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Sample records for aberrantly expressed recoverin

  1. Expression changes of Rhodopsin and recoverin in MNU-induced photoreceptor degeneration in rats

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    Wei Jin

    2014-10-01

    Full Text Available AIM: To investigate the time-effect relationship between the expression of rhodopsin and recoverin and photoreceptor damage induced by N-nethl-N-nitrosourea(MNU. METHODS: Thirty-six 7-week old Sprague-Dawley(SDrats were intraperitoneally injected with MNU(60mg/kgand were put to death by dislocation of cervical vertebra 6, 12, 24h; 3, 7d after injection(6 per group, respectively. As a control, six rats were injected with phosphate buffer saline(PBS5mL/kg and sacrificed on d3 after injection. The degree of photoreceptor apoptosis was detected by HE staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling(TUNELand transmission electron microscope(TEMin the right eyes. The mRNA expressions of rhodopsin and recoverin were detected different time after injection by Western blot and immunohistochemical method in the left eyes. RESULTS: The dissolution of photoreceptor nucleus and apoptosis body were first perceived at 12h by TEM; most of cells at outer nuclear layer were presented positive reaction. The apoptotic index reached peak(29.7%±2.3%at 24h which was coincided with the observation of TEM. The results of immunohistochemistry displayed that rhodopsin and recoverin were on a declining curve with time extension. Furthermore, the results of Western blot indicated that rhodopsin had dramatic decline at 6h after injection(P0.05, and extremely significant difference comparing to control group after 12h(P0.01; while recoverin dramatic declined at 12h, and extremely significant difference after 24h(P0.01. CONCLUSION: 60mg/kg MNU intraperitoneally injection one-time may specifically induce photoreceptor apoptosis, The mechanism of down-regulation of rhodopsin and recoverin may be related to the selected apoptosis of photoreceptors.

  2. The cancer-retina antigen recoverin as a potential biomarker for renal tumors.

    Science.gov (United States)

    Golovastova, Marina O; Tsoy, Larisa V; Bocharnikova, Anna V; Korolev, Dmitry O; Gancharova, Olga S; Alekseeva, Ekaterina A; Kuznetsova, Ekaterina B; Savvateeva, Lyudmila V; Skorikova, Elena E; Strelnikov, Vladimir V; Varshavsky, Vladimir A; Vinarov, Andrey Z; Nikolenko, Vladimir N; Glybochko, Peter V; Zernii, Evgeni Yu; Zamyatnin, Andrey A; Bazhin, Alexandr V; Philippov, Pavel P

    2016-07-01

    The renal cell carcinoma is the ninth most common cancer with an increasing occurrence and mortality. Recoverin is the first retina-specific photoreceptor protein that was shown to undergo aberrant expression, due to its promoter demethylation, as a cancer-retina antigen in a number of malignant tumors. In this work, we demonstrated that recoverin is indeed expressed in 68.4 % of patients with different subtypes of renal cell carcinoma, and this expression has tendency to correlate with tumor size. Interestingly, 91.7 % of patients with the benign renal tumor, oncocytoma, express recoverin as well in their tumor. Epigenetic analysis of the recoverin gene promoter revealed a stable mosaic methylation pattern with the predominance of the methylated state, with the exception of -80 and 56 CpG dinucleotides (CpGs). While the recoverin expression does not correlate withoverall survival of the tumor patients, the methylation of the recoverin gene promoter at -80 position is associated with better overall survival of the patients. This work is the first report pointing towards the association of overall survival of renal cell carcinoma (RCC) patients with promoter methylation of a cancer-retina antigen. Taken together, these data allow to consider recoverin as a potential therapeutic target and/or marker for renal tumors.

  3. Establishment of a novel small cell lung carcinoma cell line with specific recoverin expression from a patient with cancer-associated retinopathy.

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    Kobayashi, Makoto; Ikezoe, Takayuki; Uemura, Yoshiki; Takeuchi, Tamotsu; Ueno, Hisayuki; Ohtsuki, Yuji; Taguchi, Hirokuni

    2007-06-01

    We analysed the biologic properties of a small cell lung carcinoma cell line (designated KK0206) established from a patient with SCLC who had cancer-associated retinopathy (CAR). Morphological and immunohistochemical studies showed that KK0206 cells have features of the classic type of SCLC. KK0206 cells grew in suspension, forming relatively small clumps of cells with a doubling time of 72 h. On light microscopy, the cells were relatively small with little cytoplasm. On immunohistochemistry using anti-bovine recoverin rabbit antibody, the cells were intensely positive for recoverin. In addition, they were positive for NSE, Ki-67, and TP53. They also expressed human recoverin, a photoreceptor protein, whose presence was confirmed by RT-PCR analysis with cDNA sequencing and Western blot analysis. The point mutation of their TP53 gene (exon 156) was detected as well. The present study demonstrates that human recoverin is expressed in SCLC cells cultured from an anti-recoverin antibody-negative patient with CAR. KK0206 might be important for further research on SCLC related retinopathy.

  4. Aberrant Gene Expression in Acute Myeloid Leukaemia

    DEFF Research Database (Denmark)

    Bagger, Frederik Otzen

    model to investigate the role of telomerase in AML, we were able to translate the observed effect into human AML patients and identify specific genes involved, which also predict survival patterns in AML patients. During these studies we have applied methods for investigating differentially expressed......Summary Acute Myeloid Leukaemia (AML) is an aggressive cancer of the bone marrow, affecting formation of blood cells during haematopoiesis. This thesis presents investigation of AML using mRNA gene expression profiles (GEP) of samples extracted from the bone marrow of healthy and diseased subjects....... Here GEPs from purified healthy haematopoietic populations, with different levels of differentiation, form the basis for comparison with diseased samples. We present a mathematical transformation of mRNA microarray data to make it possible to compare AML samples, carrying expanded aberrant...

  5. Expressions for third-order aberration theory for holographic images

    Indian Academy of Sciences (India)

    S K Tripathy; S Ananda Rao

    2003-01-01

    Expressions for third-order aberration in the reconstructed wave front of point objects are established by Meier. But Smith, Neil Mohon, Sweatt independently reported that their results differ from that of Meier. We found that coefficients for spherical aberration, astigmatism, tally with Meier’s while coefficients for distortion and coma differ.

  6. Structural basis for calcium-induced inhibition of rhodopsin kinase by recoverin.

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    Ames, James B; Levay, Konstantin; Wingard, Jennifer N; Lusin, Jacqueline D; Slepak, Vladlen Z

    2006-12-01

    Recoverin, a member of the neuronal calcium sensor branch of the EF-hand superfamily, serves as a calcium sensor that regulates rhodopsin kinase (RK) activity in retinal rod cells. We report here the NMR structure of Ca(2+)-bound recoverin bound to a functional N-terminal fragment of rhodopsin kinase (residues 1-25, called RK25). The overall main-chain structure of recoverin in the complex is similar to structures of Ca(2+)-bound recoverin in the absence of target (<1.8A root-mean-square deviation). The first eight residues of recoverin at the N terminus are solvent-exposed, enabling the N-terminal myristoyl group to interact with target membranes, and Ca(2+) is bound at the second and third EF-hands of the protein. RK25 in the complex forms an amphipathic helix (residues 4-16). The hydrophobic face of the RK25 helix (Val-9, Val-10, Ala-11, Ala-14, and Phe-15) interacts with an exposed hydrophobic groove on the surface of recoverin lined by side-chain atoms of Trp-31, Phe-35, Phe-49, Ile-52, Tyr-53, Phe-56, Phe-57, Tyr-86, and Leu-90. Residues of recoverin that contact RK25 are highly conserved, suggesting a similar target binding site structure in all neuronal calcium sensor proteins. Site-specific mutagenesis and deletion analysis confirm that the hydrophobic residues at the interface are necessary and sufficient for binding. The recoverin-RK25 complex exhibits Ca(2+)-induced binding to rhodopsin immobilized on concanavalin-A resin. We propose that Ca(2+)-bound recoverin is bound between rhodopsin and RK in a ternary complex on rod outer segment disk membranes, thereby blocking RK interaction with rhodopsin at high Ca(2+).

  7. The effect of recombinant recoverin on the photoresponse of truncated rod photoreceptors

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    Erickson, Martha A.; Lagnado, Leon; Zozulya, Sergey; Neubert, Thomas A.; Stryer, Lubert; Baylor, Denis A.

    1998-01-01

    Recoverin is a heterogeneously acylated calcium-binding protein thought to regulate visual transduction. Its effect on the photoresponse was investigated by dialyzing the recombinant protein into truncated salamander rod outer segments. At high Ca2+ (Ca), myristoylated recoverin (Ca-recoverin) prolonged the recovery phase of the bright flash response but had less effect on the dim flash response. The prolongation of recovery had an apparent Kd for Ca of 13 μM and a Hill coefficient of 2. The prolongation was shown to be mediated by inhibition of rhodopsin deactivation. After a sudden imposed drop in Ca concentration, the effect of recoverin switched off with little lag. The myristoyl (C14:0) modification of recoverin increased its activity 12-fold, and the C12:0 or C14:2 acyl group gave similar effects. These experiments support the notion that recoverin mediates Ca-dependent inhibition of rhodopsin phosphorylation and thereby controls light-triggered phosphodiesterase activity, particularly at high light levels. PMID:9600991

  8. Prognostic significance of aberrantly silenced ANPEP expression in prostate cancer

    DEFF Research Database (Denmark)

    Sørensen, Karina Dalsgaard; Abildgaard, Mette Opstrup; Haldrup, Christa

    2013-01-01

    Background:Novel biomarkers for prostate cancer (PC) are urgently needed. This study investigates the expression, epigenetic regulation, and prognostic potential of ANPEP in PC.Methods:Aminopeptidase N (APN; encoded by ANPEP) expression was analysed by immunohistochemistry using tissue microarrays...... representing 267 radical prostatectomy (RP) and 111 conservatively treated (CT) PC patients. Clinical end points were recurrence-free survival (RFS) and cancer-specific survival (CSS), respectively. The ANPEP promoter methylation levels were determined by bisulphite sequencing or MethyLight analysis in 278...... nonmalignant and PC tissue samples, and in cell lines.Results:The APN expression was significantly downregulated in PC compared with nonmalignant prostate tissue samples. Aberrant promoter hypermethylation was frequently observed in PC tissue samples, and 5-aza-2'-deoxycytidine induced ANPEP expression...

  9. Aberrant microRNA expression in multiple myeloma

    DEFF Research Database (Denmark)

    Dimopoulos, Konstantinos; Gimsing, Peter; Grønbæk, Kirsten

    2013-01-01

    Multiple myeloma (MM) is a devastating disease with a complex biology, and in spite of improved survivability by novel treatment strategies over the last decade, MM is still incurable by current therapy. MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression at a post......-transcriptional level. More than half of all protein coding genes are estimated to be controlled by miRNAs, and their expression is frequently deregulated in many diseases, including cancer. Recent studies have reported aberrant miRNA expression patterns in MM, and the function of individual miRNAs in MM has been...... investigated in detail in cell culture and animal models. Here, we review the current knowledge on the role of miRNAs in MM pathogenesis and discuss their potential as prognostic biomarkers and targets for treatment....

  10. Heterogeneity of aberrant immunoglobulin expression in cancer cells

    Institute of Scientific and Technical Information of China (English)

    Duosha Hu; Ya Cao; Zhi Duan; Ming Li; Yiqun Jiang; Haidan Liu; Hui Zheng; Lili Li; Ann M Bode; Zigang Dong

    2011-01-01

    Accumulating evidence has shown that immunoglobulin (Ig) is 'unexpectedly' expressed by epithelial cancer cells and that it can promote tumor growth.The main purpose of this study was to explore the components of the cancerous Ig and its possible function.The presence of cancerous Ig in the Golgi apparatus was confirmed by immunofluorescence,indirectly suggesting that the cancerous Ig was processed and packaged in cancer cells.Western blot analysis and ELISA results indicated that cancer cells produced membrane Ig and secreted Ig into the supernatant fraction.The cancerous Ig consists of an α heavy chain and a κ light chain.Finally,by analyzing the Ig components pulled down by protein A beads,the cancerous Ig was found to be structurally distinct from normal Ig.The cancerous Ig was truncated or aberrant.Although the underlying mechanism that causes the abnormalities has not been determined,our current discoveries strengthen our previous findings and promise fruitful future explorations.

  11. Alzheimer's disease shares gene expression aberrations with purinergic dysregulation of HPRT deficiency (Lesch-Nyhan disease).

    Science.gov (United States)

    Kang, Tae Hyuk; Friedmann, Theodore

    2015-03-17

    Transcriptomic studies of murine D3 embryonic stem (ES) cells deficient in the purinergic biosynthetic function hypoxanthine guanine phosphoribosyltransferase (HPRT) and undergoing dopaminergic neuronal differentiation has demonstrated a marked shift from neuronal to glial gene expression and aberrant expression of multiple genes also known to be aberrantly expressed in Alzheimer's and other CNS disorders. Such genetic dysregulations may indicate some shared pathogenic metabolic mechanisms in diverse CNS diseases. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Observation of lens aberrations for high resolution electron microscopy II: Simple expressions for optimal estimates

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    Saxton, W. Owen, E-mail: wos1@cam.ac.uk

    2015-04-15

    This paper lists simple closed-form expressions estimating aberration coefficients (defocus, astigmatism, three-fold astigmatism, coma / misalignment, spherical aberration) on the basis of image shift or diffractogram shape measurements as a function of injected beam tilt. Simple estimators are given for a large number of injected tilt configurations, optimal in the sense of least-squares fitting of all the measurements, and so better than most reported previously. Standard errors are given for most, allowing different approaches to be compared. Special attention is given to the measurement of the spherical aberration, for which several simple procedures are given, and the effect of foreknowledge of this on other aberration estimates is noted. Details and optimal expressions are also given for a new and simple method of analysis, requiring measurements of the diffractogram mirror axis direction only, which are simpler to make than the focus and astigmatism measurements otherwise required. - Highlights: • Optimal estimators for CTEM lens aberrations are more accurate and/or use fewer observations. • Estimators have been found for defocus, astigmatism, three-fold astigmatism, coma and spherical aberration. • Estimators have been found relying on diffractogram shape, image shift and diffractogram orientation only, for a variety of beam tilts. • The standard error for each estimator has been found.

  13. A genome-wide map of aberrantly expressed chromosomal islands in colorectal cancer

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    Castanos-Velez Esmeralda

    2006-09-01

    Full Text Available Abstract Background Cancer development is accompanied by genetic phenomena like deletion and amplification of chromosome parts or alterations of chromatin structure. It is expected that these mechanisms have a strong effect on regional gene expression. Results We investigated genome-wide gene expression in colorectal carcinoma (CRC and normal epithelial tissues from 25 patients using oligonucleotide arrays. This allowed us to identify 81 distinct chromosomal islands with aberrant gene expression. Of these, 38 islands show a gain in expression and 43 a loss of expression. In total, 7.892 genes (25.3% of all human genes are located in aberrantly expressed islands. Many chromosomal regions that are linked to hereditary colorectal cancer show deregulated expression. Also, many known tumor genes localize to chromosomal islands of misregulated expression in CRC. Conclusion An extensive comparison with published CGH data suggests that chromosomal regions known for frequent deletions in colon cancer tend to show reduced expression. In contrast, regions that are often amplified in colorectal tumors exhibit heterogeneous expression patterns: even show a decrease of mRNA expression. Because for several islands of deregulated expression chromosomal aberrations have never been observed, we speculate that additional mechanisms (like abnormal states of regional chromatin also have a substantial impact on the formation of co-expression islands in colorectal carcinoma.

  14. Deciphering causal and statistical relations of molecular aberrations and gene expressions in NCI-60 cell lines

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    Li Shyh-Dar

    2011-11-01

    Full Text Available Abstract Background Cancer cells harbor a large number of molecular alterations such as mutations, amplifications and deletions on DNA sequences and epigenetic changes on DNA methylations. These aberrations may dysregulate gene expressions, which in turn drive the malignancy of tumors. Deciphering the causal and statistical relations of molecular aberrations and gene expressions is critical for understanding the molecular mechanisms of clinical phenotypes. Results In this work, we proposed a computational method to reconstruct association modules containing driver aberrations, passenger mRNA or microRNA expressions, and putative regulators that mediate the effects from drivers to passengers. By applying the module-finding algorithm to the integrated datasets of NCI-60 cancer cell lines, we found that gene expressions were driven by diverse molecular aberrations including chromosomal segments' copy number variations, gene mutations and DNA methylations, microRNA expressions, and the expressions of transcription factors. In-silico validation indicated that passenger genes were enriched with the regulator binding motifs, functional categories or pathways where the drivers were involved, and co-citations with the driver/regulator genes. Moreover, 6 of 11 predicted MYB targets were down-regulated in an MYB-siRNA treated leukemia cell line. In addition, microRNA expressions were driven by distinct mechanisms from mRNA expressions. Conclusions The results provide rich mechanistic information regarding molecular aberrations and gene expressions in cancer genomes. This kind of integrative analysis will become an important tool for the diagnosis and treatment of cancer in the era of personalized medicine.

  15. Aberrant expression of Wnt antagonist SFRP1 in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    BU Xian-min; ZHAO Cheng-hai; DAI Xian-wei

    2008-01-01

    @@ Pancreatic cancer is one of the malignant tumor with a very poor prognosis. Both genetic and epigenetic alterations are involved in the pathogenetic mechanisms of pancreatic cancer. Hypermethylation and subsequent loss of expression of some tumor suppressor genes and tumor-related genes occur frequently in pancreatic cancer, such as loss of expression of pl6,1 RASSF1A,2 SOCS-1,3 and hMLH14 genes were repoted.

  16. Aberrant Expression of Notch1 in Cervical Cancer

    Institute of Scientific and Technical Information of China (English)

    Li Sun; Qimin Zhan; Wenhua Zhang; Yongmei Song; Tong Tong

    2007-01-01

    OBJECTIVE To investigate the putative role of the Notch1 receptor in cervical cancer carcinogenesis and progression.METHODS The expression of the Notch1 protein was analyzed by a Western-blotting approach in 40 cervical cancer and 30 normal cervical tissues.Some tissues were examined using RT-PCR To determine Mrna levels.Celluar localization of the Notch1 protein in the paraffin-embedded cervical tissues was also analyzed by immunohistochemistry.RESULTS The Notch1 protein was detected in all 30 normal cervical tissues.In contrast.only 6 samples of 40 cervical cancer tissues showed Notch1 expression.The level of the Notch1 protein expression was significantly lower in cervical cancer tissues than that in normal tissue samples.In agreement with these observations.levels of Notch1 Mrna were found to be substantially down-regulated in cervical cancer tissues.In the immunohistochemistry staining assay,the Notch1 protein was shown to localize predominantly in the cytoplasm and nucleoli of the normal cervical squamous epithelium of the cervix,but no staining was observed in the cervical cancer cells.Notch1 expression was observed to correlate with the clinical disease stage.but there were no correlations with age,tumor size,grade or lymph node metastasis (P>0.05).The levels of Notchl protein expression were significantly higher in early stages(I~lla,66.7%) compared to those in the advanced stages (Iib~IV,12.6%)(P=0.001).CONCLUSION Notch1 may play a role as a tumor suppressor in cervical tumorigenesis.Determination of Notch1 expression may be helpful for preoperative diagnosis and accuracy of staging.But its clinical use for cervical cancer requires further investigation.

  17. From DNA Copy Number to Gene Expression: Local aberrations, Trisomies and Monosomies

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    Shay, Tal

    The goal of my PhD research was to study the effect of DNA copy number changes on gene expression. DNA copy number aberrations may be local, encompassing several genes, or on the level of an entire chromosome, such as trisomy and monosomy. The main dataset I studied was of Glioblastoma, obtained in the framework of a collaboration, but I worked also with public datasets of cancer and Down's Syndrome. The molecular basis of expression changes in Glioblastoma. Glioblastoma is the most common and aggressive type of primary brain tumors in adults. In collaboration with Prof. Hegi (CHUV, Switzerland), we analyzed a rich Glioblastoma dataset including clinical information, DNA copy number (array CGH) and expression profiles. We explored the correlation between DNA copy number and gene expression at the level of chromosomal arms and local genomic aberrations. We detected known amplification and over expression of oncogenes, as well as deletion and down-regulation of tumor suppressor genes. We exploited that information to map alterations of pathways that are known to be disrupted in Glioblastoma, and tried to characterize samples that have no known alteration in any of the studied pathways. Identifying local DNA aberrations of biological significance. Many types of tumors exhibit chromosomal losses or gains and local amplifications and deletions. A region that is aberrant in many tumors, or whose copy number change is stronger, is more likely to be clinically relevant, and not just a by-product of genetic instability. We developed a novel method that defines and prioritizes aberrations by formalizing these intuitions. The method scores each aberration by the fraction of patients harboring it, its length and its amplitude, and assesses the significance of the score by comparing it to a null distribution obtained by permutations. This approach detects genetic locations that are significantly aberrant, generating a 'genomic aberration profile' for each sample. The 'genomic

  18. Aberrant ADAM10 expression correlates with osteosarcoma progression

    Science.gov (United States)

    2014-01-01

    Background Osteosarcoma is the most common type of bone cancer and is notorious for its rapid progression. The Notch signaling pathway has recently been shown to be involved in osteosarcoma. As a major sheddase of Notch receptors, ADAM10 has been implicated in many types of cancers, but its role in osteosarcoma has not been investigated. Previous studies have shown that the expression of CD31 was significantly elevated in metastatic osteosarcoma; however, its expression in nonmetastatic groups is not known. In addition, the mysterious multinucleated giant cell in giant cell-rich osteosarcoma was previously regarded as an osteoclast-like cell, but its exact identity is unclear. Method Tissue chip samples from 40 cases of nonmetastatic osteosarcoma were stained for cytoplasmic ADAM10, activated Notch1 and CD31. Osteoclasts in tumor sections were also stained for tartrate-resistant acid phosphatase (TRAP). Results Immunofluorescence staining revealed that ADAM10 expression significantly increased with the progression of osteosarcoma as well as in osteoblastic osteosarcoma, whereas the expression of the Notch intracellular domain (NICD) and CD31 was not significantly altered between different pathological stages. In addition, multinucleated giant cells in giant cell-rich osteosarcoma were also found to coexpress CD31, ADAM10 and NICD, but were negative for TRAP staining. Conclusions Our results highlight the importance of ADAM10 in the progression of osteosarcoma and suggest that the protein might be a potential therapeutic target in osteosarcoma treatment. This study also demonstrates that the multinucleated giant cell is an angiogenic tumor cell, rather than an osteoclast, and involves ADAM10/Notch1 signaling activation. PMID:24548763

  19. Aberrant phenotypes of transgenic mice expressing dimeric human erythropoietin

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    Yun Seong-Jo

    2012-01-01

    Full Text Available Abstract Background Dimeric human erythropoietin (dHuEPO peptides are reported to exhibit significantly higher biological activity than the monomeric form of recombinant EPO. The objective of this study was to produce transgenic (tg mice expressing dHuEPO and to investigate the characteristics of these mice. Methods A dHuEPO-expressing vector under the control of the goat beta-casein promoter, which produced a dimer of human EPO molecules linked by a 2-amino acid peptide linker (Asp-Ile, was constructed and injected into 1-cell fertilized embryos by microinjection. Mice were screened using genomic DNA samples obtained from tail biopsies. Blood samples were obtained by heart puncture using heparinized tubes, and hematologic parameters were assessed. Using the microarray analysis tool, we analyzed differences in gene expression in the spleens of tg and control mice. Results A high rate of spontaneous abortion or death of the offspring was observed in the recipients of dHuEPO embryos. We obtained 3 founder lines (#4, #11, and #47 of tg mice expressing the dHuEPO gene. However, only one founder line showed stable germline integration and transmission, subsequently establishing the only transgenic line (#11. We obtained 2 F1 mice and 3 F2 mice from line #11. The dHuEPO protein could not be obtained because of repeated spontaneous abortions in the tg mice. Tg mice exhibited symptoms such as short lifespan and abnormal blood composition. The red blood cell count, white blood cell count, and hematocrit levels in the tg mice were remarkably higher than those in the control mice. The spleens of the tg mice (F1 and F2 females were 11- and -21-fold larger than those of the control mice. Microarray analysis revealed 2,672 spleen-derived candidate genes; more genes were downregulated than upregulated (849/764. Reverse transcriptase-polymerase chain reaction (RT-PCR and quantitative real-time PCR (qRT-PCR were used for validating the results of the microarray

  20. Aberrant maspin expression in gallbladder epithelium is associated with intestinal metaplasia in patients with cholelithiasis

    Science.gov (United States)

    Maesawa, C; Ogasawara, S; Yashima‐Abo, A; Kimura, T; Kotani, K; Masuda, S; Nagata, Y; Iwaya, T; Suzuki, K; Oyake, T; Akiyama, Y; Kawamura, H; Masuda, T

    2006-01-01

    Objective Aberrant expression of maspin protein related to DNA hypomethylation in the promoter region is frequently observed in gallbladder carcinomas, whereas the non‐tumorous gallbladder epithelium is maspin negative. We investigated maspin expression in non‐tumorous gallbladder epithelium in patients with cholelithiasis. Methods An immunohistochemical study of maspin expression was performed in 69 patients with cholelithiasis and 30 patients with gastric cancer without cholelithiasis. Results Immunoreactivity for maspin was observed in focal and patchy regions of the gallbladder epithelium. Positive immunoreactivity for maspin was significantly associated with the presence of intestinal metaplasia in patients with cholelithiasis (p<0.05). Conclusion The high incidence of aberrant maspin expression in both intestinal metaplasia and carcinoma of the gallbladder supports the assumption that intestinal metaplasia of the gallbladder may predispose to gallbladder carcinoma. PMID:16505288

  1. Aberrant expression of nuclear matrix proteins during HMBA-induced differentiation of gastric cancer cells

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM: To investigate the aberrant expression of nuclear matrix proteins in human gastric cancer cells before and after hexamethylene bisacetamide (HMBA) treatment.METHODS: Proteomics analysis of differential nuclear matrix proteins was performed by two dimensional electrophoresis polyacrylamide gel electrophoresis and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.The expression levels of three nuclear matrix proteins were further confirmed by Western blotting and their location...

  2. Dysregulation of microRNA expression drives aberrant DNA hypermethylation in basal-like breast cancer.

    Science.gov (United States)

    Sandhu, Rupninder; Rivenbark, Ashley G; Mackler, Randi M; Livasy, Chad A; Coleman, William B

    2014-02-01

    Basal-like breast cancers frequently express aberrant DNA hypermethylation associated with concurrent silencing of specific genes secondary to DNMT3b overexpression and DNMT hyperactivity. DNMT3b is known to be post-transcriptionally regulated by microRNAs. The objective of the current study was to determine the role of microRNA dysregulation in the molecular mechanism governing DNMT3b overexpression in primary breast cancers that express aberrant DNA hypermethylation. The expression of microRNAs (miRs) that regulate (miR-29a, miR-29b, miR-29c, miR-148a and miR-148b) or are predicted to regulate DNMT3b (miR‑26a, miR-26b, miR-203 and miR-222) were evaluated among 70 primary breast cancers (36 luminal A-like, 13 luminal B-like, 5 HER2‑enriched, 16 basal-like) and 18 normal mammoplasty tissues. Significantly reduced expression of miR-29c distinguished basal-like breast cancers from other breast cancer molecular subtypes. The expression of aberrant DNA hypermethylation was determined in a subset of 33 breast cancers (6 luminal A-like, 6 luminal B-like, 5 HER2-enriched and 16 basal-like) through examination of methylation‑sensitive biomarker gene expression (CEACAM6, CDH1, CST6, ESR1, GNA11, MUC1, MYB, TFF3 and SCNN1A), 11/33 (33%) cancers exhibited aberrant DNA hypermethylation including 9/16 (56%) basal-like cancers, but only 2/17 (12%) non-basal-like cancers (luminal A-like, n=1; HER2-enriched, n=1). Breast cancers with aberrant DNA hypermethylation express diminished levels of miR-29a, miR-29b, miR-26a, miR-26b, miR-148a and miR-148b compared to cancers lacking aberrant DNA hypermethylation. A total of 7/9 (78%) basal-like breast cancers with aberrant DNA hypermethylation exhibit diminished levels of ≥6 regulatory miRs. The results show that i) reduced expression of miR-29c is characteristic of basal-like breast cancers, ii) miR and methylation-sensitive gene expression patterns identify two subsets of basal-like breast cancers, and iii) the subset of basal

  3. Aberrant expression of connexin 26 is associated with lung metastasis of colorectal cancer.

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    Ezumi, Koji; Yamamoto, Hirofumi; Murata, Kohei; Higashiyama, Masahiko; Damdinsuren, Bazarragchaa; Nakamura, Yurika; Kyo, Naganori; Okami, Jiro; Ngan, Chew Yee; Takemasa, Ichiro; Ikeda, Masataka; Sekimoto, Mitsugu; Matsuura, Nariaki; Nojima, Hiroshi; Monden, Morito

    2008-02-01

    Connexin 26 (Cx26) is one of the gap junction-forming family members classically considered to be tumor suppressors. However, recent studies show association of elevated expression of Cx26 with poor prognosis in several human malignancies. Furthermore, Cx26 has been observed to be indispensable to spontaneous metastasis of melanoma cells. Here, we assessed Cx26 expression in primary colorectal cancer (CRC) and the metastatic lesions to elucidate its role in metastasis. Cx26 expression was assessed in 25 adenomas, 167 CRCs, and normal mucosa, together with the metastatic lesions. Normal mucosa and adenomatous tissue expressed Cx26 mainly in the plasma membrane, whereas cancer cells mostly contained Cx26 in the cytoplasm. The incidence of aberrant Cx26 expression varied widely in CRC (mean, 49.5 +/- 35.5%), and the expression levels were confirmed by Western blot and quantitative reverse transcription-PCR. Clinicopathologic survey revealed association of high expression with less differentiated histology and venous invasion (P = 0.0053 and P = 0.0084, respectively). Notably, high Cx26 expression was associated with shorter disease-free survival and shorter lung metastasis-free survival in 154 curatively resected CRC sets (P = 0.041 and P = 0.028, respectively). Survey of metastatic lesions revealed that lung metastasis, but not liver and lymph nodes metastases, expressed higher Cx26 than the CRC series or corresponding primary CRCs (P < 0.0001 and P = 0.0001, respectively). These findings suggest that aberrant expression of Cx26 plays an essential role in lung metastasis. Thus, Cx26 is a promising therapeutic target, particularly for CRC patients who develop lung metastasis.

  4. Aberrant epigenetic changes and gene expression in cloned cattle dying around birth

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    Zhao Dingsheng

    2008-02-01

    Full Text Available Abstract Background Aberrant reprogramming of donor somatic cell nuclei may result in many severe problems in animal cloning. To assess the extent of abnormal epigenetic modifications and gene expression in clones, we simultaneously examined DNA methylation, histone H4 acetylation and expression of six genes (β-actin, VEGF, oct4, TERT, H19 and Igf2 and a repetitive sequence (art2 in five organs (heart, liver, spleen, lung and kidney from two cloned cattle groups that had died at different stages. In the ED group (early death, n = 3, the cloned cattle died in the perinatal period. The cattle in the LD group (late death, n = 3 died after the perinatal period. Normally reproduced cattle served as a control group (n = 3. Results Aberrant DNA methylation, histone H4 acetylation and gene expression were observed in both cloned groups. The ED group showed relatively fewer severe DNA methylation abnormalities (p Conclusion Deaths of clones may be ascribed to abnormal expression of a very limited number of genes.

  5. Hypermethylation and aberrant expression of secreted fizzled-related protein genes in pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Xian-Min Bu; Cheng-Hai Zhao; Ning Zhang; Feng Gao; Shuai Lin; Xian-Wei Dai

    2008-01-01

    AIM:To determine the methylation status and aberrant expression of some secreted frizzled-related protein (SFRP) genes in pancreatic cancer and explore their role in pancreatic carcinogenesis. METHODS:Methylation status and expression of SFRP genes were detected by methylation-specific PCR (MSPCR) and reverse-transcription PCR (RT-PCR) respectively. RESULTS:The frequencies of methylation for SFRP genes 1,2,4,5 were 70%, 48.3%,60% and 76.7% in pancreatic cancer samples, and 21.7%, 20%,10% and 36.7% in matched cancer adjacent normal tissue samples,respectively (χ2=28.23,P<0.0001 for SFRP gene 1; χ2=10.71,P=0.001 for SFRP gene 2;χ2=32.97,P<0.0001 for SFRP gene 4;χ2=19.55,P<0.0001 for SFRP gene 5). Expression loss of SFRP genes 1,2,4 and 5 was found in 65%,40%,55% and 71.7% of 60 pancreatic cancer samples, and 25%,15%,18.3% and 31.7% of matched cancer adjacent normal tissue samples,respectively (χ2=19.39,P<0.0001 for SFRP gene 1;χ2=9.40,P=0.002 for SFRP gene 2;χ2=17.37,P<0.0001 for SFRP gene 4;χ2=19.22,P<0.0001 for SFRP gene 5).SFRP gene 1 was methylated but not expressed in PC-3 and PANC-1,SFRP gene 2 was methylated but not expressed in PANC-1 and CFPAC-1,SFRP gene 4 was methylated but not expressed in PC-3,and SFRP gene 5 was methylated but not expressed in CFPAC-1. CONCLUSION:Hypermethylation and aberrant expression of SFRP genes are common in pancreatic cancer,which may be involved in pancreatic carcinogenesis.

  6. Aberrant expression of krüppel-like factor 6 protein in colorectal cancers

    Institute of Scientific and Technical Information of China (English)

    Yong-Gu Cho; Byung-Jun Choi; Jae-Whie Song; Su-Young Kim; Suk-Woo Nam; Sug-Hyung Lee; Nam-Jin Yoo; Jung-Young Lee; Won-Sang Park

    2006-01-01

    AIM: To investigate whether kr(U)ppel-like factor 6 (KLF6)plays an important role in the development and/or progression of colorectal cancer.METHODS: A total of 123 formalin-fixed and paraffinembedded colorectal cancer specimens were analyzed by immunohistochemistry using tissue microarray for the expression of KLF6 protein. The specimens were collected over a 3-year period in the laboratories at our large teaching hospital in Seoul, Republic of Korea. The correlation of KLF6 expression with clinicopathologic parameters was analyzed by x2 test and Bartholomew test.RESULTS: Normal colonic epithelium showed weak to moderate expression of KLF6, whereas reduced KLF 6expression or loss of KLF6 expression was seen in 45(36.6%) of the 123 colorectal carcinoma specimens.Interestingly, aberrant expression of KLF6 was detected in 25 (43.1%) of 58 cases with metastasis to regional lymph node and in 31 (47.0%) of 66 tumors more than 5 cm in size. Statistically, loss of KLF6 expression was significantly associated with tumor size (P<0.05).However, there was no significant correlation between KLF6 expression and Dukes' stage (Bartholomew test,P> 0.05), tumor location and lymph node metastasis (x2test, P> 0.05).CONCLUSION: Loss of KLF6 expression may be a common and early event in colorectal carcinogenesis.

  7. Sonic Hedgehog Signaling Affected by Promoter Hypermethylation Induces Aberrant Gli2 Expression in Spina Bifida.

    Science.gov (United States)

    Lu, Xiao-Lin; Wang, Li; Chang, Shao-Yan; Shangguan, Shao-Fang; Wang, Zhen; Wu, Li-Hua; Zou, Ji-Zhen; Xiao, Ping; Li, Rui; Bao, Yi-Hua; Qiu, Z-Y; Zhang, Ting

    2016-10-01

    GLI2 is a key mediator of the sonic hedgehog (Shh) signaling pathway and plays an important role in neural tube development during vertebrate embryogenesis; however, the role of gli2 in human folate-related neural tube defects remains unclear. In this study, we compared methylation status and polymorphisms of gli2 between spina bifida patients and a control group to explore the underlying mechanisms related to folate deficiency in spina bifida. No single nucleotide polymorphism was found to be significantly different between the two groups, although gli2 methylation levels were significantly increased in spina bifida samples, accompanied by aberrant GLI2 expression. Moreover, a prominent negative correlation was found between the folate level in brain tissue and the gli2 methylation status (r = -0.41, P = 0.014), and gli2 hypermethylation increased the risk of spina bifida with an odds ratio of 12.45 (95 % confidence interval: 2.71-57.22, P = 0.001). In addition, we established a cell model to illustrate the effect of gli2 expression and the accessibility of chromatin affected by methylation. High gli2 and gli1 mRNA expression was detected in 5-Aza-treated cells, while gli2 hypermethylation resulted in chromatin inaccessibility and a reduced association with nuclear proteins containing transcriptional factors. More meaningful to the pathway, the effect gene of the Shh pathway, gli1, was found to have a reduced level of expression along with a decreased expression of gli2 in our cell model. Aberrant high methylation resulted in the low expression of gli2 in spina bifida, which was affected by the change in chromatin status and the capacity of transcription factor binding.

  8. Gene expression and epigenetic aberrations in F1-placentas fathered by obese males.

    Science.gov (United States)

    Mitchell, Megan; Strick, Reiner; Strissel, Pamela L; Dittrich, Ralf; McPherson, Nicole O; Lane, Michelle; Pliushch, Galyna; Potabattula, Ramya; Haaf, Thomas; El Hajj, Nady

    2017-02-10

    Gene expression and/or epigenetic deregulation may have consequences for sperm and blastocysts, as well as for the placenta, together potentially contributing to problems observed in offspring. We previously demonstrated specific perturbations of fertilization, blastocyst formation, implantation, as well as aberrant glucose metabolism and adiposity in offspring using a mouse model of paternal obesity. The current investigation analyzed gene expression and methylation of specific CpG residues in F1 placentas of pregnancies fathered by obese and normal-weight male mice, using real-time PCR and bisulfite pyrosequencing. Our aim was to determine if paternal obesity deregulated placental gene expression and DNA methylation when compared to normal-weight males. Gene methylation of sperm DNA was analyzed and compared to placentas to address epigenetic transmission. Of the 10 paternally expressed genes (Pegs), 11 genes important for development and transport of nutrients, and the long-terminal repeat Intracisternal A particle (IAP) elements, derived from a member of the class II endogenous retroviral gene family, we observed a significant effect of paternal diet-induced obesity on deregulated expression of Peg3, Peg9, Peg10, and the nutrient transporter gene Slc38a2, and aberrant DNA methylation of the Peg9 promoter in F1 placental tissue. Epigenetic changes in Peg9 were also found in sperm from obese fathers. We therefore propose that paternal obesity renders changes in gene expression and/or methylation throughout the placental genome, which could contribute to the reproductive problems related to fertility and to the metabolic, long-term health impact on offspring.

  9. 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; Chauhan, Subhash C

    2012-11-01

    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.

  10. Aberrant expression of Sonic hedgehog signaling in Peutz-Jeghers syndrome.

    Science.gov (United States)

    Xu, Xiaoping; Su, Juan; Li, Ran; Wang, Yadong; Zeng, Di; Wu, Baoping

    2016-04-01

    The SHH signaling pathway is critical for gastrointestinal development and organic patterning, and dysregulation of SHH pathway molecules has been detected in multiple gastrointestinal neoplasms. This study investigated the role of the SHH signaling pathway in PJS. Expression of SHH, PTCH, and GLI1 was examined by real-time PCR and immunohistochemistry in 20 normal tissues and 75 colorectal lesions (25 PJPs, 25 adenomas, and 25 adenocarcinomas). Expression of SHH, PTCH, and GLI1 mRNA was higher in PJPs than in normal tissue (P < .05) and gradually increased along the PJP-adenoma-adenocarcinoma sequence (P < .05). Immunostaining indicated that SHH expression was present in 60% of PJPs, 72% of adenomas, and 84% of carcinomas, whereas 68% of PJPs, 72% of adenomas, and 88% of carcinomas exhibited cytoplasmic expression of PTCH. Moreover, high GLI1 expression was detected in 56% of PJPs, 64% of adenomas, and 80% of carcinomas; and high nuclear expression of GLI1 was observed in 8 adenomas with atypia and 15 carcinomas. Increased SHH, PTCH, and GLI1 protein correlated positively with tumor grade (P = .012, P = .003, and P = .007, respectively), tumor depth (P = .024, P = .007, and P = .01), and lymph node metastasis (P = .05, P = .015, and P = .005). This study identified aberrant expression of SHH pathway molecules in PJS, and the findings may supply a novel mechanism for the development of PJ polyps.

  11. Aberrant and unstable expression of immunoglobulin genes in persons infected with human immunodeficiency virus.

    Science.gov (United States)

    Bessudo, A; Rassenti, L; Havlir, D; Richman, D; Feigal, E; Kipps, T J

    1998-08-15

    We examined the IgM VH gene subgroup use-distribution in serial blood samples of 37 human immunodeficiency virus (HIV)-infected patients and a group of HIV-seronegative healthy adults. The IgM VH gene repertoires of healthy adults were relatively similar to one another and were stable over time. In contrast, individuals infected with HIV had IgM VH gene repertoires that were significantly more heterogeneous and unstable. Persons at early stages of HIV infection generally had abnormal expression levels of Ig VH3 genes and frequently displayed marked fluctuations in the relative expression levels of this VH gene subgroup over time. In contrast, persons with established acquired immunodeficiency syndrome (AIDS) had a significantly lower incidence of abnormalities in Ig VH3 expression levels, although continued to display abnormalities and instability in the expression levels of the smaller Ig VH gene subgroups. Moreover, the skewing and/or fluctuations in the expressed-IgM VH gene repertoire appeared greatest for persons at earlier stages of HIV infection. These studies show that persons infected with HIV have aberrant and unstable expression of immunoglobulin genes suggestive of a high degree humoral immune dysregulation and ongoing humoral immune responses to HIV-associated antigens and superantigens.

  12. Regulation of MYC gene expression by aberrant Wnt/β-catenin signaling in colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Sherri; Rennoll; Gregory; Yochum

    2015-01-01

    The Wnt/β-catenin signaling pathway controls intestinal homeostasis and mutations in components of this pathway are prevalent in human colorectal cancers(CRCs).These mutations lead to inappropriate expression of genes controlled by Wnt responsive DNA elements(WREs). T-cell factor/Lymphoid enhancer factor transcription factors bind WREs and recruit the β-catenin transcriptional co-activator to activate target gene expression. Deregulated expression of the c-MYC proto-oncogene(MYC) by aberrant Wnt/β-catenin signaling drives colorectal carcinogenesis. In this review,we discuss the current literature pertaining to the identification and characterization of WREs that control oncogenic MYC expression in CRCs. A common theme has emerged whereby these WREs often map distally to the MYC genomic locus and control MYC gene expression through long-range chromatin loops with the MYC proximal promoter. We propose that by determining which of these WREs is critical for CRC pathogenesis,novel strategies can be developed to treat individuals suffering from this disease.

  13. Aberrant Expression of Xist in Aborted Porcine Fetuses Derived from Somatic Cell Nuclear Transfer Embryos

    Directory of Open Access Journals (Sweden)

    Lin Yuan

    2014-11-01

    Full Text Available Cloned pigs generated by somatic cell nuclear transfer (SCNT show a greater ratio of early abortion during mid-gestation than normal controls. X-linked genes have been demonstrated to be important for the development of cloned embryos. To determine the relationship between the expression of X-linked genes and abortion of cloned porcine fetuses, the expression of X-linked genes were investigated by quantitative real-time polymerase chain reaction (q-PCR and the methylation status of Xist DMR was performed by bisulfate-specific PCR (BSP. q-PCR analysis indicated that there was aberrant expression of X-linked genes, especially the upregulated expression of Xist in both female and male aborted fetuses compared to control fetuses. Results of BSP suggested that hypomethylation of Xist occurred in aborted fetuses, whether male or female. These results suggest that the abnormal expression of Xist may be associated with the abortion of fetuses derived from somatic cell nuclear transfer embryos.

  14. Aberrant Expression and Secretion of Heat Shock Protein 90 in Patients with Bullous Pemphigoid

    Science.gov (United States)

    Tukaj, Stefan; Kleszczyński, Konrad; Vafia, Katerina; Groth, Stephanie; Meyersburg, Damian; Trzonkowski, Piotr; Ludwig, Ralf J.; Zillikens, Detlef; Schmidt, Enno; Fischer, Tobias W.; Kasperkiewicz, Michael

    2013-01-01

    The cell stress chaperone heat shock protein 90 (Hsp90) has been implicated in inflammatory responses and its inhibition has proven successful in different mouse models of autoimmune diseases, including epidermolysis bullosa acquisita. Here, we investigated expression levels and secretory responses of Hsp90 in patients with bullous pemphigoid (BP), the most common subepidermal autoimmune blistering skin disease. In comparison to healthy controls, the following observations were made: (i) Hsp90 was highly expressed in the skin of BP patients, whereas its serum levels were decreased and inversely associated with IgG autoantibody levels against the NC16A immunodominant region of the BP180 autoantigen, (ii) in contrast, neither aberrant levels of circulating Hsp90 nor any correlation of this protein with serum autoantibodies was found in a control cohort of autoimmune bullous disease patients with pemphigus vulgaris, (iii) Hsp90 was highly expressed in and restrictedly released from peripheral blood mononuclear cells of BP patients, and (iv) Hsp90 was potently induced in and restrictedly secreted from human keratinocyte (HaCaT) cells by BP serum and isolated anti-BP180 NC16A IgG autoantibodies, respectively. Our results reveal an upregulated Hsp90 expression at the site of inflammation and an autoantibody-mediated dysregulation of the intracellular and extracellular distribution of this chaperone in BP patients. These findings suggest that Hsp90 may play a pathophysiological role and represent a novel potential treatment target in BP. PMID:23936217

  15. Aberrant Expression of miRNA and mRNAs in Lesioned Tissues of Graves' Disease

    Directory of Open Access Journals (Sweden)

    Qiu Qin

    2015-03-01

    Full Text Available Background and Aims: Abnormal microRNA (miRNA expression is found in many diseases including autoimmune diseases. However, little is known about the role of miRNA regulation in Graves' disease (GD. Here, we simultaneously detected different expressions of miRNA and mRNAs in thyroid tissues via a high-throughput transcriptomics approach, known as microarray, in order to reveal the relationship between aberrant expression of miRNAs and mRNAs spectrum and GD. Methods: Totally 7 specimens of thyroid tissue from 4 GD patients and 3 controls were obtained by surgery for microarray analysis. Then, 30 thyroid specimens (18 GD and 12 controls were also collected for further validation by quantitative real-time PCR ( qRT-PCR . Results: Statistical analysis showed that the expressions of 5 specific miRNA were increased significantly while those of other 18 miRNA were decreased in thyroid tissue of GD patients (FC≥1.3 or≤0.77 and pConclusion: Our study highlights the possibility that miRNA-target gene network may be involved in the pathogenesis of GD and could provide new insights into understanding the pathophysiological mechanisms of GD.

  16. Aberrant Expression of Posterior HOX Genes in Well Differentiated Histotypes of Thyroid Cancers

    Directory of Open Access Journals (Sweden)

    Gerardo Botti

    2013-11-01

    Full Text Available Molecular etiology of thyroid cancers has been widely studied, and several molecular alterations have been identified mainly associated with follicular and papillary histotypes. However, the molecular bases of the complex pathogenesis of thyroid carcinomas remain poorly understood. HOX genes regulate normal embryonic development, cell differentiation and other critical processes in eukaryotic cell life. Several studies have shown that HOX genes play a role in neoplastic transformation of several human tissues. In particular, the genes belonging to HOX paralogous group 13 seem to hold a relevant role in both tumor development and progression. We have identified a significant prognostic role of HOX D13 in pancreatic cancer and we have recently showed the strong and progressive over-expression of HOX C13 in melanoma metastases and deregulation of HOX B13 expression in bladder cancers. In this study we have investigated, by immunohistochemisty and quantitative Real Time PCR, the HOX paralogous group 13 genes/proteins expression in thyroid cancer evolution and progression, also evaluating its ability to discriminate between main histotypes. Our results showed an aberrant expression, both at gene and protein level, of all members belonging to paralogous group 13 (HOX A13, HOX B13, HOX C13 and HOX D13 in adenoma, papillary and follicular thyroid cancers samples. The data suggest a potential role of HOX paralogous group 13 genes in pathogenesis and differential diagnosis of thyroid cancers.

  17. Immunohistochemical expression of aberrant Notch-1 signaling in vitiligo: an implication for pathogenesis.

    Science.gov (United States)

    Seleit, Iman; Bakry, Ola Ahmed; Abdou, Asmaa Gaber; Dawoud, Noha Mohammed

    2014-06-01

    The etiopathogenetic mechanisms leading to pigment loss in vitiligo are not fully understood. Notch signaling is required for development and maintenance of melanocyte lineage and acts as a key component among keratinocyte-melanocyte interactions. The current study aimed to investigate the possible role of Notch signaling and its effect on the whole melanocyte lineage in vitiligo and correlating it with the different clinicopathologic parameters. Using immunohistochemical technique, Notch-1 expression was evaluated in 50 lesional and 20 perilesional biopsies of patients with vitiligo in comparison with 20 normal skin biopsies as a control group. Lesional biopsies were stained with human melanoma black-45 and tyrosinase-related protein-2 to demonstrate the melanocyte lineage. Membranous and/or nuclear expression of Notch-1 was in favor of control and perilesional skin, whereas cytoplasmic expression appeared only in vitiliginous lesions (P vitiligo were associated with mild to moderate Notch-1 intensity, whereas generalized vitiligo was associated with strong intensity of expression (P = .02). In conclusion, Notch-1 signaling is inactivated in vitiligo with consequent loss of epidermal and/or follicular active melanocytes. Aberrant Notch signaling in vitiliginous white hair and acral and segmental vitiligo may be the cause of their treatment resistance.

  18. Aberrant expression and secretion of heat shock protein 90 in patients with bullous pemphigoid.

    Directory of Open Access Journals (Sweden)

    Stefan Tukaj

    Full Text Available The cell stress chaperone heat shock protein 90 (Hsp90 has been implicated in inflammatory responses and its inhibition has proven successful in different mouse models of autoimmune diseases, including epidermolysis bullosa acquisita. Here, we investigated expression levels and secretory responses of Hsp90 in patients with bullous pemphigoid (BP, the most common subepidermal autoimmune blistering skin disease. In comparison to healthy controls, the following observations were made: (i Hsp90 was highly expressed in the skin of BP patients, whereas its serum levels were decreased and inversely associated with IgG autoantibody levels against the NC16A immunodominant region of the BP180 autoantigen, (ii in contrast, neither aberrant levels of circulating Hsp90 nor any correlation of this protein with serum autoantibodies was found in a control cohort of autoimmune bullous disease patients with pemphigus vulgaris, (iii Hsp90 was highly expressed in and restrictedly released from peripheral blood mononuclear cells of BP patients, and (iv Hsp90 was potently induced in and restrictedly secreted from human keratinocyte (HaCaT cells by BP serum and isolated anti-BP180 NC16A IgG autoantibodies, respectively. Our results reveal an upregulated Hsp90 expression at the site of inflammation and an autoantibody-mediated dysregulation of the intracellular and extracellular distribution of this chaperone in BP patients. These findings suggest that Hsp90 may play a pathophysiological role and represent a novel potential treatment target in BP.

  19. Aberrant microRNA expression in patients with painful peripheral neuropathies.

    Science.gov (United States)

    Leinders, Mathias; Üçeyler, Nurcan; Thomann, Anna; Sommer, Claudia

    2017-09-15

    Changes in the neuro-immune balance play a major role in the induction and maintenance of neuropathic pain. We recently reported pathophysiologically relevant alterations in skin and sural nerve cytokine expression in peripheral neuropathies of different etiologies. Immune processes and cytokine expression are under tight control of microRNAs (miRNAs). To identify potential master switches in the neuro-immune balance, we aimed at characterizing inflammation-regulating miRNA profiles in patients with peripheral neuropathies. In an unselected patient cohort with polyneuropathies of different etiologies seen at our neuromuscular center between 2014 and 2015, we determined the systemic and local relative expression of miR-21-5p, miR-146a, and miR-155. In white blood cells we found higher miR-21 (pneuropathies. In painful neuropathies, skin biopsies from the lower leg had reduced miR-146a (pneuropathies are associated with aberrant miRNA expression in white blood cells, sural nerve, and skin. These miRNA patterns may help to identify factors that determine the painfulness of peripheral neuropathies and lead to druggable targets. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. RDX induces aberrant expression of microRNAs in mouse brain and liver.

    Science.gov (United States)

    Zhang, Baohong; Pan, Xiaoping

    2009-02-01

    Although microRNAs (miRNAs) have been found to play an important role in many biological and metabolic processes, their functions in animal response to environmental toxicant exposure are largely unknown. We used hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX), a common environmental contaminant, as a toxicant stressor to investigate toxicant-induced changes in miRNA expression in B6C3F1 mice and the potential mechanism of RDX-induced toxic action. B6C3F1 mice were fed diets with or without 5 mg/kg RDX for 28 days. After the feeding trials, we isolated RNAs from both brain and liver tissues and analyzed the expression profiles of 567 known mouse miRNAs using microarray and quantitative real-time polymerase chain reaction technologies. RDX exposure induced significant changes in miRNA expression profiles. A total of 113 miRNAs, belonging to 75 families, showed significantly altered expression patterns after RDX exposure. Of the 113 miRNAs, 10 were significantly up-regulated and 3 were significantly down-regulated (p RDX exposure. Specifically, expression of seven miRNAs was up-regulated in the brain but down-regulated in the liver or up-regulated in the liver but down-regulated in the brain (p < 0.01). Many aberrantly expressed miRNAs were related to various cancers, toxicant-metabolizing enzymes, and neurotoxicity. We found a significant up-regulation of oncogenic miRNAs and a significant down-regulation of tumor-suppressing miRNAs, which included let-7, miR-17-92, miR-10b, miR-15, miR-16, miR-26, and miR-181. Environmental toxicant exposure alters the expression of a suite of miRNAs.

  1. Aberrant gene expression patterns in extraembryonic tissue from cloned porcine embryos.

    Science.gov (United States)

    Park, Mi-Ryung; Im, Gi-Sun; Kim, Sung Woo; Hwang, Seongsoo; Park, Jae-Hong; Kim, Hyun; Do, Yoon Jung; Park, Soo Bon; Yang, Bo-Suck; Song, Young Min; Cho, Jae-Hyeon; Ko, Yeoung-Gyu

    2013-06-01

    The abnormal development of embryos reconstructed by somatic cell nuclear transfer (SCNT) is considered to be associated with consequent changes in gene expression following errors in epigenetic reprogramming. In this study, we carried out SCNT using donor fibroblast cells derived from 3-way hybrids (Landrace×Duroc×Yorkshire). A total of 655 SCNT embryos were transferred, and 6.97±2.3 cloned fetuses were successfully recovered from three surrogates at gestational day 30. An analysis of the 6.97±2.3 cloned embryos revealed that most had severe extraembryonic defects. The extraembryonic tissue from the SCNT embryos was abnormally small compared with that of the control. To investigate the differentially expressed genes between the SCNT and control extraembryonic tissues, we compared the gene expression profiles of the extraembryonic tissues from gestational day 30 cloned pig embryos with those from the control using an annealing control primer-based GeneFishing polymerase chain reaction. As a result, we found that a total of 50 genes were differentially expressed by utilizing 120 ACPs, 38 genes of which were known. Among them, 26 genes were up-regulated, whereas 12 genes were down-regulated. Real-time RT-PCR showed that apoptosis-related genes were expressed significantly higher in SCNT extraembryonic tissue than in the control, whereas metabolism-related genes were expressed at significantly lower levels in the SCNT extraembryonic tissue. These observations strongly indicate that early gestational death of SCNT embryo is caused, at least in part, by the disruption of developing extraembryonic tissues as a result of aberrant gene expression, which results in abnormal apoptosis and metabolism.

  2. Chemokine receptor co-expression reveals aberrantly distributed TH effector memory cells in GPA patients.

    Science.gov (United States)

    Lintermans, Lucas L; Rutgers, Abraham; Stegeman, Coen A; Heeringa, Peter; Abdulahad, Wayel H

    2017-06-14

    Persistent expansion of circulating CD4(+) effector memory T cells (TEM) in patients with granulomatosis with polyangiitis (GPA) suggests their fundamental role in disease pathogenesis. Recent studies have shown that distinct functional CD4(+) TEM cell subsets can be identified based on expression patterns of chemokine receptors. The current study aimed to determine different CD4(+) TEM cell subsets based on chemokine receptor expression in peripheral blood of GPA patients. Identification of particular circulating CD4(+) TEM cells subsets may reveal distinct contributions of specific CD4(+) TEM subsets to the disease pathogenesis in GPA. Peripheral blood of 63 GPA patients in remission and 42 age- and sex-matched healthy controls was stained immediately after blood withdrawal with fluorochrome-conjugated antibodies for cell surface markers (CD3, CD4, CD45RO) and chemokine receptors (CCR4, CCR6, CCR7, CRTh2, CXCR3) followed by flow cytometry analysis. CD4(+) TEM memory cells (CD3(+)CD4(+)CD45RO(+)CCR7(-)) were gated, and the expression patterns of chemokine receptors CXCR3(+)CCR4(-)CCR6(-)CRTh2(-), CXCR3(-)CCR4(+)CCR6(-)CRTh2(+), CXCR3(-)CCR4(+)CCR6(+)CRTh2(-), and CXCR3(+)CCR4(-)CCR6(+)CRTh2(-) were used to distinguish TEM1, TEM2, TEM17, and TEM17.1 cells, respectively. The percentage of CD4(+) TEM cells was significantly increased in GPA patients in remission compared to HCs. Chemokine receptor co-expression analysis within the CD4(+) TEM cell population demonstrated a significant increase in the proportion of TEM17 cells with a concomitant significant decrease in the TEM1 cells in GPA patients compared to HC. The percentage of TEM17 cells correlated negatively with TEM1 cells in GPA patients. Moreover, the circulating proportion of TEM17 cells showed a positive correlation with the number of organs involved and an association with the tendency to relapse in GPA patients. Interestingly, the aberrant distribution of TEM1 and TEM17 cells is modulated in CMV

  3. Aberrant neuronal activity-induced signaling and gene expression in a mouse model of RASopathy

    Science.gov (United States)

    Nakhaei-Rad, Saeideh; Montenegro-Venegas, Carolina; Pina-Fernández, Eneko; Marini, Claudia; Santos, Monica; Ahmadian, Mohammad R.; Stork, Oliver; Zenker, Martin

    2017-01-01

    Noonan syndrome (NS) is characterized by reduced growth, craniofacial abnormalities, congenital heart defects, and variable cognitive deficits. NS belongs to the RASopathies, genetic conditions linked to mutations in components and regulators of the Ras signaling pathway. Approximately 50% of NS cases are caused by mutations in PTPN11. However, the molecular mechanisms underlying cognitive impairments in NS patients are still poorly understood. Here, we report the generation and characterization of a new conditional mouse strain that expresses the overactive Ptpn11D61Y allele only in the forebrain. Unlike mice with a global expression of this mutation, this strain is viable and without severe systemic phenotype, but shows lower exploratory activity and reduced memory specificity, which is in line with a causal role of disturbed neuronal Ptpn11 signaling in the development of NS-linked cognitive deficits. To explore the underlying mechanisms we investigated the neuronal activity-regulated Ras signaling in brains and neuronal cultures derived from this model. We observed an altered surface expression and trafficking of synaptic glutamate receptors, which are crucial for hippocampal neuronal plasticity. Furthermore, we show that the neuronal activity-induced ERK signaling, as well as the consecutive regulation of gene expression are strongly perturbed. Microarray-based hippocampal gene expression profiling revealed profound differences in the basal state and upon stimulation of neuronal activity. The neuronal activity-dependent gene regulation was strongly attenuated in Ptpn11D61Y neurons. In silico analysis of functional networks revealed changes in the cellular signaling beyond the dysregulation of Ras/MAPK signaling that is nearly exclusively discussed in the context of NS at present. Importantly, changes in PI3K/AKT/mTOR and JAK/STAT signaling were experimentally confirmed. In summary, this study uncovers aberrant neuronal activity-induced signaling and regulation

  4. Aberrant RNA splicing in cancer; expression changes and driver mutations of splicing factor genes.

    Science.gov (United States)

    Sveen, A; Kilpinen, S; Ruusulehto, A; Lothe, R A; Skotheim, R I

    2016-05-12

    Alternative splicing is a widespread process contributing to structural transcript variation and proteome diversity. In cancer, the splicing process is commonly disrupted, resulting in both functional and non-functional end-products. Cancer-specific splicing events are known to contribute to disease progression; however, the dysregulated splicing patterns found on a genome-wide scale have until recently been less well-studied. In this review, we provide an overview of aberrant RNA splicing and its regulation in cancer. We then focus on the executors of the splicing process. Based on a comprehensive catalog of splicing factor encoding genes and analyses of available gene expression and somatic mutation data, we identify cancer-associated patterns of dysregulation. Splicing factor genes are shown to be significantly differentially expressed between cancer and corresponding normal samples, and to have reduced inter-individual expression variation in cancer. Furthermore, we identify enrichment of predicted cancer-critical genes among the splicing factors. In addition to previously described oncogenic splicing factor genes, we propose 24 novel cancer-critical splicing factors predicted from somatic mutations.

  5. Do aberrant crypt foci have predictive value for the occurrence of colorectal tumours? Potential of gene expression profiling in tumours

    NARCIS (Netherlands)

    Wijnands, M.V.W.; Erk, van M.J.; Doornbos, R.P.; Krul, C.A.M.; Woutersen, R.A.

    2004-01-01

    The effects of different dietary compounds on the formation of aberrant crypt foci (ACF) and colorectal tumours and on the expression of a selection of genes were studied in rats. Azoxymethane-treated male F344 rats were fed either a control diet or a diet containing 10% wheat bran (WB), 0.2%

  6. Differential Isotope Labeling Strategy for Determining the Structure of Myristoylated Recoverin by NMR Spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, Toshiyuki [University of Tsukuba, Center for Tsukuba Advanced Research Alliance and Institute of Applied Biochemistry (Japan); Ames, James B. [Stanford University School of Medicine, Department of Neurobiology (United States); Kainosho, Masatsune [Tokyo Metropolitan University, Department of Chemistry (Japan); Stryer, Lubert [Stanford University School of Medicine, Department of Neurobiology (United States); Ikura, Mitsuhiko [University of Tsukuba, Center for Tsukuba Advanced Research Alliance and Institute of Applied Biochemistry (Japan)

    1998-02-15

    The three-dimensional solution structure of recombinant bovine myristoylated recoverin in the Ca2+-free state has been refined using an array of isotope-assisted multidimensional heteronuclear NMR techniques. In some experiments, the myristoyl group covalently attached to the protein N-terminus was labeled with 13C and the protein was unlabeled or vice versa; in others, both were 13C-labeled. This differential labeling strategy was essential for structural refinement and can be applied to other acylated proteins. Stereospecific assignments of 41 pairs of {beta}-methylene protons and 48 methyl groups of valine and leucine were included in the structure refinement. The refined structure was constructed using a total of 3679 experimental NMR restraints, comprising 3242 approximate interproton distance restraints (including 153 between the myristoyl group and the polypeptide), 140 distance restraints for 70 backbone hydrogen bonds, and 297 torsion angle restraints. The atomic rms deviations about the averaged minimized coordinate positions for the secondary structure region of the N-terminal and C-terminal domains are 0.44 {+-} 0.07 and 0.55 {+-} 0.18 A for backbone atoms, and 1.09 {+-} 0.07 and 1.10 {+-} 0.15 A for all heavy atoms, respectively. The refined structure allows for a detailed analysis of the myristoyl binding pocket. The myristoyl group is in a slightly bent conformation: the average distance between C1 and C14 atoms of the myristoyl group is 14.6 A. Hydrophobic residues Leu28, Trp31, and Tyr32 form a cluster that interacts with the front end of the myristoyl group (C1-C8), whereas residues Phe49, Phe56, Tyr86, Val87, and Leu90 interact with the tail end (C9-C14). The relatively deep hydrophobic pocket that binds the myristoyl group (C14:0) could also accommodate other naturally occurring acyl groups such as C12:0, C14:1, and C14:2 chains.

  7. Genetic background of aberrant thermogenin expression (UCP1) in obesity leading to metabolic syndrome.

    Science.gov (United States)

    Stosio, Małgorzata; Witkowicz, Agata; Kowalska, Anna; Karabon, Lidia

    2016-12-31

    Cardiovascular and metabolic disturbances individually and interdependently lead to chronic pathological conditions observed in cardio-metabolic diseases (CMDs). In Europe, the morbidity and mortality caused by cardiovascular disease are the highest among all diseases. Therefore, it seems important to search for new and alternative therapies for obesity, which is the main cause of type 2 diabetes (T2D) and cardiovascular disease (CD). Great attention has been paid to the role of brown adipose tissue in fat burning and the possibility of transformation of the white adipose tissue to cells with brown adipose tissue function as a potential form of treatment of obesity. The best-characterized marker of brown adipose tissue is uncoupling protein 1 (UCP1), which has the ability to dissipate energy as heat in the process called non-shivering thermogenesis. Numerous studies have shown that altered expression of this protein can lead to disturbances in fat metabolism. One possible reason for the aberrant expression of UCP1 may be inherited variations in the gene encoding that protein. Therefore, several studies investigating the role of polymorphisms in the gene encoding UCP1 in susceptibility to obesity or metabolic syndrome have been performed. Here we summarize the results of studies describing the associations between the UCP1 gene polymorphisms A-3826G, A-1766G, Met229Leu and Ala64Thr and polymorphism Trp64Arg in the β3-AR gene, their correlations and their associations with the occurrence of metabolic syndrome.

  8. Clinical Omics Analysis of Colorectal Cancer Incorporating Copy Number Aberrations and Gene Expression Data

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    Tsuyoshi Yoshida

    2010-07-01

    Full Text Available Background: Colorectal cancer (CRC is one of the most frequently occurring cancers in Japan, and thus a wide range of methods have been deployed to study the molecular mechanisms of CRC. In this study, we performed a comprehensive analysis of CRC, incorporating copy number aberration (CRC and gene expression data. For the last four years, we have been collecting data from CRC cases and organizing the information as an “omics” study by integrating many kinds of analysis into a single comprehensive investigation. In our previous studies, we had experienced difficulty in finding genes related to CRC, as we observed higher noise levels in the expression data than in the data for other cancers. Because chromosomal aberrations are often observed in CRC, here, we have performed a combination of CNA analysis and expression analysis in order to identify some new genes responsible for CRC. This study was performed as part of the Clinical Omics Database Project at Tokyo Medical and Dental University. The purpose of this study was to investigate the mechanism of genetic instability in CRC by this combination of expression analysis and CNA, and to establish a new method for the diagnosis and treatment of CRC. Materials and methods: Comprehensive gene expression analysis was performed on 79 CRC cases using an Affymetrix Gene Chip, and comprehensive CNA analysis was performed using an Affymetrix DNA Sty array. To avoid the contamination of cancer tissue with normal cells, laser micro-dissection was performed before DNA/RNA extraction. Data analysis was performed using original software written in the R language. Result: We observed a high percentage of CNA in colorectal cancer, including copy number gains at 7, 8q, 13 and 20q, and copy number losses at 8p, 17p and 18. Gene expression analysis provided many candidates for CRC-related genes, but their association with CRC did not reach the level of statistical significance. The combination of CNA and gene

  9. Aberrant expression and localization of deoxyribonucleic acid methyltransferase 3B in endometriotic stromal cells.

    Science.gov (United States)

    Dyson, Matthew T; Kakinuma, Toshiyuki; Pavone, Mary Ellen; Monsivais, Diana; Navarro, Antonia; Malpani, Saurabh S; Ono, Masanori; Bulun, Serdar E

    2015-10-01

    To define the expression and function of DNA methyltransferases (DNMTs) in response to decidualizing stimuli in endometriotic cells compared with healthy endometrial stroma. Basic science. University research center. Premenopausal women with or without endometriosis. Primary cultures of stromal cells from healthy endometrium (E-IUM) or endometriomas (E-OSIS) were subjected to in vitro decidualization (IVD) using 1 μM medroxyprogesterone acetate, 35 nM 17β-estradiol, and 0.05 mM 8-Br-cAMP. Expression of DNMT1, DNMT3A, and DNMT3B in E-IUM and E-OSIS were assessed by quantitative real-time polymerase chain reaction and immunoblotting. Recruitment of DNMT3B to the promoters of steroidogenic factor 1 (SF-1) and estrogen receptor α (ESR1) was examined by chromatin immunoprecipitation. IVD treatment reduced DNMT3B messenger RNA (74%) and protein levels (81%) only in E-IUM; DNMT1 and DNMT3A were unchanged in both cell types. Significantly more DNMT3B bound to the SF-1 promoter in E-IUM compared with E-OSIS, and IVD treatment reduced binding in E-IUM to levels similar to those in E-OSIS. Enrichment of DNMT3B across 3 ESR1 promoters was reduced in E-IUM after IVD, although the more-distal promoter showed increased DNMT3B enrichment in E-OSIS after IVD. The inability to downregulate DNMT3B expression in E-OSIS may contribute to an aberrant epigenetic fingerprint that misdirects gene expression in endometriosis and contributes to its altered response to steroid hormones. Copyright © 2015 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  10. The aberrant expression and localization of DNA methyltransferase 3B in endometriotic stromal cells

    Science.gov (United States)

    Dyson, Matthew T.; Kakinuma, Toshiyuki; Pavone, Mary Ellen; Monsivais, Diana; Navarro, Antonia; Malpani, Saurabh S.; Ono, Masanori; Bulun, Serdar E.

    2015-01-01

    Objective To define the expression and function of DNA methyltransferases (DNMTs) in response to decidualizing stimuli in endometriotic cells compared with healthy endometrial stroma. Design Basic science. Setting University research center. Patients Premenopausal women with or without endometriosis. Interventions Primary cultures of stromal cells from healthy endometrium (E-IUM) or endometriomas (E-OSIS) were subjected to in vitro decidualization (IVD) using 1 µM medroxyprogesterone acetate, 35 nM 17β-estradiol, and 0.05 mM 8-Br-cAMP. Main Outcome Measure(s) DNMT1, DNMT3A, and DNMT3B expression in E-IUM and E-OSIS were assessed by qRT-PCR and immunoblotting. DNMT3B recruitment to the promoters of steroidogenic factor 1 (SF-1) and estrogen receptor α (ESR1) was examined by chromatin immunoprecipitation Results IVD treatment reduced DNMT3B mRNA (74%) and protein levels (81%) only in E-IUM. DNMT1 and DNMT3A were unchanged in both cell types. Significantly more DNMT3B bound to the SF-1 promoter in E-IUM compared with E-OSIS, and IVD treatment reduced binding in E-IUM to levels similar to those in E-OSIS. DNMT3B enrichment across three ESR1 promoters was reduced in E-IUM after IVD, although the more distal promoter showed increased DNMT3B enrichment in E-OSIS after IVD. Conclusions The inability to downregulate DNMT3B expression in E-OSIS may contribute to an aberrant epigenetic fingerprint that misdirects gene expression in endometriosis and contributes to its altered response to steroid hormones. PMID:26239024

  11. MicroRNAs and their therapeutic potential for human diseases: aberrant microRNA expression in Alzheimer's disease brains.

    Science.gov (United States)

    Satoh, Jun-ichi

    2010-01-01

    MicroRNAs (miRNAs) are a group of small noncoding RNAs that regulate translational repression of multiple target mRNAs. The miRNAs in a whole cell regulate greater than 30% of all protein-coding genes. The vast majority of presently identified miRNAs are expressed in the brain in a spatially and temporally controlled manner. They play a key role in neuronal development, differentiation, and synaptic plasticity. However, at present, the pathological implications of deregulated miRNA expression in neurodegenerative diseases remain largely unknown. This review will briefly summarize recent studies that focus attention on aberrant miRNA expression in Alzheimer's disease brains.

  12. Aberrant expression of nuclear HDAC3 and cytoplasmic CDH1 predict a poor prognosis for patients with pancreatic cancer.

    Science.gov (United States)

    Jiao, Feng; Hu, Hai; Han, Ting; Zhuo, Meng; Yuan, Cuncun; Yang, Haiyan; Wang, Lei; Wang, Liwei

    2016-03-29

    Previous studies showed that aberrant CDH1 or/and HDAC3 localization is essential for the progression of some human cancers. Here, we investigate the prognostic significance of aberrant CDH1 and HDAC3 localization in 84 pancreatic cancer patients. Our results show that increases in both membrane and cytoplasmic CDH1 correlate with lymph node metastasis (P = 0.026 and P 0.05). Multivariate analysis showed that nuclear HDAC3 and cytoplasmic CDH1 (P = 0.001 and P = 0.010, respectively), as well as tumor differentiation (P = 0.009) are independent prognostic factors. Most importantly, patients with high co-expression of nuclear HDAC3 and cytoplasmic CDH1 had shorter survival times (P CDH1 have independent prognostic value in pancreatic cancer and provide novel targets for prognostic therapeutics.

  13. Novel Genomic Aberrations in Testicular Germ Cell Tumors by Array-CGH, and Associated Gene Expression Changes

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    Rolf I. Skotheim

    2006-01-01

    Full Text Available Introduction: Testicular germ cell tumors of adolescent and young adult men (TGCTs generally have near triploid and complex karyotypes. The actual genes driving the tumorigenesis remain essentially to be identified. Materials and Methods: To determine the detailed DNA copy number changes, and investigate their impact on gene expression levels, we performed an integrated microarray profiling of TGCT genomes and transcriptomes. We analyzed 17 TGCTs, three precursor lesions, and the embryonal carcinoma cell lines, NTERA2 and 2102Ep, by comparative genomic hybridization microarrays (array-CGH, and integrated the data with transcriptome profiles of the same samples. Results: The gain of chromosome arm 12p was, as expected, the most common aberration, and we found CCND2, CD9, GAPD, GDF3, NANOG, and TEAD4 to be the therein most highly over-expressed genes. Additional frequent genomic aberrations revealed some shorter chromosomal segments, which are novel to TGCT, as well as known aberrations for which we here refined boundaries. These include gains from 7p15.2 and 21q22.2, and losses of 4p16.3 and 22q13.3. Integration of DNA copy number information to gene expression profiles identified that BRCC3, FOS, MLLT11, NES, and RAC1 may act as novel oncogenes in TGCT. Similarly, DDX26, ERCC5, FZD4, NME4, OPTN, and RB1 were both lost and under-expressed genes, and are thus putative TGCT suppressor genes. Conclusion: This first genome-wide integrated array-CGH and gene expression profiling of TGCT provides novel insights into the genome biology underlying testicular tumorigenesis.

  14. Cell cycle aberration in ameloblastoma and adenomatoid odontogenic tumor: As evidenced by the expression of p53 and survivin.

