivated by a previous study originating in the twisted mass collaboration. The initial tetraquark candidate of choice is the a{sub 0}(980), an isovector in the nonet of light scalars (J{sup P}=0{sup +}). This channel is still poorly understood. It displays an inverted mass hierarchy to what is expected from the conventional quark model and the a{sub 0}(980) and f{sub 0}(980) feature a surprising mass degeneracy. For this reasons the a{sub 0}(980) is a long assumed tetraquark candidate in the literature. We follow a methodological approach by studying the sensitivity of the scalar spectrum with fully dynamical quarks to a large basis of two-quark and four-quark creation operators. Ultimately, the candidate has to be identified in the direct vicinity of two two-particles states, which is understandably inevitable for a tetraquark candidate. To succeed in this difficult task two-meson creation operators are essential to employ in this channel. By localized four-quark operators we intend to probe the Hamiltonian on eigenstates with a closely bound four-quark structure.

  13. Local staging of sigmoid colon cancer using MRI

    DEFF Research Database (Denmark)

    Dam, Claus; Lindebjerg, Jan; Jakobsen, Anders

    2017-01-01

    BACKGROUND: An accurate radiological staging of colon cancer is crucial to select patients who may benefit from neoadjuvant chemotherapy. PURPOSE: To evaluate the diagnostic accuracy of preoperative magnetic resonance imaging (MRI) in identifying locally advanced sigmoid colon cancer, poor...... prognostic factors, and the inter-observer variation of the tumor apparent diffusion coefficient (ADC) values of diffusion-weighted imaging (DWI). MATERIAL AND METHODS: Using 1.5 T MRI with high resolution T2-weighted (T2W) imaging, DWI, and no contrast enhancement, 35 patients with sigmoid colon cancer were...... the measured mean ADC values were below 1.0 × 10(-3) mm(2)/s with an intra-class correlation coefficient in T3cd-T4 tumors of 0.85. CONCLUSION: Preoperative MRI can identify locally advanced sigmoid colon cancer and has potential as the imaging of choice to select patients for neoadjuvant chemotherapy. Initial...

  14. Murine colon proteome and characterization of the protein pathways

    Directory of Open Access Journals (Sweden)

    Magdeldin Sameh

    2012-08-01

    Full Text Available Abstract Background Most of the current proteomic researches focus on proteome alteration due to pathological disorders (i.e.: colorectal cancer rather than normal healthy state when mentioning colon. As a result, there are lacks of information regarding normal whole tissue- colon proteome. Results We report here a detailed murine (mouse whole tissue- colon protein reference dataset composed of 1237 confident protein (FDR I and Mw ranged from 3–12 and 4–600 KDa, respectively. Gravy index scoring predicted 19.5% membranous and 80.5% globularly located proteins. GO hierarchies and functional network analysis illustrated proteins function together with their relevance and implication of several candidates in malignancy such as Mitogen- activated protein kinase (Mapk8, 9 in colorectal cancer, Fibroblast growth factor receptor (Fgfr 2, Glutathione S-transferase (Gstp1 in prostate cancer, and Cell division control protein (Cdc42, Ras-related protein (Rac1,2 in pancreatic cancer. Protein abundances calculated with 3 different algorithms (NSAF, PAF and emPAI provide a relative quantification under normal condition as guidance. Conclusions This highly confidence colon proteome catalogue will not only serve as a useful reference for further experiments characterizing differentially expressed proteins induced from diseased conditions, but also will aid in better understanding the ontology and functional absorptive mechanism of the colon as well.

  15. How many segments are necessary to characterize delayed colonic transit time?

    Science.gov (United States)

    Bouchoucha, Michel; Devroede, Ghislain; Bon, Cyriaque; Raynaud, Jean-Jacques; Bejou, Bakhtiar; Benamouzig, Robert

    2015-10-01

    Measuring colonic transit time with radiopaque markers is simple, inexpensive, and very useful in constipated patients. Yet, the algorithm used to identify colonic segments is subjective, rather than founded on prior experimentation. The aim of the present study is to describe a rational way to determine the colonic partition in the measurement of colonic transit time. Colonic transit time was measured in seven segments: ascending colon, hepatic flexure, right and left transverse colon, splenic flexure, descending colon, and rectosigmoid in 852 patients with functional bowel and anorectal disorders. An unsupervised algorithm for modeling Gaussian mixtures served to estimate the number of subgroups from this oversegmented colonic transit time. After that, we performed a k-means clustering that separated the observations into homogenous groups of patients according to their oversegmented colonic transit time. The Gaussian mixture followed by the k-means clustering defined 4 populations of patients: "normal and fast transit" (n = 548) and three groups of patients with delayed colonic transit time "right delay" (n = 82) in which transit is delayed in the right part of the colon, "left delay" (n = 87) with transit delayed in the left part of colon and "outlet constipation" (n = 135) for patients with transit delayed in the terminal intestine. Only 3.7 % of patients were "erroneously" classified in the 4 groups recognized by clustering. This unsupervised analysis of segmental colonic transit time shows that the classical division of the colon and the rectum into three segments is sufficient to characterize delayed segmental colonic transit time.

  16. MALToma of the Transverse colon, Ascending colon and Caecum: A ...

    African Journals Online (AJOL)

    TNHJOURNALPH

    RESULT. We herein report a case of a 40-year-old male with mucosa - associated lymphoid tissue. [MALT] lymphoma of the transverse colon, ascending colon and caecum. He presented with severe abdominal pains and a centrally located huge abdominal mass for which a surgical resection was done. Histologically.

  17. BEEF CATTLE MUSCULARITY CANDIDATE GENES

    Directory of Open Access Journals (Sweden)

    Irida Novianti

    2010-04-01

    Full Text Available Muscularity is a potential indicator for the selection of more productive cattle. Mapping quantitative trait loci (QTL for traits related to muscularity is useful to identify the genomic regions where the genes affecting muscularity reside. QTL analysis from a Limousin-Jersey double backcross herd was conducted using QTL Express software with cohort and breed as the fixed effects. Nine QTL suggested to have an association with muscularity were identified on cattle chromosomes BTA 1, 2, 3, 4, 5, 8, 12, 14 and 17. The myostatin gene is located at the centromeric end of chromosome 2 and not surprisingly, the Limousin myostatin F94L variant accounted for the QTL on BTA2. However, when the myostatin F94L genotype was included as an additional fixed effect, the QTL on BTA17 was also no longer significant. This result suggests that there may be gene(s that have epistatic effects with myostatin located on cattle chromosome 17. Based on the position of the QTL in base pairs, all the genes that reside in the region were determined using the Ensembl data base (www.ensembl.org. There were two potential candidate genes residing within these QTL regions were selected. They were Smad nuclear interacting protein 1 (SNIP1 and similar to follistatin-like 5 (FSTL5. (JIIPB 2010 Vol 20 No 1: 1-10

  18. Diverticular disease and the risk of colon cancer - a population-based case-control study.

    Science.gov (United States)

    Granlund, J; Svensson, T; Granath, F; Hjern, F; Ekbom, A; Blomqvist, P; Schmidt, P T

    2011-09-01

    Colon cancer and diverticular disease are most common in the Western world and their incidences tend to increase with advancing age. The association between the diseases remains unclear. To analyse the risk of colon cancer after hospitalisation for diverticular disease. Nationwide case-control study. A total of 41,037 patients with colon cancer during 1992-2006, identified from the Swedish Cancer Register were included. Each case was matched with two control subjects. From the Swedish Inpatient Register, cases and control subjects hospitalised for diverticular disease were identified. Odds ratios (OR) and confidence intervals for receiving a diagnosis of colon cancer after hospital discharge for diverticular disease were calculated. Colon cancer mortality was compared between patients with or without diverticular disease. Within 6months after an admission due to diverticular disease, OR of having a colon cancer diagnosis were up to 31.49 (19.00-52.21). After 12 months, there was no increased risk. The number of discharges for diverticular disease did not affect the risk. Colon cancer mortality did not differ between patients with and without diverticular disease. Diverticular disease does not increase the risk of colon cancer in the long term, and a history of diverticular disease does not affect colon cancer mortality. The increased risk of colon cancer within the first 12months after diagnosing diverticular disease is most likely due to surveillance and misclassification. Examination of the colon should be recommended after a primary episode of symptomatic diverticular disease. © 2011 Blackwell Publishing Ltd.

  19. Five kepler target stars that show multiple transiting exoplanet candidates

    DEFF Research Database (Denmark)

    Steffen..[], Jason H.; Batalha, N. M.; Broucki, W J.

    2010-01-01

    We present and discuss five candidate exoplanetary systems identified with the Kepler spacecraft. These five systems show transits from multiple exoplanet candidates. Should these objects prove to be planetary in nature, then these five systems open new opportunities for the field of exoplanets a...

  20. Colonic duplication in an adult

    International Nuclear Information System (INIS)

    Baro, P.; Dario Casas, J.; Sanchez, D.

    1988-01-01

    A case of colonic duplication that was diagnosed radiologically in an adult is reported. A long duplicated segment below the normal transverse colon, with a wide anastomosis at the hepatic flexure level, was observed on barium enema. The rarity of this anomaly unassociated with other malformations is emphasized. (orig.)

  1. Prehistoric human colonization of India

    Indian Academy of Sciences (India)

    Unknown

    2. Earliest human colonization of south Asia. The early human colonization of south Asia is represented largely by an abundance of stone tool assemblages. The oldest known tools ..... component among finished tools is conspicuous in the hinterland riverine ...... sativum), green gram (Vigna radiata), gram/chicken pea.

  2. Colonic Diverticulitis in the Elderly

    Directory of Open Access Journals (Sweden)

    Chien-Kuo Liu

    2009-03-01

    Full Text Available Diverticular disease of the colon is a disease that mainly affects the elderly and presents in 50–70% of those aged 80 years or older. The most common complication is colonic diverticulitis. Eighty percent of patients who present with colonic diverticulitis are aged 50 years and older. Diagnosis and treatment of colonic diverticulitis in the elderly is more difficult and complicated owing to more comorbid conditions. Computed tomography is recommended for diagnosis when colonic diverticulitis is suspected. Most patients admitted with acute colonic diverticulitis respond to conservative treatment, but 15–30% of patients require surgery. Because surgery for acute colonic diverticulitis carries significant rates of morbidity and mortality, conservative treatment is recommended in the elderly. Conservative treatment of colonic diverticulitis with antibiotics, bowel rest, possibly including parenteral alimentation, is usually applied for 1–2 weeks. In the absence of a response to conservative treatment, frequent recurrence or complications (abscesses, fistulas, bowel obstructions, and free perforations, surgery is indicated.

  3. Colonic perforation following endoscopic retrograde ...

    African Journals Online (AJOL)

    She developed severe upper abdominal pain after the ... non-surgical management of pancreatitis and associated complications, colonic perforation should be considered in patients who deteriorate ... To our knowledge this is the first case of a secure pre-operative diagnosis of colonic perforation due to to pancreatitis.

  4. Risk factors for fecal colonization with multiple distinct strains of Escherichia coli among long-term care facility residents.

    Science.gov (United States)

    Lautenbach, Ebbing; Tolomeo, Pam; Black, Nicole; Maslow, Joel N

    2009-05-01

    Of 49 long-term care facility residents, 21 (43%) were colonized with 2 or more distinct strains of Escherichia coli. There were no significant risk factors for colonization with multiple strains of E. coli. These results suggest that future efforts to efficiently identify the diversity of colonizing strains will be challenging.

  5. Drill Sergeant Candidate Transformation

    Science.gov (United States)

    2009-02-01

    leadership styles of NCOs entering Drill Sergeant School (DSS). ARI also developed and administered a prototype DS Assessment Battery to assess...preferred leadership styles . DSS training increases both the degree to which the DSC feels obligated to and identifies with the Army. DSS training...4 TABLE 3. PREFERRED LEADERSHIP STYLES DEFINITIONS .............................................6 TABLE 4. DSC CHANGE IN

  6. Dietary patterns and colon cancer risk in Whites and African Americans in the North Carolina Colon Cancer Study.

    Science.gov (United States)

    Satia, Jessie A; Tseng, Marilyn; Galanko, Joseph A; Martin, Christopher; Sandler, Robert S

    2009-01-01

    We examined associations of dietary patterns with colon cancer risk in African Americans and Whites from a case-control study in North Carolina. Incident colon cancer cases, 40 to 80 yr (n = 636), and matched controls (n = 1,042) were interviewed in person to elicit information on potential colon cancer risk factors. A validated food frequency questionnaire adapted to include regional foods captured diet over the year prior to diagnosis (cases) or interview date (controls). Three meaningful intake patterns were identified in both Whites and African Americans: "Western-Southern," "fruit-vegetable," and "metropolitan." Compared to the Western-Southern pattern, the fruit-vegetable and metropolitan patterns were associated with more healthful dietary behaviors (e.g., higher vegetable intake and lower red meat consumption), and demographic/lifestyle characteristics typically correlated with low colon cancer risk, for example, lower BMI, higher education, and higher NSAID use. The fruit-vegetable pattern was significantly inversely associated with colon cancer risk in Whites (OR = 0.4, 95% CI = 0.3-0.6) and the metropolitan pattern with a nonsignificant 30% risk reduction in both Whites and African Americans after adjustment for education. The Western-Southern pattern was not associated with colon cancer risk. These findings may explain some of the racial differences in colon cancer incidence and underscore the importance of examining diet-cancer associations in different population subgroups.

  7. Gene expression changes in the colon epithelium are similar to those of intact colon during late inflammation in interleukin-10 gene deficient mice.

    Directory of Open Access Journals (Sweden)

    Anna E Russ

    Full Text Available In addition to their role in absorption and secretion, epithelial cells play an important role in the protection of the colon mucosa from the resident microbiota and are important for the maintenance of homeostasis. Microarray analysis of intact colon samples is widely used to gain an overview of the cellular pathways and processes that are active in the colon during inflammation. Laser microdissection of colon epithelial cells allows a more targeted analysis of molecular pathways in the mucosa, preceding and during inflammation, with potentially increased sensitivity to changes in specific cell populations. The aim of this study was to investigate the molecular changes that occur in early and late inflammation stages in colon epithelium of a mouse model of inflammatory bowel diseases. Microarray analysis of intact colon samples and microdissected colon epithelial cell samples from interleukin-10 gene deficient and control mice at 6 and 12 weeks of age was undertaken. Results of gene set enrichment analysis showed that more immune-related pathways were identified between interleukin-10 gene deficient and control mice at 6 weeks of age in epithelial cells than intact colon. This suggests that targeting epithelial cells could increase sensitivity for detecting immune changes that occur early in the inflammatory process. However, in the later stages of inflammation, microarray analyses of intact colon and epithelium both provide a similar overview of gene expression changes in the colon mucosa at the pathway level.

  8. Radiation-associated colon cancer: A case report.

    Science.gov (United States)

    Sasaki, Kazuhito; Ishihara, Soichiro; Hata, Keisuke; Kiyomatsu, Tomomichi; Nozawa, Hiroaki; Kawai, Kazushige; Tanaka, Toshiaki; Nishikawa, Takeshi; Otani, Kensuke; Yasuda, Koji; Kaneko, Manabu; Murono, Koji; Abe, Hiroyuki; Morikawa, Teppei; Watanabe, Toshiaki

    2017-06-01

    Radiation-associated colon cancer is a rare clinical entity. We herein describe the case of a patient with radiation-associated colon cancer who had undergone low anterior resection for rectal cancer following preoperative radiotherapy. Certain characteristics of radiation-associated colon cancer are highlighted. The patient was a 48-year-old man who had undergone low anterior resection for rectal cancer following preoperative radiotherapy at a total dose of 50 Gy, at the age of 29 years. When the patient presented at the University of Tokyo Hospital, 19 years after the surgery, he complained of severe anal pain and frequent defecation. Colonoscopy revealed two flat tumors in the sigmoid colon, located 10 cm to the oral side of the anastomosis site, which were diagnosed as well-differentiated adenocarcinomas. In addition, colonoscopy identified five flat polyps near the tumors, which were resected endoscopically. Computed tomography and magnetic resonance imaging revealed a mass in the sigmoid colon and no evidence of distant metastasis. Laparoscopic-assisted intersphincteric resection of the rectum and sigmoid colon with diverting ileostomy was performed. There were no specific postoperative complications and the patient was discharged from the hospital on the 20th postoperative day. On pathological examination, the resected rectum and sigmoid colon contained two separate tumors and six flat polyps. The two tumors were diagnosed as well-differentiated adenocarcinomas with invasion of the subserosa and submucosa, respectively. A total of 17 regional lymph nodes without metastasis were resected. The six flat polyps were diagnosed as tubular adenomas. We herein present a case of a radiation-associated colon cancer in a patient who had undergone low anterior resection for rectal cancer following preoperative radiotherapy 19 years prior. Colonoscopic surveillance of radiation-associated colon cancer may be indicated for rectal cancer patients treated with preoperative

  9. Registration of central paths and colonic polyps between supine and prone scans in computed tomography colonography: Pilot study

    International Nuclear Information System (INIS)

    Li Ping; Napel, Sandy; Acar, Burak; Paik, David S.; Jeffrey, R. Brooke Jr.; Beaulieu, Christopher F.

    2004-01-01

    Computed tomography colonography (CTC) is a minimally invasive method that allows the evaluation of the colon wall from CT sections of the abdomen/pelvis. The primary goal of CTC is to detect colonic polyps, precursors to colorectal cancer. Because imperfect cleansing and distension can cause portions of the colon wall to be collapsed, covered with water, and/or covered with retained stool, patients are scanned in both prone and supine positions. We believe that both reading efficiency and computer aided detection (CAD) of CTC images can be improved by accurate registration of data from the supine and prone positions. We developed a two-stage approach that first registers the colonic central paths using a heuristic and automated algorithm and then matches polyps or polyp candidates (CAD hits) by a statistical approach. We evaluated the registration algorithm on 24 patient cases. After path registration, the mean misalignment distance between prone and supine identical anatomic landmarks was reduced from 47.08 to 12.66 mm, a 73% improvement. The polyp registration algorithm was specifically evaluated using eight patient cases for which radiologists identified polyps separately for both supine and prone data sets, and then manually registered corresponding pairs. The algorithm correctly matched 78% of these pairs without user input. The algorithm was also applied to the 30 highest-scoring CAD hits in the prone and supine scans and showed a success rate of 50% in automatically registering corresponding polyp pairs. Finally, we computed the average number of CAD hits that need to be manually compared in order to find the correct matches among the top 30 CAD hits. With polyp registration, the average number of comparisons was 1.78 per polyp, as opposed to 4.28 comparisons without polyp registration

  10. Reducing stigma and discrimination: Candidate interventions

    OpenAIRE

    Thornicroft, Graham; Brohan, Elaine; Kassam, Aliya; Lewis-Holmes, Elanor

    2008-01-01

    Abstract This paper proposes that stigma in relation to people with mental illness can be understood as a combination of problems of knowledge (ignorance), attitudes (prejudice) and behaviour (discrimination). From a literature review, a series of candidate interventions are identified which may be effective in reducing stigmatisation and discrimination at the following levels: individuals with mental illness and their family members; the workplace; and local, national and international. The ...

  11. Prostate and Colon Cancer Screening Messages in Popular Magazines

    Science.gov (United States)

    Katz, Mira L; Sheridan, Stacey; Pignone, Michael; Lewis, Carmen; Battle, Jamila; Gollop, Claudia; O'Malley, Michael

    2004-01-01

    OBJECTIVES To 1) compare the number of articles published about prostate, colon, and breast cancer in popular magazines during the past 2 decades, and 2) evaluate the content of in-depth prostate and colon cancer screening articles identified from 1996 to 2001. DESIGN We used a searchable database to identify the number of prostate, colon, and breast cancer articles published in three magazines with the highest circulation from six categories. In addition, we performed a systematic review on the in-depth (≥2 pages) articles on prostate and colon cancer screening that appeared from 1996 through 2001. RESULTS Although the number of magazine articles on prostate and colon cancer published in the 1990s increased compared to the 1980s, the number of articles is approximately one third of breast cancer articles. There were 36 in-depth articles from 1996 to 2001 in which prostate or colon cancer screening were mentioned. Over 90% of the articles recommended screening. However, of those articles, only 76% (25/33; 95% confidence interval [CI], 58% to 89%) cited screening guidelines. The benefits of screening were mentioned in 89% (32/36; 95% CI, 74% to 97%) but the harms were only found in 58% (21/36; 95% CI, 41% to 75%). Only 28% (10/36; 95% CI, 14% to 45%) of the articles provided all the necessary information needed for the reader to make an informed decision. CONCLUSIONS In-depth articles about prostate and colon cancer in popular magazines do not appear as frequently as articles about breast cancer. The available articles on prostate and colon cancer screening often do not provide the information necessary for the reader to make an informed decision about screening. PMID:15242469

  12. Clostridium difficile colonization and infection in patients with hepatic cirrhosis.

    Science.gov (United States)

    Yan, Dong; Chen, Yunbo; Lv, Tao; Huang, Yandi; Yang, Jiezuan; Li, Yongtao; Huang, Jianrong; Li, Lanjuan

    2017-10-01

    The aim of this study was to investigate the toxigenic Clostridium difficile colonization (CDC, colonization with toxigenic C. difficile but without symptoms) and C. difficile infection (CDI, active C. difficile infection resulting in disease symptoms) in hepatic cirrhosis patients, identify the risk factors of CDC, and determine the correlation between CDC and CDI. The strains of toxigenic C. difficile were isolated from patients with hepatic cirrhosis within 48 h after admission, followed by multilocus sequence typing (MLST). Patients were divided into toxigenic CDC group and noncolonized (NC) group according to the colonization. Logistic regression analysis was performed to analyse the risk factors for the CDC. Besides, the CDI incidence was compared between the two groups. Colonization of toxigenic C. difficile was identified in 104 cases (19.8 %). Eighteen sequence types (STs) were identified, among which ST-3, ST-54, ST-35 and ST-37 were the predominant types. Child-Pugh class C(relative risk, RR, 3.025; 95 % CI: 1.410-6.488), decrease of prothrombin time activity (PTA) (RR 2.180; 95 % CI: 1.368-3.476), decrease of platelet (RR 2.746; 95 % CI: 0.931-8.103) and concurrent hepatic encephalopathy (RR 1.740; 95 % CI: 1.012-2.990) were identified as the risk factors for the hepatic cirrhosis patients with CDC. The CDI incidence in the CDC group was also significantly higher than that of the NC group (26.0 % vs 1.7 %, Pdifficile colonization. Child's class C, decrease of PTA and platelet, and concurrent hepatic encephalopathy were the risk factors for the hepatic cirrhosis patients with C. difficile colonization. Hepatic cirrhosis patients with C. difficile colonization were more susceptible to CDI.

  13. Diverticulosis of colon: Case report

    International Nuclear Information System (INIS)

    Han, Chang Yul

    1972-01-01

    The authors reports 2 cases of diverticulosis involving the sacending colon and cecum: one, 55 year old, 85 kg Korean male admitted to Paik Hospital because of abdominal palm, constipation and tenderness in the right lower abdomen. The other, 48 year old, 78 kg male visited to our hospital for the routine examination. According to late European and American statistics, the colonic diverticulosis was discovered in late middle life about 20%, however, the incidence of colonic diverticulosis is rare in Korea. This paper presents a brief review of literature on the etiology, incidence and symptom

  14. Vasohibin-1 suppresses colon cancer

    Science.gov (United States)

    Liu, Shuai; Han, Bing; Zhang, Qunyuan; Dou, Jie; Wang, Fang; Lin, Wenli; Sun, Yuping; Peng, Guangyong

    2015-01-01

    Vasohibin-1 (VASH1) is an endogenous angiogenesis inhibitor. However, the clinical relevance of VASH1 in colon cancer and its regulations on cancer angiogenesis and cancer cell biological characteristics are still unknown. Here we showed that stromal VASH1 levels were negatively correlated with tumor size, advanced clinical stage and distant metastases in colon cancer patients. Overexpression of VASH1 in colon cancer cells induced apoptosis and senescence, inhibiting cancer cell growth and colony formation in vitro and tumor growth in vivo. In addition, knockdown of VASH1 in cancer cells promoted cell growth, adhesion and migration in vitro, and enhanced tumorigenesis and metastasis in vivo. PMID:25797264

  15. Colonic motility in proctalgia fugax.

    Science.gov (United States)

    Harvey, R F

    1979-10-06

    Intraluminal pressure recordings were obtained from the rectum and sigmoid colon in two patients experiencing attacks of proctalgia fugax. In each patient the pain appeared to result from contractions of the sigmoid colon, and not from spasm of the levator ani, rectal wall muscle, or anal sphincters, all of which have previously been suggested as the source of such pain. Proctalgia fugax therefore appears, at least in some patients, to be an unusual variant of the irritable bowel syndrome, in which pain is referred from the sigmoid colon to the rectum.

  16. Vasohibin-1 suppresses colon cancer.

    Science.gov (United States)

    Liu, Shuai; Han, Bing; Zhang, Qunyuan; Dou, Jie; Wang, Fang; Lin, Wenli; Sun, Yuping; Peng, Guangyong

    2015-04-10

    Vasohibin-1 (VASH1) is an endogenous angiogenesis inhibitor.However, the clinical relevance of VASH1 in colon cancer and its regulations on cancer angiogenesis and cancer cell biological characteristics are still unknown. Here we showed that stromal VASH1 levels were negatively correlated with tumor size, advanced clinical stage and distant metastases in colon cancer patients. Overexpression of VASH1 in colon cancer cells induced apoptosis and senescence, inhibiting cancer cell growth and colony formation in vitro and tumor growth in vivo. In addition, knockdown of VASH1 in cancer cells promoted cell growth, adhesion and migration in vitro, and enhanced tumorigenesis and metastasis in vivo.