    Science.gov (United States)

    Shaikh, Zulfin; Niranjan, K C

    2015-01-01

    p53 and survivin are involved in cell cycle progression and inhibition of apoptosis, respectively. Survivin is a unique protein which functions in progression of cell division and inhibits apoptosis leading to cell proliferation and cell survival. According to the literature, mutation of p53 leads to promotion of survivin function. Thus, the importance of cell cycle aberration and uncontrolled proliferation resulting from mutation of p53 and up-regulation of survivin is discussed. To assess the role of p53 and survivin in ameloblastoma and adenomatoid odontogenic tumor (AOT). The percentages of positive tumor cells were considered for statistical evaluation. Nuclear labeling index for p53 and nuclear, cytoplasmic and combined labeling index for survivin was obtained from the stained slides. Immunohistochemical expression of p53 and survivin was done qualitatively and quantitatively in 25 cases each of ameloblastoma and AOT. Mann-Whitney U-test, Wilcoxon signed ranks test and Pearson's correlation test. Quantitatively, p53 and survivin expression was statistically significant in AOT (P = 0.003) and qualitatively, in ameloblastoma (P = 0.004). Survivin expression was significant (P = 0.002) between the study groups unlike that of p53 (P = 0.554). There was no much difference in p53 expression in ameloblastoma and AOT suggestive of cell cycle aberration in both the odontogenic tumors, but significant difference in survivin expression in ameloblastoma and AOT with higher percentage of positive cells in ameloblastoma may be indicative of an aggressive behavior of ameloblastoma.

  15. Mouse Lymphoblastic Leukemias Induced by Aberrant Prdm14 Expression Demonstrate Widespread Copy Number Alterations Also Found in Human ALL

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    Stephen J. Simko

    2012-10-01

    Full Text Available Aberrant expression and activation of oncogenes in somatic cells has been associated with cancer initiation. Required for reacquisition of pluripotency in the developing germ cell, PRDM14 initiates lymphoblastic leukemia when misexpressed in murine bone marrow. Activation of pluripotency in somatic cells can lead to aneuploidy and copy number alterations during iPS cell generation, and we hypothesized that PRDM14-induced lymphoblastic leukemias would demonstrate significant chromosomal damage. High-resolution oligo array comparative genomic hybridization demonstrated infrequent aneuploidy but frequent amplification and deletion, with amplifications occurring in a 5:1 ratio with deletions. Many deletions (i.e., Cdkn2a, Ebf1, Pax5, Ikzf1 involved B-cell development genes and tumor suppressor genes, recapitulating deletions occurring in human leukemia. Pathways opposing senescence were frequently deactivated via Cdkn2a deletion or Tbx2 amplification, with corollary gene expression. Additionally, gene expression studies of abnormal pre-leukemic B-precursors showed downregulation of genes involved in chromosomal stability (i.e., Xrcc6 and failure to upregulate DNA repair pathways. We propose a model of leukemogenesis, triggered by pluripotency genes like Prdm14, which involves ongoing DNA damage and failure to activate non-homologous end-joining secondary to aberrant gene expression.

  16. Differences in aberrant expression and splicing of sarcomeric proteins in the myotonic dystrophies DM1 and DM2

    OpenAIRE

    2010-01-01

    Aberrant transcription and mRNA processing of multiple genes due to RNA-mediated toxic gain-of-function has been suggested to cause the complex phenotype in myotonic dystrophies type 1 and 2 (DM1 and DM2). However, the molecular basis of muscle weakness and wasting and the different pattern of muscle involvement in DM1 and DM2 are not well understood. We have analyzed the mRNA expression of genes encoding muscle-specific proteins and transcription factors by microarray profiling and studied s...

  17. Aberrant expression of Notch1, HES1, and DTX1 genes in glioblastoma formalin-fixed paraffin-embedded tissues.

    Science.gov (United States)

    Narayanappa, Rajeswari; Rout, Pritilata; Aithal, Madhuri G S; Chand, Ashis Kumar

    2016-05-01

    Glioblastoma is the most common malignant brain tumor accounting for more than 54 % of all gliomas. Despite aggressive treatments, median survival remains less than 1 year. This might be due to the unavailability of effective molecular diagnostic markers and targeted therapy. Thus, it is essential to discover molecular mechanisms underlying disease by identifying dysregulated pathways involved in tumorigenesis. Notch signaling is one such pathway which plays an important role in determining cell fates. Since it is found to play a critical role in many cancers, we investigated the role of Notch genes in glioblastoma with an aim to identify biomarkers that can improve diagnosis. Using real-time PCR, we assessed the expression of Notch genes including receptors (Notch1, Notch2, Notch3, and Notch4), ligands (JAG1, JAG2, and DLL3), downstream targets (HES1 and HEY2), regulator Deltex1 (DTX1), inhibitor NUMB along with transcriptional co-activator MAML1, and a component of gamma-secretase complex APH1A in 15 formalin-fixed paraffin-embedded (FFPE) patient samples. Relative quantification was done by the 2(-ΔΔCt) method; the data are presented as fold change in gene expression normalized to an internal control gene and relative to the calibrator. The data revealed aberrant expression of Notch genes in glioblastoma compared to normal brain. More than 85 % of samples showed high Notch1 (P = 0.0397) gene expression and low HES1 (P = 0.011) and DTX1 (P = 0.0001) gene expression. Our results clearly show aberrant expression of Notch genes in glioblastoma which can be used as putative biomarkers together with histopathological observation to improve diagnosis, therapeutic strategies, and patient prognosis.

  18. Oligoamine analogues in combination with 2-difluoromethylornithine synergistically induce re-expression of aberrantly silenced tumour-suppressor genes.

    Science.gov (United States)

    Wu, Yu; Steinbergs, Nora; Murray-Stewart, Tracy; Marton, Laurence J; Casero, Robert A

    2012-03-15

    Epigenetic gene silencing is an important mechanism in the initiation and progression of cancer. Abnormal DNA CpG island hypermethylation and histone modifications are involved in aberrant silencing of tumour-suppressor genes. LSD1 (lysine-specific demethylase 1) was the first enzyme identified to specifically demethylate H3K4 (Lys(4) of histone H3). Methylated H3K4 is an important mark associated with transcriptional activation. The flavin adenine dinucleotide-binding amine oxidase domain of LSD1 is homologous with two polyamine oxidases, SMO (spermine oxidase) and APAO (N(1)-acetylpolyamine oxidase). We have demonstrated previously that long-chain polyamine analogues, the oligoamines, are inhibitors of LSD1. In the present paper we report the synergistic effects of specific oligoamines in combination with DFMO (2-difluoromethylornithine), an inhibitor of ornithine decarboxylase, in human colorectal cancer cells. DFMO treatment depletes natural polyamines and increases the uptake of exogenous polyamines. The combination of oligoamines and DFMO results in a synergistic re-expression of aberrantly silenced tumour-suppressor genes, including SFRP2 (secreted frizzled-related protein 2), which encodes a Wnt signalling pathway antagonist and plays an anti-tumorigenic role in colorectal cancer. The treatment-induced re-expression of SFRP2 is associated with increased H3K4me2 (di-methyl H3K4) in the gene promoter. The combination of LSD1-inhibiting oligoamines and DFMO represents a novel approach to epigenetic therapy of cancer.

  19. Differences in aberrant expression and splicing of sarcomeric proteins in the myotonic dystrophies DM1 and DM2.

    Science.gov (United States)

    Vihola, Anna; Bachinski, Linda L; Sirito, Mario; Olufemi, Shodimu-Emmanuel; Hajibashi, Shohrae; Baggerly, Keith A; Raheem, Olayinka; Haapasalo, Hannu; Suominen, Tiina; Holmlund-Hampf, Jeanette; Paetau, Anders; Cardani, Rosanna; Meola, Giovanni; Kalimo, Hannu; Edström, Lars; Krahe, Ralf; Udd, Bjarne

    2010-04-01

    Aberrant transcription and mRNA processing of multiple genes due to RNA-mediated toxic gain-of-function has been suggested to cause the complex phenotype in myotonic dystrophies type 1 and 2 (DM1 and DM2). However, the molecular basis of muscle weakness and wasting and the different pattern of muscle involvement in DM1 and DM2 are not well understood. We have analyzed the mRNA expression of genes encoding muscle-specific proteins and transcription factors by microarray profiling and studied selected genes for abnormal splicing. A subset of the abnormally regulated genes was further analyzed at the protein level. TNNT3 and LDB3 showed abnormal splicing with significant differences in proportions between DM2 and DM1. The differential abnormal splicing patterns for TNNT3 and LDB3 appeared more pronounced in DM2 relative to DM1 and are among the first molecular differences reported between the two diseases. In addition to these specific differences, the majority of the analyzed genes showed an overall increased expression at the mRNA level. In particular, there was a more global abnormality of all different myosin isoforms in both DM1 and DM2 with increased transcript levels and a differential pattern of protein expression. Atrophic fibers in DM2 patients expressed only the fast myosin isoform, while in DM1 patients they co-expressed fast and slow isoforms. However, there was no increase of total myosin protein levels, suggesting that aberrant protein translation and/or turnover may also be involved.

  20. Enhanced expression of ADCY1 underlies aberrant neuronal signalling and behaviour in a syndromic autism model

    Science.gov (United States)

    Sethna, Ferzin; Feng, Wei; Ding, Qi; Robison, Alfred J.; Feng, Yue; Wang, Hongbing

    2017-01-01

    Fragile X syndrome (FXS), caused by the loss of functional FMRP, is a leading cause of autism. Neurons lacking FMRP show aberrant mRNA translation and intracellular signalling. Here, we identify that, in Fmr1 knockout neurons, type 1 adenylyl cyclase (Adcy1) mRNA translation is enhanced, leading to excessive production of ADCY1 protein and insensitivity to neuronal stimulation. Genetic reduction of Adcy1 normalizes the aberrant ERK1/2- and PI3K-mediated signalling, attenuates excessive protein synthesis and corrects dendritic spine abnormality in Fmr1 knockout mice. Genetic reduction of Adcy1 also ameliorates autism-related symptoms including repetitive behaviour, defective social interaction and audiogenic seizures. Moreover, peripheral administration of NB001, an experimental compound that preferentially suppresses ADCY1 activity over other ADCY subtypes, attenuates the behavioural abnormalities in Fmr1 knockout mice. These results demonstrate a connection between the elevated Adcy1 translation and abnormal ERK1/2 signalling and behavioural symptoms in FXS. PMID:28218269

  1. TGF-{beta}-stimulated aberrant expression of class III {beta}-tubulin via the ERK signaling pathway in cultured retinal pigment epithelial cells

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    Chung, Eun Jee [Department of Ophthalmology, National Health Insurance Corporation Ilsan Hospital, Gyeonggi-do (Korea, Republic of); Chun, Ji Na; Jung, Sun-Ah [Konyang University Myunggok Medical Research Institute, Kim' s Eye Hospital, Konyang University College of Medicine, Seoul (Korea, Republic of); Cho, Jin Won [Department of Biology, Yonsei University, 134 Shinchon-dong, Seodaemun-gu, Seoul 120-749 (Korea, Republic of); Lee, Joon H., E-mail: joonhlee@konyang.ac.kr [Konyang University Myunggok Medical Research Institute, Kim' s Eye Hospital, Konyang University College of Medicine, Seoul (Korea, Republic of)

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer TGF-{beta} induces aberrant expression of {beta}III in RPE cells via the ERK pathway. Black-Right-Pointing-Pointer TGF-{beta} increases O-GlcNAc modification of {beta}III in RPE cells. Black-Right-Pointing-Pointer Mature RPE cells have the capacity to express a neuron-associated gene by TGF-{beta}. -- Abstract: The class III {beta}-tubulin isotype ({beta}{sub III}) is expressed exclusively by neurons within the normal human retina and is not present in normal retinal pigment epithelial (RPE) cells in situ or in the early phase of primary cultures. However, aberrant expression of class III {beta}-tubulin has been observed in passaged RPE cells and RPE cells with dedifferentiated morphology in pathologic epiretinal membranes from idiopathic macular pucker, proliferative vitreoretinopathy (PVR) and proliferative diabetic retinopathy (PDR). Transforming growth factor-{beta} (TGF-{beta}) has been implicated in dedifferentiation of RPE cells and has a critical role in the development of proliferative vitreoretinal diseases. Here, we investigated the potential effects of TGF-{beta} on the aberrant expression of class III {beta}-tubulin and the intracellular signaling pathway mediating these changes. TGF-{beta}-induced aberrant expression and O-linked-{beta}-N-acetylglucosamine (O-GlcNac) modification of class III {beta}-tubulin in cultured RPE cells as determined using Western blotting, RT-PCR and immunocytochemistry. TGF-{beta} also stimulated phosphorylation of ERK. TGF-{beta}-induced aberrant expression of class III {beta}-tubulin was significantly reduced by pretreatment with U0126, an inhibitor of ERK phosphorylation. Our findings indicate that TGF-{beta} stimulated aberrant expression of class III {beta}-tubulin via activation of the ERK signaling pathway. These data demonstrate that mature RPE cells have the capacity to express a neuron-associated gene in response to TGF-{beta} stimulation and provide useful information

  2. Potassium Channel Ether à go-go1 Is Aberrantly Expressed in Human Liposarcoma and Promotes Tumorigenesis

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    Jin Wu

    2014-01-01

    Full Text Available The ether à go-go1 (Eag1 channel is overexpressed in a variety of cancers. However, the expression and function of Eag1 in liposarcoma are poorly understood. In the present study, the mRNA expression of Eag1 in different adipose tissue samples was examined by real-time PCR. Then, the protein expression of Eag1 in 131 different adipose tissues from 109 patients was detected by immunohistochemistry. Next, the associations between Eag1 expression and clinicopathological features of liposarcoma were analyzed. In addition, the effects of Eag1 on liposarcoma cell proliferation and cycle were evaluated by CCK-8, colony formation, xenograft mouse model, and flow cytometry, respectively. Finally, the activation of p38 mitogen-activated protein kinase (MAPK was detected by Western blot analysis to explain the detailed mechanisms of oncogenic potential of Eag1 in liposarcoma. It was found that Eag1 was aberrantly expressed in over 67% liposarcomas, with a higher frequency than in lipoma, hyperplasia, inflammation, and normal adipose tissues. However, Eag1 expression was not correlated with clinicopathological features of liposarcoma. Eag1 inhibitor imipramine or Eag1-shRNA significantly suppressed the proliferation of liposarcoma cells in vitro and in vivo, accompanying with accumulation of cells in the G1 phase. These results suggest that Eag1 plays an important role in regulating the proliferation and cell cycle of liposarcoma cells and might be a potential therapeutic target for liposarcoma.

  3. Aberrant expression of ether à go-go potassium channel in colorectal cancer patients and cell lines

    Institute of Scientific and Technical Information of China (English)

    Xiang-Wu Ding; Juan-Juan Yan; Ping An; Peng Lü; He-Sheng Luo

    2007-01-01

    AIM: To study the expression of ether à go-go (Eag1) potassium channel in colorectal cancer and the relation ship between their expression and clinico-pathological features.METHODS: The expression levels of Eag1 protein were determined in 76 cancer tissues with paired noncancerous matched tissues as well as 9 colorectal adenoma tissues by immunohistochemistry. Eag1 mRNA expression was detected in 13 colorectal cancer tissues with paired non-cancerous matched tissues and 4 colorectal adenoma tissues as well as two colorectal cancer cell lines (LoVo and HT-29) by reverse transcription PCR.RESULTS: The frequency of positive expression of Eag1 protein was 76.3% (58/76) and Eag1 mRNA was 76.9% (10/13) in colorectal cancer tissue. Expression level of Eag1 protein was dependent on the tumor size,lymphatic node metastasis, other organ metastases and Dukes' stage (P < 0.05), while not dependent on age,sex, site and degree of differentiation. Eag1 protein and mRNA were negative in normal colorectal tissue, and absolutely negative in colorectal adenomas except that one case was positively stained for Eag1 protein.CONCLUSION: Eag1 protein and mRNA are aberrantly expressed in colorectal cancer and occasionally expressed in colorectal adenoma. The high frequency of expression of Eag1 in tumors and the restriction of normal expression to the brain suggest the potential of this protein for diagnostic, prognostic and therapeutic purposes.

  4. Up-regulated expression and aberrant DNA methylation of LEP and SH3PXD2A in pre-eclampsia.

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    Yuqian Xiang

    Full Text Available The primary mechanism underlying pre-eclampsia (PE remains one of the most burning problems in the obstetrics and gynecology. In this study, we performed an expression profiling screen and detected 1312 genes that were differentially expressed (p1.5 in PE placentas, including LEP and SH3PXD2A. After validating the microarray results, we conducted the quantitative methylation analysis of LEP and SH3PXD2A in preeclamptic (n = 16 versus normal placentas (n = 16. Our results showed that many CpG sites close to the transcriptional start site (TSS of LEP gene were hypomethylated in placentas from pregnancies with PE compared with those of in controls, including the TSS position (p = 0.001, the binding sites of Sp1 (p = 1.57×10(-4, LP1 (p = 0.023 and CEBPα (p = 0.031. Luciferase reporter analysis confirmed the aberrant methylation of LEP promoter and CEBPα co-transfection had a role in the regulation of gene expression. Our results indicated the aberrant LEP promoter methylation was involved in the development of PE. We did not find a significant methylation differences between groups in the promoter region of SH3PXD2A, however, a CGI region in the gene body (CGI34 presented a higher methylation in preeclamptic placentas (p = 1.57×10(-4, which might promote the efficiency of gene transcription. We speculated that SH3PXD2A may take part in the pathogenesis of PE through its role in the regulation of trophoblast cell invasion in the period of placenta formation.

  5. Aberrant expression of zinc transporter ZIP4 (SLC39A4) significantly contributes to human pancreatic cancer pathogenesis and progression.

    Science.gov (United States)

    Li, Min; Zhang, Yuqing; Liu, Zijuan; Bharadwaj, Uddalak; Wang, Hao; Wang, Xinwen; Zhang, Sheng; Liuzzi, Juan P; Chang, Shou-Mei; Cousins, Robert J; Fisher, William E; Brunicardi, F Charles; Logsdon, Craig D; Chen, Changyi; Yao, Qizhi

    2007-11-20

    Zinc is an essential trace element and catalytic/structural component used by many metalloenzymes and transcription factors. Recent studies indicate a possible correlation of zinc levels with the cancer risk; however, the exact role of zinc and zinc transporters in cancer progression is unknown. We have observed that a zinc transporter, ZIP4 (SLC39A4), was substantially overexpressed in 16 of 17 (94%) clinical pancreatic adenocarcinoma specimens compared with the surrounding normal tissues, and ZIP4 mRNA expression was significantly higher in human pancreatic cancer cells than human pancreatic ductal epithelium (HPDE) cells. This indicates that aberrant ZIP4 up-regulation may contribute to the pancreatic cancer pathogenesis and progression. We studied the effects of ZIP4 overexpression in pancreatic cancer cell proliferation in vitro and pancreatic cancer progression in vivo. We found that forced expression of ZIP4 increased intracellular zinc levels, increased cell proliferation by 2-fold in vitro, and significantly increased tumor volume by 13-fold in the nude mice model with s.c. xenograft compared with the control cells. In the orthotopic nude mice model, overexpression of ZIP4 not only increased the primary tumor weight (7.2-fold), it also increased the peritoneal dissemination and ascites incidence. Moreover, increased cell proliferation and higher zinc content were also observed in the tumor tissues that overexpressed ZIP4. These data reveal an important outcome of aberrant ZIP4 expression in contributing to pancreatic cancer pathogenesis and progression. It may suggest a therapeutic strategy whereby ZIP4 is targeted to control pancreatic cancer growth.

  6. Expression of Leukemia-Associated Nup98 Fusion Proteins Generates an Aberrant Nuclear Envelope Phenotype.

    Directory of Open Access Journals (Sweden)

    Birthe Fahrenkrog

    Full Text Available Chromosomal translocations involving the nucleoporin NUP98 have been described in several hematopoietic malignancies, in particular acute myeloid leukemia (AML. In the resulting chimeric proteins, Nup98's N-terminal region is fused to the C-terminal region of about 30 different partners, including homeodomain (HD transcription factors. While transcriptional targets of distinct Nup98 chimeras related to immortalization are relatively well described, little is known about other potential cellular effects of these fusion proteins. By comparing the sub-nuclear localization of a large number of Nup98 fusions with HD and non-HD partners throughout the cell cycle we found that while all Nup98 chimeras were nuclear during interphase, only Nup98-HD fusion proteins exhibited a characteristic speckled appearance. During mitosis, only Nup98-HD fusions were concentrated on chromosomes. Despite the difference in localization, all tested Nup98 chimera provoked morphological alterations in the nuclear envelope (NE, in particular affecting the nuclear lamina and the lamina-associated polypeptide 2α (LAP2α. Importantly, such aberrations were not only observed in transiently transfected HeLa cells but also in mouse bone marrow cells immortalized by Nup98 fusions and in cells derived from leukemia patients harboring Nup98 fusions. Our findings unravel Nup98 fusion-associated NE alterations that may contribute to leukemogenesis.

  7. Expression of Leukemia-Associated Nup98 Fusion Proteins Generates an Aberrant Nuclear Envelope Phenotype.

    Science.gov (United States)

    Fahrenkrog, Birthe; Martinelli, Valérie; Nilles, Nadine; Fruhmann, Gernot; Chatel, Guillaume; Juge, Sabine; Sauder, Ursula; Di Giacomo, Danika; Mecucci, Cristina; Schwaller, Jürg

    2016-01-01

    Chromosomal translocations involving the nucleoporin NUP98 have been described in several hematopoietic malignancies, in particular acute myeloid leukemia (AML). In the resulting chimeric proteins, Nup98's N-terminal region is fused to the C-terminal region of about 30 different partners, including homeodomain (HD) transcription factors. While transcriptional targets of distinct Nup98 chimeras related to immortalization are relatively well described, little is known about other potential cellular effects of these fusion proteins. By comparing the sub-nuclear localization of a large number of Nup98 fusions with HD and non-HD partners throughout the cell cycle we found that while all Nup98 chimeras were nuclear during interphase, only Nup98-HD fusion proteins exhibited a characteristic speckled appearance. During mitosis, only Nup98-HD fusions were concentrated on chromosomes. Despite the difference in localization, all tested Nup98 chimera provoked morphological alterations in the nuclear envelope (NE), in particular affecting the nuclear lamina and the lamina-associated polypeptide 2α (LAP2α). Importantly, such aberrations were not only observed in transiently transfected HeLa cells but also in mouse bone marrow cells immortalized by Nup98 fusions and in cells derived from leukemia patients harboring Nup98 fusions. Our findings unravel Nup98 fusion-associated NE alterations that may contribute to leukemogenesis.

  8. Aberrant expressions of c-KIT and DOG-1 in mucinous and nonmucinous colorectal carcinomas and relation to clinicopathologic features and prognosis.

    Science.gov (United States)

    Foda, Abd Al-Rahman Mohammad; Mohamed, Mie Ali

    2015-10-01

    c-KIT and DOG-1 are 2 highly expressed proteins in gastrointestinal stromal tumors. Few studies had investigated c-KIT, but not DOG-1, expression in colorectal carcinoma (CRC). This study aims to investigate expressions of c-KIT and DOG-1 in colorectal mucinous carcinoma and nonmucinous carcinoma using manual tissue microarray technique. In this work, we studied tumor tissue specimens from 150 patients with colorectal mucinous (MA) and nonmucinous adenocarcinoma (NMA). High-density manual tissue microarrays were constructed using modified mechanical pencil tip technique, and immunohistochemistry for c-KIT and DOG-1 was done. We found that aberrant c-KIT expression was detected in 12 cases (8%); 6 cases (4%) showed strong expression. Aberrant DOG-1 expression was detected in 15 cases (10%); among them, only 4 cases (2.7%) showed strong expression. Nonmucinous adenocarcinoma showed a significantly high expression of c-KIT, but not DOG-1, than MA. Aberrant c-KIT and DOG-1 expressions were significantly unrelated but were associated with excessive microscopic abscess formation. Neither c-KIT nor DOG-1 expression showed a significant impact on disease-free survival or overall survival. In conclusion, aberrant c-KIT and DOG-1 expressions in CRC are rare events, either in NMA or MA. Nonmucinous adenocarcinoma showed a significantly higher expression of c-KIT, but not DOG-1, than MA. The expressions of both in CRC are significantly unrelated but are associated with microscopic abscess formation. Neither c-KIT nor DOG-1 expression showed a significant impact on disease-free survival or overall survival. So, c-KIT and DOG-1 immunostaining is not a cost-effective method of identifying patients with CRC who may benefit from treatment with tyrosine kinase inhibitors. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Aberrant Expression of TNF-α and TGF-β1 mRNA in Spontaneous Abortion

    Institute of Scientific and Technical Information of China (English)

    Ji-fen HU; Hong-chu BAO; Feng-chuan ZHU; Cai-ling YOU

    2004-01-01

    Objective To investigate the aberrant expressions of TNF-α and TGF-β1 in peripheral blood mononuclear cells (PBMCs) and placental tissues in patients with early spontaneous abortionMethods Using the technique of semi-quantitative reverse transcript-polymerase chain reaction (RT-PCR), TNF-α mRNA and TGF-β1 mRNA in PBMCs were measured in spontaneous abortion group (30 cases), normal pregnancy group (25 cases) and nonpregnant group (25 cases). The expressive intension of TNF-α protein and TGF-β1 protein in placental tissues was also identified by immunohistochemistry.Results Both levels of TNF-α mRNA and TGF-β1 mRNA expressed in PBMCs were significantly different between the three groups respectively (P<0. 05). Levels of TNF-α in syncytiotrophoblastic and cytotrophoblastic cells of the two aborted groups were substantially higher than those of the non-pregnant group (P<0. 01), but the levels of TGF-β1 in syncytiotrophoblastic cells of the two aborted groups were markedly lower than those of the non-pregnant group (P<0. 01).Conclusion There is potential relation between TGF-β1 at the fetomaternal interface and spontaneous abortion. TGF-β1 may contribute to the maintenance of pregnancy,and low-level expression of TGF-β1 may be associated with pregnancy failure.

  10. Aberrant expression of tumor-associated carbohydrate antigen Globo H in thyroid carcinoma.

    Science.gov (United States)

    Cheng, Shih-Ping; Yang, Po-Sheng; Chien, Ming-Nan; Chen, Ming-Jen; Lee, Jie-Jen; Liu, Chien-Liang

    2016-12-01

    The induction of tumor-associated carbohydrate antigen results from altered glycosylation in transformed cells. Globo H is a hexasaccharide glycosphingolipid overexpressed on malignancies of epithelial origin and has become an attractive vaccine target. We aimed to investigate the expression patterns and prognostic value of Globo H in thyroid neoplasms. Globo H expression was examined by immunohistochemical analysis using commercial and in-house tissue microarrays. The expression was correlated with clinicopathologic characteristics in papillary thyroid cancer. Normal or benign thyroid lesions were negative for Globo H expression. Globo H was positive in 33% medullary, 24% papillary, 11% undifferentiated, and 8% follicular thyroid cancer. Globo H expression in papillary thyroid cancer was associated with extrathyroidal invasion (P = 0.017), BRAF mutation (P = 0.010), AMES high risk (P = 0.045), and increased ATA risk of recurrence (P = 0.022). Globo H is specifically expressed in a subset of thyroid malignancies. In papillary thyroid cancer, Globo H expression is associated with invasiveness and BRAF mutation. Immunotherapy targeting Globo H may have potential applications in thyroid cancer. J. Surg. Oncol. 2016;114:853-858. © 2016 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. Aberrant EphB/ephrin-B expression in experimental gastric lesions and tumor cells

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    Uchiyama, Shintaro; Saeki, Noritaka; Ogawa, Kazushige

    2015-01-01

    AIM: To determine whether the expression profiles of EphB receptor and ephrin-B ligand can be used as markers for dysplastic/oncogenic transformation in gastric mucosa. METHODS: The protein expression and localization of EphB and ephrin-B in normal, ulcerated regenerating, and dysplastic gastric mucosa were examined in a rat experimental model by immunolabeling, and mRNA expression was assessed in four human gastric carcinoma cell lines by reverse transcription-polymerase chain reaction. RESULTS: Ephrin-B- and EphB-expressing regions were divided along the pit-gland axis in normal gastric units. EphB2 was transiently upregulated in the experimental ulcer, and its expression domain extended to gastric pits and/or the luminal surface where ephrin-B-expressing pit cells reside. EphB2, B3, and B4 and ephrin-B1 were coexpressed in the experimental gastric dysplasia, and more than one ligand-receptor pair was highly expressed in each of the gastric carcinoma cell lines. CONCLUSION: Robust and stable coexpression of EphB and ephrin-B is a feature common to experimentally induced gastric dysplasia and human gastric carcinoma cell lines as compared to normal gastric and ulcerated regenerating epithelia. Thus, EphB/ephrin-B may be a useful marker combination for dysplastic/oncogenic transformation in gastric cancer. PMID:25593460

  12. Aberrant large tumor suppressor 2 (LATS2) gene expression correlates with EGFR mutation and survival in lung adenocarcinomas

    Science.gov (United States)

    Luo, Susan Y.; Sit, Ko-Yung; Sihoe, Alan D.L.; Suen, Wai-Sing; Au, Wing-Kuk; Tang, Ximing; Ma, Edmond S.K.; Chan, Wai-Kong; Wistuba, Ignacio I.; Minna, John D.; Tsao, George S.W.; Lam, David C.L.

    2015-01-01

    Background Large tumor suppressor 2 (LATS2) gene is a putative tumor suppressor gene with potential roles in regulation of cell proliferation and apoptosis in lung cancer. The aim of this study is to explore the association of aberrant LATS2 expression with EGFR mutation and survival in lung adenocarcinoma (AD), and the effects of LATS2 silencing in both lung AD cell lines. Methods LATS2 mRNA and protein expression in resected lung AD were correlated with demographic characteristics, EGFR mutation and survival. LATS2-specific siRNA was transfected into four EGFR wild-type (WT) and three EGFR mutant AD cell lines and the changes in LATS2 expression and relevant signaling molecules before and after LATS2 knockdown were assayed. Results Fifty resected lung AD were included (M:F = 23:27, smokers:non-smokers = 19:31, EGFR mutant:wild-type = 21:29) with LATS2 mRNA levels showed no significant difference between gender, age, smoking and pathological stages while LATS2 immunohistochemical staining on an independent set of 79 lung AD showed similar trend. LATS2 mRNA level was found to be a significant independent predictor for survival status (disease-free survival RR = 0.217; p = 0.003; Overall survival RR = 0.238; p = 0.036). siRNA-mediated suppression of LATS2 expression resulted in augmentation of ERK phosphorylation in EGFR wild-type AD cell lines with high basal LATS2 expression, discriminatory modulation of Akt signaling between EGFR wild-type and mutant cells, and induction of p53 accumulation in AD cell lines with low baseline p53 levels. Conclusions LATS2 expression level is predictive of survival in patients with resected lung AD. LATS2 may modulate and contribute to tumor growth via different signaling pathways in EGFR mutant and wild-type tumors. PMID:24976335

  13. Aberrant LncRNA Expression Profile in a Contusion Spinal Cord Injury Mouse Model

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    Ya Ding

    2016-01-01

    Full Text Available Long noncoding RNAs (LncRNAs play a crucial role in cell growth, development, and various diseases related to the central nervous system. However, LncRNA differential expression profiles in spinal cord injury are yet to be reported. In this study, we profiled the expression pattern of LncRNAs using a microarray method in a contusion spinal cord injury (SCI mouse model. Compared with a spinal cord without injury, few changes in LncRNA expression levels were noted 1 day after injury. The differential changes in LncRNA expression peaked 1 week after SCI and subsequently declined until 3 weeks after injury. Quantitative real-time polymerase chain reaction (qRT-PCR was used to validate the reliability of the microarray, demonstrating that the results were reliable. Gene ontology (GO analysis indicated that differentially expressed mRNAs were involved in transport, cell adhesion, ion transport, and metabolic processes, among others. Kyoto Encyclopedia of Genes and Genomes (KEGG enrichment analysis showed that the neuroactive ligand-receptor interaction, the PI3K-Akt signaling pathway, and focal adhesions were potentially implicated in SCI pathology. We constructed a dynamic LncRNA-mRNA network containing 264 LncRNAs and 949 mRNAs to elucidate the interactions between the LncRNAs and mRNAs. Overall, the results from this study indicate for the first time that LncRNAs are differentially expressed in a contusion SCI mouse model.

  14. Expression of the pluripotency transcription factor OCT4 in the normal and aberrant mammary gland

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    Foteini eHassiotou

    2013-04-01

    Full Text Available Breast cancers with lactating features, some of which are associated with pregnancy and lactation, are often poorly differentiated, lack estrogen receptor, progesterone receptor and HER2 expression and have high mortality. Very little is known about the molecular mechanisms that drive uncontrolled cell proliferation in these tumors and confer lactating features. We have recently reported expression of OCT4 and associated embryonic stem cell (ESC self-renewal genes in the normal lactating breast and breastmilk stem cells (hBSCs. This prompted us to examine OCT4 expression in breast cancers with lactating features and compare it with that observed during normal lactation, using rare specimens of human lactating breast. In accordance with previous literature, the normal resting breast (from non-pregnant, non-lactating women showed minimal OCT4 nuclear expression (0.9%. However, this increased in the normal lactating breast (11.4%, with further increase in lactating adenomas, lactating carcinomas and pregnancy-associated breast cancer (30.7-48.3%. OCT4 was expressed in the epithelium and at lower levels in the stroma, and was co-localized with NANOG. Comparison of normal non-tumorigenic hBSCs with OCT4-overexpressing tumorigenic breast cell lines (OTBCs demonstrated upregulation of OCT4, SOX2 and NANOG in both systems, but OTBCs expressed OCT4 at significantly higher levels than SOX2 and NANOG. Similar to hBSCs, OTBCs displayed multi-lineage differentiation potential, including the ability to differentiate into functional lactocytes synthesizing milk proteins both in vitro and in vivo. Based on these findings, we propose a hypothesis of normal and malignant transformation in the breast, which centers on OCT4 and its associated gene network. Although minimal expression of these embryonic genes can be seen in the breast in its resting state throughout life, a controlled program of upregulation of this gene network may be a potential regulator of the

  15. Aberration of miRNAs Expression in leukocytes from sporadic amyotrophic lateral sclerosis

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    Yongping Chen

    2016-08-01

    Full Text Available Background: Accumulating evidence indicates that miRNAs play an important role in the development of amyotrophic lateral sclerosis (ALS. Most of previous studies on miRNA dysregulation in ALS focused on the alterative expression in ALS animal model or in limited samples from European patients with ALS. In the present study, the miRNA expression profiles were investigated in Chinese ALS patients to explore leukocytes miRNAs as a potential biomarker for the diagnosis of ALS.Methods: We analyzed the expression profiles of 1733 human mature miRNAs using microarray technology in leukocytes obtained from 5 patients with sporadic ALS (SALS and 5 healthy controls. An independent group of 83 SALS patients, 24 Parkinson’s disease (PD patients and 61 controls was used for validation by real-time polymerase chain reaction assay. Area under the receiver operating characteristic curve (AUC was used to evaluate diagnostic accuracy. In addition, target genes and signaling information of validated differential expression miRNAs were predicted using Bioinformatics.Results: Eleven miRNAs, including four over-expressed and seven under-expressed miRNAs detected in SALS patients compared to healthy controls were selected for validation. Four under-expressed microRNAs, including hsa-miR-183, hsa-miR-193b, hsa-miR-451 and hsa-miR-3935, were confirmed in validation stage by comparison of 83 SALS patients and 61 HCs. Moreover, we identified a miRNA panel (hsa-miR-183, hsa-miR-193b, hsa-miR-451 and hsa-miR-3935 having a high diagnostic accuracy of SALS (AUC 0.857 for the validation group. However, only hsa-miR-183 was significantly lower in SALS patients than that in PD patients and in HCs, while no differences were found between PD patients and HCs. By bioinformatics analysis, we obtained a large number of target genes and signaling information that are linked to neurodegeneration. Conclusion: This study provided evidence of abnormal miRNA expression patterns in the

  16. Aberration of miRNAs Expression in Leukocytes from Sporadic Amyotrophic Lateral Sclerosis

    Science.gov (United States)

    Chen, YongPing; Wei, QianQian; Chen, XuePing; Li, ChunYu; Cao, Bei; Ou, RuWei; Hadano, Shinji; Shang, Hui-Fang

    2016-01-01

    Background: Accumulating evidence indicates that miRNAs play an important role in the development of amyotrophic lateral sclerosis (ALS). Most of previous studies on miRNA dysregulation in ALS focused on the alterative expression in ALS animal model or in limited samples from European patients with ALS. In the present study, the miRNA expression profiles were investigated in Chinese ALS patients to explore leukocytes miRNAs as a potential biomarker for the diagnosis of ALS. Methods: We analyzed the expression profiles of 1733 human mature miRNAs using microarray technology in leukocytes obtained from 5 patients with sporadic ALS (SALS) and 5 healthy controls. An independent group of 83 SALS patients, 24 Parkinson's disease (PD) patients and 61 controls was used for validation by real-time polymerase chain reaction assay. Area under the receiver operating characteristic curve (AUC) was used to evaluate diagnostic accuracy. In addition, target genes and signaling information of validated differential expression miRNAs were predicted using Bioinformatics. Results: Eleven miRNAs, including four over-expressed and seven under-expressed miRNAs detected in SALS patients compared to healthy controls were selected for validation. Four under-expressed microRNAs, including hsa-miR-183, hsa-miR-193b, hsa-miR-451, and hsa-miR-3935, were confirmed in validation stage by comparison of 83 SALS patients and 61 HCs. Moreover, we identified a miRNA panel (hsa-miR-183, hsa-miR-193b, hsa-miR-451, and hsa-miR-3935) having a high diagnostic accuracy of SALS (AUC 0.857 for the validation group). However, only hsa-miR-183 was significantly lower in SALS patients than that in PD patients and in HCs, while no differences were found between PD patients and HCs. By bioinformatics analysis, we obtained a large number of target genes and signaling information that are linked to neurodegeneration. Conclusion: This study provided evidence of abnormal miRNA expression patterns in the peripheral

  17. Aberrant Expression of proPTPRN2 in Cancer Cells Confers Resistance to Apoptosis.

    Science.gov (United States)

    Sorokin, Alexey V; Nair, Binoj C; Wei, Yongkun; Aziz, Kathryn E; Evdokimova, Valentina; Hung, Mien-Chie; Chen, Junjie

    2015-05-01

    The protein tyrosine phosphatase receptor PTPRN2 is expressed predominantly in endocrine and neuronal cells, where it functions in exocytosis. We found that its immature isoform proPTPRN2 is overexpressed in various cancers, including breast cancer. High proPTPRN2 expression was associated strongly with lymph node-positive breast cancer and poor clinical outcome. Loss of proPTPRN2 in breast cancer cells promoted apoptosis and blocked tumor formation in mice, whereas enforced expression of proPTPRN2 in nontransformed human mammary epithelial cells exerted a converse effect. Mechanistic investigations suggested that ProPTPRN2 elicited these effects through direct interaction with TRAF2, a hub scaffold protein for multiple kinase cascades, including ones that activate NF-κB. Overall, our results suggest PTPRN2 as a novel candidate biomarker and therapeutic target in breast cancer. ©2015 American Association for Cancer Research.

  18. Integrating chromosomal aberrations and gene expression profiles to dissect rectal tumorigenesis

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    Eilers Paul HC

    2008-10-01

    Full Text Available Abstract Background Accurate staging of rectal tumors is essential for making the correct treatment choice. In a previous study, we found that loss of 17p, 18q and gain of 8q, 13q and 20q could distinguish adenoma from carcinoma tissue and that gain of 1q was related to lymph node metastasis. In order to find markers for tumor staging, we searched for candidate genes on these specific chromosomes. Methods We performed gene expression microarray analysis on 79 rectal tumors and integrated these data with genomic data from the same sample series. We performed supervised analysis to find candidate genes on affected chromosomes and validated the results with qRT-PCR and immunohistochemistry. Results Integration of gene expression and chromosomal instability data revealed similarity between these two data types. Supervised analysis identified up-regulation of EFNA1 in cases with 1q gain, and EFNA1 expression was correlated with the expression of a target gene (VEGF. The BOP1 gene, involved in ribosome biogenesis and related to chromosomal instability, was over-expressed in cases with 8q gain. SMAD2 was the most down-regulated gene on 18q, and on 20q, STMN3 and TGIF2 were highly up-regulated. Immunohistochemistry for SMAD4 correlated with SMAD2 gene expression and 18q loss. Conclusion On basis of integrative analysis this study identified one well known CRC gene (SMAD2 and several other genes (EFNA1, BOP1, TGIF2 and STMN3 that possibly could be used for rectal cancer characterization.

  19. Aberrant expression of Arpin in human breast cancer and its clinical significance.

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    Liu, Xiangping; Zhao, Bin; Wang, Haibo; Wang, Yu; Niu, Mengdi; Sun, Ming; Zhao, Yang; Yao, Ruyong; Qu, Zhiqiang

    2016-03-01

    Arpin (Arp2/3 complex inhibitor), a novel protein found in 2013, plays a pivotal role in cell motility and migration. However, the precise role of Arpin in cancer is unclear. This study investigated the expression of Arpin in breast cancer and evaluated its correlation with the characteristics of clinical pathology and prognosis of breast cancer patients. Immunohistochemistry (IHC) for Arpin protein was performed on formalin-fixed, paraffin-embedded 176 breast cancer tissues and 43 normal breast tissues while qRT-PCR for Arpin mRNA with 104 paired tumour and paratumoural tissues from breast cancer patients respectively. The association of Arpin expression with clinical pathological features and survival was assessed in a retrospective cohort analysis of patients. The results showed that the expression of Arpin protein in cancer tissues was lower compared to that in normal breast and the expression of Arpin mRNA was also lower in cancer tissues than that in the matched paratumoural tissues. Among the 176 breast cancer patients, the lower expression of Arpin was significantly associated with advanced tumour, nodes and metastasis system stage, and the reduced Arpin expression was strongly associated with axillary lymph node metastasis using univariate and multivariate logistic regression analysis [odds ratio: 3.242; 95% confidence interval (CI): 1.526, 6.888; P breast cancer tissues with qRT-PCR and IHC, our results suggest that Arpin downregulation may contribute to the initiation and development of breast cancer metastasis. Therefore, as a potential predictive marker, Arpin deserves future studies.

  20. Targeting aberrant expression of Notch-1 in ALDH(+) cancer stem cells in breast cancer.

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    Pal, Deeksha; Kolluru, Venkatesh; Chandrasekaran, Balaji; Baby, Becca V; Aman, Masarath; Suman, Suman; Sirimulla, Suman; Sanders, Mary Ann; Alatassi, Houda; Ankem, Murali K; Damodaran, Chendil

    2017-03-01

    We have previously reported that high aldehyde dehydrogenase (ALDH) enzyme activity in breast cancer cells results in breast cancer stem cell (BCSC) properties by upregualting Notch-1 and epithelial mesenchymal markers. This results in chemoresistance in breast cancer. Here, we examined the functional and clinical significance of ALDH expression by measuring the ALDH levels in breast cancer tissues by immunohistochemistry. There was a significantly higher ALDH expression in higher grade breast cancer tumor tissues (Grade- II and III) versus normal breast tissues. Injection of BCSC (ALDH(+) and CD44(+) /CD22(-) ) cells resulted in aggressive tumor growth in athymic mice versus ALDH(-) cells. The ALDH(+) and CD44(+) /CD22(-) tumors grow rapidly and are larger than ALDH(-) tumors which were slow growing and smaller. Molecularly, ALDH(+) tumors expressed higher expression of Notch-1 and EMT markers than ALDH(-) tumors. Oral administration of the naturally occurring Psoralidin (Pso, 25 mg/kg of body weight) significantly inhibited the growth in ALDH(+) and ALDH(-) tumors as well. Psoralidin inhibited Notch-1 mediated EMT activation in ALDH(+) and ALDH(-) tumors-this confirms our in vitro findings. Our results suggest that Notch-1 could be an attractive target and inhibition of Notch-1 by Psoralidin may prevent pathogenesis of breast cancer as well as metastasis. © 2016 Wiley Periodicals, Inc.

  1. Subgroup J avian leukosis virus infection of chicken dendritic cells induces apoptosis via the aberrant expression of microRNAs.

    Science.gov (United States)

    Liu, Di; Dai, Manman; Zhang, Xu; Cao, Weisheng; Liao, Ming

    2016-02-01

    Subgroup J avian leukosis virus (ALV-J) is an oncogenic retrovirus that causes immunosuppression and enhances susceptibility to secondary infection. The innate immune system is the first line of defense in preventing bacterial and viral infections, and dendritic cells (DCs) play important roles in innate immunity. Because bone marrow is an organ that is susceptible to ALV-J, the virus may influence the generation of bone marrow-derived DCs. In this study, DCs cultured in vitro were used to investigate the effects of ALV infection. The results revealed that ALV-J could infect these cells during the early stages of differentiation, and infection of DCs with ALV-J resulted in apoptosis. miRNA sequencing data of uninfected and infected DCs revealed 122 differentially expressed miRNAs, with 115 demonstrating upregulation after ALV-J infection and the other 7 showing significant downregulation. The miRNAs that exhibited the highest levels of upregulation may suppress nutrient processing and metabolic function. These results indicated that ALV-J infection of chicken DCs could induce apoptosis via aberrant microRNA expression. These results provide a solid foundation for the further study of epigenetic influences on ALV-J-induced immunosuppression.

  2. Mice expressing aberrant sperm-specific protein PMIS2 produce normal-looking but fertilization-incompetent spermatozoa.

    Science.gov (United States)

    Yamaguchi, Ryo; Fujihara, Yoshitaka; Ikawa, Masahito; Okabe, Masaru

    2012-07-01

    Eight kinds of gene-disrupted mice (Clgn, Calr3, Pdilt, Tpst2, Ace, Adam1a, Adam2, and Adam3) show impaired sperm transition into the oviducts and defective sperm binding to the zona pellucida. All of these knockout strains are reported to lack or show aberrant expression of a disintegrin and metallopeptidase domain 3 (ADAM3) on the sperm membrane. We performed proteomic analyses of the proteins of these infertile spermatozoa to clarify whether the abnormal function is caused exclusively by a deficiency in ADAM3 expression. Two proteins, named PMIS1 and PMIS2, were missing in spermatozoa from Clgn-disrupted mice. To study their roles, we generated two gene-disrupted mouse lines. Pmis1-knockout mice were fertile, but Pmis2-knockout males were sterile because of a failure of sperm transport into the oviducts. Pmis2-deficient spermatozoa also failed to bind to the zona pellucida. However, they showed normal fertilizing ability when eggs surrounded with cumulus cells were used for in vitro fertilization. Further analysis revealed that these spermatozoa lacked the ADAM3 protein, but the amount of PMIS2 was also severely reduced in Adam3-deficient spermatozoa. These results suggest that PMIS2 might function both as the ultimate factor regulating sperm transport into the oviducts and in modulating sperm-zona binding.

  3. Aberrant microRNA expression in Chinese patients with chronic lymphocytic leukemia.

    Science.gov (United States)

    Zhu, Dan-Xia; Miao, Kou-Rong; Fang, Cheng; Fan, Lei; Zhu, Wei; Zhu, Hua-Yuan; Zhuang, Yun; Hong, Ming; Liu, Peng; Xu, Wei; Li, Jian-Yong

    2011-06-01

    MicroRNAs (miRNAs) are a class of small endogenous RNAs that play important regulatory roles by targeting mRNAs for cleavage or translational repression. Many reports have indicated that miRNAs play a critical role in malignancies, and regulations in the progression of leukemia. However, the miRNAs expression level in Chinese patients with chronic lymphocytic leukemia (CLL), and its prognostic value remain elusive. We identified various degrees of down-regulation of miR-15a, miR-16-1, miR-29b, miR-181a and miR-181b in CLL mononuclear cells. Moreover, we have identified miR-29b and miR-181a/b expression significantly correlated with IGHV mutational status. Transcript levels of predicted target genes BCL-2 and TCL-1 were also determined, and the expression levels were significantly upregulated in CLL patients compared with normal controls (PmiR-181b) and BCL-2 level; furthermore, an inverse correlation was also observed between miRNAs (miR-16-1, miR-181a, miR-181b) and TCL-1, which suggest that these miRNAs may implicate in negatively regulating target mRNA at transcriptional level. These different miRNAs may play an important role in the pathogenesis of CLL and might be applied for the assessment of prognosis in patients with CLL.

  4. Aberrantly Over-Expressed TRPM8 Channels in Pancreatic Adenocarcinoma: Correlation with Tumor Size/Stage and Requirement for Cancer Cells Invasion

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    Nelson S. Yee

    2014-05-01

    Full Text Available The transient receptor potential melastatin-subfamily member 8 (TRPM8 channels control Ca2+ homeostasis. Recent studies indicate that TRPM8 channels are aberrantly expressed and required for cellular proliferation in pancreatic adenocarcinoma. However, the functional significance of TRPM8 in pancreatic tissues is mostly unknown. The objectives of this study are to examine the expression of TRPM8 in various histopathological types of pancreatic tissues, determine its clinical significance in pancreatic adenocarcinoma, and investigate its functional role in cancer cells invasion. We present evidence that, in normal pancreatic tissues, anti-TRPM8 immunoreactivity is detected in the centroacinar cells and the islet endocrine cells. In pre-malignant pancreatic tissues and malignant neoplasms, TRPM8 is aberrantly expressed to variable extents. In the majority of pancreatic adenocarcinoma, TRPM8 is expressed at moderate or high levels, and anti-TRPM8 immunoreactivity positively correlates with the primary tumor size and stage. In the pancreatic adenocarcinoma cell lines that express relatively high levels of TRPM8, short hairpin RNA-mediated interference of TRPM8 expression impaired their ability of invasion. These data suggest that aberrantly expressed TRPM8 channels play contributory roles in pancreatic tumor growth and metastasis, and support exploration of TRPM8 as a biomarker and target of pancreatic adenocarcinoma.

  5. Aberrant DNA hypermethylation-silenced SOX21-AS1 gene expression and its clinical importance in oral cancer.

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    Yang, Cheng-Mei; Wang, Tsung-Han; Chen, Hung-Chih; Li, Sung-Chou; Lee, Ming-Chien; Liou, Huei-Han; Liu, Pei-Feng; Tseng, Yu-Kai; Shiue, Yow-Ling; Ger, Luo-Ping; Tsai, Kuo-Wang

    2016-01-01

    Long noncoding RNAs (lncRNAs) are more than 200 nucleotides in length and lack transcriptional ability. The biological function of lncRNAs in oral squamous cell carcinoma (OSCC) remains unclear. The aim of this study was to identify the dysfunction of lncRNA in OSCC. We analyzed the transcriptome profiles of human OSCC tissues and paired adjacent normal tissues from two patients through a next-generation sequencing approach. A total of 14 lncRNAs were upregulated (fold change ≥3) and 13 were downregulated (fold change ≤-3) in OSCC tissues compared with the adjacent normal tissues. SOX21-AS1 was subjected to further analysis, revealing that the expression levels of SOX21-AS1 significantly decreased in OSCC compared with the adjacent normal tissue. The promoter activity of SOX21-AS1 was obviously suppressed by in vitro methylation. The DNA methylation status of the SOX21-AS1 promoter was analyzed using combined bisulfite restriction analysis, revealing that the aberrant promoter hypermethylation of SOX21-AS1 was observed frequently in OSCC tissues. The effects of SOX21-AS1 on cell proliferation and invasion were examined through transient transfection. Our data showed that SOX21-AS1 could significantly suppress oral cancer cell growth and invasion. Furthermore, the low expression level of SOX21-AS1 was significantly correlated with an advanced stage (P = 0.047), large tumor size (P = 0.033), and poor disease-specific survival in OSCC patients (P = 0.002). SOX21-AS1 was identified as susceptible dysfunction correlated with promoter hypermethylation in OSCC. Low SOX21-AS1 expression may be an adverse prognostic biomarker for OSCC.

  6. Periodontitis contributes to aberrant metabolism in type 2 diabetes mellitus rats by stimulating the expression of adipokines.

    Science.gov (United States)

    Luo, S; Yang, X; Wang, D; Ni, J; Wu, J; Xu, Z; Xuan, D; Zhang, J

    2016-08-01

    Periodontitis has been associated with type 2 diabetes mellitus. We investigated the effects of local aberrant secretion of adipokines in diabetic rats on systemic metabolism. Otsuka Long-Evans Tokushima Fatty (OLETF) and non-diabetic Long-Evans Tokushima Otsuka rats were used as a diabetic model and associated control, respectively. Periodontitis was induced using a silk ligature for 36 wk. Rats were grouped into OLETF with (OP+) or without (OP-) periodontitis and Long-Evans Tokushima Otsuka with (LP+) or without (LP-) periodontitis. Alveolar bone resorption and destruction were evaluated by micro-computed tomography and hematoxylin and eosin staining. After 20 wk of periodontitis induction, lipids, insulin, interleukin-1, leptin and plasminogen activator inhibitor-1 were analyzed, and mRNA expressions of NF-κB, Mark8, TLR2 and -4, IKBKB and Nampt were evaluated by quantitative polymerase chain reaction in adipose tissue. After ligation, OLETF rats exhibited typical periodontitis lesions with the clinical features of type 2 diabetes mellitus. When compared with the OP(-) group, the area under curve of the oral glucose tolerance test and homeostatic model assessment-insulin resistance values were significantly higher in the OP(+) group. Micro-computed tomography showed that the OP(+) group had more bone resorption than the OP(-) group. When compared with the OP(-) group, the OP(+) group also exhibited higher total cholesterol (p 0.05) and higher expression of Nampt (p periodontitis can alter lipid profiles in affected rats, elevate adipose tissue expression of Nampt and affect the metabolism of adipose tissue through the NF-κB pathway to inflame diabetes. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Hypomethylation and Aberrant Expression of the Glioma Pathogenesis-Related 1 Gene in Wilms Tumors

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    Laxmi Chilukamarri

    2007-11-01

    Full Text Available Wilms tumors (WTs have a complex etiology, displaying genetic and epigenetic changes, including loss of imprinting (LOI and tumor suppressor gene silencing. To identify new regions of epigenetic perturbation in WTs, we screened kidney and tumor DNA using CpG island (CGI tags associated with cancer-specific DNA methylation changes. One such tag corresponded to a paralog of the glioma pathogenesis-related 1/related to testis-specific, vespid, and pathogenesis proteins 1 (GLIPR1/RTVP-1 gene, previously reported to be a tumor-suppressor gene silenced by hypermethylation in prostate cancer. Here we report methylation analysis of the GLIPR1/RTVP-1 gene in WTs and normal fetal and pediatric kidneys. Hypomethylation of the GLIPR1/RTVP-1 5'-region in WTs relative to normal tissue is observed in 21/24 (87.5% of WTs analyzed. Quantitative analysis of GLIPR1/RTVP-1 expression in 24 WTs showed elevated transcript levels in 16/24 WTs (67%, with 12 WTs displaying in excess of 20-fold overexpression relative to fetal kidney (FK control samples. Immunohistochemical analysis of FK and WT corroborates the RNA expression data and reveals high GLIPR1/RTVP-1 in WT blastemal cells together with variable levels in stromal and epithelial components. Hypomethylation is also evident in the WT precursor lesions and nephrogenic rests (NRs, supporting a role for GLIPR1/RTVP-1 deregulation early in Wilms tumorigenesis. Our data show that, in addition to gene dosage changes arising from LOI and hypermethylation-induced gene silencing, gene activation resulting from hypomethylation is also prevalent in WTs.

  8. Aberrant TRPV1 Expression in Heat Hyperalgesia Associated with Trigeminal Neuropathic Pain

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    Hiroko Urano, Toshiaki Ara, Yoshiaki Fujinami, B. Yukihiro Hiraoka

    2012-01-01

    Full Text Available Trigeminal neuropathic pain is a facial pain syndrome associated with trigeminal nerve injury. However, the mechanism of trigeminal neuropathic pain is poorly understood. This study aimed to determine the role of transient receptor potential vanilloid 1 (TRPV1 in heat hyperalgesia in a trigeminal neuropathic pain model. We evaluated nociceptive responses to mechanical and heat stimuli using a partial infraorbital nerve ligation (pIONL model. Withdrawal responses to mechanical and heat stimuli to vibrissal pads (VP were assessed using von Frey filaments and a thermal stimulator equipped with a heat probe, respectively. Changes in withdrawal responses were measured after subcutaneous injection of the TRP channel antagonist capsazepine. In addition, the expression of TRPV1 in the trigeminal ganglia was examined. Mechanical allodynia and heat hyperalgesia were observed in VP by pIONL. Capsazepine suppressed heat hyperalgesia but not mechanical allodynia. The number of TRPV1-positive neurons in the trigeminal ganglia was significantly increased in the large-diameter-cell group. These results suggest that TRPV1 plays an important role in the heat hyperalgesia observed in the pIONL model.

  9. Aberrant Expression of MHC Class II in Melanoma Attracts Inflammatory Tumor-Specific CD4+ T- Cells, Which Dampen CD8+ T-cell Antitumor Reactivity

    DEFF Research Database (Denmark)

    Donia, Marco; Andersen, Rikke; Kjeldsen, Julie W

    2015-01-01

    In the absence of a local inflammatory response, expression of MHC class II molecules is restricted mainly to hematopoietic cells and thymus epithelium. However, certain tumors, such as melanoma, may acquire aberrant constitutive expression of MHC class II. In a set of primary melanoma cell popul...... mechanism that can be activated by aberrant expression of MHC class II molecules, which by attracting tumor-specific CD4(+) T cells elicit a local inflammatory response dominated by TNF that, in turn, inhibits cytotoxic CD8(+) T-cell responses......In the absence of a local inflammatory response, expression of MHC class II molecules is restricted mainly to hematopoietic cells and thymus epithelium. However, certain tumors, such as melanoma, may acquire aberrant constitutive expression of MHC class II. In a set of primary melanoma cell...... were dominated by TNF production. TNF reduced CD8(+) T-cell activation in IFNγ-rich environments resembling a tumor site. Conversely, direct CD4(+) T-cell responses had no influence on either the proliferation or viability of melanoma cells. Taken together, our results illustrate a novel immune escape...

  10. Altered expression of MGMT in high-grade gliomas results from the combined effect of epigenetic and genetic aberrations.

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    João Ramalho-Carvalho

    Full Text Available MGMT downregulation in high-grade gliomas (HGG has been mostly attributed to aberrant promoter methylation and is associated with increased sensitivity to alkylating agent-based chemotherapy. However, HGG harboring 10q deletions also benefit from treatment with alkylating agents. Because the MGMT gene is mapped at 10q26, we hypothesized that both epigenetic and genetic alterations might affect its expression and predict response to chemotherapy. To test this hypothesis, promoter methylation and mRNA levels of MGMT were determined by quantitative methylation-specific PCR (qMSP or methylation-specific multiplex ligation dependent probe amplification (MS-MLPA and quantitative RT-PCR, respectively, in a retrospective series of 61 HGG. MGMT/chromosome 10 copy number variations were determined by FISH or MS-MLPA analysis. Molecular findings were correlated with clinical parameters to assess their predictive value. Overall, MGMT methylation ratios assessed by qMSP and MS-MLPA were inversely correlated with mRNA expression levels (best coefficient value obtained with MS-MLPA. By FISH analysis in 68.3% of the cases there was loss of 10q26.1 and in 15% of the cases polysomy was demonstrated; the latter displayed the highest levels of transcript. When genetic and epigenetic data were combined, cases with MGMT promoter methylation and MGMT loss depicted the lowest transcript levels, although an impact in response to alkylating agent chemotherapy was not apparent. Cooperation between epigenetic (promoter methylation and genetic (monosomy, locus deletion changes affecting MGMT in HGG is required for effective MGMT silencing. Hence, evaluation of copy number alterations might add relevant prognostic and predictive information concerning response to alkylating agent-based chemotherapy.

  11. 1q12 chromosome translocations form aberrant heterochromatic foci associated with changes in nuclear architecture and gene expression in B cell lymphoma

    Science.gov (United States)

    Fournier, Alexandra; McLeer-Florin, Anne; Lefebvre, Christine; Duley, Samuel; Barki, Leila; Ribeyron, Juliana; Kassambara, Alboukadel; Hamaidia, Sieme; Granjon, Aurélie; Gressin, Rémy; Lajmanovich, Alicia; Bonnefoix, Thierry; Chauvelier, Stéphanie; Debernardi, Alexandra; Rousseaux, Sophie; de Fraipont, Florence; Figeac, Martin; Kerckaert, Jean-Pierre; De Vos, John; Usson, Yves; Delaval, Katia; Grichine, Alexei; Vourc'h, Claire; Khochbin, Saadi; Feil, Robert; Leroux, Dominique; Callanan, Mary B

    2010-01-01

    Epigenetic perturbations are increasingly described in cancer cells where they are thought to contribute to deregulated gene expression and genome instability. Here, we report the first evidence that a distinct category of chromosomal translocations observed in human tumours—those targeting 1q12 satellite DNA—can directly mediate such perturbations by promoting the formation of aberrant heterochromatic foci (aHCF). By detailed investigations of a 1q12 translocation to chromosome 2p, in a case of human B cell lymphoma, aberrant aHCF were shown to be localized to the nuclear periphery and to arise as a consequence of long range ‘pairing’ between the translocated 1q12 and chromosome 2 centromeric regions. Remarkably, adjacent 2p sequences showed increased levels of repressive histone modifications, including H4K20me3 and H3K9me3, and were bound by HP1. aHCF were associated to aberrant spatial localization and deregulated expression of a novel 2p gene (GMCL1) that was found to have prognostic impact in diffuse large B cell lymphoma. Thus constitutive heterochromatin rearrangements can contribute to tumourigenesis by perturbing gene expression via long range epigenetic mechanisms. PMID:20432501

  12. Aberrant Low Expression of A20 in Tumor Necrosis Factor-α-stimulated SLE Monocytes Mediates Sustained NF-κB Inflammatory Response.

    Science.gov (United States)

    Shi, Xiaowei; Qian, Tian; Li, Min; Chen, Fangru; Chen, Yan; Hao, Fei

    2015-01-01

    The aberrantly activated monocytes and nuclear factor-kappaB (NF-κB) pathway contribute to the pathogenesis of systemic lupus erythematosus (SLE), and the aberrantly activated NF-κB is associated with defects in the anti-inflammatory A20 in SLE. However, whether SLE monocytes express A20 and whether the A20 expression under sustained proinflammatory stimulation is altered to contribute to the uncontrolled NF-κB inflammatory response are unclear. In this study, we found that the freshly isolated monocytes from SLE patients and healthy controls did not differ in expression levels of IL-1β, IκBα and A20. After TNF-α stimulation for 48 h, the monocytes from both groups expressed higher levels of IL-1β and IκBα than the monocytes without TNF-α treatment. Although the increased levels of NF-κB were observed in the nucleus of both the SLE and control monocytes after 24 h of TNF-α stimulation, the enhancement in SLE monocytes was significantly more robust than in the control monocytes. In addition, while the p-IκBα level in healthy monocytes was increased, the p-IκBα level in SLE monocytes was slightly decreased after TNF-α stimulation. Interestingly, after TNF-α treatment, the A20 expression in SLE monocytes was not markedly altered compared with the untreated SLE monocytes; moreover, the SLE monocytes expressed significantly lower A20 than healthy monocytes with TNF-α treatment at each time point. Results in this study demonstrate that TNF-α activates a significant NF-κB inflammatory response in SLE monocytes, which is at least partially mediated by the aberrantly low expression of A20 upon TNF-α stimulation, contributing to the prolonged inflammatory response in SLE.

  13. Aberrant Expression of Calretinin, D2-40 and Mesothelin in Mucinous and Non-Mucinous Colorectal Carcinomas and Relation to Clinicopathological Features and Prognosis.

    Science.gov (United States)

    Foda, Abd AlRahman Mohammad; El-Hawary, Amira Kamal; Hamed, Hazem

    2016-10-01

    CRC is a heterogeneous disease in terms of morphology, invasive behavior, metastatic capacity, and clinical outcome. Recently, many so-called mesothelial markers, including calretinin, D2-40, WT1, thrombomodulin, mesothelin, and others, have been certified. The aim of this study was to assess the immunohistochemical expression of calretinin and other mesothelial markers (D2-40 and mesothelin) in colorectal mucinous adenocarcinoma (MA) and non mucinous adenocarcinoma (NMA) specimens and relation to clinicopathological features and prognosis using manual tissue microarray technique. We studied tumor tissue specimens from 150 patients with colorectal MA and NMA who underwent radical surgery from January 2007 to January 2012. High-density manual tissue microarrays were constructed using a modified mechanical pencil tip technique, and paraffin sections were submitted for immunohistochemistry using Calretinin, D2-40 and mesothelin expressions. We found that NMA showed significantly more calretinin and D2-40 expression than MA In contrast, no statistically significant difference between NMA and MA was detected in mesothelin expression. There were no statistically significant relations between any of the clinicopathological or histological parameters and any of the three markers. In a univariate analysis, neither calretinin nor D2-40 expressions showed any significant relations to DFS or OS. However, mesothelin luminal expression was significantly associated with worse DFS. Multivariate Cox regression analysis proved that luminal mesothelin expression was an independent negative prognostic factor in NMA. In conclusion, Calretinin, D2-40 and mesothelin are aberrantly expressed in a proportion of CRC cases with more expression in NMA than MA. Aberrant expression of these mesothelial markers was not associated with clinicopathological or histological features of CRCs. Only mesothelin expression appears to be a strong predictor of adverse prognosis.

  14. Tumoral Environment Triggers Transcript Anomalies in Established Tumors: Induction of Altered Gene Expression and of Aberrant, Truncated and B2 Repeat-Containing Gene Transcripts

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    Pieter Rottiers

    1999-12-01

    Full Text Available In addition to eugenetic changes, cancerous cells exhibit extensive modifications in the expression levels of a variety of genes. The phenotypic switch observed after inoculation of T lymphoma cells into syngenic mice illustrates the active participation of tumoral environment in the induction of an aberrant gene expression pattern. To further substantiate this contribution, we performed polymerase chain reaction (PCR-based subtraction suppression hybridization (SSH to identify genes that are differentially expressed in tumor-derived EL4/13.3 cells compared to the same cells isolated from cultures. Besides a number of unknown genes, the subtracted library contained several known genes that have been reported to be expressed at increased levels in tumors and/or to contribute to carcinogenesis. Apart from clones representing translated transcripts, the subtracted library also contained a high number of clones representing B2 repeat elements, viz. short interspersed repetitive elements that are transcribed by RNA polymerase III. Northern blotting confirmed the induction of B2 transcripts in tumor tissue and also revealed induction of chimeric, B2 repeat-containing mRNA. The appearance of chimeric transcripts was accompanied by aberrant, shorter-than-full-length transcripts, specifically from upregulated genes. Accordingly, in addition to altered gene expression, tumoral environmental triggers constitute a potent mechanism to create an epigenetic diversity in cancers by inducing extensive transcript anomalies.

  15. Aberrant p63 and WT-1 expression in myoepithelial cells of pregnancy-associated breast cancer: implications for tumor aggressiveness and invasiveness

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    Zheli Xu, Wan Wang, Chu-Xia Deng, Yan-gao Man

    2009-01-01

    Full Text Available Our recent studies revealed that focal alterations in breast myoepithelial cell layers significantly impact the biological presentation of associated epithelial cells. As pregnancy-associated breast cancer (PABC has a significantly more aggressive clinical course and mortality rate than other forms of breast malignancies, our current study compared tumor suppressor expression in myoepithelial cells of PABC and non-PABC, to determine whether myoepithelial cells of PABC may have aberrant expression of tumor suppressors. Tissue sections from 20 cases of PABC and 20 cases of stage, grade, and age matched non-PABC were subjected to immunohistochemistry, and the expression of tumor suppressor maspin, p63, and Wilms' tumor 1 (WT-1 in calponin positive myoepithelial cells were statistically compared. The expression profiles of maspin, p63, and WT-1 in myoepithelial cells of all ducts encountered were similar between PABC and non-PABC. PABC, however, displayed several unique alterations in terminal duct and lobular units (TDLU, acini, and associated tumor tissues that were not seen in those of non-PABC, which included the absence of p63 and WT-1 expression in a vast majority of the myoepithelial cells, cytoplasmic localization of p63 in the entire epithelial cell population of some lobules, and substantially increasing WT-1 expression in vascular structures of the invasive cancer component. All or nearly all epithelial cells with aberrant p63 and WT-1 expression lacked the expression of estrogen receptor and progesterone receptor, whereas they had a substantially higher proliferation index than their counterparts with p63 and WT-1 expression. Hyperplastic cells with cytoplasmic p63 expression often adjacent to, and share a similar immunohistochemical and cytological profile with, invasive cancer cells. To our best knowledge, our main finings have not been previously reported. Our findings suggest that the functional status of myoepithelial cells may be

  16. Aberrant p63 and WT-1 expression in myoepithelial cells of pregnancy-associated breast cancer: implications for tumor aggressiveness and invasiveness.

    Science.gov (United States)

    Xu, Zheli; Wang, Wan; Deng, Chu-Xia; Man, Yan-Gao

    2009-01-01

    Our recent studies revealed that focal alterations in breast myoepithelial cell layers significantly impact the biological presentation of associated epithelial cells. As pregnancy-associated breast cancer (PABC) has a significantly more aggressive clinical course and mortality rate than other forms of breast malignancies, our current study compared tumor suppressor expression in myoepithelial cells of PABC and non-PABC, to determine whether myoepithelial cells of PABC may have aberrant expression of tumor suppressors. Tissue sections from 20 cases of PABC and 20 cases of stage, grade, and age matched non-PABC were subjected to immunohistochemistry, and the expression of tumor suppressor maspin, p63, and Wilms' tumor 1 (WT-1) in calponin positive myoepithelial cells were statistically compared. The expression profiles of maspin, p63, and WT-1 in myoepithelial cells of all ducts encountered were similar between PABC and non-PABC. PABC, however, displayed several unique alterations in terminal duct and lobular units (TDLU), acini, and associated tumor tissues that were not seen in those of non-PABC, which included the absence of p63 and WT-1 expression in a vast majority of the myoepithelial cells, cytoplasmic localization of p63 in the entire epithelial cell population of some lobules, and substantially increasing WT-1 expression in vascular structures of the invasive cancer component. All or nearly all epithelial cells with aberrant p63 and WT-1 expression lacked the expression of estrogen receptor and progesterone receptor, whereas they had a substantially higher proliferation index than their counterparts with p63 and WT-1 expression. Hyperplastic cells with cytoplasmic p63 expression often adjacent to, and share a similar immunohistochemical and cytological profile with, invasive cancer cells. To our best knowledge, our main finings have not been previously reported. Our findings suggest that the functional status of myoepithelial cells may be significantly

  17. Optical Aberrations and Wavefront

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    Nihat Polat

    2014-08-01

    Full Text Available The deviation of light to create normal retinal image in the optical system is called aberration. Aberrations are divided two subgroup: low-order aberrations (defocus: spherical and cylindrical refractive errors and high-order aberrations (coma, spherical, trefoil, tetrafoil, quadrifoil, pentafoil, secondary astigmatism. Aberrations increase with aging. Spherical aberrations are compensated by positive corneal and negative lenticular spherical aberrations in youth. Total aberrations are elevated by positive corneal and positive lenticular spherical aberrations in elderly. In this study, we aimed to analyze the basic terms regarding optic aberrations which have gained significance recently. (Turk J Ophthalmol 2014; 44: 306-11

  18. Gene Expression Meta-Analysis identifies Cytokine Pathways and 5q Aberrations involved in Metastasis of ERBB2 Amplified and Basal Breast Cancer

    DEFF Research Database (Denmark)

    Thomassen, Mads; Tan, Qihua; Burton, Mark

    2013-01-01

    Background: Breast tumors have been described by molecular subtypes characterized by pervasively different gene expression profiles. The subtypes are associated with different clinical parameters and origin of precursor cells. However, the biological pathways and chromosomal aberrations that differ...... the subgroups impact metastasis. Results: We have scrutinized publicly available gene expression datasets and identified molecular subtypes in 1,394 breast tumors with outcome data. By analysis of chromosomal regions and pathways using “Gene set enrichment analysis” followed by a meta-analysis, we identified...... show that high expression of 5q14 genes and low levels of TNFR2 pathway genes were associated with poor survival in basal-like cancers. Furthermore, low expression of 5q33 genes and interleukin-12 pathway genes were associated with poor outcome exclusively in ERBB2-like tumors. Conclusion...

  19. Aberrant Behaviours of Reaction Diffusion Self-organisation Models on Growing Domains in the Presence of Gene Expression Time Delays

    KAUST Repository

    Seirin Lee, S.

    2010-03-23

    Turing\\'s pattern formation mechanism exhibits sensitivity to the details of the initial conditions suggesting that, in isolation, it cannot robustly generate pattern within noisy biological environments. Nonetheless, secondary aspects of developmental self-organisation, such as a growing domain, have been shown to ameliorate this aberrant model behaviour. Furthermore, while in-situ hybridisation reveals the presence of gene expression in developmental processes, the influence of such dynamics on Turing\\'s model has received limited attention. Here, we novelly focus on the Gierer-Meinhardt reaction diffusion system considering delays due the time taken for gene expression, while incorporating a number of different domain growth profiles to further explore the influence and interplay of domain growth and gene expression on Turing\\'s mechanism. We find extensive pathological model behaviour, exhibiting one or more of the following: temporal oscillations with no spatial structure, a failure of the Turing instability and an extreme sensitivity to the initial conditions, the growth profile and the duration of gene expression. This deviant behaviour is even more severe than observed in previous studies of Schnakenberg kinetics on exponentially growing domains in the presence of gene expression (Gaffney and Monk in Bull. Math. Biol. 68:99-130, 2006). Our results emphasise that gene expression dynamics induce unrealistic behaviour in Turing\\'s model for multiple choices of kinetics and thus such aberrant modelling predictions are likely to be generic. They also highlight that domain growth can no longer ameliorate the excessive sensitivity of Turing\\'s mechanism in the presence of gene expression time delays. The above, extensive, pathologies suggest that, in the presence of gene expression, Turing\\'s mechanism would generally require a novel and extensive secondary mechanism to control reaction diffusion patterning. © 2010 Society for Mathematical Biology.