  17. Laboratory Mice Are Frequently Colonized with Staphylococcus aureus and Mount a Systemic Immune Response—Note of Caution for In vivo Infection Experiments

    Science.gov (United States)

    Schulz, Daniel; Grumann, Dorothee; Trübe, Patricia; Pritchett-Corning, Kathleen; Johnson, Sarah; Reppschläger, Kevin; Gumz, Janine; Sundaramoorthy, Nandakumar; Michalik, Stephan; Berg, Sabine; van den Brandt, Jens; Fister, Richard; Monecke, Stefan; Uy, Benedict; Schmidt, Frank; Bröker, Barbara M.; Wiles, Siouxsie; Holtfreter, Silva

    2017-01-01

    Whether mice are an appropriate model for S. aureus infection and vaccination studies is a matter of debate, because they are not considered as natural hosts of S. aureus. We previously identified a mouse-adapted S. aureus strain, which caused infections in laboratory mice. This raised the question whether laboratory mice are commonly colonized with S. aureus and whether this might impact on infection experiments. Publicly available health reports from commercial vendors revealed that S. aureus colonization is rather frequent, with rates as high as 21% among specific-pathogen-free mice. In animal facilities, S. aureus was readily transmitted from parents to offspring, which became persistently colonized. Among 99 murine S. aureus isolates from Charles River Laboratories half belonged to the lineage CC88 (54.5%), followed by CC15, CC5, CC188, and CC8. A comparison of human and murine S. aureus isolates revealed features of host adaptation. In detail, murine strains lacked hlb-converting phages and superantigen-encoding mobile genetic elements, and were frequently ampicillin-sensitive. Moreover, murine CC88 isolates coagulated mouse plasma faster than human CC88 isolates. Importantly, S. aureus colonization clearly primed the murine immune system, inducing a systemic IgG response specific for numerous S. aureus proteins, including several vaccine candidates. Phospholipase C emerged as a promising test antigen for monitoring S. aureus colonization in laboratory mice. In conclusion, laboratory mice are natural hosts of S. aureus and therefore, could provide better infection models than previously assumed. Pre-exposure to the bacteria is a possible confounder in S. aureus infection and vaccination studies and should be monitored. PMID:28512627

  18. Laboratory Mice Are Frequently Colonized with Staphylococcus aureus and Mount a Systemic Immune Response—Note of Caution for In vivo Infection Experiments

    Directory of Open Access Journals (Sweden)

    Silva Holtfreter

    2017-05-01

    Full Text Available Whether mice are an appropriate model for S. aureus infection and vaccination studies is a matter of debate, because they are not considered as natural hosts of S. aureus. We previously identified a mouse-adapted S. aureus strain, which caused infections in laboratory mice. This raised the question whether laboratory mice are commonly colonized with S. aureus and whether this might impact on infection experiments. Publicly available health reports from commercial vendors revealed that S. aureus colonization is rather frequent, with rates as high as 21% among specific-pathogen-free mice. In animal facilities, S. aureus was readily transmitted from parents to offspring, which became persistently colonized. Among 99 murine S. aureus isolates from Charles River Laboratories half belonged to the lineage CC88 (54.5%, followed by CC15, CC5, CC188, and CC8. A comparison of human and murine S. aureus isolates revealed features of host adaptation. In detail, murine strains lacked hlb-converting phages and superantigen-encoding mobile genetic elements, and were frequently ampicillin-sensitive. Moreover, murine CC88 isolates coagulated mouse plasma faster than human CC88 isolates. Importantly, S. aureus colonization clearly primed the murine immune system, inducing a systemic IgG response specific for numerous S. aureus proteins, including several vaccine candidates. Phospholipase C emerged as a promising test antigen for monitoring S. aureus colonization in laboratory mice. In conclusion, laboratory mice are natural hosts of S. aureus and therefore, could provide better infection models than previously assumed. Pre-exposure to the bacteria is a possible confounder in S. aureus infection and vaccination studies and should be monitored.

  19. Colonic complications following human bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    Paulino Martínez Hernández-Magro

    2015-01-01

    Full Text Available Background: Human bone marrow transplantation (BMT becomes an accepted treatment of leukemia, aplastic anemia, immunodeficiency syndromes, and hematologic malignancies. Colorectal surgeons must know how to determine and manage the main colonic complications. Objective: To review the clinical features, clinical and pathological staging of graft vs host disease (GVHD, and treatment of patients suffering with colonic complications of human bone marrow transplantation. Patients and methods: We have reviewed the records of all patients that received an allogeneic bone marrow transplant and were evaluated at our Colon and Rectal Surgery department due to gastrointestinal symptoms, between January 2007 and January 2012. The study was carried out in patients who developed colonic complications, all of them with clinical, histopathological or laboratory diagnosis. Results: The study group was constituted by 77 patients, 43 male and 34 female patients. We identified colonic complications in 30 patients (38.9%; five patients developed intestinal toxicity due to pretransplant chemotherapy (6.4%; graft vs. host disease was present in 16 patients (20%; 13 patients (16.8% developed acute colonic GVHD, and 3 (3.8% chronic GVHD. Infection was identified in 9 patients (11.6%. Conclusions: The three principal colonic complications are the chemotherapy toxicity, GVHD, and superinfection; the onset of symptoms could help to suspect the type of complication (0–20 day chemotherapy toxicity, 20 and more GVHD, and infection could appear in any time of transplantation. Resumo: Experiência: O transplante de medula óssea humana (MOH passou a ser um tratamento adotado para leucemia, anemia aplástica, síndromes de imunodeficiência e neoplasias hematológicas. Cirurgiões colorretais devem saber como determinar e tratar as principais complicações do cólon. Objetivo: Revisar as características clínicas, estadiamentos clínico e patológico da doença do enxerto

  20. Colonization and environment

    International Nuclear Information System (INIS)

    Garcia Gutierrez, E.

    1999-01-01

    It stands out the man's paper in the deterioration of the soil and in the phenomenon of the desertization, the conflicts of the use of the soil in the country and the underestimate that it is made of this resource in the environmental analysis. The man's relationships are discussed with the earth and the problem of the soils of the Colombian Orinoquia is examined in terms of the excess of toxic elements as To the, Fe and Mn and the other elements like P, S, Ca, Mg, K, B, and Zn. It is examined the degradation and poverty of the organic complex of the soil, the physical degradation and chemistry and their susceptibility to the erosion, as well as the excess conditions and deficit of humidity. It is recognized that it lacks calibration of the analytic methods for the soils oxisoils of the Orinoquia and the Amazonia. The importance of the soils of the humid tropic is stood out as seat of colonization that have failed when not having an appropriate technology for its handling that it forces to undertake systems of migratory agriculture and to the transformation of the forest in prairie, phenomenon that comes accompanied by the degradation of the soils, illicit cultivations, social conflicts and alteration of the essential ecological processes for the survival

  1. Multidetector CT of the colon

    International Nuclear Information System (INIS)

    Luboldt, W.; Hoepffner, N.; Holzer, K.

    2003-01-01

    Multidetector technology, enabling faster imaging, higher spatial resolution and reduction in radiation dose, increases the role of CT in colonic diagnostic. The higher spatial resolution in the z-direction also changes the way to analyze the images. Instead of reading axial sections, now the colon can be systematically assessed in 3D by scrolling through multiplanar reconstructions or in CT colonography by virtual endoscopy. With ongoing improvements in computer-aided diagnosis CT colonography becomes an alternative to fiberoptic colonocopy for screening (http://www.multiorganscreening.org). In this article we propose a CT examination protocol for the colon, describe the typical imaging findings of different colonic diseases, and summarize the current status of CT colonography. (orig.)

  2. Understanding your colon cancer risk

    Science.gov (United States)

    ... for women and 2 drinks per day for men DO NOT smoke You can also have genetic testing done to assess your risk for colon cancer. If you have a strong family history of the disease, talk with your ...

  3. Colon Cleansing: Health or Hype?

    Science.gov (United States)

    ... cramps Dizziness Dehydration Bowel perforation Infection Depletion of probiotics, sodium and potassium Kidney damage Plus, colon cleansing ... goodbye to bacon, sausage, deli meats and hot dogs. Cancer-causing substances form when meats are preserved. ...

  4. CD133+CD24lo defines a 5-Fluorouracil-resistant colon cancer stem cell-like phenotype

    Science.gov (United States)

    Paschall, Amy V.; Yang, Dafeng; Lu, Chunwan; Redd, Priscilla S.; Choi, Jeong-Hyeon; Heaton, Christopher M.; Lee, Jeffrey R.; Nayak-Kapoor, Asha; Liu, Kebin

    2016-01-01

    The chemotherapeutic agent 5-Fluorouracil (5-FU) is the most commonly used drug for patients with advanced colon cancer. However, development of resistance to 5-FU is inevitable in almost all patients. The mechanism by which colon cancer develops 5-FU resistance is still unclear. One recently proposed theory is that cancer stem-like cells underlie colon cancer 5-FU resistance, but the phenotypes of 5-FU-resistant colon cancer stem cells are still controversial. We report here that 5-FU treatment selectively enriches a subset of CD133+ colon cancer cells in vitro. 5-FU chemotherapy also increases CD133+ tumor cells in human colon cancer patients. However, sorted CD133+ colon cancer cells exhibit no increased resistance to 5-FU, and CD133 levels exhibit no correlation with colon cancer patient survival or cancer recurrence. Genome-wide analysis of gene expression between sorted CD133+ colon cancer cells and 5-FU-selected colon cancer cells identifies 207 differentially expressed genes. CD24 is one of the genes whose expression level is lower in the CD133+ and 5-FU-resistant colon cancer cells as compared to CD133+ and 5-FU-sensitive colon cancer cells. Consequently, CD133+CD24lo cells exhibit decreased sensitivity to 5-FU. Therefore, we determine that CD133+CD24lo phenotype defines 5-FU-resistant human colon cancer stem cell-like cells. PMID:27659530

  5. Assessing colonic anatomy normal values based on air contrast enemas in children younger than 6 years.

    Science.gov (United States)

    Koppen, Ilan J N; Yacob, Desale; Di Lorenzo, Carlo; Saps, Miguel; Benninga, Marc A; Cooper, Jennifer N; Minneci, Peter C; Deans, Katherine J; Bates, D Gregory; Thompson, Benjamin P

    2017-03-01

    Contrast enemas with barium or water-soluble contrast agents are sometimes performed in children with severe intractable constipation to identify anatomical abnormalities. However there are no clear definitions for normal colonic size or abnormalities such as colonic dilation or sigmoid redundancy in children. To describe characteristics of colonic anatomy on air contrast enemas in children without constipation to provide normal values for colonic size ratios in children. We performed a retrospective chart review of children aged 0-5 years who had undergone air contrast enemas for intussusception. The primary outcome measures were the ratios of the diameters and lengths of predetermined colonic segments (lengths of rectosigmoid and descending colon; diameters of rectum, sigmoid, descending colon, transverse colon and ascending colon) in relation to the L2 vertebral body width. We included 119 children (median age 2.0 years, range 0-5 years, 68% boys). Colonic segment length ratios did not change significantly with age, although the differences for the rectosigmoid/L2 ratio were borderline significant (P = 0.05). The ratios that involved the rectal and ascending colon diameters increased significantly with age, while diameter ratios involving the other colonic segments did not. Differences by gender and race were not significant. These data can be used for reference purposes in young children undergoing contrast studies of the colon.

  6. Primary closure in colon trauma.

    Science.gov (United States)

    Salinas-Aragón, Luis Enrique; Guevara-Torres, Lorenzo; Vaca-Pérez, Enrique; Belmares-Taboada, Jaime Arístides; Ortiz-Castillo, Fátima de Guadalupe; Sánchez-Aguilar, Martín

    2009-01-01

    Primary repair of colon injuries is an accepted therapeutic option; however, controversy persists regarding its safety. Our objective was to report the evolution and presence of complications in patients with colon injury who underwent primary closure and to determine if the time interval (>6 h), degree of injury, contamination, anatomic site injured, PATI (Penetrating Abdominal Trauma Index) >25, and the presence of other injuries in colon trauma are associated with increased morbidity and mortality. This was a prospective, observational, longitudinal and descriptive study conducted at the Central Hospital "Dr. Ignacio Morones Prieto," San Luis Potosí, Mexico, from January 1, 2003 to December 31, 2007. We included patients with abdominal trauma with colon injury subjected to surgical treatment. chi(2) was used for basic statistical analysis. There were 481 patients with abdominal trauma who underwent surgery; 77(16.1%) had colon injury. Ninety percent (n = 69) were treated in the first 6 h; 91% (n = 70) were due to penetrating injuries, and gunshot wound accounted for 48% (n = 37). Transverse colon was the most frequently injured (38%) (n = 29). Grade I and II injuries accounted for 75.3% (n = 58). Procedures included primary repair (76.66 %) (n = 46); resection with anastomosis (8.3%) (n = 5); and colostomy (15%) (n = 9). Associated injuries were present in 76.6% (n = 59). There was some degree of contamination in 85.7% (n = 66); 82.8% (58) had PATI colon injury. Primary repair is a safe procedure for treatment of colon injuries. Patients with primary repair had lower morbidity (p <0.009). Surgery during the first 6 h (p <0.006) and in hemodynamically stable patients (p <0.014) had a lower risk of complications.

  7. Colon in acute intestinal infection.

    Science.gov (United States)

    Guarino, Alfredo; Buccigrossi, Vittoria; Armellino, Carla

    2009-04-01

    The colon is actively implicated in intestinal infections not only as a target of enteric pathogens and their products but also as a target organ for treatment. In the presence of diarrhea, both of osmotic and secretory nature, the colon reacts with homeostatic mechanisms to increase ion absorption. These mechanisms can be effectively exploited to decrease fluid discharge. A model of intestinal infections using rotavirus (RV) in colonic cells was set up and used to define a dual model of secretory and osmotic diarrhea in sequence. Using this model, antidiarrheal drugs were tested, namely zinc and the enkephalinase inhibitor racecadotril. Zinc was able to decrease the enterotoxic activity responsible for secretory diarrhea. It also inhibited the cytotoxic effect of RV. The mechanism of zinc was related at least in part to the activation of MAPK activity, but also a direct antiviral effect was observed. Racecadotril showed a potent and selective inhibition of active secretion, being particularly effective in the first phase of RV diarrhea. The use of drugs active at the colonic level, therefore, offers effective options to treat intestinal infections in childhood. In addition, the colon is the natural site of colonic microflora, a target of probiotic therapy, which is the first line of approach recommended by the European Society for Paediatric Gastroenterology, Hepatology and Nutrition to treat infectious diarrhea.

  8. MicroRNA-449a deficiency promotes colon carcinogenesis.

    Science.gov (United States)

    Niki, Masanori; Nakajima, Kohei; Ishikawa, Daichi; Nishida, Jun; Ishifune, Chieko; Tsukumo, Shin-Ichi; Shimada, Mitsuo; Nagahiro, Shinji; Mitamura, Yoshinori; Yasutomo, Koji

    2017-09-06

    MicroRNAs have broad roles in tumorigenesis and cell differentiation through regulation of target genes. Notch signaling also controls cell differentiation and tumorigenesis. However, the mechanisms through which Notch mediates microRNA expression are still unclear. In this study, we aimed to identify microRNAs regulated by Notch signaling. Our analysis found that microRNA-449a (miR-449a) was indirectly regulated by Notch signaling. Although miR-449a-deficient mice did not show any Notch-dependent defects in immune cell development, treatment of miR-449a-deficient mice with azoxymethane (AOM) or dextran sodium sulfate (DSS) increased the numbers and sizes of colon tumors. These effects were associated with an increase in intestinal epithelial cell proliferation following AOM/DSS treatment. In patients with colon cancer, miR-449a expression was inversely correlated with disease-free survival and histological scores and was positively correlated with the expression of MLH1 for which loss-of function mutations have been shown to be involved in colon cancer. Colon tissues of miR-449a-deficient mice showed reduced Mlh1 expression compared with those of wild-type mice. Thus, these data suggested that miR-449a acted as a key regulator of colon tumorigenesis by controlling the proliferation of intestinal epithelial cells. Additionally, activation of miR-449a may represent an effective therapeutic strategy and prognostic marker in colon cancer.

  9. Resection and anastomosis of the descending colon in 43 horses.

    Science.gov (United States)

    Prange, Timo; Holcombe, Susan J; Brown, Jennifer A; Dechant, Julie E; Fubini, Susan L; Embertson, Rolf M; Peroni, John; Rakestraw, Peter C; Hauptman, Joe G

    2010-08-01

    To determine (1) the short- (to hospital discharge) and long- (>6 months) term survival, (2) factors associated with short-term survival, and (3) the perioperative course for horses with resection and anastomosis of the descending colon. Multicentered case series. Horses (n=43) that had descending colon resection and anastomosis. Medical records (January 1995-June 2009) of 7 equine referral hospitals were reviewed for horses that had descending colon resection and anastomosis and were recovered from anesthesia. Retrieved data included history, results of clinical and clinicopathologic examinations, surgical findings, postsurgical treatment and complications, and short-term survival (hospital discharge). Long-term survival was defined as survival > or =6 months after hospital discharge. Of 43 horses, 36 (84%) were discharged from the hospital. Twenty-eight of 30 horses with follow-up information survived > or =6 months. No significant associations between perioperative factors and short-term survival were identified. Lesions included strangulating lipoma (n=27), postfoaling trauma (4), infarction (4), intraluminal obstruction (2), and other (6). Common postoperative complications included fever and diarrhea. During hospitalization 7 horses were euthanatized or died because of septic peritonitis (3), endotoxemia (3), and colic and ileus (1). Descending colon resection and anastomosis has a favorable prognosis for hospital discharge and survival > or =6 months. The most common cause of small colon incarceration was strangulating lipoma. Complications include postoperative fever and diarrhea but the prognosis is good after small colon resection and anastomosis.

  10. Colonic diverticulosis is not a risk factor for colonic adenoma.

    Science.gov (United States)

    Hong, Wandong; Dong, Lemei; Zippi, Maddalena; Stock, Simon; Geng, Wujun; Xu, Chunfang; Zhou, Mengtao

    2018-01-01

    Colonic diverticulosis may represent a risk factor for colonic adenomas by virtue of the fact that evolving data suggest that these 2 conditions may share common risk factors such as Western dietary pattern and physical inactivity. This study aims to investigate the association between colonic diverticulosis and colonic adenomas in mainland China. We conducted a cross-sectional study on patients who underwent colonoscopic examination between October 2013 and December 2014 in a university hospital in mainland China. Age, gender, colonic adenomas, advanced adenomas, and distribution of diverticulosis were recorded during the procedures. Multivariate logistic regression and stratified analysis were used to evaluate the associations between the prevalence of diverticulosis and age, sex, and presence of colonic adenomas and advanced adenomas. A total of 17,456 subjects were enrolled. The prevalence of colonic diverticulosis and adenoma was 2.4% and 13.2%, respectively. With regard to distribution of diverticula, most (365/424, 86.1%) were right-sided. Multiple logistic regression analysis suggested that age and male gender were independent risk factors for adenoma and advanced adenoma. There was no relationship between diverticulosis or location of diverticulosis and presence of adenoma and advanced adenoma adjusting by age and gender. In a stratified analysis according to age and gender, similar results were also noted. There was no statistical relationship between diverticulosis and the risk of adenoma and advanced adenoma. Our results may not be generalized to the Western population due to the fact that left-sided diverticular cases were very small in our study.

  11. Spectroscopic follow up of Kepler planet candidates

    DEFF Research Database (Denmark)

    Latham..[], D. W.; Cochran, W. D.; Marcy, G.W.

    2010-01-01

    Spectroscopic follow-up observations play a crucial role in the confirmation and characterization of transiting planet candidates identified by Kepler. The most challenging part of this work is the determination of radial velocities with a precision approaching 1 m/s in order to derive masses from...... spectroscopic orbits. The most precious resource for this work is HIRES on Keck I, to be joined by HARPS-North on the William Herschel Telescope when that new spectrometer comes on line in two years. Because a large fraction of the planet candidates are in fact stellar systems involving eclipsing stars...... and not planets, our strategy is to start with reconnaissance spectroscopy using smaller telescopes, to sort out and reject as many of the false positives as possible before going to Keck. During the first Kepler observing season in 2009, more than 100 nights of telescope time were allocated for this work, using...

  12. Discriminating dark matter candidates using direct detection

    International Nuclear Information System (INIS)

    Belanger, G.; Nezri, E.; Pukhov, A.

    2009-01-01

    We examine the predictions for both the spin-dependent and spin-independent direct detection rates in a variety of new particle physics models with dark matter candidates. We show that a determination of both spin-independent and spin-dependent amplitudes on protons and neutrons can in principle discriminate different candidates of dark matter up to a few ambiguities. We emphasize the importance of making measurements with different spin-dependent sensitive detector materials and the need for significant improvement of the detector sensitivities. Scenarios where exchange of new colored particles contributes significantly to the elastic scattering cross sections are often the most difficult to identify, the LHC should give an indication whether such scenarios are relevant for direct detection.

  13. Age-related loss of EGF-receptor related protein (ERRP) in the aging colon is a potential risk factor for colon cancer.

    Science.gov (United States)

    Schmelz, Eva M; Levi, Edi; Du, Jianhua; Xu, Hu; Majumdar, Adhip P N

    2004-12-01

    Although in Fischer-344 rats, aging is associated with increased activation of EGF-receptor (EGFR) in mucosa of much of the gastrointestinal tract, including the colon, regulation of this process is poorly understood. We hypothesize that loss of suppressor of EGFR may partly be responsible for this process. To test this hypothesis, we examined the expression of EGFR related protein (ERRP), a recently identified negative regulator of EGFR, in the colonic mucosa during aging and following administration of the colonic carcinogen dimethylhydrazine (DMH) that resulted in the formation of aberrant crypt foci (ACF), which are considered to be precursor of adenoma and carcinoma. In Fischer-344 rats, aging is associated with increased activation of EGFR in the colonic mucosa, as evidenced by 30-35% increase in the levels of tyrosine phosphorylated EGFR in the proximal and distal colon of aged (20-22 months old) than in young (4-6 months old) rats. In contrast, the levels of ERRP in both regions of the colon of aged rats were decreased by 50-60%, compared to their younger counterparts. Administration of DMH, which induced a greater number of ACF in the colon of aged rats than in young animals, resulted in a corresponding reduction in ERRP in the colon. These results suggest that loss of ERRP expression is a common event during aging and early stages of chemically induced colon cancer. We also suggest that loss of ERRP could be a risk factor for developing colorectal cancer in the older population.

  14. Colonization and environment

    International Nuclear Information System (INIS)

    Garcia Gutierrez, E.

    1999-01-01

    The environmental results of the colonization, process and their consequences are analyzed in the local, national and international order, the activities through which the acts on the means and the nature of these. It is examined the meaning of the sustainable development, the phenomenon of the exhaustion of the ecosystems and their responsible ones. It discusses the importance of the Orinoquia in the mark of the environmental problems in the international order, the region has been intensely exploded by means of intensive production systems, what has led to the exhaustion of these areas in the world environment. The colonist's paper is exposed in the environmental deterioration, in front of the function of the tropical humid forest and it confirms a focus that it approaches the environmental problem from a perspective that makes emphasis in the social component of that problem, in opposition to the conservators where the ecosystem is the only valid reason and the social groups that intervene him, they should simply disappear. It is necessary the necessity to focus of integral way, the colonist's nature like element of a social group, the list that completes in the mark of the nation and their development model, the political economic system and the nationality inside which makes their economic decisions and of production. It is recognized that they are not enough solutions of technical order to impact on the use and sustainable handling of the Orinoquia, but rather it should be contemplated the economic, social, environmental and political aspects of the problem simultaneously, as well as the growing and resolved participation of the social group in their group

  15. Increased Expression and Aberrant Localization of Mucin 13 in Metastatic Colon Cancer

    Science.gov (United States)

    Gupta, Brij K.; Maher, Diane M.; Ebeling, Mara C.; Sundram, Vasudha; Koch, Michael D.; Lynch, Douglas W.; Bohlmeyer, Teresa; Watanabe, Akira; Aburatani, Hiroyuki; Puumala, Susan E.; Jaggi, Meena

    2012-01-01

    MUC13 is a newly identified transmembrane mucin. Although MUC13 is known to be overexpressed in ovarian and gastric cancers, limited information is available regarding the expression of MUC13 in metastatic colon cancer. Herein, we investigated the expression profile of MUC13 in colon cancer using a novel anti-MUC13 monoclonal antibody (MAb, clone ppz0020) by immunohistochemical (IHC) analysis. A cohort of colon cancer samples and tissue microarrays containing adjacent normal, non-metastatic colon cancer, metastatic colon cancer, and liver metastasis tissues was used in this study to investigate the expression pattern of MUC13. IHC analysis revealed significantly higher (pcolon cancer samples compared with faint or very low expression in adjacent normal tissues. Interestingly, metastatic colon cancer and liver metastasis tissue samples demonstrated significantly (pcolon cancer and adjacent normal colon samples. Moreover, cytoplasmic and nuclear MUC13 expression correlated with larger and poorly differentiated tumors. Four of six tested colon cancer cell lines also expressed MUC13 at RNA and protein levels. These studies demonstrate a significant increase in MUC13 expression in metastatic colon cancer and suggest a correlation between aberrant MUC13 localization (cytoplasmic and nuclear expression) and metastatic colon cancer. PMID:22914648

  16. Patterns of DNA methylation in the normal colon vary by anatomical location, gender, and age

    Science.gov (United States)

    Kaz, Andrew M; Wong, Chao-Jen; Dzieciatkowski, Slavomir; Luo, Yanxin; Schoen, Robert E; Grady, William M

    2014-01-01

    Alterations in DNA methylation have been proposed to create a field cancerization state in the colon, where molecular alterations that predispose cells to transformation occur in histologically normal tissue. However, our understanding of the role of DNA methylation in field cancerization is limited by an incomplete characterization of the methylation state of the normal colon. In order to determine the colon’s normal methylation state, we extracted DNA from normal colon biopsies from the rectum, sigmoid, transverse, and ascending colon and assessed the methylation status of the DNA by pyrosequencing candidate loci as well as with HumanMethylation450 arrays. We found that methylation levels of repetitive elements LINE-1 and SAT-α showed minimal variability throughout the colon in contrast to other loci. Promoter methylation of EVL was highest in the rectum and progressively lower in the proximal segments, whereas ESR1 methylation was higher in older individuals. Genome-wide methylation analysis of normal DNA revealed 8388, 82, and 93 differentially methylated loci that distinguished right from left colon, males from females, and older vs. younger individuals, respectively. Although variability in methylation between biopsies and among different colon segments was minimal for repetitive elements, analyses of specific cancer-related genes as well as a genome-wide methylation analysis demonstrated differential methylation based on colon location, individual age, and gender. These studies advance our knowledge regarding the variation of DNA methylation in the normal colon, a prerequisite for future studies aimed at understanding methylation differences indicative of a colon field effect. PMID:24413027

  17. The relation between lymph node status and survival in Stage I-III colon cancer

    DEFF Research Database (Denmark)

    Lykke, J.; Roikjær, Ole; Jess, P.

    2013-01-01

    Aim: This study involved a large nationwide Danish cohort to evaluate the hypothesis that a high lymph node harvest has a positive effect on survival in curative resected Stage I-III colon cancer and a low lymph node ratio has a positive effect on survival in Stage III colon cancer. Method......: Analysis of overall survival was conducted using a nationwide Danish cohort of patients treated with curative resection of Stage I-III colon cancer. All 8901 patients in Denmark diagnosed with adenocarcinoma of the colon and treated with curative resection in the period 2003-2008 were identified from...... independent prognostic factors in multivariate analysis. Conclusion: High lymph node count was associated with improved overall survival in colon cancer. Lymph node ratio was superior to N-stage in differentiating overall survival in Stage III colon cancer. Stage migration was observed....

  18. Enfermedad Diverticular del Colon

    Directory of Open Access Journals (Sweden)

    Gonzalo López Escobar

    1991-06-01

    Full Text Available

    Los divertículos del colon han sido reconocidos por varios observadores desde hace más de un siglo, pero en su mayor parte se trataba de casos aislados, hoy se la considera como la enfermedad del siglo XX, la de la era moderna y de los países industrializados y de avanzada tecnología (5,18,33.

    Según el diccionario de la Real Academia Española (11, divertículo, del latín, diverticulum, quiere decir desviación de un camino; y desde el punto de vista anatómico, apéndice hueco y terminado en fondo de saco. (Gráfica No. 1.

    Goligher (17 lo define como la “posada al borde del camino, probablemente un lugar, a menudo, de mala reputación”.

    Historia

    Según Hackford (18, el proceso fué descrito brevemente por Littre a comienzos del siglo XVIII; pero se le atribuye a Cruveilhier la primera descripción como proceso patológico en 1849, quien, además, mencionó: “encontramos, no rara vez, en el sigmoide, entre las bandas de fibras musculares longitudinales, una serie de pequeños tumores piriformes oscuros, que están formados por hernias de la mucosa a través de brechas en la capa muscular” (17.

    Fleischman en 1815 hizo la primera observación de la enfermedad y empleó el término divertículo (45.

    Rokitansky en 1.849, habló de una enfermedad adquirida y consideró que su causa consistía en la constipación (45.

    Virchowen 1853 describió la perisigmoiditis (45.

    En 1859 Sidney Jones informó de una fístula colo-vesical debida a diverticulitis (5,45.

    Loomis en 1870 describe una peritonitis como resultante de una diverticulitis (45.

    En 1877 Ball describió la anatomía patológica de la enfermedad y presentó dos casos de fístula colovesical debidas a diverticulitis (9. Cripps en 1.888 popularizó la colostomía de desviación como tratamiento para la fístula colovesical(18...

  19. High mortality rates after nonelective colon cancer resection : results of a national audit

    NARCIS (Netherlands)

    Bakker, I. S.; Snijders, H. S.; Grossmann, I.; Karsten, T. M.; Havenga, K.; Wiggers, T.

    AimColon cancer resection in a nonelective setting is associated with high rates of morbidity and mortality. The aim of this retrospective study is to identify risk factors for overall mortality after colon cancer resection with a special focus on nonelective resection. MethodData were obtained from

  20. Assessing colonic anatomy normal values based on air contrast enemas in children younger than 6 years

    NARCIS (Netherlands)

    Koppen, Ilan J. N.; Yacob, Desale; Di Lorenzo, Carlo; Saps, Miguel; Benninga, Marc A.; Cooper, Jennifer N.; Minneci, Peter C.; Deans, Katherine J.; Bates, D. Gregory; Thompson, Benjamin P.

    2017-01-01

    Contrast enemas with barium or water-soluble contrast agents are sometimes performed in children with severe intractable constipation to identify anatomical abnormalities. However there are no clear definitions for normal colonic size or abnormalities such as colonic dilation or sigmoid redundancy

  1. Colonic sensory and motor function in irritable bowel syndrome and diverticular disease

    NARCIS (Netherlands)

    Clemens, C.H.M. (Cornelis Hermanus Maria)

    2003-01-01

    Chapter 1 is a general introduction. Chapter 2: left-colonic motility patterns were studied in fully ambulant non-constipated IBS patients compared to healthy controls. (HAPCs) were identified. In IBS the descending colon had a decreased overall frequency of phasic contractions and motility index

  2. Staphylococcus aureus nasal colonization in HIV-seropositive and HIV-seronegative drug users

    NARCIS (Netherlands)

    K.A. Holbrook; R.S. Klein; D. Hartel; D.A. Elliott; T. B. Barsky; L. H. Rothschild; F. D. Lowy

    1997-01-01

    textabstractNasal colonization plays an important role in the pathogenesis of Staphylococcus aureus infections. To identify characteristics associated with colonization, we studied a cross-section of a well-described cohort of HIV-seropositive and -seronegative active and former drug users

  3. EMT is the dominant program in human colon cancer

    Directory of Open Access Journals (Sweden)

    Tollenaar Rob AEM

    2011-01-01

    Full Text Available Abstract Background Colon cancer has been classically described by clinicopathologic features that permit the prediction of outcome only after surgical resection and staging. Methods We performed an unsupervised analysis of microarray data from 326 colon cancers to identify the first principal component (PC1 of the most variable set of genes. PC1 deciphered two primary, intrinsic molecular subtypes of colon cancer that predicted disease progression and recurrence. Results Here we report that the most dominant pattern of intrinsic gene expression in colon cancer (PC1 was tightly correlated (Pearson R = 0.92, P -135 with the EMT signature-- both in gene identity and directionality. In a global micro-RNA screen, we further identified the most anti-correlated microRNA with PC1 as MiR200, known to regulate EMT. Conclusions These data demonstrate that the biology underpinning the native, molecular classification of human colon cancer--previously thought to be highly heterogeneous-- was clarified through the lens of comprehensive transcriptome analysis.

  4. Percutaneous drainage of colonic diverticular abscess: is colon resection necessary?

    Science.gov (United States)

    Gaertner, Wolfgang B; Willis, David J; Madoff, Robert D; Rothenberger, David A; Kwaan, Mary R; Belzer, George E; Melton, Genevieve B

    2013-05-01

    Recurrent diverticulitis has been reported in up to 30% to 40% of patients who recover from an episode of colonic diverticular abscess, so elective interval resection is traditionally recommended. The aim of this study was to review the outcomes of patients who underwent percutaneous drainage of colonic diverticular abscess without subsequent operative intervention. This was an observational study. This investigation was conducted at a tertiary care academic medical center and a single-hospital health system. Patients treated for symptomatic colonic diverticular abscess from 2002 through 2007 were included. The primary outcomes measured were complications, recurrence, and colectomy-free survival. Two hundred eighteen patients underwent percutaneous drainage of colonic diverticular abscesses. Thirty-two patients (15%) did not undergo subsequent colonic resection. Abscess location was pelvic (n = 9) and paracolic (n = 23), the mean abscess size was 4.2 cm, and the median duration of percutaneous drainage was 20 days. The comorbidities of this group of patients included severe cardiac disease (n = 16), immunodeficiency (n = 7), and severe pulmonary disease (n = 6). Freedom from recurrence at 7.4 years was 0.58 (95% CI 0.42-0.73). All recurrences were managed nonoperatively. Recurrence was significantly associated with an abscess size larger than 5 cm. Colectomy-free survival at 7.4 years was 0.17 (95% CI 0.13-0.21). This study was limited by its retrospective, nonexperimental design and short follow-up. In selected patients, observation after percutaneous drainage of colonic diverticular abscess appears to be a safe and low-risk management option.

  5. Specific extracellular matrix remodeling signature of colon hepatic metastases.

    Directory of Open Access Journals (Sweden)

    Maguy Del Rio

    Full Text Available To identify genes implicated in metastatic colonization of the liver in colorectal cancer, we collected pairs of primary tumors and hepatic metastases before chemotherapy in 13 patients. We compared mRNA expression in the pairs of patients to identify genes deregulated during metastatic evolution. We then validated the identified genes using data obtained by different groups. The 33-gene signature was able to classify 87% of hepatic metastases, 98% of primary tumors, 97% of normal colon mucosa, and 95% of normal liver tissues in six datasets obtained using five different microarray platforms. The identified genes are specific to colon cancer and hepatic metastases since other metastatic locations and hepatic metastases originating from breast cancer were not classified by the signature. Gene Ontology term analysis showed that 50% of the genes are implicated in extracellular matrix remodeling, and more precisely in cell adhesion, extracellular matrix organization and angiogenesis. Because of the high efficiency of the signature to classify colon hepatic metastases, the identified genes represent promising targets to develop new therapies that will specifically affect hepatic metastasis microenvironment.

  6. Complete colonic duplication in children.

    Science.gov (United States)

    Khaleghnejad Tabari, Ahmad; Mirshemirani, Alireza; Khaleghnejad Tabari, Nasibeh

    2012-01-01

    Complete colonic duplication is a very rare congenital anomaly that may have different presentations according to its location and size. Complete colonic duplication can occur in 15% of gastrointestinal duplication. We report two cases of complete colonic duplications, and their characteristics. We present two patients with complete colonic duplication with different types and presentations. Case 1: A 2- year old boy presented to the clinic with abdominal protrusion, difficulty to defecate, chronic constipation and mucosal prolaps covered bulging (rectocele) since he was 6 months old. The patient had palpable pelvic mass with doughy consistency. Rectal exam confirmed perirectal mass with soft consistency. The patient underwent a surgical operation that had total tubular colorectal duplication with one blind end and was treated with simple fenestration of distal end, and was discharged without complication. After two years follow up, he had normal defecation and good weight gain. Case 2: A 2 -day old infant was referred with imperforate anus and complete duplication of recto-sigmoid colon, diphallus, double bladder, and hypospadiasis. After clinical and paraclinical investigations, he underwent operations in several stages in different periods, and was discharged without complications. After four years follow up, he led a normal life. The patients with complete duplication have to be examined carefully because of the high incidence of other systemic anomalies. Treatment includes simple resection of distal common wall, fenestration, and repair other associated anomalies.

  7. A CATALOG OF MOVING GROUP CANDIDATES IN THE SOLAR NEIGHBORHOOD

    International Nuclear Information System (INIS)

    Zhao Jingkun; Zhao Gang; Chen Yuqin

    2009-01-01

    Based on the kernel estimator and wavelet technique, we have identified 22 moving group candidates in the solar neighborhood from a sample which includes around 14,000 dwarfs and 6000 giants. Six of them were previously known as the Hercules stream, the Sirus-UMa stream, the Hyades stream, the Caster group, the Pleiades stream, and the IC 2391; five of them have also been reported by other authors. 11 moving group candidates, not previously reported in the literature, show prominent structures in dwarf or giant samples. A catalog of moving group candidates in the solar neighborhood is presented in this work.

  8. Triptolide downregulates Rac1 and the JAK/STAT3 pathway and inhibits colitis-related colon cancer progression

    DEFF Research Database (Denmark)

    Wang, Zhipeng; Jin, Haifeng; Xu, Ruodan

    2009-01-01

    ability to block progress of colitis to colon cancer, and its molecular mechanism of action are investigated. A mouse model for colitis-induced colorectal cancer was used to test the effect of triptolide on cancer progression. Treatment of mice with triptolide decreased the incidence of colon cancer...... formation, and increased survival rate. Moreover, triptolide decreased the incidence of tumors in nude mice inoculated with cultured colon cancer cells dose-dependently. In vitro, triptolide inhibited the proliferation, migration and colony formation of colon cancer cells. Secretion of IL6 and levels of JAK....... This suggests that triptolide might be a candidate for prevention of colitis induced colon cancer because it reduces inflammation and prevents tumor formation and development....

  9. Evaluation of an in vitro faecal degradation method for early assessment of the impact of colonic degradation on colonic absorption in humans.

    Science.gov (United States)

    Tannergren, Christer; Borde, Anders; Boreström, Cecilia; Abrahamsson, Bertil; Lindahl, Anders

    2014-06-16

    The objective of this study was to develop and evaluate an in vitro method to investigate bacterial-mediated luminal degradation of drugs in colon in humans. This would be a valuable tool for the assessment of drug candidates during early drug development, especially for compounds intended to be developed as oral extended release formulations. Freshly prepared faecal homogenate from healthy human volunteers (n=3-18), dog (n=6) and rat (colon and caecal content, n=3) was homogenised with 3.8 parts (w/w) physiological saline under anaerobical conditions. Four model compounds (almokalant, budesonide, ximelagatran and metoprolol) were then incubated (n=3-18) separately in the human faecal homogenate for up to 120min at 37°C. In addition, ximelagatran was also incubated in the faecal or colonic content from dog and rat. The mean (±SD) in vitro half-life for almokalant, budesonide and ximelagatran was 39±1, 68±21 and 26±12min, respectively, in the human faecal homogenate. Metoprolol was found to be stable in the in vitro model. The in vitro degradation data was then compared to literature data on fraction absorbed after direct colon administration in humans. The percentage of drug remaining after 60min of in vitro incubation correlated (R(2)=0.90) with the fraction absorbed from colon in humans. The mean in vitro half-life of ximelagatran was similar in human faeces (26±12min) and rat colon content (34±31min), but significantly (pdegradation in vivo was rapidly degraded in the faecal homogenates as well as quantitatively since a correlation was established between percentage degraded in vitro at 60min and fraction absorbed in the colon for the model drugs, which have no other absorption limiting properties. Also, the method is easy to use from a technical point of view, which suggests that the method is suitable for use in early assessment of colonic absorption of extended release formulation candidates. Further improvement of the confidence in the use of the

  10. Caffeine Consumption Among Naval Aviation Candidates.

    Science.gov (United States)

    Sather, Thomas E; Williams, Ronald D; Delorey, Donald R; Woolsey, Conrad L

    2017-04-01

    Education frequently dictates students need to study for prolonged periods of time to adequately prepare for examinations. This is especially true with aviation preflight indoctrination (API) candidates who have to assimilate large volumes of information in a limited amount of time during API training. The purpose of this study was to assess caffeine consumption patterns (frequency, type, and volume) among naval aviation candidates attending API to determine the most frequently consumed caffeinated beverage and to examine if the consumption of a nonenergy drink caffeinated beverage was related to energy drink consumption. Data were collected by means of an anonymous 44-item survey administered and completed by 302 students enrolled in API at Naval Air Station Pensacola, FL. Results indicated the most frequently consumed caffeinated beverage consumed by API students was coffee (86.4%), with daily coffee consumption being approximately 28% and the most frequent pattern of consumption being 2 cups per day (85%). The least frequently consumed caffeinated beverages reported were energy drinks (52%) and energy shots (29.1%). The present study also found that the consumption patterns (weekly and daily) of caffeinated beverages (coffee and cola) were positively correlated to energy drink consumption patterns. Naval aviation candidates' consumption of caffeinated beverages is comparable to other college and high school cohorts. This study found that coffee and colas were the beverages of choice, with energy drinks and energy shots being the least frequently reported caffeinated beverages used. Additionally, a relationship between the consumption of caffeinated beverages and energy drinks was identified.Sather TE, Williams RD, Delorey DR, Woolsey CL. Caffeine consumption among naval aviation candidates. Aerosp Med Hum Perform. 2017; 88(4):399-405.

  11. Reducing stigma and discrimination: Candidate interventions

    Directory of Open Access Journals (Sweden)

    Kassam Aliya

    2008-04-01

    Full Text Available Abstract This paper proposes that stigma in relation to people with mental illness can be understood as a combination of problems of knowledge (ignorance, attitudes (prejudice and behaviour (discrimination. From a literature review, a series of candidate interventions are identified which may be effective in reducing stigmatisation and discrimination at the following levels: individuals with mental illness and their family members; the workplace; and local, national and international. The strongest evidence for effective interventions at present is for (i direct social contact with people with mental illness at the individual level, and (ii social marketing at the population level.

  12. Reducing stigma and discrimination: Candidate interventions.

    Science.gov (United States)

    Thornicroft, Graham; Brohan, Elaine; Kassam, Aliya; Lewis-Holmes, Elanor

    2008-04-13

    This paper proposes that stigma in relation to people with mental illness can be understood as a combination of problems of knowledge (ignorance), attitudes (prejudice) and behaviour (discrimination). From a literature review, a series of candidate interventions are identified which may be effective in reducing stigmatisation and discrimination at the following levels: individuals with mental illness and their family members; the workplace; and local, national and international. The strongest evidence for effective interventions at present is for (i) direct social contact with people with mental illness at the individual level, and (ii) social marketing at the population level.

  13. Teacher Candidate Selection and Evaluation.

    Science.gov (United States)

    Collins, Mary Lynn; And Others

    Summaries are presented of three papers presented at a summer workshop on Quality Assurance in Teacher Education conducted by the Association of Teacher Educators. The general topic covered by these presentations was teacher candidate selection and evaluation. Papers focused upon the following questions: (1) What entry level criteria should be…

  14. Candidate Prediction Models and Methods

    DEFF Research Database (Denmark)

    Nielsen, Henrik Aalborg; Nielsen, Torben Skov; Madsen, Henrik

    2005-01-01

    This document lists candidate prediction models for Work Package 3 (WP3) of the PSO-project called ``Intelligent wind power prediction systems'' (FU4101). The main focus is on the models transforming numerical weather predictions into predictions of power production. The document also outlines...... the possibilities w.r.t. different numerical weather predictions actually available to the project....

  15. Predicting opportunities to increase utilization of laparoscopy for colon cancer.

    Science.gov (United States)

    Keller, Deborah S; Parikh, Niraj; Senagore, Anthony J

    2017-04-01

    Despite proven safety and efficacy, rates of minimally invasive approaches for colon cancer remain low in the USA. Given the known benefits, investigating the root causes of underutilization and methods to increase laparoscopy is warranted. Our goal was to develop a predictive model of factors impacting use of laparoscopic surgery for colon cancer. The Premier Hospital Database was reviewed for elective colorectal resections for colon cancer (2009-2014). Patients were identified by ICD-9-CM diagnosis code and then stratified into open or laparoscopic approaches by ICD-9-CM procedure codes. An adjusted multivariate logistic regression model identified variables predictive of use of laparoscopy for colon cancer. A total of 24,245 patients were included-12,523 (52 %) laparoscopic and 11,722 (48 %) open. General surgeons performed the majority of all procedures (77.99 % open, 71.60 % laparoscopic). Overall use of laparoscopy increased from 48.94 to 52.03 % over the study period (p colon cancer laparoscopically. Colorectal surgeons were 32 % more likely to approach a case laparoscopically than general surgeons (OR 1.315, 95 % CI [1.222, 1.415], p characteristics that can be identified preoperatively to predict who will undergo surgery for colon cancer using laparoscopy. However, additional patients may be eligible for laparoscopy based on patient-level characteristics. These results have implications for regionalization and increasing teaching of MIS. Recognizing and addressing these variables with training and recruiting could increase use of minimally invasive approaches, with the associated clinical and financial benefits.

  16. The Economics of Colon Cancer.

    Science.gov (United States)

    Orangio, Guy R

    2018-04-01

    The economic burden of cancer on the national health expenditure is billions of dollars. The economic cost is measured on direct and indirect medical costs, which vary depending on stage at diagnosis, patient age, type of medical services, and site of service. Costs vary by region, physician behavior, and patient preferences. When analyzing the economic burden of survivors of colon cancer, we cannot forget the societal burden. Post-acute care and readmissions are major economic burdens. People with colon cancer have to be followed for their lifetime. Economic models are being studied to give cost-effective solutions to this problem. Copyright © 2017 Elsevier Inc. All rights reserved.

  17. Neurological manifestation of colonic adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Uzair Chaudhary

    2012-04-01

    Full Text Available Paraneoplastic neurologic disorders are extremely rare in cancer patients and are most commonly associated with certain tumors, such as ovarian cancer, small cell lung cancer, and breast cancer. We report here a paraneoplastic neurological syndrome in a 53-year-old man with colonic adenocarcinoma with a solitary liver metastasis. His paraneoplastic syndrome was successfully treated by methylprednisolone and primary oncologic therapies including neoadjuvant chemotherapy and definitive surgery. This is also the first documented case of simultaneous manifestation of a sensory neuropathy and limbic encephalitis with colon cancer.

  18. Microbial colonization of silicone voice prostheses used in laryngectomized patients

    NARCIS (Netherlands)

    Eerenstein, S. E.; Grolman, W.; Schouwenburg, P. F.

    1999-01-01

    The aim of this study was to identify the microbial colonization of dysfunctioning voice prostheses in laryngectomized patients and determine the influence of patient radiation therapy on prosthesis life span. In a 40-month period, 257 outpatient voice prosthesis replacements were carried out in a

  19. Mucin expression patterns in histological grades of colonic cancers ...

    African Journals Online (AJOL)

    Pathological expression of mucins has been noted in cancer development and progression. This study sought to identify and quantify the types of mucins produced during various histological grades of colon cancer and to assess the diagnostic significance. Methods: Formalin fixed, paraffin-embedded tissue blocks, ...

  20. The role of colonic microbiota in lactose intolerance

    NARCIS (Netherlands)

    Zhong, Y; Priebe, M. G.; Vonk, R. J.; Huang, CY; Antoine, JM; He, T; Harmsen, HJM; Welling, GW

    In a previous study we observed a clear difference in lactose intolerance symptoms after a 25-g lactose load in two groups of persons with lactase nonpersistence and similar small intestinal lactase activity. From this observation we hypothesized a colon resistance factor. To identify this factor,

  1. MALToma of the Transverse colon, Ascending colon and Caecum: A ...

    African Journals Online (AJOL)

    Background The stomach is the most common site formucosa - associated lymphoid tissue [MALT] lymphoma (MALToma). MALToma of the colon is a rare occurrence. It is on this background that we report this case. Methods The case records a patient with a MALT lymphoma and a review of the literature on the subject ...

  2. EnviroAtlas - Candidate Areas for Ecological Restoration for the Conterminous United States

    Data.gov (United States)

    U.S. Environmental Protection Agency — This EnviroAtlas dataset shows the candidate areas for ecological restoration, identified as close but geographically disjunct vegetated regions. Ecological...

  3. Exploring the chemotactic attraction of Campylobacter jejuni in chicken colonization

    DEFF Research Database (Denmark)

    Vegge, Christina Skovgaard; Brøndsted, Lone; Ingmer, Hanne

    Campylobacter jejuni is the primary food borne bacterial pathogen in the developed world. The most important reservoir for C. jejuni is the gut of chickens, which are colonized commensally and efficiently by this organism. Predominantly the mucus filled crypts of the lower gastrointestinal tract....... These mutants will be analyzed for their chemotatic capacity in order to investigate the chemoreceptor function and to identify matching chemoeffectors. Furthermore, selected mutants will be investigated for their ability to colonize chickens with focus on establishment, level, and persistence. Special emphasis...

  4. Risk factors for anastomotic dehiscence in colon cancer surgery

    DEFF Research Database (Denmark)

    Gessler, Bodil; Bock, David; Pommergaard, Hans-Christian

    2016-01-01

    PURPOSE: The aim of this was to assess potential risk factors for anastomotic dehiscence in colon cancer surgery in a national cohort. METHODS: All patients, who had undergone a resection of a large bowel segment with an anastomosis between 2008 and 2011, were identified in the Swedish Colon Cancer...... Registry. Patient factors, socioeconomic factors, surgical factors, and medication and hospital data were combined to evaluate risk factors for anastomotic dehiscence. RESULTS: The prevalence of anastomotic dehiscence was 4.3 % (497/11 565). Male sex, ASA classification III-IV, prescribed medications...

  5. Identification of colonic fibroblast secretomes reveals secretory factors regulating colon cancer cell proliferation.

    Science.gov (United States)

    Chen, Sun-Xia; Xu, Xiao-En; Wang, Xiao-Qing; Cui, Shu-Jian; Xu, Lei-Lei; Jiang, Ying-Hua; Zhang, Yang; Yan, Hai-Bo; Zhang, Qian; Qiao, Jie; Yang, Peng-Yuan; Liu, Feng

    2014-10-14

    Stromal microenvironment influences tumor cell proliferation and migration. Fibroblasts represent the most abundant stromal constituents. Here, we established two pairs of normal fibroblast (NF) and cancer-associated fibroblast (CAF) cultures from colorectal adenocarcinoma tissues and the normal counterparts. The NFs and CAFs were stained positive for typical fibroblast markers and inhibited colon cancer (CC) cell proliferation in in vitro cocultures and in xenograft mouse models. The fibroblast conditioned media were analyzed using LC-MS and 227 proteins were identified at a false discovery rate of 1.3%, including 131 putative secretory and 20 plasma membrane proteins. These proteins were enriched for functional categories of extracellular matrix, adhesion, cell motion, inflammatory response, redox homeostasis and peptidase inhibitor. Secreted protein acidic and rich in cysteine, transgelin, follistatin-related protein 1 (FSTL1) and decorin was abundant in the fibroblast secretome as confirmed by Western blot. Silencing of FSTL1 and transgelin in colonic fibroblast cell line CCD-18Co induced an accelerated proliferation of CC cells in cocultures. Exogenous FSTL1 attenuates CC cell proliferation in a negative fashion. FSTL1 was upregulated in CC patient plasma and cancerous tissues but had no implication in prognosis. Our results provided novel insights into the molecular signatures and modulatory role of CC associated fibroblasts. In this study, a label-free LC-MS was performed to analyze the secretomes of two paired primary fibroblasts, which were isolated from fresh surgical specimen of colorectal adenocarcinoma and adjacent normal colonic tissues and exhibited negative modulatory activity for colon cancer cell growth in in vitro cocultures and in vivo xenograph mouse models. Follistatin-related protein 1 was further revealed to be one of the stroma-derived factors of potential suppression role for colon cancer cell proliferation. Our results provide novel

  6. Colonic smooth muscle responses in patients with diverticular disease of the colon: effect of the NK2 receptor antagonist SR48968.

    Science.gov (United States)

    Maselli, M A; Piepoli, A L; Guerra, V; Caruso, M L; Pezzolla, F; Lorusso, D; Demma, I; De Ponti, F

    2004-05-01

    Little is known about the pathophysiology of diverticular disease. To compare passive and active stress and the response to carbachol of colonic smooth muscle specimens from patients with diverticular disease and patients with colon cancer. The effect of the NK2 receptor antagonist, SR48968, on electrically evoked contractions of circular muscle was also investigated. Sigmoid colon segments were obtained from 16 patients (51-83 years) undergoing elective sigmoid resection for diverticular disease and 39 patients (50-88 years) undergoing left hemicolectomy for non-obstructive sigmoid colon cancer. Isometric tension was measured on circular or longitudinal taenial muscle. Strips were stretched gradually to Lo (length allowing the development of optimal active tension with carbachol) and were also exposed to increasing carbachol concentrations. The effects of atropine, tetrodotoxin and SR48968 on electrically evoked (supramaximal strength, 0.3 ms, 0.1-10 Hz) contractions of circular strips from 8 patients with diverticular disease and 19 patients with colon cancer were also studied. Both passive and active stress in circular muscle strips obtained from patients with diverticular disease was higher than in patients with colon cancer (P colon cancer, whereas a tetrodotoxin-resistant component was identified in patients with diverticular disease. The changes in both passive and active stress in specimens from patients with diverticular disease may reflect circular smooth muscle dysfunction. Acetylcholine and tachykinins are the main excitatory neurotransmitters mediating electrically evoked contractions in human sigmoid colon circular muscle.