  20. Epigenetic reprogramming and aberrant expression of PRAME are associated with increased metastatic risk in Class 1 and Class 2 uveal melanomas

    Science.gov (United States)

    Field, Matthew G.; Durante, Michael A.; Decatur, Christina L.; Tarlan, Bercin; Oelschlager, Kristen M.; Stone, John F.; Kuznetsov, Jeffim; Bowcock, Anne M.; Kurtenbach, Stefan; Harbour, J. William

    2016-01-01

    Background We previously identified PRAME as a biomarker for metastatic risk in Class 1 uveal melanomas. In this study, we sought to define a threshold value for positive PRAME expression (PRAME+) in a large dataset, identify factors associated with PRAME expression, evaluate the prognostic value of PRAME in Class 2 uveal melanomas, and determine whether PRAME expression is associated with aberrant hypomethylation of the PRAME promoter. Results Among 678 samples analyzed by qPCR, 498 (73.5%) were PRAME- and 180 (26.5%) were PRAME+. Class 1 tumors were more likely to be PRAME-, whereas Class 2 tumors were more likely to be PRAME+ (P < 0.0001). PRAME expression was associated with shorter time to metastasis and melanoma specific mortality in Class 2 tumors (P = 0.01 and P = 0.02, respectively). In Class 1 tumors, PRAME expression was directly associated with SF3B1 mutations (P < 0.0001) and inversely associated with EIF1AX mutations (P = 0.004). PRAME expression was strongly associated with hypomethylation at 12 CpG sites near the PRAME promoter. MATERIALS AND METHODS Analyses included PRAME mRNA expression, Class 1 versus Class 2 status, chromosomal copy number, mutation status of BAP1, EIF1AX, GNA11, GNAQ and SF3B1, and genomic DNA methylation status. Analyses were performed on 555 de-identified samples from Castle Biosciences, 123 samples from our center, and 80 samples from the TCGA. Conclusions PRAME is aberrantly hypomethylated and activated in Class 1 and Class 2 uveal melanomas and is associated with increased metastatic risk in both classes. Since PRAME has been successfully targeted for immunotherapy, it may prove to be a companion prognostic biomarker. PMID:27486988

  1. Expression of a dynamin 2 mutant associated with Charcot-Marie-Tooth disease leads to aberrant actin dynamics and lamellipodia formation.

    Science.gov (United States)

    Yamada, Hiroshi; Kobayashi, Kinue; Zhang, Yubai; Takeda, Tetsuya; Takei, Kohji

    2016-08-15

    Specific mutations in dynamin 2 are linked to Charcot-Marie-Tooth disease (CMT), an inherited peripheral neuropathy. However, the effects of these mutations on dynamin function, particularly in relation to the regulation of the actin cytoskeleton remain unclear. Here, selected CMT-associated dynamin mutants were expressed to examine their role in the pathogenesis of CMT in U2OS cells. Ectopic expression of the dynamin CMT mutants 555Δ3 and K562E caused an approximately 50% decrease in serum stimulation-dependent lamellipodia formation; however, only K562E caused aberrations in the actin cytoskeleton. Immunofluorescence analysis showed that the K562E mutation resulted in the disappearance of radially aligned actin bundles and the simultaneous appearance of F-actin clusters. Live-cell imaging analyses showed F-actin polymers of decreased length assembled into immobile clusters in K562E-expressing cells. The K562E dynamin mutant colocalized with the F-actin clusters, whereas its colocalization with clathrin-coated pit marker proteins was decreased. Essentially the same results were obtained using another cell line, HeLa and NG108-15 cells. The present study is the first to show the association of dynamin CMT mutations with aberrant actin dynamics and lamellipodia, which may contribute to defective endocytosis and myelination in Schwann cells in CMT. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  2. Aberrant c-erbB2 expression in cell clusters overlying focally disrupted breast myoepithelial cell layers: a trigger or sign for emergence of more aggressive cell clones?

    Directory of Open Access Journals (Sweden)

    Xichen Zhang, Shahreyar Shar Hashemi, Morvarid Yousefi, Jinsong Ni, Qiuyue Wang, Ling Gao, Pengtao Gong, Chunling Gao, Joy Sheng, Jeffrey Mason, Yan-gao Man

    2008-01-01

    Full Text Available Our recent studies revealed that cell clusters overlying focal myoepithelial cell layer disruption (FMCLD had a significantly higher frequency of genetic instabilities and expression of invasion-related genes than their adjacent counterparts within the same duct. Our current study attempted to assess whether these cell clusters would also have elevated c-erbB2 expression. Human breast tumors (n=50 with a high frequency of FMCLD were analyzed with double immunohistochemistry, real-time RT-PCR, and chromogenic in situ hybridization for c-erbB2 protein and gene expression. Of 448 FMCLD detected, 404 (90.2% were associated with cell clusters that had intense c-erbB2 immunoreactivities primarily in their cytoplasm, in contrast to their adjacent counterparts within the same duct, which had no or barely detectable c-erbB2 expression. These c-erbB2 positive cells were arranged as tongue-like projections, “puncturing” into the stroma, and about 20% of them were in direct continuity with tube-like structures that resembled blood vessels. Aberrant c-erbB2 expression was also seen in clusters of architecturally normal-appearing ducts that had distinct cytological abnormalities in both ME and epithelial cells, whereas not in their clear-cut normal counterparts. Molecular assays detected markedly higher c-erbB2 mRNA and gene amplification in cell clusters associated with FMCLD than in those associated with non-disrupted ME cell layers. Our findings suggest that cell clusters overlying FMCLD may represent the precursors of pending invasive lesions, and that aberrant cerbB2 expression may trigger or signify the emergence of biologically more aggressive cell clones.

  3. Ectopic expression of homeobox gene NKX2-1 in diffuse large B-cell lymphoma is mediated by aberrant chromatin modifications.

    Directory of Open Access Journals (Sweden)

    Stefan Nagel

    Full Text Available Homeobox genes encode transcription factors ubiquitously involved in basic developmental processes, deregulation of which promotes cell transformation in multiple cancers including hematopoietic malignancies. In particular, NKL-family homeobox genes TLX1, TLX3 and NKX2-5 are ectopically activated by chromosomal rearrangements in T-cell neoplasias. Here, using transcriptional microarray profiling and RQ-PCR we identified ectopic expression of NKL-family member NKX2-1, in a diffuse large B-cell lymphoma (DLBCL cell line SU-DHL-5. Moreover, in silico analysis demonstrated NKX2-1 overexpression in 5% of examined DLBCL patient samples. NKX2-1 is physiologically expressed in lung and thyroid tissues where it regulates differentiation. Chromosomal and genomic analyses excluded rearrangements at the NKX2-1 locus in SU-DHL-5, implying alternative activation. Comparative expression profiling implicated several candidate genes in NKX2-1 regulation, variously encoding transcription factors, chromatin modifiers and signaling components. Accordingly, siRNA-mediated knockdown and overexpression studies confirmed involvement of transcription factor HEY1, histone methyltransferase MLL and ubiquitinated histone H2B in NKX2-1 deregulation. Chromosomal aberrations targeting MLL at 11q23 and the histone gene cluster HIST1 at 6p22 which we observed in SU-DHL-5 may, therefore, represent fundamental mutations mediating an aberrant chromatin structure at NKX2-1. Taken together, we identified ectopic expression of NKX2-1 in DLBCL cells, representing the central player in an oncogenic regulative network compromising B-cell differentiation. Thus, our data extend the paradigm of NKL homeobox gene deregulation in lymphoid malignancies.

  4. Integrated genome-wide genotyping and gene expression profiling reveals BCL11B as a putative oncogene in acute myeloid leukemia with 14q32 aberrations.

    Science.gov (United States)

    Abbas, Saman; Sanders, Mathijs A; Zeilemaker, Annelieke; Geertsma-Kleinekoort, Wendy M C; Koenders, Jasper E; Kavelaars, Francois G; Abbas, Zabiollah G; Mahamoud, Souad; Chu, Isabel W T; Hoogenboezem, Remco; Peeters, Justine K; van Drunen, Ellen; van Galen, Janneke; Beverloo, H Berna; Löwenberg, Bob; Valk, Peter J M

    2014-05-01

    Acute myeloid leukemia is a neoplasm characterized by recurrent molecular aberrations traditionally demonstrated by cytogenetic analyses. We used high density genome-wide genotyping and gene expression profiling to reveal acquired cryptic abnormalities in acute myeloid leukemia. By genome-wide genotyping of 137 cases of primary acute myeloid leukemia, we disclosed a recurrent focal amplification on chromosome 14q32, which included the genes BCL11B, CCNK, C14orf177 and SETD3, in two cases. In the affected cases, the BCL11B gene showed consistently high mRNA expression, whereas the expression of the other genes was unperturbed. Fluorescence in situ hybridization on 40 cases of acute myeloid leukemia with high BCL11B mRNA expression [2.5-fold above median; 40 out of 530 cases (7.5%)] revealed 14q32 abnormalities in two additional cases. In the four BCL11B-rearranged cases the 14q32 locus was fused to different partner chromosomes. In fact, in two cases, we demonstrated that the focal 14q32 amplifications were integrated into transcriptionally active loci. The translocations involving BCL11B result in increased expression of full-length BCL11B protein. The BCL11B-rearranged acute myeloid leukemias expressed both myeloid and T-cell markers. These biphenotypic acute leukemias all carried FLT3 internal tandem duplications, a characteristic marker of acute myeloid leukemia. BCL11B mRNA expression in acute myeloid leukemia appeared to be strongly associated with expression of other T-cell-specific genes. Myeloid 32D(GCSF-R) cells ectopically expressing Bcl11b showed decreased proliferation rate and less maturation. In conclusion, by an integrated approach involving high-throughput genome-wide genotyping and gene expression profiling we identified BCL11B as a candidate oncogene in acute myeloid leukemia.

  5. The tumor-selective over-expression of the human Hsp 70 gene is attributed to the aberrant controls at both initiation and elongation levels of transcription

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    The tumor selective over-expression of the human Hsp70 gene has been well documented in human tumors, linked to the poor prognosis, being refractory to chemo- and radio-therapies as well as the advanced stage of tumorous lesions in particular. However, both the nature and details of aberrations in the control of the Hsp70 expression in tumor remain enigmatic. By comparing various upstream segments of the Hsp70gene for each's ability to drive the luciferase reporter genes in the context of the tumor cell lines varying in their p53 status and an immortal normal liver cell line, we demonstrated in a great detail the defects in the control mechanisms at the both initiation and elongation levels of transcription being instrumental to the tumor selective profile of its expression. Our data should not only offer new insights into our understanding of the tumor specific over-expression of the human Hsp70 gene, but also paved the way for the rational utilization of the tumor selective mechanism with the Hsp70 at the central stage for targeting the therapeutic gene expression to human tumors.

  6. Genome-wide profiling of methylation identifies novel targets with aberrant hypermethylation and reduced expression in low-risk myelodysplastic syndromes.

    Science.gov (United States)

    del Rey, M; O'Hagan, K; Dellett, M; Aibar, S; Colyer, H A A; Alonso, M E; Díez-Campelo, M; Armstrong, R N; Sharpe, D J; Gutiérrez, N C; García, J L; De Las Rivas, J; Mills, K I; Hernández-Rivas, J M

    2013-03-01

    Gene expression profiling signatures may be used to classify the subtypes of Myelodysplastic syndrome (MDS) patients. However, there are few reports on the global methylation status in MDS. The integration of genome-wide epigenetic regulatory marks with gene expression levels would provide additional information regarding the biological differences between MDS and healthy controls. Gene expression and methylation status were measured using high-density microarrays. A total of 552 differentially methylated CpG loci were identified as being present in low-risk MDS; hypermethylated genes were more frequent than hypomethylated genes. In addition, mRNA expression profiling identified 1005 genes that significantly differed between low-risk MDS and the control group. Integrative analysis of the epigenetic and expression profiles revealed that 66.7% of the hypermethylated genes were underexpressed in low-risk MDS cases. Gene network analysis revealed molecular mechanisms associated with the low-risk MDS group, including altered apoptosis pathways. The two key apoptotic genes BCL2 and ETS1 were identified as silenced genes. In addition, the immune response and micro RNA biogenesis were affected by the hypermethylation and underexpression of IL27RA and DICER1. Our integrative analysis revealed that aberrant epigenetic regulation is a hallmark of low-risk MDS patients and could have a central role in these diseases.

  7. Hypermethylation of the HIC1 promoter and aberrant expression of HIC1/SIRT1 contribute to the development of thyroid papillary carcinoma.

    Science.gov (United States)

    Wu, Wenyi; Zhang, Liting; Lin, Jianqing; Huang, Hanwei; Shi, Bai; Lin, Xingong; Huang, Zhongxin; Wang, Chaoyang; Qiu, Jianlong; Wei, Xiaolong

    2016-12-20

    Hypermethylation leading to the loss of hypermethylated in cancer-1 (HIC1) gene expression occurs in many different types of human cancer. HIC1 is a transcriptional repressor that directly binds to the promoter region of NAD-dependent deacetylase sirtuin-1 (SIRT1). SIRT1 functions in cell growth, is anti-apoptotic, protect neurons, functions in senescence, and regulates energy restriction. Epigenetic modification and dysregulation affecting the HIC1/SIRT1 axis is potentially important for the development of malignancies. However, the importance of HIC1 expression in the development of papillary thyroid carcinoma, especially in Chinese patients, is uncertain. Therefore, we assessed the level of methylation in the HIC1 promoter and the mRNA and protein expression levels of HIC1 and SIRT1 in human thyroid papillary carcinoma and tumor adjacent control tissues. The demethylation reagent 5-aza-2'-deoxyctidine (5-aza-dc) and an HIC1 overexpression plasmid were used to manipulate the HIC1/SIRT1 pathway, and the effects on cell senescence, apoptosis, and cell cycle progression were assessed. Compared to normal thyroid tissue, thyroid tumors had lower expression of HIC1 and higher SIRT1 expression. The level of HIC1 methylation was also higher in thyroid carcinoma tissues than adjacent tissues. HIC1 expression was closely correlated with patient age and tumor progression. Restoration of HIC1 expression through an overexpression plasmid or 5-aza-dC treatment reduced SIRT1 expression and cell proliferation, and led to senescence, cell cycle arrest, and apoptosis. Aberrant expression of HIC1/SIRT1 and hypermethylation of the HIC1 promoter may be critical for the development and progression of papillary thyroid cancer.

  8. Aberrant expression of mucin core proteins and o-linked glycans associated with progression of pancreatic cancer

    DEFF Research Database (Denmark)

    Remmers, Neeley; Anderson, Judy M; Linde, Erin M;

    2013-01-01

    Mucin expression is a common feature of most adenocarcinomas and features prominently in current attempts to improve diagnosis and therapy for pancreatic cancer and other adenocarcinomas. We investigated the expression of a number of mucin core proteins and associated O-linked glycans expressed...

  9. Aberrant expression of microRNAs as biomarker for schizophrenia: from acute state to partial remission, and from peripheral blood to cortical tissue.

    Science.gov (United States)

    Lai, C-Y; Lee, S-Y; Scarr, E; Yu, Y-H; Lin, Y-T; Liu, C-M; Hwang, T-J; Hsieh, M H; Liu, C-C; Chien, Y-L; Udawela, M; Gibbons, A S; Everall, I P; Hwu, H-G; Dean, B; Chen, W J

    2016-01-19

    Based on our previous finding of a seven-miRNA (hsa-miR-34a, miR-449a, miR-564, miR-432, miR-548d, miR-572 and miR-652) signature as a potential biomarker for schizophrenia, this study aimed to examine if hospitalization could affect expressions of these miRNAs. We compared their expression levels between acute state and partial remission state in people with schizophrenia (n=48) using quantitative PCR method. Further, to examine whether the blood and brain show similar expression patterns, the expressions of two miRNAs (hsa-miR-34a and hsa-miR-548d) were examined in the postmortem brain tissue of people with schizophrenia (n=25) and controls (n=27). The expression level of the seven miRNAs did not alter after ~2 months of hospitalization with significant improvement in clinical symptoms, suggesting the miRNAs could be traits rather than state-dependent markers. The aberrant expression seen in the blood of hsa-miR-34a and hsa-miR-548d were not present in the brain samples, but this does not discount the possibility that the peripheral miRNAs could be clinically useful biomarkers for schizophrenia. Unexpectedly, we found an age-dependent increase in hsa-miR-34a expressions in human cortical (Brodmann area 46 (BA46)) but not subcortical region (caudate putamen). The correlation between hsa-miR-34a expression level in BA46 and age was much stronger in the controls than in the cases, and the corresponding correlation in the blood was only seen in the cases. The association between the miRNA dysregulations, the disease predisposition and aging warrants further investigation. Taken together, this study provides further insight on the candidate peripheral miRNAs as stable biomarkers for the diagnostics of schizophrenia.

  10. Homeotic-like modification of stamens to petals is associated with aberrant mitochondrial gene expression in cytoplasmic male sterile Ogura Brassica juncea

    Indian Academy of Sciences (India)

    Gargi Meur; K. Gaikwad; S. R. Bhat; S. Prakash; P. B. Kirti

    2006-08-01

    We have previously reported correction of severe leaf chlorosis in the cytoplasmic male sterile Ogura (also called Ogu) Brassica juncea line carrying Ogura cytoplasm by plastid substitution via protoplast fusion. Two cybrids obtained from the fusion experiment, Og1 and Og2, were green and carried the plastid genome of B. juncea cv. RLM198. While Og1 displayed normal flower morphology comparable to that of its euplasmic B. juncea counterpart except for sterile anthers, Og2 retained homeotic-like floral modification of stamens to petal-like structures and several other floral deformities observed in the chlorotic (Ogu) B. juncea cv. RLM198 (or OgRLM). With respect to the mitochondrial genome, Og1 showed 81% genetic similarity to the fertile cultivar RLM while Og2 showed 93% similarity to OgRLM. In spite of recombination and rearrangements in the mitochondrial genomes in the cybrids, expression patterns of 10 out of 11 mitochondrial genes were similar in all the three CMS lines; the only exception was atp6, whose expression was altered. While Og1 showed normal atp6 transcript similar to that in RLM, in Og2 and OgRLM weak expression of a longer transcript was detected. These results suggest that the homeotic-like changes in floral patterning leading to petaloid stamens in Og2 and OgRLM may be associated with aberrant mitochondrial gene expression.

  11. Illumina Sequencing Reveals Aberrant Expression of MicroRNAs and Their Variants in Whitefish (Coregonus lavaretus Liver after Exposure to Microcystin-LR.

    Directory of Open Access Journals (Sweden)

    Paweł Brzuzan

    Full Text Available Molecular analyses show that challenging fish with microcystin-LR (MC-LR causes perturbations of microRNA (miRNA signaling. However, the significance and scope of these alterations is currently unknown. To address this issue, we studied miRNA gene expression in the liver of juvenile whitefish, C. lavaretus, during 28 days of exposure to a subacute dose of MC-LR (100 μg·kg-1 body mass. Using genomic resources of Atlantic salmon (AGKD03, the mature miRNA library of Atlantic salmon (miRBase-21 and bioinformatics tools (sRNAbench, we discovered and annotated a total of 377 distinct mature miRNAs belonging to 93 families of evolutionary conserved miRNAs, as well as 24 novel mature miRNA candidates that were mapped to 14 distinct S. salar miRNA precursors. miRNA-Seq transcriptome profiling of liver tissues revealed differential miRNA expression in control and treated fish at 14 days (73 miRNAs were modulated and at 28 days (83 miRNAs of the treatment, subsequently validated by qPCR for nine selected differentially expressed miRNAs. Additional qPCR study confirmed the miRNA-Seq data and revealed consistent, aberrant miRNAs expression profile in the later phase of MC-LR hepatotoxicity (7-28 d. Functional annotation analysis revealed that the aberrantly expressed miRNAs have target genes involved in cytoskeletal remodeling, cell metabolism, cell cycle regulation and apoptosis; dysregulation of these processes in liver cells leads to cirrhosis and hepatocellular carcinoma in humans. To enable deeper insight into the molecular responses of liver cells in fish exposed to MC-LR, we expanded the miRNAome analysis by inclusion of miRNA variants (isomiRs profiles, and we showed that the isomiR profiles of liver specific MiR122, and a few other miRNAs, correlated with MC-LR treatment. Given the importance of isomiRs for disease biology in mammals, we believe that further research focused on the miRNA isoforms will bring us closer to better understanding the

  12. FBXW7-mutated colorectal cancer cells exhibit aberrant expression of phosphorylated-p53 at Serine-15

    Science.gov (United States)

    Normatova, Makhliyo; Babaei-Jadidi, Roya; Tomlinson, Ian; Nateri, Abdolrahman S.

    2015-01-01

    FBXW7 mutations occur in a variety of human cancers including colorectal cancer (CRC). Elucidating its mechanism of action has become crucial for cancer therapy; however, it is also complicated by the fact that FBXW7 can influence many pathways due to its role as an E3-ubiquitin ligase in proteasome degradation. FBXW7 and TP53 are tumour suppressors intensively implicated in colorectal carcinogenesis. Deletion mutations in these two genes in animal models mark the progression from adenoma to carcinoma. Although still largely unknown, the last defense mechanism against CRC at the molecular level could be through a synergistic effect of the two genes. The underlying mechanism requires further investigation. In our laboratory, we have used a phospho-kinase profiler array to illustrate a potential molecular link between FBXW7 and p53 in CRC cells. In vitro and in vivo assessments demonstrated aberrant induction of phosphorylated p53 at Serine 15 [phospho-p53(Ser15)] in human FBXW7-deficient CRC cells as compared to their FBXW7-wild-type counterparts. FBXW7 loss in HCT116 cells promoted resistance to oxaliplatin. Immunoblotting data further confirmed that reduction of phospho-p53(Ser15) may contribute to the decreased efficacy of therapy in FBXW7-mutated CRC cells. The findings may suggest the applicability of phospho-p53(Ser15) as an indicative marker of FBXW7-mutations. Phospho-p53(Ser15) regulation by FBXW7 E3-ligase activity could provide important clues for understanding FBXW7 behavior in tumour progression and grounds for its clinical applicability thereafter. PMID:25860929

  13. Correlations between corneal and total wavefront aberrations

    Science.gov (United States)

    Mrochen, Michael; Jankov, Mirko; Bueeler, Michael; Seiler, Theo

    2002-06-01

    Purpose: Corneal topography data expressed as corneal aberrations are frequently used to report corneal laser surgery results. However, the optical image quality at the retina depends on all optical elements of the eye such as the human lens. Thus, the aim of this study was to investigate the correlations between the corneal and total wavefront aberrations and to discuss the importance of corneal aberrations for representing corneal laser surgery results. Methods: Thirty three eyes of 22 myopic subjects were measured with a corneal topography system and a Tschernig-type wavefront analyzer after the pupils were dilated to at least 6 mm in diameter. All measurements were centered with respect to the line of sight. Corneal and total wavefront aberrations were calculated up to the 6th Zernike order in the same reference plane. Results: Statistically significant correlations (p corneal and total wavefront aberrations were found for the astigmatism (C3,C5) and all 3rd Zernike order coefficients such as coma (C7,C8). No statistically significant correlations were found for all 4th to 6th order Zernike coefficients except for the 5th order horizontal coma C18 (p equals 0.003). On average, all Zernike coefficients for the corneal aberrations were found to be larger compared to Zernike coefficients for the total wavefront aberrations. Conclusions: Corneal aberrations are only of limited use for representing the optical quality of the human eye after corneal laser surgery. This is due to the lack of correlation between corneal and total wavefront aberrations in most of the higher order aberrations. Besides this, the data present in this study yield towards an aberration balancing between corneal aberrations and the optical elements within the eye that reduces the aberration from the cornea by a certain degree. Consequently, ideal customized ablations have to take both, corneal and total wavefront aberrations, into consideration.

  14. Eradication of hepatitis C virus subgenomic replicon by interferon results in aberrant retinol-related protein expression.

    Science.gov (United States)

    Koike, Kazuko; Takaki, Akinobu; Kato, Nobuyuki; Ouchida, Mamoru; Kanzaki, Hirotaka; Yasunaka, Tetsuya; Shiraha, Hidenori; Miyake, Yasuhiro; Yamamoto, Kazuhide

    2012-01-01

    Hepatitis C virus (HCV) infection induces several changes in hepatocytes, such as oxidative stress, steatosis, and hepatocarcinogenesis. Although considerable progress has been made during recent years, the mechanisms underlying these functions remain unclear. We employed proteomic techniques in HCV replicon-harboring cells to determine the effects of HCV replication on host-cell protein expression. We examined two-dimensional electrophoresis (2-DE) and mass spectrometry to compare and identify differentially expressed proteins between HCV subgenomic replicon-harboring cells and their "cured" cells. One of the identified proteins was confirmed using enzyme-linked immunosorbent assay (ELISA) and Western blot analysis. Full-length HCV genome RNA replicating and cured cells were also assessed using ELISA. Replicon-harboring cells showed higher expression of retinal dehydrogenase 1 (RALDH-1), which converts retinol to retinoic acid, and the cured cells showed higher expression of retinol-binding protein (RBP), which transports retinol from the liver to target tissues. The alteration in RBP expression was also confirmed by ELISA and Western blot analysis. We conclude that protein expression profiling demonstrated that HCV replicon eradication affected retinol-related protein expression.

  15. Eradication of Hepatitis C Virus Subgenomic Replicon by Interferon Results in Aberrant Retinol-Related Protein Expression

    Directory of Open Access Journals (Sweden)

    Koike,Kazuko

    2012-12-01

    Full Text Available Hepatitis C virus (HCV infection induces several changes in hepatocytes, such as oxidative stress, steatosis, and hepatocarcinogenesis. Although considerable progress has been made during recent years, the mechanisms underlying these functions remain unclear. We employed proteomic techniques in HCV replicon-harboring cells to determine the effects of HCV replication on host-cell protein expression. We examined two-dimensional electrophoresis (2-DE and mass spectrometry to compare and identify differentially expressed proteins between HCV subgenomic replicon-harboring cells and their “cured” cells. One of the identified proteins was confirmed using enzyme-linked immunosorbent assay (ELISA and Western blot analysis. Full-length HCV genome RNA replicating and cured cells were also assessed using ELISA. Replicon-harboring cells showed higher expression of retinal dehydrogenase 1 (RALDH-1, which converts retinol to retinoic acid, and the cured cells showed higher expression of retinol-binding protein (RBP, which transports retinol from the liver to target tissues. The alteration in RBP expression was also confirmed by ELISA and Western blot analysis. We conclude that protein expression profiling demonstrated that HCV replicon eradication affected retinol-related protein expression.

  16. Inferring a role for methylation of intergenic DNA in the regulation of genes aberrantly expressed in precursor B-cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Almamun, Md; Kholod, Olha; Stuckel, Alexei J; Levinson, Benjamin T; Johnson, Nathan T; Arthur, Gerald L; Davis, J Wade; Taylor, Kristen H

    2017-01-17

    A complete understanding of the mechanisms involved in the development of pre-B ALL is lacking. In this study, we integrated DNA methylation data and gene expression data to elucidate the impact of aberrant intergenic DNA methylation on gene expression in pre-B ALL. We found a subset of differentially methylated intergenic loci that were associated with altered gene expression in pre-B ALL patients. Notably, 84% of these regions were also bound by transcription factors (TF) known to play roles in differentiation and B-cell development in a lymphoblastoid cell line. Further, an overall downregulation of eRNA transcripts was observed in pre-B ALL patients and these transcripts were associated with the downregulation of putative target genes involved in B-cell migration, proliferation, and apoptosis. The identification of novel putative regulatory regions highlights the significance of intergenic DNA sequences and may contribute to the identification of new therapeutic targets for the treatment of pre-B ALL.

  17. Aberrant expression of leukemia inhibitory factor receptor (LIFR) and leukemia inhibitory factor (LIF) is associated with tubal pregnancy occurrence

    OpenAIRE

    Li, Yong; Sun, Lizhou; ZHAO, Denmei; Ouyang, Jun; Xiang, Mei

    2015-01-01

    Tubal pregnancy is a major cause of maternal death in the first trimester and exploration of its underlying molecular mechanism is of great importance. This study aimed to explore the association of tubal pregnancy with leukemia inhibitory factor (LIF) and leukemia inhibitory factor receptor (LIFR) expression in oviduct tissues. Materials and methods: Immunohistochemistry was performed to probe the differential expression of LIF and LIFR in oviduct tissues among a control group (including NP...

  18. Frequent attenuation of the WWOX tumor suppressor in osteosarcoma is associated with increased tumorigenicity and aberrant RUNX2 expression.

    Science.gov (United States)

    Kurek, Kyle C; Del Mare, Sara; Salah, Zaidoun; Abdeen, Suhaib; Sadiq, Hussain; Lee, Suk-Hee; Gaudio, Eugenio; Zanesi, Nicola; Jones, Kevin B; DeYoung, Barry; Amir, Gail; Gebhardt, Mark; Warman, Matthew; Stein, Gary S; Stein, Janet L; Lian, Jane B; Aqeilan, Rami I

    2010-07-01

    The WW domain-containing oxidoreductase (WWOX) is a tumor suppressor that is deleted or attenuated in most human tumors. Wwox-deficient mice develop osteosarcoma (OS), an aggressive bone tumor with poor prognosis that often metastasizes to lung. On the basis of these observations, we examined the status of WWOX in human OS specimens and cell lines. In human OS clinical samples, WWOX expression was absent or reduced in 58% of tumors examined (P < 0.0001). Compared with the primary tumors, WWOX levels frequently increased in tumors resected following chemotherapy. In contrast, tumor metastases to lung often exhibited reduced WWOX levels relative to the primary tumor. In human OS cell lines having reduced WWOX expression, ectopic expression of WWOX inhibited proliferation and attenuated invasion in vitro, and suppressed tumorigenicity in nude mice. Expression of WWOX was associated with reduced RUNX2 expression in OS cell lines, whereas RUNX2 levels were elevated in femurs of Wwox-deficient mice. Furthermore, WWOX reconstitution in HOS cells was associated with downregulation of RUNX2 levels and RUNX2 target genes, consistent with the ability of WWOX to suppress RUNX2 transactivation activity. In clinical samples, RUNX2 was expressed in the majority of primary tumors and undetectable in most tumors resected following chemotherapy, whereas most metastases were RUNX2 positive. Our results deepen the evidence of a tumor suppressor role for WWOX in OS, furthering its prognostic and therapeutic significance in this disease. Copyright 2010 AACR.

  19. Tacrolimus increases Nox4 expression in human renal fibroblasts and induces fibrosis-related genes by aberrant TGF-beta receptor signalling.

    Science.gov (United States)

    Kern, Georg; Mair, Sabine M; Noppert, Susie-Jane; Jennings, Paul; Schramek, Herbert; Rudnicki, Michael; Mueller, Gerhard A; Mayer, Gert; Koppelstaetter, Christian

    2014-01-01

    Chronic nephrotoxicity of immunosuppressives is one of the main limiting factors in the long-term outcome of kidney transplants, leading to tissue fibrosis and ultimate organ failure. The cytokine TGF-β is considered a key factor in this process. In the human renal fibroblast cell line TK-173, the macrolide calcineurin inhibitor tacrolimus (FK-506) induced TGF-β-like effects, manifested by increased expression of NAD(P)H-oxidase 4 (Nox4), transgelin, tropomyosin 1, and procollagen α1(V) mRNA after three days. The macrolide mTOR inhibitor rapamycin had similar effects, while cyclosporine A did not induce fibrose-related genes. Concentration dependence curves were sigmoid, where mRNA expression was induced already at low nanomolar levels of tacrolimus, and reached saturation at 100-300 nM. The effects were independent of extracellular TGF-β as confirmed by the use of neutralizing antibodies, and thus most likely caused by aberrant TGF-β receptor signaling, where binding of tacrolimus to the regulatory FKBP12 protein results in a "leaky" TGF-β receptor. The myofibroblast marker α-smooth muscle actin was neither induced by tacrolimus nor by TGF-β1, indicating an incomplete activation of TK-173 fibroblasts under culture conditions. Tacrolimus- and TGF-β1-induced Nox4 protein upregulation was confirmed by Western blotting, and was accompanied by a rise in intracellular H2O2 concentration. Si-RNA mediated knock-down of Nox4 expression prevented up-regulation of procollagen α1(V) mRNA in tacrolimus-treated cells, but induced procollagen α1(V) expression in control cells. Nox4 knock-down had no significant effect on the other genes tested. TGF-β is a key molecule in fibrosis, and the constant activation of aberrant receptor signaling by tacrolimus might contribute to the long-term development of interstitial kidney fibrosis in immunosuppressed patients. Nox4 levels possibly play a regulatory role in these processes.

  20. Tacrolimus increases Nox4 expression in human renal fibroblasts and induces fibrosis-related genes by aberrant TGF-beta receptor signalling.

    Directory of Open Access Journals (Sweden)

    Georg Kern

    Full Text Available Chronic nephrotoxicity of immunosuppressives is one of the main limiting factors in the long-term outcome of kidney transplants, leading to tissue fibrosis and ultimate organ failure. The cytokine TGF-β is considered a key factor in this process. In the human renal fibroblast cell line TK-173, the macrolide calcineurin inhibitor tacrolimus (FK-506 induced TGF-β-like effects, manifested by increased expression of NAD(PH-oxidase 4 (Nox4, transgelin, tropomyosin 1, and procollagen α1(V mRNA after three days. The macrolide mTOR inhibitor rapamycin had similar effects, while cyclosporine A did not induce fibrose-related genes. Concentration dependence curves were sigmoid, where mRNA expression was induced already at low nanomolar levels of tacrolimus, and reached saturation at 100-300 nM. The effects were independent of extracellular TGF-β as confirmed by the use of neutralizing antibodies, and thus most likely caused by aberrant TGF-β receptor signaling, where binding of tacrolimus to the regulatory FKBP12 protein results in a "leaky" TGF-β receptor. The myofibroblast marker α-smooth muscle actin was neither induced by tacrolimus nor by TGF-β1, indicating an incomplete activation of TK-173 fibroblasts under culture conditions. Tacrolimus- and TGF-β1-induced Nox4 protein upregulation was confirmed by Western blotting, and was accompanied by a rise in intracellular H2O2 concentration. Si-RNA mediated knock-down of Nox4 expression prevented up-regulation of procollagen α1(V mRNA in tacrolimus-treated cells, but induced procollagen α1(V expression in control cells. Nox4 knock-down had no significant effect on the other genes tested. TGF-β is a key molecule in fibrosis, and the constant activation of aberrant receptor signaling by tacrolimus might contribute to the long-term development of interstitial kidney fibrosis in immunosuppressed patients. Nox4 levels possibly play a regulatory role in these processes.

  1. Aberrant expression and potency as a cancer immunotherapy target of alpha-methylacyl-coenzyme A racemase in prostate cancer

    Directory of Open Access Journals (Sweden)

    Masumori Naoya

    2009-12-01

    Full Text Available Abstract Alpha-methylacyl-CoA racemase (AMACR is an enzyme playing an important role in the beta-oxidation of branched-chain fatty acids and fatty acid derivatives. High expression levels of AMACR have been described in various cancers, including prostate cancer, colorectal cancer and kidney cancer. Because of its cancer-specific and frequent expression, AMACR could be an attractive target for cytotoxic T-lymphocyte (CTL-based immunotherapy for cancer. In the present study, we examined the induction of AMACR-specific CTLs from prostate cancer patients' peripheral blood mononuclear cells (PBMCs and determined HLA-A24-restricted CTL epitopes. RT-PCR and immunohistochemical analysis revealed that AMACR was strongly expressed in prostate cancer cell lines and tissues as compared with benign or normal prostate tissues. Four AMACR-derived peptides carrying the HLA-A24-binding motif were synthesized from the amino acid sequence of this protein and analyzed to determine their binding affinities to HLA-A24. By stimulating patient's PBMCs with the peptides, specific CTLs were successfully induced in 6 of 11 patients. The peptide-specific CTLs exerted significant cytotoxic activity against AMACR-expressing prostate cancer cells in the context of HLA-A24. Our study demonstrates that AMACR could become a target antigen for prostate cancer immunotherapy, and that the AMACR-derived peptides might be good peptide vaccine candidates for HLA-A24-positive AMACR-expressing cancer patients.

  2. Aberrant promoter methylation and gene expression of H-cadherin gene is associated with tumor progression and recurrence in epithelial ovarian carcinoma

    Directory of Open Access Journals (Sweden)

    Rahul Bhagat

    2014-01-01

    Full Text Available Background: Loss of expression of cadherins by promoter hypermethylation has been described in many epithelial cancers, and it may play a role in tumor cell invasion and metastasis. Previously, we reported that E-cadherin gene is frequently methylated in epithelial ovarian cancer. Aim: The aim of this study was to compare the promoter hypermethylation of H-cadherin gene in ovarian epithelial neoplasms to better understand the role of epigenetic silencing in carcinogenesis. Materials and Methods: We examined the promoter methylation of the H-cadherin gene in 134 epithelial ovarian carcinomas (EOC, 23 low malignant potential (LMP tumors, 26 benign cystadenomas and 15 normal ovarian tissues. Methylation was investigated by methylation specific polymerase chain reaction (MSP and the results confirmed by bisulfite DNA sequencing. Relative gene expression of H-cadherin was done using quantitative reverse transcriptase PCR on 51 EOC cases, 9 LMP tumors, 7 benign cystadenomas with 5 normal ovarian tissues. Results: Aberrant methylation of H-cadherin was present in 20 of 134 (15% carcinoma cases, 2 of 23 (09% LMP tumors and 1 of 26 (4% benign cystadenomas. No methylation was observed in any of the normal ovarian tissues. The mRNA expression level of H-cadherin was significantly down-regulated in EOC and LMP tumors than the corresponding normal tissues, whereas the expression level was normal in benign cystadenomas. A significant correlation of H-cadherin promoter methylation was observed with reduced gene expression in EOC. The prevalence of H-cadherin methylation was associated significantly with stage, histopathological grade, and menopausal status of the patient. H-cadherin methylation also had significant association with recurrence and differentiation of tumor. Conclusion: Our findings suggest an association between H-cadherin methylation, tumor progression and recurrence in EOC.

  3. Aberrant expression of CKLF-like MARVEL transmembrane member 5 (CMTM5) by promoter methylation in myeloid leukemia.

    Science.gov (United States)

    Niu, Jihong; Li, Henan; Zhang, Yao; Li, Jinlan; Xie, Min; Li, Lingdi; Qin, Xiaoying; Qin, Yazhen; Guo, Xiaohuan; Jiang, Qian; Liu, Yanrong; Chen, Shanshan; Huang, Xiaojun; Han, Wenling; Ruan, Guorui

    2011-06-01

    CMTM5 has been shown to exhibit tumor suppressor activities, however, its role in leukemia is unclear. Herein we firstly reported the expression and function of CMTM5 in myeloid leukemia. CMTM5 was down-regulated, or undetectable, in leukemia cell lines and bone marrow cells from leukemia patients with promoter methylation. Ectopic expression of CMTM5-v1 strongly inhibited the proliferation of K562 and MEG-01 cells. In addition, significant negative correlations were observed between CMTM5 and three leukemia-specific fusion genes (AML1-ETO, PML-RARα and BCR/ABL1). CMTM5 expression was up-regulated in patients who had undergone treatment. Therefore, CMTM5 may be involved in the pathomechanism of myeloid leukemias. Copyright © 2010 Elsevier Ltd. All rights reserved.

  4. Aberrant E-cadherin and gamma-catenin expression in malignant mesothelioma and its diagnostic and biological relevance.

    Science.gov (United States)

    Orecchia, Sara; Schillaci, Francesca; Salvio, Michela; Libener, Roberta; Betta, Pier-Giacomo

    2004-08-01

    Cadherins and their associated cytoplasmic proteins, catenins, are critical to the maintenance of normal tissue integrity and the suppression of cancer invasion. The cadherin profile in malignant mesothelioma (MM) is not well defined and the role of the cadherin-catenin system in the pathogenesis of MM remains to be determined. By means of Western blot analysis and immunohistochemistry the expression of E (epithelial)-, N (neural)-, P (placental)-cadherin, and alpha-, beta- and gamma-catenins was studied in nine human MM cell lines and five human mesothelial cell lines. Mesothelial cells consistently expressed only N-cadherin and alpha- and beta-catenins. All but one MM cell line were N-cadherin-positive and all of them were also positive for alpha- and beta-catenins. E-cadherin was found in six (66.7%) and gamma-catenin in seven (77.8%) MM cell lines. Five of these E-cadherin-positive lines co-expressed N-cadherin and the remaining one was also P-cadherin-positive. Double immunofluorescence staining revealed the plasma membrane co-localisation of both cadherin types in MM cell lines that co-expressed E- and N-cadherin or E- and P-cadherin, respectively. Immunoprecipitation showed complexes of beta-catenin with both cadherin types when co-expressed. The results point to upregulation of E-cadherin and gamma-catenin in most MM cases and demonstrate that cadherin expression is more heterogeneous and less mutually exclusive in MM compared with the mesothelium, although the biological significance of this finding remains unclear.

  5. Aberrant gene expression patterns in placentomes are associated with phenotypically normal and abnormal cattle cloned by somatic cell nuclear transfer.

    Science.gov (United States)

    Everts, Robin E; Chavatte-Palmer, Pascale; Razzak, Anthony; Hue, Isabelle; Green, Cheryl A; Oliveira, Rosane; Vignon, Xavier; Rodriguez-Zas, Sandra L; Tian, X Cindy; Yang, Xiangzhong; Renard, Jean-Paul; Lewin, Harris A

    2008-03-14

    Transcription profiling of placentomes derived from somatic cell nuclear transfer (SCNT, n = 20), in vitro fertilization (IVF, n = 9), and artificial insemination (AI, n = 9) at or near term development was performed to better understand why SCNT and IVF often result in placental defects, hydrops, and large offspring syndrome (LOS). Multivariate analysis of variance was used to distinguish the effects of SCNT, IVF, and AI on gene expression, taking into account the effects of parturition (term or preterm), sex of fetus, breed of dam, breed of fetus, and pathological finding in the offspring (hydrops, normal, or other abnormalities). Differential expression of 20 physiologically important genes was confirmed with quantitative PCR. The largest effect on placentome gene expression was attributable to whether placentas were collected at term or preterm (i.e., whether the collection was because of disease or to obtain stage-matched controls) followed by placentome source (AI, IVF, or SCNT). Gene expression in SCNT placentomes was dramatically different from AI (n = 336 genes; 276 >2-fold) and from IVF (n = 733 genes; 162 >2-fold) placentomes. Functional analysis of differentially expressed genes (DEG) showed that IVF has significant effects on genes associated with cellular metabolism. In contrast, DEG associated with SCNT are involved in multiple pathways, including cell cycle, cell death, and gene expression. Many DEG were shared between the gene lists for IVF and SCNT comparisons, suggesting that common pathways are affected by the embryo culture methods used for IVF and SCNT. However, the many unique gene functions and pathways affected by SCNT suggest that cloned fetuses may be starved and accumulating toxic wastes due to placental insufficiency caused by reprogramming errors. Many of these genes are candidates for hydrops and LOS.

  6. Hornerin, an S100 family protein, is functional in breast cells and aberrantly expressed in breast cancer

    Directory of Open Access Journals (Sweden)

    Fleming Jodie M

    2012-06-01

    Full Text Available Abstract Background Recent evidence suggests an emerging role for S100 protein in breast cancer and tumor progression. These ubiquitous proteins are involved in numerous normal and pathological cell functions including inflammatory and immune responses, Ca2+ homeostasis, the dynamics of cytoskeleton constituents, as well as cell proliferation, differentiation, and death. Our previous proteomic analysis demonstrated the presence of hornerin, an S100 family member, in breast tissue and extracellular matrix. Hornerin has been reported in healthy skin as well as psoriatic and regenerating skin after wound healing, suggesting a role in inflammatory/immune response or proliferation. In the present study we investigated hornerin’s potential role in normal breast cells and breast cancer. Methods The expression levels and localization of hornerin in human breast tissue, breast tumor biopsies, primary breast cells and breast cancer cell lines, as well as murine mammary tissue were measured via immunohistochemistry, western blot analysis and PCR. Antibodies were developed against the N- and C-terminus of the protein for detection of proteolytic fragments and their specific subcellular localization via fluorescent immunocytochemisty. Lastly, cells were treated with H2O2 to detect changes in hornerin expression during induction of apoptosis/necrosis. Results Breast epithelial cells and stromal fibroblasts and macrophages express hornerin and show unique regulation of expression during distinct phases of mammary development. Furthermore, hornerin expression is decreased in invasive ductal carcinomas compared to invasive lobular carcinomas and less aggressive breast carcinoma phenotypes, and cellular expression of hornerin is altered during induction of apoptosis. Finally, we demonstrate the presence of post-translational fragments that display differential subcellular localization. Conclusions Our data opens new possibilities for hornerin and its

  7. Aberrant Expression of Critical Genes during Secondary Cell Wall Biogenesis in a Cotton Mutant, Ligon Lintless-1 (Li-1

    Directory of Open Access Journals (Sweden)

    James J. Bolton

    2009-01-01

    Full Text Available Over ninety percent of the value of cotton comes from its fiber; however, the genetic mechanisms governing fiber development are poorly understood. Due to their biochemical and morphological diversity in fiber cells cotton fiber mutants have been useful in examining fiber development; therefore, using the Ligon Lintless (Li-1 mutant, a monogenic dominant cotton mutant with very short fibers, we employed the high throughput approaches of microarray technology and real time PCR to gain insights into what genes were critical during the secondary cell wall synthesis stage. Comparative transcriptome analysis of the normal TM-1 genotype and the near isogenic Li-1 revealed that over 100 transcripts were differentially expressed at least 2-fold during secondary wall biogenesis, although the genetic profile of the expansion phase showed no significant differences in the isolines. Of particular note, we identified three candidate gene families-expansin, sucrose synthase, and tubulin—whose expression in Li-1 deviates from normal expression patterns of its parent, TM-1. These genes may contribute to retarded growth of fibers in Li-1 since they are fiber-expressed structural and metabolic genes. This work provides more details into the mechanisms of fiber development, and suggests the Li gene is active during the later stages of fiber development.

  8. Targeted expression of SV40 T antigen in the hair follicle of transgenic mice produces an aberrant hair phenotype.

    Science.gov (United States)

    Keough, R; Powell, B; Rogers, G

    1995-03-01

    Directed expression of SV40 large T antigen (TAg) in transgenic mice can induce tissue-specific tumorigenesis and useful cell lines exhibiting differentiated characteristics can be established from resultant tumor cells. In an attempt to produce an immortalised mouse hair follicle cortical cell line for the study of hair keratin gene control, SV40 TAg expression was targeted to the hair follicles of transgenic mice using a sheep hair gene promoter. Expression of SV40 TAg in the follicle cortex disrupted normal fiber ultrastructure, producing a marked phenotypic effect. Affected hairs were wavy or severely kinked (depending on the severity of the phenotype) producing an appearance ranging from a ruffled coat to a stubble covering the back of the mouse. The transgenic hairs appeared to be weakened at the base of the fibers, leading to premature hair-loss and a thinner pelage, or regions of temporary nudity. No follicle tumors or neoplasia were apparent and immortalisation of cortical cells could not be established in culture. In situ hybridisation studies in the hair follicle using histone H3 as a cell proliferation marker suggested that cell proliferation had ceased prior to commencement of K2.10-TAg expression and was not re-established in the differentiating cortical cells. Hence, TAg was unable to induce cell immortalisation at that stage of cortical cell differentiation. However, transgenic mice developed various other abnormalities including vertebral abnormalities and bladder, liver and intestinal tumors, which resulted in reduced life expectancy.

  9. Aberrant expression of shared master-key genes contributes to the immunopathogenesis in patients with juvenile spondyloarthritis.

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    Lovro Lamot

    Full Text Available Association of juvenile spondyloarthritis (jSpA with the HLA-B27 genotype is well established, but there is little knowledge of other genetic factors with a role in the development of the disease. To date, only a few studies have tried to find those associated genes by obtaining expression profiles, but with inconsistent results due to various patient selection criteria and methodology. The aim of the present study was to identify and confirm gene signatures and novel biomarkers in highly homogeneous cohorts of untreated and treated patients diagnosed with jSpA and other forms of juvenile idiopathic arthritis (JIA according to ILAR criteria. For the purposes of the research, total RNA was isolated from whole blood of 45 children with jSpA and known HLA genotype, 11 children with oligo- and polyarticular forms of JIA, as well as 12 age and sex matched control participants without diagnosis of inflammatory disease. DNA microarray gene expression was performed in 11 patients with jSpA and in four healthy controls, along with bioinformatical analysis of retrieved data. Carefully selected differentially expressed genes where analyzed by qRT-PCR in all participants of the study. Microarray results and bioinformatical analysis revealed 745 differentially expressed genes involved in various inflammatory processes, while qRT-PCR analysis of selected genes confirmed data universality and specificity of expression profiles in jSpA patients. The present study indicates that jSpA could be a polygenic disease with a possible malfunction in antigen recognition and activation of immunological response, migration of inflammatory cells and regulation of the immune system. Among genes involved in these processes TLR4, NLRP3, CXCR4 and PTPN12 showed almost consistent expression in study patients diagnosed with jSpA. Those genes and their products could therefore potentially be used as novel biomarkers, possibly predictive of disease prognosis and response to

  10. Aberrant expression of regulatory cytokine IL-35 and pattern recognition receptor NOD2 in patients with allergic asthma.

    Science.gov (United States)

    Wong, Chun Kwok; Leung, Ting Fan; Chu, Ida Miu Ting; Dong, Jie; Lam, Yvonne Yi On; Lam, Christopher Wai Kei

    2015-02-01

    We investigated the plasma concentration of the novel regulatory cytokine IL-35 and intracytosolic pattern recognition receptors nucleotide-binding oligomerization domain (NOD)-like receptors in granulocytes and explored their potential implication in disease severity monitoring of allergic asthma. The expression of circulating IL-35 and other pro-inflammatory mediators in asthmatic patients or control subjects were evaluated using enzyme-linked immunosorbent assay (ELISA). The intracellular expressions of NOD1 and NOD2 in CCR3+ granulocytes were assessed using flow cytometry. Plasma concentrations of IL-35, IL-17A, basophil activation marker basogranulin, and eosinophilic airway inflammation biomarker periostin were significantly elevated in allergic asthmatic patients compared to non-atopic control subjects (all probability (p) IL-35 concentration in asthmatic patients (all p IL-35 and periostin with disease severity score in asthmatic patients (both p IL-35 (p IL-35 may serve as a potential surrogate biomarker for disease severity of allergic asthma.

  11. Inhibition of p300 histone acetyltransferase activity in palate mesenchyme cells attenuates Wnt signaling via aberrant E-cadherin expression.

    Science.gov (United States)

    Warner, Dennis R; Smith, Scott C; Smolenkova, Irina A; Pisano, M Michele; Greene, Robert M

    2016-03-01

    p300 is a multifunctional transcriptional coactivator that interacts with numerous transcription factors and exhibits protein/histone acetyltransferase activity. Loss of p300 function in humans and in mice leads to craniofacial defects. In this study, we demonstrated that inhibition of p300 histone acetyltransferase activity with the compound, C646, altered the expression of several genes, including Cdh1 (E-cadherin) in mouse maxillary mesenchyme cells, which are the cells that give rise to the secondary palate. The increased expression of plasma membrane-bound E-cadherin was associated with reduced cytosolic β-catenin, that led to attenuated signaling through the canonical Wnt pathway. Furthermore, C646 reduced both cell proliferation and the migratory ability of these cells. These results suggest that p300 histone acetyltransferase activity is critical for Wnt-dependent palate mesenchymal cell proliferation and migration, both processes that play a significant role in morphogenesis of the palate.

  12. The expression of Lamin A mutant R321X leads to endoplasmic reticulum stress with aberrant Ca(2+) handling.

    Science.gov (United States)

    Carmosino, Monica; Gerbino, Andrea; Schena, Giorgia; Procino, Giuseppe; Miglionico, Rocchina; Forleo, Cinzia; Favale, Stefano; Svelto, Maria

    2016-11-01

    Mutations in the Lamin A/C gene (LMNA), which encodes A-type nuclear Lamins, represent the most frequent genetic cause of dilated cardiomyopathy (DCM). This study is focused on a LMNA nonsense mutation (R321X) identified in several members of an Italian family that produces a truncated protein isoform, which co-segregates with a severe form of cardiomyopathy with poor prognosis. However, no molecular mechanisms other than nonsense mediated decay of the messenger and possible haploinsufficiency were proposed to explain DCM. Aim of this study was to gain more insights into the disease-causing mechanisms induced by the expression of R321X at cellular level. We detected the expression of R321X by Western blotting from whole lysate of a mutation carrier heart biopsy. When expressed in HEK293 cells, GFP- (or mCherry)-tagged R321X mislocalized in the endoplasmic reticulum (ER) inducing the PERK-CHOP axis of the ER stress response. Of note, confocal microscopy showed phosphorylation of PERK in sections of the mutation carrier heart biopsy. ER mislocalization of mCherry-R321X also induced impaired ER Ca(2+) handling, reduced capacitative Ca(2+) entry at the plasma membrane and abnormal nuclear Ca(2+) dynamics. In addition, expression of R321X by itself increased the apoptosis rate. In conclusion, R321X is the first LMNA mutant identified to date, which mislocalizes into the ER affecting cellular homeostasis mechanisms not strictly related to nuclear functions. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  13. Reduced PU.1 expression underlies aberrant neutrophil maturation and function in β-thalassemia mice and patients.

    Science.gov (United States)

    Siwaponanan, Panjaree; Siegers, Jurre Ynze; Ghazali, Razi; Ng, Thian; McColl, Bradley; Ng, Garrett Zhen-Wei; Sutton, Philip; Wang, Nancy; Ooi, Isabelle; Thiengtavor, Chayada; Fucharoen, Suthat; Chaichompoo, Pornthip; Svasti, Saovaros; Wijburg, Odilia; Vadolas, Jim

    2017-06-08

    β-Thalassemia is associated with several abnormalities of the innate immune system. Neutrophils in particular are defective, predisposing patients to life-threatening bacterial infections. The molecular and cellular mechanisms involved in impaired neutrophil function remain incompletely defined. We used the Hbb(th3/+) β-thalassemia mouse and hemoglobin E (HbE)/β-thalassemia patients to investigate dysregulated neutrophil activity. Mature neutrophils from Hbb(th3/+) mice displayed a significant reduction in chemotaxis, opsonophagocytosis, and production of reactive oxygen species, closely mimicking the defective immune functions observed in β-thalassemia patients. In Hbb(th3/+) mice, the expression of neutrophil CXCR2, CD11b, and reduced NAD phosphate oxidase components (p22phox, p67phox, and gp91phox) were significantly reduced. Morphological analysis of Hbb(th3/+) neutrophils showed that a large percentage of mature phenotype neutrophils (Ly6G(hi)Ly6C(low)) appeared as band form cells, and a striking expansion of immature (Ly6G(low)Ly6C(low)) hyposegmented neutrophils, consisting mainly of myelocytes and metamyelocytes, was noted. Intriguingly, expression of an essential mediator of neutrophil terminal differentiation, the ets transcription factor PU.1, was significantly decreased in Hbb(th3/+) neutrophils. In addition, in vivo infection with Streptococcus pneumoniae failed to induce PU.1 expression or upregulate neutrophil effector functions in Hbb(th3/+) mice. Similar changes to neutrophil morphology and PU.1 expression were observed in splenectomized and nonsplenectomized HbE/β-thalassemia patients. This study provides a mechanistic insight into defective neutrophil maturation in β-thalassemia patients, which contributes to deficiencies in neutrophil effector functions. © 2017 by The American Society of Hematology.

  14. Aberrations of Gradient-Index Lenses.

    Science.gov (United States)

    Matthews, A. L.

    Available from UMI in association with The British Library. In this thesis, the primary aberrations of lenses with a radial focussing gradient-of-index are analysed. Such a lens has a refractive index profile which decreases continuously and radially outward from the optical axis, so that the surfaces of constant refractive index are circular cylinders which are coaxial with the optical axis. Current applications of these lenses include photocopiers, medical endoscopes, telecommunications systems and compact disc systems. Closed formulae for the primary wavefront aberrations for a gradient-index lens with curved or plane entry and exit faces are obtained from the differential equations of such a lens to assess the primary transverse ray aberrations that it introduces. Identical expressions are then obtained by using the difference in optical path length produced between two rays by the lens. This duplication of the derivations of the primary wavefront aberrations acts as a confirmation of the validity of the expressions. One advantage of these equations is that the contributions due to the primary spherical aberration, coma, astigmatism, field curvature and distortion can be assessed individually. A Fortran 77 program has been written to calculate each of these individual contributions, the total primary wavefront aberrations and the primary transverse ray aberrations. Further confirmation of the validity of the expressions is obtained by using this program to show that the coma and distortion were both zero for fully symmetric systems working at unit magnification. The program is then used to assess the primary wavefront aberrations for a gradient-index lens which is currently of interest to the telecommunications industry. These results are compared with values obtained using a finite ray-tracing program for the total wavefront aberrations. This shows that the primary wavefront aberrations are the completely dominant contribution to the total wavefront

  15. Chicago aberration correction work.

    Science.gov (United States)

    Beck, V D

    2012-12-01

    The author describes from his personal involvement the many improvements to electron microscopy Albert Crewe and his group brought by minimizing the effects of aberrations. The Butler gun was developed to minimize aperture aberrations in a field emission electron gun. In the 1960s, Crewe anticipated using a spherical aberration corrector based on Scherzer's design. Since the tolerances could not be met mechanically, a method of moving the center of the octopoles electrically was developed by adding lower order multipole fields. Because the corrector was located about 15 cm ahead of the objective lens, combination aberrations would arise with the objective lens. This fifth order aberration would then limit the aperture of the microscope. The transformation of the off axis aberration coefficients of a round lens was developed and a means to cancel anisotropic coma was developed. A new method of generating negative spherical aberration was invented using the combination aberrations of hexapoles. Extensions of this technique to higher order aberrations were developed. An electrostatic electron mirror was invented, which allows the cancellation of primary spherical aberration and first order chromatic aberration. A reduction of chromatic aberration by two orders of magnitude was demonstrated using such a system.

  16. Lymphocytes with Aberrant Expression of Fas or Fas-ligand Attenuate Immune Bone Marrow Failure in a Mouse Model

    Science.gov (United States)

    Omokaro, Stephanie O.; Desierto, Marie J.; Eckhaus, Michael A.; Ellison, Felicia M.; Chen, Jichun; Young, Neal S.

    2012-01-01

    Bone marrow (BM) and lymphocyte samples from aplastic anemia patients show up-regulated Fas and Fas-ligand (FasL) expression respectively, supporting a relationship between immune-mediated BM destruction and the Fas apoptotic pathway. Mice with spontaneous lymphoproliferation (lpr) and generalized lymphoproliferative disease (gld) mutations exhibit abnormal expression of Fas and FasL; serving as potential models to elucidate underlying mechanisms of BM failure. We examined cellular and functional characteristics of lpr and gld mutants on the C57BL/6 (B6) background. Lymph node (LN) cells from lpr and gld mice produced less apoptosis when co-incubated with C.B10-H2b/LilMcd (C.B10) BM cells in vitro. This functional difference was confirmed by infusing lpr, gld, and B6 LN cells into sub-lethally irradiated CB10 mice; all donor LN cells showed significant T cell expansion and activation but only B6 LN cells caused severe BM destruction. Mice infused with gld LN cells developed mild to moderate BM failure, despite receiving FasL-deficient effectors, thus suggesting the existence of alternative pathways or incomplete penetrance of the mutation. Paradoxically, mice that received Fas-deficient lpr LN cells also had reduced BM failure, likely due to down-regulation of pro-apoptotic genes, an effect that can be overcome by higher doses of lpr LN cells. Our model demonstrates that abnormal Fas or FasL expression interferes with the development of pancytopenia and marrow hypoplasia, validating a major role for the Fas/FasL cytotoxic pathway in immune-mediated BM failure, although disruption of this pathway does not completely abolish marrow destruction. PMID:19265119

  17. Lymphocytes with aberrant expression of Fas or Fas ligand attenuate immune bone marrow failure in a mouse model.

    Science.gov (United States)

    Omokaro, Stephanie O; Desierto, Marie J; Eckhaus, Michael A; Ellison, Felicia M; Chen, Jichun; Young, Neal S

    2009-03-15

    Bone marrow (BM) and lymphocyte samples from aplastic anemia patients show up-regulated Fas and Fas-ligand (FasL) expression, respectively, supporting a relationship between immune-mediated BM destruction and the Fas apoptotic pathway. Mice with spontaneous lymphoproliferation (lpr) and generalized lymphoproliferative disease (gld) mutations exhibit abnormal expression of Fas and FasL, serving as potential models to elucidate underlying mechanisms of BM failure. We examined cellular and functional characteristics of lpr and gld mutants on the C57BL/6 (B6) background. Lymph node (LN) cells from lpr and gld mice produced less apoptosis when coincubated with C.B10-H2(b)/LilMcd (C.B10) BM cells in vitro. This functional difference was confirmed by infusing lpr, gld, and B6 LN cells into sublethally irradiated CB10 mice. All donor LN cells showed significant T cell expansion and activation, but only B6 LN cells caused severe BM destruction. Mice infused with gld LN cells developed mild to moderate BM failure despite receiving FasL-deficient effectors, thus suggesting the existence of alternative pathways or incomplete penetrance of the mutation. Paradoxically, mice that received Fas-deficient lpr LN cells also had reduced BM failure, likely due to down-regulation of proapoptotic genes, an effect that can be overcome by higher doses of lpr LN cells. Our model demonstrates that abnormal Fas or FasL expression interferes with the development of pancytopenia and marrow hypoplasia, validating a major role for the Fas/FasL cytotoxic pathway in immune-mediated BM failure, although disruption of this pathway does not completely abolish marrow destruction.

  18. Chicago aberration correction work

    Energy Technology Data Exchange (ETDEWEB)

    Beck, V.D., E-mail: vnlbeck@earthlink.net [1 Hobby Drive, Ridgefield, CT 06877-01922 (United States)

    2012-12-15

    The author describes from his personal involvement the many improvements to electron microscopy Albert Crewe and his group brought by minimizing the effects of aberrations. The Butler gun was developed to minimize aperture aberrations in a field emission electron gun. In the 1960s, Crewe anticipated using a spherical aberration corrector based on Scherzer's design. Since the tolerances could not be met mechanically, a method of moving the center of the octopoles electrically was developed by adding lower order multipole fields. Because the corrector was located about 15 cm ahead of the objective lens, combination aberrations would arise with the objective lens. This fifth order aberration would then limit the aperture of the microscope. The transformation of the off axis aberration coefficients of a round lens was developed and a means to cancel anisotropic coma was developed. A new method of generating negative spherical aberration was invented using the combination aberrations of hexapoles. Extensions of this technique to higher order aberrations were developed. An electrostatic electron mirror was invented, which allows the cancellation of primary spherical aberration and first order chromatic aberration. A reduction of chromatic aberration by two orders of magnitude was demonstrated using such a system. -- Highlights: Black-Right-Pointing-Pointer Crewe and his group made significant advances in aberration correction and reduction. Black-Right-Pointing-Pointer A deeper understanding of the quadrupole octopole corrector was developed. Black-Right-Pointing-Pointer A scheme to correct spherical aberration using hexapoles was developed. Black-Right-Pointing-Pointer Chromatic aberration was corrected using a uniform field mirror.

  19. Gene expression profile of brain regions reflecting aberrations in nervous system development targeting the process of neurite extension of rat offspring exposed developmentally to glycidol.

    Science.gov (United States)

    Akane, Hirotoshi; Saito, Fumiyo; Shiraki, Ayako; Imatanaka, Nobuya; Akahori, Yumi; Itahashi, Megu; Wang, Liyun; Shibutani, Makoto

    2014-12-01

    We previously found that exposure to glycidol at 1000 ppm in drinking water caused axonopathy in maternal rats and aberrations in late-stage hippocampal neurogenesis, targeting the process of neurite extension in offspring. To identify the profile of developmental neurotoxicity of glycidol, pregnant Sprague-Dawley rats were given drinking water containing glycidol from gestational day 6 until weaning on day 21 after delivery, and offspring at 0, 300 and 1000 ppm were subjected to region-specific global gene expression profiling. Four brain regions were selected to represent both cerebral and cerebellar tissues, i.e., the cingulate cortex, corpus callosum, hippocampal dentate gyrus and cerebellar vermis. Downregulated genes in the dentate gyrus were related to axonogenesis (Nfasc), myelination (Mal, Mrf and Ugt8), and cell proliferation (Aurkb and Ndc80) at ≥ 300 ppm, and upregulated genes were related to neural development (Frzb and Fzd6) at 1000 ppm. Upregulation was observed for genes related to myelination (Kl, Igf2 and Igfbp2) in the corpus callosum and axonogenesis and neuritogenesis (Efnb3, Tnc and Cd44) in the cingulate cortex, whereas downregulation was observed for genes related to synaptic transmission (Thbs2 and Ccl2) in the cerebellar vermis; all of these changes were mostly observed at 1000 ppm. Altered gene expression of Cntn3, which functions on neurite outgrowth-promotion, was observed in all four brain regions at 1000 ppm. Gene expression profiles suggest that developmental exposure to glycidol affected plasticity of neuronal networks in the broad brain areas, and dentate gyrus neurogenesis may be the sensitive target of this type of toxicity.

  20. Pediatric T-cell prolymphocytic leukemia with an isolated 12(p13 deletion and aberrant CD117 expression

    Directory of Open Access Journals (Sweden)

    Bellone Michael

    2012-04-01

    Full Text Available Abstract T-cell Prolymphocytic leukemia (T-PLL is a rare post-thymic T-cell malignancy that follows an aggressive clinical course. The classical presentation includes an elevated white blood cell (WBC count with anemia and thrombocytopenia, hepatosplenomegaly, and lymphadenopathy. T-PLL is a disease of the elderly and to our knowledge it has never been described in the pediatric age group. We report a case of T-PLL in a 9 year old male who was initially diagnosed with T-cell acute lymphoblastic lymphoma (ALL, the diagnosis was later refined to T-PLL following additional analysis of bone marrow morphology and immunophenotype. Two unusual findings in our patient included CD117 expression and an isolated chromosomal 12(p13 deletion. The patient failed to respond to standard ALL induction chemotherapy, but achieved complete remission following treatment with a fludarabine and alemtuzumab-based regimen.

  1. Aberrant gonadotropin-releasing hormone receptor (GnRHR) expression and its regulation of CYP11B2 expression and aldosterone production in adrenal aldosterone-producing adenoma (APA).

    Science.gov (United States)

    Nakamura, Yasuhiro; Hattangady, Namita G; Ye, Ping; Satoh, Fumitoshi; Morimoto, Ryo; Ito-Saito, Takako; Sugawara, Akira; Ohba, Koji; Takahashi, Kazuhiro; Rainey, William E; Sasano, Hironobu

    2014-03-25

    Aberrant expression of gonadotropin-releasing hormone receptor (GnRHR) has been reported in human adrenal tissues including aldosterone-producing adenoma (APA). However, the details of its expression and functional role in adrenals are still not clear. In this study, quantitative RT-PCR analysis revealed the mean level of GnRHR mRNA was significantly higher in APAs than in human normal adrenal (NA) (P=0.004). GnRHR protein expression was detected in human NA and neoplastic adrenal tissues. In H295R cells transfected with GnRHR, treatment with GnRH resulted in a concentration-dependent increase in CYP11B2 reporter activity. Chronic activation of GnRHR with GnRH (100nM), in a cell line with doxycycline-inducible GnRHR (H295R-TR/GnRHR), increased CYP11B2 expression and aldosterone production. These agonistic effects were inhibited by blockers for the calcium signaling pathway, KN93 and calmidazolium. These results suggest GnRH, through heterotopic expression of its receptor, may be a potential regulator of CYP11B2 expression levels in some cases of APA. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  2. Linear and non-linear dependencies between copy number aberrations and mRNA expression reveal distinct molecular pathways in breast cancer

    Directory of Open Access Journals (Sweden)

    Frigessi Arnoldo

    2011-05-01

    Full Text Available Abstract Background Elucidating the exact relationship between gene copy number and expression would enable identification of regulatory mechanisms of abnormal gene expression and biological pathways of regulation. Most current approaches either depend on linear correlation or on nonparametric tests of association that are insensitive to the exact shape of the relationship. Based on knowledge of enzyme kinetics and gene regulation, we would expect the functional shape of the relationship to be gene dependent and to be related to the gene regulatory mechanisms involved. Here, we propose a statistical approach to investigate and distinguish between linear and nonlinear dependences between DNA copy number alteration and mRNA expression. Results We applied the proposed method to DNA copy numbers derived from Illumina 109 K SNP-CGH arrays (using the log R values and expression data from Agilent 44 K mRNA arrays, focusing on commonly aberrated genomic loci in a collection of 102 breast tumors. Regression analysis was used to identify the type of relationship (linear or nonlinear, and subsequent pathway analysis revealed that genes displaying a linear relationship were overall associated with substantially different biological processes than genes displaying a nonlinear relationship. In the group of genes with a linear relationship, we found significant association to canonical pathways, including purine and pyrimidine metabolism (for both deletions and amplifications as well as estrogen metabolism (linear amplification and BRCA-related response to damage (linear deletion. In the group of genes displaying a nonlinear relationship, the top canonical pathways were specific pathways like PTEN and PI13K/AKT (nonlinear amplification and Wnt(B and IL-2 signalling (nonlinear deletion. Both amplifications and deletions pointed to the same affected pathways and identified cancer as the top significant disease and cell cycle, cell signaling and cellular

  3. Fish Oil Contaminated with Persistent Organic Pollutants Induces Colonic Aberrant Crypt Foci Formation and Reduces Antioxidant Enzyme Gene Expression in Rats.

    Science.gov (United States)

    Hong, Mee Young; Hoh, Eunha; Kang, Brian; DeHamer, Rebecca; Kim, Jin Young; Lumibao, Jan

    2017-08-01

    Background: Epidemiologic, clinical, and experimental studies have suggested that fish oil (FO), a rich source of n-3 (ω-3) polyunsaturated fatty acids, protects against colon cancer. However, this message is confounded by the FDA's warning that the consumption of certain types of fish should be restricted because of contamination with persistent organic pollutants (POPs), such as polychlorinated biphenyls (PCBs) and organochlorine pesticides.Objective: We examined FO contaminated with POPs (PCBs, dichlorodiphenyltrichloroethane, and chlordane) compared with unmodified FO on the risk factors of colon cancer development.Methods: Male Sprague-Dawley rats aged 28 d (n = 30) were allocated into 3 groups and fed 15% corn oil (CO), FO, or POP-contaminated FO for 9 wk with a subcutaneous injection of colon carcinogen azoxymethane at weeks 3 and 4. Colonic aberrant crypt foci (ACF) and cell proliferation were enumerated, and the gene expression of inflammation, antioxidant enzymes, and repair enzymes were determined with the use of real-time quantitative polymerase chain reaction analysis.Results: FO-fed rats had a lower number of ACF (mean ± SE: 29 ± 4.0 for FO compared with 53 ± 8.4 for CO and 44 ± 4.6 for POP FO) and higher-multiplicity ACF than the CO and POP FO groups (4.7 ± 0.9 for FO compared with 11 ± 1.5 for CO and 9.6 ± 1.8 for POP FO) (P < 0.05). FO feeding lowered the proliferation index compared with the CO and POP FO feeding groups (18% ± 1.1% for FO compared with 25% ± 1.6% for CO and 23% ± 0.7% for POP FO) (P = 0.009). Superoxide dismutase [2.4 ± 0.6 relative quantification (RQ) for FO compared with 1.2 ± 0.2 RQ for CO and 1.3 ± 0.3 RQ for POP FO] and catalase gene expression (10 ± 2.0 RQ for FO compared with 5.4 ± 1.1 RQ for CO and 6.6 ± 1.5 RQ for POP FO) were higher in the FO group than in the CO and POP FO groups (P < 0.05). There were no differences between CO and POP FO on the variables.Conclusion: These results indicate that POPs in

  4. Rice OsRAD21-2 is Expressed in Actively Dividing Tissues and its Ectopic Expression in Yeast Results in Aberrant Cell Division and Growth

    Institute of Scientific and Technical Information of China (English)

    Chunyan Gong; Tang Li; Qi Li; Longfeng Yan; Tai Wang

    2011-01-01

    Rad21 and its meiotic counterpart Rec8,the key components of the cohesin complex,are essential for sister chromatid cohesion and chromosome segregation in mitosis and meiosis,respectively.In contrast to yeast and vertebrates,which have only two RAD21/REC8 genes,the rice genome encodes four Rad21/Rec8 proteins.Here,we report on the cloning and characterization of OsRAD21-2 from rice (Oryza sativa L.).Phylogenetic analysis of the full-length amino acids showed that OsRad21-2 was grouped into the plant-specific Rad21 subfamily.Semi-quantitative reverse transcription-polymerase chain reaction revealed OsRAD21-2 preferentially expressed in premeiotic flowers.Further RNA in situ hybridization analysis and promoter::β-glucuronidase staining indicated that OsRAD21-2 was mainly expressed in actively dividing tissues including premeiotic stamen,stem intercalary meristem,leaf meristem,and root pericycle.Ectopic expression of OsRAD21-2 in fission yeast resulted in cell growth delay and morphological abnormality.Flow cytometric analysis revealed that the OsRAD21-2-expressed cells were arrested in G2 phase.Our results suggest that OsRad21-2 functions in regulation of cell division and growth.

  5. Aberration Corrected Emittance Exchange

    CERN Document Server

    Nanni, Emilio A

    2015-01-01

    Full exploitation of emittance exchange (EEX) requires aberration-free performance of a complex imaging system including active radio-frequency (RF) elements which can add temporal distortions. We investigate the performance of an EEX line where the exchange occurs between two dimensions with normalized emittances which differ by orders of magnitude. The transverse emittance is exchanged into the longitudinal dimension using a double dog-leg emittance exchange setup with a 5 cell RF deflector cavity. Aberration correction is performed on the four most dominant aberrations. These include temporal aberrations that are corrected with higher order magnetic optical elements located where longitudinal and transverse emittance are coupled. We demonstrate aberration-free performance of emittances differing by 4 orders of magnitude, i.e. an initial transverse emittance of $\\epsilon_x=1$ pm-rad is exchanged with a longitudinal emittance of $\\epsilon_z=10$ nm-rad.

  6. Developmental expression of neurokinin-1 and neurokinin-3 receptors in the rat retina.

    Science.gov (United States)

    Casini, G; Brecha, N C; Bosco, L; Rickman, D W

    2000-05-29

    Tachykinin (TK) peptides act on retinal neurons through neurokinin (NK) receptors. We examined the expression of neurokinin-1 (NK1; the substance P receptor), NK3 [the neurokinin B (NKB) receptor], and TK peptides in developing rat retinas. NK1 immunolabeling was found in newborn retinas in rare amacrine cells and in putative ganglion cells. At postnatal day 2 (PND 2), NK1 immunostaining was reduced greatly among ganglion cells, and it appeared in many amacrine cells and in fibers in the inner plexiform layer (IPL), with the highest density in laminae 1, 3, and 5. A similar pattern was found at PND 7. At PND 12, interplexiform NK1-immunoreactive (-IR) cells were detected, and NK1-IR fibers in the IPL were concentrated in lamina 2, similar to what was seen in adults. NK3 was expressed mainly by OFF-cone bipolar cells, and the developmental pattern of NK3 was compared with that of cone bipolar cells that were labeled with antibodies to recoverin. Immature recoverin-IR cone bipolar cells were seen at PND 2. NK3 immunolabeling was detected first in the outer plexiform layer and in sparse bipolar cell somata at PND 10, when recoverin-IR cone bipolar cells are nearly mature. By PND 15, both the NK3 immunostaining pattern and the recoverin immunostaining pattern were similar to the patterns seen in adults. TK immunoreactivity was present at PND 0 in amacrine cells and displaced amacrine cells. By PND 10, the morphologic maturation of TK-IR cells was complete. These findings indicate that, in early postnatal retinas, substance P may act on NK1 receptors, whereas NKB/NK3 interactions are unlikely, suggesting that there are different levels of importance for different TK peptides in the developing retina. Copyright 2000 Wiley-Liss, Inc.

  7. MicroRNA-137 Inhibits EFNB2 Expression Affected by a Genetic Variant and Is Expressed Aberrantly in Peripheral Blood of Schizophrenia Patients

    Directory of Open Access Journals (Sweden)

    Shanshan Wu

    2016-10-01

    Full Text Available MicroRNAs (miRNAs are a class of endogenous and non-coding single-stranded RNAs of approximately 22 nucleotides, many of which are evolutionarily conserved. Genome-wide association studies have identified a robust statistical association between the MIR137 gene and schizophrenia in Europeans, which was replicated in the Han Chinese population in a case-control study. In the previous study, we provided evidence for a significant association between the EFNB2 gene and schizophrenia in Han Chinese subjects. In the current study, we utilized computational analysis, vector construction of point mutations, luciferase reporter assays and gene expression assays including RT-qPCR and western blotting methods to investigate miR-137 directly targeting EFNB2 gene and explore the reversal effect of a genetic variant of SNP rs550067317 in the putative seed-pair region of EFNB2 3′-UTR. We also found that miR-137 could be detected in the peripheral blood of a cohort of first-onset schizophrenia patients and healthy controls, and the area under curve was 0.795 (95% confidence interval 0.700–0.890, which is a middle diagnostic value for disease, suggesting that it might be valuable for diagnosing schizophrenia. In summary, this study would improve our understanding of the role of miR-137 in schizophrenia-associated signaling pathways and identify the genetic basis of rs550067317 for schizophrenia. Furthermore, we provided new evidence for the involvement of miR-137 in the etiology and diagnosis of schizophrenia, which might contribute to the discovery of new biomarkers and therapeutic targets for the disease.

  8. MicroRNA-137 Inhibits EFNB2 Expression Affected by a Genetic Variant and Is Expressed Aberrantly in Peripheral Blood of Schizophrenia Patients.

    Science.gov (United States)

    Wu, Shanshan; Zhang, Rui; Nie, Fayi; Wang, Xiaoli; Jiang, Congshan; Liu, Meng; Valenzuela, Robert K; Liu, Wanqing; Shi, Yongyong; Ma, Jie

    2016-10-01

    MicroRNAs (miRNAs) are a class of endogenous and non-coding single-stranded RNAs of approximately 22 nucleotides, many of which are evolutionarily conserved. Genome-wide association studies have identified a robust statistical association between the MIR137 gene and schizophrenia in Europeans, which was replicated in the Han Chinese population in a case-control study. In the previous study, we provided evidence for a significant association between the EFNB2 gene and schizophrenia in Han Chinese subjects. In the current study, we utilized computational analysis, vector construction of point mutations, luciferase reporter assays and gene expression assays including RT-qPCR and western blotting methods to investigate miR-137 directly targeting EFNB2 gene and explore the reversal effect of a genetic variant of SNP rs550067317 in the putative seed-pair region of EFNB2 3'-UTR. We also found that miR-137 could be detected in the peripheral blood of a cohort of first-onset schizophrenia patients and healthy controls, and the area under curve was 0.795 (95% confidence interval 0.700-0.890), which is a middle diagnostic value for disease, suggesting that it might be valuable for diagnosing schizophrenia. In summary, this study would improve our understanding of the role of miR-137 in schizophrenia-associated signaling pathways and identify the genetic basis of rs550067317 for schizophrenia. Furthermore, we provided new evidence for the involvement of miR-137 in the etiology and diagnosis of schizophrenia, which might contribute to the discovery of new biomarkers and therapeutic targets for the disease.

  9. Nodal aberration theory for wild-filed asymmetric optical systems

    Science.gov (United States)

    Chen, Yang; Cheng, Xuemin; Hao, Qun

    2016-10-01

    Nodal Aberration Theory (NAT) was used to calculate the zero field position in Full Field Display (FFD) for the given aberration term. Aiming at wide-filed non-rotational symmetric decentered optical systems, we have presented the nodal geography behavior of the family of third-order and fifth-order aberrations. Meanwhile, we have calculated the wavefront aberration expressions when one optical element in the system is tilted, which was not at the entrance pupil. By using a three-piece-cellphone lens example in optical design software CodeV, the nodal geography is testified under several situations; and the wavefront aberrations are calculated when the optical element is tilted. The properties of the nodal aberrations are analyzed by using Fringe Zernike coefficients, which are directly related with the wavefront aberration terms and usually obtained by real ray trace and wavefront surface fitting.

  10. Prenatal hydronephrosis caused by aberrant renal vessels

    DEFF Research Database (Denmark)

    Lenz, K; Thorup, Jørgen Mogens; Rabol, A;

    1996-01-01

    With routine use of obstetric ultrasonography, fetal low-grade hydronephrosis is commonly detected, but may resolve spontaneously after birth. Two cases are presented to illustrate that in some cases such findings can express intermittent hydronephrosis caused by aberrant renal vessels. Renal...

  11. Differential algebraic method for arbitrary order curvilinear-axis combined geometric-chromatic aberration analysis

    CERN Document Server

    Cheng Min; Lu Yi Long; Yao Zhen Hua

    2003-01-01

    The principle of differential algebra is applied to analyse and calculate arbitrary order curvilinear-axis combined geometric-chromatic aberrations of electron optical systems. Expressions of differential algebraic form of high order combined aberrations are obtained and arbitrary order combined aberrations can be calculated numerically. As an example, a typical wide electron beam focusing system with curved optical axes named magnetic immersion lens has been studied. All the second-order and third-order combined geometric-chromatic aberrations of the lens have been calculated, and the patterns of the corresponding geometric aberrations and combined aberrations have been given as well.

  12. Aberrant expression of proteins involved in signal transduction and DNA repair pathways in lung cancer and their association with clinical parameters.

    Directory of Open Access Journals (Sweden)

    Yong He

    Full Text Available BACKGROUND: Because cell signaling and cell metabolic pathways are executed through proteins, protein signatures in primary tumors are useful for identifying key nodes in signaling networks whose alteration is associated with malignancy and/or clinical outcomes. This study aimed to determine protein signatures in primary lung cancer tissues. METHODOLOGY/ PRINCIPAL FINDINGS: We analyzed 126 proteins and/or protein phosphorylation sites in case-matched normal and tumor samples from 101 lung cancer patients with reverse-phase protein array (RPPA assay. The results showed that 18 molecules were significantly different (p<0.05 by at least 30% between normal and tumor tissues. Most of those molecules play roles in cell proliferation, DNA repair, signal transduction and lipid metabolism, or function as cell surface/matrix proteins. We also validated RPPA results by Western blot and/or immunohistochemical analyses for some of those molecules. Statistical analyses showed that Ku80 levels were significantly higher in tumors of nonsmokers than in those of smokers. Cyclin B1 levels were significantly overexpressed in poorly differentiated tumors while Cox2 levels were significantly overexpressed in neuroendocrinal tumors. A high level of Stat5 is associated with favorable survival outcome for patients treated with surgery. CONCLUSIONS/ SIGNIFICANCE: Our results revealed that some molecules involved in DNA damage/repair, signal transductions, lipid metabolism, and cell proliferation were drastically aberrant in lung cancer tissues, and Stat5 may serve a molecular marker for prognosis of lung cancers.

  13. Lack of Correlation between Aberrant p16, RAR-β2, TIMP3, ERCC1, and BRCA1 Protein Expression and Promoter Methylation in Squamous Cell Carcinoma Accompanying Candida albicans-Induced Inflammation.

    Directory of Open Access Journals (Sweden)

    Yui Terayama

    Full Text Available Hyperplastic candidiasis is characterized by thickening of the mucosal epithelia with Candida albicans infection with occasional progression to squamous cell carcinoma (SCC. C. albicans is a critical factor in tumor development; however, the oncogenic mechanism is unclear. We have previously produced an animal model for hyperplastic candidiasis in the rat forestomach. In the present study, we investigate whether impaired DNA methylation and associated protein expression of tumor suppressor and DNA repair genes are involved in the SCC carcinogenesis process using this hyperplastic candidiasis model. Promoter methylation and protein expression were analyzed by methylation specific PCR and immunohistochemical staining, respectively, of 5 areas in the forestomachs of alloxan-induced diabetic rats with hyperplastic candidiasis: normal squamous epithelia, squamous hyperplasia, squamous hyperplasia adjacent to SCC, squamous hyperplasia transitioning to SCC, and SCC. We observed nuclear p16 overexpression despite increases in p16 gene promoter methylation during the carcinogenic process. TIMP3 and RAR-β2 promoter methylation progressed until the precancerous stage but disappeared upon malignant transformation. In comparison, TIMP3 protein expression was suppressed during carcinogenesis and RAR-β2 expression was attenuated in the cytoplasm but enhanced in nuclei. ERCC1 and BRCA1 promoters were not methylated at any stage; however, their protein expression disappeared beginning at hyperplasia and nuclear protein re-expression in SCC was observed only for ERCC1. These results suggest that aberrant p16, RAR-β2, TIMP3, ERCC1, and BRCA1 expression might occur that is inconsistent with the respective gene promoter methylation status, and that this overexpression might serve to promote the inflammatory carcinogenesis caused by C. albicans infection.

  14. Lack of Correlation between Aberrant p16, RAR-β2, TIMP3, ERCC1, and BRCA1 Protein Expression and Promoter Methylation in Squamous Cell Carcinoma Accompanying Candida albicans-Induced Inflammation.

    Science.gov (United States)

    Terayama, Yui; Matsuura, Tetsuro; Ozaki, Kiyokazu

    2016-01-01

    Hyperplastic candidiasis is characterized by thickening of the mucosal epithelia with Candida albicans infection with occasional progression to squamous cell carcinoma (SCC). C. albicans is a critical factor in tumor development; however, the oncogenic mechanism is unclear. We have previously produced an animal model for hyperplastic candidiasis in the rat forestomach. In the present study, we investigate whether impaired DNA methylation and associated protein expression of tumor suppressor and DNA repair genes are involved in the SCC carcinogenesis process using this hyperplastic candidiasis model. Promoter methylation and protein expression were analyzed by methylation specific PCR and immunohistochemical staining, respectively, of 5 areas in the forestomachs of alloxan-induced diabetic rats with hyperplastic candidiasis: normal squamous epithelia, squamous hyperplasia, squamous hyperplasia adjacent to SCC, squamous hyperplasia transitioning to SCC, and SCC. We observed nuclear p16 overexpression despite increases in p16 gene promoter methylation during the carcinogenic process. TIMP3 and RAR-β2 promoter methylation progressed until the precancerous stage but disappeared upon malignant transformation. In comparison, TIMP3 protein expression was suppressed during carcinogenesis and RAR-β2 expression was attenuated in the cytoplasm but enhanced in nuclei. ERCC1 and BRCA1 promoters were not methylated at any stage; however, their protein expression disappeared beginning at hyperplasia and nuclear protein re-expression in SCC was observed only for ERCC1. These results suggest that aberrant p16, RAR-β2, TIMP3, ERCC1, and BRCA1 expression might occur that is inconsistent with the respective gene promoter methylation status, and that this overexpression might serve to promote the inflammatory carcinogenesis caused by C. albicans infection.

  15. Recent advances of aberrant expression of nucleophosmin in acute leukemia%急性白血病中核仁磷酸蛋白异常表达的研究进展

    Institute of Scientific and Technical Information of China (English)

    王凌燕

    2014-01-01

    核仁磷酸蛋白(NPM)是一种在各种类型的细胞中广泛表达的多功能蛋白质.NPM基因的异常表达可导致细胞的恶性增殖,参与肿瘤的发生与发展.NPM的基因表达异常主要有过表达、基因重排、基因突变三种情况.NPM高表达于增殖活跃的细胞中,参与实体瘤与白血病的发生、发展.NPM还可与其他基因(RARα、MLF1、ALK)形成致癌性的融合蛋白,促进急性早幼粒细胞白病(M3)、骨髓增生异常综合征(MDS)和淋巴瘤的发生.NPM1突变是导致白血病发生的主要分子事件之一,可以累及AML的多种亚型,影响AML的预后.文章就急性白血病NPM基因表达异常的进展作一综述.%Nucleophosmin (NPM) is regularly identified as multifunctional nuclear protein which is widely expressed in different kinds of cells.NPM is identified not only as a potential regulator for cell proliferation,but also as an important player in tumor genesis procession.Aberrant expression of NPM,such as over-expression,rearrangement and mutation could lead to malignant transformation in solid tumor and leukemia cells.Over-expression of NPM had been detected as a poor prognostic factor and was related to drug-resistance development.It is reported that rearrangement of NPM gene played an important role in acute promyelocytic leukemia (APL,M3),myelodysplastic syndrome (MDS) and lymphoma.As the main molecular event in AML,NPM1 mutation occurred in kinds of subtypes of AML,which predicted a different prognosis.The aberrant expression of NPM in acute leukemia was reviewed.

  16. Aberrant decrease of microRNA19b regulates TSLP expression and contributes to Th17 cells development in myasthenia gravis related thymomas.

    Science.gov (United States)

    Wang, Zhongkui; Chen, Yuping; Xu, Shengjie; Yang, Yanhua; Wei, Dongning; Wang, Wei; Huang, Xusheng

    2015-11-15

    Myasthenia gravis (MG) is an organ-specific autoimmune disease. The imbalance of T helper type 17 cells (Th17) plays a key role in the pathogenesis of thymomatous MG. But the regulatory mechanism for Th17 cell development in MG-related thymoma remains undefined. Here we demonstrated that thymic stromal lymphopoietin (TSLP) is significantly decreased in thymomas. We also proved that TSLP was post-trancriptionally regulated by microRNA-19b. The expression of microRNA-19b was negatively correlated with the expression of TSLP mRNA and protein in thymomas. This study indicated that the elevation of microRNA-19b suppressed TSLP expression and then influenced T cell development in thymomatous MG.

  17. Equine sarcoids: Bovine Papillomavirus type 1 transformed fibroblasts are sensitive to cisplatin and UVB induced apoptosis and show aberrant expression of p53

    Directory of Open Access Journals (Sweden)

    Finlay Margaret

    2012-12-01

    Full Text Available Abstract Bovine papillomavirus type 1 infects not only cattle but also equids and is a causative factor in the pathogenesis of commonly occurring equine sarcoid tumours. Whilst treatment of sarcoids is notoriously difficult, cisplatin has been shown to be one of the most effective treatment strategies for sarcoids. In this study we show that in equine fibroblasts, BPV-1 sensitises cells to cisplatin-induced and UVB-induced apoptosis, a known cofactor for papillomavirus associated disease, however BPV-1 transformed fibroblasts show increased clonogenic survival, which may potentially limit the therapeutic effects of repeated cisplatin treatment. Furthermore we show that BPV-1 increases p53 expression in sarcoid cell lines and p53 expression can be either nuclear or cytoplasmic. The mechanism and clinical significance of increase/abnormal p53 expression remains to be established.

  18. Aberrant over-expression of TRPM7 ion channels in pancreatic cancer: required for cancer cell invasion and implicated in tumor growth and metastasis

    Directory of Open Access Journals (Sweden)

    Nelson S. Yee

    2015-03-01

    Full Text Available Our previous studies in zebrafish development have led to identification of the novel roles of the transient receptor potential melastatin-subfamily member 7 (TRPM7 ion channels in human pancreatic cancer. However, the biological significance of TRPM7 channels in pancreatic neoplasms was mostly unexplored. In this study, we determined the expression levels of TRPM7 in pancreatic tissue microarrays and correlated these measurements in pancreatic adenocarcinoma with the clinicopathological features. We also investigated the role of TRPM7 channels in pancreatic cancer cell invasion using the MatrigelTM-coated transwell assay. In normal pancreas, TRPM7 is expressed at a discernable level in the ductal cells and centroacinar cells and at a relatively high level in the islet endocrine cells. In chronic pancreatitis, pre-malignant tissues, and malignant neoplasms, there is variable expression of TRPM7. In the majority of pancreatic adenocarcinoma specimens examined, TRPM7 is expressed at either moderate-level or high-level. Anti-TRPM7 immunoreactivity in pancreatic adenocarcinoma significantly correlates with the size and stages of tumors. In human pancreatic adenocarcinoma cells in which TRPM7 is highly expressed, short hairpin RNA-mediated suppression of TRPM7 impairs cell invasion. The results demonstrate that TRPM7 channels are over-expressed in a proportion of the pre-malignant lesions and malignant tumors of the pancreas, and they are necessary for invasion by pancreatic cancer cells. We propose that TRPM7 channels play important roles in development and progression of pancreatic neoplasm, and they may be explored as clinical biomarkers and targets for its prevention and treatment.

  19. Aberrant expression of miR-218 and miR-204 in human mesial temporal lobe epilepsy and hippocampal sclerosis-Convergence on axonal guidance

    DEFF Research Database (Denmark)

    Kaalund, Sanne Simone; Venø, Morten T; Bak, Mads

    2014-01-01

    R-204 and miR-218 showed strong changes in expression during fetal development of the hippocampus in pigs, and we identified four target genes, involved in axonal guidance and synaptic plasticity, ROBO1, GRM1, SLC1A2, and GNAI2, as bona fide targets of miR-218. GRM1 was also shown to be a direct target...

  20. Downregulation of retinoic acid receptor-β2expression is linked to aberrant methylation in esophageal squamous cell carcinoma cell lines

    Institute of Scientific and Technical Information of China (English)

    Zhong-Min Liu; Fang Ding; Ming-Zhou Guo; Li-Yong Zhang; Min Wu; Zhi-Hua Liu

    2004-01-01

    AIM: To study the role of hypermethylation in the loss ofretinoic acid receptorβ2(RARβ2) in esophageal squamous cell carcinoma (ESCC).METHODS: The role of hypermethylation in RAR,β2 gene silencing in 6 ESCC cell lines was determined by methylationspecific PCR (MSP), and its methylation status was compared with RARβ2 mRNA expression by RT-PCR. The MSP results were confirmed by bisulfite sequencing of RARβ2promoter regions. RESULTS: Methylation was detected in 4 of the 6 cell lines, and the expression of RARβ2was markedly downregulated in 3 of the 4 methylated cell lines. The expression of RARβ2was restored in one RARβ2-downregulated cell line with the partial demethylation of promoter region of RARβ after 5aza-2'-deoxycytidine (5-aza-dc) treatment.CONCLUSION: The methylation of the 5' region may play an important role in the downregulation of RARβ2 in someESCC cell lines, suggesting that multiple mechanisms contribute to the loss of RARβ2expression in ESCC cell lines. This study may have clinical applications for treatment and prevention of ESCC.

  1. Decreased expression of BRCA1 in SK-BR-3 cells is the result of aberrant activation of the GABP Beta promoter by an NRF-1-containing complex

    Directory of Open Access Journals (Sweden)

    MacDonald Gwen

    2011-05-01

    Full Text Available Abstract Background BRCA1 has recently been identified as a potential regulator of mammary stem/progenitor cell differentiation, and this function may explain the high prevalence of breast cancer in BRCA1 mutation carriers, as well as the downregulation of BRCA1 in a large proportion of sporadic breast cancers. That is, loss of BRCA1 function results in blocked differentiation with expansion of the mammary stem/progenitor cells. Because BRCA1 also maintains genomic integrity, its loss could produce a pool of genetically unstable stem/progenitor cells that are prime targets for further transforming events. Thus, elucidating the regulatory mechanisms of BRCA1 expression is important to our understanding of normal and malignant breast differentiation. Results Loss of BRCA1 expression in the ErbB2-amplified SK-BR-3 cell line was found to be the result of loss of activity of the ets transcription factor GABP, a previously characterized regulator of BRCA1 transcription. The expression of the non-DNA binding GABPβ subunit was shown to be deficient, while the DNA binding subunit, GABPα was rendered unstable by the absence of GABPβ. Deletion analysis of the GABPβ proximal promoter identified a potential NRF-1 binding site as being critical for expression. Supershift analysis, the binding of recombinant protein and chromatin immunoprecipitation confirmed the role of NRF-1 in regulating the expression of GABPβ. The siRNA knockdown of NRF-1 resulted in decreased GABPβ and BRCA1 expression in MCF-7 cells indicating that they form a transcriptional network. NRF-1 levels and activity did not differ between SK-BR-3 and MCF-7 cells, however the NRF-1 containing complex on the GABPβ promoter differed between the two lines and appears to be the result of altered coactivator binding. Conclusions Both NRF-1 and GABP have been linked to the regulation of nuclear-encoded mitochondrial proteins, and the results of this study suggest their expression is

  2. Promoter histone H3 lysine 9 di-methylation is associated with DNA methylation and aberrant expression of p16 in gastric cancer cells.

    Science.gov (United States)

    Meng, Chun-Feng; Zhu, Xin-Jiang; Peng, Guo; Dai, Dong-Qiu

    2009-11-01

    In the course of gastric cancer development, gene silencing by DNA hypermethylation is an important mechanism. While DNA methylation often co-exists with histone modifications to regulate gene expression, the function of histone modifications in gene silencing in gastric cancer has not been evaluated in detail. p16, a well-known tumor suppressor gene, is frequently silenced in DNA hypermethylation manner in gastric cancer. Accordingly, we chose p16 to clarify whether there is a correlation among histone H3 lysine 9 (H3-K9) di-methylation, H3-K9 acetylation, DNA methylation and p16 expression in human gastric cancer. Three gastric cancer cells, MKN-45, SGC-7901 and BGC-823, were treated with 5-aza-2'-deoxycytidine (5-Aza-dC) and/or trichostatin A (TSA). We investigated p16 promoter DNA methylation status, p16 mRNA levels, regional and global levels of di-methyl-H3-K9 and acetyl-H3-K9 in four groups: i) 5-Aza-dC, ii) TSA, iii) the combination of 5-Aza-dC and TSA and iv) control group with no treatments. p16 silencing is characterized by DNA hypermethylation, H3-K9 hypoacetylation and H3-K9 hypermethylation at the promoter region. Treatment with TSA, increased H3-K9 acetylation at the hypermethylated promoter, but did not affect H3-K9 di-methylation or p16 expression. By contrast, treatment with 5-Aza-dC, reduced H3-K9 di-methylation, increased H3-K9 acetylation at the hypermethylated promoter and reactivated the expression of p16. Combined treatment restored the expression of p16 synergistically. In addition, 5-Aza-dC and the combined treatment did not result in global alteration of H3-K9 di-methylation. These results suggest that H3-K9 di-methylation, H3-K9 acetylation and DNA methylation work in combination to silence p16 in gastric cancer. The decreased H3-K9 di-methylation correlates with DNA demethylation and reactivation of p16. H3-K9 di-methylation as well as DNA methylation related to p16 silencing is limited to the promoter region. In addition to its effect

  3. Aberrantly glycosylated MUC1 is expressed on the surface of breast cancer cells and a target for antibody-dependent cell-mediated cytotoxicity

    DEFF Research Database (Denmark)

    Lavrsen, Kirstine; Madsen, Caroline B; Rasch, Morten G

    2013-01-01

    not covered by immunological tolerance in MUC1 humanized mice and man. The objective of this study was to determine if mouse antibodies to this Tn-MUC1 epitope induce antibody-dependent cellular cytotoxicity (ADCC) pivotal for their potential use in cancer immunotherapy. Binding affinity of mAb 5E5 directed...... is expressed on the surface of breast cancer cells and a target for antibody-dependent cell-mediated cytotoxicity suggesting that antibodies targeting glycopeptide epitopes on mucins are strong candidates for cancer-specific immunotherapies.......Protein glycosylation often changes during cancer development, resulting in the expression of cancer-associated carbohydrate antigens. In particular mucins such as MUC1 are subject to these changes. We previously identified an immunodominant Tn-MUC1 (GalNAc-α-MUC1) cancer-specific epitope...

  4. Aberrant expression of VEGF-C is related to grade of cervical intraepithelial neoplasia (CIN) and high risk HPV, but does not predict virus clearance after treatment of CIN or prognosis of cervical cancer.

    Science.gov (United States)

    Branca, M; Giorgi, C; Santini, D; Di Bonito, L; Ciotti, M; Benedetto, A; Paba, P; Costa, S; Bonifacio, D; Di Bonito, P; Accardi, L; Favalli, C; Syrjänen, K

    2006-01-01

    Increased angiogenesis leads to invasion in cervical cancer. Vascular endothelial growth factors (VEGFs) are involved in angiogenesis, but molecular links to the most important aetiological agent, human papillomavirus (HPV), need clarifying. Archival samples-150 squamous cell carcinomas (SCCs) and 152 cervical intraepithelial neoplasia (CIN) lesions-were examined immunohistochemically for anti-VEGF-C antibody and for HPV by polymerase chain reaction (PCR). Follow up data were available for all SCC cases, and 67 CIN lesions were monitored with serial PCR to assess HPV clearance/persistence after treatment. High risk (HR) HPV types were closely associated with CIN (odds ratio, 19.12; 95% confidence interval, 2.31 to 157.81) and SCC (27.25; 3.28 to 226.09). There was a linear increase of VEGF-C expression-weak in CIN1 and intense in CIN3 and SCC (20.49; 8.69 to 48.26). VEGF-C upregulation was a sensitive (93.5%; 95% CI, 90.1% to 96.9%) marker of HR-HPV type (4.70; 2.17 to 10.21), but lost its significance in multivariate regression-p16(INK4a) and survivin were equally strong independent predictors of HR-HPV. Aberrant expression of VEGF-C did not predict clearance/persistence of HR-HPV after treatment of CIN. In cervical cancer, VEGF-C had no prognostic value in univariate or multivariate survival analysis. After adjustment for HR-HPV, FIGO stage, age, and tumour grade, only FIGO stage and age remained independent prognostic predictors. VEGF-C is an early marker of cervical carcinogenesis, with linearly increasing expression starting from low grade CIN. VEGF-C expression is closely related to HR-HPV in cervical lesions, probably because of its p53 independent upregulation by the E6 oncoprotein of HR-HPV.

  5. CD229 is expressed on the surface of plasma cells carrying an aberrant phenotype and chemotherapy-resistant precursor cells in multiple myeloma.

    Science.gov (United States)

    Yousef, Sara; Kovacsovics-Bankowski, Magdalena; Salama, Mohamed E; Bhardwaj, Neelam; Steinbach, Mary; Langemo, Amanda; Kovacsovics, Tibor; Marvin, James; Binder, Mascha; Panse, Jens; Kröger, Nicolaus; Luetkens, Tim; Atanackovic, Djordje

    2015-01-01

    Multiple Myeloma (MM) is a plasma cell (PC) malignancy, which despite significant therapeutic advances, is still considered incurable. This is due to the persistence of chemotherapy-resistant minimal residual disease in the patients' bone marrow (BM) after an effective induction therapy. Immunotherapies targeting surface molecules expressed on the bulk of tumor cells and the chemotherapy-resistant, myeloma-propagating cells could play a central role in this clinical setting. We recently described surface molecule CD229 as a potential therapeutic target for MM. In our current study we assessed the expression of CD229 on different PC subtypes and on cells with a myeloma-propagating phenotype in a total of 77 patients with PC dyscrasias independently at 2 different cancer centers. We found that CD229 was strongly and homogeneously overexpressed on the PC of patients with monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma, MM, and PC leukemia. CD229 was particularly overexpressed on those PC showing an abnormal phenotype such as expression of CD56. Most importantly, CD229 was also highly expressed on those cells in the patients' BM displaying the phenotype of chemotherapy-resistant and myeloma-propagating cells. In conclusion, our combined findings suggest that immunotherapies targeting CD229 will not only be effective for the bulk of tumor cells but will also help to eradicate chemotherapy-resistant cells remaining in the patients' BM after induction treatment. Hopefully, the design of CD229-specific monoclonal antibodies or chimeric antigen receptor-transduced T cells will help to achieve prolonged remissions or even cures in MM patients.

  6. Aberrant expression and distribution of enzymes of the urea cycle and other ammonia metabolizing pathways in dogs with congenital portosystemic shunts.

    Science.gov (United States)

    van Straten, Giora; van Steenbeek, Frank G; Grinwis, Guy C M; Favier, Robert P; Kummeling, Anne; van Gils, Ingrid H; Fieten, Hille; Groot Koerkamp, Marian J A; Holstege, Frank C P; Rothuizen, Jan; Spee, Bart

    2014-01-01

    The detoxification of ammonia occurs mainly through conversion of ammonia to urea in the liver via the urea cycle and glutamine synthesis. Congenital portosystemic shunts (CPSS) in dogs cause hyperammonemia eventually leading to hepatic encephalopathy. In this study, the gene expression of urea cycle enzymes (carbamoylphosphate synthetase (CPS1), ornithine carbamoyltransferase (OTC), argininosuccinate synthetase (ASS1), argininosuccinate lyase (ASL), and arginase (ARG1)), N-acetylglutamate synthase (NAGS), Glutamate dehydrogenase (GLUD1), and glutamate-ammonia ligase (GLUL) was evaluated in dogs with CPSS before and after surgical closure of the shunt. Additionally, immunohistochemistry was performed on urea cycle enzymes and GLUL on liver samples of healthy dogs and dogs with CPSS to investigate a possible zonal distribution of these enzymes within the liver lobule and to investigate possible differences in distribution in dogs with CPSS compared to healthy dogs. Furthermore, the effect of increasing ammonia concentrations on the expression of the urea cycle enzymes was investigated in primary hepatocytes in vitro. Gene-expression of CPS1, OTC, ASL, GLUD1 and NAGS was down regulated in dogs with CPSS and did not normalize after surgical closure of the shunt. In all dogs GLUL distribution was localized pericentrally. CPS1, OTC and ASS1 were localized periportally in healthy dogs, whereas in CPSS dogs, these enzymes lacked a clear zonal distribution. In primary hepatocytes higher ammonia concentrations induced mRNA levels of CPS1. We hypothesize that the reduction in expression of urea cycle enzymes, NAGS and GLUD1 as well as the alterations in zonal distribution in dogs with CPSS may be caused by a developmental arrest of these enzymes during the embryonic or early postnatal phase.

  7. Gene expression in mdx mouse muscle in relation to age and exercise: aberrant mechanical-metabolic coupling and implications for pre-clinical studies in Duchenne muscular dystrophy.

    Science.gov (United States)

    Camerino, Giulia Maria; Cannone, Maria; Giustino, Arcangela; Massari, Ada Maria; Capogrosso, Roberta Francesca; Cozzoli, Anna; De Luca, Annamaria

    2014-11-01

    Weakness and fatigability are typical features of Duchenne muscular dystrophy patients and are aggravated in dystrophic mdx mice by chronic treadmill exercise. Mechanical activity modulates gene expression and muscle plasticity. Here, we investigated the outcome of 4 (T4, 8 weeks of age) and 12 (T12, 16 weeks of age) weeks of either exercise or cage-based activity on a large set of genes in the gastrocnemius muscle of mdx and wild-type (WT) mice using quantitative real-time PCR. Basal expression of the exercise-sensitive genes peroxisome-proliferator receptor γ coactivator 1α (Pgc-1α) and Sirtuin1 (Sirt1) was higher in mdx versus WT mice at both ages. Exercise increased Pgc-1α expression in WT mice; Pgc-1α was downregulated by T12 exercise in mdx muscles, along with Sirt1, Pparγ and the autophagy marker Bnip3. Sixteen weeks old mdx mice showed a basal overexpression of the slow Mhc1 isoform and Serca2; T12 exercise fully contrasted this basal adaptation as well as the high expression of follistatin and myogenin. Conversely, T12 exercise was ineffective in WT mice. Damage-related genes such as gp91-phox (NADPH-oxidase2), Tgfβ, Tnfα and c-Src tyrosine kinase were overexpressed in mdx muscles and not affected by exercise. Likewise, the anti-inflammatory adiponectin was lower in T12-exercised mdx muscles. Chronic exercise with minor adaptive effects in WT muscles leads to maladaptation in mdx muscles with a disequilibrium between protective and damaging signals. Increased understanding of the pathways involved in the altered mechanical-metabolic coupling may help guide appropriate physical therapies while better addressing pharmacological interventions in translational research.

  8. Nonallelic homologous recombination of the FCGR2/3 locus results in copy number variation and novel chimeric FCGR2 genes with aberrant functional expression.

    Science.gov (United States)

    Nagelkerke, S Q; Tacke, C E; Breunis, W B; Geissler, J; Sins, J W R; Appelhof, B; van den Berg, T K; de Boer, M; Kuijpers, T W

    2015-09-01

    The human FCGR2/3 locus, containing five highly homologous genes encoding the major IgG receptors, shows extensive copy number variation (CNV) associated with susceptibility to autoimmune diseases. Having genotyped >4000 individuals, we show that all CNV at this locus can be explained by nonallelic homologous recombination (NAHR) of the two paralogous repeats that constitute the majority of the locus, and describe four distinct CNV regions (CNRs) with a highly variable prevalence in the population. Apart from CNV, NAHR events also created several hitherto unidentified chimeric FCGR2 genes. These include an FCGR2A/2C chimeric gene that causes a decreased expression of FcγRIIa on phagocytes, resulting in a decreased production of reactive oxygen species in response to immune complexes, compared with wild-type FCGR2A. Conversely, FCGR2C/2A chimeric genes were identified to lead to an increased expression of FCGR2C. Finally, a rare FCGR2B null-variant allele was found, in which a polymorphic stop codon of FCGR2C is introduced into one FCGR2B gene, resulting in a 50% reduction in protein expression. Our study on CNRs and the chimeric genes is essential for the correct interpretation of association studies on FCGR genes as a determinant for disease susceptibility, and may explain some as yet unidentified extreme phenotypes of immune-mediated disease.

  9. Anisoplanatism in adaptive optics systems due to pupil aberrations

    Energy Technology Data Exchange (ETDEWEB)

    Bauman, B

    2005-08-01

    Adaptive optics systems typically include an optical relay that simultaneously images the science field to be corrected and also a set of pupil planes conjugate to the deformable mirror of the system. Often, in the optical spaces where DM's are placed, the pupils are aberrated, leading to a displacement and/or distortion of the pupil that varies according to field position--producing a type of anisoplanatism, i.e., a degradation of the AO correction with field angle. The pupil aberration phenomenon is described and expressed in terms of Seidel aberrations. An expression for anisoplanatism as a function of pupil distortion is derived, an example of an off-axis parabola is given, and a convenient method for controlling pupil-aberration-generated anisoplanatism is proposed.

  10. Aberration Correction in Electron Microscopy

    CERN Document Server

    Rose, Harald H

    2005-01-01

    The resolution of conventional electron microscopes is limited by spherical and chromatic aberrations. Both defects are unavoidable in the case of static rotationally symmetric electromagnetic fields (Scherzer theorem). Multipole correctors and electron mirrros have been designed and built, which compensate for these aberrations. The principles of correction will be demonstrated for the tetrode mirror, the quadrupole-octopole corrector and the hexapole corrector. Electron mirrors require a magnetic beam separator free of second-order aberrations. The multipole correctors are highly symmetric telescopic systems compensating for the defects of the objective lens. The hexapole corrector has the most simple structure yet eliminates only the spherical aberration, whereas the mirror and the quadrupole-octopole corrector are able to correct for both aberrations. Chromatic correction is achieved in the latter corrector by cossed electric and magnetic quadrupoles acting as first-order Wien filters. Micrographs obtaine...

  11. Camera processing with chromatic aberration.

    Science.gov (United States)

    Korneliussen, Jan Tore; Hirakawa, Keigo

    2014-10-01

    Since the refractive index of materials commonly used for lens depends on the wavelengths of light, practical camera optics fail to converge light to a single point on an image plane. Known as chromatic aberration, this phenomenon distorts image details by introducing magnification error, defocus blur, and color fringes. Though achromatic and apochromatic lens designs reduce chromatic aberration to a degree, they are complex and expensive and they do not offer a perfect correction. In this paper, we propose a new postcapture processing scheme designed to overcome these problems computationally. Specifically, the proposed solution is comprised of chromatic aberration-tolerant demosaicking algorithm and post-demosaicking chromatic aberration correction. Experiments with simulated and real sensor data verify that the chromatic aberration is effectively corrected.

  12. Glioma progression is mediated by an addiction to aberrant IGFBP2 expression and can be blocked using anti-IGFBP2 strategies.

    Science.gov (United States)

    Phillips, Lynette M; Zhou, Xinhui; Cogdell, David E; Chua, Corrine Yingxuan; Huisinga, Anouk; R Hess, Kenneth; Fuller, Gregory N; Zhang, Wei

    2016-07-01

    Insulin-like growth factor binding protein 2 (IGFBP2) overexpression is common in high-grade glioma and is both a strong biomarker of aggressive behaviour and a well-documented prognostic factor. IGFBP2 is a member of the secreted IGFBP family that functions by interacting with circulating IGFs to modulate IGF-mediated signalling. This traditional view of IGFBP2 activities has been challenged by the recognition of the diverse functions and cellular locations of members of the IGFBP family. IGFBP2 has been previously established as a driver of glioma progression to a higher grade. In this study, we sought to determine whether IGFBP2-overexpressing tumours are dependent on continued oncogene expression and whether IGFBP2 is a viable therapeutic target in glioma. We took advantage of the well-characterized RCAS/Ntv-a mouse model to create a doxycycline-inducible IGFBP2 model of glioma and demonstrated that the temporal expression of IGFBP2 has dramatic impacts on tumour progression and survival. Further, we demonstrated that IGFBP2-driven tumours are dependent on the continued expression of IGFBP2, as withdrawal of this oncogenic signal led to a significant decrease in tumour progression and prolonged survival. Inhibition of IGFBP2 also impaired tumour cell spread. To assess a therapeutically relevant inhibition strategy, we evaluated a neutralizing antibody against IGFBP2 and demonstrated that it impaired downstream IGFBP2-mediated oncogenic signalling pathways. The studies presented here indicate that IGFBP2 not only is a driver of glioma progression and a prognostic factor but is also required for tumour maintenance and thus represents a viable therapeutic target in the treatment of glioma. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  13. Epigenetic Perturbations by Arg882-Mutated DNMT3A Potentiate Aberrant Stem Cell Gene-Expression Program and Acute Leukemia Development.

    Science.gov (United States)

    Lu, Rui; Wang, Ping; Parton, Trevor; Zhou, Yang; Chrysovergis, Kaliopi; Rockowitz, Shira; Chen, Wei-Yi; Abdel-Wahab, Omar; Wade, Paul A; Zheng, Deyou; Wang, Gang Greg

    2016-07-11

    DNA methyltransferase 3A (DNMT3A) is frequently mutated in hematological cancers; however, the underlying oncogenic mechanism remains elusive. Here, we report that the DNMT3A mutational hotspot at Arg882 (DNMT3A(R882H)) cooperates with NRAS mutation to transform hematopoietic stem/progenitor cells and induce acute leukemia development. Mechanistically, DNMT3A(R882H) directly binds to and potentiates transactivation of stemness genes critical for leukemogenicity including Meis1, Mn1, and Hoxa gene cluster. DNMT3A(R882H) induces focal epigenetic alterations, including CpG hypomethylation and concurrent gain of active histone modifications, at cis-regulatory elements such as enhancers to facilitate gene transcription. CRISPR/Cas9-mediated ablation of a putative Meis1 enhancer carrying DNMT3A(R882H)-induced DNA hypomethylation impairs Meis1 expression. Importantly, DNMT3A(R882H)-induced gene-expression programs can be repressed through Dot1l inhibition, providing an attractive therapeutic strategy for DNMT3A-mutated leukemias.

  14. Aberrant expression of glucagon receptors in adrenal glands of a patient with Cushing's syndrome and ACTH-independent macronodular adrenal hyperplasia

    Directory of Open Access Journals (Sweden)

    Valeria de Miguel

    2010-06-01

    Full Text Available Adrenocorticotropin (ACTH independent bilateral macronodular adrenal hyperplasia (AIMAH is a rare cause of Cushing´s syndrome, characterized by bilateral adrenal lesions and excess cortisol production despite ACTH suppression. Cortisol synthesis is produced in response to abnormal activation of G-protein- coupled receptors, such as gastric inhibitory peptide, vasopressin, beta adrenergic agonists, LH/hCG and serotonin receptors. The aim of this study was to analyze the expression of glucagon receptors in adrenal glands from an AIMAH patient. A patient with ACTH-independent Cushing´s syndrome and bilateral macronodular adrenal hyperplasia was screened for altered activation of adrenal receptors by physiological (mixed meal and pharmacological (gonadotrophin releasing hormone, ACTH and glucagon tests. The results showed abnormally high levels of serum cortisol after stimulation with glucagon. Hypercortisolism was successfully managed with ketoconazole treatment. Interestingly, a 4-month treatment with a somatostatin analogue (octreotide was also able to reduce cortisol secretion. Finally, Cushing's syndrome was cured after bilateral adrenalectomy. Abnormal mRNA expression for glucagon receptor in the patient´s adrenal glands was observed by Real-Time PCR procedure. These results strongly suggest that the mechanism of AIMAH causing Cushing´s syndrome in this case involves the illicit activation of adrenal glucagon receptors. This is the first case reported of AIMAH associated with ectopic glucagon receptors.

  15. Delayed cutaneous wound healing and aberrant expression of hair follicle stem cell markers in mice selectively lacking Ctip2 in epidermis.

    Directory of Open Access Journals (Sweden)

    Xiaobo Liang

    Full Text Available BACKGROUND: COUP-TF interacting protein 2 [(Ctip2, also known as Bcl11b] is an important regulator of skin homeostasis, and is overexpressed in head and neck cancer. Ctip2(ep-/- mice, selectively ablated for Ctip2 in epidermal keratinocytes, exhibited impaired terminal differentiation and delayed epidermal permeability barrier (EPB establishment during development, similar to what was observed in Ctip2 null (Ctip2(-/- mice. Considering that as an important role of Ctip2, and the fact that molecular networks which underlie cancer progression partially overlap with those responsible for tissue remodeling, we sought to determine the role of Ctip2 during cutaneous wound healing. METHODOLOGY/PRINCIPAL FINDINGS: Full thickness excisional wound healing experiments were performed on Ctip2(L2/L2 and Ctip2(ep-/- animals per time point and used for harvesting samples for histology, immunohistochemistry (IHC and immunoblotting. Results demonstrated inherent defects in proliferation and migration of Ctip2 lacking keratinocytes during re-epithelialization. Mutant mice exhibited reduced epidermal proliferation, delayed keratinocyte activation, altered cell-cell adhesion and impaired ECM development. Post wounding, Ctip2(ep-/- mice wounds displayed lack of E-Cadherin suppression in the migratory tongue, insufficient expression of alpha smooth muscle actin (alpha SMA in the dermis, and robust induction of K8. Importantly, dysregulated expression of several hair follicle (HF stem cell markers such as K15, NFATc1, CD133, CD34 and Lrig1 was observed in mutant skin during wound repair. CONCLUSIONS/SIGNIFICANCE: Results confirm a cell autonomous role of keratinocytic Ctip2 to modulate cell migration, proliferation and/or differentiation, and to maintain HF stem cells during cutaneous wounding. Furthermore, Ctip2 in a non-cell autonomous manner regulated granulation tissue formation and tissue contraction during wound closure.

  16. Altered expression of BRG1 and histone demethylases, and aberrant H3K4 methylation in less developmentally competent embryos at the time of embryonic genome activation.

    Science.gov (United States)

    Glanzner, Werner G; Wachter, Audrey; Coutinho, Ana Rita S; Albornoz, Marcelo S; Duggavathi, Raj; GonÇAlves, Paulo B D; Bordignon, Vilceu

    2017-01-01

    Epigenetics is a fundamental regulator underlying many biological functions, such as development and cell differentiation. Epigenetic modifications affect key chromatin regulation, including transcription and DNA repair, which are critical for normal embryo development. In this study, we profiled the expression of epigenetic modifiers and patterns of epigenetic changes in porcine embryos around the period of embryonic genome activation (EGA). We observed that Brahma-related gene 1 (BRG1) and Lysine demethylase 1A (KDM1A), which can alter the methylation status of lysine 4 in histone 3 (H3K4), localize to the nucleus at Day 3-4 of development. We then compared the abundance of epigenetic modifiers between early- and late-cleaving embryos, which were classified based on the time to the first cell cleavage, to investigate if their nuclear localization contributes to developmental competence. The mRNA abundance of BRG1, KDM1A, as well as other lysine demethylases (KDM1B, KDM5A, KDM5B, and KDM5C), were significantly higher in late- compared to early-cleaving embryos near the EGA period, although these difference disappeared at the blastocyst stage. The abundance of H3K4 mono- (H3K4me) and di-methylation (H3K4me2) during the EGA period was reduced in late-cleaving and less developmentally competent embryos. By contrast, BRG1, KDM1A, and H3K4me2 abundance was greater in embryos with more than eight cells at Day 3-4 of development compared to those with fewer than four cells. These findings suggest that altered epigenetic modifications of H3K4 around the EGA period may affect the developmental capacity of porcine embryos to reach the blastocyst stage. Mol. Reprod. Dev. 84: 19-29, 2017. © 2016 Wiley Periodicals, Inc.

  17. Phase aberration effects in elastography.

    Science.gov (United States)

    Varghese, T; Bilgen, M; Ophir, J

    2001-06-01

    In sonography, phase aberration plays a role in the corruption of sonograms. Phase aberration does not have a significant impact on elastography, if statistically similar phase errors are present in both the pre- and postcompression signals. However, if the phase errors are present in only one of the pre- or postcompression signal pairs, the precision of the strain estimation process will be reduced. In some cases, increased phase errors may occur only in the postcompression signal due to changes in the tissue structure with the applied compression. Phase-aberration effects increase with applied strain and may be viewed as an image quality derating factor, much like frequency-dependent attenuation or undesired lateral tissue motion. In this paper, we present a theoretical and simulation study of the effects of phase aberration on the elastographic strain-estimation process, using the strain filter approach.

  18. Historical aspects of aberration correction.

    Science.gov (United States)

    Rose, Harald H

    2009-06-01

    A brief history of the development of direct aberration correction in electron microscopy is outlined starting from the famous Scherzer theorem established in 1936. Aberration correction is the long story of many seemingly fruitless efforts to improve the resolution of electron microscopes by compensating for the unavoidable resolution-limiting aberrations of round electron lenses over a period of 50 years. The successful breakthrough, in 1997, can be considered as a quantum step in electron microscopy because it provides genuine atomic resolution approaching the size of the radius of the hydrogen atom. The additional realization of monochromators, aberration-free imaging energy filters and spectrometers has been leading to a new generation of analytical electron microscopes providing elemental and electronic information about the object on an atomic scale.

  19. Aberrant Glycosylation as Biomarker for Cancer: Focus on CD43

    Directory of Open Access Journals (Sweden)

    Franca Maria Tuccillo

    2014-01-01

    Full Text Available Glycosylation is a posttranslational modification of proteins playing a major role in cell signalling, immune recognition, and cell-cell interaction because of their glycan branches conferring structure variability and binding specificity to lectin ligands. Aberrant expression of glycan structures as well as occurrence of truncated structures, precursors, or novel structures of glycan may affect ligand-receptor interactions and thus interfere with regulation of cell adhesion, migration, and proliferation. Indeed, aberrant glycosylation represents a hallmark of cancer, reflecting cancer-specific changes in glycan biosynthesis pathways such as the altered expression of glycosyltransferases and glycosidases. Most studies have been carried out to identify changes in serum glycan structures. In most cancers, fucosylation and sialylation are significantly modified. Thus, aberrations in glycan structures can be used as targets to improve existing serum cancer biomarkers. The ability to distinguish differences in the glycosylation of proteins between cancer and control patients emphasizes glycobiology as a promising field for potential biomarker identification. In this review, we discuss the aberrant protein glycosylation associated with human cancer and the identification of protein glycoforms as cancer biomarkers. In particular, we will focus on the aberrant CD43 glycosylation as cancer biomarker and the potential to exploit the UN1 monoclonal antibody (UN1 mAb to identify aberrant CD43 glycoforms.

  20. Automated computational aberration correction method for broadband interferometric imaging techniques.

    Science.gov (United States)

    Pande, Paritosh; Liu, Yuan-Zhi; South, Fredrick A; Boppart, Stephen A

    2016-07-15

    Numerical correction of optical aberrations provides an inexpensive and simpler alternative to the traditionally used hardware-based adaptive optics techniques. In this Letter, we present an automated computational aberration correction method for broadband interferometric imaging techniques. In the proposed method, the process of aberration correction is modeled as a filtering operation on the aberrant image using a phase filter in the Fourier domain. The phase filter is expressed as a linear combination of Zernike polynomials with unknown coefficients, which are estimated through an iterative optimization scheme based on maximizing an image sharpness metric. The method is validated on both simulated data and experimental data obtained from a tissue phantom, an ex vivo tissue sample, and an in vivo photoreceptor layer of the human retina.

  1. Aberrant expression of Tiel gene in venous valves in great saphenous varicose vein%Tiel基因在曲张大隐静脉瓣膜的异常表达

    Institute of Scientific and Technical Information of China (English)

    王鑫; 乔彤; 刘长建

    2012-01-01

    Objective To investigate the aberrant expression of Tiel gene in venous valves in great saphenous varicose vein,and its role in pathogenesis of varicose vein of lower extremity.Methods Varicose veins group ( 15 samples) and normal control group ( 11 samples) were set up.By using immunohistochemistry staining,the expression of CD31 and Tiel in the first valves in great saphenous veins was detected.Western blotting was used to check the expression of Tiel protein in venous valves.Results In normal control group valves,there was no difference between proximal and distal sides endothelium in expressing CD31 (P > 0.05 ).The proximal side endothelium expressed Tie1 stronger than distal side at the basal part (P < 0.05 ),but this difference was not found at valve cusp (P > 0.05 ).In varicose veins group,besides morphological changes of valves,the proximal side endothelia expressed CD31 weaker than diatal side endothelia ( P < 0.05 ),and expressed Tiel much weaker than diatal side endothelia ( P <0.01 ).The expression of Tiel protein was undetectable in venous valves.Conclusion The decreased expression of Tiel in proximal side of venous valves may play a role in the pathogenesis of primary lower extremity varicose veins.%目的 观察下肢静脉曲张疾病中,Tiel基因在曲张大隐静脉第1对瓣膜中的异常表达,探讨其与下肢静脉曲张发病机制之间的关系.方法 大隐静脉曲张组15例,正常对照组11例;用免疫组织化学法检测大隐静脉第一对瓣膜CD31及Tiel的表达,并用Western blot检测瓣膜中Tiel蛋白的表达.结果 正常对照组中瓣膜两侧内皮细胞表达CD31差异无统计学意义(P>0.05),在瓣膜根部近心侧内皮细胞表达Tiel强于远心侧(P<0.05),但在瓣膜尖部差异无统计学意义(P>0.05);静脉曲张组中瓣膜除了形态发生变化外,瓣膜近心侧内皮细胞CD31的表达稍弱于远心侧(P<0.05),而Tiel的表达显著弱于远心侧(P<0.01);Western blot

  2. Aberrant splicing in transgenes containing introns, exons, and V5 epitopes: lessons from developing an FSHD mouse model expressing a D4Z4 repeat with flanking genomic sequences.

    Directory of Open Access Journals (Sweden)

    Eugénie Ansseau

    Full Text Available The DUX4 gene, encoded within D4Z4 repeats on human chromosome 4q35, has recently emerged as a key factor in the pathogenic mechanisms underlying Facioscapulohumeral muscular dystrophy (FSHD. This recognition prompted development of animal models expressing the DUX4 open reading frame (ORF alone or embedded within D4Z4 repeats. In the first published model, we used adeno-associated viral vectors (AAV and strong viral control elements (CMV promoter, SV40 poly A to demonstrate that the DUX4 cDNA caused dose-dependent toxicity in mouse muscles. As a follow-up, we designed a second generation of DUX4-expressing AAV vectors to more faithfully genocopy the FSHD-permissive D4Z4 repeat region located at 4q35. This new vector (called AAV.D4Z4.V5.pLAM contained the D4Z4/DUX4 promoter region, a V5 epitope-tagged DUX4 ORF, and the natural 3' untranslated region (pLAM harboring two small introns, DUX4 exons 2 and 3, and the non-canonical poly A signal required for stabilizing DUX4 mRNA in FSHD. AAV.D4Z4.V5.pLAM failed to recapitulate the robust pathology of our first generation vectors following delivery to mouse muscle. We found that the DUX4.V5 junction sequence created an unexpected splice donor in the pre-mRNA that was preferentially utilized to remove the V5 coding sequence and DUX4 stop codon, yielding non-functional DUX4 protein with 55 additional residues on its carboxyl-terminus. Importantly, we further found that aberrant splicing could occur in any expression construct containing a functional splice acceptor and sequences resembling minimal splice donors. Our findings represent an interesting case study with respect to AAV.D4Z4.V5.pLAM, but more broadly serve as a note of caution for designing constructs containing V5 epitope tags and/or transgenes with downstream introns and exons.

  3. The suppression of aberrant crypt multiplicity in colonic tissue of 1,2-dimethylhydrazine-treated C57BL/6J mice by dietary flavone is associated with an increased expression of Krebs cycle enzymes.

    Science.gov (United States)

    Winkelmann, Isabel; Diehl, Daniela; Oesterle, Doris; Daniel, Hannelore; Wenzel, Uwe

    2007-07-01

    Colorectal cancer is the second leading cause of cancer deaths worldwide with diet playing a prominent role in disease initiation and progression. Flavonoids are secondary plant compounds that are suggested as protective ingredients of a diet rich in fruits and vegetables. We here tested whether flavone, a flavonoid that proved to be an effective apoptosis inducer in colon cancer cells in culture, can affect the development of aberrant crypt foci (ACFs) in C57BL/6J mice in vivo when preneoplastic lesions were induced by the carcinogen 1,2-dimethylhydrazine (DMH). Flavone applied at either a low dose (15 mg/kg body wt per day) or a high dose (400 mg/kg body wt per day) reduced the numbers of ACFs significantly, independent of whether it was supplied simultaneously with the carcinogen (blocking group) or subsequent to the tumor induction phase (suppressing group). Proteome analysis performed in colonic tissue samples revealed that flavone treatment increased the expression of a number of Krebs cycle enzymes in the suppressing group and this was associated with reduced crypt multiplicity. It suggests that mitochondrial substrate oxidation is increased by flavone in colonic cells in vivo as already observed in HT-29 cells in vitro as the prime mechanism underlying tumor cell apoptosis induction by flavone. In conclusion, flavone reduces the number of ACFs in DMH-treated mice at doses that can be achieved for flavonoids by a diet rich in fruits and vegetables. Moreover, reduction in crypt multiplicity by flavone is most probably due to the preservation of a normal oxidative metabolism.

  4. Polarization aberrations of radiation at the lens focus

    NARCIS (Netherlands)

    Sokolov, AL

    2005-01-01

    The polarization aberrations of radiation at the lens focus are calculated with allowance for diffraction effects. Calculations are performed using the representation of radiation as a coherent set of Hermite-Gauss modes with certain amplitudes, phases, and polarizations. An expression for the longi

  5. Ⅰ型钙黏蛋白基因异常甲基化及其功能蛋白表达与肺癌的相关性%Aberrant hypermethylation and expression of cadherin 1 in lung cancer

    Institute of Scientific and Technical Information of China (English)

    段勇; 杨兰辉; 袁育林; 黄韬; 王玉明; 金克炜

    2008-01-01

    Objective To explore the relationship between hypermethylation and expression of cadherin 1(CDH1)with lung cancer.Methods The semi-quantitative real-time methylation specific polymerage chsin reaction(MSP)were used to detect the promoter's relative methylation ratio of CDH1 in all 30 cases of lung cancer tissues,para-cancer lung tissues,distal lung tissues and 5 non-cancer lung tissue samples.Nested RT-PCR was used to detect the expression ratio of CDH1 mRNA.The western blot analysis was used to detect the expression of E-cad protein.The immunohistoeheroical method was used to confirm some negative results of western blot analysis.Results The relative methylation ratios was 0.13%-450.67%(median:33.61%)in cancer tissues,0.00%-177.02%(median:18.04%)in para-cancer tissues,and 0.00%-51.68%(median:13.69%)in far-cancer tissues.Statistical significance between cancer and pars-cancer tissues(Z=-2.355,P<0.05)and between cancer and disial tissues(Z=-3.527,P<0.01)were found.The results of nested RT-PCR showed that there were statistical sigaificance of mRNA expression between lung cancer tissues and pars-cancer tissues,distal lung tissues or non-cancer lung tissues(F=9.081,P<0.01).The results of western blot showed that the positive expression rate of E-cad was 36.7% in lung cancer tissues,70.0%in para-cancer tissues,and 96.7% in far-cancer lung tissues,respectively.There was a statistical significance of positive rate pf E-cad expression between lung cancer tissues and pars-cancer tissues or diatal tissues(X2=6.70,24.30,7.68,P<0.01).Conclusions The study showed that transcription of CDH1 mRNA would be silenced by hypermethylation of CDH1 promoter,resulting in the decreased expression of E-cad.The aberrant hypermethylation of E-cad is implicated in lung cancer.%目的 探讨Ⅰ型钙黏蛋白(cadherin 1,CDH1)基因甲基化及其功能蛋白表达与肺癌的相关性.方法 分别提取基因组DNA、总RNA和总蛋白,用半定量荧光甲基化特异PCR(MSP)、巢

  6. Using geometric algebra to study optical aberrations

    Energy Technology Data Exchange (ETDEWEB)

    Hanlon, J.; Ziock, H.

    1997-05-01

    This paper uses Geometric Algebra (GA) to study vector aberrations in optical systems with square and round pupils. GA is a new way to produce the classical optical aberration spot diagrams on the Gaussian image plane and surfaces near the Gaussian image plane. Spot diagrams of the third, fifth and seventh order aberrations for square and round pupils are developed to illustrate the theory.

  7. Phase Aberrations in Diffraction Microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Marchesini, S; Chapman, H N; Barty, A; Howells, M R; Spence, J H; Cui, C; Weierstall, U; Minor, A M

    2005-09-29

    In coherent X-ray diffraction microscopy the diffraction pattern generated by a sample illuminated with coherent x-rays is recorded, and a computer algorithm recovers the unmeasured phases to synthesize an image. By avoiding the use of a lens the resolution is limited, in principle, only by the largest scattering angles recorded. However, the imaging task is shifted from the experiment to the computer, and the algorithm's ability to recover meaningful images in the presence of noise and limited prior knowledge may produce aberrations in the reconstructed image. We analyze the low order aberrations produced by our phase retrieval algorithms. We present two methods to improve the accuracy and stability of reconstructions.

  8. Chromosome aberrations induced by zebularine in triticale.

    Science.gov (United States)

    Ma, Xuhui; Wang, Qing; Wang, Yanzhi; Ma, Jieyun; Wu, Nan; Ni, Shuang; Luo, Tengxiao; Zhuang, Lifang; Chu, Chenggen; Cho, Seong-Woo; Tsujimoto, Hisashi; Qi, Zengjun

    2016-07-01

    Chromosome engineering is an important approach for generating wheat germplasm. Efficient development of chromosome aberrations will facilitate the introgression and application of alien genes in wheat. In this study, zebularine, a DNA methylation transferase inhibitor, was successfully used to induce chromosome aberrations in the octoploid triticale cultivar Jinghui#1. Dry seeds were soaked in zebularine solutions (250, 500, and 750 μmol/L) for 24 h, and the 500 μmol/L treatment was tested in three additional treatment times, i.e., 12, 36, and 48 h. All treatments induced aberrations involving wheat and rye chromosomes. Of the 920 cells observed in 67 M1 plants, 340 (37.0%) carried 817 aberrations with an average of 0.89 aberrations per cell (range: 0-12). The aberrations included probable deletions, telosomes and acentric fragments (49.0%), large segmental translocations (28.9%), small segmental translocations (17.1%), intercalary translocations (2.6%), long chromosomes that could carry more than one centromere (2.0%), and ring chromosomes (0.5%). Of 510 M2 plants analyzed, 110 (21.6%) were found to carry stable aberrations. Such aberrations included 79 with varied rye chromosome numbers, 7 with wheat and rye chromosome translocations, 15 with possible rye telosomes/deletions, and 9 with complex aberrations involving variation in rye chromosome number and wheat-rye translocations. These indicated that aberrations induced by zebularine can be steadily transmitted, suggesting that zebularine is a new efficient agent for chromosome manipulation.

  9. Atom lens without chromatic aberrations

    CERN Document Server

    Efremov, Maxim A; Schleich, Wolfgang P

    2012-01-01

    We propose a lens for atoms with reduced chromatic aberrations and calculate its focal length and spot size. In our scheme a two-level atom interacts with a near-resonant standing light wave formed by two running waves of slightly different wave vectors, and a far-detuned running wave propagating perpendicular to the standing wave. We show that within the Raman-Nath approximation and for an adiabatically slow atom-light interaction, the phase acquired by the atom is independent of the incident atomic velocity.

  10. The misalignment induced aberrations of TMA telescopes.

    Science.gov (United States)

    Thompson, Kevin P; Schmid, Tobias; Rolland, Jannick P

    2008-12-08

    The next major space-borne observatory, the James Webb Space Telescope, will be a 6.6M field-biased, obscured, three-mirror anastigmat (TMA). Over the used field of view, the performance of TMA telescopes is dominated by 3(rd) order misalignment aberrations. Here it is shown that two dominant 3(rd) order misalignment aberrations arise for any TMA telescope. One aberration, field constant 3(rd) order coma is a well known misalignment aberration commonly seen in two-mirror Ritchey Chretien telescopes. The second aberration, field-asymmetric, field-linear, 3(rd) order astigmatism is a new and unique image orientation dependence with field derived here for the first time using nodal aberration theory.

  11. Ocular wavefront aberrations in the common marmoset Callithrix jacchus: effects of age and refractive error.

    Science.gov (United States)

    Coletta, Nancy J; Marcos, Susana; Troilo, David

    2010-11-23

    The common marmoset, Callithrix jacchus, is a primate model for emmetropization studies. The refractive development of the marmoset eye depends on visual experience, so knowledge of the optical quality of the eye is valuable. We report on the wavefront aberrations of the marmoset eye, measured with a clinical Hartmann-Shack aberrometer (COAS, AMO Wavefront Sciences). Aberrations were measured on both eyes of 23 marmosets whose ages ranged from 18 to 452 days. Twenty-one of the subjects were members of studies of emmetropization and accommodation, and two were untreated normal subjects. Eleven of the 21 experimental subjects had worn monocular diffusers and 10 had worn binocular spectacle lenses of equal power. Monocular deprivation or lens rearing began at about 45 days of age and ended at about 108 days of age. All refractions and aberration measures were performed while the eyes were cyclopleged; most aberration measures were made while subjects were awake, but some control measurements were performed under anesthesia. Wavefront error was expressed as a seventh-order Zernike polynomial expansion, using the Optical Society of America's naming convention. Aberrations in young marmosets decreased up to about 100 days of age, after which the higher-order RMS aberration leveled off to about 0.10 μm over a 3 mm diameter pupil. Higher-order aberrations were 1.8 times greater when the subjects were under general anesthesia than when they were awake. Young marmoset eyes were characterized by negative spherical aberration. Form-deprived eyes of the monocular deprivation animals had greater wavefront aberrations than their fellow untreated eyes, particularly for asymmetric aberrations in the odd-numbered Zernike orders. Both lens-treated and form-deprived eyes showed similar significant increases in Z3(-3) trefoil aberration, suggesting the increase in trefoil may be related to factors that do not involve visual feedback.

  12. Detection of epigenetic aberrations in the development of hepatocellular carcinoma.

    Science.gov (United States)

    Zhang, Yujing

    2015-01-01

    Hepatocellular carcinoma (HCC) is the third most common cause of cancer death worldwide. Hepatocarcinogenesis is a complex, multistep process. It is now recognized that HCC is a both genetic and epigenetic disease; genetic and epigenetic components cooperate at all stages of hepatocarcinogenesis. Epigenetic changes involve aberrant DNA methylation, posttranslational histone modifications and aberrant expression of microRNAs all of which can affect the expression of oncogenes, tumor suppressor genes and other tumor-related genes and alter the pathways in cancer development. Several risk factors for HCC, including hepatitis B and C virus infections and exposure to the chemical carcinogen aflatoxin B1 have been found to influence epigenetic changes. Their interactions could play an important role in the initiation and progression of HCC. Discovery and detection of biomarkers for epigenetic changes is a promising area for early diagnosis and risk prediction of HCC.

  13. Chromatic aberration measurement for transmission interferometric testing.

    Science.gov (United States)

    Seong, Kibyung; Greivenkamp, John E

    2008-12-10

    A method of chromatic aberration measurement is described based on the transmitted wavefront of an optical element obtained from a Mach-Zehnder interferometer. The chromatic aberration is derived from transmitted wavefronts measured at five different wavelengths. Reverse ray tracing is used to remove induced aberrations associated with the interferometer from the measurement. In the interferometer, the wavefront transmitted through the sample is tested against a plano reference, allowing for the absolute determination of the wavefront radius of curvature. The chromatic aberrations of a singlet and a doublet have been measured.

  14. Mechanisms for the induction of gastric cancer by Helicobacter pylori infection: aberrant DNA methylation pathway.

    Science.gov (United States)

    Maeda, Masahiro; Moro, Hiroshi; Ushijima, Toshikazu

    2017-03-01

    Multiple pathogenic mechanisms by which Helicobacter pylori infection induces gastric cancer have been established in the last two decades. In particular, aberrant DNA methylation is induced in multiple driver genes, which inactivates them. Methylation profiles in gastric cancer are associated with specific subtypes, such as microsatellite instability. Recent comprehensive and integrated analyses showed that many cancer-related pathways are more frequently altered by aberrant DNA methylation than by mutations. Aberrant DNA methylation can even be present in noncancerous gastric mucosae, producing an "epigenetic field for cancerization." Mechanistically, H. pylori-induced chronic inflammation, but not H. pylori itself, plays a direct role in the induction of aberrant DNA methylation. The expression of three inflammation-related genes, Il1b, Nos2, and Tnf, is highly associated with the induction of aberrant DNA methylation. Importantly, the degree of accumulated aberrant DNA methylation is strongly correlated with gastric cancer risk. A recent multicenter prospective cohort study demonstrated the utility of epigenetic cancer risk diagnosis for metachronous gastric cancer. Suppression of aberrant DNA methylation by a demethylating agent was shown to inhibit gastric cancer development in an animal model. Induction of aberrant DNA methylation is the major pathway by which H. pylori infection induces gastric cancer, and this can be utilized for translational opportunities.

  15. Aberrant histone H4 acetylation in dead somatic cell-cloned calves

    Institute of Scientific and Technical Information of China (English)

    Lei Zhang; Shaohua Wang; Qiang Li; Xiangdong Ding; Yunping Dai; Ning Li

    2008-01-01

    In somatic cell-cloned animals, inefficient epigenetic reprogramming can result in an inappropriate gene expression and histone H4 acetylation is one of the key epigenetic modifications regulating gene expression. In this study, we investigated the levels of histone H4 acetylation of 11 development-related genes and expression levels of 19 genes in lungs of three normal control calves and nine aber-rant somatic cell-cloned calves. The results showed that nine studied genes had decreased acetylation levels in aberrant clones (p 0.05). Whereas 13 genes had significantly decreased expression (p 0.05), and only one gene had higher expression level in clones (p < 0.05). Furthermore, FGFR, GHR, HGFR and IGF1 genes showed lowered levels of both histone H4 acetylation and expression in aberrant clones than in controls, and the level of histone H4 acetylation was even more lowered in aberrant clones than those in controls. It was suggested that the lower levels of histone H4 acetylation in aberrant clones caused by the previous memory of cell differentiation might not support enough chromatin reprogramming, thus affecting appropriate gene expressions, and growth and development of the cloned calves. To our knowledge, this is the first study on how histone H4 acetylation affects gene expression in organs of somatic cell-cloned calves.

  16. Aberration of Light and Motion of Real Particle

    CERN Document Server

    Klacka, J

    2000-01-01

    Correct and complete (to terms of $\\vec{v} / c$ -- $\\vec{v}$ is particle's velocity, $c$ is the speed of light) derivation of equation of motion for real dust particle under the action of electromagnetic radiation is derived. The effect of aberration of light is used. Equation of motion is expressed in terms of particle's optical properties, standardly used in optics for stationary particles.

  17. Polarization Aberrations of Optical Coatings

    Science.gov (United States)

    Jota, Thiago

    This work does not limit itself to its title and touches on a number of related topics beyond it. Starting with the title, Polarization Aberrations of Optical Coatings, the immediate question that comes to mind is: what coatings? All coatings? Not all coatings, but just enough that a third person could take this information and apply it anywhere: to all coatings. The computational work-flow required to break-down the aberrations caused by polarizing events (3D vector forms of reflection and refraction) in dielectric and absorbing materials and for thick and thin films is presented. Therefore, it is completely general and of interest to the wide optics community. The example system is a Ritchey-Chretien telescope. It looks very similar to a Cassegrain, but it is not. It has hyperbolic surfaces, which allows for more optical aberration corrections. A few modern systems that use this configuration are the Hubble Space Telescope and the Keck telescopes. This particular system is a follow-up on this publication, where an example Cassegrain with aluminum coatings is characterized, and I was asked to simply evaluate it at another wavelength. To my surprise, I found a number of issues which lead me to write a completely new, one-of-its-kind 3D polarization ray-tracing code. It can do purely geometrical ray-tracing with add-on the polarization analysis capability, and more importantly: it keeps your data at your fingertips while offering all the outstanding facilities of Mathematica. The ray-tracing code and its extensive library, which can do several advanced computations, is documented in the appendix. The coatings of the Ritchey-Chretien induce a number of aberrations, primarily, but not limited to: tilt, defocus, astigmatism, and coma. I found those forms to exist in both aluminum and with a reflectance-enhancing dielectric quarter-wave multilayer coating over aluminum. The thickness of the film stack varies as function of position to present a quarter-wave of optical

  18. Study on intra-ocular lens aberration measurement in-air

    Science.gov (United States)

    Wang, Yuanyuan; Chen, Jiaojie; Fen, Haihua; Hu, Chuan; Li, Yiyi

    2010-10-01

    In clinical ophthalmology, the wavefront aberration of human eyes is expressed by Zernike polynomial after cataract surgery and intraocular lens implantation, the human eyes aberration will change. The problem of objective evaluation of wavefront aberration introduced by the Intra-ocular (IOL) in-vivo remains unsolved. This paper introduced the measurement principal of IOL wavefront aberration with expression by Zernike polynominal in air. A Hartmann-Shack wavefront sensor system was constructed to measure the wavefront of IOL and to get the corresponding grid patterns. After a series of computer image processing steps, 7th order with 35 items Zernike coefficients was obtained. The IOL of 20.0D power was measured 5 times by this system to get the spherical aberration about 6.73+/-0.02μm, demonstrating the good repeatability of the system. Ten IOLs with the same 20.0D power but difference in surface curvature were chosen for measurement. The spherical aberration observed were in the range of 2.74μm-11.26μm. These results are valuable for the optical design of IOLs and the aberration analysis of human eyes post-operation.

  19. Artificial neural network for the determination of Hubble Space Telescope aberration from stellar images

    Science.gov (United States)

    Barrett, Todd K.; Sandler, David G.

    1993-01-01

    An artificial-neural-network method, first developed for the measurement and control of atmospheric phase distortion, using stellar images, was used to estimate the optical aberration of the Hubble Space Telescope. A total of 26 estimates of distortion was obtained from 23 stellar images acquired at several secondary-mirror axial positions. The results were expressed as coefficients of eight orthogonal Zernike polynomials: focus through third-order spherical. For all modes other than spherical the measured aberration was small. The average spherical aberration of the estimates was -0.299 micron rms, which is in good agreement with predictions obtained when iterative phase-retrieval algorithms were used.

  20. Psychometric Characteristics of the Aberrant Behavior Checklist.

    Science.gov (United States)

    Aman, Michael G.; And Others

    1985-01-01

    Information is presented on the psychometric characteristics of the Aberrant Behavior Checklist, a measure of psychotropic drug effects. Internal consistency and test-retest reliability of the checklist appeared very good. Interrater reliability was generally in the moderate range. In general, validity was established for most Aberrant Behavior…

  1. Aberration coefficients of curved holographic optical elements

    Science.gov (United States)

    Verboven, P. E.; Lagasse, P. E.

    1986-11-01

    A general formula is derived that gives all aberration terms of holographic optical elements on substrates of any shape. The spherical substrate shape and the planar substrate shape are treated as important special cases. A numerical example illustrates the need of including higher-order aberrations.

  2. Repeatability of peripheral aberrations in young emmetropes.

    Science.gov (United States)

    Baskaran, Karthikeyan; Theagarayan, Baskar; Carius, Staffan; Gustafsson, Jörgen

    2010-10-01

    The purpose of this study is to assess the intrasession repeatability of ocular aberration measurements in the peripheral visual field with a commercially available Shack-Hartmann aberrometer (complete ophthalmic analysis system-high definition-vision research). The higher-order off-axis aberrations data in young healthy emmetropic eyes are also reported. The aberrations of the right eye of 18 emmetropes were measured using an aberrometer with an open field of view that allows peripheral measurements. Five repeated measures of ocular aberrations were obtained and assessed in steps of 10° out to ±40° in the horizontal visual field (nasal + and temporal -) and -20° in the inferior visual field. The coefficient of repeatability, coefficient of variation, and the intraclass correlation coefficient were calculated as a measure of intrasession repeatability. In all eccentric angles, the repeatability of the third- and fourth-order aberrations was better than the fifth and sixth order aberrations. The coefficient of variation was coefficient was >0.90 for the third and fourth order but reduced gradually for higher orders. There was no statistical significant difference in variance of total higher-order root mean square between on- and off-axis measurements (p > 0.05). The aberration data in this group of young emmetropes showed that the horizontal coma (C(3)(1)) was most positive at 40° in the temporal field, decreasing linearly toward negative values with increasing off-axis angle into the nasal field, whereas all other higher-order aberrations showed little or no change. The complete ophthalmic analysis system-high definition-vision research provides fast, repeatable, and valid peripheral aberration measurements and can be used efficiently to measure off-axis aberrations in the peripheral visual field.