  7. Vascular map combined with CT colonography for evaluating candidates for laparoscopic colorectal surgery

    International Nuclear Information System (INIS)

    Flor, Nicola; Ceretti, Andrea Pisani; Maroni, Nirvana; Opocher, Enrico; Cornalba, Gianpaolo; Campari, Alessandro; Ravelli, Anna; Lombardi, Maria Antonietta

    2015-01-01

    Contrast-enhanced computed tomography colonography (CE-CTC) is a useful guide for the laparoscopic surgeon to avoid incorrectly removing the colonic segment and the failure to diagnose of synchronous colonic and extra-colonic lesions. Lymph node dissection and vessel ligation under a laparoscopic approach can be time-consuming and can damage vessels and organs. Moreover, mesenteric vessels have extreme variations in terms of their courses and numbers. We describe the benefit of using an abdominal vascular map created by CE-CTC in laparoscopic colorectal surgery candidates. We describe patients with different diseases (colorectal cancer, diverticular disease, and inflammatory bowel disease) who underwent CE-CTC just prior to laparoscopic surgery

  8. Vascular map combined with CT colonography for evaluating candidates for laparoscopic colorectal surgery

    Energy Technology Data Exchange (ETDEWEB)

    Flor, Nicola; Ceretti, Andrea Pisani; Maroni, Nirvana; Opocher, Enrico; Cornalba, Gianpaolo [Azienda Ospedaliera San Paolo, Milan (Italy); Campari, Alessandro; Ravelli, Anna; Lombardi, Maria Antonietta [University degli Studi di Milano, Milan (Italy)

    2015-08-15

    Contrast-enhanced computed tomography colonography (CE-CTC) is a useful guide for the laparoscopic surgeon to avoid incorrectly removing the colonic segment and the failure to diagnose of synchronous colonic and extra-colonic lesions. Lymph node dissection and vessel ligation under a laparoscopic approach can be time-consuming and can damage vessels and organs. Moreover, mesenteric vessels have extreme variations in terms of their courses and numbers. We describe the benefit of using an abdominal vascular map created by CE-CTC in laparoscopic colorectal surgery candidates. We describe patients with different diseases (colorectal cancer, diverticular disease, and inflammatory bowel disease) who underwent CE-CTC just prior to laparoscopic surgery.

  9. Colonic perforation with peritonitis in amoebiasis: a tropical disease with high mortality.

    Science.gov (United States)

    Jain, Bhupendra Kumar; Garg, Pankaj Kumar; Kumar, Anjay; Mishra, Kiran; Mohanty, Debajyoti; Agrawal, Vivek

    2013-01-01

    Invasive colonic amoebiasis presents primarily with dysentery; colonic perforation occurs rarely. Cases of amoebic colonic perforations have been reported sporadically over the past 20 years. A retrospective study was done in the surgical unit of a tertiary care hospital in North India. The case records of those patients were reviewed who underwent exploratory laparotomy from January 2011 to September 2012 and were diagnosed with amoebic colonic perforation on histopathological examination. Details concerning the clinical presentation, investigations, intraoperative findings, operative procedures, and postoperative outcomes were retrieved. Amongst, a total of 186 emergency exploratory laparotomies carried out during the study, 15 patients of amoebic colonic perforation were identified. The median age of the patients was 42 years (IQR 32.0-58.0) and the male to female ratio was 13:2. Previous history of colitis was present in only 1 patient. The preoperative diagnosis was perforation peritonitis in 12 patients; and intussusception, intestinal obstruction and ruptured liver abscess in 1 patient each. Ten patients had single perforation while 5 had multiple colonic perforations. All the patients except one had perforations in the right colon. Bowel resection was performed depending upon the site and extent of the colon involved-right hemicolectomy (8), limited ileocolic resection (6) and sigmoidectomy (1). Bowel continuity could be restored only in 2 of the 15 patients and a stoma was constructed in the remaining 13 patients. The overall mortality rate was found to be 40% (6/15). Amoebic colonic perforation is associated with unusually high mortality.

  10. Expression and location of α-fetoprotein during rat colon development

    Science.gov (United States)

    Liu, Xiao-Yan; Dong, Dan; Sun, Peng; Du, Jun; Gu, Luo; Ge, Ying-Bin

    2009-01-01

    AIM: To investigate the expression of α-fetoprotein (AFP), a cancer-associated fetal glycoprotein, and its involvement during rat colon development. METHODS: Colons from Sprague-Dawley rat fetuses, young and adult (8 wk old) animals were used in this study. Expression levels of AFP in colons of different development stage were detected by reverse-transcriptase PCR (RT-PCR) and Western blotting. To identify the cell location of AFP in the developing rat colons, double-immunofluorescent staining was performed using antibodies to specific cell markers and AFP, respectively. RESULTS: The highest levels of AFP mRNA were detected in colons of rats at embryonic day 18.5 (e18.5). Compared to e18.5 d, the AFP expression was significantly decreased during rat development [85% for e20.5, P colon from the embryo to the weaning stage by immunofluorescence and presents 72-kDa isoform in the developing rat colons by Western blotting. The dynamic expression of AFP in the various developmental stages of the colon indicates that AFP might be involved in many aspects of colon development. PMID:19360917

  11. Volvulus of the ascending colon in a non-rotated midgut: Plain film and MDCT findings.

    Science.gov (United States)

    Camera, Luigi; Calabrese, Milena; Mainenti, Pier Paolo; Masone, Stefania; Vecchio, Walter Del; Persico, Giovanni; Salvatore, Marco

    2012-10-28

    Colonic volvulus is a relatively uncommon cause of large bowel obstruction usually involving mobile, intra-peritoneal, colonic segments. Congenital or acquired anatomic variation may be associated with an increased risk of colonic volvulus which can occasionally involve retro-peritoneal segments. We report a case of 54-year-old female who presented to our Institution to perform a plain abdominal film series for acute onset of cramping abdominal pain. Both the upright and supine films showed signs of acute colonic obstruction which was thought to be due to an internal hernia of the transverse colon into the lesser sac. The patient was therefore submitted to a multi-detector contrast-enhanced computed tomography (CT). CT findings were initially thought to be consistent with the presumed diagnosis of internal hernia but further evaluation and coronal reformatting clearly depicted the presence of a colonic volvulus possibly resulting from a retro-gastric colon. At surgery, a volvulus of the ascending colon was found and a right hemi-colectomy had to be performed. However, a non rotated midgut with a right-sided duodeno-jejunal flexure and a left sided colon was also found at laparotomy and overlooked in the pre-operative CT. Retrospective evaluation of CT images was therefore performed and a number of CT signs of intestinal malrotation could be identified.

  12. Activins and their related proteins in colon carcinogenesis: insights from early and advanced azoxymethane rat models of colon cancer.

    Science.gov (United States)

    Refaat, Bassem; El-Shemi, Adel Galal; Mohamed, Amr Mohamed; Kensara, Osama Adnan; Ahmad, Jawwad; Idris, Shakir

    2016-11-11

    Activin-A may exert pro- or anti-tumorigenic activities depending on cellular context. However, little is known about its role, or the other mature activin proteins, in colorectal carcinoma (CRC). This study measured the expression of activin βA- & βB-subunits, activin type IIA & IIB receptors, smads 2/3/4/6/7 and follistatin in CRC induced by azoxymethane (AOM) in rats. The results were compared with controls and disseminated according to the characteristics of histopathological lesions. Eighty male Wistar rats were allocated into 20 controls and the remaining were equally divided between short 'S-AOM' (15 weeks) and long 'L-AOM' (35 weeks) groups following injecting AOM for 2 weeks. Subsequent to gross and histopathological examinations and digital image analysis, the expression of all molecules was measured by immunohistochemistry and quantitative RT-PCR. Activin-A, activin-B, activin-AB and follistatin were measured by ELISA in serum and colon tissue homogenates. Colonic pre-neoplastic and cancerous lesions were identified in both AOM groups and their numbers and sizes were significantly (P colonic epithelial cells. There was a significantly (P cancerous tissues. Oppositely, a significant (P colonic lesions. Normal rat colon epithelial cells are capable of synthesising, controlling as well as responding to activins in a paracrine/autocrine manner. Colonic activin systems are pathologically altered during tumorigenesis and appear to be time and lesion-dependent. Activins could also be potential sensitive markers and/or molecular targets for the diagnosis and/or treatment of CRC. Further studies are required to illustrate the clinical value of activins and their related proteins in colon cancer.

  13. Evolving colon injury management: a review.

    Science.gov (United States)

    Greer, Lauren T; Gillern, Suzanne M; Vertrees, Amy E

    2013-02-01

    The colon is the second most commonly injured intra-abdominal organ in penetrating trauma. Management of traumatic colon injuries has evolved significantly over the past 200 years. Traumatic colon injuries can have a wide spectrum of severity, presentation, and management options. There is strong evidence that most non-destructive colon injuries can be successfully managed with primary repair or primary anastomosis. The management of destructive colon injuries remains controversial with most favoring resection with primary anastomosis and others favor colonic diversion in specific circumstances. The historical management of traumatic colon injuries, common mechanisms of injury, demographics, presentation, assessment, diagnosis, management, and complications of traumatic colon injuries both in civilian and military practice are reviewed. The damage control revolution has added another layer of complexity to management with continued controversy.

  14. Colon Trauma: Evidence-Based Practices.

    Science.gov (United States)

    Yamamoto, Ryo; Logue, Alicia J; Muir, Mark T

    2018-01-01

    Colon injury is not uncommon and occurs in about a half of patients with penetrating hollow viscus injuries. Despite major advances in the operative management of penetrating colon wounds, there remains discussion regarding the appropriate treatment of destructive colon injuries, with a significant amount of scientific evidence supporting segmental resection with primary anastomosis in most patients without comorbidities or large transfusion requirement. Although literature is sparse concerning the management of blunt colon injuries, some studies have shown operative decision based on an algorithm originally defined for penetrating wounds should be considered in blunt colon injuries. The optimal management of colonic injuries in patients requiring damage control surgery (DCS) also remains controversial. Studies have recently reported that there is no increased risk compared with patients treated without DCS if fascial closure is completed on the first reoperation, or that a management algorithm for penetrating colon wounds is probably efficacious for colon injuries in the setting of DCS as well.

  15. Plant colonization by pink-pigmented facultative methylotrophic bacteria (PPFMs).

    Science.gov (United States)

    Omer, Zahra S; Tombolini, Riccardo; Gerhardson, Berndt

    2004-03-01

    Bacteria belonging to the genus Methylobacterium are characterized by being able to rely on methanol as a sole carbon and energy source and by presenting a more or less intense pink reddish pigmentation. These bacteria, also referred to as pink-pigmented methylotrophic bacteria (PPFMs), are common inhabitants of the phyllosphere and are found in many other environmental samples. Since they grow slowly they are often overlooked and their impact on phyllosphere microbial communities and on the plants harboring them is not well studied nor has their ecology been elucidated. In a survey of PPFM colonization in three different agricultural sites, PPFM populations were identified on both red clover and winter wheat, but red clover was more consistently colonized. Isolations from collected leaves showed PPFM populations to decrease from spring towards summer, but they increased again towards the end of the cropping season. Isolates from red clover readily colonized winter wheat leaves and vice versa in greenhouse experiments, but population sizes were dependent on the application procedure. Tested isolates had also good potential to colonize the rhizosphere, especially after seed inoculations. Confocal scanning laser microscopy showed gfp-tagged isolates to colonize the surface of clover leaves by forming large aggregates.

  16. Volvulus of the Sigmoid Colon during Pregnancy: A Case Report

    Directory of Open Access Journals (Sweden)

    Enzo Fabrício Ribeiro Nascimento

    2012-01-01

    Full Text Available Colonic obstruction due to sigmoid colon volvulus during pregnancy is a rare but complication with significant maternal and fetal mortality. We describe a case of sigmoid volvulus in a patient with 33 weeks of gestation that developed complete necrosis of the left colon. Case. 27-year-old woman was admitted with 3 days of abdominal distention, vomit, and the stoppage of the passage of gases and feces. She was admitted with poor clinical conditions with septic shock, acute respiratory distress syndrome, and signs of diffuse peritonitis. Abdominal radiography showed severe dilation of the colon with horseshoe signal suggesting a sigmoid volvulus, pneumoperitoneum and we could not we could not identify fetal heartbeats. With a diagnosis of complicate sigmoid volvulus she was underwent to the laparotomy where we found necrosis of all descending colon due to double twist volvulus of the sigmoid. We performed a colectomy with a confection of a proximal colostomy, and closing of the rectal stump. Due to an uncontrollable uterine bleeding during cesarean due, it was required a hysterectomy. The patient had an uneventful postoperative course thereafter and was discharged on a regular diet on the 15th postoperative day.

  17. Variation in positron emission tomography use after colon cancer resection.

    Science.gov (United States)

    Bailey, Christina E; Hu, Chung-Yuan; You, Y Nancy; Kaur, Harmeet; Ernst, Randy D; Chang, George J

    2015-05-01

    Colon cancer surveillance guidelines do not routinely include positron emission tomography (PET) imaging; however, its use after surgical resection has been increasing. We evaluated the secular patterns of PET use after surgical resection of colon cancer among elderly patients and identified factors associated with its increasing use. We used the SEER-linked Medicare database (July 2001 through December 2009) to establish a retrospective cohort of patients age ≥ 66 years who had undergone surgical resection for colon cancer. Postoperative PET use was assessed with the test for trends. Patient, tumor, and treatment characteristics were analyzed using univariable and multivariable logistic regression analyses. Of the 39,221 patients with colon cancer, 6,326 (16.1%) had undergone a PET scan within 2 years after surgery. The use rate steadily increased over time. The majority of PET scans had been performed within 2 months after surgery. Among patients who had undergone a PET scan, 3,644 (57.6%) had also undergone preoperative imaging, and 1,977 (54.3%) of these patients had undergone reimaging with PET within 2 months after surgery. Marriage, year of diagnosis, tumor stage, preoperative imaging, postoperative visit to a medical oncologist, and adjuvant chemotherapy were significantly associated with increased PET use. PET use after colon cancer resection is steadily increasing, and further study is needed to understand the clinical value and effectiveness of PET scans and the reasons for this departure from guideline-concordant care. Copyright © 2015 by American Society of Clinical Oncology.

  18. [Colon and rectum histoplasmosis in a patient from Peru].

    Science.gov (United States)

    Alcántara Figueroa, Christian; Sánchez Cerna, Víctor

    2016-01-01

    We report a case of a male patient of 52 years old with a 3 months history of pushing, tenesmus, hematochezia, pain while defecating, lost of 18 kg of weight, fever, fecaloid and purulent discharge through an perianal hole. During the colonoscopy procedure, we found many ulcers in the ascending, transverse and descending colon.We also found an elevated lesion of about 5 cm in the rectum. We used hematoxylin - eosin and Gomori-Grocott stain in the biopsies and identified many microorganisms inside macrophages which were compatible with histoplasmosis. ELISA tests for HIV, HTLV I- II were negative. Colon and rectal histoplasmosis in an immunocompetent patient is extremely rare. There are few cases of colonic histoplasmosis reported.

  19. Recurrent rectal prolapse caused by colonic duplication in a dog.

    Science.gov (United States)

    Landon, B P; Abraham, L A; Charles, J A; Edwards, G A

    2007-09-01

    A 9-month-old female Shar Pei cross-bred dog was presented with a history of recurrent rectal prolapse over 7 months. Repeated reduction and anal purse string sutures and subsequent incisional colopexy failed to prevent recurrent rectal prolapse. Digital rectal examination following reduction of the prolapse identified a faeces-filled sac within the ventral wall of the rectum and an orifice in the ventral colonic wall, cranial to the pubic brim. A ventral, communicating tubular colonic duplication was diagnosed by means of a barium enema. Surgical excision of the duplicated colonic tube was performed via a caudal ventral midline laparotomy. At 20 weeks post-operation, there has been no recurrence of rectal prolapse.

  20. Mining biological databases for candidate disease genes

    Science.gov (United States)

    Braun, Terry A.; Scheetz, Todd; Webster, Gregg L.; Casavant, Thomas L.

    2001-07-01

    The publicly-funded effort to sequence the complete nucleotide sequence of the human genome, the Human Genome Project (HGP), has currently produced more than 93% of the 3 billion nucleotides of the human genome into a preliminary `draft' format. In addition, several valuable sources of information have been developed as direct and indirect results of the HGP. These include the sequencing of model organisms (rat, mouse, fly, and others), gene discovery projects (ESTs and full-length), and new technologies such as expression analysis and resources (micro-arrays or gene chips). These resources are invaluable for the researchers identifying the functional genes of the genome that transcribe and translate into the transcriptome and proteome, both of which potentially contain orders of magnitude more complexity than the genome itself. Preliminary analyses of this data identified approximately 30,000 - 40,000 human `genes.' However, the bulk of the effort still remains -- to identify the functional and structural elements contained within the transcriptome and proteome, and to associate function in the transcriptome and proteome to genes. A fortuitous consequence of the HGP is the existence of hundreds of databases containing biological information that may contain relevant data pertaining to the identification of disease-causing genes. The task of mining these databases for information on candidate genes is a commercial application of enormous potential. We are developing a system to acquire and mine data from specific databases to aid our efforts to identify disease genes. A high speed cluster of Linux of workstations is used to analyze sequence and perform distributed sequence alignments as part of our data mining and processing. This system has been used to mine GeneMap99 sequences within specific genomic intervals to identify potential candidate disease genes associated with Bardet-Biedle Syndrome (BBS).

  1. Prehistoric human colonization of India

    Indian Academy of Sciences (India)

    Unknown

    J. Biosci. | Vol. 26 | No. 4 | Suppl. | November 2001. V N Misra. 492 ... humans differ from the other apes in their upright posture, ... characterized by Levallois flakes and blades and by the ... and the coastal region running parallel to them, northeast ..... November 2001. Prehistoric human colonization of India. 497. Figure 1.

  2. Acute pseudo-obstruction of the colon

    International Nuclear Information System (INIS)

    Beese, M.; Heller, M.

    1988-01-01

    The radiological correlate to the pseudo-obstruction of the colon is not specific, but it does supply a pointer to the disease of it shows dilation of the caecum, colon ascendens and colon transversum with air-pockets and reflected imaging as well as a usually not dilated colon descendens with remarkably little air. To make the diagnosis quite sure we must exclude intestinal obstruction by using X-ray contrast media or by coloscopy. (orig./GDG) [de

  3. Candidate genes in panic disorder

    DEFF Research Database (Denmark)

    Howe, A. S.; Buttenschön, Henriette N; Bani-Fatemi, A.

    2016-01-01

    The utilization of molecular genetics approaches in examination of panic disorder (PD) has implicated several variants as potential susceptibility factors for panicogenesis. However, the identification of robust PD susceptibility genes has been complicated by phenotypic diversity, underpowered...... association studies and ancestry-specific effects. In the present study, we performed a succinct review of case-control association studies published prior to April 2015. Meta-analyses were performed for candidate gene variants examined in at least three studies using the Cochrane Mantel-Haenszel fixed......-effect model. Secondary analyses were also performed to assess the influences of sex, agoraphobia co-morbidity and ancestry-specific effects on panicogenesis. Meta-analyses were performed on 23 variants in 20 PD candidate genes. Significant associations after correction for multiple testing were observed...

  4. CALCIUM AND THE PREVENTION OF COLON CANCER

    NARCIS (Netherlands)

    WELBERG, JWM; KLEIBEUKER, JH; VANDERMEER, R; MULDER, NH; DEVRIES, EGE

    1991-01-01

    Diet is a major determinant of colon cancer risk. Calcium may protect against colon cancer, presumably by binding cytotoxic bile acids and fatty acids. Numerous studies support this proposition. In subjects at risk for colon cancer oral calcium supplementation has been shown to reduce rectal

  5. Congenital Diverticular Disease of the Entire Colon

    Directory of Open Access Journals (Sweden)

    A. Patel

    2013-01-01

    Full Text Available Congenital or true colonic diverticulosis is a rare condition typified by the preservation of the colonic wall architecture within the diverticular outpouching. Cases of multiple jejunal diverticula have been reported as well as cases of solitary giant diverticula of the colon. There have been no reports in the literature of pancolonic congenital diverticulosis.

  6. Ensemble candidate classification for the LOTAAS pulsar survey

    Science.gov (United States)

    Tan, C. M.; Lyon, R. J.; Stappers, B. W.; Cooper, S.; Hessels, J. W. T.; Kondratiev, V. I.; Michilli, D.; Sanidas, S.

    2018-03-01

    One of the biggest challenges arising from modern large-scale pulsar surveys is the number of candidates generated. Here, we implemented several improvements to the machine learning (ML) classifier previously used by the LOFAR Tied-Array All-Sky Survey (LOTAAS) to look for new pulsars via filtering the candidates obtained during periodicity searches. To assist the ML algorithm, we have introduced new features which capture the frequency and time evolution of the signal and improved the signal-to-noise calculation accounting for broad profiles. We enhanced the ML classifier by including a third class characterizing RFI instances, allowing candidates arising from RFI to be isolated, reducing the false positive return rate. We also introduced a new training data set used by the ML algorithm that includes a large sample of pulsars misclassified by the previous classifier. Lastly, we developed an ensemble classifier comprised of five different Decision Trees. Taken together these updates improve the pulsar recall rate by 2.5 per cent, while also improving the ability to identify pulsars with wide pulse profiles, often misclassified by the previous classifier. The new ensemble classifier is also able to reduce the percentage of false positive candidates identified from each LOTAAS pointing from 2.5 per cent (˜500 candidates) to 1.1 per cent (˜220 candidates).

  7. On security arguments of the second round SHA-3 candidates

    DEFF Research Database (Denmark)

    Andreeva, Elena; Bogdanov, Andrey; Mennink, Bart

    2012-01-01

    of which got accepted to the first round. 14 candidates were left in the second round, out of which five candidates have been recently chosen for the final round. An important criterion in the selection process is the SHA-3 hash function security. We identify two important classes of security arguments...... for the new designs: (1) the possible reductions of the hash function security to the security of its underlying building blocks and (2) arguments against differential attack on building blocks. In this paper, we compare the state of the art provable security reductions for the second round candidates...... and review arguments and bounds against classes of differential attacks.We discuss all the SHA-3 candidates at a high functional level, analyze, and summarize the security reduction results and bounds against differential attacks. Additionally, we generalize the well-known proof of collision resistance...

  8. 275 Candidates and 149 Validated Planets Orbiting Bright Stars in K2 Campaigns 0–10

    DEFF Research Database (Denmark)

    Mayo, Andrew W.; Vanderburg, Andrew; Latham, David W.

    2018-01-01

    Since 2014, NASA’s K2 mission has observed large portions of the ecliptic plane in search of transiting planets and has detected hundreds of planet candidates. With observations planned until at least early 2018, K2 will continue to identify more planet candidates. We present here 275 planet...... candidates observed during Campaigns 0–10 of the K2 mission that are orbiting stars brighter than 13 mag (in Kepler band) and for which we have obtained high-resolution spectra ( R = 44,000). These candidates are analyzed using the vespa package in order to calculate their false-positive probabilities (FPP......). We find that 149 candidates are validated with an FPP lower than 0.1%, 39 of which were previously only candidates and 56 of which were previously undetected. The processes of data reduction, candidate identification, and statistical validation are described, and the demographics of the candidates...

  9. Design of colon targeting drug delivery systems using natural polymeric carriers and their evaluation by gamma scintigraphy technique

    International Nuclear Information System (INIS)

    Soni, P.S.; Sawarkar, S.P.; Deshpande, S.G.; Bajaj, A.N.

    2004-01-01

    Of late, there has been a great awareness in the concept of drug targeting and delivery to a specific site (organ, tissue or cell) in the body to maximize therapeutic effect and reduce toxicity. The various approaches of site-specific drug delivery are implantable pumps, adhesive patches impregnated with drugs, vesicle enclosed drugs and drug carriers. Colonic drug delivery is intended for local and systemic treatment in the diseases of colon like inflammatory bowel conditions. Several approaches using viz. pro-drugs, biodegradable polymers and pH sensitive polymer coatings have been used to achieve colonic delivery. Natural polysaccarides like guar gum and pectin are promising candidates because they are susceptible to degradation by colonic bacteria and thus can release the entrapped drug in the colonic region. These indigenous natural polymers are cheaply and readily available. They comprise of polygalactouronic acid and refractory to host enzymes present in the upper gastrointestinal tract and are degraded by the enzymes produced by the colonic microflora. They were evaluated as a colonic carrier using 5-amino salicylic acid (5-ASA) as a model drug. After successful in vitro testing, gamma scintigraphy technique was used to assess in-vivo behavior of the colon specific drug delivery after a coat of Guar gum and Pectin

  10. Dientamoeba fragilis colonization is not associated with gastrointestinal symptoms in children at primary care level

    NARCIS (Netherlands)

    Holtman, Gea A.; Kranenberg, Justin J.; Blanker, Marco H.; Ott, Alewijn; Lisman-van Leeuwen, Yvonne; Berger, Marjolein Y.

    2017-01-01

    Background. Dientamoeba fragilis is commonly identified in children in primary care and is suspected to cause gastrointestinal disease. Objective. To determine the association between D. fragilis colonization and gastrointestinal symptoms in children. Methods. We performed a cross-sectional study

  11. Control of Colon Cancer Progression by the Colon Microbiome

    Science.gov (United States)

    2015-08-01

    Award  Number:    W81XWH-­14-­1-­0235   TITLE:      Control of Colon Cancer Progression by the Colon Microbiome PRINCIPAL  INVESTIGATOR:    Frank  J... Microbiome Table  of  Contents   Page   1. Introduction………………………………………………………….4 2. Keywords…………………………………………………………….5 3. Accomplishments………..…………………………………………5

  12. Exploring mechanisms of diet-colon cancer associations through candidate molecular interaction networks

    DEFF Research Database (Denmark)

    Westergaard, David; Li, Jun; Jensen, Kasper

    2014-01-01

    Background: Epidemiological studies in the recent years have investigated the relationship between dietary habits and disease risk demonstrating that diet has a direct effect on public health. Especially plant-based diets-fruits, vegetables and herbs-are known as a source of molecules with pharma...