  3. Higher-Order Aberrations in Myopic Eyes

    Directory of Open Access Journals (Sweden)

    Farid Karimian

    2010-01-01

    Full Text Available Purpose: To evaluate the correlation between refractive error and higher-order aberrations (HOAs in patients with myopic astigmatism. Methods: HOAs were measured using the Zywave II aberrometer over a 6 mm pupil. Correlations between HOAs and myopia, astigmatism, and age were analyzed. Results: One hundred and twenty-six eyes of 63 subjects with mean age of 26.4±5.9 years were studied. Mean spherical equivalent refractive error and refractive astigmatism were -4.94±1.63 D and 0.96±1.06 D, respectively. The most common higher-order aberration was primary horizontal trefoil with mean value of 0.069±0.152 μm followed by spherical aberration (-0.064±0.130 μm and primary vertical coma (-0.038±0.148 μm. As the order of aberration increased from third to fifth, its contribution to total HOA decreased: 53.9% for third order, 31.9% for fourth order, and 14.2% for fifth order aberrations. Significant correlations were observed between spherical equivalent refractive error and primary horizontal coma (R=0.231, P=0.022, and root mean square (RMS of spherical aberration (R=0.213, P=0.031; between astigmatism and RMS of total HOA (R=0.251, P=0.032, RMS of fourth order aberration (R=0.35, P<0.001, and primary horizontal coma (R=0.314, P=0.004. Spherical aberration (R=0.214, P=0.034 and secondary vertical coma (R=0.203, P=0.031 significantly increased with age. Conclusion: Primary horizontal trefoil, spherical aberration and primary vertical coma are the predominant higher-order aberrations in eyes with myopic astigmatism.

  4. Micro-Scale Genomic DNA Copy Number Aberrations as Another Means of Mutagenesis in Breast Cancer

    Science.gov (United States)

    Chao, Hann-Hsiang; He, Xiaping; Parker, Joel S.; Zhao, Wei; Perou, Charles M.

    2012-01-01

    Introduction In breast cancer, the basal-like subtype has high levels of genomic instability relative to other breast cancer subtypes with many basal-like-specific regions of aberration. There is evidence that this genomic instability extends to smaller scale genomic aberrations, as shown by a previously described micro-deletion event in the PTEN gene in the Basal-like SUM149 breast cancer cell line. Methods We sought to identify if small regions of genomic DNA copy number changes exist by using a high density, gene-centric Comparative Genomic Hybridizations (CGH) array on cell lines and primary tumors. A custom tiling array for CGH (244,000 probes, 200 bp tiling resolution) was created to identify small regions of genomic change, which was focused on previously identified basal-like-specific, and general cancer genes. Tumor genomic DNA from 94 patients and 2 breast cancer cell lines was labeled and hybridized to these arrays. Aberrations were called using SWITCHdna and the smallest 25% of SWITCHdna-defined genomic segments were called micro-aberrations (micro-aberrations, most of which are undetectable using typical-density genome-wide aCGH arrays. The basal-like subtype exhibited the highest incidence of these events. These micro-aberrations sometimes altered expression of the involved gene. We confirmed the presence of the PTEN micro-amplification in SUM149 and by mRNA-seq showed that this resulted in loss of expression of all exons downstream of this event. Micro-aberrations disproportionately affected the 5′ regions of the affected genes, including the promoter region, and high frequency of micro-aberrations was associated with poor survival. Conclusion Using a high-probe-density, gene-centric aCGH microarray, we present evidence of small-scale genomic aberrations that can contribute to gene inactivation. These events may contribute to tumor formation through mechanisms not detected using conventional DNA copy number analyses. PMID:23284754

  5. 原发性皮肤边缘区B细胞淋巴瘤的BCL10表达与染色体异常%BCL10 expression and chromosomal aberration in primary cutaneous marginal zone B-cell lymphoma

    Institute of Scientific and Technical Information of China (English)

    李百周; 孔蕴毅; 杨文涛; 周晓燕; 范月珍; 陆洪芬; 施达仁

    2008-01-01

    目的 探讨原发性皮肤边缘区B细胞淋巴瘤(PCMZL)中BCL10蛋白的表达和相关染色体的异常.方法 收集17例PCMZL,用免疫组化检测BCL10的表达,用荧光原位杂交(FISH)的方法分别检测API2-MALT1、BCL10、MALT1和IgH基因的异常.结果 在17例PCMZL中,BCL10的阳性率为94.1%(16/17),其中细胞质阳性率为64.7%(11/17),细胞核阳性率为29.4%(5/17).在FISH检测中,所有病例都不存在t(11;18),t(1;14)和t(14;18)染色体异常.与其他部位的MALT淋巴瘤相比较,在PCMZL中染色体易位的发生率不常见,可能这些遗传学异常不是PCMZL发生中的重要因素,而有其他目前未知的因素参与肿瘤的发生.结论 BCL10的核表达与是否出现上述的染色体异常无关,是否代表更具侵袭性的一种预后标记,尚需长期随访观察.%Objective To study the expression of BCL10 and associated chromosomal aberration in primary cutaneous marginal zone B-cell lymphoma (PCMZL). Methods Tissue specimens were collected from 17 patients with PCMZL. Immunohistochemistry was used to detect the expression of BCL10. Fluorescence in situ hybridization (FISH) was performed to examine the presence of API2-MALT1 fusion gene and chromosomal aberration in BCL10, MALT1 as well as IgH genes in these cases. Results Of these patients,94.1% (16/17) expressed BCL10 protein. The cytoplasmic expression of BCL10 was observed in 64.7% (11/17) of the patients, and nuclear expression in 29.4% (5/17). As shown by FISH test, neither API2-MALT1 fusion gene nor chromosomal aberration in BCL10, MALT1 or IgH genes was present in these patients. Conclusions Compared with MALT lymphomas originating from tissues other than skin, PCMZL is uncommonly associated with chromosomal abnormalities; it is possible that there are unknown factors contributing to its tumorigenesis. Nuclear BCL10 is unrelated to the presence of chromosomal aberration in BCL10, MALT1 or IgH genes. Further follow-up is required to clarify the

  6. Analysis of the Aberration in Directly-writing Atom Lithography

    Institute of Scientific and Technical Information of China (English)

    LI Chuanwen; CAI Weiquan; WANG Yuzhu

    2000-01-01

    After deriving the approximation solution which describes the motion of neutral atoms in an optical standing wave field with large detuning, the spherical aberration and the chromatic aberration are analyzed and possible methods to reduce these aberrations are discussed.

  7. Chromosome aberration assays in Allium

    Energy Technology Data Exchange (ETDEWEB)

    Grant, W.F.

    1982-01-01

    The common onion (Allium cepa) is an excellent plant for the assay of chromosome aberrations after chemical treatment. Other species of Allium (A. cepa var. proliferum, A. carinatum, A. fistulosum and A. sativum) have also been used but to a much lesser extent. Protocols have been given for using root tips from either bulbs or seeds of Allium cepa to study the cytological end-points, such as chromosome breaks and exchanges, which follow the testing of chemicals in somatic cells. It is considered that both mitotic and meiotic end-points should be used to a greater extent in assaying the cytogenetic effects of a chemical. From a literature survey, 148 chemicals are tabulated that have been assayed in 164 Allium tests for their clastogenic effect. Of the 164 assays which have been carried out, 75 are reported as giving a positive reaction, 49 positive and with a dose response, 1 positive and temperature-related, 9 borderline positive, and 30 negative; 76% of the chemicals gave a definite positive response. It is proposed that the Allium test be included among those tests routinely used for assessing chromosomal damage induced by chemicals.

  8. Aberration correction past and present.

    Science.gov (United States)

    Hawkes, P W

    2009-09-28

    Electron lenses are extremely poor: if glass lenses were as bad, we should see as well with the naked eye as with a microscope! The demonstration by Otto Scherzer in 1936 that skillful lens design could never eliminate the spherical and chromatic aberrations of rotationally symmetric electron lenses was therefore most unwelcome and the other great electron optician of those years, Walter Glaser, never ceased striving to find a loophole in Scherzer's proof. In the wartime and early post-war years, the first proposals for correcting C(s) were made and in 1947, in a second milestone paper, Scherzer listed these and other ways of correcting lenses; soon after, Dennis Gabor invented holography for the same purpose. These approaches will be briefly summarized and the work that led to the successful implementation of quadupole-octopole and sextupole correctors in the 1990 s will be analysed. In conclusion, the elegant role of image algebra in describing image formation and processing and, above all, in developing new methods will be mentioned.

  9. On aberration in gravitational lensing

    CERN Document Server

    Sereno, M

    2008-01-01

    It is known that a relative translational motion between the deflector and the observer affects gravitational lensing. In this paper, a lens equation is obtained to describe such effects on actual lensing observables. Results can be easily interpreted in terms of aberration of light-rays. Both radial and transverse motions with relativistic velocities are considered. The lens equation is derived by first considering geodesic motion of photons in the rest-frame Schwarzschild spacetime of the lens, and, then, light-ray detection in the moving observer's frame. Due to the transverse motion images are displaced and distorted in the observer's celestial sphere, whereas the radial velocity along the line of sight causes an effective re-scaling of the lens mass. The Einstein ring is distorted to an ellipse whereas the caustics in the source plane are still point-like. Either for null transverse motion or up to linear order in velocities, the critical curve is still a circle with its radius corrected by a factor (1+z...

  10. Image-based EUVL aberration metrology

    Science.gov (United States)

    Fenger, Germain Louis

    A significant factor in the degradation of nanolithographic image fidelity is optical wavefront aberration. As resolution of nanolithography systems increases, effects of wavefront aberrations on aerial image become more influential. The tolerance of such aberrations is governed by the requirements of features that are being imaged, often requiring lenses that can be corrected with a high degree of accuracy and precision. Resolution of lithographic systems is driven by scaling wavelength down and numerical aperture (NA) up. However, aberrations are also affected from the changes in wavelength and NA. Reduction in wavelength or increase in NA result in greater impact of aberrations, where the latter shows a quadratic dependence. Current demands in semiconductor manufacturing are constantly pushing lithographic systems to operate at the diffraction limit; hence, prompting a need to reduce all degrading effects on image properties to achieve maximum performance. Therefore, the need for highly accurate in-situ aberration measurement and correction is paramount. In this work, an approach has been developed in which several targets including phase wheel, phase disk, phase edges, and binary structures are used to generate optical images to detect and monitor aberrations in extreme ultraviolet (EUV) lithographic systems. The benefit of using printed patterns as opposed to other techniques is that the lithography system is tested under standard operating conditions. Mathematical models in conjunction with iterative lithographic simulations are used to determine pupil phase wavefront errors and describe them as combinations of Zernike polynomials.

  11. Analysis of nodal aberration properties in off-axis freeform system design.

    Science.gov (United States)

    Shi, Haodong; Jiang, Huilin; Zhang, Xin; Wang, Chao; Liu, Tao

    2016-08-20

    Freeform surfaces have the advantage of balancing off-axis aberration. In this paper, based on the framework of nodal aberration theory (NAT) applied to the coaxial system, the third-order astigmatism and coma wave aberration expressions of an off-axis system with Zernike polynomial surfaces are derived. The relationship between the off-axis and surface shape acting on the nodal distributions is revealed. The nodal aberration properties of the off-axis freeform system are analyzed and validated by using full-field displays (FFDs). It has been demonstrated that adding Zernike terms, up to nine, to the off-axis system modifies the nodal locations, but the field dependence of the third-order aberration does not change. On this basis, an off-axis two-mirror freeform system with 500 mm effective focal length (EFL) and 300 mm entrance pupil diameter (EPD) working in long-wave infrared is designed. The field constant aberrations induced by surface tilting are corrected by selecting specific Zernike terms. The design results show that the nodes of third-order astigmatism and coma move back into the field of view (FOV). The modulation transfer function (MTF) curves are above 0.4 at 20 line pairs per millimeter (lp/mm) which meets the infrared reconnaissance requirement. This work provides essential insight and guidance for aberration correction in off-axis freeform system design.

  12. Demonstrating optical aberrations in the laboratory

    CSIR Research Space (South Africa)

    Naidoo, Darryl

    2009-07-01

    Full Text Available in the laboratory D. Naidoo1,2 , C. Mafusire1,2 and A. Forbes1,2 1 CSIR National Laser Centre 2 School of Physics, University of KwaZulu-Natal AN OPTICAL ABERRATION IS A DISTORTION OF AN IMAGE AS COMPARED TO THE OBJECT DUE TO DEFECTS IN AN OPTICAL SYSTEM TILT... COEFFICIENT ODDWEIGHTING EVEN ODD ABERRATION PHASE EVENWEIGHTING COEFFICIENT COEFFICIENT ZERNIKE POLYNOMIALS ARE FITTED TO 3-DIMENSIONAL DATA TO DESCRIBE THE ABERRATIONS OF WAVEFRONT MEASUREMENTS IMPORTANT ELEMENTS OF DESIGN INCLUDE A LENSLET ARRAY...

  13. Multinodal fifth-order optical aberrations of optical systems without rotational symmetry: the comatic aberrations.

    Science.gov (United States)

    Thompson, Kevin P

    2010-06-01

    Building on an earlier work on the nodal aberration theory of the 3rd-order aberrations [J. Opt. Soc. Am. A22, 1389 (2005)] and the first paper in this series on the nodal aberration theory of higher-order aberrations [J. Opt. Soc. Am. A26, 1090 (2009)], this paper continues the derivation and presentation of the intrinsic, characteristic, often multinodal geometry for each type/family of the 3rd- and 5th-order optical aberrations as categorized by parallel developments for rotationally symmetric optics. The first paper in this series on the higher-order terms developed the nodal properties of the spherical aberration family, including W(060), W(240M), and W(242), and for completeness 7th-order spherical aberration W(080). This second paper in the series develops and presents the intrinsic, characteristic, often multinodal properties of the family of comatic aberrations through 5th order, specifically W(151), W(331M), and W(333) [field-linear, 5th-order aperture coma; field-cubed, 3rd-order aperture coma; and field-cubed, elliptical coma (a 3rd-order in aperture 5th-order vector aberration)]. This paper will present the first derivations of trinodal aberrations by the author.

  14. Flow cytometric detection of aberrant chromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Gray, J.W.; Lucas, J.; Yu, L.C.; Langlois, R.

    1983-05-11

    This report describes the quantification of chromosomal aberrations by flow cytometry. Both homogeneously and heterogeneously occurring chromosome aberrations were studied. Homogeneously occurring aberrations were noted in chromosomes isolated from human colon carcinoma (LoVo) cells, stained with Hoechst 33258 and chromomycin A3 and analyzed using dual beam flow cytometry. The resulting bivariate flow karyotype showed a homogeneously occurring marker chromosome of intermediate size. Heterogeneously occurring aberrations were quantified by slit-scan flow cytometry in chromosomes isolated from control and irradiated Chinese hamster cells and stained with propidium iodide. Heterogeneously occurring dicentric chromosomes were detected by their shapes (two centrometers). The frequencies of such chromosomes estimated by slit-scan flow cytometry correlated well with the frequencies determined by visual microscopy.

  15. Catadioptric aberration correction in cathode lens microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Tromp, R.M. [IBM T.J. Watson Research Center, PO Box 218, Yorktown Heights, NY 10598 (United States); Kamerlingh Onnes Laboratory, Leiden Institute of Physics, Niels Bohrweg 2, 2333 CA Leiden (Netherlands)

    2015-04-15

    In this paper I briefly review the use of electrostatic electron mirrors to correct the aberrations of the cathode lens objective lens in low energy electron microscope (LEEM) and photo electron emission microscope (PEEM) instruments. These catadioptric systems, combining electrostatic lens elements with a reflecting mirror, offer a compact solution, allowing simultaneous and independent correction of both spherical and chromatic aberrations. A comparison with catadioptric systems in light optics informs our understanding of the working principles behind aberration correction with electron mirrors, and may point the way to further improvements in the latter. With additional developments in detector technology, 1 nm spatial resolution in LEEM appears to be within reach. - Highlights: • The use of electron mirrors for aberration correction in LEEM/PEEM is reviewed. • A comparison is made with similar systems in light optics. • Conditions for 1 nm spatial resolution are discussed.

  16. Generalized pupil aberrations of optical imaging systems

    Science.gov (United States)

    Elazhary, Tamer T.

    In this dissertation fully general conditions are presented to correct linear and quadratic field dependent aberrations that do not use any symmetry. They accurately predict the change in imaging aberrations in the presence of lower order field dependent aberrations. The definitions of the image, object, and coordinate system are completely arbitrary. These conditions are derived using a differential operator on the scalar wavefront function. The relationships are verified using ray trace simulations of a number of systems with varying degrees of complexity. The math is shown to be extendable to provide full expansion of the scalar aberration function about field. These conditions are used to guide the design of imaging systems starting with only paraxial surface patches, then growing freeform surfaces that maintain the analytic conditions satisfied for each point in the pupil. Two methods are proposed for the design of axisymmetric and plane symmetric optical imaging systems. Design examples are presented as a proof of the concept.

  17. Telecentric confocal optics for aberration correction of acousto-optic tunable filters.

    Science.gov (United States)

    Suhre, Dennis R; Denes, Louis J; Gupta, Neelam

    2004-02-20

    A telecentric confocal optical arrangement is presented that greatly reduces the diffraction aberrations of the acousto-optic tunable filter (AOTF). Analytical expressions for the aberrations were identified based on the fundamental properties of Bragg diffraction, and additional aberrations due to focusing through the AOTF were also included. The analysis was verified by use of a geometrical ray trace optical code, and an experimental AOTF system was analyzed. Considerable improvement in the potential spatial resolution is predicted with confocal optics, which could accommodate large pixel-limited image fields of greater than 10(6) pixels. When the image quality of the experimental system was assessed, the resolution was found to be improved by the confocal optics and was diffraction limited. Higher resolution could have been obtained with the use of larger optics to increase the throughput before being limited by the aberrations.

  18. Sensing Phase Aberrations behind Lyot Coronagraphs

    Science.gov (United States)

    Sivaramakrishnan, Anand; Soummer, Rémi; Pueyo, Laurent; Wallace, J. Kent; Shao, Michael

    2008-11-01

    Direct detection of young extrasolar planets orbiting nearby stars can be accomplished from the ground with extreme adaptive optics and coronagraphy in the near-infrared, as long as this combination can provide an image with a dynamic range of 107 after the data are processed. Slowly varying speckles due to residual phase aberrations that are not measured by the primary wave-front sensor are the primary obstacle to achieving such a dynamic range. In particular, non-common optical path aberrations occurring between the wave-front sensor and the coronagraphic occulting spot degrade performance the most. We analyze the passage of both low and high spatial frequency phase ripples, as well as low-order Zernike aberrations, through an apodized pupil Lyot coronagraph in order to demonstrate the way coronagraphic filtering affects various aberrations. We derive the coronagraphically induced cutoff frequency of the filtering and estimate coronagraphic contrast losses due to low-order Zernike aberrations: tilt, astigmatism, defocus, coma, and spherical aberration. Such slowly varying path errors can be measured behind a coronagraph and corrected by a slowly updated optical path delay precompensation or offset asserted on the wave front by the adaptive optics (AO) system. We suggest ways of measuring and correcting all but the lowest spatial frequency aberrations using Lyot plane wave-front data, in spite of the complex interaction between the coronagraph and those mid-spatial frequency aberrations that cause image plane speckles near the coronagraphic focal plane mask occulter's edge. This investigation provides guidance for next-generation coronagraphic instruments currently under construction.

  19. Aberrant genomic imprinting in rhesus monkey embryonic stem cells.

    Science.gov (United States)

    Fujimoto, Akihisa; Mitalipov, Shoukhrat M; Kuo, Hung-Chih; Wolf, Don P

    2006-03-01

    Genomic imprinting involves modification of a gene or a chromosomal region that results in the differential expression of parental alleles. Disruption or inappropriate expression of imprinted genes is associated with several clinically significant syndromes and tumorigenesis in humans. Additionally, abnormal imprinting occurs in mouse embryonic stem cells (ESCs) and in clonally derived animals. Imprinted gene expression patterns in primate ESCs are largely unknown, despite the clinical potential of the latter in the cell-based treatment of human disease. Because of the possible implications of abnormal gene expression to cell or tissue replacement therapies involving ESCs, we examined allele specific expression of four imprinted genes in the rhesus macaque. Genomic and complementary DNA from embryos and ESC lines containing useful single nucleotide polymorphisms were subjected to polymerase chain reaction-based amplification and sequence analysis. In blastocysts, NDN expression was variable indicating abnormal or incomplete imprinting whereas IGF2 and SNRPN were expressed exclusively from the paternal allele and H19 from the maternal allele as expected. In ESCs, both NDN and SNRPN were expressed from the paternal allele while IGF2 and H19 showed loss of imprinting and biallelic expression. In differentiated ESC progeny, these expression patterns were maintained. The implications of aberrant imprinted gene expression to ESC differentiation in vitro and on ESC-derived cell function in vivo after transplantation are unknown.

  20. Individual eye model based on wavefront aberration

    Science.gov (United States)

    Guo, Huanqing; Wang, Zhaoqi; Zhao, Qiuling; Quan, Wei; Wang, Yan

    2005-03-01

    Based on the widely used Gullstrand-Le Grand eye model, the individual human eye model has been established here, which has individual corneal data, anterior chamber depth and the eyeball depth. Furthermore, the foremost thing is that the wavefront aberration calculated from the individual eye model is equal to the eye's wavefront aberration measured with the Hartmann-shack wavefront sensor. There are four main steps to build the model. Firstly, the corneal topography instrument was used to measure the corneal surfaces and depth. And in order to input cornea into the optical model, high-order aspheric surface-Zernike Fringe Sag surface was chosen to fit the corneal surfaces. Secondly, the Hartmann-shack wavefront sensor, which can offer the Zernike polynomials to describe the wavefront aberration, was built to measure the wavefront aberration of the eye. Thirdly, the eye's axial lengths among every part were measured with A-ultrasonic technology. Then the data were input into the optical design software-ZEMAX and the crystalline lens's shapes were optimized with the aberration as the merit function. The individual eye model, which has the same wavefront aberrations with the real eye, is established.

  1. Aberrant CBFA2T3B gene promoter methylation in breast tumors

    Directory of Open Access Journals (Sweden)

    Bais Anthony J

    2004-08-01

    Full Text Available Abstract Background The CBFA2T3 locus located on the human chromosome region 16q24.3 is frequently deleted in breast tumors. CBFA2T3 gene expression levels are aberrant in breast tumor cell lines and the CBFA2T3B isoform is a potential tumor suppressor gene. In the absence of identified mutations to further support a role for this gene in tumorigenesis, we explored whether the CBFA2T3B promoter region is aberrantly methylated and whether this correlates with expression. Results Aberrant hypo and hypermethylation of the CBFA2T3B promoter was detected in breast tumor cell lines and primary breast tumor samples relative to methylation index interquartile ranges in normal breast counterpart and normal whole blood samples. A statistically significant inverse correlation between aberrant CBFA2T3B promoter methylation and gene expression was established. Conclusion CBFA2T3B is a potential breast tumor suppressor gene affected by aberrant promoter methylation and gene expression. The methylation levels were quantitated using a second-round real-time methylation-specific PCR assay. The detection of both hypo and hypermethylation is a technicality regarding the methylation methodology.

  2. Characterization of immunophenotypic aberrancies in adult and childhood acute lymphoblastic leukemia: A study from Northern India

    Directory of Open Access Journals (Sweden)

    Manupriya Sharma

    2016-01-01

    Conclusion: In summary, CD117 is a relatively frequently expressed myeloid marker contrary to earlier reports which describes its rare expression. Pediatric and adult ALL cases with low blast count and CD34 positivity are more likely to express aberrant myeloid markers. Current study also supports that myeloid antigen expression in both adult and pediatric ALL is not associated with adverse presenting clinical and biological features.

  3. Aberrant Phenotype in Iranian Patients with Acute Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Mehdi Jahedi

    2014-03-01

    Full Text Available Purpose: The aim of this study was to evaluate the incidence of aberrant phenotypes and possible prognostic value in peripheral and bone marrow blood mononuclear cells of Iranian patients with AML. Methods: 56 cases of de novo AML (2010-2012 diagnosed by using an acute panel of monoclonal antibodies by multiparametric flowcytometry. Immunophenotyping was done on fresh bone marrow aspirate and/or peripheral blood samples using the acute panel of MoAbs is stained with Phycoerythrin (PE /fluorescein isothiocyanate (FITC, Allophycocyanin (APC and Peridinin-chlorophyll protein complex (perCP. We investigated Co-expression of lymphoid-associated markers CD2, CD3, CD7, CD 10, CD19, CD20 and CD22 in myeloblasts. Results: Out of the 56 cases, 32 (57.1% showed AP. CD7 was positive in 72.7% of cases in M1 and 28.5% in M2 but M3 and M4 cases lacked this marker. We detected CD2 in 58.35 of M1cases, 21.40% of M2 cases, 33.3 of M3 and 20% of M5; but M4 patients lacked this marker. The CBC analysis demonstrated a wide range of haemoglobin concentration, Platelet and WBC count which varied from normal to anaemia, thrombocytopenia to thrombocytosis and leukopenia to hyper leukocytosis. Conclusions: Our findings showed that CD7 and CD2 were the most common aberrant marker in Iranian patients with AML. However, we are not find any significant correlation between aberrant phenotype changing and MRD in our population. Taken together, this findings help to provide new insights in to the investigation of other aberrant phenotypes that may play roles in diagnosis and therapeutic of AML.

  4. Pulse compressor with aberration correction

    Energy Technology Data Exchange (ETDEWEB)

    Mankos, Marian [Electron Optica, Inc., Palo Alto, CA (United States)

    2015-11-30

    In this SBIR project, Electron Optica, Inc. (EOI) is developing an electron mirror-based pulse compressor attachment to new and retrofitted dynamic transmission electron microscopes (DTEMs) and ultrafast electron diffraction (UED) cameras for improving the temporal resolution of these instruments from the characteristic range of a few picoseconds to a few nanoseconds and beyond, into the sub-100 femtosecond range. The improvement will enable electron microscopes and diffraction cameras to better resolve the dynamics of reactions in the areas of solid state physics, chemistry, and biology. EOI’s pulse compressor technology utilizes the combination of electron mirror optics and a magnetic beam separator to compress the electron pulse. The design exploits the symmetry inherent in reversing the electron trajectory in the mirror in order to compress the temporally broadened beam. This system also simultaneously corrects the chromatic and spherical aberration of the objective lens for improved spatial resolution. This correction will be found valuable as the source size is reduced with laser-triggered point source emitters. With such emitters, it might be possible to significantly reduce the illuminated area and carry out ultrafast diffraction experiments from small regions of the sample, e.g. from individual grains or nanoparticles. During phase I, EOI drafted a set of candidate pulse compressor architectures and evaluated the trade-offs between temporal resolution and electron bunch size to achieve the optimum design for two particular applications with market potential: increasing the temporal and spatial resolution of UEDs, and increasing the temporal and spatial resolution of DTEMs. Specialized software packages that have been developed by MEBS, Ltd. were used to calculate the electron optical properties of the key pulse compressor components: namely, the magnetic prism, the electron mirror, and the electron lenses. In the final step, these results were folded

  5. Study of ocular aberrations with age.

    Science.gov (United States)

    Athaide, Helaine Vinche Zampar; Campos, Mauro; Costa, Charles

    2009-01-01

    Aging has various effects on visual system. Vision deteriorate, contrast sensitivity decreases and ocular aberrations apparently make the optical quality worse across the years. To prospective evaluate ocular aberrations along the ages. Three hundred and fifteen patients were examined, 155 were male (39.36%) and 160 were female (60.63%). Ages ranged from 5 to 64 year-old, the study was performed from February to November, 2004. Patients were divided into 4 age-groups according to IBGE (Instituto Brasileiro de Geografia e Estatística) classification: 68 patients from 5 to 14 year-old, 55 patients from 15 to 24 year-old, 116 from 25 to 44 year-old and 76 from 45 to 67 year-old. All patients had the following characteristics: best corrected visual acuity > 20/25, emmetropia or spherical equivalent < 3.50 SD, refractive astigmatism < 1.75 CD on cycloplegic refraction, normal ophthalmologic exam and no previous ocular surgeries. This protocol was approved by Federal University of São Paulo Institutional Review Board. Total optical aberrations were measured by H-S sensor LadarWave Custom Cornea Wavefront System (Alcon Laboratories Inc, Orlando, FLA, USA) and were statistically analysed. Corneal aberrations were calculated using CT-View software Version 6.89 (Sarver and Associates, Celebration, FL, USA). Lens aberrations were calculated by subtraction. High-order (0.32 e 0.48 microm) and ocular spherical aberrations (0.02 e 0.26 microm) increased respectively in child and middle age groups. High order (0.27 microm) and corneal spherical aberrations (0.05 microm) did not show changes with age. Lens showed a statistically significant spherical aberration increase (from -0.02 to 0.22 microm). Vertical (from 0.10 to -0.07 microm) and horizontal coma (from 0.01 to -0.12 microm) presented progressively negative values with aging. High-order and spherical aberrations increased with age due to lens contribution. The cornea did not affect significantly changes observed on ocular

  6. Clinical and prognostic significance of aberrant T-cell marker expression in 225 cases of de novo diffuse large B-cell lymphoma and 276 cases of other B-cell lymphomas.

    Science.gov (United States)

    Tsuyama, Naoko; Ennishi, Daisuke; Yokoyama, Masahiro; Baba, Satoko; Asaka, Reimi; Mishima, Yuko; Terui, Yasuhito; Hatake, Kiyohiko; Takeuchi, Kengo

    2017-03-23

    Expression of T-cell markers, generally investigated for immunophenotyping of T-cell lymphomas, is also observed in several types of B-cell lymphomas, including diffuse large B-cell lymphoma (DLBCL). We previously reported that CD5 expression in DLBCL is an inferior prognostic factor in the era of rituximab. However, data regarding the frequencies, histological relevance, and prognostic importance of T-cell markers other than CD5 are currently unavailable. In the present study, we comprehensively evaluated the expression of T-cell markers (CD2, CD3, CD4, CD5, CD7, and CD8) in 501 B-cell lymphomas, including 225 DLBCLs, by flow cytometry and subsequent immunohistochemistry. T-cell markers other than CD5, such as CD2, CD4, CD7, and CD8, were expressed in 27 (5%) patients, and notably, all of these cases were classified as large B-cell lymphoma subtypes: 25 DLBCLs and 2 intravascular large B-cell lymphomas. CD5 and other T-cell markers were expressed in 15% (31/225) and 10% (25/225) of DLBCL cases, respectively. Five of them co-expressed CD5 and other T-cell markers. Retrospectively analyzing the prognostic relevance of T-cell markers in 169 patients with primary DLBCL treated with rituximab-based chemotherapy, we showed that only CD5 was a strong predictor of poor survival. This study provides information about the occurrence of T-cell markers other than CD5 in B-cell lymphomas, their frequent histological subtypes, and their prognostic significance in DLBCL. CD5 was reconfirmed as a negative prognostic marker in DLBCL patients receiving rituximab-inclusive chemotherapy, whereas T-cell markers other than CD5 were found to have no impact on clinicopathological and survival analyses.

  7. Aberrations in shift-invariant linear optical imaging systems using partially coherent fields

    CERN Document Server

    Beltran, Mario A; Paganin, David M

    2014-01-01

    Here the role and influence of aberrations in optical imaging systems employing partially coherent complex scalar fields is studied. Imaging systems require aberrations to yield contrast in the output image. For linear shift-invariant optical systems, we develop an expression for the output cross-spectral density under the space-frequency formulation of statistically stationary partially coherentfields. We also develop expressions for the output cross{spectral density and associated spectral density for weak-phase, weak-phase-amplitude, and single-material objects in one transverse spatial dimension.

  8. Computation of astigmatic and trefoil figure errors and misalignments for two-mirror telescopes using nodal-aberration theory.

    Science.gov (United States)

    Ju, Guohao; Yan, Changxiang; Gu, Zhiyuan; Ma, Hongcai

    2016-05-01

    In active optics systems, one concern is how to quantitatively separate the effects of astigmatic and trefoil figure errors and misalignments that couple together in determining the total aberration fields when wavefront measurements are available at only a few field points. In this paper, we first quantitatively describe the impact of mount-induced trefoil deformation on the net aberration fields by proposing a modified theoretical formulation for the field-dependent aberration behavior of freeform surfaces based on the framework of nodal aberration theory. This formulation explicitly expresses the quantitative relationships between the magnitude of freeform surfaces and the induced aberration components where the freeform surfaces can be located away from the aperture stop and decentered from the optical axis. On this basis, and in combination with the mathematical presentation of nodal aberration theory for the effects of misalignments, we present the analytic expressions for the aberration fields of two-mirror telescopes in the presence of astigmatic primary mirror figure errors, mount-induced trefoil deformations on both mirrors, and misalignments. We quantitatively separate these effects using the analytical expressions with wavefront measurements at a few field points and pointing errors. Valuable insights are provided on how to separate these coupled effects in the computation process. Monte Carlo simulations are conducted to demonstrate the correctness and accuracy of the analytic method presented in this paper.

  9. Aberrant O-glycosylation and anti-glycan antibodies in an autoimmune disease IgA nephropathy and breast adenocarcinoma

    DEFF Research Database (Denmark)

    Stuchlová Horynová, Milada; Raška, Milan; Clausen, Henrik

    2013-01-01

    Glycosylation abnormalities have been observed in autoimmune diseases and cancer. Here, we compare mechanisms of aberrant O-glycosylation, i.e., formation of Tn and sialyl-Tn structures, on MUC1 in breast cancer, and on IgA1 in an autoimmune disease, IgA nephropathy. The pathways of aberrant O......-glycosylation, although different for MUC1 and IgA1, include dysregulation in glycosyltransferase expression, stability, and/or intracellular localization. Moreover, these aberrant glycoproteins are recognized by antibodies, although with different consequences. In breast cancer, elevated levels of antibodies recognizing...... aberrant MUC1 are associated with better outcome, whereas in IgA nephropathy, the antibodies recognizing aberrant IgA1 are part of the pathogenetic process....

  10. Analysis of Proteins That Rapidly Change Upon Mechanistic/Mammalian Target of Rapamycin Complex 1 (mTORC1) Repression Identifies Parkinson Protein 7 (PARK7) as a Novel Protein Aberrantly Expressed in Tuberous Sclerosis Complex (TSC)*

    Science.gov (United States)

    Niere, Farr; Namjoshi, Sanjeev; Song, Ehwang; Dilly, Geoffrey A.; Schoenhard, Grant; Zemelman, Boris V.; Mechref, Yehia; Raab-Graham, Kimberly F.

    2016-01-01

    Many biological processes involve the mechanistic/mammalian target of rapamycin complex 1 (mTORC1). Thus, the challenge of deciphering mTORC1-mediated functions during normal and pathological states in the central nervous system is challenging. Because mTORC1 is at the core of translation, we have investigated mTORC1 function in global and regional protein expression. Activation of mTORC1 has been generally regarded to promote translation. Few but recent works have shown that suppression of mTORC1 can also promote local protein synthesis. Moreover, excessive mTORC1 activation during diseased states represses basal and activity-induced protein synthesis. To determine the role of mTORC1 activation in protein expression, we have used an unbiased, large-scale proteomic approach. We provide evidence that a brief repression of mTORC1 activity in vivo by rapamycin has little effect globally, yet leads to a significant remodeling of synaptic proteins, in particular those proteins that reside in the postsynaptic density. We have also found that curtailing the activity of mTORC1 bidirectionally alters the expression of proteins associated with epilepsy, Alzheimer's disease, and autism spectrum disorder—neurological disorders that exhibit elevated mTORC1 activity. Through a protein–protein interaction network analysis, we have identified common proteins shared among these mTORC1-related diseases. One such protein is Parkinson protein 7, which has been implicated in Parkinson's disease, yet not associated with epilepsy, Alzheimers disease, or autism spectrum disorder. To verify our finding, we provide evidence that the protein expression of Parkinson protein 7, including new protein synthesis, is sensitive to mTORC1 inhibition. Using a mouse model of tuberous sclerosis complex, a disease that displays both epilepsy and autism spectrum disorder phenotypes and has overactive mTORC1 signaling, we show that Parkinson protein 7 protein is elevated in the dendrites and

  11. Analysis of Proteins That Rapidly Change Upon Mechanistic/Mammalian Target of Rapamycin Complex 1 (mTORC1) Repression Identifies Parkinson Protein 7 (PARK7) as a Novel Protein Aberrantly Expressed in Tuberous Sclerosis Complex (TSC).

    Science.gov (United States)

    Niere, Farr; Namjoshi, Sanjeev; Song, Ehwang; Dilly, Geoffrey A; Schoenhard, Grant; Zemelman, Boris V; Mechref, Yehia; Raab-Graham, Kimberly F

    2016-02-01

    Many biological processes involve the mechanistic/mammalian target of rapamycin complex 1 (mTORC1). Thus, the challenge of deciphering mTORC1-mediated functions during normal and pathological states in the central nervous system is challenging. Because mTORC1 is at the core of translation, we have investigated mTORC1 function in global and regional protein expression. Activation of mTORC1 has been generally regarded to promote translation. Few but recent works have shown that suppression of mTORC1 can also promote local protein synthesis. Moreover, excessive mTORC1 activation during diseased states represses basal and activity-induced protein synthesis. To determine the role of mTORC1 activation in protein expression, we have used an unbiased, large-scale proteomic approach. We provide evidence that a brief repression of mTORC1 activity in vivo by rapamycin has little effect globally, yet leads to a significant remodeling of synaptic proteins, in particular those proteins that reside in the postsynaptic density. We have also found that curtailing the activity of mTORC1 bidirectionally alters the expression of proteins associated with epilepsy, Alzheimer's disease, and autism spectrum disorder-neurological disorders that exhibit elevated mTORC1 activity. Through a protein-protein interaction network analysis, we have identified common proteins shared among these mTORC1-related diseases. One such protein is Parkinson protein 7, which has been implicated in Parkinson's disease, yet not associated with epilepsy, Alzheimers disease, or autism spectrum disorder. To verify our finding, we provide evidence that the protein expression of Parkinson protein 7, including new protein synthesis, is sensitive to mTORC1 inhibition. Using a mouse model of tuberous sclerosis complex, a disease that displays both epilepsy and autism spectrum disorder phenotypes and has overactive mTORC1 signaling, we show that Parkinson protein 7 protein is elevated in the dendrites and colocalizes

  12. Exercise protects against methamphetamine-induced aberrant neurogenesis

    Science.gov (United States)

    Park, Minseon; Levine, Harry; Toborek, Michal

    2016-01-01

    While no effective therapy is available for the treatment of methamphetamine (METH)-induced neurotoxicity, aerobic exercise is being proposed to improve depressive symptoms and substance abuse outcomes. The present study focuses on the effect of exercise on METH-induced aberrant neurogenesis in the hippocampal dentate gyrus in the context of the blood-brain barrier (BBB) pathology. Mice were administered with METH or saline by i.p. injections for 5 days with an escalating dose regimen. One set of mice was sacrificed 24 h post last injection of METH, and the remaining animals were either subjected to voluntary wheel running (exercised mice) or remained in sedentary housing (sedentary mice). METH administration decreased expression of tight junction (TJ) proteins and increased BBB permeability in the hippocampus. These changes were preserved post METH administration in sedentary mice and were associated with the development of significant aberrations of neural differentiation. Exercise protected against these effects by enhancing the protein expression of TJ proteins, stabilizing the BBB integrity, and enhancing the neural differentiation. In addition, exercise protected against METH-induced systemic increase in inflammatory cytokine levels. These results suggest that exercise can attenuate METH-induced neurotoxicity by protecting against the BBB disruption and related microenvironmental changes in the hippocampus. PMID:27677455

  13. Widespread alternative and aberrant splicing revealed by lariat sequencing

    Science.gov (United States)

    Stepankiw, Nicholas; Raghavan, Madhura; Fogarty, Elizabeth A.; Grimson, Andrew; Pleiss, Jeffrey A.

    2015-01-01

    Alternative splicing is an important and ancient feature of eukaryotic gene structure, the existence of which has likely facilitated eukaryotic proteome expansions. Here, we have used intron lariat sequencing to generate a comprehensive profile of splicing events in Schizosaccharomyces pombe, amongst the simplest organisms that possess mammalian-like splice site degeneracy. We reveal an unprecedented level of alternative splicing, including alternative splice site selection for over half of all annotated introns, hundreds of novel exon-skipping events, and thousands of novel introns. Moreover, the frequency of these events is far higher than previous estimates, with alternative splice sites on average activated at ∼3% the rate of canonical sites. Although a subset of alternative sites are conserved in related species, implying functional potential, the majority are not detectably conserved. Interestingly, the rate of aberrant splicing is inversely related to expression level, with lowly expressed genes more prone to erroneous splicing. Although we validate many events with RNAseq, the proportion of alternative splicing discovered with lariat sequencing is far greater, a difference we attribute to preferential decay of aberrantly spliced transcripts. Together, these data suggest the spliceosome possesses far lower fidelity than previously appreciated, highlighting the potential contributions of alternative splicing in generating novel gene structures. PMID:26261211

  14. Aberrant WNT/β-catenin signaling in parathyroid carcinoma

    Directory of Open Access Journals (Sweden)

    Åkerström Göran

    2010-11-01

    Full Text Available Abstract Background Parathyroid carcinoma (PC is a very rare malignancy with a high tendency to recur locally, and recurrent disease is difficult to eradicate. In most western European countries and United States, these malignant neoplasms cause less than 1% of the cases with primary hyperparathyroidism, whereas incidence as high as 5% have been reported from Italy, Japan, and India. The molecular etiology of PC is poorly understood. Results The APC (adenomatous polyposis coli tumor suppressor gene was inactivated by DNA methylation in five analyzed PCs, as determined by RT-PCR, Western blotting, and quantitative bisulfite pyrosequencing analyses. This was accompanied by accumulation of stabilized active nonphosphorylated β-catenin, strongly suggesting aberrant activation of the WNT/β-catenin signaling pathway in these tumors. Treatment of a primary PC cell culture with the DNA hypomethylating agent 5-aza-2'-deoxycytidine (decitabine, Dacogen(r induced APC expression, reduced active nonphosphorylated β-catenin, inhibited cell growth, and caused apoptosis. Conclusion Aberrant WNT/β-catenin signaling by lost expression and DNA methylation of APC, and accumulation of active nonphosphorylated β-catenin was observed in the analyzed PCs. We suggest that adjuvant epigenetic therapy should be considered as an additional option in the treatment of patients with recurrent or metastatic parathyroid carcinoma.

  15. miRNA gene promoters are frequent targets of aberrant DNA methylation in human breast cancer.

    Science.gov (United States)

    Vrba, Lukas; Muñoz-Rodríguez, José L; Stampfer, Martha R; Futscher, Bernard W

    2013-01-01

    miRNAs are important regulators of gene expression that are frequently deregulated in cancer, with aberrant DNA methylation being an epigenetic mechanism involved in this process. We previously identified miRNA promoter regions active in normal mammary cell types and here we analyzed which of these promoters are targets of aberrant DNA methylation in human breast cancer cell lines and breast tumor specimens. Using 5-methylcytosine immunoprecipitation coupled to miRNA tiling microarray hybridization, we performed comprehensive evaluation of DNA methylation of miRNA gene promoters in breast cancer. We found almost one third (55/167) of miRNA promoters were targets for aberrant methylation in breast cancer cell lines. Breast tumor specimens displayed DNA methylation of majority of these miRNA promoters, indicating that these changes in DNA methylation might be clinically relevant. Aberrantly methylated miRNA promoters were, similar to protein coding genes, enriched for promoters targeted by polycomb in normal cells. Detailed analysis of selected miRNA promoters revealed decreased expression of miRNA linked to increased promoter methylation for mir-31, mir-130a, let-7a-3/let-7b, mir-155, mir-137 and mir-34b/mir-34c genes. The proportion of miRNA promoters we found aberrantly methylated in breast cancer is several fold larger than that observed for protein coding genes, indicating an important role of DNA methylation in miRNA deregulation in cancer.

  16. Analysis of transverse RMS emittance growth of a beam induced by spherical and chromatic aberration in a solenoidal field

    Energy Technology Data Exchange (ETDEWEB)

    Dash, Radhakanta, E-mail: radhakanta.physics@gmail.com [Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai 400094 (India); Accelerator and Pulse Power Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India); Nayak, Biswaranjan [Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai 400094 (India); Sharma, Archana; Mittal, Kailash C. [Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai 400094 (India); Accelerator and Pulse Power Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India)

    2016-01-21

    In a medium energy beam transport line transverse rms emittance growth associated with spherical aberration is analysed. An analytical expression is derived for beam optics in a solenoid field considering terms up to the third order in the radial displacement. Two important phenomena: effect of spherical aberrations in axial-symmetric focusing lens and influence of nonlinear space charge forces on beam emittance growth are discussed for different beam distributions. In the second part nonlinear effect associated with chromatic aberration that describes the growth of emittance and distortion of phase space area is discussed.

  17. Analysis of transverse RMS emittance growth of a beam induced by spherical and chromatic aberration in a solenoidal field

    Science.gov (United States)

    Dash, Radhakanta; Nayak, Biswaranjan; Sharma, Archana; Mittal, Kailash C.

    2016-01-01

    In a medium energy beam transport line transverse rms emittance growth associated with spherical aberration is analysed. An analytical expression is derived for beam optics in a solenoid field considering terms up to the third order in the radial displacement. Two important phenomena: effect of spherical aberrations in axial-symmetric focusing lens and influence of nonlinear space charge forces on beam emittance growth are discussed for different beam distributions. In the second part nonlinear effect associated with chromatic aberration that describes the growth of emittance and distortion of phase space area is discussed.

  18. Effect of spherical aberration on the emittance growth and frequency of oscillation of a beam crossing an RF gap

    Energy Technology Data Exchange (ETDEWEB)

    Nayak, B., E-mail: biswaranjan.nayak1@gmail.com [Accelerator and Pulsed Power Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India); Dash, R.; Mittal, K.C. [Accelerator and Pulsed Power Division, Bhabha Atomic Research Centre, Trombay, Mumbai 400085 (India); Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai 400094 (India)

    2014-05-11

    This paper presents the effect of spherical aberration on the transverse emittance growth and frequency of oscillation of a beam envelope inside an RF cavity. This paper is organized into two sections. In the first section, the coefficient of spherical aberration which arises due to third order terms of on-axis electric field component is discussed. An expression is derived for the growth of transverse emittance in an RF gap which includes the coupling between the phase spread of the beam and spherical aberration. In the second part, using reduced envelope equation for a laminar beam, effect of aberration on the invariant envelope solution is discussed. An expression is found using the Lindstedt–Poincare theory for solution of the envelope equation. The shift in frequency of oscillation of the beam envelope in the RF field is calculated.

  19. The correction of electron lens aberrations

    Energy Technology Data Exchange (ETDEWEB)

    Hawkes, P.W., E-mail: peter.hawkes@cemes.fr

    2015-09-15

    The progress of electron lens aberration correction from about 1990 onwards is chronicled. Reasonably complete lists of publications on this and related topics are appended. A present for Max Haider and Ondrej Krivanek in the year of their 65th birthdays. By a happy coincidence, this review was completed in the year that both Max Haider and Ondrej Krivanek reached the age of 65. It is a pleasure to dedicate it to the two leading actors in the saga of aberration corrector design and construction. They would both wish to associate their colleagues with such a tribute but it is the names of Haider and Krivanek (not forgetting Joachim Zach) that will remain in the annals of electron optics, next to that of Harald Rose. I am proud to know that both regard me as a friend as well as a colleague. - Highlights: • Geometrical aberration correction. • Chromatic aberration correction. • 50 pm resolution. • High-resolution electron energy-loss spectroscopy. • Extensive bibliographies.

  20. Functional Analysis and Treatment of Aberrant Behavior.

    Science.gov (United States)

    Mace, F. Charles; And Others

    1991-01-01

    This article reviews general classes of variables which help to maintain aberrant behavior including attention seeking, sensory and perceptual consequences, and access to materials or activities. Suggestions for a methodology providing a comprehensive functional analysis are offered which include descriptive analysis, hypothesis forming,…

  1. Assessing the construct validity of aberrant salience.

    Science.gov (United States)

    Schmidt, Kristin; Roiser, Jonathan P

    2009-01-01

    We sought to validate the psychometric properties of a recently developed paradigm that aims to measure salience attribution processes proposed to contribute to positive psychotic symptoms, the Salience Attribution Test (SAT). The "aberrant salience" measure from the SAT showed good face validity in previous results, with elevated scores both in high-schizotypy individuals, and in patients with schizophrenia suffering from delusions. Exploring the construct validity of salience attribution variables derived from the SAT is important, since other factors, including latent inhibition/learned irrelevance (LIrr), attention, probabilistic reward learning, sensitivity to probability, general cognitive ability and working memory could influence these measures. Fifty healthy participants completed schizotypy scales, the SAT, a LIrr task, and a number of other cognitive tasks tapping into potentially confounding processes. Behavioural measures of interest from each task were entered into a principal components analysis, which yielded a five-factor structure accounting for approximately 75% of the variance in behaviour. Implicit aberrant salience was found to load onto its own factor, which was associated with elevated "Introvertive Anhedonia" schizotypy, replicating our previous finding. LIrr loaded onto a separate factor, which also included implicit adaptive salience, but was not associated with schizotypy. Explicit adaptive and aberrant salience, along with a measure of probabilistic learning, loaded onto a further factor, though this also did not correlate with schizotypy. These results suggest that the measures of LIrr and implicit adaptive salience might be based on similar underlying processes, which are dissociable both from implicit aberrant salience and explicit measures of salience.

  2. [Aberrant pancreas with a double intestinal location].

    Science.gov (United States)

    Yenon, K; Lethurgie, C; Bokobza, B

    2005-01-01

    The authors report one exceptional case of aberrant pancreas with a double intestinal location (jejunum and Meckel's diverticulum) in a thirty-year-old patient. Digestive haemorrhage and the abdominal colic were the revealing clinical signs. The enteroscopy guided by the enteroscanner, was the indicated complementary investigation for the preoperative diagnosis. The research of other locations during the operation should be systematic.

  3. Optical advantages of astigmatic aberration corrected heliostats

    Science.gov (United States)

    van Rooyen, De Wet; Schöttl, Peter; Bern, Gregor; Heimsath, Anna; Nitz, Peter

    2016-05-01

    Astigmatic aberration corrected heliostats adapt their shape in dependence of the incidence angle of the sun on the heliostat. Simulations show that this optical correction leads to a higher concentration ratio at the target and thus in a decrease in required receiver aperture in particular for smaller heliostat fields.

  4. Quality factor of aberrated gaussian laser beams

    CSIR Research Space (South Africa)

    Mafusire, C

    2010-09-01

    Full Text Available A model is used to calculate the beam quality factor of a laser beam from Zernike coefficients. It is tested by programming aberration coefficients on a laser beam and measuring the beam quality using a Shack-Hartmann wavefront sensor. The two show...

  5. Anti-forensics of chromatic aberration

    Science.gov (United States)

    Mayer, Owen; Stamm, Matthew C.

    2015-03-01

    Over the past decade, a number of information forensic techniques have been developed to identify digital image manipulation and falsification. Recent research has shown, however, that an intelligent forger can use anti-forensic countermeasures to disguise their forgeries. In this paper, an anti-forensic technique is proposed to falsify the lateral chromatic aberration present in a digital image. Lateral chromatic aberration corresponds to the relative contraction or expansion between an image's color channels that occurs due to a lens's inability to focus all wavelengths of light on the same point. Previous work has used localized inconsistencies in an image's chromatic aberration to expose cut-and-paste image forgeries. The anti-forensic technique presented in this paper operates by estimating the expected lateral chromatic aberration at an image location, then removing deviations from this estimate caused by tampering or falsification. Experimental results are presented that demonstrate that our anti-forensic technique can be used to effectively disguise evidence of an image forgery.

  6. The Oncoprotein BRD4-NUT Generates Aberrant Histone Modification Patterns

    Science.gov (United States)

    Zee, Barry M.; Dibona, Amy B.; Alekseyenko, Artyom A.; French, Christopher A.; Kuroda, Mitzi I.

    2016-01-01

    Defects in chromatin proteins frequently manifest in diseases. A striking case of a chromatin-centric disease is NUT-midline carcinoma (NMC), which is characterized by expression of NUT as a fusion partner most frequently with BRD4. ChIP-sequencing studies from NMC patients revealed that BRD4-NUT (B4N) covers large genomic regions and elevates transcription within these domains. To investigate how B4N modulates chromatin, we performed affinity purification of B4N when ectopically expressed in 293-TREx cells and quantified the associated histone posttranslational modifications (PTM) using proteomics. We observed significant enrichment of acetylation particularly on H3 K18 and of combinatorial patterns such as H3 K27 acetylation paired with K36 methylation. We postulate that B4N complexes override the preexisting histone code with new PTM patterns that reflect aberrant transcription and that epigenetically modulate the nucleosome environment toward the NMC state. PMID:27698495

  7. The Aberrant Coronary Artery - The Management Approach.

    Science.gov (United States)

    King, Nina-Marie; Tian, David D; Munkholm-Larsen, Stine; Buttar, Sana N; Chow, Vincent; Yan, Tristan

    2017-07-03

    An aberrant coronary artery is a rare clinical occurrence with an incidence of 0.05-1.2%. Often it is an incidental finding detected on coronary angiography or at autopsy. However, symptomatic patients can experience angina, arrhythmia, sudden death or non-specific symptoms such as dyspnoea and syncope. At present, there are no guidelines or dedicated studies assessing the treatment of an aberrant coronary artery leaving management options for these patients controversial. Selected international cardiothoracic surgeons were surveyed electronically in November 2016 to determine whether consensus exists on different management aspects for patients with an aberrant coronary artery arising from the contralateral sinus with an interarterial course. For asymptomatic patients with either an aberrant left main coronary artery (ALMCA) arising from the contralateral sinus or an aberrant right main coronary artery (ARMCA) arising from the contralateral sinus, there was no consensus on surgical correction of the anomaly. If myocardial ischaemia was demonstrated on either coronary angiography with fractional flow reserve measurements and/or stress myocardial perfusion scan, surgical correction was the consensus between the surveyed surgeons. If surgery was deemed appropriate, coronary artery bypass surgery utilising the internal mammary artery was marginally preferred by the respondents in patients with an ALMCA whilst unroofing of the coronary ostium was preferred in patients with an ARMCA. Although no consensus was reached, a large proportion of respondents would not treat a patient over the age of 30 years differently compared to those under 30 years old. For symptomatic patients or if myocardial ischaemia is demonstrated on either coronary angiography with fractional flow reserve measurements and/or stress myocardial perfusion scan, surgical correction is indicated. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the

  8. Aberrant expression pattern of a novel mutation in connexin 26 gene resulting in autosomal recessive deafness%连接蛋白基因一个新致聋突变体p.Y155X及功能分析

    Institute of Scientific and Technical Information of China (English)

    杨中纯; 肖自安; 谢鼎华; 夏昆

    2010-01-01

    Objective To report a novel deafness-causing mutation c. 465T→A, p. Y155X in connexin 26 (CX26) (also called gap junction protein β-2, GJB2 ), and perform functional analysis of the mutated protein p. Y155X in Hela cells to explore the underlying mechanism on deafness. Methods Mutations in CX26 gene of the proband in an autosomal recessive inherited deafness family were tested by direct DNA sequencing method. Mutant p. Y155X, which was found in the deafness family, and wild type CX26 (wtCX26), were directionally subcloned into the pEGFP-N1 plasmid to construct the recombinant fusion protein expression vector of CX26 p. Y155X-EGFP and wtCX26-EGFP, followed by transfecting into HeLa cells. The expression of the mutated and wild type proteins was analyzed using Western blot analysis. The intracellular localization of proteins and the formation of gap junction-like plaques at plasma membrane were observed under confocal microscope. Gap junction coupling was tested by calcein-AM dye transfer experiment. Results A novel nonsense mutation c. 465T→A, p. Y155X in the CX26 gene was found in the autosomal recessive deafness family. The molecular weight of protein p. Y155X was smaller than that of wtCX26 in transiently expressed HeLa cells. The mutated protein failed to reach the cell surface to form gap junction plaques, and displayed cytoplasmic accumulation. Also, no calcein-AM dye was transferred from the donor cells to the recipient cells when both were transfected with CX26 p. Y155X. The wtCX26 protein localized at the cell membrane to form gap junction plaques with permeability to fluorescent dye calcein-AM. Conclusion CX26 p. Y155X could not be targeted to the plasma membrane and there was no formation of gap junction channels between the adjacent cells. The mutation c. 465T→A, p. Y155X in CX26 gene was responsible for the autosomal recessive hearing impairment in this family.%目的 观察连接蛋白(connexin 26,CX26)基因的一个新致聋突变c.465T

  9. 精神分裂症患者血浆MicroRNA异常表达的对照研究%A case-control study of aberrant expression of microRNA in schizophrenia patients

    Institute of Scientific and Technical Information of China (English)

    孙欣羊; 宋红涛; 赵林; 仲爱芳; 牛威; 张梁; 张理义; 卢正斌; 载运华

    2013-01-01

    Objective To test the microRNAs (miRNA) expression levels in schizophrenia (SZ) patients,in an effort to explore and validate if miRNA can serve as specific SZ biomarkers.Methods A total of 64 SZ patients and 64 healthy controls matched in gender and age with the SZ patients were continuously enrolled for this study.Based on adequate literature survey,10 most reported miRNAs (miR-30e,miR-34a,miR-181b,miR-195,miR-346,miR-432,miR-7,miR-132,miR-212 and miR-137) were selected as target miRNAs for blood-based expression study using quantitative RT-PCR.Results The expression levels of miR-30e,miR-34a,miR-181b,miR-346 and miR-7 in SZ group(2.99±1.59,2.29±0.77,4.24± 1.51,9.94± 1.52,11.08±2.24,respectively)were significantly up-regulated compared with the control group(3.74± 1.28,2.87±0.90,4.65±0.99,10.90± 1.99,12.00± 1.95) (P<0.05-0.001).ROC curve analysis revealed that these five miRNA,as combined biomarkers,had significantly diagnostic values in differentiating SZ (AUC was 0.705,sensitivity and specificity were 34.5% and 90.2% respectively).Logistic regression analysis demonstrated that miR-181b had the greatest relative risk for SZ (OR=2.483).Conclusion MiR-30e,miR-34a,miR-181b,miR-346 and miR-7 might serve as specific combined SZ biomarkers for SZ diagnosis.%目的 检测microRNA(miRNA或miR)在精神分裂症患者中的异常表达,探究miRNA能否作为精神分裂症的生物标记物.方法 连续入组64例精神分裂症患者和64例配对正常对照,使用实时荧光定量RT-PCR技术检测病例组和对照组血浆10种miRNA(miR-30e、miR-34a、miR-181b、miR-195、miR-346、miR-432、miR-7、miR-132、miR-137 and miR-212)的相对表达水平.结果 病例组血浆miR-30e、miR-181b、miR-346、miR-34a和miR-7表达水平(2.99±1.59,2.29±0.77,4.24±1.51,9.94±1.52,11.08±2.24)较对照组(3.74± 1.28,2.87±0.90,4.65±0.99,10.90±1.99,12.00±1.95)显著上调(P<0.05 / 0.001).ROC曲线分析显示,5种miRNA作为联合生物标记物

  10. Genomic aberrations in lung adenocarcinoma in never smokers.

    Directory of Open Access Journals (Sweden)

    Bastien Job

    Full Text Available BACKGROUND: Lung cancer in never smokers would rank as the seventh most common cause of cancer death worldwide. METHODS AND FINDINGS: We performed high-resolution array comparative genomic hybridization analysis of lung adenocarcinoma in sixty never smokers and identified fourteen new minimal common regions (MCR of gain or loss, of which five contained a single gene (MOCS2, NSUN3, KHDRBS2, SNTG1 and ST18. One larger MCR of gain contained NSD1. One focal amplification and nine gains contained FUS. NSD1 and FUS are oncogenes hitherto not known to be associated with lung cancer. FISH showed that the amplicon containing FUS was joined to the next telomeric amplicon at 16p11.2. FUS was over-expressed in 10 tumors with gain of 16p11.2 compared to 30 tumors without that gain. Other cancer genes present in aberrations included ARNT, BCL9, CDK4, CDKN2B, EGFR, ERBB2, MDM2, MDM4, MET, MYC and KRAS. Unsupervised hierarchical clustering with adjustment for false-discovery rate revealed clusters differing by the level and pattern of aberrations and displaying particular tumor characteristics. One cluster was strongly associated with gain of MYC. Another cluster was characterized by extensive losses containing tumor suppressor genes of which RB1 and WRN. Tumors in that cluster frequently harbored a central scar-like fibrosis. A third cluster was associated with gains on 7p and 7q, containing ETV1 and BRAF, and displayed the highest rate of EGFR mutations. SNP array analysis validated copy-number aberrations and revealed that RB1 and WRN were altered by recurrent copy-neutral loss of heterozygosity. CONCLUSIONS: The present study has uncovered new aberrations containing cancer genes. The oncogene FUS is a candidate gene in the 16p region that is frequently gained in never smokers. Multiple genetic pathways defined by gains of MYC, deletions of RB1 and WRN or gains on 7p and 7q are involved in lung adenocarcinoma in never smokers.

  11. Targeting molecular aberrations in urothelial carcinoma: are we almost there?

    Science.gov (United States)

    Apolo, Andrea B; Kwiatkowski, David J

    2013-01-01

    Advances in tumor biology and cancer genetics have led to the development of effective targeted therapies in oncology over the past decade. However, targeted drug development for urothelial carcinoma has been slower than for some other malignancies. The path forward in drug development is through a better understanding of the aberrant pathways driving urothelial tumor development. Steady progress has been made in the characterization of genomic alterations in urothelial carcinoma. The Cancer Genome Atlas (TCGA) project is well underway in the analysis of a large set of urothelial cancer specimens using multiple approaches and technologies. In addition, there are already many well-established mutations and genetic alterations in urothelial carcinoma that likely contribute in an important way to tumor development. In addition, urothelial cancer genome-wide association studies have identified common variants associated with urothelial cancer risk and protein expression that can potentially be therapeutically targeted. Furthermore, the MET pathway has emerged as an exciting target in multiple tumors, including urothelial carcinoma. Our knowledge of how to clinically target many emerging molecular aberrations in urothelial cancer is still in the early stages of development. However, there is much promise in the ongoing research being conducted in urothelial cancer molecular pathogenesis.

  12. Assessing the construct validity of aberrant salience

    Directory of Open Access Journals (Sweden)

    Kristin Schmidt

    2009-12-01

    Full Text Available We sought to validate the psychometric properties of a recently developed paradigm that aims to measure salience attribution processes proposed to contribute to positive psychotic symptoms, the Salience Attribution Test (SAT. The “aberrant salience” measure from the SAT showed good face validity in previous results, with elevated scores both in high-schizotypy individuals, and in patients with schizophrenia suffering from delusions. Exploring the construct validity of salience attribution variables derived from the SAT is important, since other factors, including latent inhibition/learned irrelevance, attention, probabilistic reward learning, sensitivity to probability, general cognitive ability and working memory could influence these measures. Fifty healthy participants completed schizotypy scales, the SAT, a learned irrelevance task, and a number of other cognitive tasks tapping into potentially confounding processes. Behavioural measures of interest from each task were entered into a principal components analysis, which yielded a five-factor structure accounting for ~75% percent of the variance in behaviour. Implicit aberrant salience was found to load onto its own factor, which was associated with elevated “Introvertive Anhedonia” schizotypy, replicating our previous finding. Learned irrelevance loaded onto a separate factor, which also included implicit adaptive salience, but was not associated with schizotypy. Explicit adaptive and aberrant salience, along with a measure of probabilistic learning, loaded onto a further factor, though this also did not correlate with schizotypy. These results suggest that the measures of learned irrelevance and implicit adaptive salience might be based on similar underlying processes, which are dissociable both from implicit aberrant salience and explicit measures of salience.

  13. Cosmological parameter estimation: impact of CMB aberration

    CERN Document Server

    Catena, Riccardo

    2012-01-01

    The peculiar motion of an observer with respect to the CMB rest frame induces an apparent deflection of the observed CMB photons, i.e. aberration, and a shift in their frequency, i.e. Doppler effect. Both effects distort the temperature multipoles a_lm's via a mixing matrix at any l. The common lore when performing a CMB based cosmological parameter estimation is to consider that Doppler affects only the l=1 multipole, and neglect any other corrections. In this paper we reconsider the validity of this assumption, showing that it is actually not robust when sky cuts are included to model CMB foreground contaminations. Assuming a simple fiducial cosmological model with five parameters, we simulated CMB temperature maps of the sky in a WMAP-like and in a Planck-like experiment and added aberration and Doppler effects to the maps. We then analyzed with a MCMC in a Bayesian framework the maps with and without aberration and Doppler effects in order to assess the ability of reconstructing the parameters of the fidu...

  14. [Familial, structural aberration of the Y chromosome with fertility disorders].

    Science.gov (United States)

    Gall, H; Schmid, M; Schmidtke, J; Schempp, W; Weber, L

    1985-11-01

    Cytogenetic studies on a patient with Klinefelter's syndrome revealed an inherited, structural aberration of the Y-chromosome which has not been described before. The aberrant Y-chromosome was characterized by eight different banding methods. The value of individual staining techniques in studies on Y-heterochromatin aberrations is emphasized. Analysis of the cytogenetic studies (banding methods, restriction endonuclease of DNA, and measurement of the length of the Y-chromosome) permits an interpretation to be made on how the aberrant Y-chromosome originated. The functions of the Y-chromosome are discussed. The decrease in fertility (cryptozoospermia) in the two brothers with the same aberrant Y-chromosome was striking.

  15. DNA Repair Defects and Chromosomal Aberrations

    Science.gov (United States)

    Hada, Megumi; George, K. A.; Huff, J. L.; Pluth, J. M.; Cucinotta, F. A.

    2009-01-01

    Yields of chromosome aberrations were assessed in cells deficient in DNA doublestrand break (DSB) repair, after exposure to acute or to low-dose-rate (0.018 Gy/hr) gamma rays or acute high LET iron nuclei. We studied several cell lines including fibroblasts deficient in ATM (ataxia telangiectasia mutated; product of the gene that is mutated in ataxia telangiectasia patients) or NBS (nibrin; product of the gene mutated in the Nijmegen breakage syndrome), and gliomablastoma cells that are proficient or lacking in DNA-dependent protein kinase (DNA-PK) activity. Chromosomes were analyzed using the fluorescence in situ hybridization (FISH) chromosome painting method in cells at the first division post irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). Gamma irradiation induced greater yields of both simple and complex exchanges in the DSB repair-defective cells than in the normal cells. The quadratic dose-response terms for both simple and complex chromosome exchanges were significantly higher for the ATM- and NBS-deficient lines than for normal fibroblasts. However, in the NBS cells the linear dose-response term was significantly higher only for simple exchanges. The large increases in the quadratic dose-response terms in these repair-defective cell lines points the importance of the functions of ATM and NBS in chromatin modifications to facilitate correct DSB repair and minimize the formation of aberrations. The differences found between ATM- and NBS-deficient cells at low doses suggest that important questions should with regard to applying observations of radiation sensitivity at high dose to low-dose exposures. For aberrations induced by iron nuclei, regression models preferred purely linear dose responses for simple exchanges and quadratic dose responses for complex exchanges. Relative biological effectiveness (RBE) factors of all of

  16. Radiotherapeutical chromosomal aberrations in laryngeal cancer patients

    Directory of Open Access Journals (Sweden)

    Stošić-Divjak Svetlana L.

    2009-01-01

    Full Text Available Introduction. The authors present the results of cytogenetic analysis of 21 patients with laryngeal carcinomas diagnosed and treated in the period 1995-2000 at the Institute of Otorhinolaryngology and Maxillofacial Surgery, Clinical Center of Serbia and Clinical Center of Novi Sad. Material and methods. The patients were specially monitored and the material was analyzed at the Institute of Human Genetics of the School of Medicine in Belgrade as well as in the Laboratory for Radiological Protection of the Institute of Occupational and Radiological Health 'Dr Dragomir Karajovic' in Belgrade. Results. The incidence of chromosomal aberrations and incidence of exchange of material between sister chromatids were observed in the preparation of the metaphasic lymphocyte chromosomes of the peripheral blood obtained in the culture. Structural aberrations were found on the chromosomes in the form of breakups, rings, translocations and dicentrics as early as after a single exposure of patients to tumor radiation dose of 2 Gy in the field sized 5x7. Out of the total number of 35 cultivated blood samples obtained from 13 patients, 21 were successfully cultivated and they were proved to contain chromosomal aberrations. Some of the peripheral blood samples failed to show cell growth in vitro due to the lethal cell damages in vivo. Discussion.. We have consluded that the number of structural aberrations cannot be used as a biological measure of the absorbed ionizing radiation dose. The presence of aberrations per se is indicative of the mutagenic effect of the ionizing radiation, which was also confirmed in our series on the original model by cultivation of the peripheral blood lymphocytes in the culture of the cells of the volunteer donors upon in vitro radiation. Using the method of bromdeoxyuridylreductase, the increased incidence of SCE as a mutagenic effect was registered. Conclusion. It has been concluded that the increase of absorbed radiation dose in

  17. DNA Repair Defects and Chromosomal Aberrations

    Science.gov (United States)

    Hada, Megumi; George, K. A.; Huff, J. L.; Pluth, J. M.; Cucinotta, F. A.

    2009-01-01

    Yields of chromosome aberrations were assessed in cells deficient in DNA doublestrand break (DSB) repair, after exposure to acute or to low-dose-rate (0.018 Gy/hr) gamma rays or acute high LET iron nuclei. We studied several cell lines including fibroblasts deficient in ATM (ataxia telangiectasia mutated; product of the gene that is mutated in ataxia telangiectasia patients) or NBS (nibrin; product of the gene mutated in the Nijmegen breakage syndrome), and gliomablastoma cells that are proficient or lacking in DNA-dependent protein kinase (DNA-PK) activity. Chromosomes were analyzed using the fluorescence in situ hybridization (FISH) chromosome painting method in cells at the first division post irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). Gamma irradiation induced greater yields of both simple and complex exchanges in the DSB repair-defective cells than in the normal cells. The quadratic dose-response terms for both simple and complex chromosome exchanges were significantly higher for the ATM- and NBS-deficient lines than for normal fibroblasts. However, in the NBS cells the linear dose-response term was significantly higher only for simple exchanges. The large increases in the quadratic dose-response terms in these repair-defective cell lines points the importance of the functions of ATM and NBS in chromatin modifications to facilitate correct DSB repair and minimize the formation of aberrations. The differences found between ATM- and NBS-deficient cells at low doses suggest that important questions should with regard to applying observations of radiation sensitivity at high dose to low-dose exposures. For aberrations induced by iron nuclei, regression models preferred purely linear dose responses for simple exchanges and quadratic dose responses for complex exchanges. Relative biological effectiveness (RBE) factors of all of

  18. Derivation of various transfer functions of ideal or aberrated imaging systems from the three-dimensional transfer function.

    Science.gov (United States)

    Braat, Joseph J M; Janssen, Augustus J E M

    2015-06-01

    The three-dimensional frequency transfer function for optical imaging systems was introduced by Frieden in the 1960s. The analysis of this function and its partly back-transformed functions (two-dimensional and one-dimensional optical transfer functions) in the case of an ideal or aberrated imaging system has received relatively little attention in the literature. Regarding ideal imaging systems with an incoherently illuminated object volume, we present analytic expressions for the classical two-dimensional x-y-transfer function in a defocused plane, for the axial z-transfer function in the presence of defocusing and for the x-z-transfer function in the presence of a lateral shift δy with respect to the imaged pattern in the x-z-plane. For an aberrated imaging system we use the common expansion of the aberrated pupil function with the aid of Zernike polynomials. It is shown that the line integral appearing in Frieden's three-dimensional transfer function can be evaluated for aberrated systems using a relationship established first by Cormack between the line integral of a Zernike polynomial over a full chord of the unit disk and a Chebyshev polynomial of the second kind. Some new developments in the theory of Zernike polynomials from the last decade allow us to present explicit expressions for the line integral in the case of a weakly aberrated imaging system. We outline a similar, but more complicated, analytic scheme for the case of severely aberrated systems.

  19. Chromatic variation of aberration: the role of induced aberrations and raytrace direction

    Science.gov (United States)

    Berner, A.; Nobis, T.; Shafer, D.; Gross, H.

    2015-09-01

    The design and optimization process of an optical system contains several first order steps. The definition of the appropriate lens type and the fixation of the raytrace direction are some of them. The latter can be understood as a hidden assumption rather than an aware design step. This is usually followed by the determination of the paraxial lens layout calculated for the primary wavelength. It is obvious, that for this primary wavelength the paraxial calculations are independent of raytrace direction. Today, most of the lens designs are specified not to work only for one wavelength, but in a certain wavelength range. Considering such rays of other wavelengths, one can observe that depending on the direction there will already occur differences in the first order chromatic aberrations and additionally in the chromatic variation of the third-order aberrations. The reason for this effect are induced aberrations emerging from one surface to the following surfaces by perturbed ray heights and ray angles. It can be shown, that the total amount of surface-resolved first order chromatic aberrations and the chromatic variation of the five primary aberrations can be split into an intrinsic part and an induced part. The intrinsic part is independent of the raytrace direction whereas the induced part is not.

  20. High incidence of t(11;18)/API2-MALT1 and BCL10 aberrant nuclear expression in pulmonary mucosa-associated lymphoid tissue lymphomus%肺黏膜相关B淋巴细胞淋巴瘤中BCL10蛋白表达和染色体易位的关系

    Institute of Scientific and Technical Information of China (English)

    李百周; 杨文涛; 陆洪芬; 范月珍; 周晓燕; 施达仁

    2008-01-01

    Objective To detect the BCL10 expression and chromosomal translocations in pulmonary mucosa-associated lymphoid tissue (MALT) lymphomas, including t (11;18)/API2-MALT1 ; t(1 ;14)/IgH-BCLI0 and t(14;18)/MALTI-IgH, and to determine if aberrant nuclear BCL10 expression is related with chromosomal translocations. Methods Twenty-three cases of pulmonary MALT lymphomas were collected from Cancer Hospital of Fudan University. BCLIO was detected by immunohistoehemistry of EnVision method, and API2.-MALT1, BCLI0, MALTI, IgH chromosomal abnormalities were detected by fluorescent in situ hybridization (FISH) technique. Results BCLI0 was expressed in 82. 6% (19/23) of the pulmonary MALT lymphomas. Among those eases, 9 of 23 (39.1%) were expressed in the cytoplasm, and 10 of 23 (43.5%) were in the nucleus. In the FISH results, 9 cases (39.1%, 9/23) showed API2MALT1 fusion gene, 1 case with possible BCLI0-IgH abnormality, but none showed chromosomal abnormalities related with MALTI and IgH gene simultaneously. Among 10 BCL10 nuclear expressive cases only 5 harbored genetic abnormalities. There was no correlation between BCL10 abrerrant nuclear expression and chromosoma(translocations) (X2=0.306,P=0.685). Follow-up of 10 eases for a period of 7 to 35 months showed that all the patients were alive. Because different treatments applied in different patients(chemotherapy only, surgery with chemotherapy or surgery only), best available treatment could not be confirmed in this study. Conclusions t (11;18)/API2-MALT1 was the most common chromosomal abnormality in pulmonary MALT lymphomas, but t(1;14)/BCLI0-IgH and t(14; 18)/MALTl-lgH were rare. Pulmonary MALT lymphomas also had higher nuclear BCLI0 expression, which was not correlated with chromosomal abnormalities. As a result, BCLIO nuclear expression and cytogenetic aberration may be helpful in the diagnosis, especially for small biopsy specimens.%目的 检测肺黏膜相关B淋巴细胞淋巴瘤(MALT淋巴瘤)中BCL10蛋白表达

  1. Aberrant signal transduction and protein expression in acute myeloid leukemia

    NARCIS (Netherlands)

    Schepers, Hein

    2007-01-01

    Het proces van hematopoiese voorziet het lichaam van miljarden bloedcellen per dag. Het is een strak geregisseerd proces. Acute myeloide leukemie (AML) is een afwijking in de bloedcelontwikkeling. Behandeling van deze en andere vormen van leukemie is veelal gebaseerd op het principe van de geprogram

  2. Myc Expression Drives Aberrant Lipid Metabolism in Lung Cancer

    OpenAIRE

    Hall, Z.; Ament, Z; Wilson, CH; Burkhart, DL; Ashmore, T; Koulman, A.; Littlewood, T; Evan, GI; Griffin, JL

    2016-01-01

    MYC-mediated pathogenesis in lung cancer continues to attract interest for new therapeutic strategies. In this study, we describe a transgenic mouse model of KRAS-driven lung adenocarcinoma that affords reversible activation of MYC, used here as a tool for lipidomic profiling of MYC-dependent lung tumors formed in this model. Advanced mass spectrometric imaging and surface analysis techniques were used to characterize the spatial and temporal changes in lipid composition in lung tissue. We fo...

  3. Acquisition of Genetic Aberrations by Activation-Induced Cytidine Deaminase (AID during Inflammation-Associated Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Tsutomu Chiba

    2011-06-01

    Full Text Available Genetic abnormalities such as nucleotide alterations and chromosomal disorders that accumulate in various tumor-related genes have an important role in cancer development. The precise mechanism of the acquisition of genetic aberrations, however, remains unclear. Activation-induced cytidine deaminase (AID, a nucleotide editing enzyme, is essential for the diversification of antibody production. AID is expressed only in activated B lymphocytes under physiologic conditions and induces somatic hypermutation and class switch recombination in immunoglobulin genes. Inflammation leads to aberrant AID expression in various gastrointestinal organs and increased AID expression contributes to cancer development by inducing genetic alterations in epithelial cells. Studies of how AID induces genetic disorders are expected to elucidate the mechanism of inflammation-associated carcinogenesis.

  4. Acquisition of Genetic Aberrations by Activation-Induced Cytidine Deaminase (AID) during Inflammation-Associated Carcinogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Takai, Atsushi; Marusawa, Hiroyuki, E-mail: maru@kuhp.kyoto-u.ac.jp; Chiba, Tsutomu [Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, 54 Shogoin-Kawahara-cho, Sakyo-ku, Kyoto 606-8507 (Japan)

    2011-06-22

    Genetic abnormalities such as nucleotide alterations and chromosomal disorders that accumulate in various tumor-related genes have an important role in cancer development. The precise mechanism of the acquisition of genetic aberrations, however, remains unclear. Activation-induced cytidine deaminase (AID), a nucleotide editing enzyme, is essential for the diversification of antibody production. AID is expressed only in activated B lymphocytes under physiologic conditions and induces somatic hypermutation and class switch recombination in immunoglobulin genes. Inflammation leads to aberrant AID expression in various gastrointestinal organs and increased AID expression contributes to cancer development by inducing genetic alterations in epithelial cells. Studies of how AID induces genetic disorders are expected to elucidate the mechanism of inflammation-associated carcinogenesis.

  5. Chromosomal aberrations in ISS crew members

    Science.gov (United States)

    Johannes, Christian; Goedecke, Wolfgang; Antonopoulos, Alexandra

    2012-07-01

    High energy radiation is a major risk factor in manned space missions. Astronauts and cosmonauts are exposed to ionising radiations of cosmic and solar origin, while on the Earth's surface people are well protected by the atmosphere and a deflecting magnetic field. There are now data available describing the dose and the quality of ionising radiation on-board of the International Space Station (ISS). Nonetheless, the effect of increased radiation dose on mutation rates of ISS crew members are hard to predict. Therefore, direct measurements of mutation rates are required in order to better estimate the radiation risk for longer duration missions. The analysis of chromosomal aberrations in peripheral blood lymphocytes is a well established method to measure radiation-induced mutations. We present data of chromosome aberration analyses from lymphocyte metaphase spreads of ISS crew members participating in short term (10-14 days) or long term (around 6 months) missions. From each subject we received two blood samples. The first sample was drawn about 10 days before launch and a second one within 3 days after return from flight. From lymphocyte cultures metaphase plates were prepared on glass slides. Giemsa stained and in situ hybridised metaphases were scored for chromosome changes in pre-flight and post-flight blood samples and the mutation rates were compared. Results obtained in chromosomal studies on long-term flight crew members showed pronounced inter-individual differences in the response to elevated radiation levels. Overall slight but significant elevations of typical radiation induced aberrations, i.e., dicentric chromosomes and reciprocal translocations have been observed. Our data indicate no elevation of mutation rates due to short term stays on-board the ISS.

  6. Wavefront aberrations of x-ray dynamical diffraction beams.

    Science.gov (United States)

    Liao, Keliang; Hong, Youli; Sheng, Weifan

    2014-10-01

    The effects of dynamical diffraction in x-ray diffractive optics with large numerical aperture render the wavefront aberrations difficult to describe using the aberration polynomials, yet knowledge of them plays an important role in a vast variety of scientific problems ranging from optical testing to adaptive optics. Although the diffraction theory of optical aberrations was established decades ago, its application in the area of x-ray dynamical diffraction theory (DDT) is still lacking. Here, we conduct a theoretical study on the aberration properties of x-ray dynamical diffraction beams. By treating the modulus of the complex envelope as the amplitude weight function in the orthogonalization procedure, we generalize the nonrecursive matrix method for the determination of orthonormal aberration polynomials, wherein Zernike DDT and Legendre DDT polynomials are proposed. As an example, we investigate the aberration evolution inside a tilted multilayer Laue lens. The corresponding Legendre DDT polynomials are obtained numerically, which represent balanced aberrations yielding minimum variance of the classical aberrations of an anamorphic optical system. The balancing of classical aberrations and their standard deviations are discussed. We also present the Strehl ratio of the primary and secondary balanced aberrations.

  7. Aberrations in Fresnel Lenses and Mirrors

    Science.gov (United States)

    Gregory, Don

    1999-01-01

    The NASA/MSFC Shooting Star program revealed a number of technical problems that must be solved before solar thermal propulsion can become a reality. The fundamental problem of interest here is the collection of solar energy. This is the first step in the propulsion process and indeed the most important. Everything else depends on the efficiency and focusing ability of the collection lens or mirror. An initial model of Fresnel lens behavior using a wave optics approach has been completed and the results were encouraging enough to warrant an experimental investigation. This experimental investigation confirmed some of the effects predicted and produced invaluable photographic evidence of coherence based diffraction and aberration.

  8. Aberrant lymphatic endothelial progenitors in lymphatic malformation development.

    Directory of Open Access Journals (Sweden)

    June K Wu

    Full Text Available Lymphatic malformations (LMs are vascular anomalies thought to arise from dysregulated lymphangiogenesis. These lesions impose a significant burden of disease on affected individuals. LM pathobiology is poorly understood, hindering the development of effective treatments. In the present studies, immunostaining of LM tissues revealed that endothelial cells lining aberrant lymphatic vessels and cells in the surrounding stroma expressed the stem cell marker, CD133, and the lymphatic endothelial protein, podoplanin. Isolated patient-derived CD133+ LM cells expressed stem cell genes (NANOG, Oct4, circulating endothelial cell precursor proteins (CD90, CD146, c-Kit, VEGFR-2, and lymphatic endothelial proteins (podoplanin, VEGFR-3. Consistent with a progenitor cell identity, CD133+ LM cells were multipotent and could be differentiated into fat, bone, smooth muscle, and lymphatic endothelial cells in vitro. CD133+ cells were compared to CD133- cells isolated from LM fluids. CD133- LM cells had lower expression of stem cell genes, but expressed circulating endothelial precursor proteins and high levels of lymphatic endothelial proteins, VE-cadherin, CD31, podoplanin, VEGFR-3 and Prox1. CD133- LM cells were not multipotent, consistent with a differentiated lymphatic endothelial cell phenotype. In a mouse xenograft model, CD133+ LM cells differentiated into lymphatic endothelial cells that formed irregularly dilated lymphatic channels, phenocopying human LMs. In vivo, CD133+ LM cells acquired expression of differentiated lymphatic endothelial cell proteins, podoplanin, LYVE1, Prox1, and VEGFR-3, comparable to expression found in LM patient tissues. Taken together, these data identify a novel LM progenitor cell population that differentiates to form the abnormal lymphatic structures characteristic of these lesions, recapitulating the human LM phenotype. This LM progenitor cell population may contribute to the clinically refractory behavior of LMs.

  9. SiRNA and epigenetic aberrations in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Hamed Mirzaei

    2016-01-01

    Full Text Available Ovarian cancer has the most noteworthy lethal rate around gynecologic malignancies, and it is also considered as the fourth most frequent cancer in the woman in world. Two most critical barriers to treatment of ovarian malignancy are absence of early diagnostic markers and advancement of drug resistance after therapy, especially in advanced stages. Various epigenetic changes have been recognized in ovarian cancer. Recent progresses in our understanding of molecular pathogenesis of ovarian malignancy have dramatically provided potential new targets for molecularly targeted therapies. In very recent years, small interfering RNA (siRNA-mediated gene silencing has been emerging as a novel treatment modality in preclinical studies in the light of its strong gene-specific silencing. Gene suppression mediated by RNA interference (RNAi significantly suppressed gene expression at the messenger RNA (mRNA and protein levels. SiRNAs have therapeutic potential for ovarian cancer through various mechanisms. In this review, we not only provide an overview of siRNA designing for epigenetic silencing of genes aberrantly expressed in ovarian cancer but also we will highlight that the epigenetically silenced genes offer new targets for therapeutic approaches based on re-expression of tumor suppressor genes via demethylating and deacetylating drugs.

  10. Aberration measurement from specific photolithographic images: a different approach.

    Science.gov (United States)

    Nomura, H; Tawarayama, K; Kohno, T

    2000-03-01

    Techniques for measurement of higher-order aberrations of a projection optical system in photolithographic exposure tools have been established. Even-type and odd-type aberrations are independently obtained from printed grating patterns on a wafer by three-beam interference under highly coherent illumination. Even-type aberrations, i.e., spherical aberration and astigmatism, are derived from the best focus positions of vertical, horizontal, and oblique grating patterns by an optical microscope. Odd-type aberrations, i.e., coma and three-foil, are obtained by detection of relative shifts of a fine grating pattern to a large pattern by an overlay inspection tool. Quantitative diagnosis of lens aberrations with a krypton fluoride (KrF) excimer laser scanner is demonstrated.

  11. Correcting Aberrations in Complex Magnet Systems for Muon Cooling Channels

    Energy Technology Data Exchange (ETDEWEB)

    J.A. Maloney, B. Erdelyi, A. Afanaciev, R.P. Johnson, Y.S. Derbenev, V.S. Morozov

    2011-03-01

    Designing and simulating complex magnet systems needed for cooling channels in both neutrino factories and muon colliders requires innovative techniques to correct for both chromatic and spherical aberrations. Optimizing complex systems, such as helical magnets for example, is also difficult but essential. By using COSY INFINITY, a differential algebra based code, the transfer and aberration maps can be examined to discover what critical terms have the greatest influence on these aberrations.

  12. Higher order aberrations of the eye: Part one

    Directory of Open Access Journals (Sweden)

    Marsha Oberholzer

    2016-03-01

    Full Text Available This article is the first in a series of two articles that provide a comprehensive literature review of higher order aberrations (HOAs of the eye. The present article mainly explains the general principles of such HOAs as well as HOAs of importance, and the measuring apparatus used to measure HOAs of the eye. The second article in the series discusses factors contributing to variable results in measurements of HOAs of the eye.Keywords: Higher order aberrations; wavefront aberrations; aberrometer

  13. Calibration and removal of lateral chromatic aberration in images

    OpenAIRE

    Mallon, John; Whelan, Paul F.

    2007-01-01

    This paper addresses the problem of compensating for lateral chromatic aberration in digital images through colour plane realignment. Two main contributions are made: the derivation of a model for lateral chromatic aberration in images, and the subsequent calibration of this model from a single view of a chess pattern. These advances lead to a practical and accurate alternative for the compensation of lateral chromatic aberrations. Experimental results validate the proposed models and calibra...

  14. Expression

    Directory of Open Access Journals (Sweden)

    Wang-Xia Wang

    2014-02-01

    Full Text Available The miR-15/107 family comprises a group of 10 paralogous microRNAs (miRNAs, sharing a 5′ AGCAGC sequence. These miRNAs have overlapping targets. In order to characterize the expression of miR-15/107 family miRNAs, we employed customized TaqMan Low-Density micro-fluid PCR-array to investigate the expression of miR-15/107 family members, and other selected miRNAs, in 11 human tissues obtained at autopsy including the cerebral cortex, frontal cortex, primary visual cortex, thalamus, heart, lung, liver, kidney, spleen, stomach and skeletal muscle. miR-103, miR-195 and miR-497 were expressed at similar levels across various tissues, whereas miR-107 is enriched in brain samples. We also examined the expression patterns of evolutionarily conserved miR-15/107 miRNAs in three distinct primary rat brain cell preparations (enriched for cortical neurons, astrocytes and microglia, respectively. In primary cultures of rat brain cells, several members of the miR-15/107 family are enriched in neurons compared to other cell types in the central nervous system (CNS. In addition to mature miRNAs, we also examined the expression of precursors (pri-miRNAs. Our data suggested a generally poor correlation between the expression of mature miRNAs and their precursors. In summary, we provide a detailed study of the tissue and cell type-specific expression profile of this highly expressed and phylogenetically conserved family of miRNA genes.

  15. Fifth-order field aberration coefficients for an optical surface of rotational symmetry.

    Science.gov (United States)

    Gaj, M

    1971-07-01

    The approximate formulas for the principal ray parameters, such as directional cosines and heights of incidence, as well as for the paraxial sagittal quantities h(s) and H (s) have been expressed by paraxial quantities and Seidel aberrations to fifth-order accuracy. On the basis of these relations an expression for the sagittal radius of curvature r(s), (for a given y ) has been obtained. These quantities are used to derive fifth-order field aberration coefficients for arbitrary surfaces of rotational symmetry by using the wave aberration formula for sagittal focus {M. Gaj, Opt. Spectrosk. 21, 373 (1966) [Opt. Spectrosc. 21, 209 (1966)]}. The resulting expression has four terms. The first one depends only on asphericity and tends to equal zero when the surface becomes spherical. The second is a disturbance term and disappears in the Seidel region. The third and fourth terms may be treated as a generalization of the Petzval curvature and of the Seidel astigmatism, respectively. The limits of the terms, when h tends to zero, has been examined.

  16. Aberrant angiogenesis: The gateway to diabetic complications

    Directory of Open Access Journals (Sweden)

    Sunil K Kota

    2012-01-01

    Full Text Available Diabetes Mellitus is a metabolic cum vascular syndrome with resultant abnormalities in both micro- and macrovasculature. The adverse long-term effects of diabetes mellitus have been described to involve many organ systems. Apart from hyperglycemia, abnormalities of angiogenesis may cause or contribute toward many of the clinical manifestations of diabetes. These are implicated in the pathogenesis of vascular abnormalities of the retina, kidneys, and fetus, impaired wound healing, increased risk of rejection of transplanted organs, and impaired formation of coronary collaterals. A perplexing feature of the aberrant angiogenesis is that excessive and insufficient angiogenesis can occur in different organs in the same individual. The current article hereby reviews the molecular mechanisms including abnormalities in growth factors, cytokines, and metabolic derangements, clinical implications, and therapeutic options of dealing with abnormal angiogenesis in diabetes.

  17. Effect of chromatic aberration on atomic-resolved spherical aberration corrected STEM images.

    Science.gov (United States)

    Kuramochi, Koji; Yamazaki, Takashi; Kotaka, Yasutoshi; Ohtsuka, Masahiro; Hashimoto, Iwao; Watanabe, Kazuto

    2009-12-01

    The effect of the chromatic aberration (C(c)) coefficient in a spherical aberration (C(s))- corrected electromagnetic lens on high-resolution high-angle annular dark field (HAADF) scanning transmission electron microscope (STEM) images is explored in detail. A new method for precise determination of the C(c) coefficient is demonstrated, requiring measurement of an atomic-resolution one-frame through-focal HAADF STEM image. This method is robust with respect to instrumental drift, sample thickness, all lens parameters except C(c), and experimental noise. It is also demonstrated that semi-quantitative structural analysis on the nanometer scale can be achieved by comparing experimental C(s)- corrected HAADF STEM images with their corresponding simulated images when the effects of the C(c) coefficient and spatial incoherence are included.

  18. Design of an aberration corrected low-voltage SEM

    NARCIS (Netherlands)

    Aken, R.H. van; Maas, D.J.; Hagen, C.W.; Barth, J.E.; Kruit, P.

    2010-01-01

    The low-voltage foil corrector is a novel type of foil aberration corrector that can correct for both the spherical and chromatic aberration simultaneously. In order to give a realistic example of the capabilities of this corrector, a design for a low-voltage scanning electron microscope with the lo

  19. Adaptive aberration correction using a triode hyperbolic electron mirror.

    Science.gov (United States)

    Fitzgerald, J P S; Word, R C; Könenkamp, R

    2011-01-01

    A converging electron mirror can be used to compensate spherical and chromatic aberrations in an electron microscope. This paper presents an analytical solution to a novel triode (three electrode) hyperbolic mirror as an improvement to the well-known diode (two electrode) hyperbolic mirror for aberration correction. A weakness of the diode mirror is a lack of flexibility in changing the chromatic and spherical aberration coefficients independently without changes in the mirror geometry. In order to remove this limitation, a third electrode can be added. We calculate the optical properties of the resulting triode mirror analytically on the basis of a simple model field distribution. We present the optical properties-the object/image distance, z(0), and the coefficients of spherical and chromatic aberration, C(s) and C(c), of both mirror types from an analysis of electron trajectories in the mirror field. From this analysis, we demonstrate that while the properties of both designs are similar, the additional parameters in the triode mirror improve the range of aberration that can be corrected. The triode mirror is also able to provide a dynamic adjustment range of chromatic aberration for fixed spherical aberration and focal length, or any permutation of these three parameters. While the dynamic range depends on the values of aberration correction needed, a nominal 10% tuning range is possible for most configurations accompanied by less than 1% change in the other two properties.

  20. Investigation of spherical aberration effects on coherent lidar performance

    DEFF Research Database (Denmark)

    Hu, Qi; Rodrigo, Peter John; Iversen, Theis Faber Quist

    2013-01-01

    In this paper we demonstrate experimentally the performance of a monostatic coherent lidar system under the influence of phase aberrations, especially the typically predominant spherical aberration (SA). The performance is evaluated by probing the spatial weighting function of the lidar system...

  1. Numerical correction of aberrations via phase retrieval with speckle illumination

    DEFF Research Database (Denmark)

    Almoro, Percival; Gundu, Phanindra Narayan; Hanson, Steen Grüner

    2009-01-01

    What we believe to be a novel technique for wavefront aberration measurement using speckle patterns is presented. The aberration correction is done numerically. A tilted lens is illuminated with a partially developed speckle field, and the transmitted light intensity is sampled at axially displaced...

  2. MAPCLASS a code to optimize high order aberrations

    CERN Document Server

    Tomás, R

    2006-01-01

    MAPCLASS is a code written in PYTHON conceived to optimize the non-linear aberrations of the Final Focus System of CLIC. MAPCLASS calls MADX-PTC to obtain the map coefficients and uses optimization algorithms like the Simplex to compensate the high order aberrations.

  3. Pattern of chromosomal aberrations in patients from north East iran.

    Science.gov (United States)

    Ghazaey, Saeedeh; Mirzaei, Farzaneh; Ahadian, Mitra; Keifi, Fatemeh; Semiramis, Tootian; Abbaszadegan, Mohammad Reza

    2013-01-01

    Chromosomal aberrations are common causes of multiple anomaly syndromes. Recurrent chromosomal aberrations have been identified by conventional cytogenetic methods used widely as one of the most important clinical diagnostic techniques. In this retrospective study, the incidences of chromosomal aberrations were evaluated in a six year period from 2005 to 2011 in Pardis Clinical and Genetics Laboratory on patients referred to from Mashhad and other cities in Khorasan province. Karyotyping was performed on 3728 patients suspected of having chromosomal abnormalities. The frequencies of the different types of chromosomal abnormalities were determined, and the relative frequencies were calculated in each group. Among these patients, 83.3% had normal karyotypes with no aberrations. The overall incidences of chromosomal abnormalities were 16.7% including sex and autosomal chromosomal anomalies. Of those, 75.1 % showed autosomal chromosomal aberrations. Down syndrome (DS) was the most prevalent autosomal aberration in the patients (77.1%). Pericentric inversion of chromosome 9 was seen in 5% of patients. This inversion was prevalent in patients with recurrent spontaneous abortion (RSA). Sex chromosomal aberrations were observed in 24.9% of abnormal patients of which 61% had Turner's syndrome and 33.5% had Klinefelter's syndrome. According to the current study, the pattern of chromosomal aberrations in North East of Iran demonstrates the importance of cytogenetic evaluation in patients who show clinical abnormalities. These findings provide a reason for preparing a local cytogenetic data bank to enhance genetic counseling of families who require this service.

  4. Prospects for electron beam aberration correction using sculpted phase masks

    Energy Technology Data Exchange (ETDEWEB)

    Shiloh, Roy, E-mail: royshilo@post.tau.ac.il; Remez, Roei; Arie, Ady

    2016-04-15

    Technological advances in fabrication methods allowed the microscopy community to take incremental steps towards perfecting the electron microscope, and magnetic lens design in particular. Still, state of the art aberration-corrected microscopes are yet 20–30 times shy of the theoretical electron diffraction limit. Moreover, these microscopes consume significant physical space and are very expensive. Here, we show how a thin, sculpted membrane is used as a phase-mask to induce specific aberrations into an electron beam probe in a standard high resolution TEM. In particular, we experimentally demonstrate beam splitting, two-fold astigmatism, three-fold astigmatism, and spherical aberration. - Highlights: • Thin membranes can be used as aberration correctors in electron columns. • We demonstrate tilt, twofold-, threefold-astigmatism, and spherical aberrations. • Experimental and physical-optics simulation results are in good agreement. • Advantages in cost, size, nonmagnetism, and nearly-arbitrary correction.

  5. Effects of aberrations in spatiotemporal focusing of ultrashort laser pulses.

    Science.gov (United States)

    Sun, Bangshan; Salter, Patrick S; Booth, Martin J

    2014-04-01

    Spatiotemporal focusing, or simultaneous spatial and temporal focusing (SSTF), has already been adopted for various applications in microscopy, photoactivation for biological studies, and laser fabrication. We investigate the effects of aberrations on focus formation in SSTF, in particular, the effects of phase aberrations related to low-order Zernike modes and a refractive index mismatch between the immersion medium and sample. By considering a line focus, we are able to draw direct comparison between the performance of SSTF and conventional spatial focusing (SF). Wide-field SSTF is also investigated and is found to be much more robust to aberrations than either line SSTF or SF. These results show the sensitivity of certain focusing methods to specific aberrations, and can inform on the necessity and benefit of aberration correction.

  6. Chromosome aberrations in pesticide-exposed greenhouse workers

    DEFF Research Database (Denmark)

    Lander, B F; Knudsen, Lisbeth E.; Gamborg, M O

    2000-01-01

    OBJECTIVES: The aim of this study was to investigate the possibility of subtoxic exposure to pesticides causing chromosome aberrations in greenhouse workers. METHODS: In a cross-sectional and prospective study design chromosome aberration frequencies in cultured lymphocytes were examined for 116 ...... pesticide exposure. In general, the findings indicate the importance of personal protection, during high-exposure re-entry activities, in preventing pesticide uptake and genetic damage.......OBJECTIVES: The aim of this study was to investigate the possibility of subtoxic exposure to pesticides causing chromosome aberrations in greenhouse workers. METHODS: In a cross-sectional and prospective study design chromosome aberration frequencies in cultured lymphocytes were examined for 116...... workers when they were compared with the referents. After a summer season of pesticide spraying in the greenhouses, the total frequencies of cells with chromosome aberrations were significantly higher than in the preseason samples (P=0.02) and also higher than for the referents (P=0.05). This finding...

  7. Age-related changes in ocular aberrations with accommodation.

    Science.gov (United States)

    Radhakrishnan, Hema; Charman, W Neil

    2007-05-30

    This study investigates the changes in aberrations with monocular accommodation as a function of age. Second-order and higher order wavefront aberrations and pupil size were measured as a function of accommodation demand over the range of 0-4 D in the right eyes of 47 normal subjects with ages between 17 and 56 years. Higher order ocular Zernike aberrations were analyzed for the natural pupil size in terms of their equivalent defocus and were also determined for fixed pupil diameters of 4.5 mm in the unaccommodated eyes and 2.5 mm in the accommodating eyes. With relaxed accommodation (0 D accommodation stimulus), the major change with age was in the value of C4(0), which increased in positive value over the age range studied, although the total higher order RMS wavefront aberration did not increase. When the data were analyzed for natural pupils, spherical aberration was again found to change systematically in the positive direction with age. The equivalent defocus of total higher order RMS error for natural pupils showed no significant correlation with age (p > .05). With active accommodation, spherical aberration was found to decrease and become negative as the accommodative response increased in the younger subjects (40 years), the spherical aberration showed only small changes, some of which were positive, within the limited amplitude of accommodation available. Other higher order aberrations and the RMS of higher order aberrations did not appear to change systematically with accommodation, except in the oldest subjects. The change with age in the relationship between aberration and accommodation is interpreted in terms of the changing gradients of refractive index and surface curvatures of the crystalline lens.

  8. Phosphatidylinositol-3-kinase pathway aberrations in gastric and colorectal cancer: meta-analysis, co-occurrence and ethnic variation.

    Science.gov (United States)

    Chong, Mei-Ling; Loh, Marie; Thakkar, Bhavin; Pang, Brendan; Iacopetta, Barry; Soong, Richie

    2014-03-01

    Inhibition of the phosphatidylinositol-3-kinase (PI3K) signaling pathway is a cancer treatment strategy that has entered into clinical trials. We performed a meta-analysis on the frequency of prominent genetic (PIK3CA mutation, PIK3CA amplification and PTEN deletion) and protein expression (high PI3K, PTEN loss and high pAkt) aberrations in the PI3K pathway in gastric cancer (GC) and colorectal cancer (CRC). We also performed laboratory analysis to investigate the co-occurrence of these aberrations. The meta-analysis indicated that East Asian and Caucasian GC patients differ significantly for the frequencies of PIK3CA Exon 9 and 20 mutations (7% vs. 15%, respectively), PTEN deletion (21% vs. 4%) and PTEN loss (47% vs. 78%), while CRC patients differed for PTEN loss (57% vs. 26%). High study heterogeneity (I(2) > 80) was observed for all aberrations except PIK3CA mutations. Laboratory analysis of tumors from East Asian patients revealed significant differences between GC (n = 79) and CRC (n = 116) for the frequencies of PIK3CA amplification (46% vs. 4%) and PTEN loss (54% vs. 78%). The incidence of GC cases with 0, 1, 2 and 3 concurrent aberrations was 14%, 52%, 27% and 8%, respectively, while for CRC it was 10%, 60%, 25% and 4%, respectively. Our study consolidates knowledge on the frequency, co-occurrence and clinical relevance of PI3K pathway aberrations in GC and CRC. Up to 86% of GC and 90% of CRC have at least one aberration in the PI3K pathway, and there are significant differences in the frequencies of these aberrations according to cancer type and ethnicity.

  9. High order aberrations calculation of a hexapole corrector using a differential algebra method

    Science.gov (United States)

    Kang, Yongfeng; Liu, Xing; Zhao, Jingyi; Tang, Tiantong

    2017-02-01

    A differential algebraic (DA) method is proved as an unusual and effective tool in numerical analysis. It implements conveniently differentiation up to arbitrary high order, based on the nonstandard analysis. In this paper, the differential algebra (DA) method has been employed to compute the high order aberrations up to the fifth order of a practical hexapole corrector including round lenses and hexapole lenses. The program has been developed and tested as well. The electro-magnetic fields of arbitrary point are obtained by local analytic expressions, then field potentials are transformed into new forms which can be operated in the DA calculation. In this paper, the geometric and chromatic aberrations up to fifth order of a practical hexapole corrector system are calculated by the developed program.

  10. Aberrant promoter CpG methylation and its translational applications in breast cancer

    Institute of Scientific and Technical Information of China (English)

    Ting-Xiu Xiang; Ying Yuan; Li-Li Li; Zhao-Hui Wang; Liang-Ying Dan; Yan Chen; Guo-Sheng Ren; Qian Tao

    2013-01-01

    Breast cancer is a complex disease driven by multiple factors including both genetic and epigenetic alterations.Recent studies revealed that abnormal gene expression induced by epigenetic changes,including aberrant promoter methylation and histone modification,plays a critical role in human breast carcinogenesis.Silencing of tumor suppressor genes (TSGs) by promoter CpG methylation facilitates cells growth and survival advantages and further results in tumor initiation and progression,thus directly contributing to breast tumorigenesis.Usually,aberrant promoter methylation of TSGs,which can be reversed by pharmacological reagents,occurs at the early stage of tumorigenesis and therefore may serve as a potential tumor marker for early diagnosis and therapeutic targeting of breast cancer.In this review,we summarize the epigenetic changes of multiple TSGs involved in breast pathogenesis and their potential clinical applications as tumor markers for early detection and treatment of breast cancer.

  11. Epigenetic aberrations and therapeutic implications in gliomas.

    Science.gov (United States)

    Natsume, Atsushi; Kondo, Yutaka; Ito, Motokazu; Motomura, Kazuya; Wakabayashi, Toshihiko; Yoshida, Jun

    2010-06-01

    Almost all cancer cells have multiple epigenetic abnormalities, which combine with genetic changes to affect many cellular processes, including cell proliferation and invasion, by silencing tumor-suppressor genes. In this review, we focus on the epigenetic mechanisms of DNA hypomethylation and CpG island hypermethylation in gliomas. Aberrant hypermethylation in promoter CpG islands has been recognized as a key mechanism involved in the silencing of cancer-associated genes and occurs at genes with diverse functions related to tumorigenesis and tumor progression. Such promoter hypermethylation can modulate the sensitivity of glioblastomas to drugs and radiotherapy. As an example, the methylation of the O6-methylguanine DNA methyltransferase (MGMT) promoter is a specific predictive biomarker of tumor responsiveness to chemotherapy with alkylating agents. Further, we reviewed reports on pyrosequencing - a simple technique for the accurate and quantitative analysis of DNA methylation. We believe that the quantification of MGMT methylation by pyrosequencing might enable the selection of patients who are most likely to benefit from chemotherapy. Finally, we also evaluated the potential of de novo NY-ESO-1, the most immunogenic cancer/testis antigen (CTA) discovered thus far, as an immunotherapy target. The use of potent epigenetics-based therapy for cancer cells might restore the abnormally regulated epigenomes to a more normal state through epigenetic reprogramming. Thus, epigenetic therapy may be a promising and potent treatment for human neoplasia.

  12. Aberrant DNA methylation in cloned ovine embryos

    Institute of Scientific and Technical Information of China (English)

    LIU Lei; HOU Jian; LEI TingHua; BAI JiaHua; GUAN Hong; AN XiaoRong

    2008-01-01

    By using the approach of immunofluorescence staining with an antibody against 5-methylcytosine (5MeC), the present study detected the DNA methylation patterns of cloned ovine embryos. The em-bryos derived from in vitro fertilization were also examined for reference purpose. The results showed that: (1) during the pre-implantation development, cloned embryos displayed a similar demethylation profile to the fertilized embryos; that is, the methylation level decreased to the lowest at 8-cell stage, and then increased again at morulae stage. However, methylation level was obviously higher in cloned embryos than in stage-matched fertilized embryos, especially at 8-cell stage and afterwards; (2) at blastocyst stage, the methylation pattern in cloned embryos was different from that in fertilized em-bryos. In cloned blastocyst, inner cell mass (ICM) exhibited a comparable level to trophectoderm cells (TE), while in in-vitro fertilized blastocyst the methylation level of ICM was lower than that of TE, which is not consistent with that reported by other authors. These results indicate that DNA methylation is abnormally reprogrammed in cloned embryos, implying that aberrant DNA methylation reprogramming may be one of the factors causing cloned embryos developmental failure.

  13. Chromosome aberrations in solid tumors have a stochastic nature

    Energy Technology Data Exchange (ETDEWEB)

    Castro, Mauro A.A. [Departamento de Bioquimica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600-anexo, Porto Alegre 90035-003 (Brazil) and Departamento de Medicina Interna, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2350, Porto Alegre 90035-903 (Brazil) and Instituto de Fisica, Universidade Federal do Rio Grande do Sul, Av. Bento Goncalves 9500, Porto Alegre 91501-970 (Brazil) and Universidade Luterana do Brasil, Rua Miguel Tostes 101, Canoas 92420-280 (Brazil)]. E-mail: mauro@ufrgs.br; Onsten, Tor G.H. [Departamento de Medicina Interna, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2350, Porto Alegre 90035-903 (Brazil); Universidade Luterana do Brasil, Rua Miguel Tostes 101, Canoas 92420-280 (Brazil); Moreira, Jose C.F. [Departamento de Bioquimica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600-anexo, Porto Alegre 90035-003 (Brazil); Almeida, Rita M.C. de [Instituto de Fisica, Universidade Federal do Rio Grande do Sul, Av. Bento Goncalves 9500, Porto Alegre 91501-970 (Brazil)

    2006-08-30

    An important question nowadays is whether chromosome aberrations are random events or arise from an internal deterministic mechanism, which leads to the delicate task of quantifying the degree of randomness. For this purpose, we have defined several Shannon information functions to evaluate disorder inside a tumor and between tumors of the same kind. We have considered 79 different kinds of solid tumors with 30 or more karyotypes retrieved from the Mitelman Database of Chromosome Aberrations in Cancer. The Kaplan-Meier cumulative survival was also obtained for each solid tumor type in order to correlate data with tumor malignance. The results here show that aberration spread is specific for each tumor type, with high degree of diversity for those tumor types with worst survival indices. Those tumor types with preferential variants (e.g. high proportion of a given karyotype) have shown better survival statistics, indicating that aberration recurrence is a good prognosis. Indeed, global spread of both numerical and structural abnormalities demonstrates the stochastic nature of chromosome aberrations by setting a signature of randomness associated to the production of disorder. These results also indicate that tumor malignancy correlates not only with karyotypic diversity taken from different tumor types but also taken from single tumors. Therefore, by quantifying aberration spread, we could confront diverse models and verify which of them points to the most likely outcome. Our results suggest that the generating process of chromosome aberrations is neither deterministic nor totally random, but produces variations that are distributed between these two boundaries.

  14. Aberrant crypt foci as microscopic precursors of colorectal cancer

    Institute of Scientific and Technical Information of China (English)

    Lei Cheng; Mao-De Lai

    2003-01-01

    Since the first detection of aberrant crypt foci (ACF) in carcinogen-treated mice, there have been numerous studies focusing on these microscopically visible lesions both in rodents and in humans. ACF have been generally accepted as precancerous lesions in regard to histopathological characteristics, biochemical and immunohistochemical alterations, and genetic and epigenetic alterations. ACF show variable histological features, ranging from hyperplasia to dysplasia. ACF in human colon are more frequently located in the distal parts than in the proximal parts, which is in accordance with those in colorectal cancer (CRC). The immunohistochemical expressions of carcinoembryonic antigen (CEA), β-catenin, placental cadherin (P-cadherin),epithelial cadherin (E-cadherin), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), and P16INK4a are found to be altered. Genetic mutations of K-ras, APC and p53, and the epigenetic alterations of CpG island methylation of ACF have also been demonstrated. Genomic instabilities due to the defect of mismatch repair (MMR) system are detectable in ACF Two hypotheses have been proposed.One is the "dysplasia ACF-adenoma-carcinoma sequence",the other is "heteroplastic ACF-adenoma-carcinoma sequence". The malignant potential of ACF, especially dyspiastic ACF, makes it necessary to reveal the nature of these lesions, and to prevent CRC from the earliest possible stage. The technique of magnifying chromoscope makes it possible to detect "in vivo' ACF, which is beneficial to colon cancer research, identifying high-risk populations for CRC,and developing preventive procedures.

  15. Study of residual aberration for non-imaging focusing heliostat

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Y.T.; Chong, K.K.; Lim, B.H.; Lim, C.S. [Institute of Energy and Environment, Malaysia University of Science and Technology, No. 17, Jalan SS7/26, Kelana Jaya, 47301 Petaling Jaya, Selangor (Malaysia)

    2003-08-01

    Instead of using a specific focusing geometry, a non-imaging focusing heliostat has no fixed geometry but is composed of many small movable element mirrors that can be manoeuvred to eliminate the first-order aberration. Following our previous publication on the principle of non-imaging focusing heliostat, this paper further explores higher order residual aberration that limits the size of the focusing spot. The residual aberration can be partially corrected by offsetting the pivot point of mirrors and pre-setting the tilting angles of mirrors.

  16. High order aberration and straylight evaluation after cataract surgery with implantation of an aspheric,aberration correcting monofocal intraocular lens

    Institute of Scientific and Technical Information of China (English)

    Florian; T; A; Kretz; Tamer; Tandogan; Ramin; Khoramnia; Gerd; U; Auffarth

    2015-01-01

    ·AIM: To evaluate the quality of vision in respect to high order aberrations and straylight perception after implantation of an aspheric, aberration correcting,monofocal intraocular lens(IOL).·METHODS: Twenty-one patients(34 eyes) aged 50 to83 y underwent cataract surgery with implantation of an aspheric, aberration correcting IOL(Tecnis ZCB00,Abbott Medical Optics). Three months after surgery they were examined for uncorrected(UDVA) and corrected distance visual acuity(CDVA), contrast sensitivity(CS)under photopic and mesopic conditions with and without glare source, ocular high order aberrations(HOA, Zywave II) and retinal straylight(C-Quant).· RESULTS: Postoperatively, patients achieved a postoperative CDVA of 0.0 log MAR or better in 97.1% of eyes. Mean values of high order abberations were +0.02±0.27(primary coma components) and-0.04 ±0.16(spherical aberration term). Straylight values of the C-Quant were 1.35±0.44 log which is within normal range of age matched phakic patients. The CS measurements under mesopic and photopic conditions in combination with and without glare did not show any statistical significance in the patient group observed(P ≥0.28).· CONCLUSION: The implantation of an aspherical aberration correcting monofocal IOL after cataractsurgery resulted in very low residual higher order aberration(HOA) and normal straylight.

  17. I. THE THEORY OF ABERRATIONS OF QUADRUPOLE FOCUSING ARRAYS. II. ION OPTICAL DESIGN OF HIGH QUALITY EXTRACTED SYNCHROTRON BEAMS WITH APPLICATION TO THE BEVATRON

    Energy Technology Data Exchange (ETDEWEB)

    Meads Jr., Philip Francis

    1963-05-15

    In Part One they formulate in a general way the problem of analyzing and evaluating the aberrations of quadrupole magnet beam systems, and of characterizing the shapes and other properties of the beam envelopes in the neighborhood of foci. They consider all aberrations, including those due to misalignments and faulty construction, through third order in small parameters, for quadrupole beam systems. One result of this study is the development of analytic and numerical techniques for treating these aberrations, yielding useful expressions for the comparison of the aberrations of different beam systems. A second result of this study is a comprehensive digital computer program that determines the magnitude and nature of the aberrations of such beam systems. The code, using linear programming techniques, will adjust the parameters of a beam system to obtain specified optical properties and to reduce the magnitude of aberrations that limit the performance of that system. They examine numerically, in detail, the aberrations of two typical beam systems. In Part Two, they examine the problem of extracting the proton beam from a synchrotron of 'H' type magnet construction. They describe the optical studies that resulted in the design of an external beam from the Bevatron that is optimized with respect to linear, dispersive, and aberration properties and that uses beam elements of conservative design. The design of the beam is the result of the collaboration of many people representing several disciplines. They describe the digital computer programs developed to carry out detailed orbit studies which were required because of the existence of large second order aberrations in the beam.

  18. Aberrant Right Subclavian Artery: A Life‑threatening Anomaly that ...

    African Journals Online (AJOL)

    Aberrant Right Subclavian Artery: A Life‑threatening Anomaly that should be ... of the retroesophageal space during esophagectomy, may prevent any injury to the .... Source of Support: Nil, Conflict of Interest: None declared. [Downloaded free ...

  19. Are persistent delusions in schizophrenia associated with aberrant salience?

    Directory of Open Access Journals (Sweden)

    Rafeef Abboud

    2016-06-01

    Conclusion: These findings do not support the hypothesis that persistent delusions are related to aberrant motivational salience processing in TRS patients. However, they do support the view that patients with schizophrenia have impaired reward learning.

  20. Automated spherical aberration correction in scanning confocal microscopy

    NARCIS (Netherlands)

    Yoo, H.W.; Royen, M.E.; van Cappellen, W.A.; Houtsmuller, A.B.; Verhaegen, M.H.G.; Schitter, G.

    2014-01-01

    Mismatch between the refractive indexes of immersion media and glass coverslips introduces spherical aberrations in microscopes especially for high numerical aperture objectives. This contribution demonstrates an automated adjustment of the coverslip correction collar in scanning confocal microscopy

  1. Impact of primary aberrations on coherent lidar performance

    DEFF Research Database (Denmark)

    Hu, Qi; Rodrigo, Peter John; Iversen, Theis Faber Quist;

    2014-01-01

    In this work we investigate the performance of a monostatic coherent lidar system in which the transmit beam is under the influence of primary phase aberrations: spherical aberration (SA) and astigmatism. The experimental investigation is realized by probing the spatial weighting function...... of the lidar system using different optical transceiver configurations. A rotating belt is used as a hard target. Our study shows that the lidar weighting function suffers from both spatial broadening and shift in peak position in the presence of aberration. It is to our knowledge the first experimental...... effciency, the optimum truncation of the transmit beam and the spatial sensitivity of a CW coherent lidar system. Under strong degree of aberration, the spatial confinement is significantly degraded. However for SA, the degradation of the spatial confinement can be reduced by tuning the truncation...

  2. Intrinsic Third Order Aberrations in Electrostatic and Magnetic Quadrupoles

    CERN Document Server

    Baartman, R

    2015-01-01

    Intrinsic aberrations are those which occur due to the finite length of the desired field configuration. They are often loosely ascribed to the fringing field. This is misleading as it implies that the effects can be minimized by shaping the fields. In fact, there is an irreducible component related to the broken symmetry. It is present even in the hard-edge limit, and moreover, the other (soft-edge) effects can be simply ascribed to the intrinsic aberration spread over a finite length. We rederive the aberration formulas for quadrupoles using a Hamiltonian formalism. This allows for an easy comparison of electrostatic and magnetic quadrupoles. For different combinations of large and small emittances in the two transverse planes, it is found that in some situations electrostatic quadrupoles have lower aberrations, while in others, magnetic quadrupoles are better. As well, we discuss the ways in which existing transport codes handle quadrupole fringe fields. Pitfalls are pointed out and improvements proposed.

  3. Aberrant internal carotid artery in the middle ear

    Energy Technology Data Exchange (ETDEWEB)

    Roh, Keun Tak; Kang, Hyun Koo [Dept. of Radiology, Seoul Veterans Hospital, Seoul (Korea, Republic of)

    2014-10-15

    The knowledge about the aberrant internal carotid artery (ICA) in the middle ear is essential for clinicians, because a misdiagnosis of the aberrant ICA could have serious consequences such as excessive aural bleeding during a middle ear surgery. A 38-year-old woman presented with tinnitus and hearing difficulties of the left ear that had started 5 years ago. During otoscopy, an anteroinferior bluish mass was seen in the tympanic space. Computed tomography and magnetic resonance imaging demonstrated a left-side aberrant ICA with bony dehiscence of the carotid canal in the middle ear and a reduced diameter of the tympanic ICA. Herein we report a case of an aberrant ICA in the middle ear. We also review the literature regarding this important vascular anomaly of the temporal bone which may lead to disastrous surgical complications.

  4. CYTOGENETIC STUDY OF CHROMOSOMAL ABERRATIONS ASSOCIATED WITH CHRONIC LEUKEMIA

    National Research Council Canada - National Science Library

    Dharma Niranjan Mishra; Sitansu Kumar Panda; Saurjya Ranjan Das; Jami Sagar Prusti; Santosh Sahu; Priyambada Panda; Chinmayi Mohapatra

    2016-01-01

    ... in the Hematology section of Pathology Department from the coastal District of Orissa. The chromosomal aberrations were taken into account in this present study and arranged in tables, Bar charts and Pie charts for comparison...

  5. Aberrant splicing of the DMP1-ARF-MDM2-p53 pathway in cancer.

    Science.gov (United States)

    Inoue, Kazushi; Fry, Elizabeth A

    2016-07-01

    Alternative splicing (AS) of mRNA precursors is a ubiquitous mechanism for generating numerous transcripts with different activities from one genomic locus in mammalian cells. The gene products from a single locus can thus have similar, dominant-negative or even opposing functions. Aberrant AS has been found in cancer to express proteins that promote cell growth, local invasion and metastasis. This review will focus on the aberrant splicing of tumor suppressor/oncogenes that belong to the DMP1-ARF-MDM2-p53 pathway. Our recent study shows that the DMP1 locus generates both tumor-suppressive DMP1α (p53-dependent) and oncogenic DMP1β (p53-independent) splice variants, and the DMP1β/α ratio increases with neoplastic transformation of breast epithelial cells. This process is associated with high DMP1β protein expression and shorter survival of breast cancer (BC) patients. Accumulating pieces of evidence show that ARF is frequently inactivated by aberrant splicing in human cancers, demonstrating its involvement in human malignancies. Splice variants from the MDM2 locus promote cell growth in culture and accelerate tumorigenesis in vivo. Human cancers expressing these splice variants are associated with advanced stage/metastasis, and thus have negative clinical impacts. Although they lack most of the p53-binding domain, their activities are mostly dependent on p53 since they bind to wild-type MDM2. The p53 locus produces splice isoforms that have either favorable (β/γ at the C-terminus) or negative impact (Δ40, Δ133 at the N-terminus) on patients' survival. As the oncogenic AS products from these loci are expressed only in cancer cells, they may eventually become targets for molecular therapies.

  6. Pattern of Chromosomal Aberrations in Patients from North East Iran

    Directory of Open Access Journals (Sweden)

    Saeedeh Ghazaey

    2013-01-01

    Full Text Available Objective: Chromosomal aberrations are common causes of multiple anomaly syndromes. Recurrent chromosomal aberrations have been identified by conventional cytogenetic methods used widely as one of the most important clinical diagnostic techniques.Materials and Methods: In this retrospective study, the incidences of chromosomal aberrations were evaluated in a six year period from 2005 to 2011 in Pardis Clinical and Genetics Laboratory on patients referred to from Mashhad and other cities in Khorasan province. Karyotyping was performed on 3728 patients suspected of having chromosomal abnormalities.Results: The frequencies of the different types of chromosomal abnormalities were determined, and the relative frequencies were calculated in each group. Among these patients, 83.3% had normal karyotypes with no aberrations. The overall incidences of chromosomal abnormalities were 16.7% including sex and autosomal chromosomal anomalies. Of those, 75.1 % showed autosomal chromosomal aberrations. Down syndrome (DS was the most prevalent autosomal aberration in the patients (77.1%. Pericentric inversion of chromosome 9 was seen in 5% of patients. This inversion was prevalent in patients with recurrent spontaneous abortion (RSA. Sex chromosomal aberrations were observed in 24.9% of abnormal patients of which 61% had Turner’s syndrome and 33.5% had Klinefelter’s syndrome.Conclusion: According to the current study, the pattern of chromosomal aberrations in North East of Iran demonstrates the importance of cytogenetic evaluation in patients who show clinical abnormalities. These findings provide a reason for preparing a local cytogenetic data bank to enhance genetic counseling of families who require this service.

  7. Aberrant cervical thymus mimicking thyroid on ultrasonography: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jeong Sub; Park, Ju Hyun; Kim, Bong Soo; Park, Ji Kang; Choi, Jae Hyuck [Jeju National Univ. Hospital/Jeju National Univ. School of Medicine, Jeju (Korea, Republic of)

    2012-10-15

    Aberrant cervical thymus is rarely reported in adults. We report a case of solid aberrant cervical thymus in a 27 year old female, which was found incidentally on ultrasonography for the evaluation of the thyroid cancer. On ultrasonography, the lesion was found between the left thyroid and common carotid artery without any remarkable interface echo, and had similar echogenicity to the thyroid. The lesion extended to the upper pole of the left thyroid.

  8. Wide-angle chromatic aberration corrector for the human eye.

    Science.gov (United States)

    Benny, Yael; Manzanera, Silvestre; Prieto, Pedro M; Ribak, Erez N; Artal, Pablo

    2007-06-01

    The human eye is affected by large chromatic aberration. This may limit vision and makes it difficult to see fine retinal details in ophthalmoscopy. We designed and built a two-triplet system for correcting the average longitudinal chromatic aberration of the eye while keeping a reasonably wide field of view. Measurements in real eyes were conducted to examine the level and optical quality of the correction. We also performed some tests to evaluate the effect of the corrector on visual performance.

  9. Cellular origin of prognostic chromosomal aberrations in AML patients

    DEFF Research Database (Denmark)

    Mora-Jensen, H.; Jendholm, J.; Rapin, N.

    2015-01-01

    aberrations that were present in the fully transformed committed HPCs together with the prognostic driver aberration. Adding to this vast heterogeneity and complexity of AML genomes and their clonal evolution, a recent study of a murine AML model demonstrated that t(9;11) AML originating from HSCs responded...... poorly to in vivo chemotherapy treatment as compared with t(9;11) AML originating from HPCs....

  10. Study of the wavefront aberrations in children with amblyopia

    Institute of Scientific and Technical Information of China (English)

    ZHAO Peng-fei; ZHOU Yue-hua; WANG Ning-li; ZHANG Jing

    2010-01-01

    Background Amblyopia is a common ophthalmological condition and the wavefront aberrometer is a relatively new diagnostic tool used globally to measure optical characteristics of human eyes as well as to study refractive errors in amblyopic eyes. We studied the wavefront aberration of the amblyopic children's eyes and analyzed the mechanism of the wavefront aberration in the formation of the amblyopia, try to investigate the new evidence of the treatment of the amblyopia, especially in the refractory amblyopia.Methods The WaveScan Wavefront System (VISX, USA) aberrometer was used to investigate four groups of children under dark accommodation and cilliary muscle paralysis. There were 45 cases in the metropic group, 87 in the amblyopic group, 92 in the corrected-amblyopic group and 38 in the refractory amblyopic group. One-way analysis of variance (ANOVA), t-test and multivariate linear regression were used to analyze all the data.Results Third order to 6th order aberrations showed a decreasing trend whereas in the higher order aberrations the main ones were 3rd order coma (Z3-1-Z31), trefoil (Z3-3-Z33) and 4th order aberration (Z40); and 3rd order coma represented the highest percentage of all three main aberrations. Within 3rd order coma, vertical coma (Z3-1) accounted for a greater percentage than horizontal coma (Z31). Significant differences of vertical coma were found among all clinical groups of children: vertical coma in the amblyopic group (0.17±0.15) was significantly higher than in the metropic group (0.11±0.13, P0.05).Conclusions Although lower order aberrations such as defocus (myopia and hyperopia) and astigmatism are major factors determining the quality of the retinal image, higher order aberrations also need to be considered in amblyopic eyes as their effects are significant.

  11. Multiplexed aberration measurement for deep tissue imaging in vivo

    OpenAIRE

    Wang, Chen; Liu, Rui; Milkie, Daniel E; Sun, Wenzhi; Tan, Zhongchao; Kerlin, Aaron; Chen, Tsai-Wen; Kim, Douglas S.; Ji, Na

    2014-01-01

    We describe a multiplexed aberration measurement method that modulates the intensity or phase of light rays at multiple pupil segments in parallel to determine their phase gradients. Applicable to fluorescent-protein-labeled structures of arbitrary complexity, it allows us to obtain diffraction-limited resolution in various samples in vivo. For the strongly scattering mouse brain, a single aberration correction improves structural and functional imaging of fine neuronal processes over a large...

  12. Multiplexed aberration measurement for deep tissue imaging in vivo

    Science.gov (United States)

    Wang, Chen; Liu, Rui; Milkie, Daniel E.; Sun, Wenzhi; Tan, Zhongchao; Kerlin, Aaron; Chen, Tsai-Wen; Kim, Douglas S.; Ji, Na

    2014-01-01

    We describe a multiplexed aberration measurement method that modulates the intensity or phase of light rays at multiple pupil segments in parallel to determine their phase gradients. Applicable to fluorescent-protein-labeled structures of arbitrary complexity, it allows us to obtain diffraction-limited resolution in various samples in vivo. For the strongly scattering mouse brain, a single aberration correction improves structural and functional imaging of fine neuronal processes over a large imaging volume. PMID:25128976

  13. Longitudinal Trajectories of Aberrant Behavior in Fragile X Syndrome

    OpenAIRE

    Hustyi, Kristin M; Hall, Scott S.; Jo, Booil; Lightbody, Amy A; Reiss, Allan L.

    2014-01-01

    The Aberrant Behavior Checklist—Community (ABC-C; Aman, Burrow, & Wolford, 1995) has been increasingly adopted as a primary tool for measuring behavioral change in clinical trials for individuals with fragile X syndrome (FXS). To our knowledge, however, no study has documented the longitudinal trajectory of aberrant behaviors in individuals with FXS using the ABC-C. As part of a larger longitudinal study, we examined scores obtained on the ABC-C subscales for 124 children and adolescents (64 ...

  14. Test Mass Temperature Field and Laser Aberration Modeling in Advanced LIGO

    Science.gov (United States)

    Ramette, Joshua; Kasprzack, Marie; Gonzalez, Gabriela; Brooks, Aidan; Blair, Carl; Kandhasamy, Shivaraj; Wang, Haoyu; LIGO Collaboration

    2017-01-01

    Advanced LIGO uses high laser power in the main interferometer arm cavities to achieve design sensitivity. A small part of this power is absorbed in the interferometer cavity mirrors where it creates thermal lenses. Actuation by ``ring heaters,'' additional heater elements aimed to reduce the temperature gradients in the mirrors, minimizes aberrations in the main laser beam due to thermal lensing. We derive the first analytical model of the temperature field contribution in the mirrors generated by an ideal ring heater. In addition, we simulate the test mass temperature field using finite element analysis software and find agreement with the prediction of our ring heater analytical model and existing models for self-heating of the test mass by the main laser beam. From our ring heater temperature field models, we then express the resulting optical aberration contribution in the main laser and compare to Hartmann wavefront sensor measurements of the aberration. Used in conjunction with wavefront measurements, our model provides a more complete understanding of the thermal state of the cavity mirrors and will allow a more efficient use of the ring heaters in Advanced LIGO. We thank the National Science Foundation for supporting this work (NSF grant #1262890 and #1205882).

  15. Protection of Chloroplast Membranes by VIPP1 Rescues Aberrant Seedling Development in Arabidopsis nyc1 Mutant

    Directory of Open Access Journals (Sweden)

    Lingang eZhang

    2016-04-01

    Full Text Available Chlorophylls (Chl in photosynthetic apparatuses, along with other macromolecules in chloroplasts, are known to undergo degradation during leaf senescence. Several enzymes involved in Chl degradation, by which detoxification of Chl is safely implemented, have been identified. Chl degradation also occurs during embryogenesis and seedling development. Some genes encoding Chl degradation enzymes such as Chl b reductase (CBR function during these developmental stages. Arabidopsis mutants lacking CBR (NYC1 and NOL reportedly exhibit reduced seed storability and compromised germination and cotyledon development. This study examined aberrant cotyledon development, finding that NYC1 is solely responsible for this phenotype. We inferred that oxidative damage of chloroplast membranes caused the aberrant cotyledon. To test the inference, we attempted to trans-complement nyc1 mutant with overexpressing VIPP1 protein that is unrelated to Chl degradation but which supports chloroplast membrane integrity. VIPP1 expression actually complemented the aberrant cotyledon of nyc1, whereas stay-green phenotype during leaf senescence remained. The swollen chloroplasts observed in unfixed cotyledons of nyc1, which are characteristics of chloroplasts receiving envelope membrane damage, were recovered by overexpressing VIPP1. These results suggest that chloroplast membranes are a target for oxidative damage caused by the impairment in Chl degradation. Trans-complementation of nyc1 with VIPP1 also suggests that VIPP1 is useful for protecting chloroplasts against oxidative stress.

  16. Array CGH demonstrates characteristic aberration signatures in human papillary thyroid carcinomas governed by RET/PTC.

    Science.gov (United States)

    Unger, K; Malisch, E; Thomas, G; Braselmann, H; Walch, A; Jackl, G; Lewis, P; Lengfelder, E; Bogdanova, T; Wienberg, J; Zitzelsberger, H

    2008-07-31

    The aim of this study is to investigate additional genetic alterations in papillary thyroid carcinomas (PTCs) with known RET/PTC rearrangements. We applied array-based comparative genomic hybridization (array CGH) to 33 PTC (20 PTC from adults, 13 post-Chernobyl PTC from children) with known RET/PTC status. Principal component analysis and hierarchical cluster analysis identified cases with similar aberration patterns. Significant deviations between tumour-groups were obtained by statistical testing (Fisher's exact test in combination with Benjamini-Hochberg FDR-controlling procedure). FISH analysis on FFPE sections was applied to validate the array CGH data. Deletions were found more frequently in RET/PTC-positive and RET/PTC-negative tumours than amplifications. Specific aberration signatures were identified that discriminated between RET/PTC-positive and RET/PTC-negative cases (aberrations on chromosomes 1p, 3q, 4p, 7p, 9p/q, 10q, 12q, 13q and 21q). In addition, childhood and adult RET/PTC-positive cases differ significantly for a deletion on the distal part of chromosome 1p. There are additional alterations in RET/PTC-positive tumours, which may act as modifiers of RET activation. In contrast, alterations in RET/PTC-negative tumours indicate alternative routes of tumour development. The data presented serve as a starting point for further studies on gene expression and function of genes identified in this study.

  17. STRADalpha deficiency results in aberrant mTORC1 signaling during corticogenesis in humans and mice.

    Science.gov (United States)

    Orlova, Ksenia A; Parker, Whitney E; Heuer, Gregory G; Tsai, Victoria; Yoon, Jason; Baybis, Marianna; Fenning, Robert S; Strauss, Kevin; Crino, Peter B

    2010-05-01

    Polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome (PMSE) is a rare human autosomal-recessive disorder characterized by abnormal brain development, cognitive disability, and intractable epilepsy. It is caused by homozygous deletions of STE20-related kinase adaptor alpha (STRADA). The underlying pathogenic mechanisms of PMSE and the role of STRADA in cortical development remain unknown. Here, we found that a human PMSE brain exhibits cytomegaly, neuronal heterotopia, and aberrant activation of mammalian target of rapamycin complex 1 (mTORC1) signaling. STRADalpha normally binds and exports the protein kinase LKB1 out of the nucleus, leading to suppression of the mTORC1 pathway. We found that neurons in human PMSE cortex exhibited abnormal nuclear localization of LKB1. To investigate this further, we modeled PMSE in mouse neural progenitor cells (mNPCs) in vitro and in developing mouse cortex in vivo by knocking down STRADalpha expression. STRADalpha-deficient mNPCs were cytomegalic and showed aberrant rapamycin-dependent activation of mTORC1 in association with abnormal nuclear localization of LKB1. Consistent with the observations in human PMSE brain, knockdown of STRADalpha in vivo resulted in cortical malformation, enhanced mTORC1 activation, and abnormal nuclear localization of LKB1. Thus, we suggest that the aberrant nuclear accumulation of LKB1 caused by STRADalpha deficiency contributes to hyperactivation of mTORC1 signaling and disruption of neuronal lamination during corticogenesis, and thereby the neurological features associated with PMSE.

  18. STRADα deficiency results in aberrant mTORC1 signaling during corticogenesis in humans and mice

    Science.gov (United States)

    Orlova, Ksenia A.; Parker, Whitney E.; Heuer, Gregory G.; Tsai, Victoria; Yoon, Jason; Baybis, Marianna; Fenning, Robert S.; Strauss, Kevin; Crino, Peter B.

    2010-01-01

    Polyhydramnios, megalencephaly, and symptomatic epilepsy syndrome (PMSE) is a rare human autosomal-recessive disorder characterized by abnormal brain development, cognitive disability, and intractable epilepsy. It is caused by homozygous deletions of STE20-related kinase adaptor α (STRADA). The underlying pathogenic mechanisms of PMSE and the role of STRADA in cortical development remain unknown. Here, we found that a human PMSE brain exhibits cytomegaly, neuronal heterotopia, and aberrant activation of mammalian target of rapamycin complex 1 (mTORC1) signaling. STRADα normally binds and exports the protein kinase LKB1 out of the nucleus, leading to suppression of the mTORC1 pathway. We found that neurons in human PMSE cortex exhibited abnormal nuclear localization of LKB1. To investigate this further, we modeled PMSE in mouse neural progenitor cells (mNPCs) in vitro and in developing mouse cortex in vivo by knocking down STRADα expression. STRADα-deficient mNPCs were cytomegalic and showed aberrant rapamycin-dependent activation of mTORC1 in association with abnormal nuclear localization of LKB1. Consistent with the observations in human PMSE brain, knockdown of STRADα in vivo resulted in cortical malformation, enhanced mTORC1 activation, and abnormal nuclear localization of LKB1. Thus, we suggest that the aberrant nuclear accumulation of LKB1 caused by STRADα deficiency contributes to hyperactivation of mTORC1 signaling and disruption of neuronal lamination during corticogenesis, and thereby the neurological features associated with PMSE. PMID:20424326

  19. Dimensions of driving anger and their relationships with aberrant driving.

    Science.gov (United States)

    Zhang, Tingru; Chan, Alan H S; Zhang, Wei

    2015-08-01

    The purpose of this study was to investigate the relationship between driving anger and aberrant driving behaviours. An internet-based questionnaire survey was administered to a sample of Chinese drivers, with driving anger measured by a 14-item short Driving Anger Scale (DAS) and the aberrant driving behaviours measured by a 23-item Driver Behaviour Questionnaire (DBQ). The results of Confirmatory Factor Analysis demonstrated that the three-factor model (hostile gesture, arrival-blocking and safety-blocking) of the DAS fitted the driving anger data well. The Exploratory Factor Analysis on DBQ data differentiated four types of aberrant driving, viz. emotional violation, error, deliberate violation and maintaining progress violation. For the anger-aberration relation, it was found that only "arrival-blocking" anger was a significant positive predictor for all four types of aberrant driving behaviours. The "safety-blocking" anger revealed a negative impact on deliberate violations, a finding different from previously established positive anger-aberration relation. These results suggest that drivers with different patterns of driving anger would show different behavioural tendencies and as a result intervention strategies may be differentially effective for drivers of different profiles.

  20. Aberrant reward processing in Parkinson's disease is associated with dopamine cell loss.

    Science.gov (United States)

    Aarts, Esther; Helmich, Rick C; Janssen, Marcel J R; Oyen, Wim J G; Bloem, Bastiaan R; Cools, Roshan

    2012-02-15

    Dopamine has been implicated in reward-related impulsivity, but the exact relationship between dopamine, reward and impulsivity in humans remains unknown. We address this question in Parkinson's disease (PD), which is characterized by severe dopamine depletion. PD is associated primarily with motor and cognitive inflexibility, but can also be accompanied by reward-related impulsivity. This paradoxical symptom of PD has often been attributed to dopaminergic overstimulation by antiparkinson medication, which is necessary to relieve the motor and cognitive inflexibility. However, factors other than medication may also contribute to aberrant impact of reward. Here we assess whether cognitive inflexibility and aberrant reward impact in PD are two sides of the same coin, namely dopamine cell loss. To measure dopamine cell loss, we employed (123)I-FP-CIT Single Photon Emission Computed Tomography (SPECT) in 32 PD patients (10 never-medicated patients and 22 patients after withdrawal of all medication for >12h) and related the values to behavior on a rewarded task-switching paradigm. Dopamine cell loss was associated not only with cognitive inflexibility (under low reward), but also with aberrant impact of reward. These effects could not be attributed to medication use. Relative to controls (n=26), aberrant reward processing in PD was particularly expressed as reduced capacity to maintain (i.e., repeat) the current task-set under high reward. Our findings demonstrate that factors intrinsically related to PD may underlie the paradoxical symptoms of inflexibility and reward-related impulsivity in PD. The present results concur with observations that low baseline dopamine states predispose to drug and other addictions.

  1. The significance of PTEN and AKT aberrations in pediatric T-cell acute lymphoblastic leukemia

    Science.gov (United States)

    Zuurbier, Linda; Petricoin, Emanuel F.; Vuerhard, Maartje J.; Calvert, Valerie; Kooi, Clarissa; Buijs-Gladdines, Jessica G.C.A.M.; Smits, Willem K.; Sonneveld, Edwin; Veerman, Anjo J.P.; Kamps, Willem A.; Horstmann, Martin; Pieters, Rob; Meijerink, Jules P.P.

    2012-01-01

    Background PI3K/AKT pathway mutations are found in T-cell acute lymphoblastic leukemia, but their overall impact and associations with other genetic aberrations is unknown. PTEN mutations have been proposed as secondary mutations that follow NOTCH1-activating mutations and cause cellular resistance to γ-secretase inhibitors. Design and Methods The impact of PTEN, PI3K and AKT aberrations was studied in a genetically well-characterized pediatric T-cell leukemia patient cohort (n=146) treated on DCOG or COALL protocols. Results PTEN and AKT E17K aberrations were detected in 13% and 2% of patients, respectively. Defective PTEN-splicing was identified in incidental cases. Patients without PTEN protein but lacking exon-, splice-, promoter mutations or promoter hypermethylation were present. PTEN/AKT mutations were especially abundant in TAL- or LMO-rearranged leukemia but nearly absent in TLX3-rearranged patients (P=0.03), the opposite to that observed for NOTCH1-activating mutations. Most PTEN/AKT mutant patients either lacked NOTCH1-activating mutations (P=0.006) or had weak NOTCH1-activating mutations (P=0.011), and consequently expressed low intracellular NOTCH1, cMYC and MUSASHI levels. T-cell leukemia patients without PTEN/AKT and NOTCH1-activating mutations fared well, with a cumulative incidence of relapse of only 8% versus 35% for PTEN/AKT and/or NOTCH1-activated patients (P=0.005). Conclusions PI3K/AKT pathway aberrations are present in 18% of pediatric T-cell acute lymphoblastic leukemia patients. Absence of strong NOTCH1-activating mutations in these cases may explain cellular insensitivity to γ-secretase inhibitors. PMID:22491738

  2. Automated aberration compensation in high numerical aperture systems for arbitrary laser modes (Conference Presentation)

    Science.gov (United States)

    Hering, Julian; Waller, Erik H.; von Freymann, Georg

    2017-02-01

    Since a large number of optical systems and devices are based on differently shaped focal intensity distributions (point-spread-functions, PSF), the PSF's quality is crucial for the application's performance. E.g., optical tweezers, optical potentials for trapping of ultracold atoms as well as stimulated-emission-depletion (STED) based microscopy and lithography rely on precisely controlled intensity distributions. However, especially in high numerical aperture (NA) systems, such complex laser modes are easily distorted by aberrations leading to performance losses. Although different approaches addressing phase retrieval algorithms have been recently presented[1-3], fast and automated aberration compensation for a broad variety of complex shaped PSFs in high NA systems is still missing. Here, we report on a Gerchberg-Saxton[4] based algorithm (GSA) for automated aberration correction of arbitrary PSFs, especially for high NA systems. Deviations between the desired target intensity distribution and the three-dimensionally (3D) scanned experimental focal intensity distribution are used to calculate a correction phase pattern. The target phase distribution plus the correction pattern are displayed on a phase-only spatial-light-modulator (SLM). Focused by a high NA objective, experimental 3D scans of several intensity distributions allow for characterization of the algorithms performance: aberrations are reliably identified and compensated within less than 10 iterations. References 1. B. M. Hanser, M. G. L. Gustafsson, D. A. Agard, and J. W. Sedat, "Phase-retrieved pupil functions in wide-field fluorescence microscopy," J. of Microscopy 216(1), 32-48 (2004). 2. A. Jesacher, A. Schwaighofer, S. Frhapter, C. Maurer, S. Bernet, and M. Ritsch-Marte, "Wavefront correction of spatial light modulators using an optical vortex image," Opt. Express 15(9), 5801-5808 (2007). 3. A. Jesacher and M. J. Booth, "Parallel direct laser writing in three dimensions with spatially dependent

  3. Aberrant dopamine D2-like receptor function in a rodent model of schizophrenia.

    Science.gov (United States)

    Perez, Stephanie M; Lodge, Daniel J

    2012-11-01

    Based on the observation that antipsychotic medications display antagonist properties at dopamine D2-like receptors, aberrant dopamine signaling has been proposed to underlie psychosis in patients with schizophrenia. Thus, it is not surprising that considerable research has been devoted to understanding the mechanisms involved in the antipsychotic action of these compounds. It is important to note that the majority of these studies have been performed in "normal" experimental animals. Given that these animals do not possess the aberrant neuronal information processing typically associated with schizophrenia, the aim of the current study was to examine the dopamine D2 receptor system in a rodent model of schizophrenia. Here, we demonstrate that methylazoxymethanol acetate (MAM)-treated rats display an enhanced effect of quinpirole on dopamine neuron activity and an aberrant locomotor response to D2-like receptor activation, suggesting changes in postsynaptic D2-like receptor function. To better understand the mechanisms underlying the enhanced response to D2-like ligands in MAM-treated rats, we examined the expression of D2, D3, and dopamine transporter mRNA in the nucleus accumbens and ventral tegmental area by quantitative reverse transcription-polymerase chain reaction. MAM-treated rats displayed a significant increase in dopamine D3 receptor mRNA expression in the nucleus accumbens with no significant changes in the expression of the D2 receptor. Taken together, these data demonstrate robust alterations in dopamine D2-like receptor function in a rodent model of schizophrenia and provide evidence that preclinical studies examining the mechanisms of antipsychotic drug action should be performed in animal models that mirror aspects of the abnormal neuronal transmission thought to underlie symptoms of schizophrenia.

  4. Optical aberrations of intraocular lenses measured in vivo and in vitro

    Science.gov (United States)

    Barbero, Sergio; Marcos, Susana; Jiménez-Alfaro, Ignacio

    2003-10-01

    Corneal and ocular aberrations were measured in a group of eyes before and after cataract surgery with spherical intraocular lens (IOL) implantation by use of well-tested techniques developed in our laboratory. By subtraction of corneal from total aberration maps, we also estimated the optical quality of the intraocular lens in vivo. We found that aberrations in pseudophakic eyes are not significantly different from aberrations in eyes before cataract surgery or from previously reported aberrations in healthy eyes of the same age. However, aberrations in pseudophakic eyes are significantly higher than in young eyes. We found a slight increase of corneal aberrations after surgery. The aberrations of the IOL and the lack of balance of the corneal spherical aberrations by the spherical aberrations of the intraocular lens also degraded the optical quality in pseudophakic eyes. We also measured the aberrations of the IOL in vitro, using an eye cell model, and simulated the aberrations of the IOL on the basis of the IOL's physical parameters. We found a good agreement among in vivo, in vitro, and simulated measures of spherical aberration: Unlike the spherical aberration of the young crystalline lens, which tends to be negative, the spherical aberration of the IOL is positive and increases with lens power. Computer simulations and in vitro measurements show that tilts and decentrations might be contributors to the increased third-order aberrations in vivo in comparison with in vitro measurements.

  5. Persistence of Early Emerging Aberrant Behavior in Children with Developmental Disabilities

    Science.gov (United States)

    Green, Vanessa A.; O'Reilly, Mark; Itchon, Jonathan; Sigafoos, Jeff

    2005-01-01

    This study examined the persistence of early emerging aberrant behavior in 13 preschool children with developmental disabilities. The severity of aberrant behavior was assessed every 6 months over a 3-year period. Teachers completed the assessments using the Aberrant Behavior Checklist [Aman, M. G., & Singh, N. N. (1986). "Aberrant Behavior…

  6. Volumetric optical coherence microscopy enabled by aberrated optics (Conference Presentation)

    Science.gov (United States)

    Mulligan, Jeffrey A.; Liu, Siyang; Adie, Steven G.

    2017-02-01

    Optical coherence microscopy (OCM) is an interferometric imaging technique that enables high resolution, non-invasive imaging of 3D cell cultures and biological tissues. Volumetric imaging with OCM suffers a trade-off between high transverse resolution and poor depth-of-field resulting from defocus, optical aberrations, and reduced signal collection away from the focal plane. While defocus and aberrations can be compensated with computational methods such as interferometric synthetic aperture microscopy (ISAM) or computational adaptive optics (CAO), reduced signal collection must be physically addressed through optical hardware. Axial scanning of the focus is one approach, but comes at the cost of longer acquisition times, larger datasets, and greater image reconstruction times. Given the capabilities of CAO to compensate for general phase aberrations, we present an alternative method to address the signal collection problem without axial scanning by using intentionally aberrated optical hardware. We demonstrate the use of an astigmatic spectral domain (SD-)OCM imaging system to enable single-acquisition volumetric OCM in 3D cell culture over an extended depth range, compared to a non-aberrated SD-OCM system. The transverse resolution of the non-aberrated and astigmatic imaging systems after application of CAO were 2 um and 2.2 um, respectively. The depth-range of effective signal collection about the nominal focal plane was increased from 100 um in the non-aberrated system to over 300 um in the astigmatic system, extending the range over which useful data may be acquired in a single OCM dataset. We anticipate that this method will enable high-throughput cellular-resolution imaging of dynamic biological systems over extended volumes.