  13. Transverse loop colostomy and colonic motility.

    Science.gov (United States)

    Pucciani, F; Ringressi, M N; Maltinti, G; Bechi, P

    2014-11-01

    The motility of the defunctionalized colon, distal to transverse loop colostomy, has never been studied "in vivo." The aim of our study was to evaluate the influence of transverse loop colostomy on colonic motility. Thirteen patients were examined before stoma closure by means of clinical evaluation and colonic manometry; we studied both the right and distal colon in both fasting and fed patients in order to detect motor activity. Quantitative and qualitative manometric analyses showed that the diverted colon had motor activity even if no regular colonic motor pattern was observed. The spreading of aboral propagated contractions (PCs) was sometimes recorded from the right colon to the distal colon. The response of the proximal and distal colon to a standard meal, when compared to fasting values, increased more than 40 and 35 %, respectively. Stool and gas ejections from the colostomy were never related to a particular type of colonic motility: Motor quiescence such as PCs was chaotically related to stool escape. In conclusion, motility of the defunctionalized colon is preserved in patients with transverse loop colostomy.

  14. An outbreak of Burkholderia stabilis colonization in a nasal ward.

    Science.gov (United States)

    Wang, Lijun; Wang, Mei; Zhang, Junyi; Wu, Wei; Lu, Yuan; Fan, Yanyan

    2015-04-01

    The aim of this study was to describe an outbreak of Burkholderia stabilis colonization among patients in a nasal ward. Multilocus sequence typing (MLST) was used for the molecular typing of B. stabilis isolates. Microbiological records were reviewed to delineate the colonization outbreak period. One hundred seventy-one cultures of environment and equipment samples from the nasal ward were performed to trace the source of contamination. Infection control measures were taken in order to end the outbreak. All B. stabilis isolates were identified as a new MLST type, ST821. A total of 53 patients carried this B. stabilis in the nasal ward between March and September 2013, which was defined as the outbreak period. The source of the colonization was not determined because all environment cultures were negative for Burkholderia cepacia complex. No further B. stabilis carriers have been found in the ward since the implementation of interventions. Attention must be paid to asymptomatic colonization in order to identify outbreaks early. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. Diagnosis of pediatric colonic volvulus with abdominal radiography: how good are we?

    Energy Technology Data Exchange (ETDEWEB)

    Marine, Megan B.; Cooper, Matthew L.; Delaney, Lisa R.; Karmazyn, Boaz [Riley Hospital for Children, Department of Radiology and Imaging Sciences, Indianapolis, IN (United States); Indiana University School of Medicine, Department of Radiology and Imaging Sciences, Indianapolis, IN (United States); Jennings, Samuel Gregory [Indiana University School of Medicine, Department of Radiology and Imaging Sciences, Indianapolis, IN (United States); Rescorla, Frederick J. [Indiana University School of Medicine, Department of Pediatric Surgery, Indianapolis, IN (United States)

    2017-04-15

    Colonic volvulus is rare in children and associated with colonic dysmotility. Diagnosis of colonic volvulus on radiographs in these patients can be challenging. The purpose of the study was to identify the accuracy of abdominal radiographs and findings suggestive of colonic volvulus. A retrospective (2003- 2014) study of all children with colonic volvulus proven surgically or endoscopically reviewed their medical charts for underlying disease and clinical presentation as well as their original radiograph reports. Two pediatric radiologists (reader 1 and reader 2) independently reviewed the radiographs. The kappa test was used to evaluate interobserver variability. There were 19 cases of colonic volvulus in 18 patients (11 males) a mean age 14 years. Cecal volvulus was the most common finding at 14/19 cases (74%). Sixteen of 18 (89%) patients had neurological impairment and 10 of 18 (56%) had intestinal dysmotility. The most common presentation was abdominal distension (14/19 [74%]) and pain (11/19 [58%]). Colonic volvulus was diagnosed in only 7/16 (44%) of the abdominal radiographs. The specific finding of a coffee-bean sign was retrospectively observed only by reader 2 in two cases. Absence of rectal gas and focal colonic loop dilation were the most common findings by the readers (average 73.5% and 87%, respectively) with Kappa values of 0.3 and 0.38, respectively. Diagnosis of colonic volvulus in children can be challenging. Radiologists should be alerted to the possibility of colonic volvulus when there is focal colonic loop distention or absent rectal gas. (orig.)

  16. Diagnosis of pediatric colonic volvulus with abdominal radiography: how good are we?

    International Nuclear Information System (INIS)

    Marine, Megan B.; Cooper, Matthew L.; Delaney, Lisa R.; Karmazyn, Boaz; Jennings, Samuel Gregory; Rescorla, Frederick J.

    2017-01-01

    Colonic volvulus is rare in children and associated with colonic dysmotility. Diagnosis of colonic volvulus on radiographs in these patients can be challenging. The purpose of the study was to identify the accuracy of abdominal radiographs and findings suggestive of colonic volvulus. A retrospective (2003- 2014) study of all children with colonic volvulus proven surgically or endoscopically reviewed their medical charts for underlying disease and clinical presentation as well as their original radiograph reports. Two pediatric radiologists (reader 1 and reader 2) independently reviewed the radiographs. The kappa test was used to evaluate interobserver variability. There were 19 cases of colonic volvulus in 18 patients (11 males) a mean age 14 years. Cecal volvulus was the most common finding at 14/19 cases (74%). Sixteen of 18 (89%) patients had neurological impairment and 10 of 18 (56%) had intestinal dysmotility. The most common presentation was abdominal distension (14/19 [74%]) and pain (11/19 [58%]). Colonic volvulus was diagnosed in only 7/16 (44%) of the abdominal radiographs. The specific finding of a coffee-bean sign was retrospectively observed only by reader 2 in two cases. Absence of rectal gas and focal colonic loop dilation were the most common findings by the readers (average 73.5% and 87%, respectively) with Kappa values of 0.3 and 0.38, respectively. Diagnosis of colonic volvulus in children can be challenging. Radiologists should be alerted to the possibility of colonic volvulus when there is focal colonic loop distention or absent rectal gas. (orig.)

  17. Diagnosis of pediatric colonic volvulus with abdominal radiography: how good are we?

    Science.gov (United States)

    Marine, Megan B; Cooper, Matthew L; Delaney, Lisa R; Jennings, Samuel Gregory; Rescorla, Frederick J; Karmazyn, Boaz

    2017-04-01

    Colonic volvulus is rare in children and associated with colonic dysmotility. Diagnosis of colonic volvulus on radiographs in these patients can be challenging. The purpose of the study was to identify the accuracy of abdominal radiographs and findings suggestive of colonic volvulus. A retrospective (2003- 2014) study of all children with colonic volvulus proven surgically or endoscopically reviewed their medical charts for underlying disease and clinical presentation as well as their original radiograph reports. Two pediatric radiologists (reader 1 and reader 2) independently reviewed the radiographs. The kappa test was used to evaluate interobserver variability. There were 19 cases of colonic volvulus in 18 patients (11 males) a mean age 14 years. Cecal volvulus was the most common finding at 14/19 cases (74%). Sixteen of 18 (89%) patients had neurological impairment and 10 of 18 (56%) had intestinal dysmotility. The most common presentation was abdominal distension (14/19 [74%]) and pain (11/19 [58%]). Colonic volvulus was diagnosed in only 7/16 (44%) of the abdominal radiographs. The specific finding of a coffee-bean sign was retrospectively observed only by reader 2 in two cases. Absence of rectal gas and focal colonic loop dilation were the most common findings by the readers (average 73.5% and 87%, respectively) with Kappa values of 0.3 and 0.38, respectively. Diagnosis of colonic volvulus in children can be challenging. Radiologists should be alerted to the possibility of colonic volvulus when there is focal colonic loop distention or absent rectal gas.

  18. Risk factors for Staphylococcus aureus nasal colonization in Danish middle-aged and elderly twins

    DEFF Research Database (Denmark)

    Andersen, P S; Larsen, Lisbeth Aagaard; Fowler, V G

    2013-01-01

    on S. aureus carriage in Danish middle-aged and elderly twins, which indicated no significant heritability that could account for the observed S. aureus carriage. In the present study, we performed a questionnaire-based study of S. aureus colonization on the same cohort of 2,196 Danish middle......-aged and elderly twins to identify specific risk factors for S. aureus nasal colonization, including analyzing the paired twins (n = 478) that were discordant for S. aureus colonization. We found associations between risk factors and S. aureus nasal colonization among middle-aged and elderly twins, including age......, male gender, psoriasis, and atopic diseases. Also, present living on a farm is clearly associated with S. aureus colonization, while smoking had a borderline statistically significant protective effect....

  19. Indirect effects of land-use legacies determine tree colonization patterns in abandoned heathland

    DEFF Research Database (Denmark)

    Kepfer Rojas, Sebastian; Verheyen, Kris; Johannsen, Vivian Kvist

    2015-01-01

    of tree/shrubs in the heathland. Further, we used high-resolution LiDAR data to classify the vegetation and identify forest patches. In the analysis, we first used a logistic mixed model to test whether colonization of tree and shrub species differed between areas with different land-use history......Questions How do land-use legacies and distance to forest patches influence tree colonization at a post-agricultural heathland? Are colonizing species with different life-history traits affected differently by these factors? Is the effect of increased nutrient availability from land-use legacies...... and whether it was influenced by the distance to forest patches and life-history traits (seed mass) of colonizing species. Then, to determine how different factors influence colonization, we explored the direct and indirect relationships among nutrient availability, density of adult trees, canopy cover, cover...

  20. Decreased risk of surgery for small bowel obstruction after laparoscopic colon cancer surgery compared with open surgery

    DEFF Research Database (Denmark)

    Jensen, Kristian Kiim; Andersen, Peter; Erichsen, Rune

    2016-01-01

    cancer resection. METHODS: This was a nationwide cohort study of patients undergoing elective colonic cancer resection with primary anastomosis in Denmark between 2001 and 2008. All included patients were operated with curative intent. Patients were identified in the Danish Colorectal Cancer Group....... The HR for mortality after colonic resection was 2.54 (CI 1.91 to 3.38, P ... surgery. Further, subsequent SBO surgery was associated with increased mortality after colonic cancer resection....

  1. Colonic surveillance by CT colonography using axial images only

    International Nuclear Information System (INIS)

    Bruzzi, John F.; Brennan, Darren D.; Fenlon, Helen M.; Moss, Alan C.; MacMathuna, Padraic

    2004-01-01

    Patients at increased risk of colon cancer require strict colon surveillance. Our objective was to establish the efficacy of 2D axial CT colonography as a surveillance test when performed in routine clinical practice. Eighty-two patients at increased risk of colon cancer underwent CT colonography followed by conventional colonoscopy on the same morning. CT colonography studies were performed on a four-ring multidetector CT scanner (100 mAs, 120 kVp, 4 x 2.5 collimation) and were interpreted by two radiologists using 2D axial images only. Results were correlated with findings at colonoscopy. Note was made of subsequent histology reports from polypectomy specimens. A total of 52 polyps were detected at colonoscopy. Using 2D axial images alone, with no recourse to 2D multiplanar or 3D views, the sensitivity of CT colonography was 100, 33 and 19% for polyps larger than 9, 6-9 and smaller than 6 mm, respectively. Per-patient specificities were 98.8, 96 and 81.5%, respectively. Twenty-nine percent of polyps smaller than 1 cm were adenomatous and there were no histological features of severe dysplasia. CT colonography is a useful colon surveillance tool for patients at increased risk of colon cancer. It has a high specificity for identifying patients who should proceed to colonoscopy and polypectomy, while allowing further colon examination to be deferred in patients with normal studies. Using 2D axial images only, CT colonography can be performed as part of the daily CT workload, with a very low rate of referral for unnecessary colonoscopy. (orig.)

  2. Schwannoma of the sigmoid colon

    OpenAIRE

    Çakır, Tuğrul; Aslaner, Arif; Yaz, Müjgan; Gündüz, Umut rıza

    2015-01-01

    Colonic schwannomas are very rare gastrointestinal tumours originating from Schwann cells, which form the neural sheath. Primary schwannomas of the lower gastrointestinal tract are very rare and usually benign in nature. However, if they are not surgically removed, malign degeneration can occur. We report a case of a 79-year-old woman who presented to our clinic with rectal bleeding and constipation. She underwent a lower gastrointestinal tract endoscopy. A mass subtotally obstructing the lum...

  3. Oral yeast colonization throughout pregnancy

    OpenAIRE

    Rio, Rute; Sim?es-Silva, Liliana; Garro, Sofia; Silva, M?rio-Jorge; Azevedo, ?lvaro; Sampaio-Maia, Benedita

    2017-01-01

    Background Recent studies suggest that placenta may harbour a unique microbiome that may have origin in maternal oral microbiome. Although the major physiological and hormonal adjustments observed in pregnant women lead to biochemical and microbiological modifications of the oral environment, very few studies evaluated the changes suffered by the oral microbiota throughout pregnancy. So, the aim of our study was to evaluate oral yeast colonization throughout pregnancy and to compare it with n...

  4. Alternative dark matter candidates. Axions

    International Nuclear Information System (INIS)

    Ringwald, Andreas

    2017-01-01

    The axion is arguably one of the best motivated candidates for dark matter. For a decay constant >or similar 10 9 GeV, axions are dominantly produced non-thermally in the early universe and hence are ''cold'', their velocity dispersion being small enough to fit to large scale structure. Moreover, such a large decay constant ensures the stability at cosmological time scales and its behaviour as a collisionless fluid at cosmological length scales. Here, we review the state of the art of axion dark matter predictions and of experimental efforts to search for axion dark matter in laboratory experiments.

  5. Alternative dark matter candidates. Axions

    Energy Technology Data Exchange (ETDEWEB)

    Ringwald, Andreas

    2017-01-15

    The axion is arguably one of the best motivated candidates for dark matter. For a decay constant >or similar 10{sup 9} GeV, axions are dominantly produced non-thermally in the early universe and hence are ''cold'', their velocity dispersion being small enough to fit to large scale structure. Moreover, such a large decay constant ensures the stability at cosmological time scales and its behaviour as a collisionless fluid at cosmological length scales. Here, we review the state of the art of axion dark matter predictions and of experimental efforts to search for axion dark matter in laboratory experiments.

  6. Fine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants.

    Directory of Open Access Journals (Sweden)

    Mengmeng Du

    Full Text Available Genome-wide association studies (GWAS have identified many common single nucleotide polymorphisms (SNPs associated with colorectal cancer risk. These SNPs may tag correlated variants with biological importance. Fine-mapping around GWAS loci can facilitate detection of functional candidates and additional independent risk variants. We analyzed 11,900 cases and 14,311 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. To fine-map genomic regions containing all known common risk variants, we imputed high-density genetic data from the 1000 Genomes Project. We tested single-variant associations with colorectal tumor risk for all variants spanning genomic regions 250-kb upstream or downstream of 31 GWAS-identified SNPs (index SNPs. We queried the University of California, Santa Cruz Genome Browser to examine evidence for biological function. Index SNPs did not show the strongest association signals with colorectal tumor risk in their respective genomic regions. Bioinformatics analysis of SNPs showing smaller P-values in each region revealed 21 functional candidates in 12 loci (5q31.1, 8q24, 11q13.4, 11q23, 12p13.32, 12q24.21, 14q22.2, 15q13, 18q21, 19q13.1, 20p12.3, and 20q13.33. We did not observe evidence of additional independent association signals in GWAS-identified regions. Our results support the utility of integrating data from comprehensive fine-mapping with expanding publicly available genomic databases to help clarify GWAS associations and identify functional candidates that warrant more onerous laboratory follow-up. Such efforts may aid the eventual discovery of disease-causing variant(s.

  7. An inventory of continental U.S. terrestrial candidate ecological restoration areas based on landscape context

    Science.gov (United States)

    James Wickham; Kurt Riitters; Peter Vogt; Jennifer Costanza; Anne Neale

    2017-01-01

    Landscape context is an important factor in restoration ecology, but the use of landscape context for site prioritization has not been as fully developed.We used morphological image processing to identify candidate ecological restoration areas based on their proximity to existing natural vegetation. We identified 1,102,720 candidate ecological restoration areas across...

  8. Elemental abundances of solar sibling candidates

    International Nuclear Information System (INIS)

    Ramírez, I.; Lambert, D. L.; Endl, M.; Cochran, W. D.; MacQueen, P. J.; Bajkova, A. T.; Bobylev, V. V.; Roederer, I. U.; Wittenmyer, R. A.

    2014-01-01

    Dynamical information along with survey data on metallicity and in some cases age have been used recently by some authors to search for candidates of stars that were born in the cluster where the Sun formed. We have acquired high-resolution, high signal-to-noise ratio spectra for 30 of these objects to determine, using detailed elemental abundance analysis, if they could be true solar siblings. Only two of the candidates are found to have solar chemical composition. Updated modeling of the stars' past orbits in a realistic Galactic potential reveals that one of them, HD 162826, satisfies both chemical and dynamical conditions for being a sibling of the Sun. Measurements of rare-element abundances for this star further confirm its solar composition, with the only possible exception of Sm. Analysis of long-term high-precision radial velocity data rules out the presence of hot Jupiters and confirms that this star is not in a binary system. We find that chemical tagging does not necessarily benefit from studying as many elements as possible but instead from identifying and carefully measuring the abundances of those elements that show large star-to-star scatter at a given metallicity. Future searches employing data products from ongoing massive astrometric and spectroscopic surveys can be optimized by acknowledging this fact.

  9. Oral yeast colonization throughout pregnancy.

    Science.gov (United States)

    Rio, R; Simões-Silva, L; Garro, S; Silva, M-J; Azevedo, Á; Sampaio-Maia, B

    2017-03-01

    Recent studies suggest that placenta may harbour a unique microbiome that may have origin in maternal oral microbiome. Although the major physiological and hormonal adjustments observed in pregnant women lead to biochemical and microbiological modifications of the oral environment, very few studies evaluated the changes suffered by the oral microbiota throughout pregnancy. So, the aim of our study was to evaluate oral yeast colonization throughout pregnancy and to compare it with non-pregnant women. The oral yeast colonization was assessed in saliva of 30 pregnant and non-pregnant women longitudinally over a 6-months period. Demographic information was collected, a non-invasive intra-oral examination was performed and saliva flow and pH were determined. Pregnant and non-pregnant groups were similar regarding age and level of education. Saliva flow rate did not differ, but saliva pH was lower in pregnant than in non-pregnant women. Oral yeast prevalence was higher in pregnant than in non-pregnant women, either in the first or in the third trimester, but did not attain statistical significance. In individuals colonized with yeast, the total yeast quantification (Log10CFU/mL) increase from the 1st to the 3rd trimester in pregnant women, but not in non-pregnant women. Pregnancy may favour oral yeast growth that may be associated with an acidic oral environment.

  10. Applicability of an established management algorithm for colon injuries following blunt trauma.

    Science.gov (United States)

    Sharpe, John P; Magnotti, Louis J; Weinberg, Jordan A; Shahan, Charles P; Cullinan, Darren R; Fabian, Timothy C; Croce, Martin A

    2013-02-01

    Operative management at our institution for all colon injuries have followed a defined algorithm (ALG) based on risk factors originally identified for penetrating injuries. The purpose of this study was to evaluate the applicability of the ALG to blunt colon injuries. Patients with blunt colon injuries during 13 years were identified. As per the ALG, nondestructive (ND) injuries are treated with primary repair. Patients with destructive wounds (serosal tear of ≥50% colon circumference, mesenteric devascularization, and perforations) and concomitant risk factors (transfusion of >6 U packed red blood cells and/or presence of significant comorbidities) are diverted, while patients with no risk factors undergo resection plus anastomosis (RA). Outcomes included suture line failure (SLF), abscess, and mortality. Stratification analysis was performed to determine additional risk factors in the management of blunt colon injuries. A total 151 patients were identified: 76 with destructive injuries and 75 with ND injuries. Of those with destructive injuries, 44 (59%) underwent RA and 29 (39%) underwent diversion. All ND injuries underwent primary repair. Adherence to the ALG was 95%: three patients with destructive injuries underwent primary repair, and five patients with risk factors underwent RA. There were three SLFs (2%) (one involved deviation from the ALG) and eight abscesses (5%). Colon-related mortality was 2.1%. Stratification analysis based on mesenteric involvement, degree of shock, and need for abbreviated laparotomy failed to identify additional risk factors for SLF following RA for blunt colon injuries. Adherence to an ALG, originally defined for penetrating colon injuries, simplified the management of blunt colon injuries. ND injuries should be primarily repaired. For destructive wounds, management based on a defined ALG achieves an acceptably low morbidity and mortality rate. Prognostic/epidemiologic study, level III; therapeutic study, level IV.

  11. Detection of unsuspected colonic abnormalities using the pneumocolon technique during small bowel meal examination

    International Nuclear Information System (INIS)

    Chou, S.; Skehan, S.J.; Brown, A.L.; Rawlinson, J.; Somers, S.

    2000-01-01

    AIMS: The pneumocolon technique in small bowel meal examination is used to obtain double-contrast views of the distal ileum. The purpose of this study was to determine the proportion of cases in which an overhead pneumocolon radiograph demonstrated clinically relevant findings in the colon. METHODS: The overhead pneumocolon radiographs in 151 patients who underwent small bowel meals were evaluated retrospectively. A chart review was performed on those patients with positive colonic findings to determine if the suspected abnormalities affected patient management. RESULTS: Colonic abnormalities were identified in 34 of the 151 patients. One patient had a previously undiagnosed ascending colonic cancer; 17 had evidence of acute or chronic colitis; 13 had diverticulosis; one had a caecal polyp; one had an ileosigmoid fistula; one had a filling defect in the ascending colon. In 25 cases the colonic abnormality was visible only on the pneumocolon radiograph and not on the preceding single-contrast images. Management was altered by the colonic findings in seven cases. False-positive findings occurred in two cases. CONCLUSIONS: A routine overhead radiograph following use of the pneumocolon technique is a useful adjunct to small bowel meal examination as it can yield unsuspected and clinically significant colonic findings. Chou, S. (2000)

  12. Necl 4 and RNase 5 Are Important Biomarkers for Gastric and Colon Adenocarcinomas.

    Science.gov (United States)

    Sayar, İlyas; Gökçe, Aysun; Demirtas, Levent; Eken, Hüseyin; Çimen, Ferda Keskin; Çimen, Orhan

    2017-05-31

    BACKGROUND There is a need to identify new prognostic factors that may be used in addition to the known risk factors in gastrointestinal adenocarcinomas. In this study, we aimed to determine the expression of Necl 4 and RNase 5 biomarkers in gastric and colon adenocarcinomas, as well as the prognostic efficacy of these biomarkers in gastric and colon adenocarcinomas. MATERIAL AND METHODS Ninety-two cases resected due to stomach and colon adenocarcinoma were included in the study. The expression of Necl 4 and RNase 5 biomarkers was evaluated by immunohistochemical staining of the stomach and colon normal mucosa and adenocarcinoma areas. RESULTS In colon adenocarcinomas, there was a significant association between Necl 4 and lymphovascular invasion, vascular invasion, and perineural invasion (p<0.05). There was a significant association between RNase 5 and histological differentiation in colon adenocarcinomas (p<0.05). There was no association between RNase 5 and Necl 4 in gastric or colon adenocarcinomas. CONCLUSIONS Necl 4 may have prognostic value in colon adenocarcinomas, but it is difficult to ascertain in gastric adenocarcinomas.

  13. Management of colon wounds in the setting of damage control laparotomy: a cautionary tale.

    Science.gov (United States)

    Weinberg, Jordan A; Griffin, Russell L; Vandromme, Marianne J; Melton, Sherry M; George, Richard L; Reiff, Donald A; Kerby, Jeffrey D; Rue, Loring W

    2009-11-01

    Although colon wounds are commonly treated in the setting of damage control laparotomy (DCL), a paucity of data exist to guide management. The purpose of this study was to evaluate our experience with the management of colonic wounds in the context of DCL, using colonic wound outcomes after routine, single laparotomy (SL) as a benchmark. Consecutive patients during a 7-year period with full-thickness or devitalizing colon injury were identified. Early deaths (Colon-related complications (abscess, suture or staple leak, and stomal ischemia) were compared between those managed in the setting of DCL versus those managed by SL, both overall and as stratified by procedure (primary repair, resection and anastomosis, and resection and colostomy). One hundred fifty-seven patients met study criteria: 101 had undergone SL and 56 had undergone DCL. Comparison of DCL patients with SL patients was notable for a significant difference in colon-related complications (30% vs. 12%, p colon-related complications among those that underwent resection and anastomosis (DCL: 39% vs. SL: 18%, p colonic wounds in the setting of DCL is associated with a relatively high incidence of complications. The excessive incidence of leak overall and morbidity particular to resection and anastomosis, however, give us pause. Although stoma construction is not without its own complications in the setting of DCL, it may be the safer alternative.

  14. 11 CFR 100.154 - Candidate debates.

    Science.gov (United States)

    2010-01-01

    ... 11 Federal Elections 1 2010-01-01 2010-01-01 false Candidate debates. 100.154 Section 100.154 Federal Elections FEDERAL ELECTION COMMISSION GENERAL SCOPE AND DEFINITIONS (2 U.S.C. 431) Exceptions to Expenditures § 100.154 Candidate debates. Funds used to defray costs incurred in staging candidate debates in...

  15. 11 CFR 100.92 - Candidate debates.

    Science.gov (United States)

    2010-01-01

    ... 11 Federal Elections 1 2010-01-01 2010-01-01 false Candidate debates. 100.92 Section 100.92 Federal Elections FEDERAL ELECTION COMMISSION GENERAL SCOPE AND DEFINITIONS (2 U.S.C. 431) Exceptions to Contributions § 100.92 Candidate debates. Funds provided to defray costs incurred in staging candidate debates...

  16. MXene: a potential candidate for yarn supercapacitors.

    Science.gov (United States)

    Zhang, Jizhen; Seyedin, Shayan; Gu, Zhoujie; Yang, Wenrong; Wang, Xungai; Razal, Joselito M

    2017-12-07

    The increasing developments in wearable electronics demand compatible power sources such as yarn supercapacitors (YSCs) that can effectively perform in a limited footprint. MXene nanosheets, which have been recently shown in the literature to possess ultra-high volumetric capacitance, were used in this study for the fabrication of YSCs in order to identify their potential merit and performance in YSCs. With the aid of a conductive binder (PEDOT-PSS), YSCs with high mass loading of MXene are demonstrated. These MXene-based YSCs exhibit excellent device performance and stability even under bending and twisting. This study demonstrates that MXene is a promising candidate for YSCs and its further development can lead to flexible power sources with sufficient performance for powering miniaturized and/or wearable electronics.