  7. Induction of chromosomal aberrations in human lymphocytes by fission neutrons

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Marcia Augusta da; Coelho, Paulo Rogerio Pinto; Bartolini, Paolo; Okazaki, Kayo [Instituto de Pesquisas Energeticas e Nucleares (IPEN-CNEN/SP), Sao Paulo, SP (Brazil)], e-mail: kokazaki@ipen.br

    2009-07-01

    Chromosome aberrations induced by sparsely ionizing radiation (low-LET) are well known and cytogenetic analyses of irradiated human lymphocytes have been widely applied to biological dosimetry. However, much less is known about chromosome aberrations induced by densely ionizing radiation (high LET), such as that of alpha particles or neutrons. Such particles induce DNA strand breaks, as well as chromosome breakage and rearrangements of high complexity. This damage is more localized and less efficiently repaired than after X- or {gamma}-ray irradiation. This preferential production of complex aberrations by densely ionizing radiation is related to the unique energy deposition patterns, which produces highly localized multiple DNA damage at the chromosomal level. A better knowledge of the interactions between different types of radiation and cellular DNA is of importance, not only from the radiobiological viewpoint but also for dosimetric and therapeutic purposes. The objective of the present study was to analyse the cytogenetic effects of fission neutrons on peripheral blood lymphocytes in order to evaluate structural and numerical aberrations and number of cells in the different mitotic cycles. So, blood samples from five healthy donors, 22-25 years old, of both sexes, were irradiated in the Research Reactor IEA-R1 of our Institute (IPEN/CNEN-SP) with thermal and fast neutrons at doses of 0.2; 0.3; 0.5 and 1.0 Gy. The {gamma} contribution to the total absorbed dose was about 30%. These doses were monitored by thermoluminescent dosemeters: LiF-600 (for neutrons) and LiF-700 (for {gamma}-rays). The data concerning structural aberrations were evaluated with regard to three parameters: percentage of cells with aberrations, number of aberrations/cell and number of dicentric/cell. The cytogenetic results showed an increase in the three parameters after irradiation with neutrons, as a function of radiation dose. Apparently, there was no influence of neutrons on the

  8. The role of aberrant mitochondrial bioenergetics in diabetic neuropathy.

    Science.gov (United States)

    Chowdhury, Subir K Roy; Smith, Darrell R; Fernyhough, Paul

    2013-03-01

    Diabetic neuropathy is a neurological complication of diabetes that causes significant morbidity and, because of the obesity-driven rise in incidence of type 2 diabetes, is becoming a major international health problem. Mitochondrial phenotype is abnormal in sensory neurons in diabetes and may contribute to the etiology of diabetic neuropathy where a distal dying-back neurodegenerative process is a key component contributing to fiber loss. This review summarizes the major features of mitochondrial dysfunction in neurons and Schwann cells in human diabetic patients and in experimental animal models (primarily exhibiting type 1 diabetes). This article attempts to relate these findings to the development of critical neuropathological hallmarks of the disease. Recent work reveals that hyperglycemia in diabetes triggers nutrient excess in neurons that, in turn, mediates a phenotypic change in mitochondrial biology through alteration of the AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) signaling axis. This vital energy sensing metabolic pathway modulates mitochondrial function, biogenesis and regeneration. The bioenergetic phenotype of mitochondria in diabetic neurons is aberrant due to deleterious alterations in expression and activity of respiratory chain components as a direct consequence of abnormal AMPK/PGC-1α signaling. Utilization of innovative respirometry equipment to analyze mitochondrial function of cultured adult sensory neurons from diabetic rodents shows that the outcome for cellular bioenergetics is a reduced adaptability to fluctuations in ATP demand. The diabetes-induced maladaptive process is hypothesized to result in exhaustion of the ATP supply in the distal nerve compartment and induction of nerve fiber dissolution. The role of mitochondrial dysfunction in the etiology of diabetic neuropathy is compared with other types of neuropathy with a distal dying-back pathology such as Friedreich

  9. Derivative Form of Off-axis Aberration Correction Surface and Its Application in Solar Energy Concentration

    Institute of Scientific and Technical Information of China (English)

    LI Li; CHEN Ying-Tian; HU Sen

    2009-01-01

    By using the derivative method, we obtained the same result with that of the previous work of Chen et al.in 2006.Different from the integral form, the derivative form of the surface expression published in this paper is derived from differential equation and based on the theory of non-imaging focusing heliostat proposed by Chen et al.in 2001.The comparison of the derivative form of fixed aberration correction surface has been made with that of integral form surface as well as that of spherical surface in concentrating the solar ray.

  10. Construction of special eye models for investigation of chromatic and higher-order aberrations of eyes.

    Science.gov (United States)

    Zhai, Yi; Wang, Yan; Wang, Zhaoqi; Liu, Yongji; Zhang, Lin; He, Yuanqing; Chang, Shengjiang

    2014-01-01

    An achromatic element eliminating only longitudinal chromatic aberration (LCA) while maintaining transverse chromatic aberration (TCA) is established for the eye model, which involves the angle formed by the visual and optical axis. To investigate the impacts of higher-order aberrations on vision, the actual data of higher-order aberrations of human eyes with three typical levels are introduced into the eye model along visual axis. Moreover, three kinds of individual eye models are established to investigate the impacts of higher-order aberrations, chromatic aberration (LCA+TCA), LCA and TCA on vision under the photopic condition, respectively. Results show that for most human eyes, the impact of chromatic aberration on vision is much stronger than that of higher-order aberrations, and the impact of LCA in chromatic aberration dominates. The impact of TCA is approximately equal to that of normal level higher-order aberrations and it can be ignored when LCA exists.

  11. Chromosome aberrations as biomarkers of radiation exposure: Modelling basic mechanisms

    Science.gov (United States)

    Ballarini, F.; Ottolenghi, A.

    The space radiation environment is a mixed field consisting of different particles having different energies, including high charge and energy (HZE) ions. Conventional measurements of absorbed doses may not be sufficient to completely characterise the radiation field and perform reliable estimates of health risks. Biological dosimetry, based on the observation of specific radiation-induced endpoints (typically chromosome aberrations), can be a helpful approach in case of monitored exposure to space radiation or other mixed fields, as well as in case of accidental exposure. Furthermore, various ratios of aberrations (e.g. dicentric chromosomes to centric rings and complex exchanges to simple exchanges) have been suggested as possible fingerprints of radiation quality, although all of them have been subjected to some criticisms. In this context a mechanistic model and a Monte Carlo code for the simulation of chromosome aberration induction were developed. The model, able to provide dose-responses for different aberrations (e.g. dicentrics, rings, fragments, translocations, insertions and other complex exchanges), was further developed to assess the dependence of various ratios of aberrations on radiation quality. The predictions of the model were compared with available data, whose experimental conditions were faithfully reproduced. Particular attention was devoted to the scoring criteria adopted in different laboratories and to possible biases introduced by interphase death and mitotic delay. This latter aspect was investigated by taking into account both metaphase data and data obtained with Premature Chromosome Condensation (PCC).

  12. Antimutagenic potential of curcumin on chromosomal aberrations in Allium cepa

    Institute of Scientific and Technical Information of China (English)

    RAGUNATHAN Irulappan; PANNEERSELVAM Natarajan

    2007-01-01

    Turmeric has long been used as a spice and food colouring agent in Asia. In the present investigation, the antimutagenic potential of curcumin was evaluated in Allium cepa root meristem cells. So far there is no report on the biological properties of curcumin in plant test systems. The root tip cells were treated with sodium azide at 200 and 300 μg/ml for 3 h and curcumin was given at 5, 10 and 20 μg/ml for 16 h, prior to sodium azide treatment. The tips were squashed after colchicine treatment and the cells were analyzed for chromosome aberration and mitotic index. Curcumin induces chromosomal aberration in Allium cepa root tip cells in an insignificant manner, when compared with untreated control. Sodium azide alone induces chromosomal aberrations significantly with increasing concentrations. The total number of aberrations was significantly reduced in root tip cells pretreated with curcumin. The study reveals that curcumin has antimutagenic potential against sodium azide induced chromosomal aberrations in Allium cepa root meristem cells. In addition, it showed mild cytotoxicity by reducing the percentage of mitotic index in all curcumin treated groups, but the mechanism of action remains unknown. The antimutagenic potential of curcumin is effective at 5 μg/ml in Allium cepa root meristem cells.

  13. Nuclear mRNA quality control in yeast is mediated by Nrd1 co-transcriptional recruitment, as revealed by the targeting of Rho-induced aberrant transcripts

    Science.gov (United States)

    Honorine, Romy; Mosrin-Huaman, Christine; Hervouet-Coste, Nadège; Libri, Domenico; Rahmouni, A. Rachid

    2011-01-01

    The production of mature export-competent transcripts is under the surveillance of quality control steps where aberrant mRNP molecules resulting from inappropriate or inefficient processing and packaging reactions are subject to exosome-mediated degradation. Previously, we have shown that the heterologous expression of bacterial Rho factor in yeast interferes in normal mRNP biogenesis leading to the production of full-length yet aberrant transcripts that are degraded by the nuclear exosome with ensuing growth defect. Here, we took advantage of this new tool to investigate the molecular mechanisms by which an integrated system recognizes aberrancies at each step of mRNP biogenesis and targets the defective molecules for destruction. We show that the targeting and degradation of Rho-induced aberrant transcripts is associated with a large increase of Nrd1 recruitment to the transcription complex via its CID and RRM domains and a concomitant enrichment of exosome component Rrp6 association. The targeting and degradation of the aberrant transcripts is suppressed by the overproduction of Pcf11 or its isolated CID domain, through a competition with Nrd1 for recruitment by the transcription complex. Altogether, our results support a model in which a stimulation of Nrd1 co-transcriptional recruitment coordinates the recognition and removal of aberrant transcripts by promoting the attachment of the nuclear mRNA degradation machinery. PMID:21113025

  14. Aberrant DNA methylation in breast cancer cells

    OpenAIRE

    Campoy, Emanuel Martin; Laurito, Sergio Roberto; Urrutia, Guillermo; Branham, Maria Teresita; Roque Moreno, Maria

    2016-01-01

    The epigenome is regulated by a large number of macromolecular machines that are dynamically involved in various processes, including DNA methylation, histone modification and non-coding RNA signals, all of them working together to regulate the proper expression of the genome. Thus, in contrast with the genome, whose sequence is carefully conserved during cell life, the epigenome is highly dynamic. The epigenomic modifications are acquired during normal cell differentiation, replicated d...

  15. Spherical aberration and other higher-order aberrations in the human eye : from summary wave-front analysis data to optical variables relevant to visual perception

    NARCIS (Netherlands)

    Jansonius, Nomdo M.

    2010-01-01

    Wave-front analysis data from the human eye are commonly presented using the aberration coefficient c(4)(0) (primary spherical aberration) together with an overall measure of all higher-order aberrations. If groups of subjects are compared, however, the relevance of an observed difference cannot eas

  16. ∆DNMT3B4-del Contributes to Aberrant DNA Methylation Patterns in Lung Tumorigenesis

    Directory of Open Access Journals (Sweden)

    Mark Z. Ma

    2015-10-01

    Full Text Available Aberrant DNA methylation is a hallmark of cancer but mechanisms contributing to the abnormality remain elusive. We have previously shown that ∆DNMT3B is the predominantly expressed form of DNMT3B. In this study, we found that most of the lung cancer cell lines tested predominantly expressed DNMT3B isoforms without exons 21, 22 or both 21 and 22 (a region corresponding to the enzymatic domain of DNMT3B termed DNMT3B/∆DNMT3B-del. In normal bronchial epithelial cells, DNMT3B/ΔDNMT3B and DNMT3B/∆DNMT3B-del displayed equal levels of expression. In contrast, in patients with non-small cell lung cancer NSCLC, 111 (93% of the 119 tumors predominantly expressed DNMT3B/ΔDNMT3B-del, including 47 (39% tumors with no detectable DNMT3B/∆DNMT3B. Using a transgenic mouse model, we further demonstrated the biological impact of ∆DNMT3B4-del, the ∆DNMT3B-del isoform most abundantly expressed in NSCLC, in global DNA methylation patterns and lung tumorigenesis. Expression of ∆DNMT3B4-del in the mouse lungs resulted in an increased global DNA hypomethylation, focal DNA hypermethylation, epithelial hyperplastia and tumor formation when challenged with a tobacco carcinogen. Our results demonstrate ∆DNMT3B4-del as a critical factor in developing aberrant DNA methylation patterns during lung tumorigenesis and suggest that ∆DNMT3B4-del may be a target for lung cancer prevention.

  17. Correction of low order aberrations using continuous deformable mirrors.

    Science.gov (United States)

    Vdovin, Gleb; Soloviev, Oleg; Samokhin, Alexander; Loktev, Mikhail

    2008-03-03

    By analyzing the Poisson equation describing the static behavior of membrane and bimorph deformable mirrors and biharmonic equation describing the continuous facesheet mirror with push-pull actuators, we found that to achieve a high quality correction of low-order aberrations these mirrors should have sufficient number of actuators positioned outside the correction aperture. In particular, any deformable mirror described by the Poisson equation requires at least two actuators to be placed outside the working aperture per period of the azimuthal aberration of the highest expected order. Any deformable mirror described by the biharmonic equation, such as a continuous facesheet mirror with push-pull actuators, requires at least four actuators to be placed outside the working aperture per period of the azimuthal aberration of the highest expected order, and these actuators should not be positioned on a single circle.

  18. Non-Gaussianity and CMB aberration and Doppler

    CERN Document Server

    Catena, Riccardo; Notari, Alessio; Renzi, Alessandro

    2013-01-01

    The peculiar motion of an observer with respect to the CMB rest frame induces a deflection in the arrival direction of the observed photons (also known as CMB aberration) and a Doppler shift in the measured photon frequencies. As a consequence, aberration and Doppler effects induce non trivial correlations between the harmonic coefficients of the observed CMB temperature maps. In this paper we investigate whether these correlations generate a bias on Non-Gaussianity estimators $f_{NL}$. We perform this analysis simulating a large number of temperature maps with Planck-like resolution (lmax $= 2000$) as different realizations of the same cosmological fiducial model (WMAP7yr). We then add to these maps aberration and Doppler effects employing a modified version of the HEALPix code. We finally evaluate a generalization of the Komatsu, Spergel and Wandelt Non-Gaussianity estimator for all the simulated maps, both when peculiar velocity effects have been considered and when these phenomena have been neglected. Usi...

  19. An approach to remove defocused aberration on array confocal microscope

    Science.gov (United States)

    Huang, Xiangdong; Zhou, Tong; Jia, Jingguo

    2013-01-01

    In order to obtain a high resolution image required for ultra-precision measurement of microstructural object, a new approach is proposed for 3D microstructures. It uses the modulation transfer function with defocus aberration based on the ambiguity function and stable phase principle to achieve an optical phase filter, and utilizes generalized a spheric phase optical element to encode defocus images, and uses deconvolution technology to recover the images. In comparison with conventional optical system, the phase filter used in the optical system can make focal spot smaller when measure object defocusing, eliminates the effect of the defocus aberration, and improves the defocused property. Numerical results indicate the designed phase filter can improve lateral resolution of optical system, and the axial resolution of the optical system is not affect by the filter and defocus aberration. For different defocus plate, the phase filter can make character of modulation transfer function of lateral direction uniform approximation.

  20. Dynamic compensation of chromatic aberration in a programmable diffractive lens.

    Science.gov (United States)

    Millán, María S; Otón, Joaquín; Pérez-Cabré, Elisabet

    2006-10-02

    A proposal to dynamically compensate chromatic aberration of a programmable phase Fresnel lens displayed on a liquid crystal device and working under broadband illumination is presented. It is based on time multiplexing a set of lenses, designed with a common focal length for different wavelengths, and a tunable spectral filter that makes each sublens work almost monochromatically. Both the tunable filter and the sublens displayed by the spatial light modulator are synchronized. The whole set of sublenses are displayed within the integration time of the sensor. As a result the central order focalization has a unique location at the focal plane and it is common for all selected wavelengths. Transversal chromatic aberration of the polychromatic point spread function is reduced by properly adjusting the pupil size of each sublens. Longitudinal chromatic aberration is compensated by making depth of focus curves coincident for the selected wavelengths. Experimental results are in very good agreement with theory.

  1. Measuring chromatic aberrations in imaging systems using plasmonic nanoparticles

    Science.gov (United States)

    Gennaro, Sylvain D.; Roschuk, Tyler R.; Maier, Stefan A.; Oulton, Rupert F.

    2016-04-01

    Chromatic aberration in optical systems arises from the wavelength dependence of a glass's refractive index. Polychromatic rays incident upon an optical surface are refracted at slightly different angles and in traversing an optical system follow distinct paths creating images displaced according to color. Although arising from dispersion, it manifests as a spatial distortion correctable only with compound lenses with multiple glasses and accumulates in complicated imaging systems. While chromatic aberration is measured with interferometry, simple methods are attractive for their ease of use and low cost. In this letter we retrieve the longitudinal chromatic focal shift of high numerical aperture (NA) microscope objectives from the extinction spectra of metallic nanoparticles within the focal plane. The method is accurate for high NA objectives with apochromatic correction, and enables rapid assessment of the chromatic aberration of any complete microscopy systems, since it is straightforward to implement

  2. Low chromatic aberration hexapole for molecular state selection

    Science.gov (United States)

    Ke, Yi; Deng, Xiao-Bing; Hu, Zhong-Kun

    2016-01-01

    In molecular beam state-selection experiments, the electrostatic hexapole acts as an optical lens, imaging molecules from the source to the focus. The molecular longitudinal velocity spread induces the phenomenon of chromatic aberration, which will reduce the state-selection purity. We propose a scheme which can effectively reduce the chromatic aberration by changing the hexapole voltage operating manner. The hexapole is already charged before molecules arrive at the entrance of the hexapole. When molecules are completely inside the hexapole, the voltage is switched off rapidly at an appropriate time. In this manner, faster molecules travel a longer hexapole focusing region than slower molecules. Therefore the focusing positions of molecules with different velocities become close. Numerical trajectory simulations of molecular state selection are carried out, and the results show that this low chromatic aberration hexapole can significantly improve the state purity from 46.2% to 87.0%.

  3. Split-plot fractional designs: Is minimum aberration enough?

    DEFF Research Database (Denmark)

    Kulahci, Murat; Ramirez, Jose; Tobias, Randy

    2006-01-01

    Split-plot experiments are commonly used in industry for product and process improvement. Recent articles on designing split-plot experiments concentrate on minimum aberration as the design criterion. Minimum aberration has been criticized as a design criterion for completely randomized fractional...... factorial design and alternative criteria, such as the maximum number of clear two-factor interactions, are suggested (Wu and Hamada (2000)). The need for alternatives to minimum aberration is even more acute for split-plot designs. In a standard split-plot design, there are several types of two...... for completely randomized designs. Consequently, we provide a modified version of the maximum number of clear two-factor interactions design criterion to be used for split-plot designs....

  4. Prospects for electron beam aberration correction using sculpted phase masks.

    Science.gov (United States)

    Shiloh, Roy; Remez, Roei; Arie, Ady

    2016-04-01

    Technological advances in fabrication methods allowed the microscopy community to take incremental steps towards perfecting the electron microscope, and magnetic lens design in particular. Still, state of the art aberration-corrected microscopes are yet 20-30 times shy of the theoretical electron diffraction limit. Moreover, these microscopes consume significant physical space and are very expensive. Here, we show how a thin, sculpted membrane is used as a phase-mask to induce specific aberrations into an electron beam probe in a standard high resolution TEM. In particular, we experimentally demonstrate beam splitting, two-fold astigmatism, three-fold astigmatism, and spherical aberration. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. An electron microscope for the aberration-corrected era.

    Science.gov (United States)

    Krivanek, O L; Corbin, G J; Dellby, N; Elston, B F; Keyse, R J; Murfitt, M F; Own, C S; Szilagyi, Z S; Woodruff, J W

    2008-02-01

    Improved resolution made possible by aberration correction has greatly increased the demands on the performance of all parts of high-end electron microscopes. In order to meet these demands, we have designed and built an entirely new scanning transmission electron microscope (STEM). The microscope includes a flexible illumination system that allows the properties of its probe to be changed on-the-fly, a third-generation aberration corrector which corrects all geometric aberrations up to fifth order, an ultra-responsive yet stable five-axis sample stage, and a flexible configuration of optimized detectors. The microscope features many innovations, such as a modular column assembled from building blocks that can be stacked in almost any order, in situ storage and cleaning facilities for up to five samples, computer-controlled loading of samples into the column, and self-diagnosing electronics. The microscope construction is described, and examples of its capabilities are shown.

  6. Split-plot fractional designs: Is minimum aberration enough?

    DEFF Research Database (Denmark)

    Kulahci, Murat; Ramirez, Jose; Tobias, Randy

    2006-01-01

    Split-plot experiments are commonly used in industry for product and process improvement. Recent articles on designing split-plot experiments concentrate on minimum aberration as the design criterion. Minimum aberration has been criticized as a design criterion for completely randomized fractional...... factorial design and alternative criteria, such as the maximum number of clear two-factor interactions, are suggested (Wu and Hamada (2000)). The need for alternatives to minimum aberration is even more acute for split-plot designs. In a standard split-plot design, there are several types of two...... for completely randomized designs. Consequently, we provide a modified version of the maximum number of clear two-factor interactions design criterion to be used for split-plot designs....

  7. Differential aberration correction (DAC) microscopy: a new molecular ruler.

    Science.gov (United States)

    Vallotton, P

    2008-11-01

    Considerable efforts have been deployed towards measuring molecular range distances in fluorescence microscopy. In the 1-10 nm range, Förster energy transfer microscopy is difficult to beat. Above 300 nm, conventional diffraction limited microscopy is suitable. We introduce a simple experimental technique that allows bridging the gap between those two resolution scales in both 2D and 3D with a resolution of about 20 nm. The method relies on a computational approach to accurately correct optical aberrations over the whole field of view. The method is differential because the probes of interest are affected in exactly the same manner by aberrations as are the reference probes used to construct the aberration deformation field. We expect that this technique will have significant implications for investigating structural and functional questions in bio-molecular sciences.

  8. Correcting the Chromatic Aberration in Barrel Distortion of Endoscopic Images

    Directory of Open Access Journals (Sweden)

    Y. M. Harry Ng

    2003-04-01

    Full Text Available Modern endoscopes offer physicians a wide-angle field of view (FOV for minimally invasive therapies. However, the high level of barrel distortion may prevent accurate perception of image. Fortunately, this kind of distortion may be corrected by digital image processing. In this paper we investigate the chromatic aberrations in the barrel distortion of endoscopic images. In the past, chromatic aberration in endoscopes is corrected by achromatic lenses or active lens control. In contrast, we take a computational approach by modifying the concept of image warping and the existing barrel distortion correction algorithm to tackle the chromatic aberration problem. In addition, an error function for the determination of the level of centroid coincidence is proposed. Simulation and experimental results confirm the effectiveness of our method.

  9. The BHVI-EyeMapper: peripheral refraction and aberration profiles.

    Science.gov (United States)

    Fedtke, Cathleen; Ehrmann, Klaus; Falk, Darrin; Bakaraju, Ravi C; Holden, Brien A

    2014-10-01

    The aim of this article was to present the optical design of a new instrument (BHVI-EyeMapper, EM), which is dedicated to rapid peripheral wavefront measurements across the visual field for distance and near, and to compare the peripheral refraction and higher-order aberration profiles obtained in myopic eyes with and without accommodation. Central and peripheral refractive errors (M, J180, and J45) and higher-order aberrations (C[3, 1], C[3, 3], and C[4, 0]) were measured in 26 myopic participants (mean [±SD] age, 20.9 [±2.0] years; mean [±SD] spherical equivalent, -3.00 [±0.90] diopters [D]) corrected for distance. Measurements were performed along the horizontal visual field with (-2.00 to -5.00 D) and without (+1.00 D fogging) accommodation. Changes as a function of accommodation were compared using tilt and curvature coefficients of peripheral refraction and aberration profiles. As accommodation increased, the relative peripheral refraction profiles of M and J180 became significantly (p 0.05). The peripheral aberration profiles of C[3, 1], C[3, 3], and C[4, 0] became significantly (p refraction and higher-order aberration profiles occurred during accommodation in myopic eyes. With its extended measurement capabilities, that is, permitting rapid peripheral refraction and higher-order aberration measurements up to visual field angles of ±50 degrees for distance and near (up to -5.00 D), the EM is a new advanced instrument that may provide additional insights in the ongoing quest to understand and monitor myopia development.

  10. Adaptive and aberrant reward prediction signals in the human brain

    Science.gov (United States)

    Roiser, Jonathan P.; Stephan, Klaas E.; den Ouden, Hanneke E.M.; Friston, Karl J.; Joyce, Eileen M.

    2010-01-01

    Theories of the positive symptoms of schizophrenia hypothesize a role for aberrant reinforcement signaling driven by dysregulated dopamine transmission. Recently, we provided evidence of aberrant reward learning in symptomatic, but not asymptomatic patients with schizophrenia, using a novel paradigm, the Salience Attribution Test (SAT). The SAT is a probabilistic reward learning game that employs cues that vary across task-relevant and task-irrelevant dimensions; it provides behavioral indices of adaptive and aberrant reward learning. As an initial step prior to future clinical studies, here we used functional magnetic resonance imaging to examine the neural basis of adaptive and aberrant reward learning during the SAT in healthy volunteers. As expected, cues associated with high relative to low reward probabilities elicited robust hemodynamic responses in a network of structures previously implicated in motivational salience; the midbrain, in the vicinity of the ventral tegmental area, and regions targeted by its dopaminergic projections, i.e. medial dorsal thalamus, ventral striatum and prefrontal cortex (PFC). Responses in the medial dorsal thalamus and polar PFC were strongly correlated with the degree of adaptive reward learning across participants. Finally, and most importantly, differential dorsolateral PFC and middle temporal gyrus (MTG) responses to cues with identical reward probabilities were very strongly correlated with the degree of aberrant reward learning. Participants who showed greater aberrant learning exhibited greater dorsolateral PFC responses, and reduced MTG responses, to cues erroneously inferred to be less strongly associated with reward. The results are discussed in terms of their implications for different theories of associative learning. PMID:19969090

  11. Focus correction in an apodized system with spherical aberration.

    Science.gov (United States)

    Bernal-Molina, Paula; Castejón-Mochón, José Francisco; Bradley, Arthur; López-Gil, Norberto

    2015-08-01

    We performed a theoretical and computational analysis of the through-focus axial irradiance in a system with a Gaussian amplitude pupil function and fourth- and sixth-order spherical aberration (SA). Two cases are analyzed: low aberrated systems, and the human eye containing significant levels of SA and a natural apodization produced by the Stiles-Crawford effect. Results show that apodization only produces a refraction change of the plane that maximized the Strehl ratio for eyes containing significant levels of negative SA.

  12. Generalized beam quality factor of aberrated truncated Gaussian laser beams

    CSIR Research Space (South Africa)

    Mafusire, C

    2011-07-01

    Full Text Available factor of aberrated truncated Gaussian laser beams Cosmas Mafusire1,2 and Andrew Forbes1,2,* 1Council for Scientific and Industrial Research National Laser Centre, P.O. Box 395, Pretoria, South Africa 2School of Physics, University of Kwa... is verified experimentally by implementing aberrations as digital holograms in the laboratory. ? 2011 Optical Society of America OCIS codes: 140.3295, 080.1005, 120.5050. 1. INTRODUCTION The laser beam quality factor (M2) is a useful parameter...

  13. [Prenatal diagnostics of chromosomal aberrations Czech Republic: 1994-2007].

    Science.gov (United States)

    Gregor, V; Sípek, A; Sípek, A; Horácek, J '; Langhammer, P; Petrzílková, L; Calda, P

    2009-02-01

    An analysis of prenatal diagnostics efficiency of selected types of chromosomal aberrations in the Czech Republic in 2007. Update of 1994-2007 data according to particular selected diagnoses. Retrospective epidemiological analysis of pre- and postnatal chromosomal aberrations diagnostics and its efficiency. Data on pre- and postnatally diagnosed birth defects in the Czech Republic during 1994-2007 were used. Data on prenatally diagnosed birth defects (and for terminated pregnancies) were collected from particular departments of prenatal diagnostics, medical genetics and ultrasound diagnostics in the Czech Republic, data on birth defects in births from the National Birth Defects Register (Institute for Health Information and Statistics). Total numbers over the period under the study, mean incidences of selected types of chromosomal aberrations and mean prenatal diagnostics efficiencies were analyzed. Following chromosomal aberrations were studied: Down, Edwards, Patau, Turner and Klinefelter syndromes and syndromes 47,XXX and 47,XYY. A relative proportion of Down, Edwards and Patau syndromes as well as other autosomal and gonosomal aberration is presented in figures. Recently, trisomies 13, 18 and 21 present around 70% of all chromosomal aberrations in selectively aborted fetuses, in other pregnancies, "other chromosomal aberrations" category (mostly balanced reciprocal translocations and inversions) present more than 2/3 of all diagnoses. During the period under the study, following total numbers, mean relative incidences (per 10,000 live births, in brackets) and mean prenatal diagnostics efficiency (in %) were found in following chromosomal syndromes: Down syndrome 2,244 (16.58) and 63.37%, Edwards syndrome 521 (3.85) and 79.93%, Patau syndrome 201 (1.49) and 68.87%, Turner syndrome 380 (2.81) and 79.89%, 47,XXX syndrome 61 (0.45) and 59.74%, Klinefelter syndrome 163 (1.20) and 73.65% and 47,XYY syndrome 22 (0.16) and 54.76%. The study gives updated results of

  14. Aberrations of the point spread function of a multimode fiber

    CERN Document Server

    Descloux, Adrien; Pinkse, Pepijn W H

    2016-01-01

    We investigate the point spread function of a multimode fiber. The distortion of the focal spot created on the fiber output facet is studied for a variety of the parameters. We develop a theoretical model of wavefront shaping through a multimode fiber and use it to confirm our experimental results and analyze the nature of the focal distortions. We show that aberration-free imaging with a large field of view can be achieved by using an appropriate number of segments on the spatial light modulator during the wavefront-shaping procedure. The results describe aberration limits for imaging with multimode fibers as in, e.g., microendoscopy.

  15. Aberration compensation and resolution improvement of focus modulation microscopy

    Science.gov (United States)

    Zheng, Juanjuan; Gao, Peng; Shao, Xiaopeng

    2017-01-01

    Confocal laser scanning microscopy (CLSM) has wide applications in biological research and medical diagnosis. However, the spatial resolution and signal to noise ratio (SNR) of CLSM is reduced in the presence of an aberration. Here we improve the pupil-segmentation method to measure and compensate for aberrations in focus modulation CLSM (FM-CLSM), which uses Gaussian-type and doughnut-like foci to scan a sample in sequence. As a result, FM-CLSM can provide images with a high resolution and a high SNR for biomedical or industrial applications.

  16. Chromosomal aberrations in plants under magnetic fluid influence

    Energy Technology Data Exchange (ETDEWEB)

    Pavel, Angela [University of Medicine and Pharmacy Gr.T. Popa, Fac. of Pharmacy, Iasi (Romania)]. E-mail: angelapavel04@yahoo.com; Creanga, Dorina-Emilia [Faculty of Physics, University of Al. I. Cuza, Bd. Copou 11A, Iasi (Romania)]. E-mail: dorinacreanga@yahoo.com

    2005-03-15

    The study was focussed on the influence of a petroleum magnetic fluid upon the cell proliferation in young plants of agricultural interest. Zea mays plants, in their early ontogenetic stages were treated with magnetic fluid in relatively low concentrations (up to 100{mu}l/l) and root meristem was investigated by cytogenetical methods. The cell proliferation rate was found significantly enhanced as well as the percentage of chromosomal aberrations. Micronuclei, bridges, chromosome fragments and three-polar anaphases were the main types of chromosomal aberrations.

  17. Double aberration correction in a low-energy electron microscope

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, Th., E-mail: schmidtt@fhi-berlin.mpg.de [Fritz-Haber-Institut der Max-Planck-Gesellschaft, Faradayweg 6-8, D-14195 Berlin (Germany); Universitaet Wuerzburg, Experimentelle Physik II, Am Hubland, D-97074 Wuerzburg (Germany); Marchetto, H.; Levesque, P.L. [Fritz-Haber-Institut der Max-Planck-Gesellschaft, Faradayweg 6-8, D-14195 Berlin (Germany); Groh, U.; Maier, F. [Universitaet Wuerzburg, Experimentelle Physik II, Am Hubland, D-97074 Wuerzburg (Germany); Preikszas, D. [Technische Universitaet Darmstadt, Angewandte Physik, Hochschulstrasse 6, D-64289 Darmstadt (Germany); Carl Zeiss NTS GmbH, Carl-Zeiss-Strasse 56, D-73447 Oberkochen (Germany); Hartel, P.; Spehr, R. [Technische Universitaet Darmstadt, Angewandte Physik, Hochschulstrasse 6, D-64289 Darmstadt (Germany); Lilienkamp, G. [Technische Universitaet Clausthal, Physikalisches Institut, Leibnizstrasse 4, D-38678 (Germany); Engel, W. [Fritz-Haber-Institut der Max-Planck-Gesellschaft, Faradayweg 6-8, D-14195 Berlin (Germany); Fink, R. [Universitaet Erlangen-Nuernberg, Physikalische Chemie II, Egerlandstrasse 3, D-91058 Erlangen (Germany); Bauer, E. [Technische Universitaet Clausthal, Physikalisches Institut, Leibnizstrasse 4, D-38678 (Germany); Arizona State University, Department of Physics, Tempe, AZ 85287 (United States); Rose, H. [Technische Universitaet Darmstadt, Angewandte Physik, Hochschulstrasse 6, D-64289 Darmstadt (Germany); Umbach, E. [Universitaet Wuerzburg, Experimentelle Physik II, Am Hubland, D-97074 Wuerzburg (Germany); Freund, H.-J. [Fritz-Haber-Institut der Max-Planck-Gesellschaft, Faradayweg 6-8, D-14195 Berlin (Germany)

    2010-10-15

    The lateral resolution of a surface sensitive low-energy electron microscope (LEEM) has been improved below 4 nm for the first time. This breakthrough has only been possible by simultaneously correcting the unavoidable spherical and chromatic aberrations of the lens system. We present an experimental criterion to quantify the aberration correction and to optimize the electron optical system. The obtained lateral resolution of 2.6 nm in LEEM enables the first surface sensitive, electron microscopic observation of the herringbone reconstruction on the Au(1 1 1) surface.

  18. Pan-cancer analysis of ROS1 genomic aberrations

    OpenAIRE

    Wang, Yidan; 王奕丹

    2015-01-01

    The ROS proto-oncogene 1 (ROS1) encodes the ROS1 receptor kinase. ROS1 rearrangements are known to be oncogenic in glioblastoma, non–small-cell lung carcinoma (NSCLC) and cholangiocarcinoma. The clinical relevance of ROS1 genomic aberrations in other human cancers is largely unexamined. Here, we performed a pan-cancer analysis of ROS1 genomic aberrations across 20 cancer sites by interrogating the whole-exome sequencing data of the Cancer Genome Atlas (TCGA) via the cBioportal (www.cbioportal...

  19. Inhibition of lysine-specific demethylase 1 by polyamine analogues results in reexpression of aberrantly silenced genes.

    Science.gov (United States)

    Huang, Yi; Greene, Eriko; Murray Stewart, Tracy; Goodwin, Andrew C; Baylin, Stephen B; Woster, Patrick M; Casero, Robert A

    2007-05-08

    Epigenetic chromatin modification is a major regulator of eukaryotic gene expression, and aberrant epigenetic silencing of gene expression contributes to tumorigenesis. Histone modifications include acetylation, phosphorylation, and methylation, resulting in a combination of histone marks known collectively as the histone code. The chromatin marks at a given promoter determine, in part, whether specific promoters are in an open/active conformation or closed/repressed conformation. Dimethyl-lysine 4 histone H3 (H3K4me2) is a transcription-activating chromatin mark at gene promoters, and demethylation of this mark by the lysine-specific demethylase 1 (LSD1), a homologue of polyamine oxidases, may broadly repress gene expression. We now report that novel biguanide and bisguanidine polyamine analogues are potent inhibitors of LSD1. These analogues inhibit LSD1 in human colon carcinoma cells and affect a reexpression of multiple, aberrantly silenced genes important in the development of colon cancer, including members of the secreted frizzle-related proteins (SFRPs) and the GATA family of transcription factors. Furthermore, we demonstrate by chromatin immunoprecipitation analysis that the reexpression is concurrent with increased H3K4me2 and acetyl-H3K9 marks, decreased H3K9me1 and H3K9me2 repressive marks. We thus define important new agents for reversing aberrant repression of gene transcription.

  20. Aberrant Cx26 Hemichannels and Keratitis-Ichthyosis-Deafness Syndrome: Insights into Syndromic Hearing Loss

    Directory of Open Access Journals (Sweden)

    Helmuth Alberto Sanchez

    2014-10-01

    Full Text Available Mutation of the GJB2 gene, which encodes the connexin Cx26 gap junction (GJ protein, is the most common cause of hereditary, sensorineural hearing loss. Cx26 is not expressed in hair cells, but is widely expressed throughout the non-sensory epithelial cells of the cochlea. Most GJB2 mutations produce non-syndromic deafness, but a subset produces syndromic deafness in which profound hearing loss is accompanied by a diverse array of infectious and neoplastic cutaneous disorders that can be fatal. Although GJ channels, which are assembled by the docking of two, so-called hemichannels (HCs, have been the main focus of deafness-associated disease models, it is now evident that the HCs themselves can function in the absence of docking and contribute to signaling across the cell membrane as a novel class of ion channel. A notable feature of syndromic deafness mutants is that the HCs exhibit aberrant behaviors providing a plausible basis for disease that is associated with excessive or altered contributions of Cx26 HCs that, in turn, lead to compromised cell integrity. Here we discuss some of the aberrant Cx26 HC properties that have been described for mutants associated with keratitis-ichthyosis-deafness (KID syndrome, a particularly severe Cx26-associated syndrome, which shed light on genotype-phenotype relationships and causes underlying cochlear dysfunction.

  1. Osteoponin Promoter Controlled by DNA Methylation: Aberrant Methylation in Cloned Porcine Genome

    Directory of Open Access Journals (Sweden)

    Chih-Jie Shen

    2014-01-01

    Full Text Available Cloned animals usually exhibited many defects in physical characteristics or aberrant epigenetic reprogramming, especially in some important organ development. Osteoponin (OPN is an extracellular-matrix protein involved in heart and bone development and diseases. In this study, we investigated the correlation between OPN mRNA and its promoter methylation changes by the 5-aza-dc treatment in fibroblast cell and promoter assay. Aberrant methylation of porcine OPN was frequently found in different tissues of somatic nuclear transferred cloning pigs, and bisulfite sequence data suggested that the OPN promoter region −2615 to −2239 nucleotides (nt may be a crucial regulation DNA element. In pig ear fibroblast cell culture study, the demethylation of OPN promoter was found in dose-dependent response of 5-aza-dc treatment and followed the OPN mRNA reexpression. In cloned pig study, discrepant expression pattern was identified in several cloned pig tissues, especially in brain, heart, and ear. Promoter assay data revealed that four methylated CpG sites presenting in the −2615 to −2239 nt region cause significant downregulation of OPN promoter activity. These data suggested that methylation in the OPN promoter plays a crucial role in the regulation of OPN expression that we found in cloned pigs genome.

  2. Involvement of Aberrant Glycosylation in Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Eiji Miyoshi

    2010-01-01

    Full Text Available Glycosylation is one of the most common posttranslational modification reactions and nearly half of all known proteins in eukaryotes are glycosylated. In fact, changes in oligosaccharides structures are associated with many physiological and pathological events, including cell growth, migration and differentiation, and tumor invasion. Therefore, functional glycomics, which is a comprehensive study of the structures and functions of glycans, is attracting the increasing attention of scientists in various fields of life science. In cases of thyroid cancer, the biological characters and prognosis are completely different in each type of histopathology, and their oligosaccharide structures as well as the expression of glycosyltransferases are also different. In this review, we summarized our previous papers on oligosaccharides and thyroid cancers and discussed a possible function of oligosaccharides in the carcinogenesis in thyroid cancer.

  3. Aberrant activation of Sonic hedgehog signaling in chronic cholecystitis and gallbladder carcinoma.

    Science.gov (United States)

    Xie, Fang; Xu, Xiaoping; Xu, Angao; Liu, Cuiping; Liang, Fenfen; Xue, Minmin; Bai, Lan

    2014-03-01

    Sonic hedgehog (Shh) signaling has been extensively studied and is implicated in various inflammatory diseases and malignant tumors. We summarized the clinicopathological features and performed immunohistochemistry assays to examine expression of Shh signaling proteins in 10 normal mucosa, 32 gallbladder carcinoma (GBC), and 95 chronic cholecystitis (CC) specimens. The CC specimens were classified into three groups according to degree of inflammation. Compared with normal mucosa, CC, and GBC specimens exhibited increased expression of Shh. The immunoreactive score of Shh in the GBC group was higher than that in the mild to moderate CC groups but lower than that in the severe CC group (P cholecystitis to malignant tumors. Compared with CC specimens, GBC specimens showed higher cytoplasmic and membranous expression for Ptch (P < .05). Gli1 staining showed cytoplasmic expression of Gli1 in both CC (60% for mild, 77% for moderate, and 84% for severe) and GBC specimens (97%). Nuclear expression of Gli1 was detected in 16% of severe CC specimens with moderate to poor atypical hyperplasia, and in 62.5% of GBC specimens. Shh expression strongly correlated with expression of Ptch and Gli1. Furthermore, patients with strongly positive Gli1 staining had significantly lower survival rates than those with weakly positive staining. Our data indicate that the Shh signaling pathway is aberrantly activated in CC and GBC, and altered Shh signaling may be involved in the course of development from CC to gallbladder carcinogenesis.

  4. Effect of Coma Aberration on Orbital Angular Momentum Spectrum of Vortex Beams

    Institute of Scientific and Technical Information of China (English)

    CHEN Zi-Yang; PU Ji-Xiong

    2009-01-01

    Spiral spectra of vortex beams with coma aberration are studied.It is shown that the orbital angular momentum (OAM) states of vortex beams with coma aberration are different from those aberration-free vortex beams.Spiral spectra of beams with coma aberration are spreading.It is found that in the presence of coma aberration,the vortex beams contain not only the original OAM component but also other components.A larger coma aberration coefficient and/or a larger beam waist will lead to a wider spreading of the spiral spectrum. The results may have potential applications in information encoding and transmittance.

  5. Aberration of a negative ion beam caused by space charge effect

    Energy Technology Data Exchange (ETDEWEB)

    Miyamoto, K. [Naruto University of Education, 748 Nakashima, Takashima, Naruto-cho, Naruto-shi, Tokushima 772-8502 (Japan); Wada, S.; Hatayama, A. [Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522 (Japan)

    2010-02-15

    Aberrations are inevitable when the charged particle beams are extracted, accelerated, transmitted, and focused with electrostatic and magnetic fields. In this study, we investigate the aberration of a negative ion accelerator for a neutral beam injector theoretically, especially the spherical aberration caused by the negative ion beam expansion due to the space charge effect. The negative ion current density profiles with the spherical aberration are compared with those without the spherical aberration. It is found that the negative ion current density profiles in a log scale are tailed due to the spherical aberration.

  6. The Aberrant Salience Inventory: A New Measure of Psychosis Proneness

    Science.gov (United States)

    Cicero, David C.; Kerns, John G.; McCarthy, Denis M.

    2010-01-01

    Aberrant salience is the unusual or incorrect assignment of salience, significance, or importance to otherwise innocuous stimuli and has been hypothesized to be important for psychosis and psychotic disorders such as schizophrenia. Despite the importance of this concept in psychosis research, no questionnaire measures are available to assess…

  7. The pterygo-spinous muscle--an aberrant (atavic) remnant.

    Science.gov (United States)

    Nathan, H

    1989-01-01

    We report here on an aberrant pterygoid muscle found during a dissection of the infratemporal fossa. We have not noted such a muscle in hundreds of dissections in the area. A few anatomical texts (Piersol, 1911; Testut, Latarjet, 1931) have referred to its possible existence as the pterygo-spinous muscle.

  8. Aberrant behavior of preschool children: Evaluation of questionnaire

    Directory of Open Access Journals (Sweden)

    Fajgelj Stanislav

    2007-01-01

    Full Text Available In the study metric characteristics of children aberrant behavior questionnaire were analyzed. The analysis was performed on the sample of 1.165 children, aged 4-7, in preschool institutions in several towns of Vojvodina. The questionnaire contained 36 items of the Likert-type scale and was filled in by one parent of each child. The authors examined main metric characteristics of the complete questionnaire, as well as individual items under the Rasche’s measurement model. Generally, parents seldom notice aberrant behavior in their children. Most frequently they notice stubbornness, while very rarely torturing of animals. The item discrimination, on the whole, was found satisfying. The reliability of the questionnaire is 0.84., and all indicators of misfit are within satisfactory ranges. According to differential functioning of the items, the authors found gender and age specificities of parents’ evaluation of aberrant behavior of their children. Parents often notice stubbornness and moldiness in girls, and aggression in boys. According to the parent’s observations, younger children are characterized by nail nibbling, ticklishness, and fearfulness, whereas older children show a tendency to force their way by crying, waywardness and bed-wetting. By means of factor analysis of the items, three principal facets of aberrant behavior were determined: overindulgence, shyness and quarrelsomeness. Cross validation (hold out showed that these three facets were robust in relation to the selection of the sample.

  9. Using Aberrant Behaviors as Reinforcers for Autistic Children.

    Science.gov (United States)

    Charlop, Marjorie H.; And Others

    1990-01-01

    Three experiments assessed the efficacy of various reinforcers to increase correct task responding in a total of 10 autistic children, aged 6-9. Of the reinforcers used (stereotypy, delayed echolalia, perseverative behavior, and food), task performance was highest with opportunities to engage in aberrant behaviors, and lowest with edible…

  10. Thermal lensing measurement from the coefficient of defocus aberration

    CSIR Research Space (South Africa)

    Bell, Teboho

    2016-03-01

    Full Text Available We measured the thermally induced lens from the coefficient of defocus aberration using a Shack-Hartmann wavefront sensor (SHWFS). As a calibration technique, we infer the focal length of standard lenses probed by a collimated Gaussian beam...

  11. Aberrant nerve fibres within the central nervous system.

    Science.gov (United States)

    Moffie, D

    1992-01-01

    Three cases of aberrant nerve fibres in the spinal cord and medulla oblongata are described. The literature on these fibres is discussed and their possible role in regeneration. Different views on the possibility of regeneration or functional recovery of the central nervous system are mentioned in the light of recent publications, which are more optimistic than before.

  12. Intrachanges as part of complex chromosome-type exchange aberrations

    NARCIS (Netherlands)

    Boei, JJWA; Vermeulen, S; Moser, J; Mullenders, LHF; Natarajan, AT

    2002-01-01

    The chromosome-type exchange aberrations induced by ionizing radiation during the G(0)/G(1) phase of the cell cycle are believed to be the result of illegitimate rejoining of chromosome breaks. From numerous studies using chromosome painting, it has emerged that even after a moderate dose of

  13. Thermally induced lensing determination from the coefficient of defocus aberration

    CSIR Research Space (South Africa)

    Bell, Teboho

    2014-07-01

    Full Text Available The effects of a temperature gradient in a laser crystal in an end-pumped configuration in a solid-state laser resonator results in thermally induced aberrations. Of particular interest we measure the thermally induced lens from the coefficient...

  14. [Cytogenetic aberrations in histologically benign infiltratively growing sphenoid wing meningiomas].

    Science.gov (United States)

    Korshunov, A G; Cherekaev, V A; Bekiashev, A Kh; Sycheva, R V

    2007-01-01

    Meningiomas of the sphenoid wing (SW) frequently show an invasive pattern of growth and cause destruction of the adjacent structures. As a result, the rate of recurrent SW meningiomas is as high as 30%. Cytogenetic investigations showed no aberrations specific to invasively growing meningiomas. During this study, the authors evaluated 10 invasive and 5 non-invasive SW meningiomas via comparative genome hybridization (CGH) (matrix CGH), by using the gene chips of GenoSensor Array micromatrixes. The mean number of aberrations in the tumor cells was much greater in case of invasive meningiomas (67.4 versus 40.5 in case of non-invasive SW meningiomas. Furthermore, in invasive SW meningiomas, there were frequently losses in loci 1p, 6q, and 14q and gains in loci 15q and 10, which had been predetermined as molecular markers of stepwise progression of meningioma. Thus, the presence of a complex cytogenetic profile and progression-associated chromosome aberrations in benign SW meningiomas is linked with the increase of their invasive potential. Due to the fact that there are no well-defined adjuvant therapy regimens for recurring meningiomas at present, the revealed genomic aberrations may become potential targets for searching for drugs and a therapeutic intervention in future.

  15. Flare and lens aberration requirements for EUV lithographic tools

    Science.gov (United States)

    Lee, Sang Hun; Shroff, Yashesh; Chandhok, Manish

    2005-05-01

    EUV lithographic tools can support the 32 nm MPU manufacturing node and beyond. In order to meet the stringent requirements on CD control and overlay for such technology generations, wavefront error and flare of the EUV exposure systems have to be well controlled. The cross field variations of wavefront errors and flare need to be in the acceptable range in order to improve the common Depth of Focus (DoF) across the field. The impacts of lens aberration and flare to the aerial image at the system level are studied for the 32nm MPU technology node using Intel's aerial image simulation tool. The focus control budget of the exposure tools has been estimated. Useable Depth of Focus (UDoF) has been defined, and focus margin between UDoF and focus control budget from the exposure tool has been calculated for various cases. Focus margin has been used to determine the flare and lens aberration requirements for the 32nm MPU node. It is found that <10% intrinsic flare and <0.75nm rms lens aberration are required for the 32nm MPU node. Process window as a measure of individual aberration terms for the 32nm node has been also investigated.

  16. Knockout of the 15 kDa selenoprotein protects against chemically-induced aberrant crypt formation in mice.

    Directory of Open Access Journals (Sweden)

    Petra A Tsuji

    Full Text Available Evidence suggests that selenium has cancer preventive properties that are largely mediated through selenoproteins. Our previous observations demonstrated that targeted down-regulation of the 15 kDa selenoprotein (Sep15 in murine colon cancer cells resulted in the reversal of the cancer phenotype. The present study investigated the effect of Sep15 knockout in mice using a chemically-induced colon cancer model. Homozygous Sep15 knockout mice, and wild type littermate controls were given four weekly subcutaneous injections of azoxymethane (10 mg/kg. Sep15 knockout mice developed significantly (p<0.001 fewer aberrant crypt foci than controls demonstrating that loss of Sep15 protects against aberrant crypt foci formation. Dietary selenium above adequate levels did not significantly affect aberrant crypt foci formation in Sep15 knockout mice. To investigate molecular targets affected by loss of Sep15, gene expression patterns in colonic mucosal cells of knockout and wild type mice were examined using microarray analysis. Subsequent analyses verified that guanylate binding protein-1 (GBP-1 mRNA and protein expression were strongly upregulated in Sep15 knockout mice. GBP-1, which is expressed in response to interferon-γ, is considered to be an activation marker during inflammatory diseases, and up-regulation of GBP-1 in humans has been associated with a highly significant, increased five-year survival rate in colorectal cancer patients. In agreement with these studies, we observed a higher level of interferon-γ in plasma of Sep15 knockout mice. Overall, our results demonstrate for the first time, that Sep15 knockout mice are protected against chemically-induced aberrant crypt foci formation and that Sep15 appears to have oncogenic properties in colon carcinogenesis in vivo.

  17. Aberrant midsagittal fiber tracts in patients with hemimegalencephaly.

    Science.gov (United States)

    Sato, N; Ota, M; Yagishita, A; Miki, Y; Takahashi, T; Adachi, Y; Nakata, Y; Sugai, K; Sasaki, M

    2008-04-01

    In hemimegalencephaly, MR imaging often reveals midsagittal bandlike structures between the 2 lateral ventricles. To determine whether these structures are aberrant midsagittal fibers, we retrospectively reviewed them on conventional MR imaging and prospectively examined them by diffusion tensor MR and fiber tract (FT) reconstruction imaging. We retrospectively reviewed conventional MR images of 26 consecutive patients with hemimegalencephaly by 2 neuroradiologists, focusing on abnormal midsagittal structures. The distance between the 2 anterior horns and widths of midsagittal bandlike structures were measured. Prospective analysis was performed in 7 consecutive patients with hemimegalencephaly examined for midsagittal aberrant fibers by diffusion tensor imaging, and cortical distribution areas of the fibers were observed. The distance between the 2 anterior horns was wide (>4 mm) due to white matter-intensity structures in 20 of 26 patients (76.9%). Mid-sagittal bandlike structures were observed in 15 patients (57.7%). Asymmetry of the fornices was detected in 7 patients (26.9%), and both fornices were thickened in 7 (26.9%) patients. On FT reconstruction, images showed that 4 of 7 patients with hemimegalencephaly had aberrant midsagittal fibers connecting frontal, occipital, or parietal lobes, bilaterally (n = 3) or ipsilaterally (n = 1). All 4 patients had increased width between the 2 anterior horns, and 3 of them exhibited midsagittal bandlike structures on conventional MR imaging. On the other hand, these MR imaging findings were not noted in 3 patients who did not have aberrant midsagittal fibers on diffusion tensor imaging. Aberrant midsagittal FTs running intra- or interhemispherically do not infrequently exist in patients with hemimegalencephaly.

  18. Foco de criptas aberrantes e câncer da junção colorretal: análise da presença de lesões precoces microscópicas na periferia do câncer colorretal e correlação com a expressão da β-catenina e Ki-67 Aberrant crypt foci and cancer of the colorectal junction: the correlation between β-catenin/Ki-67 expression and the occurrence of early microscopic secondary lesions surrounding periphery colorectal cancer

    Directory of Open Access Journals (Sweden)

    Daniel Cury Ogata

    2010-04-01

    Full Text Available OBJETIVO: Avaliar a presença de foco de criptas aberrantes (FCA em mucosa macroscopicamente normal, localizada na periferia de um câncer colorretal (CCR e correlacionar a progressão tumoral destes FCA para o CCR, por meio da expressão da β-catenina e o Ki-67. MÉTODOS: Utilizou-se 21 espécimes cirúrgicos contendo adenocarcinoma de junção retossigmóide. Foram coletadas amostras localizadas a 1 e 5 cm proximal e distal ao tumor, quando possível, bem como um fragmento da neoplasia. Os FCA foram selecionados. Subseqüentemente foi realizado estudo imunoistoquímico com os anticorpos β-catenina e o Ki-67. RESULTADOS: A expressão nuclear da β-catenina nos adenocarcinomas, revelou freqüência de 81%. O Ki-67 apresentou a mesma freqüência. Apesar disso o coeficiente Kappa revelou fraca concordância entre estes anticorpos. Foram observados 20 FCA, sendo que 13 destes focos localizavam-se nas proximidades do tumor. Nenhum dos FCA apresentou expressão da β-catenina nuclear, tampouco para o Ki-67. CONCLUSÃO: Nas áreas situadas a 1 cm da neoplasia colorretal, foi observada maior concentração de FCA em relação às áreas situadas a 5 cm do tumor. No entanto, não se observou correlação entre a expressão da β-catenina e ki-67 nos colonócitos das criptas aberrantes das áreas estudadas, com as células neoplásicas do adenocarcinoma.OBJECTIVE: To evaluate the occurrence of aberrant crypt foci (ACF in macroscopic normal mucosa surrounding colorectal cancers (CRC; additionally, analyze tumor progression from ACF to CRC by means of β-catenin and Ki-67 expression. METHODS: Twenty-one surgical specimens showing colorectal junction adenocarcinoma were included. Macroscopic normal mucosa proximal and distal to the primary tumor was sampled at a distance of 1 and 5 cm in both sides. A primary tumor sample was also retrieved. Eventually, ACF's were selected and immunohistochemical analysis of β-catenin and Ki-67 were carried out. RESULTS

  19. Aberrant JAK/STAT Signaling Suppresses TFF1 and TFF2 through Epigenetic Silencing of GATA6 in Gastric Cancer

    Directory of Open Access Journals (Sweden)

    Cheng-Shyong Wu

    2016-09-01

    Full Text Available Aberrant Janus kinase (JAK/signal transducer and activator of transcription (STAT signaling is crucial to the development of gastric cancer. In this study, we examined the role of STAT3 in the expression and methylation of its targets in gastric cancer patients. Results from RNA sequencing identified an inverse correlation between the expression of STAT3 and GATA6 in 23 pairs of gastric cancer patient samples. We discovered that the expression of GATA6 is epigenetically silenced through promoter methylation in gastric cancer cell lines. Interestingly, the inhibition of STAT3 using a novel STAT3 inhibitor restored the expression of GATA6 and its targets, trefoil factors 1 and 2 (TFF1/2. Moreover, disruption of STAT3 binding to GATA6 promoter by small hairpin RNA restored GATA6 expression in AGS cells. A clinically significant correlation was also observed between the expression of GATA6 and TFF1/2 among tissue samples from 60 gastric cancer patients. Finally, bisulfite pyrosequencing revealed GATA6 methylation in 65% (39/60 of the patients, and those with higher GATA6 methylation tended to have shorter overall survival. In conclusion, we demonstrated that aberrant JAK/STAT signaling suppresses TFF1/2 partially through the epigenetic silencing of GATA6. Therapeutic intervention of STAT3 in reversing the epigenetic status of GATA6 could benefit the treatment of gastric cancer and is worthy of further investigation.

  20. Subjective face recognition difficulties, aberrant sensibility, sleeping disturbances and aberrant eating habits in families with Asperger syndrome

    Directory of Open Access Journals (Sweden)

    Källman Tiia

    2005-04-01

    Full Text Available Abstract Background The present study was undertaken in order to determine whether a set of clinical features, which are not included in the DSM-IV or ICD-10 for Asperger Syndrome (AS, are associated with AS in particular or whether they are merely a familial trait that is not related to the diagnosis. Methods Ten large families, a total of 138 persons, of whom 58 individuals fulfilled the diagnostic criteria for AS and another 56 did not to fulfill these criteria, were studied using a structured interview focusing on the possible presence of face recognition difficulties, aberrant sensibility and eating habits and sleeping disturbances. Results The prevalence for face recognition difficulties was 46.6% in individuals with AS compared with 10.7% in the control group. The corresponding figures for subjectively reported presence of aberrant sensibilities were 91.4% and 46.6%, for sleeping disturbances 48.3% and 23.2% and for aberrant eating habits 60.3% and 14.3%, respectively. Conclusion An aberrant processing of sensory information appears to be a common feature in AS. The impact of these and other clinical features that are not incorporated in the ICD-10 and DSM-IV on our understanding of AS may hitherto have been underestimated. These associated clinical traits may well be reflected by the behavioural characteristics of these individuals.

  1. Chromosomal Aberrations in Monozygotic and Dizygotic Twins Versus Singletons in Denmark During 1968-2009

    DEFF Research Database (Denmark)

    Kristensen, Lone Krøldrup; Larsen, Lisbeth A; Fagerberg, Christina

    2017-01-01

    BACKGROUND: Hall (Embryologic development and monozygotic twinning. Acta Geneticae Medicae et Gemellologiae, Vol. 45, 1996, pp. 53-57) hypothesized that chromosomal aberrations can lead to monozygotic (MZ) twinning. However, twinning and chromosomal aberrations increase prenatal mortality and could...

  2. Numerical and structural chromosome aberrations in cauliflower (Brassica oleracea var. botrytis) and Arabidopsis thaliana

    NARCIS (Netherlands)

    Ji, X.

    2014-01-01

    Numerical and structural chromosome aberrations in cauliflower (Brassica oleracea var. botrytis) and Arabidopsis thaliana. I studied numerical and structural chromosome aberrations in cauliflower (Brassica oleracea var. botrytis) and Arabidopsis thaliana. The large genomic changes are important for

  3. Image transfer with spatial coherence for aberration corrected transmission electron microscopes.

    Science.gov (United States)

    Hosokawa, Fumio; Sawada, Hidetaka; Shinkawa, Takao; Sannomiya, Takumi

    2016-08-01

    The formula of spatial coherence involving an aberration up to six-fold astigmatism is derived for aberration-corrected transmission electron microscopy. Transfer functions for linear imaging are calculated using the newly derived formula with several residual aberrations. Depending on the symmetry and origin of an aberration, the calculated transfer function shows characteristic symmetries. The aberrations that originate from the field's components, having uniformity along the z direction, namely, the n-fold astigmatism, show rotational symmetric damping of the coherence. The aberrations that originate from the field's derivatives with respect to z, such as coma, star, and three lobe, show non-rotational symmetric damping. It is confirmed that the odd-symmetric wave aberrations have influences on the attenuation of an image via spatial coherence. Examples of image simulations of haemoglobin and Si [211] are shown by using the spatial coherence for an aberration-corrected electron microscope.

  4. Numerical and structural chromosome aberrations in cauliflower (Brassica oleracea var. botrytis) and Arabidopsis thaliana

    NARCIS (Netherlands)

    Ji, X.

    2014-01-01

    Numerical and structural chromosome aberrations in cauliflower (Brassica oleracea var. botrytis) and Arabidopsis thaliana. I studied numerical and structural chromosome aberrations in cauliflower (Brassica oleracea var. botrytis) and Arabidopsis thaliana. The large genomic changes are important for

  5. ∆ DNMT3B4-del Contributes to Aberrant DNA Methylation Patterns in Lung Tumorigenesis

    OpenAIRE

    Ma, Mark Z.; Ruxian Lin; José Carrillo; Manisha Bhutani; Ashutosh Pathak; Hening Ren; Yaokun Li; Jiuzhou Song; Li Mao

    2015-01-01

    Aberrant DNA methylation is a hallmark of cancer but mechanisms contributing to the abnormality remain elusive. We have previously shown that ∆DNMT3B is the predominantly expressed form of DNMT3B. In this study, we found that most of the lung cancer cell lines tested predominantly expressed DNMT3B isoforms without exons 21, 22 or both 21 and 22 (a region corresponding to the enzymatic domain of DNMT3B) termed DNMT3B/∆DNMT3B-del. In normal bronchial epithelial cells, DNMT3B/ΔDNMT3B and DNMT3B/...

  6. A DNA methylation signature associated with aberrant promoter DNA hypermethylation of DNMT3B in human colorectal cancer.

    Science.gov (United States)

    Huidobro, Covadonga; Urdinguio, Rocío G; Rodríguez, Ramón María; Mangas, Cristina; Calvanese, Vincenzo; Martínez-Camblor, Pablo; Ferrero, Cecilia; Parra-Blanco, Adolfo; Rodrigo, Luis; Obaya, Alvaro J; Suárez-Fernández, Laura; Astudillo, Aurora; Hernando, Henar; Ballestar, Esteban; Fernández, Agustín F; Fraga, Mario F

    2012-09-01

    Altered promoter DNA methylation, one of the most important molecular alterations in cancer, is proposed to correlate with deregulation of DNA methyltransferases, although the molecular mechanisms implicated are still poorly understood. Here we show that the de novo DNA methyltransferase DNMT3B is frequently repressed in human colorectal cancer cell lines (CCL) and primary tumours by aberrant DNA hypermethylation of its distal promoter. At the epigenome level, DNMT3B promoter hypermethylation was associated with the hypomethylation of gene promoters usually hypermethylated in the healthy colon. Forced DNMT3B overexpression in cancer cells restored the methylation levels of these promoters in the healthy colon. Our results show a new molecular mechanism of aberrant DNMT3B regulation in colon cancer and suggest that its expression is associated with the methylation of constitutively hypermethylated promoters in the healthy colon. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Identification of RUNX1 as a Mediator of Aberrant Retinal Angiogenesis.

    Science.gov (United States)

    Lam, Jonathan D; Oh, Daniel J; Wong, Lindsay L; Amarnani, Dhanesh; Park-Windhol, Cindy; Sanchez, Angie V; Cardona-Velez, Jonathan; McGuone, Declan; Stemmer-Rachamimov, Anat O; Eliott, Dean; Bielenberg, Diane R; van Zyl, Tave; Shen, Lishuang; Gai, Xiaowu; D'Amore, Patricia A; Kim, Leo A; Arboleda-Velasquez, Joseph F

    2017-07-01

    Proliferative diabetic retinopathy (PDR) is a common cause of blindness in the developed world's working adult population and affects those with type 1 and type 2 diabetes. We identified Runt-related transcription factor 1 (RUNX1) as a gene upregulated in CD31(+) vascular endothelial cells obtained from human PDR fibrovascular membranes (FVMs) via transcriptomic analysis. In vitro studies using human retinal microvascular endothelial cells (HRMECs) showed increased RUNX1 RNA and protein expression in response to high glucose, whereas RUNX1 inhibition reduced HRMEC migration, proliferation, and tube formation. Immunohistochemical staining for RUNX1 showed reactivity in vessels of patient-derived FVMs and angiogenic tufts in the retina of mice with oxygen-induced retinopathy, suggesting that RUNX1 upregulation is a hallmark of aberrant retinal angiogenesis. Inhibition of RUNX1 activity with the Ro5-3335 small molecule resulted in a significant reduction of neovascular tufts in oxygen-induced retinopathy, supporting the feasibility of targeting RUNX1 in aberrant retinal angiogenesis. © 2017 by the American Diabetes Association.

  8. Aberrant E2F activation by polyglutamine expansion of androgen receptor in SBMA neurotoxicity.

    Science.gov (United States)

    Suzuki, Eriko; Zhao, Yue; Ito, Saya; Sawatsubashi, Shun; Murata, Takuya; Furutani, Takashi; Shirode, Yuko; Yamagata, Kaoru; Tanabe, Masahiko; Kimura, Shuhei; Ueda, Takashi; Fujiyama, Sally; Lim, Jinseon; Matsukawa, Hiroyuki; Kouzmenko, Alexander P; Aigaki, Toshiro; Tabata, Tetsuya; Takeyama, Ken-ichi; Kato, Shigeaki

    2009-03-10

    Spinal and bulbar muscular atrophy (SBMA) is a neurodegenerative disorder caused by a polyglutamine repeat (polyQ) expansion within the human androgen receptor (AR). Unlike other neurodegenerative diseases caused by abnormal polyQ expansion, the onset of SBMA depends on androgen binding to mutant human polyQ-AR proteins. This is also observed in Drosophila eyes ectopically expressing the polyQ-AR mutants. We have genetically screened mediators of androgen-induced neurodegeneration caused by polyQ-AR mutants in Drosophila eyes. We identified Rbf (Retinoblastoma-family protein), the Drosophila homologue of human Rb (Retinoblastoma protein), as a neuroprotective factor. Androgen-dependent association of Rbf or Rb with AR was remarkably potentiated by aberrant polyQ expansion. Such potentiated Rb association appeared to attenuate recruitment of histone deacetyltransferase 1 (HDAC1), a corepressor of E2F function. Either overexpression of Rbf or E2F deficiency in fly eyes reduced the neurotoxicity of the polyQ-AR mutants. Induction of E2F function by polyQ-AR-bound androgen was suppressed by Rb in human neuroblastoma cells. We conclude that abnormal expansion of polyQ may potentiate innate androgen-dependent association of AR with Rb. This appears to lead to androgen-dependent onset of SBMA through aberrant E2F transactivation caused by suppressed histone deacetylation.

  9. Contribution of the cornea and internal surfaces to the change of ocular aberrations with age

    Science.gov (United States)

    Artal, Pablo; Berrio, Esther; Guirao, Antonio; Piers, Patricia

    2002-01-01

    We studied the age dependence of the relative contributions of the aberrations of the cornea and the internal ocular surfaces to the total aberrations of the eye. We measured the wave-front aberration of the eye with a Hartmann-Shack sensor and the aberrations of the anterior corneal surface from the elevation data provided by a corneal topography system. The aberrations of the internal surfaces were obtained by direct subtraction of the ocular and corneal wave-front data. Measurements were obtained for normal healthy subjects with ages ranging from 20 to 70 years. The magnitude of the RMS wave-front aberration (excluding defocus and astigmatism) of the eye increases more than threefold within the age range considered. However, the aberrations of the anterior corneal surface increase only slightly with age. In most of the younger subjects, total ocular aberrations are lower than corneal aberrations, while in the older subjects the reverse condition occurs. Astigmatism, coma, and spherical aberration of the cornea are larger than in the complete eye in younger subjects, whereas the contrary is true for the older subjects. The internal ocular surfaces compensate, at least in part, for the aberrations associated with the cornea in most younger subjects, but this compensation is not present in the older subjects. These results suggest that the degradation of the ocular optics with age can be explained largely by the loss of the balance between the aberrations of the corneal and the internal surfaces.

  10. A Case Study of the Reduction of Aberrant, Repetitive Responses of an Adolescent with Autism.

    Science.gov (United States)

    Gunter, Philip L.; And Others

    1993-01-01

    In this case study, music was applied noncontingently and contingently across four settings with an adolescent male with autism, to reduce aberrant, repetitive vocalizations. The intervention was associated with dramatic reductions in the primary aberrant behavior and reductions in two other aberrant behaviors. Task performance was differentially…

  11. Assessment of wavefront aberration and contrast sensitivity test as evaluation of postoperative visual quality

    OpenAIRE

    Min Gong; Yi Liu; Bi Yang

    2013-01-01

    Effective methods of evaluating postoperative visual quality include wavefront aberration and contrast sensitivity test. This article provides a review of the concepts and clinical applications as well as their interactions of wavefront aberration and contrast sensitivity test.This article also provides a comprehensive assessment of the effectiveness of wavefront aberration and contrast sensitivity test as evaluation tools of postoperative visual quality.

  12. Nodular Hyperplasia Arising from the Lateral Aberrant Thyroid Tissue: A Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Min Hye; Park, Jeong Seon; Lee, Young Jun [Dept. of Radiology, Hanyang University College of Medicine, Hanyang University Hospital, Seoul (Korea, Republic of)

    2012-06-15

    The presence of aberrant thyroid tissue in the lateral neck is very rare. In addition, nodular hyperplasia in ectopic thyroid has rarely been reported. Due to the unusual location, the presence of lateral aberrant thyroid tissue could be misdiagnosed as a lymphadenopathy, neurogenic tumor, etc. We report on a case of nodular hyperplasia arising from the right lateral aberrant thyroid tissue.

  13. Aberrant DNA methylation in 5'regions of DNA methyltransferase genes in aborted bovine clones

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    High rate of abortion and developmental abnormalities is thought to be closely associated with inefficient epigenetic reprogramming of the transplanted nuclei during bovine cloning.It is known that one of the important mechanisms for epigenetic reprogramming is DNA methylation.DNA methylation is established and maintained by DNA methyltransferases(DNMTs),therefore,it is postulated that the inefficient epigenetic reprogramming of transplanted nuclei may be due to abnormal expression of DNMTs.Since DNA methylation can strongly inhibit gene expression,aberrant DNA methylation of DNMT genes may disturb gene expression.But presently,it is not clear whether the methylation abnormality of DNMT genes is related to developmental failure of somatic cell nuclear transfer embryos.In our study,we analyzed methylation patterns of the 5' regions of four DNMT genes including Dnmt3a,Dnmt3b,Dnmtl and Dnmt2 in four aborted bovine clones.Using bisulfite sequencing method,we found that 3 out of 4 aborted bovine clones(AF1,AF2 and AF3)showed either hypermethylation or hypomethylation in the 5' regions of Dnmt3a and Dnmt3b.indicating that Dnmt3a and Dnmt3b genes are not properly reprogrammed.However,the individual AF4 exhibited similar methylation level and pattern to age-matched in vitro fertilized (IVF)fetuses.Besides,we found that tle 5'regions of Dnmtl and Dnmt2 were nearly completely unmethylated in all normal adults.IVF fetuses,sperm and aborted clones.Together,our results suggest that the aberrant methylation of Dnmt3a and Dnmt3b 5' regions is probably associated with the high abortion of bovine clones.

  14. Nonhomologous DNA end joining and chromosome aberrations in human embryonic lung fibroblasts treated with environmental pollutants

    Energy Technology Data Exchange (ETDEWEB)

    Rossner, Pavel, E-mail: prossner@biomed.cas.cz; Rossnerova, Andrea; Beskid, Olena; Tabashidze, Nana; Libalova, Helena; Uhlirova, Katerina; Topinka, Jan; Sram, Radim J.

    2014-05-15

    Highlights: • We analyzed the effect of air pollutants on NHEJ and chromosome aberrations. • In HEL12469 cells B[a]P and extractable organic matter induced DSBs. • The compounds induced XRCC4 expression and a weak Ku70/80 response. • We found increased frequency of aberrations of chromosomes 1, 2, 4, 5, 7 and 17. • The tested compounds preferentially affected chromosome 7. - Abstract: In order to evaluate the ability of a representative polycyclic aromatic hydrocarbon (PAH) and PAH-containing complex mixtures to induce double strand DNA breaks (DSBs) and repair of damaged DNA in human embryonic lung fibroblasts (HEL12469 cells), we investigated the effect of benzo[a]pyrene (B[a]P) and extractable organic matter (EOM) from ambient air particles <2.5 μm (PM2.5) on nonhomologous DNA end joining (NHEJ) and induction of stable chromosome aberrations (CAs). PM2.5 was collected in winter and summer 2011 in two Czech cities differing in levels and sources of air pollutants. The cells were treated for 24 h with the following concentrations of tested chemicals: B[a]P: 1 μM, 10 μM, 25 μM; EOMs: 1 μg/ml, 10 μg/ml, 25 μg/ml. We tested several endpoints representing key steps leading from DSBs to the formation of CAs including histone H2AX phosphorylation, levels of proteins Ku70, Ku80 and XRCC4 participating in NHEJ, in vitro ligation activity of nuclear extracts of the HEL12469 cells and the frequency of stable CAs assessed by whole chromosome painting of chromosomes 1, 2, 4, 5, 7 and 17 using fluorescence in situ hybridization. Our results show that 25 μM of B[a]P and most of the tested doses of EOMs induced DSBs as indicated by H2AX phosphorylation. DNA damage was accompanied by induction of XRCC4 expression and an increased frequency of CAs. Translocations most frequently affected chromosome 7. We observed only a weak induction of Ku70/80 expression as well as ligation activity of nuclear extracts. In summary, our data suggest the induction of DSBs and

  15. Chromosomal Aberrations in Humans Induced by Urban Air Pollution

    DEFF Research Database (Denmark)

    Knudsen, Lisbeth E.; Norppa, Hannu; Gamborg, Michael O.