  17. Generating Genome-Scale Candidate Gene Lists for Pharmacogenomics

    DEFF Research Database (Denmark)

    Hansen, Niclas Tue; Brunak, Søren; Altman, R. B.

    2009-01-01

    A critical task in pharmacogenomics is identifying genes that may be important modulators of drug response. High-throughput experimental methods are often plagued by false positives and do not take advantage of existing knowledge. Candidate gene lists can usefully summarize existing knowledge...

  18. Candida spp. airway colonization: A potential risk factor for Acinetobacter baumannii ventilator-associated pneumonia.

    Science.gov (United States)

    Tan, Xiaojiang; Zhu, Song; Yan, Dongxing; Chen, Weiping; Chen, Ruilan; Zou, Jian; Yan, Jingdong; Zhang, Xiangdong; Farmakiotis, Dimitrios; Mylonakis, Eleftherios

    2016-08-01

    This retrospective study was conducted to identify potential risk factors for Acinetobacter baumannii (A. baumannii) ventilator-associated pneumonia (VAP) and evaluate the association between Candida spp. airway colonization and A. baumannii VAP. Intensive care unit (ICU) patients who were on mechanical ventilation (MV) for ≥48 hours were divided into the following groups: patients with and without Candida spp. airway colonization; colonized patients receiving antifungal treatment or not; patients with A. baumannii VAP and those without VAP. Logistic regression analysis and propensity score matching were used to identify factors independently associated with A. baumannii VAP. Among 618 eligible patients, 264 (43%) had Candida spp. airway colonization and 114 (18%) developed A. baumannii VAP. Along with MV for ≥7 days (adjusted odds ratio [aOR] 8.9, 95% confidence intervals [95% CI] 4.9-15.8) and presence of a central venous catheter (aOR 3.2, 95% CI 1.1-9), Candida spp. airway colonization (aOR 2.6, 95% CI 1.6-4.3) was identified as an independent risk factor for A. baumannii VAP. Patients with Candida spp. airway colonization were more likely to develop A. baumannii VAP than non-colonized patients (23% vs 15%, P=.01 and 34% vs. 15%, PCandida spp. airway colonization (43%) and A. baumannii VAP (18%) were common in ICU patients who were on mechanical ventilation for at least 48 hours. Candida spp. airway colonization was an independent risk factor for subsequent A. baumannii VAP. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. [Obesity studies in candidate genes].

    Science.gov (United States)

    Ochoa, María del Carmen; Martí, Amelia; Martínez, J Alfredo

    2004-04-17

    There are more than 430 chromosomic regions with gene variants involved in body weight regulation and obesity development. Polymorphisms in genes related to energy expenditure--uncoupling proteins (UCPs), related to adipogenesis and insulin resistance--hormone-sensitive lipase (HLS), peroxisome proliferator-activated receptor gamma (PPAR gamma), beta adrenergic receptors (ADRB2,3), and alfa tumor necrosis factor (TNF-alpha), and related to food intake--ghrelin (GHRL)--appear to be associated with obesity phenotypes. Obesity risk depends on two factors: a) genetic variants in candidate genes, and b) biographical exposure to environmental risk factors. It is necessary to perform new studies, with appropriate control groups and designs, in order to reach relevant conclusions with regard to gene/environmental (diet, lifestyle) interactions.

  20. Cell proliferation and ageing in mouse colon

    International Nuclear Information System (INIS)

    Hamilton, E.; Franks, L.M.

    1980-01-01

    Cell kinetic parameters in the descending colon of unirradiated mice, 3-30-months-old were compared with those in mice irradiated repeatedly from the age of 6 or 24 months. The latter animals were given 1250 rad local X-irradiation to the colon every 6 weeks. Dose-survival curves showed the colon crypts of 6 and 24-months-old mice were similarly radiosensitive. In unirradiated mice the number of crypts per colon section decreased significantly at 30 months, but no significant age-related changes were seen in crypt size or labelling index (LI). Cell proliferation returned to control levels within 6 weeks of each X-ray dose and remained at this level for 20 weeks after the final dose. Later, cell proliferation in the irradiated colon fell significantly below control. A total of 6 or 7 doses each of 1250 rad produced only 1 colon carcinoma amongst 50 mice kept until they died. (author)

  1. Historical and Current Trends in Colon Trauma

    Science.gov (United States)

    Causey, Marlin Wayne; Rivadeneira, David E.; Steele, Scott R.

    2012-01-01

    The authors discuss the evolution of the evaluation and management of colonic trauma, as well as the debate regarding primary repair versus fecal diversion. Their evidence-based review covers diagnosis, management, surgical approaches, and perioperative care of patients with colon-related trauma. The management of traumatic colon injuries has evolved significantly over the past 50 years; here the authors describe a practical approach to the treatment and management of traumatic injuries to the colon based on the most current research. However, management of traumatic colon injuries remains a challenge and continues to be associated with significant morbidity. Familiarity with the different methods to the approach and management of colonic injuries will allow surgeons to minimize unnecessary complications and mortality. PMID:24294119

  2. Complications of acromegaly: thyroid and colon.

    Science.gov (United States)

    Tirosh, Amit; Shimon, Ilan

    2017-02-01

    In acromegaly the long-term exposure to high growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels may result in specific complications in different human organs, including the thyroid gland and the colon. We will review here the evidence available regarding the characteristic thyroid and colon complications in acromegaly. This review summarizes the published data observing noncancerous structural abnormalities (thyroid nodules, colonic polyps) and thyroid and colon cancer in patients diagnosed with acromegaly. Thyroid micro-carcinomas are probably over-diagnosed among acromegalic patients. In regard to colon cancer, there is no sufficient data to suggest that colon cancer risk is higher in acromegaly compared to the general population.

  3. Image diagnostic of colonic diseases - controversial questions

    International Nuclear Information System (INIS)

    Pomakov, P.; Rizov, A.; Stancheva, I.

    2013-01-01

    In the system of colonic diseases' diagnostic algorithm, fibrocolonoscopy (FCS) is defined as 'Golden Standard'. By this reason some X-ray diagnostic methods - irrigography, etc. are currently not being used in a number of health institutions. The aim of this study is a comparative analysis of FCS and irrigography diagnostic efficacy in various colonic diseases. For 10-years period, in cooperation with a gastroenterologist-gastroscopist, 2151 patients with various colonic diseases were evaluated by FCS and irrigography with pharmaco-diagnostics/when necessary. Advantage of FCS was established in diagnosing diseases with patho-morfologic changes on the inner surface of the colon - benign and malignant neoplastic processes, chronic inflammatory diseases, etc. At the same time functional changes - irritated colon syndrome, changes in defecation act, etc., are not an object of diagnosis through FCS. Correction in colonic diseases diagnostic algorithm is necessary. FCS should be mandatory. If result is negative - irrigography with pharmaco-diagnostics should be done. (authors)

  4. PEACE: pulsar evaluation algorithm for candidate extraction - a software package for post-analysis processing of pulsar survey candidates

    Science.gov (United States)

    Lee, K. J.; Stovall, K.; Jenet, F. A.; Martinez, J.; Dartez, L. P.; Mata, A.; Lunsford, G.; Cohen, S.; Biwer, C. M.; Rohr, M.; Flanigan, J.; Walker, A.; Banaszak, S.; Allen, B.; Barr, E. D.; Bhat, N. D. R.; Bogdanov, S.; Brazier, A.; Camilo, F.; Champion, D. J.; Chatterjee, S.; Cordes, J.; Crawford, F.; Deneva, J.; Desvignes, G.; Ferdman, R. D.; Freire, P.; Hessels, J. W. T.; Karuppusamy, R.; Kaspi, V. M.; Knispel, B.; Kramer, M.; Lazarus, P.; Lynch, R.; Lyne, A.; McLaughlin, M.; Ransom, S.; Scholz, P.; Siemens, X.; Spitler, L.; Stairs, I.; Tan, M.; van Leeuwen, J.; Zhu, W. W.

    2013-07-01

    Modern radio pulsar surveys produce a large volume of prospective candidates, the majority of which are polluted by human-created radio frequency interference or other forms of noise. Typically, large numbers of candidates need to be visually inspected in order to determine if they are real pulsars. This process can be labour intensive. In this paper, we introduce an algorithm called Pulsar Evaluation Algorithm for Candidate Extraction (PEACE) which improves the efficiency of identifying pulsar signals. The algorithm ranks the candidates based on a score function. Unlike popular machine-learning-based algorithms, no prior training data sets are required. This algorithm has been applied to data from several large-scale radio pulsar surveys. Using the human-based ranking results generated by students in the Arecibo Remote Command Center programme, the statistical performance of PEACE was evaluated. It was found that PEACE ranked 68 per cent of the student-identified pulsars within the top 0.17 per cent of sorted candidates, 95 per cent within the top 0.34 per cent and 100 per cent within the top 3.7 per cent. This clearly demonstrates that PEACE significantly increases the pulsar identification rate by a factor of about 50 to 1000. To date, PEACE has been directly responsible for the discovery of 47 new pulsars, 5 of which are millisecond pulsars that may be useful for pulsar timing based gravitational-wave detection projects.

  5. Procaine Induces Epigenetic Changes in HCT116 Colon Cancer Cells

    Directory of Open Access Journals (Sweden)

    Hussein Sabit

    2016-01-01

    Full Text Available Colon cancer is the third most commonly diagnosed cancer in the world, and it is the major cause of morbidity and mortality throughout the world. The present study aimed at treating colon cancer cell line (HCT116 with different chemotherapeutic drug/drug combinations (procaine, vorinostat “SAHA,” sodium phenylbutyrate, erlotinib, and carboplatin. Two different final concentrations were applied: 3 μM and 5 μM. Trypan blue test was performed to assess the viability of the cell before and after being treated with the drugs. The data obtained showed that there was a significant decrease in the viability of cells after applying the chemotherapeutic drugs/drug combinations. Also, DNA fragmentation assay was carried out to study the effect of these drugs on the activation of apoptosis-mediated DNA degradation process. The results indicated that all the drugs/drug combinations had a severe effect on inducing DNA fragmentation. Global DNA methylation quantification was performed to identify the role of these drugs individually or in combination in hypo- or hypermethylating the CpG dinucleotide all over the genome of the HCT116 colon cancer cell line. Data obtained indicated that different combinations had different effects in reducing or increasing the level of methylation, which might indicate the effectiveness of combining drugs in treating colon cancer cells.

  6. Microbial Surface Colonization and Biofilm Development in Marine Environments

    Science.gov (United States)

    2015-01-01

    SUMMARY Biotic and abiotic surfaces in marine waters are rapidly colonized by microorganisms. Surface colonization and subsequent biofilm formation and development provide numerous advantages to these organisms and support critical ecological and biogeochemical functions in the changing marine environment. Microbial surface association also contributes to deleterious effects such as biofouling, biocorrosion, and the persistence and transmission of harmful or pathogenic microorganisms and their genetic determinants. The processes and mechanisms of colonization as well as key players among the surface-associated microbiota have been studied for several decades. Accumulating evidence indicates that specific cell-surface, cell-cell, and interpopulation interactions shape the composition, structure, spatiotemporal dynamics, and functions of surface-associated microbial communities. Several key microbial processes and mechanisms, including (i) surface, population, and community sensing and signaling, (ii) intraspecies and interspecies communication and interaction, and (iii) the regulatory balance between cooperation and competition, have been identified as critical for the microbial surface association lifestyle. In this review, recent progress in the study of marine microbial surface colonization and biofilm development is synthesized and discussed. Major gaps in our knowledge remain. We pose questions for targeted investigation of surface-specific community-level microbial features, answers to which would advance our understanding of surface-associated microbial community ecology and the biogeochemical functions of these communities at levels from molecular mechanistic details through systems biological integration. PMID:26700108

  7. Historical and Current Trends in Colon Trauma

    OpenAIRE

    Causey, Marlin Wayne; Rivadeneira, David E.; Steele, Scott R.

    2012-01-01

    The authors discuss the evolution of the evaluation and management of colonic trauma, as well as the debate regarding primary repair versus fecal diversion. Their evidence-based review covers diagnosis, management, surgical approaches, and perioperative care of patients with colon-related trauma. The management of traumatic colon injuries has evolved significantly over the past 50 years; here the authors describe a practical approach to the treatment and management of traumatic injuries to th...

  8. Perforated Solitary Diverticulitis of the Ascending Colon

    Science.gov (United States)

    2005-06-01

    postoperative day 6. DISCUSSION Diverticuli of the right colon exist in approximately 1% to 5% of patients with diverticular disease .1-3 They are...ORIGINAL REPORTS Perforated Solitary Diverticulitis of the Ascending Colon CPT David S. Kauvar, MC, USA, MAJ, Jayson Aydelotte, MC, USA, and MAJ...Michael Harnisch, MC, USA Department of Surgery, Brooke Army Medical Center, Fort Sam Houston, Texas KEY WORDS: solitary colon diverticulum

  9. Volvulus of the Small Bowel and Colon

    Science.gov (United States)

    Kapadia, Muneera R.

    2017-01-01

    Volvulus of the intestines may involve either the small bowel or colon. In the pediatric population, small bowel volvulus is more common, while in the adult population, colonic volvulus is more often seen. The two most common types of colonic volvulus include sigmoid and cecal volvulus. Prompt diagnosis and treatment is imperative, otherwise bowel ischemia may ensue. Treatment often involves emergent surgical exploration and bowel resection. PMID:28144211

  10. Colon injury after blunt abdominal trauma: results of the EAST Multi-Institutional Hollow Viscus Injury Study.

    Science.gov (United States)

    Williams, Michael D; Watts, Dorraine; Fakhry, Samir

    2003-11-01

    Blunt injury to the colon is rare. Few studies of adequate size and design exist to allow clinically useful conclusions. The Eastern Association for the Surgery of Trauma Multi-institutional Hollow Viscus Injury (HVI) Study presents a unique opportunity to definitively study these injuries. Patients with blunt HVI were identified from the registries of 95 trauma centers over 2 years (1998-1999). Patients with colon injuries (cases) were compared with blunt trauma patient undergoing a negative laparotomy (controls). Data were abstracted by chart review. Of the 227,972 patients represented, 2,632 (1.0%) had an HVI and 798 had a colonic/rectal injury (0.3%). Of patients diagnosed with HVI, 30.2% had a colon injury. No physical findings or imaging modalities were able to discriminate colonic injury. Logistic regression modeling yielded no clinically useful combination of findings that would reliably predict colonic injury. In patients undergoing laparotomy, presence of colon injury was associated with a higher risk of some complications but not mortality. Colon injury was associated with increased hospital (17.4 vs. 13.1, p colon patients (92.0%) underwent laparotomy within 24 hours of injury. Colonic injury after blunt trauma is rare and difficult to diagnose. No diagnostic test or combination of findings reliably excluded blunt colonic injury. Despite the inadequacy of current diagnostic tests, almost all patients with colonic injury were taken to the operating room within 24 hours. Even with relatively prompt surgery, patients with colon injury were at significantly higher risk for serious complications and increased length of stay. In contrast to small bowel perforation, delay in operative intervention appears to be less common but is still associated with serious morbidity.

  11. Positional mapping and candidate gene analysis of the mouse Ccs3 locus that regulates differential susceptibility to carcinogen-induced colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Charles Meunier

    Full Text Available The Ccs3 locus on mouse chromosome 3 regulates differential susceptibility of A/J (A, susceptible and C57BL/6J (B6, resistant mouse strains to chemically-induced colorectal cancer (CRC. Here, we report the high-resolution positional mapping of the gene underlying the Ccs3 effect. Using phenotype/genotype correlation in a series of 33 AcB/BcA recombinant congenic mouse strains, as well as in groups of backcross populations bearing unique recombinant chromosomes for the interval, and in subcongenic strains, we have delineated the maximum size of the Ccs3 physical interval to a ∼2.15 Mb segment. This interval contains 12 annotated transcripts. Sequencing of positional candidates in A and B6 identified many either low-priority coding changes or non-protein coding variants. We found a unique copy number variant (CNV in intron 15 of the Nfkb1 gene. The CNV consists of two copies of a 54 bp sequence immediately adjacent to the exon 15 splice site, while only one copy is found in CRC-susceptible A. The Nfkb1 protein (p105/p50 expression is much reduced in A tumors compared to normal A colonic epithelium as analyzed by immunohistochemistry. Studies in primary macrophages from A and B6 mice demonstrate a marked differential activation of the NfκB pathway by lipopolysaccharide (kinetics of stimulation and maximum levels of phosphorylated IκBα, with a more robust activation being associated with resistance to CRC. NfκB has been previously implicated in regulating homeostasis and inflammatory response in the intestinal mucosa. The interval contains another positional candidate Slc39a8 that is differentially expressed in A vs B6 colons, and that has recently been associated in CRC tumor aggressiveness in humans.

  12. Risk factors for anastomotic leakage and leak-related mortality after colonic cancer surgery in a nationwide audit

    NARCIS (Netherlands)

    Bakker, I. S.; Grossmann, I.; Henneman, D.; Havenga, K.; Wiggers, T.

    Background: Surgical resection with restoration of bowel continuity is the cornerstone of treatment for patients with colonic cancer. The aim of this study was to identify risk factors for anastomotic leakage (AL) and subsequent death after colonic cancer surgery. Methods: Data were retrieved from

  13. Sigmoid colon vaginoplasty in children.

    Science.gov (United States)

    Ekinci, S; Karnak, I; Ciftci, A O; Senocak, M E; Tanyel, F C; Büyükpamukçu, N

    2006-06-01

    Vaginal construction is necessary for the patients with aplasia of Mullerian ducts, testicular feminisation and androgen insensitivity syndromes. Many methods of vaginal construction have been described. We report here the outcomes of six adolescent patients who underwent sigmoid colon vaginoplasty with special emphasis on the surgical technique and outcomes. Between 1990 and 2003, six patients underwent sigmoid vaginoplasty after a diagnosis of 5alpha-reductase deficiency (n = 3), testicular feminisation (n = 2) or vaginal atresia (n = 1). The mean age was 16 years (13 to 18). Wide spectrum antibiotics and whole-gut preparation were used in all cases. A 15-20 cm segment of sigmoid colon was pulled through the retrovesical tunnel. The proximal end was closed in two layers in patients with 5alpha-reductase deficiency and with testicular feminisation. A distal anastomosis was carried out to the opening made on the vaginal plate (5alpha-reductase deficiency) or on the tip of the shallow rudimentary vagina (testicular feminisation). The sigmoid segment was interposed between the blind end of the atretic vagina and the perineum in the patient with vaginal atresia. Patients were instructed to perform daily vaginal irrigation. The neovagina was examined and calibrated under anaesthesia. No routine vaginal dilatation was recommended. All but one patient had an uneventful postoperative period and were discharged within 7-8 days. All patients had an excellent cosmetic result with an appropriate vaginal length. One of the patients experienced late stenosis of the introitus which responded to dilatations. Mucus discharge was not a significant problem. The patient with vaginal atresia (Bardet-Biedl syndrome) experienced deep vein thrombosis, renal failure and sepsis, resulting in death. Sigmoid colon vaginoplasty is a special procedure which appears appropriate for the construction of a new vagina in children. A sigmoid colon neovagina meets all necessary criteria after a

  14. Functional validation of candidate genes detected by genomic feature models

    DEFF Research Database (Denmark)

    Rohde, Palle Duun; Østergaard, Solveig; Kristensen, Torsten Nygaard

    2018-01-01

    Understanding the genetic underpinnings of complex traits requires knowledge of the genetic variants that contribute to phenotypic variability. Reliable statistical approaches are needed to obtain such knowledge. In genome-wide association studies, variants are tested for association with trait...... then functionally assessed whether the identified candidate genes affected locomotor activity by reducing gene expression using RNA interference. In five of the seven candidate genes tested, reduced gene expression altered the phenotype. The ranking of genes within the predictive GO term was highly correlated...

  15. Acetylcholine release by human colon cancer cells mediates autocrine stimulation of cell proliferation.

    Science.gov (United States)

    Cheng, Kunrong; Samimi, Roxana; Xie, Guofeng; Shant, Jasleen; Drachenberg, Cinthia; Wade, Mark; Davis, Richard J; Nomikos, George; Raufman, Jean-Pierre

    2008-09-01

    Most colon cancers overexpress M3 muscarinic receptors (M3R), and post-M3R signaling stimulates human colon cancer cell proliferation. Acetylcholine (ACh), a muscarinic receptor ligand traditionally regarded as a neurotransmitter, may be produced by nonneuronal cells. We hypothesized that ACh release by human colon cancer cells results in autocrine stimulation of proliferation. H508 human colon cancer cells, which have robust M3R expression, were used to examine effects of muscarinic receptor antagonists, acetylcholinesterase inhibitors, and choline transport inhibitors on cell proliferation. A nonselective muscarinic receptor antagonist (atropine), a selective M3R antagonist (p-fluorohexahydro-sila-difenidol hydrochloride), and a choline transport inhibitor (hemicholinum-3) all inhibited unstimulated H508 colon cancer cell proliferation by approximately 40% (P<0.005). In contrast, two acetylcholinesterase inhibitors (eserine-hemisulfate and bis-9-amino-1,2,3,4-tetrahydroacridine) increased proliferation by 2.5- and 2-fold, respectively (P<0.005). By using quantitative real-time PCR, expression of choline acetyltransferase (ChAT), a critical enzyme for ACh synthesis, was identified in H508, WiDr, and Caco-2 colon cancer cells. By using high-performance liquid chromatography-electrochemical detection, released ACh was detected in H508 and Caco-2 cell culture media. Immunohistochemistry in surgical specimens revealed weak or no cytoplasmic staining for ChAT in normal colon enterocytes (n=25) whereas half of colon cancer specimens (n=24) exhibited moderate to strong staining (P<0.005). We conclude that ACh is an autocrine growth factor in colon cancer. Mechanisms that regulate colon epithelial cell production and release of ACh warrant further investigation.

  16. Colonic diseases: The value of US examination

    International Nuclear Information System (INIS)

    Hollerweger, Alois

    2007-01-01

    The colon is affected by a number of diseases, mainly inflammatory, ischemic, and neoplastic conditions. Depending upon clinical indications endoscopy, US, CT, or other radiological methods are used for evaluation. The fact that US is frequently used as the initial imaging method in patients with non-specific clinical symptoms allows for greater influence in further diagnostic evaluation and with treatment, provided the investigator is familiar with the features of different intestinal diseases. This article will describe the anatomical characteristics of the colon, the US technique for examination of the colon, and the typical US features of the more common diagnoses of the colon

  17. Muscarinic Receptor Signaling in Colon Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Rosenvinge, Erik C. von, E-mail: evonrose@medicine.umaryland.edu; Raufman, Jean-Pierre [University of Maryland School of Medicine, Division of Gastroenterology & Hepatology, 22 S. Greene Street, N3W62, Baltimore, MD 21201 (United States); Department of Veterans Affairs, VA Maryland Health Care System, 10 North Greene Street, Baltimore, MD 21201 (United States)

    2011-03-02

    According to the adenoma-carcinoma sequence, colon cancer results from accumulating somatic gene mutations; environmental growth factors accelerate and augment this process. For example, diets rich in meat and fat increase fecal bile acids and colon cancer risk. In rodent cancer models, increased fecal bile acids promote colon dysplasia. Conversely, in rodents and in persons with inflammatory bowel disease, low-dose ursodeoxycholic acid treatment alters fecal bile acid composition and attenuates colon neoplasia. In the course of elucidating the mechanism underlying these actions, we discovered that bile acids interact functionally with intestinal muscarinic receptors. The present communication reviews muscarinic receptor expression in normal and neoplastic colon epithelium, the role of autocrine signaling following synthesis and release of acetylcholine from colon cancer cells, post-muscarinic receptor signaling including the role of transactivation of epidermal growth factor receptors and activation of the ERK and PI3K/AKT signaling pathways, the structural biology and metabolism of bile acids and evidence for functional interaction of bile acids with muscarinic receptors on human colon cancer cells. In murine colon cancer models, deficiency of subtype 3 muscarinic receptors attenuates intestinal neoplasia; a proof-of-concept supporting muscarinic receptor signaling as a therapeutic target for colon cancer.

  18. Muscarinic Receptor Signaling in Colon Cancer

    International Nuclear Information System (INIS)

    Rosenvinge, Erik C. von; Raufman, Jean-Pierre

    2011-01-01

    According to the adenoma-carcinoma sequence, colon cancer results from accumulating somatic gene mutations; environmental growth factors accelerate and augment this process. For example, diets rich in meat and fat increase fecal bile acids and colon cancer risk. In rodent cancer models, increased fecal bile acids promote colon dysplasia. Conversely, in rodents and in persons with inflammatory bowel disease, low-dose ursodeoxycholic acid treatment alters fecal bile acid composition and attenuates colon neoplasia. In the course of elucidating the mechanism underlying these actions, we discovered that bile acids interact functionally with intestinal muscarinic receptors. The present communication reviews muscarinic receptor expression in normal and neoplastic colon epithelium, the role of autocrine signaling following synthesis and release of acetylcholine from colon cancer cells, post-muscarinic receptor signaling including the role of transactivation of epidermal growth factor receptors and activation of the ERK and PI3K/AKT signaling pathways, the structural biology and metabolism of bile acids and evidence for functional interaction of bile acids with muscarinic receptors on human colon cancer cells. In murine colon cancer models, deficiency of subtype 3 muscarinic receptors attenuates intestinal neoplasia; a proof-of-concept supporting muscarinic receptor signaling as a therapeutic target for colon cancer

  19. Muscarinic Receptor Signaling in Colon Cancer

    Directory of Open Access Journals (Sweden)

    Jean-Pierre Raufman

    2011-03-01

    Full Text Available According to the adenoma-carcinoma sequence, colon cancer results from accumulating somatic gene mutations; environmental growth factors accelerate and augment this process. For example, diets rich in meat and fat increase fecal bile acids and colon cancer risk. In rodent cancer models, increased fecal bile acids promote colon dysplasia. Conversely, in rodents and in persons with inflammatory bowel disease, low-dose ursodeoxycholic acid treatment alters fecal bile acid composition and attenuates colon neoplasia. In the course of elucidating the mechanism underlying these actions, we discovered that bile acids interact functionally with intestinal muscarinic receptors. The present communication reviews muscarinic receptor expression in normal and neoplastic colon epithelium, the role of autocrine signaling following synthesis and release of acetylcholine from colon cancer cells, post-muscarinic receptor signaling including the role of transactivation of epidermal growth factor receptors and activation of the ERK and PI3K/AKT signaling pathways, the structural biology and metabolism of bile acids and evidence for functional interaction of bile acids with muscarinic receptors on human colon cancer cells. In murine colon cancer models, deficiency of subtype 3 muscarinic receptors attenuates intestinal neoplasia; a proof-of-concept supporting muscarinic receptor signaling as a therapeutic target for colon cancer.

  20. Leadership scheme to develop the careers of talented candidates.

    Science.gov (United States)

    Lynas, Karen

    2012-02-01

    The Top Leaders programme supports career development by identifying talented staff and equipping them with a range of management skills and approaches. The programme uses a diagnostic test to help candidates assess their strengths, leadership styles and development needs, and offers them 360 degrees feedback. This enables them to identify areas they need to develop to be effective and supportive leaders. Two case studies illustrate the programme in action.

  1. Prevalence of Staphylococcus aureus colonization in renal transplant patients

    OpenAIRE

    Lamblet,Luiz Carlos Ribeiro; Barbosa,Dulce Aparecida

    2014-01-01

    Objective to evaluate the prevalence of Staphylococcus aureus nasal colonization in renal transplant patients and to identify the related risk factors. Method Swabs were used to collect nasal samples from 160 patients who had undergone a transplant within the previous year at the Kidney and Hypertension Hospital. The ‘National Committee for Clinical Laboratory Standards’ norms were followed for the collection, isolation, identification and sensitivity measurements. Results The...

  2. [Prediction of intra-abdominal hypertension risk in patients with acute colonic obstruction under epidural analgesia].

    Science.gov (United States)

    Stakanov, A V; Potseluev, E A; Musaeva, T S

    2013-01-01

    Purpose of the study was to identify prediction possibility of direct current potential level for intra-abdominal hypertension risk in patients with acute colonic obstruction under preoperative epidural analgesia. Prospective analysis of the preoperative period was carried out in 140 patients with acute colonic obstruction caused by colon cancer. Relations between preoperative level of permanent capacity and risk of intra-abdominal hypertension was identified Direct current potential level is an independent predictor of intra-abdominal hypertension. Diagnostic significance increases from first to fifth hour of preoperative period according to AUROC data from 0.821 to 0.905 and calibration 6.9 (p > 0.37) and 4.7 (p > 0.54) by Hosmer-Lemeshou criteria. The use of epidural analgesia in the complex intensive preoperative preparation is pathogenically justified. It reduces intra-abdominal hypertension in patients with acute colonic obstruction.

  3. Generation of an inducible colon-specific Cre enzyme mouse line for colon cancer research

    NARCIS (Netherlands)

    Tetteh, Paul W.; Kretzschmar, Kai; Begthel, Harry; Van Den Born, Maaike; Korving, Jeroen; Morsink, Folkert; Farin, Henner; Van Es, Johan H.; Offerhaus, G. Johan A; Clevers, Hans

    2016-01-01

    Current mouse models for colorectal cancer often differ significantly from human colon cancer, being largely restricted to the small intestine. Here, we aim to develop a colon-specific inducible mouse model that can faithfully recapitulate human colon cancer initiation and progression. Carbonic

  4. Right colon cancer: Left behind.

    Science.gov (United States)

    Gervaz, P; Usel, M; Rapiti, E; Chappuis, P; Neyroud-Kaspar, I; Bouchardy, C

    2016-09-01

    Prognosis of colon cancer (CC) has steadily improved during the past three decades. This trend, however, may vary according to proximal (right) or distal (left) tumor location. We studied if improvement in survival was greater for left than for right CC. We included all CC recorded at the Geneva population-based registry between 1980 and 2006. We compared patients, tumor and treatment characteristics between left and right CC by logistic regression and compared CC specific survival by Cox models taking into account putative confounders. We also compared changes in survival between CC location in early and late years of observation. Among the 3396 CC patients, 1334 (39%) had right-sided and 2062 (61%) left-sided tumors. In the early 1980s, 5-year specific survival was identical for right and left CCs (49% vs. 48%). During the study period, a dramatic improvement in survival was observed for patients with left-sided cancers (Hazard ratio [HR]: 0.42, 95% confidence interval [CI]: 0.29-0.62, p colon cancer patients, those with right-sided lesions have by far the worse prognosis. Change of strategic management in this subgroup is warranted. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Dietary pattern and colonic diverticulosis.

    Science.gov (United States)

    Tursi, Antonio

    2017-09-01

    To assess the role of dietary pattern on the occurrence of colonic diverticulosis, diverticular disease and acute diverticulitis. High-fiber diet does not prevent diverticulosis occurrence, and results about prevention/treatment of diverticular disease and acute diverticulitis are still conflicting.No association was seen between nut, corn or popcorn consumption and occurrence of diverticulosis, diverticular disease and acute diverticulitis.It seems to be a mild association between high alcohol intake and diverticulosis occurrence, whereas alcohol dependence seems to show lower risk of in-hospital mortality due to acute diverticulitis.Higher red-meat consumption shows mild increased risk of acute diverticulitis, especially when consumed as unprocessed red meat (defined as consumption of 'beef or lamb as main dish', 'pork as main dish', 'hamburger' and 'beef, pork or lamb as a sandwich or mixed dish'); higher consumption of poultry (viz. white meat) was not associated with risk of acute diverticulitis.Finally, higher fish intake was associated with reduced risk of diverticulitis in age-adjusted model, but not after further adjustment for other potential confounders. Current literature data about the role of dietary pattern on the occurrence of colonic diverticulosis, diverticular disease and acute diverticulitis are still too conflicting.

  6. Ecological opportunity and incumbency in the diversification of repeated continental colonizations by muroid rodents.

    Science.gov (United States)

    Schenk, John J; Rowe, Kevin C; Steppan, Scott J

    2013-11-01

    Why some clades are more species-rich than others is a central question in macroevolution. Most hypotheses explaining exceptionally diverse clades involve the emergence of an ecological opportunity caused by a major biogeographic transition or evolution of a key innovation. The radiation of muroid rodents is an ideal model for testing theories of diversification rates in relation to biogeography and ecological opportunity because the group is exceptionally species-rich (comprising nearly one-third of all mammal species), it is ecologically diverse, and it has colonized every major landmass except New Zealand and Antarctica, thus providing multiple replicate radiations. We present an extension of the conventional ecological opportunity model to include a geographic incumbency effect, develop the largest muroid phylogeny to date, and use this phylogeny to test the new model. The nearly 300-species phylogeny based on four nuclear genes is robustly resolved throughout. Consistent with the fossil record, we identified Eurasia as the most likely origin of the group and reconstructed five to seven colonizations of Africa, five of North America, four of Southeast Asia, two of South America, two of Sahul, one of Madagascar, and eight to ten recolonizations of Eurasia. We accounted for incomplete taxon sampling by using multiple statistical methods and identified three corroborated regions of the tree with significant shifts in diversification rates. In several cases, higher rates were associated with the first colonization of a continental area, but most colonizations were not followed by bursts of speciation. We found strong evidence for diversification consistent with the ecological opportunity model (initial burst followed by density-dependent slowdown) in the first colonization of South America and partial support for this model in the first colonization of Sahul. Primary colonizers appear to inhibit the ultimate diversity of secondary colonizers, a pattern of

  7. Integrative analysis to select cancer candidate biomarkers to targeted validation

    Science.gov (United States)

    Heberle, Henry; Domingues, Romênia R.; Granato, Daniela C.; Yokoo, Sami; Canevarolo, Rafael R.; Winck, Flavia V.; Ribeiro, Ana Carolina P.; Brandão, Thaís Bianca; Filgueiras, Paulo R.; Cruz, Karen S. P.; Barbuto, José Alexandre; Poppi, Ronei J.; Minghim, Rosane; Telles, Guilherme P.; Fonseca, Felipe Paiva; Fox, Jay W.; Santos-Silva, Alan R.; Coletta, Ricardo D.; Sherman, Nicholas E.; Paes Leme, Adriana F.

    2015-01-01

    Targeted proteomics has flourished as the method of choice for prospecting for and validating potential candidate biomarkers in many diseases. However, challenges still remain due to the lack of standardized routines that can prioritize a limited number of proteins to be further validated in human samples. To help researchers identify candidate biomarkers that best characterize their samples under study, a well-designed integrative analysis pipeline, comprising MS-based discovery, feature selection methods, clustering techniques, bioinformatic analyses and targeted approaches was performed using discovery-based proteomic data from the secretomes of three classes of human cell lines (carcinoma, melanoma and non-cancerous). Three feature selection algorithms, namely, Beta-binomial, Nearest Shrunken Centroids (NSC), and Support Vector Machine-Recursive Features Elimination (SVM-RFE), indicated a panel of 137 candidate biomarkers for carcinoma and 271 for melanoma, which were differentially abundant between the tumor classes. We further tested the strength of the pipeline in selecting candidate biomarkers by immunoblotting, human tissue microarrays, label-free targeted MS and functional experiments. In conclusion, the proposed integrative analysis was able to pre-qualify and prioritize candidate biomarkers from discovery-based proteomics to targeted MS. PMID:26540631

  8. USING STELLAR DENSITIES TO EVALUATE TRANSITING EXOPLANETARY CANDIDATES

    International Nuclear Information System (INIS)

    Tingley, B.; Deeg, H. J.; Bonomo, A. S.

    2011-01-01

    One of the persistent complications in searches for transiting exoplanets is the low percentage of the detected candidates that ultimately prove to be planets, which significantly increases the load on the telescopes used for the follow-up observations to confirm or reject candidates. Several attempts have been made at creating techniques that can pare down candidate lists without the need of additional observations. Some of these techniques involve a detailed analysis of light curve characteristics; others estimate the stellar density or some proxy thereof. In this paper, we extend upon this second approach, exploring the use of independently calculated stellar densities to identify the most promising transiting exoplanet candidates. We use a set of CoRoT candidates and the set of known transiting exoplanets to examine the potential of this approach. In particular, we note the possibilities inherent in the high-precision photometry from space missions, which can detect stellar asteroseismic pulsations from which accurate stellar densities can be extracted without additional observations.

  9. Experimental evaluation of clinical colon anastomotic leakage.

    Science.gov (United States)

    Pommergaard, Hans-Christian

    2014-03-01

    Colorectal anastomotic leakage remains a frequent and serious complication in gastrointestinal surgery. Patient and procedure related risk factors for anastomotic leakage have been identified. However, the responsible pathophysiological mechanisms are still unknown. Among these, ischemia and insufficient surgical technique have been suggested to play a central role. Animal models are valuable means to evaluate pathophysiological mechanisms and may be used to test preventive measures aiming at reducing the risk of anastomotic leakage, such as external anastomotic coating. The aim of this thesis was to: Clarify the best suited animal to model clinical anastomotic leakage in humans; Create animal models mimicking anastomotic leakage in humans induced by insufficient surgical technique and tissue ischemia; Determine the best suited coating materials to prevent anastomotic leakage. This study is a systematic review using the databases MEDLINE and Rex. MEDLINE was searched up to October 2010 to identify studies on experimental animal models of clinical colon anastomotic leakage. From the Rex database, textbooks on surgical aspects as well as gastrointestinal physiology and anatomy of experimental animals were identified. The results indicated that the mouse and the pig are the best suited animals to evaluate clinical anastomotic leakage. However, the pig model is less validated and more costly to use compared with the mouse. Most frequently, rats are used as models. However, extreme interventions are needed to create clinical leakage in these animals. The knowledge from this study formed the basis for selecting the animal species most suited for the models in the next studies. STUDY 2: In this experimental study, technically insufficient colonic anastomoses were performed in 110 C57BL/6 mice. The number of sutures in the intervention group was reduced to produce a suitable leakage rate. Moreover, the analgesia and suture material were changed in order to optimize the

  10. 1-L-MT, an IDO inhibitor, prevented colitis-associated cancer by inducing CDC20 inhibition-mediated mitotic death of colon cancer cells.

    Science.gov (United States)

    Liu, Xiuting; Zhou, Wei; Zhang, Xin; Ding, Yang; Du, Qianming; Hu, Rong

    2018-04-01

    Indoleamine 2,3-dioxygenase 1 (IDO1), known as IDO, catabolizes tryptophan through kynurenine pathway, whose activity is correlated with impaired clinical outcome of colorectal cancer. Here we showed that 1-L-MT, a canonical IDO inhibitor, suppressed proliferation of human colorectal cancer cells through inducing mitotic death. Our results showed that inhibition of IDO decreased the transcription of CDC20, which resulted in G2/M cycle arrest of HCT-116 and HT-29. Furthermore, 1-L-MT induced mitochondria injuries and caused apoptotic cancer cells. Importantly, 1-L-MT protected mice from azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colon carcinogenesis, with reduced mortality, tumor number and size. What is more, IDO1-/- mice exhibited fewer tumor burdens and reduced proliferation in the neoplastic epithelium, while, 1-L-MT did not exhibit any further protective effects on IDO-/- mice, confirming the critical role of IDO and the protective effect of 1-L-MT-mediated IDO inhibition in CRC. Furthermore, 1-L-MT also alleviated CRC in Rag1-/- mice, demonstrating the modulatory effects of IDO independent of its role in modulating adaptive immunity. Taken together, our findings validated that the anti-proliferation effect of 1-L-MT in vitro and the prevention of CRC in vivo were through IDO-induced cell cycle disaster of colon cancer cells. Our results identified 1-L-MT as a promising candidate for the chemoprevention of CRC. © 2018 UICC.

  11. Face time: educating face transplant candidates.

    Science.gov (United States)

    Lamparello, Brooke M; Bueno, Ericka M; Diaz-Siso, Jesus Rodrigo; Sisk, Geoffroy C; Pomahac, Bohdan

    2013-01-01

    Face transplantation is the innovative application of microsurgery and immunology to restore appearance and function to those with severe facial disfigurements. Our group aims to establish a multidisciplinary education program that can facilitate informed consent and build a strong knowledge base in patients to enhance adherence to medication regimes, recovery, and quality of life. We analyzed handbooks from our institution's solid organ transplant programs to identify topics applicable to face transplant patients. The team identified unique features of face transplantation that warrant comprehensive patient education. We created a 181-page handbook to provide subjects interested in pursuing transplantation with a written source of information on the process and team members and to address concerns they may have. While the handbook covers a wide range of topics, it is easy to understand and visually appealing. Face transplantation has many unique aspects that must be relayed to the patients pursuing this novel therapy. Since candidates lack third-party support groups and programs, the transplant team must provide an extensive educational component to enhance this complex process. As face transplantation continues to develop, programs must create sound education programs that address patients' needs and concerns to facilitate optimal care.

  12. Spatial and environmental correlates of organism colonization and infection in the neonatal intensive care unit.

    Science.gov (United States)

    Goldstein, Neal D; Tuttle, Deborah; Tabb, Loni P; Paul, David A; Eppes, Stephen C

    2018-05-01

    To examine organism colonization and infection in the neonatal intensive care unit as a result of environmental and spatial factors. A retrospective cohort of infants admitted between 2006 and 2015 (n = 11 428), to assess the relationship between location and four outcomes: methicillin-resistant Staphylococcus aureus (MRSA) colonization; culture-confirmed late-onset sepsis; and, if intubated, endotracheal tube colonization with Pseudomonas aeruginosa or Klebsiella pneumonia. Independent risk factors were identified with mixed-effects logistic regression models and Moran's I for spatial autocorrelation. All four outcomes statistically clustered by location; neighboring colonization also influenced risk of MRSA (p < 0.05). For P. aeruginosa, being in a location with space for more medical equipment was associated with 2.61 times the odds of colonization (95% CrI: 1.19, 5.78). Extrinsic factors partially explained risk for neonatal colonization and infection. For P. aeruginosa, infection prevention efforts at locations with space for more equipment may lower future colonization.

  13. Correlation between the Intensity of Helicobacter pylori Colonization and Severity of Gastritis

    Directory of Open Access Journals (Sweden)

    Hamid Reza Ghasemi Basir

    2017-01-01

    Full Text Available Background. The most common cause of chronic gastritis is infection with Helicobacter pylori. Identifying the relationship between intensities of colonization and activity of gastritis helps the clinician in more effective treatment and posttreatment follow-ups. Methods. In this cross-sectional study, endoscopic gastric biopsy samples of 544 patients who complained symptoms of dyspepsia for more than three months referring to the laboratory were studied. To determine the colonization rate of H. pylori and other pathological findings, Giemsa and H&E stains were, respectively, used. Results. Among 544 subjects, 47 (8.64% patients had no gastritis, 203 (37.32% had mild gastritis, 278 (10.51% suffered moderate gastritis, and 16 (2.94% had severe gastritis. In this study, patients with mild H. pylori colonization rates had the highest level of mild activity (33.52%; in contrast, those with severe H. pylori colonization had the highest level of severe activity (43.75%. 93.96% of people with severe H. pylori colonization suffered from moderate and severe chronic gastritis. There is a significant statistical relationship between the intensity of H. pylori colonization and histopathological findings including intestinal metaplasia, atrophy, and lymphoid follicle formation. Conclusions. According to the present study, with increasing intensity of H. pylori colonization, chronicity and activity of gastritis and its complications increase.

  14. Colonization of fish skin is vital for Vibrio anguillarum to cause disease.

    Science.gov (United States)

    Weber, Barbara; Chen, Chang; Milton, Debra L

    2010-02-01

    Vibrio anguillarum causes a fatal haemorrhagic septicaemia in marine fish. During initial stages of infection, host surfaces are colonized; however, few virulence factors required for colonization of the host are identified. In this study, in vivo bioluminescent imaging was used to analyse directly the colonization of the whole rainbow trout animal by V. anguillarum. The wild type rapidly colonized both the skin and the intestines by 24 h; however, the bacterial numbers on the skin were significantly higher than in the intestines indicating that skin colonization may be important for disease to occur. Mutants defective for the anguibactin iron uptake system, exopolysaccharide transport, or Hfq, an RNA chaperone, were attenuated for virulence, did not colonize the skin, and penetrated skin mucus less efficiently than the wild type. These mutants, however, did colonize the intestines and were as resistant to 2% bile salts as is the wild type. Moreover, exopolysaccharide mutants were significantly more sensitive to lysozyme and antimicrobial peptides, while the Hfq and anguibactin mutants were sensitive to lysozyme compared with the wild type. Vibrio anguillarum encodes several mechanisms to protect against antimicrobial components of skin mucus enabling an amazingly abundant growth on the skin enhancing its disease opportunities. © 2010 Society for Applied Microbiology and Blackwell Publishing Ltd.

  15. Epidemiological Features of Clostridium difficile Colonizing the Intestine of Jordanian Infants

    Directory of Open Access Journals (Sweden)

    Eman N. Abu-Khader

    2017-01-01

    Full Text Available Clostridium difficile is commonly found in the intestine of infants without causing any disease. This study investigated the most important epidemiological features of C. difficile strains colonizing intestine of Jordanian infants. A total of 287 fecal samples were collected from infants admitted to the Jordan University Hospital (JUH over the period of 2015. Samples were cultured for C. difficile and their growth was identified using microbiological culture and PCR. The overall C. difficile colonization rate among hospitalized and nonhospitalized infants was 37/287 (12.9%. Neonates were less colonized than other infants (8.7% verses 19.5%. Colonization of the infants with C. difficile toxigenic strains (TcdA and TcdB was observed in 54% of the isolates, whereas those colonized with nontoxigenic strains were 46% and only one isolate was positive for binary toxin. Breast feeding of infants is a significant factor associated with decreased colonization with C. difficile. All C. difficile strains were susceptible to vancomycin and metronidazole, while high resistance rate to ciprofloxacin (78.4% and less resistance rate to erythromycin (29.7% were detected among the isolates. The results showed that 40.5% of the isolates carried mutated gyrA and gyrB genes which have cross-resistance to ciprofloxacin and moxifloxacin. This study represents useful epidemiological features about C. difficile colonizing intestine of infants living in a developing country.

  16. Automated polyp measurement based on colon structure decomposition for CT colonography

    Science.gov (United States)

    Wang, Huafeng; Li, Lihong C.; Han, Hao; Peng, Hao; Song, Bowen; Wei, Xinzhou; Liang, Zhengrong

    2014-03-01

    Accurate assessment of colorectal polyp size is of great significance for early diagnosis and management of colorectal cancers. Due to the complexity of colon structure, polyps with diverse geometric characteristics grow from different landform surfaces. In this paper, we present a new colon decomposition approach for polyp measurement. We first apply an efficient maximum a posteriori expectation-maximization (MAP-EM) partial volume segmentation algorithm to achieve an effective electronic cleansing on colon. The global colon structure is then decomposed into different kinds of morphological shapes, e.g. haustral folds or haustral wall. Meanwhile, the polyp location is identified by an automatic computer aided detection algorithm. By integrating the colon structure decomposition with the computer aided detection system, a patch volume of colon polyps is extracted. Thus, polyp size assessment can be achieved by finding abnormal protrusion on a relative uniform morphological surface from the decomposed colon landform. We evaluated our method via physical phantom and clinical datasets. Experiment results demonstrate the feasibility of our method in consistently quantifying the size of polyp volume and, therefore, facilitating characterizing for clinical management.

  17. Mast Cell Targeted Chimeric Toxin Can Be Developed as an Adjunctive Therapy in Colon Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Shan Wang

    2016-03-01

    Full Text Available The association of colitis with colorectal cancer has become increasingly clear with mast cells being identified as important inflammatory cells in the process. In view of the relationship between mast cells and cancer, we studied the effect and mechanisms of mast cells in the development of colon cancer. Functional and mechanistic insights were gained from ex vivo and in vivo studies of cell interactions between mast cells and CT26 cells. Further evidence was reversely obtained in studies of mast cell targeted Fcε-PE40 chimeric toxin. Experiments revealed mast cells could induce colon tumor cell proliferation and invasion. Cancer progression was found to be related to the density of mast cells in colonic submucosa. The activation of MAPK, Rho-GTPase, and STAT pathways in colon cancer cells was triggered by mast cells during cell-to-cell interaction. Lastly, using an Fcε-PE40 chimeric toxin we constructed, we confirmed the promoting effect of mast cells in development of colon cancer. Mast cells are a promoting factor of colon cancer and thus also a potential therapeutic target. The Fcε-PE40 chimeric toxin targeting mast cells could effectively prevent colon cancer in vitro and in vivo. Consequently, these data may demonstrate a novel immunotherapeutic approach for the treatment of tumors.

  18. Imaging of total colonic Hirschsprung disease

    International Nuclear Information System (INIS)

    Stranzinger, Enno; DiPietro, Michael A.; Strouse, Peter J.; Teitelbaum, Daniel H.

    2008-01-01

    Hirschsprung disease (HD) is a functional obstruction of the bowel caused by the absence of intrinsic enteric ganglion cells. The diagnosis of total colonic HD (TCHD) based on contrast enemas is difficult in newborns because radiological findings vary. To evaluate the radiographic and contrast enema findings in patients with pathologically proven TCHD. From 1966 to 2007, 17 records from a total of 31 patients with TCHD were retrospectively evaluated for diameter and shape of the colon, diameter of the small bowel, bowel wall contour, ileal reflux, abdominal calcifications, pneumoperitoneum, filling defects, transitional zones and rectosigmoid index. Three colonic patterns of TCHD were found: microcolon, question-mark-shape colon and normal caliber colon. Additional findings included spasmodic colon, ileal reflux, delayed evacuation and abdominal calcifications. Colonic transitional zones were found in eight patients with TCHD. The diagnosis of TCHD is difficult to establish by contrast enema studies. The length of the aganglionic small bowel and the age of the patient can influence the radiological findings in TCHD. The transitional zone and the rectosigmoid index can be false-positive in TCHD. The colon can appear normal. Consider TCHD if the contrast enema study is normal but the patient remains symptomatic and other causes of distal bowel obstruction have been excluded. (orig.)

  19. Seat belt injuries and sigmoid colon trauma.

    OpenAIRE

    Eltahir, E M; Hamilton, D

    1997-01-01

    Colonic seat belt injuries are rare but carry higher mortality rates than small bowel injuries. The case of a 44 year old man is described who had severe sigmoid colon compression injury from his seat belt a few days after a road traffic accident.

  20. A Study Of Fungal Colonization In Newborn

    Directory of Open Access Journals (Sweden)

    S Rashid Husain

    1997-04-01

    Full Text Available Research Problem: What are the factors responsible for fungal colonization in newborns? Objective: To study the pattern of and predisposing fac­tors for the development of superficial candidiasis and fungal colonization in the newborns. Study Design: Prospective study. Setting: Neonatology unitof the Paediatrics department of a teaching hospital. Participants: Randomly selected pregnant mothers admit­ted to the maternity ward and the newborns delivered to them. Sample Size: 120 pregnant mothers and the newborns delivered. Study Variables: Candida, Site of colonization. Statistical Analysis: By tests of significance Results: Candida was isolated from 23 (19.16% infants on the first day increasing to 52 (43.33% infants on the sixth day. The most common site of colonization was oral cavity. Candida colonization was more common in prema­ture infants (p<0.05. Oral thrush was seen in 29 (24.17% infants during the study and a significant number of these infants showed colonization from the first day of life. Conclusions: Fungal colonization of the newborns due to Candida species is quite common, and in the first week of life predominantly occurred in the ora I cavity. Superficial clinical candidiasis, especially oral thrush is more common in those colonized on the first day of life.

  1. Role of neutral ceramidase in colon cancer.

    Science.gov (United States)

    García-Barros, Mónica; Coant, Nicolas; Kawamori, Toshihiko; Wada, Masayuki; Snider, Ashley J; Truman, Jean-Philip; Wu, Bill X; Furuya, Hideki; Clarke, Christopher J; Bialkowska, Agnieszka B; Ghaleb, Amr; Yang, Vincent W; Obeid, Lina M; Hannun, Yusuf A

    2016-12-01

    Alterations in sphingolipid metabolism, especially ceramide and sphingosine 1-phosphate, have been linked to colon cancer, suggesting that enzymes of sphingolipid metabolism may emerge as novel regulators and targets in colon cancer. Neutral ceramidase (nCDase), a key enzyme in sphingolipid metabolism that hydrolyzes ceramide into sphingosine, is highly expressed in the intestine; however, its role in colon cancer has not been defined. Here we show that molecular and pharmacological inhibition of nCDase in colon cancer cells increases ceramide, and this is accompanied by decreased cell survival and increased apoptosis and autophagy, with minimal effects on noncancerous cells. Inhibition of nCDase resulted in loss of β-catenin and inhibition of ERK, components of pathways relevant for colon cancer development. Furthermore, inhibition of nCDase in a xenograft model delayed tumor growth and increased ceramide while decreasing proliferation. It is noteworthy that mice lacking nCDase treated with azoxymethane were protected from tumor formation. Taken together, these studies show that nCDase is pivotal for regulating initiation and development of colon cancer, and these data suggest that this enzyme is a suitable and novel target for colon cancer therapy.-García-Barros, M., Coant, N., Kawamori, T., Wada, M., Snider, A. J., Truman, J.-P., Wu, B. X., Furuya, H., Clarke, C. J., Bialkowska, A. B., Ghaleb, A., Yang, V. W., Obeid, L. M., Hannun, Y. A. Role of neutral ceramidase in colon cancer. © FASEB.

  2. Congenital segmental dilatation of the colon

    African Journals Online (AJOL)

    Congenital segmental dilatation of the colon is a rare cause of intestinal obstruction in neonates. We report a case of congenital segmental dilatation of the colon and highlight the clinical, radiological, and histopathological features of this entity. Proper surgical treatment was initiated on the basis of preoperative radiological ...

  3. Incidence of retrorenal colon during percutaneous nephrolithotomy

    Directory of Open Access Journals (Sweden)

    Mehmet Balasar

    2015-04-01

    Full Text Available Objective The aim of this study was to investigate retrorenal colon incidence in percutaneous nephrolithotomy (PNL interventions made in our clinic. Materials and Methods Clinical data of 804 PNL patients, accumulated over a 7 year period (2006-2012, was surveyed. The patient files were reviewed retrospectively, and only those who had abdominal computed tomography (CT images before PNL intervention were included in the study. In the CT images, the position of both the ascending and descending colon in relation to the right and left kidneys were evaluated. Results According to our hospital reports, 394 patients with CT images were included in the present study 27 patients (6.9% had retrorenal colon, of which 18 (4.6% were on the left side, 4 (1.0% on the right side and 5 (1.3% had bilateral retrorenal colons. Colonic perforation complication was seen only in two patients and the colonic perforation rate was 0.3%. These two cases had no CT images. Conclusions PNL, in the process of becoming the standard treatment modality, is a safe and reliable technique for renal stone treatment. Colonic injury should be taken into consideration during PNL interventions of the lower pole of the kidney (especially on the left side due to the location of retrorenal colon.

  4. The colon shuffle : A modified urinary diversion

    NARCIS (Netherlands)

    Meijer, R. P.; Mertens, L. S.; Meinhardt, W.; Verwaal, V. J.; Dik, P.; Horenblas, S.

    2015-01-01

    Aim To assess the results of a urinary diversion in patients who already have a colostomy or simultaneously require a (rectum) colon resection. The diversion is created from the distal part of the transected colon with a simultaneously created new colostomy contra-laterally (if necessary). This

  5. Colonic ischemic necrosis following therapeutic embolization

    International Nuclear Information System (INIS)

    Shenoy, S.S.; Satchidanand, S.; Wesp, E.H.; State Univ. of New York, Buffalo

    1981-01-01

    Transcatheter embolization of the middle colic artery for diverticular bleeding was followed by ischemic necrosis in the transverse colon at the site of previous anastomosis and stricture formation. This is a potential complication of intra-arterial embolization for colonic bleeding. (orig.)

  6. Colonic ischemic necrosis following therapeutic embolization

    Energy Technology Data Exchange (ETDEWEB)

    Shenoy, S S; Satchidanand, S; Wesp, E H

    1981-07-15

    Transcatheter embolization of the middle colic artery for diverticular bleeding was followed by ischemic necrosis in the transverse colon at the site of previous anastomosis and stricture formation. This is a potential complication of intra-arterial embolization for colonic bleeding.

  7. Review article: loss of the calcium-sensing receptor in colonic epithelium is a key event in the pathogenesis of colon cancer.

    LENUS (Irish Health Repository)

    Rogers, Ailín C

    2012-03-01

    The calcium-sensing receptor (CaSR) is expressed abundantly in normal colonic epithelium and lost in colon cancer, but its exact role on a molecular level and within the carcinogenesis pathway is yet to be described. Epidemiologic studies show that inadequate dietary calcium predisposes to colon cancer; this may be due to the ability of calcium to bind and upregulate the CaSR. Loss of CaSR expression does not seem to be an early event in carcinogenesis; indeed it is associated with late stage, poorly differentiated, chemo-resistant tumors. Induction of CaSR expression in neoplastic colonocytes arrests tumor progression and deems tumors more sensitive to chemotherapy; hence CaSR may be an important target in colon cancer treatment. The CaSR has a complex role in colon cancer; however, more investigation is required on a molecular level to clarify its exact function in carcinogenesis. This review describes the mechanisms by which the CaSR is currently implicated in colon cancer and identifies areas where further study is needed.

  8. Association between colonic polyps and diverticular disease

    Institute of Scientific and Technical Information of China (English)

    Tetsuo Hirata; Yuko Kawakami; Nagisa Kinjo; Susumu Arakald; Tetsu Arakaki; Akira Hokama; Fukunori Kinjo; Jim Fujita

    2008-01-01

    AIM: TO evaluate the association between colonic polyps and diverticular disease in Japan.METHODS: We retrospectively reviewed the medical records of 672 consecutive patients who underwent total colonoscopy between August 2006 and April 2007 at Nishinjo Hospital, Okinawa, Japan. Patients with ahistory of any of the following were excluded from the study: previous polypectomy, colonic resection, and inflammatory bowel diseases. The association between colonic polyps and diverticular disease was analyzed by logistic regression analysis, adjusted for age and sex.RESULTS: Prevalence of colonic polyps in all patients with diverticular disease was significantly higher than that in those without diverticular disease (adjusted odds ratio 1.7).CONCLUSION: Our data showed that patients with diverticular disease have a higher risk of colonic polyps compared to those without.

  9. Association between colonic polyps and diverticular disease

    Science.gov (United States)

    Hirata, Tetsuo; Kawakami, Yuko; Kinjo, Nagisa; Arakaki, Susumu; Arakaki, Tetsu; Hokama, Akira; Kinjo, Fukunori; Fujita, Jiro

    2008-01-01

    AIM: To evaluate the association between colonic polyps and diverticular disease in Japan. METHODS: We retrospectively reviewed the medical records of 672 consecutive patients who underwent total colonoscopy between August 2006 and April 2007 at Nishinjo Hospital, Okinawa, Japan. Patients with a history of any of the following were excluded from the study: previous polypectomy, colonic resection, and inflammatory bowel diseases. The association between colonic polyps and diverticular disease was analyzed by logistic regression analysis, adjusted for age and sex. RESULTS: Prevalence of colonic polyps in all patients with diverticular disease was significantly higher than that in those without diverticular disease (adjusted odds ratio 1.7). CONCLUSION: Our data showed that patients with diverticular disease have a higher risk of colonic polyps compared to those without. PMID:18416471

  10. Immunological comparison of ovarian and colonic CEA

    International Nuclear Information System (INIS)

    Burtin, P.; Gendron, M.C.; Maunoury, M.T.; Lamerz, R.; Schnabel, G.

    1982-01-01

    Ovarian and colonic CEA were compared immunologically by means of antisera prepared against each of them. CEAs of both origins were found identical by immunodiffusion methods. In radioimmunological experiments, slight differences were observed between some but not all ovarian CEAs and colonic CEAs and also between different preparations of colonic CEA: no organ specificity of ovarian CEA could be demonstrated. Finally, CEA level was measured in 41 sera of patients with ovarian carcinoma by two radioimmunoassays, one using colonic CEA as tracer and standard and anti-colonic CEA serum, the other using ovarian CEA and anti-ovarian CEA serum: the values given by the two assays were highly correlated (rsub(s) = 0.8107), meaning that an organ specific assay for ovarian CEA is not needed. (Auth.)

  11. Outcomes after colon trauma in the 21st century: an analysis of the U.S. National Trauma Data Bank.

    Science.gov (United States)

    Hatch, Quinton; Causey, Marlin; Martin, Matthew; Stoddard, Douglas; Johnson, Eric; Maykel, Justin; Steele, Scott

    2013-08-01

    Most colon trauma data arise from institutional series that provide descriptive analysis. We investigated the outcome of these patients by analyzing a nationwide database. We queried the U.S. National Trauma Data Bank (2007-2009) using primary International Classification of Diseases, 9th edition, Clinical Modification codes to identify colon injuries. Outcomes were stratified by injury mechanism (blunt versus penetrating), segment of colon injured, and management strategy (diversion versus in continuity). There were 6,817 patients who suffered primary colon injuries; 82% were male and 48% experienced blunt injuries. Blunt colon trauma patients were older, had lengthier intensive care stays, and greater rates of morbidity and mortality than those with penetrating injuries (all P colon injuries (24%). The overall fecal diversion rate was 9%, with the highest rates seen in patients with sigmoid colon injuries (15%). Diverted patients were older, had higher injury severity scores, and increased mortality (22% vs 12%; P colon injuries seem to be managed with fecal diversion more often than other segmental injuries. Neither blunt mechanism nor fecal diversion were independently associated with adverse outcomes in colon trauma. Copyright © 2013 Mosby, Inc. All rights reserved.

  12. Interaction of barley powdery mildew effector candidate CSEP0055 with the defence protein PR17c

    DEFF Research Database (Denmark)

    Zhang, Wenjing; Pedersen, Carsten; Kwaaitaal, Mark Adrianus Cornelis J

    2012-01-01

    A large number of effector candidates have been identified recently in powdery mildew fungi. However, their roles and how they perform their functions remain unresolved. In this study, we made use of host-induced gene silencing and confirmed that the secreted barley powdery mildew effector candid...

  13. Association of asymptomatic oral candidal carriage, oral candidiasis and CD4 lymphocyte count in HIV-positive patients in China.

    Science.gov (United States)

    Liu, X; Liu, H; Guo, Z; Luan, W

    2006-01-01

    To compare the prevalence of asymptomatic oral candidal carriage in healthy volunteers with human immunodeficiency virus (HIV)-positive patients in China, as well as to investigate the relationship between CD4+ lymphocyte count and oral candidal colonization or oral candidiasis. Oral candidal carriage and oral candidiasis were investigated in 101 patients with HIV-infection seen at Youan Hospital, Beijing, China. Two hundred and seventeen healthy volunteers were involved as a control. Culture from saliva was used to test for the presence of oral Candida. CD4+ lymphocyte count was measured by flow cytometry. All data were analyzed statistically by SAS. Asymptomatic oral candidal carriage rate (28.6%) in HIV-positive group was similar to that in the healthy group (18.0%; P = 0.07). No significant difference in CD4+ lymphocyte count was found between oral Candida carriers and non-carriers among HIV-positive subjects (P = 0.89). However, the frequency of oral candidiasis increased with the decrease in CD4+ lymphocyte count (P < 0.0001), and pseudomembranous candidiasis was predominant in HIV-positive patients with CD4+ <200 cells microl(-1) (66.7%). In HIV-positive subjects, asymptomatic oral candidal colonization is not related to CD4+ lymphocyte count of blood, and the carriage rate is similar to that in the healthy population. Oral candidiasis is more likely to be observed in HIV-positive patients who have a low CD4+ lymphocyte count.

  14. A Burkholderia pseudomallei colony variant necessary for gastric colonization.

    Science.gov (United States)

    Austin, C R; Goodyear, A W; Bartek, I L; Stewart, A; Sutherland, M D; Silva, E B; Zweifel, A; Vitko, N P; Tuanyok, A; Highnam, G; Mittelman, D; Keim, P; Schweizer, H P; Vázquez-Torres, A; Dow, S W C; Voskuil, M I

    2015-02-03

    Diverse colony morphologies are a hallmark of Burkholderia pseudomallei recovered from infected patients. We observed that stresses that inhibit aerobic respiration shifted populations of B. pseudomallei from the canonical white colony morphotype toward two distinct, reversible, yet relatively stable yellow colony variants (YA and YB). As accumulating evidence supports the importance of B. pseudomallei enteric infection and gastric colonization, we tested the response of yellow variants to hypoxia, acidity, and stomach colonization. Yellow variants exhibited a competitive advantage under hypoxic and acidic conditions and alkalized culture media. The YB variant, although highly attenuated in acute virulence, was the only form capable of colonization and persistence in the murine stomach. The accumulation of extracellular DNA (eDNA) was a characteristic of YB as observed by 4',6-diamidino-2-phenylindole (DAPI) staining of gastric tissues, as well as in an in vitro stomach model where large amounts of eDNA were produced without cell lysis. Transposon mutagenesis identified a transcriptional regulator (BPSL1887, designated YelR) that when overexpressed produced the yellow phenotype. Deletion of yelR blocked a shift from white to the yellow forms. These data demonstrate that YB is a unique B. pseudomallei pathovariant controlled by YelR that is specifically adapted to the harsh gastric environment and necessary for persistent stomach colonization. Seemingly uniform populations of bacteria often contain subpopulations that are genetically identical but display unique characteristics which offer advantages when the population is faced with infrequent but predictable stresses. The pathogen Burkholderia pseudomallei is capable of forming several reversible colony types, and it interconverted between one white type and two yellow types under certain environmental stresses. The two yellow forms exhibited distinct advantages in low-oxygen and acidic environments. One yellow

  15. [Continent colostomy and colon irrigation].

    Science.gov (United States)

    Kostov, D; Temelkov, T; Kiriazov, E; Ivanov, K; Ignatov, V; Kobakov, G

    2000-01-01

    The authors have studied a functional activity of a continent colostomy at 20 patients, undergone an abdomeno-perineal extirpation of rectum and carried out periodic colonirrigations, during a period of 6 months. A conus type, closed irrigating system has been used. The degree of an incontinency at patients has been compared before and after the beginning of the colonirrigations. The irrigating procedures have reduced spontaneous defications at patients during a week 28 times and have improved the quality of life significantly. The application of colostomy bags has been restricted in 8 (40%) patients. An intraluminal ultrasonographic investigation has been done at 12 (60%) patients at the end of 6 month irrigating period. No changes of the ultrasonographic image of the precolostomic segment of colon has been observed.

  16. Magnetomotive colon elastography: preliminary assessment

    International Nuclear Information System (INIS)

    Bruno, A. Colello; Grillo, F.W.; Sampaio, D.R.T.; Carneiro, A.A.O.

    2015-01-01

    Colorectal cancer (CRC) is the third most common malignant neoplasm worldwide and early diagnosis reduces morbidity. The standard preventive exams methods are uncomfortable for the patient, invasive, and /or are ionizing. Here, we evaluate the potential of magneto-motive ultrasound (MMUS) as a new, minimally invasive CRC screening technique. We developed a hybrid transducer (comprised of an ultrasound probe and a magnetic coil system) to construct relative elastography maps in a paraffin phantom with isoechoic inclusions. The electromagnetic component of our system manipulated ferromagnetic fluid located inside of our synthetic colon, and the captured ultrasound images were used to produce relative elastography maps. The MMUS images reveal by otherwise invisible structures based on differences in stiffness. Ultrasound elastography (relative) images by MMUs technique complements usual preventive CRC exams, is minimally invasive, has relative low cost when compared with others image methods. Also is fast diagnose and more comfortable for patient which prevents withdrawal of the screening. (author)

  17. Mouse model of proximal colon-specific tumorigenesis driven by microsatellite instability-induced Cre-mediated inactivation of Apc and activation of Kras.

    Science.gov (United States)

    Kawaguchi, Yasuo; Hinoi, Takao; Saito, Yasufumi; Adachi, Tomohiro; Miguchi, Masashi; Niitsu, Hiroaki; Sasada, Tatsunari; Shimomura, Manabu; Egi, Hiroyuki; Oka, Shiro; Tanaka, Shinji; Chayama, Kazuaki; Sentani, Kazuhiro; Oue, Naohide; Yasui, Wataru; Ohdan, Hideki

    2016-05-01

    KRAS gene mutations are found in 40-50% of colorectal cancer cases, but their functional contribution is not fully understood. To address this issue, we generated genetically engineered mice with colon tumors expressing an oncogenic Kras(G12D) allele in the context of the Adenomatous polyposis coli (Apc) deficiency to compare them to tumors harboring Apc deficiency alone. CDX2P9.5-G22Cre (referred to as G22Cre) mice showing inducible Cre recombinase transgene expression in the proximal colon controlled under the CDX2 gene promoter were intercrossed with Apc (flox/flox) mice and LSL-Kras (G12D) mice carrying loxP-flanked Apc and Lox-Stop-Lox oncogenic Kras(G12D) alleles, respectively, to generate G22Cre; Apc(flox/flox); Kras(G12D) and G22Cre; Apc(flox/flox); KrasWT mice. Gene expression profiles of the tumors were analyzed using high-density oligonucleotide arrays. Morphologically, minimal difference in proximal colon tumor was observed between the two mouse models. Consistent with previous findings in vitro, Glut1 transcript and protein expression was up-regulated in the tumors of G22Cre;Apc (flox/flox) ; Kras(G12D) mice. Immunohistochemical staining analysis revealed that GLUT1 protein expression correlated with KRAS mutations in human colorectal cancer. Microarray analysis identified 11 candidate genes upregulated more than fivefold and quantitative PCR analysis confirmed that Aqp8, Ttr, Qpct, and Slc26a3 genes were upregulated 3.7- to 30.2-fold in tumors with mutant Kras. These results demonstrated the validity of the G22Cre; Apc(flox/flox) ;Kras (G12D) mice as a new mouse model with oncogenic Kras activation. We believe that this model can facilitate efforts to define novel factors that contribute to the pathogenesis of human colorectal cancer with KRAS mutations.

  18. Oral Candida colonization and candidiasis in patients with psoriasis.

    Science.gov (United States)

    Bedair, Ahmad A; Darwazeh, Azmi M G; Al-Aboosi, Mustafa M

    2012-11-01

    The objective of this study was to investigate oral Candida colonization and candidosis in a group of patients with psoriasis and controls. A total of 100 patients with psoriasis and matched controls underwent the concentrated oral rinse test for Candida isolation. Candida species were identified by the VITEK 2 Identification System. Categorical variables were evaluated using the χ(2) test. The median Candida count was compared using the Mann-Whitney U test. Oral candidiasis was diagnosed in 3% of the patients with psoriasis. The Candida count and prevalence were significantly higher in the patients with psoriasis compared with controls (69% vs 44%, P Oral Candida was significantly higher in late-onset (at age ≥30 years) compared with early-onset psoriasis (at age oral Candida colonization and candidiasis. Further studies are needed to clarify the predisposing factor(s) for oral Candida in patients with psoriasis. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Optical density measurements on the examination of colon cancer tissues

    International Nuclear Information System (INIS)

    Touati, E.; Ajaal, T.; Hamassi, A.

    2015-01-01

    Automated quantitative image analysis can aid in cancer diagnosis and, in general, mange medical treatments managements and improve routine medical diagnosis. Early diagnosis can make big difference between life and death. Microscopic images from two tissue types forty-four normal and fifty-eight cancers, was evaluated based on their ability to identify abnormalities in colon images. Optical density approach is applied to extract parameters that exhibit cancer behavior on colon tissues images. Using statistical toolbox, a significant result of (p<0.0001) for the mean and the variance of the optical density parameter were detected, and only (p<0.001) for skewness optical density. based on linear discrimination method, the obtained result shows 905 accuracy for both sensitivity and specificity, and with an overall accuracy of 90% (author)

  20. Assessment of Lactobacillus gasseri as a candidate oral vaccine vector.

    Science.gov (United States)

    Stoeker, Laura; Nordone, Shila; Gunderson, Sara; Zhang, Lin; Kajikawa, Akinobu; LaVoy, Alora; Miller, Michael; Klaenhammer, Todd R; Dean, Gregg A

    2011-11-01

    Lactobacillus species are commensal bacteria that have long been recognized as probiotic microbes and are generally regarded as safe (GRAS) for human consumption. We have investigated the use of L. gasseri as a vaccine vector for oral immunization against mucosal pathogens. Recent research has shown that the immune response to different lactobacilli can vary widely depending on the species or subspecies of Lactobacillus being studied. While some lactobacilli seem to induce oral tolerance, others induce an adaptive immune response. This study characterized the systemic and mucosal immune response to wild-type and genetically modified L. gasseri. L. gasseri primarily activates TLR2/6, with additional activation through the TLR2 homodimer. To expand the Toll-like receptor (TLR) activation profile of L. gasseri and the immunogenicity of the vector, a plasmid containing fliC, the gene encoding bacterial flagellin, was introduced which resulted in the strong activation of TLR5. The treatment of human myeloid dendritic cells with recombinant lactobacilli expressing flagellin triggered phenotypic maturation and the release of proinflammatory cytokines. In contrast, bacterial treatment also resulted in a statistically significant increase in IL-10 production. In vivo studies established that treatment with L. gasseri led to a diversification of B-cell populations in the lamina propria of the murine colon. Furthermore, treatment with genetically modified L. gasseri led to a significant decrease in the percentage of FoxP3(+) colonic lymphocytes. Taken together, these data clarify the interaction of L. gasseri with the host immune system and support further investigation of the in vivo immunogenicity of L. gasseri expressing both flagellin and candidate vaccine antigens.

  1. Necrotizing colitis associated with carcinoma of the colon

    International Nuclear Information System (INIS)

    Woo, Seong Ku; Lim, Jae Hoon; Kim, Soon Yong; Ahn, Chi Yul

    1982-01-01

    Necrotizing colitis associated with carcinoma of the colon, known also as obstructive colitis, is a disorder characterized by anulceration and inflammation of the colon proximal to an obstructive lesion, especially carcinoma of the rectosigmoid colon, and in rare instance, leads to acute gangrene of the colon. The authors analyzed radiologic findings in four cases of necrotizing colitis associated with carcinoma of the colon. Barium enema disclosed mucosal edema, nodular filling defects, irregularity of the colonic contour and typical thumbprinting appearance of involved colon proximal to an obstructing carcinoma of the colon. The mechanism of necrotizing colitis was briefly reviewed

  2. Associations between birth weight and colon and rectal cancer risk in adulthood.

    Science.gov (United States)

    Smith, Natalie R; Jensen, Britt W; Zimmermann, Esther; Gamborg, Michael; Sørensen, Thorkild I A; Baker, Jennifer L

    2016-06-01

    Birth weight has inconsistent associations with colorectal cancer, possibly due to different anatomic features of the colon versus the rectum. The aim of this study was to investigate the association between birth weight and colon and rectal cancers separately. 193,306 children, born from 1936 to 1972, from the Copenhagen School Health Record Register were followed prospectively in Danish health registers. Colon and rectal cancer cases were defined using the International Classification of Disease version 10 (colon: C18.0-18.9, rectal: 19.9 and 20.9). Only cancers classified as adenocarcinomas were included in the analyses. Cox regressions were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Analyses were stratified by birth cohort and sex. During 3.8 million person-years of follow-up, 1465 colon and 961 rectal adenocarcinomas were identified. No significant sex differences were observed; therefore combined results are presented. Birth weight was positively associated with colon cancers with a HR of 1.14 (95% CI, 1.04-1.26) per kilogram of birth weight. For rectal cancer a significant association was not observed for birth weights below 3.5kg. Above 3.5kg an inverse association was observed (at 4.5kg, HR=0.77 [95% CI, 0.61-0.96]). Further, the associations between birth weight and colon and rectal cancer differed significantly from each other (p=0.006). Birth weight is positively associated with the risk of adult colon cancer, whereas the results for rectal cancer were inverse only above values of 3.5kg. The results underline the importance of investigating colon and rectal cancer as two different entities. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  3. High Prevalence of Antimicrobial-resistant Gram-negative Colonization in Hospitalized Cambodian Infants.

    Science.gov (United States)

    Turner, Paul; Pol, Sreymom; Soeng, Sona; Sar, Poda; Neou, Leakhena; Chea, Phal; Day, Nicholas Pj; Cooper, Ben S; Turner, Claudia

    2016-08-01

    Antimicrobial-resistant Gram-negative infections are a significant cause of mortality in young infants. We aimed to determine characteristics of, and risk factors for, colonization and invasive infection caused by 3rd generation cephalosporin (3GC) or carbapenem-resistant organisms in outborn infants admitted to a neonatal unit (NU) in Cambodia. During the first year of operation, patients admitted to the Angkor Hospital for Children NU, Siem Reap, Cambodia, underwent rectal swabbing on admission and twice weekly until discharge. Swabs were taken also from 7 environmental sites. Swabs were cultured to identify 3GC or carbapenem-resistant Acinetobacter sp., Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa. The study included 333 infants with a median age at NU admission of 10 days (range, 0-43). Colonization by ≥1 3GC-resistant organism was detected in 85.9% (286/333). Admission swabs were collected in 289 infants: 61.9% were colonized by a 3GC-resistant organism at the time of admission, and a further 23.2% were colonized during hospitalization, at a median of 4 days [95% confidence interval: 3-5]. Probiotic treatment (hazard ratio: 0.58; 95% confidence interval: 0.35-0.98) was associated with delayed colonization. Colonization by a carbapenem-resistant organism occurred in 25 (7.5%) infants. Six infants had NU-associated K. pneumoniae bacteremia; phenotypically identical colonizing strains were found in 3 infants. Environmental colonization occurred early. Colonization by antimicrobial-resistant Gram-negative organisms occurred early in hospitalized Cambodian infants and was associated with subsequent invasive infection. Trials of potential interventions such as probiotics are needed.

  4. Dissecting the organ specificity of insecticide resistance candidate genes in Anopheles gambiae: known and novel candidate genes.

    Science.gov (United States)

    Ingham, Victoria A; Jones, Christopher M; Pignatelli, Patricia; Balabanidou, Vasileia; Vontas, John; Wagstaff, Simon C; Moore, Jonathan D; Ranson, Hilary

    2014-11-25

    The elevated expression of enzymes with insecticide metabolism activity can lead to high levels of insecticide resistance in the malaria vector, Anopheles gambiae. In this study, adult female mosquitoes from an insecticide susceptible and resistant strain were dissected into four different body parts. RNA from each of these samples was used in microarray analysis to determine the enrichment patterns of the key detoxification gene families within the mosquito and to identify additional candidate insecticide resistance genes that may have been overlooked in previous experiments on whole organisms. A general enrichment in the transcription of genes from the four major detoxification gene families (carboxylesterases, glutathione transferases, UDP glucornyltransferases and cytochrome P450s) was observed in the midgut and malpighian tubules. Yet the subset of P450 genes that have previously been implicated in insecticide resistance in An gambiae, show a surprisingly varied profile of tissue enrichment, confirmed by qPCR and, for three candidates, by immunostaining. A stringent selection process was used to define a list of 105 genes that are significantly (p ≤0.001) over expressed in body parts from the resistant versus susceptible strain. Over half of these, including all the cytochrome P450s on this list, were identified in previous whole organism comparisons between the strains, but several new candidates were detected, notably from comparisons of the transcriptomes from dissected abdomen integuments. The use of RNA extracted from the whole organism to identify candidate insecticide resistance genes has a risk of missing candidates if key genes responsible for the phenotype have restricted exp