    1999-01-01

    We have studied the influence of individual susceptibility factors on the genotoxic effects of urban air pollution in 106 nonsmoking bus drivers and 101 postal workers in the Copenhagen metropolitan area. We used the frequency of chromosomal aberrations in peripheral blood lymphocytes...... that long-term exposure to urban air pollution (with traffic as the main contributor) induces chromosome damage in human somatic cells. Low DNA repair capacity and GSTM1 and NAT2 variants associated with reduced detoxification ability increase susceptibility to such damage. The effect of the GSTM1 genotype......, which was observed only in the bus drivers, appears to be associated with air pollution, whereas the NAT2 genotype effect, which affected all subjects, may influence the individual response to some other common exposure or the baseline level of chromosomal aberrations....

  16. Aberrant hippocampal neurogenesis contributes to epilepsy and associated cognitive decline.

    Science.gov (United States)

    Cho, Kyung-Ok; Lybrand, Zane R; Ito, Naoki; Brulet, Rebecca; Tafacory, Farrah; Zhang, Ling; Good, Levi; Ure, Kerstin; Kernie, Steven G; Birnbaum, Shari G; Scharfman, Helen E; Eisch, Amelia J; Hsieh, Jenny

    2015-03-26

    Acute seizures after a severe brain insult can often lead to epilepsy and cognitive impairment. Aberrant hippocampal neurogenesis follows the insult but the role of adult-generated neurons in the development of chronic seizures or associated cognitive deficits remains to be determined. Here we show that the ablation of adult neurogenesis before pilocarpine-induced acute seizures in mice leads to a reduction in chronic seizure frequency. We also show that ablation of neurogenesis normalizes epilepsy-associated cognitive deficits. Remarkably, the effect of ablating adult neurogenesis before acute seizures is long lasting as it suppresses chronic seizure frequency for nearly 1 year. These findings establish a key role of neurogenesis in chronic seizure development and associated memory impairment and suggest that targeting aberrant hippocampal neurogenesis may reduce recurrent seizures and restore cognitive function following a pro-epileptic brain insult.

  17. Aberrations and adaptive optics in super-resolution microscopy.

    Science.gov (United States)

    Booth, Martin; Andrade, Débora; Burke, Daniel; Patton, Brian; Zurauskas, Mantas

    2015-08-01

    As one of the most powerful tools in the biological investigation of cellular structures and dynamic processes, fluorescence microscopy has undergone extraordinary developments in the past decades. The advent of super-resolution techniques has enabled fluorescence microscopy - or rather nanoscopy - to achieve nanoscale resolution in living specimens and unravelled the interior of cells with unprecedented detail. The methods employed in this expanding field of microscopy, however, are especially prone to the detrimental effects of optical aberrations. In this review, we discuss how super-resolution microscopy techniques based upon single-molecule switching, stimulated emission depletion and structured illumination each suffer from aberrations in different ways that are dependent upon intrinsic technical aspects. We discuss the use of adaptive optics as an effective means to overcome this problem.

  18. Chromatic aberration control for tunable all-silicone membrane microlenses.

    Science.gov (United States)

    Waibel, Philipp; Mader, Daniel; Liebetraut, Peter; Zappe, Hans; Seifert, Andreas

    2011-09-12

    Tunable multi-chamber microfluidic membrane microlenses with achromaticity over a given focal length range are demonstrated. In analogy to a fixed-focus achromatic doublet lens, the multi-lens system is based on a stack of microfluidic cavities filled with optically optimized liquids with precisely defined refractive index and Abbe number, and these are independently pneumatically actuated. The membranes separating the cavities form the refractive optical surfaces, and the curvatures as a function of pressure are calculated using a mechanical model for deformation of flexible plates. The results are combined with optical ray tracing simulations of the multi-lens system to yield chromatic aberration behavior, which is verified experimentally. A focal length tuning range of 5-40 mm and reduction in chromatic aberration of over 30% is demonstrated, limited by the availability of optical fluids.

  19. Filtering chromatic aberration for wide acceptance angle electrostatic lenses.

    Science.gov (United States)

    Fazekas, Ádám; Tóth, László

    2014-07-01

    Chromatic aberration is a major issue for imaging mainly with large acceptance angle electrostatic lenses. Its correction is necessary to take advantage of the outstanding spatial and angular resolution that these lenses provide. We propose a method to eliminate the effect of chromatic aberration on the measured images by determining the impact resulting from higher and lower kinetic energies. Based on a spectral image sequence and a matrix, which describes the transmission function of the lens, a system of linear equations is solved to approximate the 2D spectral intensity distribution of the sample surface. We present the description of our method and preliminary test results, which show significant contrast and image quality improvement. The presented algorithm can also be applied as a software-based energy analyzer.

  20. Aberrantly methylated DNA as a biomarker in breast cancer

    DEFF Research Database (Denmark)

    Kristiansen, Søren; Jørgensen, Lars Mønster; Guldberg, Per;

    2013-01-01

    hypermethylation events, their use as tumor biomarkers is usually not hampered by analytical signals from normal cells, which is a general problem for existing protein tumor markers used for clinical assessment of breast cancer. There is accumulating evidence that DNA-methylation changes in breast cancer patients......Aberrant DNA hypermethylation at gene promoters is a frequent event in human breast cancer. Recent genome-wide studies have identified hundreds of genes that exhibit differential methylation between breast cancer cells and normal breast tissue. Due to the tumor-specific nature of DNA...... into subgroups based on DNA biomarkers may improve prognosis. Serial monitoring of DNA-methylation markers in blood during treatment may be useful, particularly when the cancer burden is below the detection level for standard imaging techniques. Overall, aberrant DNA methylation has a great potential...

  1. [Aluminum induces chromosome aberrations in wheat root meristem cells].

    Science.gov (United States)

    Bulanova, N V; Synzynys, B I; Koz'min, G V

    2001-12-01

    The yield and pattern of chromosome structure aberrations in wheat seedlings treated with aluminum nitrate and aluminum sulfate at various concentrations have been determined by the anaphase method. Aluminum has a genotoxic effect causing genome, chromatid, and chromosome aberrations in apical root meristem cells. The relationship between the total yield of structural mutations and the aluminum concentration follows a bell-shaped curve. The mutagenic activity of aluminum nitrate peaks at 10(-3) mg/ml, which is twice as high as the permissible concentration limit (PCL) of aluminum in potable water. The maximum of the mutagenic activity of aluminum sulfate is observed at 5 x 10(-4) mg/ml, i.e., one PCL. Tap water boiled for 2 h in an aluminum vessel has virtually no genotoxic effect on wheat cells.

  2. [239Pu and chromosomal aberrations in human peripheral blood lymphocytes].

    Science.gov (United States)

    Okladnikova, N D; Osovets, S V; Kudriavtseva, T I

    2009-01-01

    The genome status in somatic cells was assessed using the chromosomal aberration (CA) test in peripheral blood lymphocytes from 194 plutonium workers exposed to occupational radiation mainly from low-transportable compounds of airborne 230Pu. Pu body burden at the time of cytogenetic study varied from values close to the method sensitivity to values multiply exceeding the permissible level. Standard (routine) methods of peripheral blood lymphocytes cultivation were applied. Chromatid- and chromosomal-type structural changes were estimated. Aberrations were estimated per 100 examined metaphase cells. The quantitative relationship between the CA frequency and Pu body burden and the absorbed dose to the lung was found. Mathematical processing of results was carried out based on the phenomenological model. The results were shown as theoretical and experimental curves. The threshold of the CA yield was 0.43 +/- 0.03 kBq (Pu body burden) and 6.12 +/- 1.20 cGy (absorbed dose to the lung).

  3. Chromosome Aberrations in Human Lymphocytes Irradiated with Ionizing Radiation

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Tae Ho; Kim, Jin Hong; Kim, Jin Kyu [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2014-05-15

    The purpose of the present experiment was to provide data on the dose-dependent production of chromosome aberrations such as dicentrics, centric rings, and excess acentrics. Radiation is one of the more dangerous clastogens in the environment. Ionizing radiation causes chromosome breakages and various cytogenetic aberrations in exposed cells. In an investigation into radiation emergencies, it is important to estimate the dose to exposed persons for several reasons. Physical dosimeters (e. g., film badges) may misrepresent the actual radiation dose and may not be available in a radiological accident or terrorism incident. Biological dosimetry is suitable for estimating the radiation dose during such accidents. The dicentric chromosome assay is very sensitive and a reliable bio-indicator in cases of accidental overexposure.

  4. Mathematical Modeling of Carcinogenesis Based on Chromosome Aberration Data

    Institute of Scientific and Technical Information of China (English)

    Xiao-bo Li

    2009-01-01

    Objective: The progression of human cancer is characterized by the accumulation of genetic instability. An increasing number of experimental genetic molecular techniques have been used to detect chromosome aberrations. Previous studies on chromosome abnormalities often focused on identifying the frequent loci of chromosome alterations, but rarely addressed the issue of interrelationship of chromosomal abnormalities. In the last few years, several mathematical models have been employed to construct models of carcinogenesis, in an attempt to identify the time order and cause-and-effect relationship of chromosome aberrations. The principles and applications of these models are reviewed and compared in this paper. Mathematical modeling of carcinogenesis can contribute to our understanding of the molecular genetics of tumor development, and identification of cancer related genes, thus leading to improved clinical practice of cancer.

  5. Correction of Optical Aberrations in Elliptic Neutron Guides

    CERN Document Server

    Bentley, Phillip M; Andersen, Ken H; Rodriguez, Damian Martin; Mildner, David F R

    2012-01-01

    Modern, nonlinear ballistic neutron guides are an attractive concept in neutron beam delivery and instrumentation, because they offer increased performance over straight or linearly tapered guides. However, like other ballistic geometries they have the potential to create significantly non-trivial instrumental resolution functions. We address the source of the most prominent optical aberration, namely coma, and we show that for extended sources the off-axis rays have a different focal length from on-axis rays, leading to multiple reflections in the guide system. We illustrate how the interplay between coma, sources of finite size, and mirrors with non-perfect reflectivity can therefore conspire to produce uneven distributions in the neutron beam divergence, the source of complicated resolution functions. To solve these problems, we propose a hybrid elliptic-parabolic guide geometry. Using this new kind of neutron guide shape, it is possible to condition the neutron beam and remove almost all of the aberration...

  6. Manipulation of spatiotemporal photon distribution via chromatic aberration.

    Science.gov (United States)

    Li, Yuelin; Chemerisov, Sergey

    2008-09-01

    We demonstrate a spatiotemporal laser-pulse-shaping scheme that exploits the chromatic aberration in a dispersive lens. This normally harmful effect transforms the phase modulation into a beam-size modulation at the focal plane. In combination with the intricate diffraction effect via beam apodization, this method provides a spatiotemporal control of photon distribution with an accuracy of diffraction limit on a time scale of femtoseconds.

  7. Right cervical aortic arch with aberrant left subclavian artery.

    Science.gov (United States)

    Tjang, Yanto S; Aramendi, José I; Crespo, Alejandro; Hamzeh, Gadah; Voces, Roberto; Rodríguez, Miguel A

    2008-08-01

    The combination of right cervical aortic arch, aberrant retroesophageal left subclavian artery originating from a Kommerell's diverticulum, and a ligamentum arteriosum, constitutes a rare form of vascular ring. Two patients aged 21 days and 54 years, who were diagnosed by multislice 3-dimensional computed tomography and magnetic resonance imaging, underwent surgical division of a vascular ring. The adult required resection of a Kommerell's aneurysm and subclavian artery reimplantation.

  8. Chromosomic aberrations in female workers exposed to pesticides

    OpenAIRE

    Cuenca, Patricia; Ramírez, Vanessa

    2014-01-01

    The purpose of this work was to determine if the occupational exposure to those pesticides used at banana plantations’ packaging plants produces genetic damage to somatic cells of female workers. Chromosomal aberrations were scored in lymphocytes of 20 women, 10 female exposed workers and 10 female controls. Workers were recruited from independent farms from two locations in Costa Rica, during January through June in 1996 and 1997. These females had a minimum of three months of work, had neve...

  9. Chromosome aberrations in pesticide-exposed greenhouse workers.

    Science.gov (United States)

    Lander, B F; Knudsen, L E; Gamborg, M O; Järventaus, H; Norppa, H

    2000-10-01

    The aim of this study was to investigate the possibility of subtoxic exposure to pesticides causing chromosome aberrations in greenhouse workers. In a cross-sectional and prospective study design chromosome aberration frequencies in cultured lymphocytes were examined for 116 greenhouse workers exposed to a complex mixture of almost 50 insecticides, fungicides, and growth regulators and also for 29 nonsmoking, nonpesticide-exposed referents. The preseason frequencies of chromosome aberrations were slightly but not statistically significantly elevated for the greenhouse workers when they were compared with the referents. After a summer season of pesticide spraying in the greenhouses, the total frequencies of cells with chromosome aberrations were significantly higher than in the preseason samples (P=0.02) and also higher than for the referents (P=0.05). This finding was especially due to an increased number of cells with chromatid gaps between the first and second samples (P=0.001). The results may reflect an additive genotoxic effect of the spraying season, for which the use of insecticides and growth regulators (but not fungicides) culminates. The highest elevation in the risk of chromatid gaps was observed for persons who did not use gloves during re-entry activities such as nipping, cutting, pricking, and potting (risk ratio 2.88, 95% confidence interval 1.63-5.11). The present results suggest a genotoxic effect from a complex subtoxic occupational pesticide exposure. In general, the findings indicate the importance of personal protection, during high-exposure re-entry activities, in preventing pesticide uptake and genetic damage.

  10. Coherence and aberration effects in surface plasmon polariton imaging

    OpenAIRE

    Berthel, Martin; Jiang, Quanbo; Chartrand, Camille; Bellessa, Joel; Huant, Serge; Genet, Cyriaque; Drezet, Aurélien

    2016-01-01

    We study theoretically and experimentally coherent imaging of surface plasmon polaritons using either leakage radiation microscopy through a thin metal film or interference microscopy through a thick metal film. Using a rigorous modal formalism based on scalar Whittaker potentials we develop a systematic analytical and vectorial method adapted to the analysis of coherent imaging involving surface plasmon polaritons. The study includes geometrical aberrations due index mismatch which played an...

  11. Aberrant behavior and cognitive ability in preschool children

    Directory of Open Access Journals (Sweden)

    Bala Gustav

    2007-01-01

    Full Text Available The sample included 712 preschool boys and girls at the age of 4 to 7 years (mean 5.96 decimal years and standard deviation .96 from preschool institutions in Novi Sad, Sombor, Sremska Mitrovica and Bačka Palanka. Information concerning 36 indicators of aberrant behavior of the children were supplied by their parents, whereas their cognitive ability was tested by Raven’s progressive colored matrices. Based on factor analysis (promax method, four factors i.e. generators of aberrant behavior in children were singled out: aggression, anxiousness, dissociation, and hysteria, whose relations with cognitive functioning and age were also analyzed by factor analysis. Aberrant behavior and cognitive abilities show significant interrelatedness. Owing to orderly developed cognitive abilities, a child understands essence and reality of problems, realizes possibilities and manners of solving them, and succeeds in realizing successful psycho-social functioning. Developed cognitive abilities enable a child to recognize and understand her/his own reactions in different situations and develop manners of reacting, which leads to strengthening psycho-social safety and adapting behavior in accordance with her/his age and abilities.

  12. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes.

    Science.gov (United States)

    Biankin, Andrew V; Waddell, Nicola; Kassahn, Karin S; Gingras, Marie-Claude; Muthuswamy, Lakshmi B; Johns, Amber L; Miller, David K; Wilson, Peter J; Patch, Ann-Marie; Wu, Jianmin; Chang, David K; Cowley, Mark J; Gardiner, Brooke B; Song, Sarah; Harliwong, Ivon; Idrisoglu, Senel; Nourse, Craig; Nourbakhsh, Ehsan; Manning, Suzanne; Wani, Shivangi; Gongora, Milena; Pajic, Marina; Scarlett, Christopher J; Gill, Anthony J; Pinho, Andreia V; Rooman, Ilse; Anderson, Matthew; Holmes, Oliver; Leonard, Conrad; Taylor, Darrin; Wood, Scott; Xu, Qinying; Nones, Katia; Fink, J Lynn; Christ, Angelika; Bruxner, Tim; Cloonan, Nicole; Kolle, Gabriel; Newell, Felicity; Pinese, Mark; Mead, R Scott; Humphris, Jeremy L; Kaplan, Warren; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chou, Angela; Chin, Venessa T; Chantrill, Lorraine A; Mawson, Amanda; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Daly, Roger J; Merrett, Neil D; Toon, Christopher; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Kakkar, Nipun; Zhao, Fengmei; Wu, Yuan Qing; Wang, Min; Muzny, Donna M; Fisher, William E; Brunicardi, F Charles; Hodges, Sally E; Reid, Jeffrey G; Drummond, Jennifer; Chang, Kyle; Han, Yi; Lewis, Lora R; Dinh, Huyen; Buhay, Christian J; Beck, Timothy; Timms, Lee; Sam, Michelle; Begley, Kimberly; Brown, Andrew; Pai, Deepa; Panchal, Ami; Buchner, Nicholas; De Borja, Richard; Denroche, Robert E; Yung, Christina K; Serra, Stefano; Onetto, Nicole; Mukhopadhyay, Debabrata; Tsao, Ming-Sound; Shaw, Patricia A; Petersen, Gloria M; Gallinger, Steven; Hruban, Ralph H; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Schulick, Richard D; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Capelli, Paola; Corbo, Vincenzo; Scardoni, Maria; Tortora, Giampaolo; Tempero, Margaret A; Mann, Karen M; Jenkins, Nancy A; Perez-Mancera, Pedro A; Adams, David J; Largaespada, David A; Wessels, Lodewyk F A; Rust, Alistair G; Stein, Lincoln D; Tuveson, David A; Copeland, Neal G; Musgrove, Elizabeth A; Scarpa, Aldo; Eshleman, James R; Hudson, Thomas J; Sutherland, Robert L; Wheeler, David A; Pearson, John V; McPherson, John D; Gibbs, Richard A; Grimmond, Sean M

    2012-11-15

    Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.

  13. Analysis of chromosome aberration data by hybrid-scale models

    Energy Technology Data Exchange (ETDEWEB)

    Indrawati, Iwiq [Research and Development on Radiation and Nuclear Biomedical Center, National Nuclear Energy Agency (Indonesia); Kumazawa, Shigeru [Nuclear Technology and Education Center, Japan Atomic Energy Research Institute, Honkomagome, Tokyo (Japan)

    2000-02-01

    This paper presents a new methodology for analyzing data of chromosome aberrations, which is useful to understand the characteristics of dose-response relationships and to construct the calibration curves for the biological dosimetry. The hybrid scale of linear and logarithmic scales brings a particular plotting paper, where the normal section paper, two types of semi-log papers and the log-log paper are continuously connected. The hybrid-hybrid plotting paper may contain nine kinds of linear relationships, and these are conveniently called hybrid scale models. One can systematically select the best-fit model among the nine models by among the conditions for a straight line of data points. A biological interpretation is possible with some hybrid-scale models. In this report, the hybrid scale models were applied to separately reported data on chromosome aberrations in human lymphocytes as well as on chromosome breaks in Tradescantia. The results proved that the proposed models fit the data better than the linear-quadratic model, despite the demerit of the increased number of model parameters. We showed that the hybrid-hybrid model (both variables of dose and response using the hybrid scale) provides the best-fit straight lines to be used as the reliable and readable calibration curves of chromosome aberrations. (author)

  14. Incidence of chromosomal aberrations and micronuclei in cave tour guides.

    Science.gov (United States)

    Bilban, M; Bilban-Jakopin, C; Vrhovec, S

    2001-01-01

    An analysis of structural chromosomal aberrations (SCA) and micronucleus tests (MN) were performed in 38 subjects, cave tour guides and in appropriate control group. The dominant type of chromosomal aberrations in tourist guides were chromosomal breaks (0.013 per cell) and acentric fragments (0.011 per cell). In the control group, these aberrations were present up to 0.008 on cells. Considering the analysed cells of the guides in total (33,556), the incidence of dicentric and rings range is below 0.0008 on cells, even though three dicentric and ring chromosoms were found already in the first 1000 in vitro metaphases of some guides. Only 0.0003 dicentrics and neither other translocations were found in control group (ambiental exposure). The incidence of micronuclei in cytokinesis blocked lymphocytes ranged from 12-32 per 500 CB cells in the cave tour guides and from 4-11 per 500 CB cells in control group. Measurements of radon and its daughters were performed at different locations in the cave. Annual doses from 40-60 mSv were estimated per 2000 work hours for cave guides. The changes found in the genome of somatic cells may be related to the exposure doses of radon and its daughters, although smoking should not be ignored.

  15. Effect of therapeutic hypothermia on chromosomal aberration in perinatal asphyxia

    Directory of Open Access Journals (Sweden)

    Bahubali D Gane

    2016-01-01

    Full Text Available Introduction: Perinatal asphyxia is a major cause for neonatal mortality and morbidity around the world. The reduction of O2results in the generation of reactive oxygen species which interact with nucleic acid and make alteration in the structure and functioning of the genome. We studied the effect of therapeutic hypothermia on chromosomes with karyotyping. Subjects and Methods: Babies in the hypothermia group were cooled for the first 72 h, using gel packs. Rectal temperature of 33–34°C was maintained. Blood sample was collected after completion of therapeutic hypothermia for Chromosomal analysis. It was done with IKAROS Karyotyping system, Metasystems, based on recommendations of International system of human cytogenetic nomenclature. Results: The median chromosomal aberration was lower in hypothermia [2(0-5] than control group [4(1-7] and chromatid breakage was commonest aberration seen. Chromosomal aberration was significantly higher in severe encephalopathy group than moderate encephalopathy group. Conclusion: We conclude that the TH significantly reduces DNA damage in perinatal asphyxia.

  16. Chromosome aberrations in ataxia telangiectasia cells exposed to heavy ions

    Science.gov (United States)

    Kawata, T.; Cucinotta, F.; George, K.; Wu, H.; Shigematsu, N.; Furusawa, Y.; Uno, T.; Isobe, K.; Ito, H.

    Understanding of biological effects of heavy ions is important to assess healt h risk in space. One of the most important issues may be to take into account individual susceptibility. Ataxia telangiectasia (A-T) cells are known to exhibit abnormal responses to radiations but the mechanism of hyper radiosensitivity of A-T still remains unknown. We report chromosome aberrations in normal human fibroblasts and AT fibroblasts exposed to low- and high-LET radiations. A chemical-induced premature chromosome condensation (PCC) technique combined with chromosome- painting technique was applied to score chromosome aberrations in G2/M-phase cells. Following gamma irradiation, GM02052 cells were approximately 5 times more sensitive to g-rays than AG1522 cells. GM02052 cells had a much higher frequency of deletions and misrejoining than AG1522 cells. When the frequency of complex type aberrations was compared, GM02052 cells showed more than 10 times higher frequency than AG1522 cells. The results will be compared with those obtained from high-LET irradiations.

  17. Genomic aberrations of BRCA1-mutated fallopian tube carcinomas.

    Science.gov (United States)

    Hunter, Sally M; Ryland, Georgina L; Moss, Phillip; Gorringe, Kylie L; Campbell, Ian G

    2014-06-01

    Intraepithelial carcinomas of the fallopian tube are putative precursors to high-grade serous carcinomas of the ovary and peritoneum. Molecular characterization of these early precursors is limited but could be the key to identifying tumor biomarkers for early detection. This study presents a genome-wide copy number analysis of occult fallopian tube carcinomas identified through risk-reducing prophylactic oophorectomy from three women with germline BRCA1 mutations, demonstrating that extensive genomic aberrations are already established at this early stage. We found no indication of a difference in the level of genomic aberration observed in fallopian tube carcinomas compared with high-grade serous ovarian carcinomas. These findings suggest that spread to the peritoneal cavity may require no or very little further tumor evolution, which raises the question of what is the real window of opportunity to detect high-grade serous peritoneal carcinoma arising from the fallopian tube before it spreads. Nonetheless, the similarity of the genomic aberrations to those observed in high-grade serous ovarian carcinomas suggests that genetic biomarkers identified in late-stage disease may be relevant for early detection.

  18. Membrane based Deformable Mirror: Intrinsic aberrations and alignment issues

    CERN Document Server

    Bayanna, A Raja; Chatterjee, S; Mathew, Shibu K; Venkatakrishnan, P

    2015-01-01

    A Deformable Mirror (DM) is an important component of an Adaptive Optics system. It is known that an on-axis spherical/parabolic optical component, placed at an angle to the incident beam introduces defocus as well as astigmatism in the image plane. Although the former can be compensated by changing the focal plane position, the latter cannot be removed by mere optical re-alignment. Since the DM is to be used to compensate a turbulence-induced curvature term in addition to other aberrations, it is necessary to determine the aberrations induced by such (curved DM surface) an optical element when placed at an angle (other than 0 degree) of incidence in the optical path. To this effect, we estimate to a first order, the aberrations introduced by a DM as a function of the incidence angle and deformation of the DM surface. We record images using a simple setup in which the incident beam is reflected by a 37 channel Micro-machined Membrane Deformable Mirror for various angles of incidence. It is observed that astig...

  19. Aberration correction for time-domain ultrasound diffraction tomography.

    Science.gov (United States)

    Mast, T Douglas

    2002-07-01

    Extensions of a time-domain diffraction tomography method, which reconstructs spatially dependent sound speed variations from far-field time-domain acoustic scattering measurements, are presented and analyzed. The resulting reconstructions are quantitative images with applications including ultrasonic mammography, and can also be considered candidate solutions to the time-domain inverse scattering problem. Here, the linearized time-domain inverse scattering problem is shown to have no general solution for finite signal bandwidth. However, an approximate solution to the linearized problem is constructed using a simple delay-and-sum method analogous to "gold standard" ultrasonic beamforming. The form of this solution suggests that the full nonlinear inverse scattering problem can be approximated by applying appropriate angle- and space-dependent time shifts to the time-domain scattering data; this analogy leads to a general approach to aberration correction. Two related methods for aberration correction are presented: one in which delays are computed from estimates of the medium using an efficient straight-ray approximation, and one in which delays are applied directly to a time-dependent linearized reconstruction. Numerical results indicate that these correction methods achieve substantial quality improvements for imaging of large scatterers. The parametric range of applicability for the time-domain diffraction tomography method is increased by about a factor of 2 by aberration correction.

  20. Estimation of phase wave-front aberration distribution function using wavelet transform profilometry.

    Science.gov (United States)

    Rahbar, Kambiz; Faez, Karim; Attaran-Kakhki, Ebrahim

    2012-06-01

    Reduction of image quality under the effects of wavefront aberration of the optical system has a direct impact on the vision system's performance. This paper tries to estimate the amount of aberration with the use of wavelet transform profilometry. The basic idea is based on the principle that under aberration effects, the position of the fringes' image on the image plane will change, and this change correlates with the amount of aberration. So the distribution of aberration function can directly be extracted through measuring the amount of changes in the fringes' image on the image plane. Experimental results and the empirical validity of this idea are evaluated.

  1. Aberrant muscle syndrome: hypertrophy of the hand and arm due to aberrant muscles with or without hypertrophy of the muscles.

    Science.gov (United States)

    Ogino, Toshihiko; Satake, Hiroshi; Takahara, Masatoshi; Kikuchi, Noriaki; Watanabe, Tadayosi; Iba, Kousuke; Ishii, Seiichi

    2010-06-01

    Five patients were reported in our congenital anomaly registry who had six hands in total with muscular hyperplasia, aberrant muscles, ulnar drift of the fingers in the metacarpophalangeal (MP) joints, flexion contractures of the MP joints, and enlargement of the metacarpal spaces. Thirty patients with unilateral involvement of this condition have been reported previously. We reviewed these cases and found that the condition varied in severity and that it was reported using different names. However, this condition seems different from true macrodactyly and multiple camptodactyly, including windblown hand, and seems to be an isolated entity of congenital upper limb anomaly. The authors recommend 'aberrant muscle syndrome' or 'accessory muscle syndrome' as a diagnostic name, because this seems to be the most common pathological finding in this condition.

  2. Is 24-color FISH detection of in-vitro radiation-induced chromosomal aberrations suited to determine individual intrinsic radiosensitivity?

    Energy Technology Data Exchange (ETDEWEB)

    Kuechler, A.; Wendt, T.G. [Clinic of Radiology, Jena (Germany). Dept. of Radiotherapy; Neubauer, S.; Grabenbauer, G.G.; Sauer, R. [Erlangen Univ. (Germany). Dept. of Radiotherapy; Claussen, U.; Liehr, T. [Jena Univ. (Germany). Inst. of Human Genetics and Anthropology

    2002-04-01

    Background: Reliable determination of intrinsic radiosensitivity in individual patients is a serious need in radiation oncology. Chromosomal aberrations are sensitive indicators of a previous exposure to ionizing irradiation. Former molecular cytogenetic studies showed that such aberrations as an equivalent of intrinsic radiosensitivity can be detected by fluorescence in-situ hybridization (FISH) techniques using whole chromosome painting (wcp) probes. However, only one up to three randomly chosen wcp probes have been applied for such approaches until now. As a random distribution of chromosomal rearrangements along the chromosomes is up to now still controversial, the power of the 24-color FISH approach should be elucidated in the present study. Methods and Material: Lymphocytes derived from lymphoblastoid cell lines of one patient with Nijmegen breakage syndrome (NBS homozygote) and of two NBS heterozygotes and peripheral blood lymphocytes of two controls were analyzed. Samples of each patient/control were irradiated in vitro with 0.0 Gy, 0.7 Gy or 2.0 Gy prior to cultivation. Chromosomal aberrations were analyzed in detail and quantified by means of 24-color FISH as an expression of the individual intrinsic radiosensitivity. Results: 24-color FISH analyses were done in a total of 1,674 metaphases. After in-vitro irradiation, 21% (0.7 Gy) or 57% (2.0 Gy) of the controls' cells, 15% (0.7 Gy) or 53% (2.0 Gy) of the heterozygotes' cells and 54% (0.7 Gy) or 79% (2.0 Gy) of the homozygote's cells contained aberrations. The highest average rates of breaks per mitosis [B/M] (0.7 Gy: 1.80 B/M, 2.0 Gy: 4.03 B/M) and complex chromosomal rearrangements [CCR] (0.7 Gy: 0.20 CCR/M, 2.0 Gy: 0.47 CCR/M) were observed in the NBS patient. Moreover, the proportion of different aberration types after irradiation showed a distinct increase in the rate of CCR combined with a decrease in dicentrics in the NBS homozygote. Conclusion: To come to a more complete picture of

  3. Molecular profiling of ETS and non-ETS aberrations in prostate cancer patients from northern India.

    Science.gov (United States)

    Ateeq, Bushra; Kunju, Lakshmi P; Carskadon, Shannon L; Pandey, Swaroop K; Singh, Geetika; Pradeep, Immanuel; Tandon, Vini; Singhai, Atin; Goel, Apul; Amit, Sonal; Agarwal, Asha; Dinda, Amit K; Seth, Amlesh; Tsodikov, Alexander; Chinnaiyan, Arul M; Palanisamy, Nallasivam

    2015-07-01

    Molecular stratification of prostate cancer (PCa) based on genetic aberrations including ETS or RAF gene-rearrangements, PTEN deletion, and SPINK1 over-expression show clear prognostic and diagnostic utility. Gene rearrangements involving ETS transcription factors are frequent pathogenetic somatic events observed in PCa. Incidence of ETS rearrangements in Caucasian PCa patients has been reported, however, occurrence in Indian population is largely unknown. The aim of this study was to determine the prevalence of the ETS and RAF kinase gene rearrangements, SPINK1 over-expression, and PTEN deletion in this cohort. In this multi-center study, formalin-fixed paraffin embedded (FFPE) PCa specimens (n = 121) were procured from four major medical institutions in India. The tissues were sectioned and molecular profiling was done using immunohistochemistry (IHC), RNA in situ hybridization (RNA-ISH) and/or fluorescence in situ hybridization (FISH). ERG over-expression was detected in 48.9% (46/94) PCa specimens by IHC, which was confirmed in a subset of cases by FISH. Among other ETS family members, while ETV1 transcript was detected in one case by RNA-ISH, no alteration in ETV4 was observed. SPINK1 over-expression was observed in 12.5% (12/96) and PTEN deletion in 21.52% (17/79) of the total PCa cases. Interestingly, PTEN deletion was found in 30% of the ERG-positive cases (P = 0.017) but in only one case with SPINK1 over-expression (P = 0.67). BRAF and RAF1 gene rearrangements were detected in ∼1% and ∼4.5% of the PCa cases, respectively. This is the first report on comprehensive molecular profiling of the major spectrum of the causal aberrations in Indian men with PCa. Our findings suggest that ETS gene rearrangement and SPINK1 over-expression patterns in North Indian population largely resembled those observed in Caucasian population but differed from Japanese and Chinese PCa patients. The molecular profiling data presented in this study could help in

  4. Disruption of Tgfbr2 in odontoblasts leads to aberrant pulp calcification.

    Science.gov (United States)

    Ahn, Y H; Kim, T H; Choi, H; Bae, C H; Yang, Y M; Baek, J A; Lee, J C; Cho, E S

    2015-06-01

    Transforming growth factor β (TGF-β) signaling has been implicated in dentin formation and repair; however, the molecular mechanisms underlying dentin formation remain unclear. To address the role of TGF-β signaling in dentin formation, we analyzed odontoblast-specific Tgfbr2 conditional knockout mice. The mutant mice had aberrant teeth with thin dysplastic dentin and pulpal obliteration, similar to teeth from human patients with dentinogenesis imperfecta type II and dentin dysplasia. In mutant, the odontoblasts lost their cellular polarity, and matrix secretion was disrupted after mantle dentin formation. As a consequence, the amount of predentin decreased significantly, and an ectopic fibrous matrix was formed below the odontoblast layer. This matrix gradually calcified and obliterated the pulp chamber with increasing age. Immunohistochemistry revealed decreased expression of alkaline phosphatase in mutant odontoblasts. In mutant dentin, Dsp expression was reduced, but Dmp1 expression increased significantly. Collagen type I, biglycan, and Dsp were expressed in the ectopic matrix. These results suggest that loss of responsiveness to TGF-β in odontoblasts results in impaired matrix formation and pulpal obliteration. Our study indicates that TGF-β signaling plays an important role in dentin formation and pulp protection. Furthermore, our findings may provide new insight into possible mechanisms underlying human hereditary dentin disorders and reparative dentin formation.

  5. Network modeling of the transcriptional effects of copy number aberrations in glioblastoma

    Science.gov (United States)

    Jörnsten, Rebecka; Abenius, Tobias; Kling, Teresia; Schmidt, Linnéa; Johansson, Erik; Nordling, Torbjörn E M; Nordlander, Bodil; Sander, Chris; Gennemark, Peter; Funa, Keiko; Nilsson, Björn; Lindahl, Linda; Nelander, Sven

    2011-01-01

    DNA copy number aberrations (CNAs) are a hallmark of cancer genomes. However, little is known about how such changes affect global gene expression. We develop a modeling framework, EPoC (Endogenous Perturbation analysis of Cancer), to (1) detect disease-driving CNAs and their effect on target mRNA expression, and to (2) stratify cancer patients into long- and short-term survivors. Our method constructs causal network models of gene expression by combining genome-wide DNA- and RNA-level data. Prognostic scores are obtained from a singular value decomposition of the networks. By applying EPoC to glioblastoma data from The Cancer Genome Atlas consortium, we demonstrate that the resulting network models contain known disease-relevant hub genes, reveal interesting candidate hubs, and uncover predictors of patient survival. Targeted validations in four glioblastoma cell lines support selected predictions, and implicate the p53-interacting protein Necdin in suppressing glioblastoma cell growth. We conclude that large-scale network modeling of the effects of CNAs on gene expression may provide insights into the biology of human cancer. Free software in MATLAB and R is provided. PMID:21525872

  6. [Aberrant micro RNA and epigenetic network are associated with progression from MGUS to multiple myeloma].

    Science.gov (United States)

    Handa, Hiroshi

    2015-08-01

    In recent years, attention has been drawn to aberrant epigenetics as well as coding gene mutations in cancers. DNA methylation, histone acetylation and methylation, and micro RNA (miRNA) are included in the field of epigenetics. miRNAs are small RNAs of only 19-25 bases in length which do not encode protein but do they control gene expression by destroying mRNA or inhibiting translation. In multiple myeloma (MM), several miRNA expressions were markedly decreased, while in contrast their target genes, associated with apoptosis, the cell cycle and DNA methylation, were markedly increased. Negative correlations were found between miRNA and target genes expressions. The miR-34 family in itself was methylated, and expression was epigenetically controlled. miRNA and other epigenetic mechanisms underlie network formation, thought to be associated with MM progression. Thus, examining miRNA of MM is currently an important issue in terms of predicting patient outcomes and developing novel therapies.

  7. Installing and thereafter removing an aberrant prosthesis elicited opposite remodelling responses in growing mouse temporomandibular joints.

    Science.gov (United States)

    Zhang, H Y; Liu, Y D; Yang, H X; Zhang, M; Liao, L F; Wan, X H; Wang, M Q

    2015-09-01

    Temporomandibular joint (TMJ) displays a high remodelling capability. The current purpose was to investigate the differences between mandibular condylar remodelling responses of growing mice to installation and removal of unilateral anterior crossbite (UAC) prosthesis. Twenty-four mice were divided into one mock control group and two UAC groups. Unilateral anterior crossbite was created by installing a pair of prosthesis to left-side maxillary and mandibular incisors. Unilateral anterior crossbite was removed in removal group at 3 weeks but remained in UAC group. Temporomandibular joints were sampled at 7 weeks. Changes in condylar cartilage and subchondral bone were assessed by histology and in vivo micro-CT. Real-time PCR and immunohistochemistry were performed to evaluate expression changes in ADAMTS-5, MMP-3, MMP-9, MMP-13, IL-1, TNF-α, OPG and RANKL. Statistical analysis was performed at α = 0.05. Temporomandibular joint cartilage degradation was induced by UAC as previously reported but was reversed by removal of UAC. The dropped cartilage thickness, chondrocyte number and collagen II-positive area, the increased expression levels of Adamts-5, Mmp3, 9, 13, Tnf-α and Il-1β in cartilage, the decreased ratio of OPG/RANKL in both condylar cartilage and subchondral bone, the loss of TMJ subchondral bone and the increase in the TRAP-positive cells in subchondral bone were all reversed in the removal group (P < 0.05). The growing mouse TMJ condyle displays a high remodelling capability which can be degenerative and rehabilitative, respectively, in response to placement and thereafter removal of the aberrant prosthesis. Eliminating aberrant prosthesis is helpful to promote the degraded condyle to recover. © 2015 John Wiley & Sons Ltd.

  8. Aberration-Coreected Electron Microscopy at Brookhaven National Laboratory

    Energy Technology Data Exchange (ETDEWEB)

    Zhu,Y.; Wall, J.

    2008-04-01

    The last decade witnessed the rapid development and implementation of aberration correction in electron optics, realizing a more-than-70-year-old dream of aberration-free electron microscopy with a spatial resolution below one angstrom [1-9]. With sophisticated aberration correctors, modern electron microscopes now can reveal local structural information unavailable with neutrons and x-rays, such as the local arrangement of atoms, order/disorder, electronic inhomogeneity, bonding states, spin configuration, quantum confinement, and symmetry breaking [10-17]. Aberration correction through multipole-based correctors, as well as the associated improved stability in accelerating voltage, lens supplies, and goniometers in electron microscopes now enables medium-voltage (200-300kV) microscopes to achieve image resolution at or below 0.1nm. Aberration correction not only improves the instrument's spatial resolution but, equally importantly, allows larger objective lens pole-piece gaps to be employed thus realizing the potential of the instrument as a nanoscale property-measurement tool. That is, while retaining high spatial resolution, we can use various sample stages to observe the materials response under various temperature, electric- and magnetic- fields, and atmospheric environments. Such capabilities afford tremendous opportunities to tackle challenging science and technology issues in physics, chemistry, materials science, and biology. The research goal of the electron microscopy group at the Dept. of Condensed Matter Physics and Materials Science and the Center for Functional Nanomaterials, as well as the Institute for Advanced Electron Microscopy, Brookhaven National Laboratory (BNL), is to elucidate the microscopic origin of the physical- and chemical-behavior of materials, and the role of individual, or groups of atoms, especially in their native functional environments. We plan to accomplish this by developing and implementing various quantitative

  9. A comprehensive characterization of genome-wide copy number aberrations in colorectal cancer reveals novel oncogenes and patterns of alterations.

    Directory of Open Access Journals (Sweden)

    Tao Xie

    Full Text Available To develop a comprehensive overview of copy number aberrations (CNAs in stage-II/III colorectal cancer (CRC, we characterized 302 tumors from the PETACC-3 clinical trial. Microsatellite-stable (MSS samples (n = 269 had 66 minimal common CNA regions, with frequent gains on 20 q (72.5%, 7 (41.8%, 8 q (33.1% and 13 q (51.0% and losses on 18 (58.6%, 4 q (26% and 21 q (21.6%. MSS tumors have significantly more CNAs than microsatellite-instable (MSI tumors: within the MSI tumors a novel deletion of the tumor suppressor WWOX at 16 q23.1 was identified (p<0.01. Focal aberrations identified by the GISTIC method confirmed amplifications of oncogenes including EGFR, ERBB2, CCND1, MET, and MYC, and deletions of tumor suppressors including TP53, APC, and SMAD4, and gene expression was highly concordant with copy number aberration for these genes. Novel amplicons included putative oncogenes such as WNK1 and HNF4A, which also showed high concordance between copy number and expression. Survival analysis associated a specific patient segment featured by chromosome 20 q gains to an improved overall survival, which might be due to higher expression of genes such as EEF1B2 and PTK6. The CNA clustering also grouped tumors characterized by a poor prognosis BRAF-mutant-like signature derived from mRNA data from this cohort. We further revealed non-random correlation between CNAs among unlinked loci, including positive correlation between 20 q gain and 8 q gain, and 20 q gain and chromosome 18 loss, consistent with co-selection of these CNAs. These results reinforce the non-random nature of somatic CNAs in stage-II/III CRC and highlight loci and genes that may play an important role in driving the development and outcome of this disease.

  10. Chromosomal aberrations in ovine lymphocytes exposed in vitro to tolylfluanid.

    Science.gov (United States)

    Sutiaková, Irena; Kovalkovičová, Natália; Sutiak, Václav

    2012-01-01

    Chromosomal aberrations have been used as important cytogenetic biomarkers to study the mutagenic effects of different chemicals in vivo and in vitro. Chromosomal aberrations were evaluated in cultures of sheep lymphocytes in vitro exposed to the fungicide tolylfluanid. Lymphocyte cultures from three donors were exposed to four different concentrations of fungicide (1.10(-4) M(.)L; 1.10(-5) M(.)L; 1.10(-6) M(.)L; 1 × 10(-7) M(.)L). Chromosomal analysis showed a significant (P = 0.018 and 0.038 respectively, Anova test, P Tukey test) increase in the frequency of aberrant cells (ABC) in cultures treated with the highest negative experimental concentrations of tolylfluanid (1.10(-4) M(.)L; 1.10(-5) M(.)L) compared to control. Significantly increased numbers of chromatid breaks (7.67 ± 0.58% against 1.67 ± 2.08%, P = 0.009, Anova test, P Tukey test) and chromatid gaps (7.67 ± 1.15% against 2.67 ± 0.58%, P = 0.003, Anova test, P Tukey test) were observed in ovine cultures treated with the highest experimental concentration of tolylfluanid (1.10(-4) M(.)L). Tolylfluanid induced also chromosomal exchanges (P = 0.038, and 0.016 respectively, Anova test, P Tukey test) in ovine cultures treated with the highest experimental concentrations of tolylfluanid (1.10(-4) M(.)L; 1.10(-5) M(.)L). The mitotic index has not shown any statistical differences between the various treatments and control groups. Our results suggest a significant genotoxic effect of tolylfluanid only at the highest concentration in sheep peripheral lymphocytes in vitro.

  11. Aberrant promoter hypermethylation in serum DNA from patients with silicosis.

    Science.gov (United States)

    Umemura, Shigeki; Fujimoto, Nobukazu; Hiraki, Akio; Gemba, Kenichi; Takigawa, Nagio; Fujiwara, Keiichi; Fujii, Masanori; Umemura, Hiroshi; Satoh, Mamoru; Tabata, Masahiro; Ueoka, Hiroshi; Kiura, Katsuyuki; Kishimoto, Takumi; Tanimoto, Mitsune

    2008-09-01

    It is well established that patients with silicosis are at high risk for lung cancer; however, it is difficult to detect lung cancer by chest radiography during follow-up treatment of patients with silicosis because of preexisting diffuse pulmonary shadows. The purpose of this study is to evaluate the usefulness of detection of serum DNA methylation for early detection of lung cancer in silicosis. Serum samples from healthy controls (n = 20) and silicosis patients with (n = 11) and without (n = 67) lung cancer were tested for aberrant hypermethylation at the promoters of the DNA repair gene O(6)-methylguanine-DNA methyltransferase (MGMT), p16(INK4a), ras association domain family 1A (RASSF1A), the apoptosis-related gene death-associated protein kinase (DAPK) and retinoic acid receptor beta (RARbeta) by methylation-specific polymerase chain reaction. Aberrant promoter methylation in at least one of five tumor suppressor genes was detected more frequently in the serum DNA of silicosis patients with lung cancer than in that of patients without it (P = 0.006). Furthermore, the odds ratio of having lung cancer was 9.77 (P = 0.009) for those silicosis patients with methylation of at least one gene. Extended exposure to silica (>30 years) was correlated with an increased methylation frequency (P = 0.017); however, methylation status did not correlate with age, smoking history or radiographic findings of silicosis. These results suggest that testing for aberrant promoter methylation of tumor suppressor genes using serum DNA may facilitate early detection of lung cancer in patients with silicosis.

  12. Influence of Misalignment on High-Order Aberration Correction for Normal Human Eyes

    Institute of Scientific and Technical Information of China (English)

    ZHAO Hao-Xin; XU Bing; XUE Li-Xia; DAI Yun; LIU Qian; RAO Xue-Jun

    2008-01-01

    @@ Although a compensation device can correct aberrations of human eyes, the effect will be degraded by its misalignment, especially for high-order aberration correction. We caJculate the positioning tolerance of correction device for high-order aberrations, and within what degree the correcting effect is better than low-order aberration (defocus and astigmatism) correction. With fixed certain misalignment within the positioning tolerance, we calculate the residual wavefront rms aberration of the first-6 to first-35 terms along with the 3rd-5th terms of aberrations corrected, and the combined first-13 terms of aberrations are also studied under the same quantity of misalignment. However, the correction effect of high-order aberrations does not meliorate along with the increase of the high-order terms under some misalignment, moreover, some simple combined terms correction can achieve similar result as complex combinations. These results suggest that it is unnecessary to correct too much the terms of high-order aberrations which are diffcult to accomplish in practice, and gives confdence to correct high-order aberrations out of the laboratory.

  13. Effect of spherical aberration on scintillations of Gaussian beams in atmospheric turbulence

    Energy Technology Data Exchange (ETDEWEB)

    Ji, Xiaoling, E-mail: jiXL100@163.com; Deng, Jinping

    2014-07-18

    The effect of spherical aberration on scintillations of Gaussian beams in weak, moderate and strong turbulence is studied using numerical simulation method. It is found that the effect of the negative spherical aberration on the on-axis scintillation index is quite different from that of the positive spherical aberration. In weak turbulence, the positive spherical aberration results in a decrease of the on-axis scintillation index on propagation, but the negative spherical aberration results in an increase of the on-axis scintillation index when the propagation distance is not large. In particular, in weak turbulence the negative spherical aberration may cause peaks of the on-axis scintillation index, and the peaks disappear in moderate and strong turbulence, which is explained in physics. The strong turbulence leads to less discrepancy among scintillations of Gaussian beams with and without spherical aberration. - Highlights: • In weak turbulence scintillations can be suppressed using positive spherical aberration. • In weak turbulence scintillations may be very large due to negative spherical aberration. • The effect of spherical aberration on scintillations is less with increasing of turbulence.

  14. Anterior corneal and internal contributions to peripheral aberrations of human eyes

    Science.gov (United States)

    Atchison, David A.

    2004-03-01

    Anterior corneal and internal component contributions to overall peripheral aberrations of five human eyes were determined, based on corneal topography and overall aberration measurements. Anterior corneal position and orientation (tilt) were referenced to the line of sight. Ray tracing was performed through the anterior cornea for 6-mm-diameter pupils at angles out to 40° in both the temporal and the nasal visual fields. In general, both component and overall Zernike aberrations were greater for the nasal than for the temporal visual field. In general, the anterior corneal aberration components were considerably higher than the overall aberrations across the visual field and were balanced to a considerable degree by the internal ocular aberration components. The component and overall levels of Zernike third-order aberrations showed linear trends away from the fixation axis, and the component levels of Zernike fourth-order aberrations showed quadratic trends away from the fixation axis. The second-order, but not higher-order, aberration components were susceptible to the choice of image radius of curvature, while disregarding corneal position and orientation affected second- and higher-order aberration components.

  15. Removing lateral chromatic aberration in bright field optical microscopy.

    Science.gov (United States)

    Guzmán-Altamirano, Miguel; Gutiérrez-Medina, Braulio

    2015-06-01

    We present an efficient alternative to remove lateral chromatic aberration (LCA) in bright field light microscopy images. Our procedure is based on error calibration using time-sequential acquisition at different wavelengths, and error correction through digital image warping. Measurement of the displacements of fiducial marks in the red and green images relative to blue provide calibration factors that are subsequently used in test images to realign color channels digitally. We demonstrate quantitative improvement in the position and boundaries of objects in target slides and in the color content and morphology of specimens in stained biological samples. Our results show a reduction of LCA content below the 0.1% level.

  16. Miniaturized modules for light sheet microscopy with low chromatic aberration.

    Science.gov (United States)

    Bruns, T; Bauer, M; Bruns, S; Meyer, H; Kubin, D; Schneckenburger, H

    2016-12-01

    Two miniaturized fibre-coupled modules for light sheet-based microscopy are described and compared with respect to image quality, chromatic aberration and beam alignment. Whereas in one module the light sheet is created by an achromatic cylindrical lens, reflection by a spherical mirror and concomitant astigmatic distortion are used to create the light sheet in the second module. Test experiments with fluorescent dyes in solution and multicellular tumour spheroids are reported, and some details on construction are given for both systems. Both modules are optimized for imaging individual cell layers of 3D biological samples and can be adapted to fit commercial microscopes.

  17. Coherence and aberration effects in surface plasmon polariton imaging

    CERN Document Server

    Berthel, Martin; Chartrand, Camille; Bellessa, Joel; Huant, Serge; Genet, Cyriaque; Drezet, Aurélien

    2016-01-01

    We study theoretically and experimentally coherent imaging of surface plasmon polaritons using either leakage radiation microscopy through a thin metal film or interference microscopy through a thick metal film. Using a rigorous modal formalism based on scalar Whittaker potentials we develop a systematic analytical and vectorial method adapted to the analysis of coherent imaging involving surface plasmon polaritons. The study includes geometrical aberrations due index mismatch which played an important role in the interpretation of recent experiments using leakage radiation microscopy. We compare our theory with experiments using classical or quantum near-field scanning optical microscopy probes and show that the approach leads to a full interpretation of the recorded optical images.

  18. Adaptive dispersion formula for index interpolation and chromatic aberration correction.

    Science.gov (United States)

    Li, Chia-Ling; Sasián, José

    2014-01-13

    This paper defines and discusses a glass dispersion formula that is adaptive. The formula exhibits superior convergence with a minimum number of coefficients. Using this formula we rationalize the correction of chromatic aberration per spectrum order. We compare the formula with the Sellmeier and Buchdahl formulas for glasses in the Schott catalogue. The six coefficient adaptive formula is found to be the most accurate with an average maximum index of refraction error of 2.91 × 10(-6) within the visible band.

  19. Propagation of aberrated wavefronts using a ray transfer matrix.

    Science.gov (United States)

    Raasch, Thomas W

    2014-05-01

    A ray transfer matrix is used to calculate the propagation of aberrated wavefronts across a homogeneous refractive index. The wavefront is represented by local surface normals, i.e., by a ray bundle, and the propagation is accomplished by transferring those rays across the space. Wavefront shape is generated from the slopes and positions of the collection of rays. Calculation methods are developed for the paraxial case, for higher-order expansions, and for the exact tangent case. A numerical example is used to compare results between an analytical method and the methods developed here.

  20. Genome-wide identification of significant aberrations in cancer genome

    Directory of Open Access Journals (Sweden)

    Yuan Xiguo

    2012-07-01

    Full Text Available Abstract Background Somatic Copy Number Alterations (CNAs in human genomes are present in almost all human cancers. Systematic efforts to characterize such structural variants must effectively distinguish significant consensus events from random background aberrations. Here we introduce Significant Aberration in Cancer (SAIC, a new method for characterizing and assessing the statistical significance of recurrent CNA units. Three main features of SAIC include: (1 exploiting the intrinsic correlation among consecutive probes to assign a score to each CNA unit instead of single probes; (2 performing permutations on CNA units that preserve correlations inherent in the copy number data; and (3 iteratively detecting Significant Copy Number Aberrations (SCAs and estimating an unbiased null distribution by applying an SCA-exclusive permutation scheme. Results We test and compare the performance of SAIC against four peer methods (GISTIC, STAC, KC-SMART, CMDS on a large number of simulation datasets. Experimental results show that SAIC outperforms peer methods in terms of larger area under the Receiver Operating Characteristics curve and increased detection power. We then apply SAIC to analyze structural genomic aberrations acquired in four real cancer genome-wide copy number data sets (ovarian cancer, metastatic prostate cancer, lung adenocarcinoma, glioblastoma. When compared with previously reported results, SAIC successfully identifies most SCAs known to be of biological significance and associated with oncogenes (e.g., KRAS, CCNE1, and MYC or tumor suppressor genes (e.g., CDKN2A/B. Furthermore, SAIC identifies a number of novel SCAs in these copy number data that encompass tumor related genes and may warrant further studies. Conclusions Supported by a well-grounded theoretical framework, SAIC has been developed and used to identify SCAs in various cancer copy number data sets, providing useful information to study the landscape of cancer genomes

  1. FISH and FICTION to detect chromosomal aberrations in lymphomas.

    Science.gov (United States)

    Giefing, Maciej; Siebert, Reiner

    2013-01-01

    Fluorescence In Situ Hybridization (FISH) is a powerful and robust technique allowing the visualization of target sequences like genes in interphase nuclei. It is widely used in routine diagnostics to identify cancer specific aberrations including lymphoma associated translocations or gene copy number changes in single tumor cells. By combining FISH with immunophenotyping-a technique called Fluorescence Immunophenotyping and Interphase Cytogenetic as a Tool for Investigation Of Neoplasia (FICTION)-it is moreover possible to identify a cell population of interest. Here we describe standard protocols for FISH and FICTION as used in our laboratory in diagnosis and research.

  2. Coherence and aberration effects in surface plasmon polariton imaging

    Science.gov (United States)

    Berthel, Martin; Jiang, Quanbo; Chartrand, Camille; Bellessa, Joel; Huant, Serge; Genet, Cyriaque; Drezet, Aurélien

    2015-09-01

    We study theoretically and experimentally coherent imaging of surface plasmon polaritons using either leakage radiation microscopy through a thin metal film or interference microscopy through a thick metal film. Using a rigorous modal formalism based on scalar Whittaker potentials, we develop a systematic analytical and vectorial method adapted to the analysis of coherent imaging involving surface plasmon polaritons. The study includes geometrical aberrations due index mismatch which played an important role in the interpretation of recent experiments using leakage radiation microscopy. We compare our theory with experiments using classical or quantum near-field scanning optical microscopy probes and show that the approach leads to a full interpretation of the recorded optical images.

  3. Spatially incoherent illumination interferometry: a PSF almost insensitive to aberrations

    CERN Document Server

    Xiao, Peng; Boccara, A Claude

    2016-01-01

    We show that with spatially incoherent illumination, the point spread function width of an imaging interferometer like that used in full-field optical coherence tomography (FFOCT) is almost insensitive to aberrations that mostly induce a reduction of the signal level without broadening. This is demonstrated by comparison with traditional scanning OCT and wide-field OCT with spatially coherent illuminations. Theoretical analysis, numerical calculation as well as experimental results are provided to show this specific merit of incoherent illumination in full-field OCT. To the best of our knowledge, this is the first time that such result has been demonstrated.

  4. Generic Misalignment Aberration Patterns and the Subspace of Benign Misalignment

    CERN Document Server

    Schechter, Paul L

    2012-01-01

    Q1: Why deploy N wavefront sensors on a three mirror anastigmat (TMA) and not N + 1? Q2: Why measure M Zernike coefficients and not M + 1? Q3: Why control L rigid body degrees of freedom (total) on the secondary and tertiary and not L + 1? The usual answer: "We did a lot of ray tracing and N,M, and L seemed OK." We show how straightforward results from aberration theory may be used to address these questions. We consider, in particular, the case of a three mirror anastigmat.

  5. Three-dimensional polarization aberration functions in optical system based on three-dimensional polarization ray-tracing calculus

    Science.gov (United States)

    He, Wenjun; Fu, Yuegang; Liu, Zhiying; Zhang, Lei; Wang, Jiake; Zheng, Yang; Li, Yahong

    2017-03-01

    The polarization aberrations of a complex optical system with multi-element lens have been investigated using a 3D polarization aberration function. The 3D polarization ray-tracing matrix has been combined with the optical path difference to obtain a 3D polarization aberration function, which avoids the need for a complicated phase unwrapping process. The polarization aberrations of a microscope objective have been analyzed to include, the distributions of 3D polarization aberration functions, diattenuation aberration, retardance aberration, and polarization-dependent intensity on the exit pupil. Further, the aberrations created by the field of view and the coating on the distribution rules of 3D polarization aberration functions are discussed in detail. Finally a novel appropriate field of view and wavelength correction is proposed for a polarization aberration function which optimizes the image quality of a multi-element optical system.

  6. Aberrant herpesvirus-induced polyadenylation correlates with cellular messenger RNA destruction.

    Directory of Open Access Journals (Sweden)

    Yeon J Lee

    2009-05-01

    Full Text Available Regulation of messenger RNA (mRNA stability plays critical roles in controlling gene expression, ensuring transcript fidelity, and allowing cells to respond to environmental cues. Unregulated enhancement of mRNA turnover could therefore dampen cellular responses to such signals. Indeed, several herpesviruses instigate widespread destruction of cellular mRNAs to block host gene expression and evade immune detection. Kaposi's sarcoma-associated herpesvirus (KSHV promotes this phenotype via the activity of its viral SOX protein, although the mechanism of SOX-induced mRNA turnover has remained unknown, given its apparent lack of intrinsic ribonuclease activity. Here, we report that KSHV SOX stimulates cellular transcriptome turnover via a unique mechanism involving aberrant polyadenylation. Transcripts in SOX-expressing cells exhibit extended poly(A polymerase II-generated poly(A tails and polyadenylation-linked mRNA turnover. SOX-induced polyadenylation changes correlate with its RNA turnover function, and inhibition of poly(A tail formation blocks SOX activity. Both nuclear and cytoplasmic poly(A binding proteins are critical cellular cofactors for SOX function, the latter of which undergoes striking nuclear relocalization by SOX. SOX-induced mRNA turnover therefore represents both a novel mechanism of host shutoff as well as a new model system to probe the regulation of poly(A tail-stimulated mRNA turnover in mammalian cells.

  7. Pathway aberrations of murine melanoma cells observed in Paired-End diTag transcriptomes

    Directory of Open Access Journals (Sweden)

    Liu Edison

    2007-06-01

    Full Text Available Abstract Background Melanoma is the major cause of skin cancer deaths and melanoma incidence doubles every 10 to 20 years. However, little is known about melanoma pathway aberrations. Here we applied the robust Gene Identification Signature Paired End diTag (GIS-PET approach to investigate the melanoma transcriptome and characterize the global pathway aberrations. Methods GIS-PET technology directly links 5' mRNA signatures with their corresponding 3' signatures to generate, and then concatenate, PETs for efficient sequencing. We annotated PETs to pathways of KEGG database and compared the murine B16F1 melanoma transcriptome with three non-melanoma murine transcriptomes (Melan-a2 melanocytes, E14 embryonic stem cells, and E17.5 embryo. Gene expression levels as represented by PET counts were compared across melanoma and melanocyte libraries to identify the most significantly altered pathways and investigate the expression levels of crucial cancer genes. Results Melanin biosynthesis genes were solely expressed in the cells of melanocytic origin, indicating the feasibility of using the PET approach for transcriptome comparison. The most significantly altered pathways were metabolic pathways, including upregulated pathways: purine metabolism, aminophosphonate metabolism, tyrosine metabolism, selenoamino acid metabolism, galactose utilization, nitrobenzene degradation, and bisphenol A degradation; and downregulated pathways: oxidative phosphorylation, ATPase synthesis, TCA cycle, pyruvate metabolism, and glutathione metabolism. The downregulated pathways concurrently indicated a slowdown of mitochondrial activities. Mitochondrial permeability was also significantly altered, as indicated by transcriptional activation of ATP/ADP, citrate/malate, Mg++, fatty acid and amino acid transporters, and transcriptional repression of zinc and metal ion transporters. Upregulation of cell cycle progression, MAPK, and PI3K/Akt pathways were more limited to certain

  8. Chromosomal aberrations as etiological factors of intrauterine growth retardation

    Directory of Open Access Journals (Sweden)

    Petrović Bojana

    2008-01-01

    Full Text Available Background/Aim. Intrauterine growth retardation (IUGR is a pathological condition of pregnancy characterised by birth weight below the 10th centile. A number of fetal, placental and maternal causes can lead to IUGR; although, in most cases no specific causes can be identified. The aim of this study was to determine the part of chromosomal abnormalities in IUGR etiology. Methods. Fetal blood karyotype taken by cordocentesis from 168 fetuses with diagnosed IUGR was analyzed. Results. Chromosomal rearrangements both numerical and structural were detected in 14 cases (12.2%. Two cases were triploid. Patau syndrome, Edwards syndrome and Down syndrome were found in two cases each. There was one case of trisomy 7 (47, XY, +7 and one case of trisomy 16 (47, XX, +16; one translocation, 46, XY, t (2; 14(q23; q32 and a deletion 46, XYdel (12 (p12 as well as two cases of sex chromosomes abnormalities, 45, X (Turner syndrome and 47, XYY. Conclusion. These findings suggest that a consistent number of symmetrical IUGR cases (about 12% can be associated with chromosomal rearrangements. Chromosomal aberrations that cause IUGR are heterogeneous, aberration of autosomes, mostly autosomal trisomies, being the most common.

  9. Aberrant regulation of Wnt signaling in hepatocellular carcinoma

    Science.gov (United States)

    Liu, Li-Juan; Xie, Shui-Xiang; Chen, Ya-Tang; Xue, Jing-Ling; Zhang, Chuan-Jie; Zhu, Fan

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the most lethal malignancies in the world. Several signaling pathways, including the wingless/int-1 (Wnt) signaling pathway, have been shown to be commonly activated in HCC. The Wnt signaling pathway can be triggered via both catenin β1 (CTNNB1)-dependent (also known as “canonical”) and CTNNB1-independent (often referred to as “non-canonical”) pathways. Specifically, the canonical Wnt pathway is one of those most frequently reported in HCC. Aberrant regulation from three complexes (the cell-surface receptor complex, the cytoplasmic destruction complex and the nuclear CTNNB1/T-cell-specific transcription factor/lymphoid enhancer binding factor transcriptional complex) are all involved in HCC. Although the non-canonical Wnt pathway is rarely reported, two main non-canonical pathways, Wnt/planar cell polarity pathway and Wnt/Ca2+ pathway, participate in the regulation of hepatocarcinogenesis. Interestingly, the canonical Wnt pathway is antagonized by non-canonical Wnt signaling in HCC. Moreover, other signaling cascades have also been demonstrated to regulate the Wnt pathway through crosstalk in HCC pathogenesis. This review provides a perspective on the emerging evidence that the aberrant regulation of Wnt signaling is a critical mechanism for the development of HCC. Furthermore, crosstalk between different signaling pathways might be conducive to the development of novel molecular targets of HCC. PMID:27672271

  10. Harmonic source wavefront aberration correction for ultrasound imaging

    Science.gov (United States)

    Dianis, Scott W.; von Ramm, Olaf T.

    2011-01-01

    A method is proposed which uses a lower-frequency transmit to create a known harmonic acoustical source in tissue suitable for wavefront correction without a priori assumptions of the target or requiring a transponder. The measurement and imaging steps of this method were implemented on the Duke phased array system with a two-dimensional (2-D) array. The method was tested with multiple electronic aberrators [0.39π to 1.16π radians root-mean-square (rms) at 4.17 MHz] and with a physical aberrator 0.17π radians rms at 4.17 MHz) in a variety of imaging situations. Corrections were quantified in terms of peak beam amplitude compared to the unaberrated case, with restoration between 0.6 and 36.6 dB of peak amplitude with a single correction. Standard phantom images before and after correction were obtained and showed both visible improvement and 14 dB contrast improvement after correction. This method, when combined with previous phase correction methods, may be an important step that leads to improved clinical images. PMID:21303031

  11. Mechanistic modeling of aberrant energy metabolism in human disease

    Directory of Open Access Journals (Sweden)

    Vineet eSangar

    2012-10-01

    Full Text Available Dysfunction in energy metabolism—including in pathways localized to the mitochondria—has been implicated in the pathogenesis of a wide array of disorders, ranging from cancer to neurodegenerative diseases to type II diabetes. The inherent complexities of energy and mitochondrial metabolism present a significant obstacle in the effort to understand the role that these molecular processes play in the development of disease. To help unravel these complexities, systems biology methods have been applied to develop an array of computational metabolic models, ranging from mitochondria-specific processes to genome-scale cellular networks. These constraint-based models can efficiently simulate aspects of normal and aberrant metabolism in various genetic and environmental conditions. Development of these models leverages—and also provides a powerful means to integrate and interpret—information from a wide range of sources including genomics, proteomics, metabolomics, and enzyme kinetics. Here, we review a variety of mechanistic modeling studies that explore metabolic functions, deficiency disorders, and aberrant biochemical pathways in mitochondria and related regions in the cell.

  12. A simulation study comparing aberration detection algorithms for syndromic surveillance

    Directory of Open Access Journals (Sweden)

    Painter Ian

    2007-03-01

    Full Text Available Abstract Background The usefulness of syndromic surveillance for early outbreak detection depends in part on effective statistical aberration detection. However, few published studies have compared different detection algorithms on identical data. In the largest simulation study conducted to date, we compared the performance of six aberration detection algorithms on simulated outbreaks superimposed on authentic syndromic surveillance data. Methods We compared three control-chart-based statistics, two exponential weighted moving averages, and a generalized linear model. We simulated 310 unique outbreak signals, and added these to actual daily counts of four syndromes monitored by Public Health – Seattle and King County's syndromic surveillance system. We compared the sensitivity of the six algorithms at detecting these simulated outbreaks at a fixed alert rate of 0.01. Results Stratified by baseline or by outbreak distribution, duration, or size, the generalized linear model was more sensitive than the other algorithms and detected 54% (95% CI = 52%–56% of the simulated epidemics when run at an alert rate of 0.01. However, all of the algorithms had poor sensitivity, particularly for outbreaks that did not begin with a surge of cases. Conclusion When tested on county-level data aggregated across age groups, these algorithms often did not perform well in detecting signals other than large, rapid increases in case counts relative to baseline levels.

  13. An Aberrant Artery Arising From Common Hepatic Artery

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    Surekha D. Jadhav

    2015-01-01

    Full Text Available Common hepatic artery is the branch of celiac trunk which is chief artery of the foregut. Branches of celiac trunk supply the gastrointestinal tract and its associated glands which are derived from foregut. Anatomy and variations of hepatic arterial system have become increasingly important due to increasing number of laparoscopic procedures, oncologic surgical interventions, and organ transplant cases. This case report describes a rare anatomical variation of an aberrant artery arising from common hepatic artery before the origin of gastroduodenal artery and proper hepatic artery.The aberrant artery traversed inferiorly and behind the body of the pancreas which divided into a right and left branches. The right branch ran behind the neck of the pancreas and it ended after giving few branches to head and body of pancreas. However, the left branch gave off branches to the proximal part of the jejunum. The presence of a branch arising directly from the common hepatic artery supplying the pancreas and jejunum is uncommon. Knowledge of such a rare variation is important not only for surgeons but also interventional radiologists and those studying anatomy

  14. Biclonal chromosomal aberrations in a child with myelodysplastic syndrome.

    Science.gov (United States)

    Jakab, Z; Balogh, E; Kiss, C; Pajor, L; Oláh, E

    1999-01-01

    Hematological malignancies and premalignant diseases are generally of monoclonal origin. The prognostic and therapeutic significance of finding two genetically independent clones remains to be determined. We followed a case of childhood myelodysplastic syndrome showing biclonal chromosomal abnormalities (+8, -7) by conventional cytogenetic examination and double target fluorescence in situ hybridization (FISH). A 7-year-old girl presented with Plaut-Vincent angina and leukopenia. The cytogenetic aberration of +8 was the first sign to suggest MDS. Serial bone marrow controls, prompted by a progressive clinical course detected myelodysplastic changes and a new clonal aberration (-7). The presence of -7 and +8 in two independent clones was verified by double-target FISH. While at diagnosis and during cytokine treatment more cells showed +8, after successful all-trans retinoic acid (ATRA) therapy, the clone with -7 predominated. Following allogeneic bone marrow transplantation the patient displayed donor-derived hematopoesis. Our data stress the significance of cytogenetic and FISH examinations in detecting specific genetic abnormalities and progressive clonal changes as an indicator and guideline for therapy. Different cell clones characterized by different genetic changes might be associated with different biologic features reflected in their response to treatment.

  15. Maternal age, reproduction and chromosomal aberrations in Wistar derived rats.

    Science.gov (United States)

    Niggeschulze, A; Kast, A

    1994-01-01

    The fertility of rats ranges from one to 18 months. In standard teratogenicity testing young, mature females are used which may not reflect the situation in women above 35 years old. Reproduction among different age groups of Wistar ats (strain Chbb: THOM) was compared at 3, 6, 9, 12, 15 and 18 months. At least 20 virgin females were inseminated per age group. The copulation rate did not differ between the groups. From the maternal age of 12 months, the pregnancy rate was significantly decreased, from the age of 9 months, the litter values were significantly lowered and the resorption rates were increased. Maternal age did not influence the incidence of fetal variations and malformations. Additionally, the chromosomal aberration rate in the bone marrow was evaluated in male and female rats. Twelve animals of each sex were scheduled per group, and studied at the age of 1, 3, 6, 12, 15, 18, 21 or 24 months. In males, the aberration rate increased continuously from 0.18 through 3%, while in females the increase continued from 0.33 to 2.29% at 15 months old when a plateau was reached. When testing new compounds for embryotoxicity or genotoxicity in female rats, the animals should be of comparable age to man in order to avoid a misinterpretation of spontaneous abnormalities. From these studies, however, it was concluded that the use of higher age groups of female rats in teratogenicity studies would not improve the risk assessment.

  16. Prompt cytomolecular identification of chromosome aberration in irradiated blood cells

    Directory of Open Access Journals (Sweden)

    Seyed Akbar Moosavi

    2017-02-01

    Full Text Available Background: understanding the genomic alteration induced by ionizing radiation still remains to be a methodological challenge in genetic field. The energy released from this type of radiation can potentially causes structural and numerical alterations in lymphocytes, which in turn converts them into abnormal tumor cells. Chromosomal abnormalities associated with specific type of hematological malignancies are determinant factors in evaluation of radiation dose and its potential in harming the body. None the less early detection of chromosomal aberration (CA is crucial in prognosis and selection of therapy for the people exposed to irradiations. The aim of this study was to explore a swift and accurate genetic test that identifies CAs in radiologist exposed to X-rays. In addition synergistic effect of other clastogens in irradiated workers was also evaluated. Material and methods: thirty four heparinized blood samples were obtained from radiology workers exposed to X-rays. Blood samples were cultured in RPMI 1640 and F-10 Medias with and without PHA stimulation. Lymphocytes were harvested, separated and arrested at metaphase and their chromosomes were analyzed by solid and G-Banding techniques. Lymphocytic CA was also analyzed through whole chromosome painting FISH. Results: of the 37 blood sample from workers, 60% had various structural aberrations in which both the frequency and type of CAs were intensified among tobacco smokers. Conclusion: the results did not show any significant differences between the genders but other carcinogen like smoking can significantly increases the rate of CAs

  17. An experimental study of aero-optical aberration and dithering of supersonic mixing layer via BOS

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The optical performance of supersonic mixing layer is heavily deteriorated by the aero-optical aberration and dithering of coherent structures, but current measuring methods limit the spatiotemporal resolution in relevant studies. A high resolution whole-field aero-optical aberration and dithering measuring method based on the Background Orient Schlieren (BOS) technique was studied. The systematic structure, sensitivity and resolution of BOS are analyzed in this paper. The aero-optical aberration and dithering of streamwise structures in supersonic mixing layers were quantificationally studied with BOS. The aberration field of spanwise structures revealed the ribbon-like aberration structures, which heavily restrict the optical performance of a mixing layer. The quantifications of aero-optical aberration and dithering are very important in studying aero-optical performance of supersonic mixing layer.

  18. Influence of spherical aberrations on fundamental mode beam quality under different laser resonators

    Institute of Scientific and Technical Information of China (English)

    Xiang Zhen; Hu Miao; Ge Jian-Hong; Zhao Zhi-Gang; Wang Sha; Liu Chong; Chen Jun

    2009-01-01

    Spherical aberrations of the thermal lens of the active media are severe when solid state lasers are strongly pumped.The fundamental mode profile deteriorates due to the aberrations. Self-consistent modes of a resonator with aberrations are calculated by using the Fox-Li diffraction iterative algorithm. Calculation results show that the aberration induced fundamental mode beam quality deterioration depends greatly on the resonator design. The tolerance of a flat-flat resonator to the aberration coefficient is about 30λ in the middle of stability, where λ is the wavelength of laser beam. But for a dynamically stable resonator, 2λ of spherical aberration will create diffraction loss of more than 40%, if inappropriate design criteria are used. A birefringence compensated laser resonator with two Nd:YAG rods is experimentally studied. The experimental data are in quite good agreement with simulation results.

  19. Tunable liquid crystal cylindrical micro-optical array for aberration compensation.

    Science.gov (United States)

    Algorri, J F; Urruchi, V; Bennis, N; Sánchez-Pena, J M; Otón, J M

    2015-06-01

    A tunable aberration compensation device for rectangular micro-optical systems is proposed and demonstrated. This device, which is based in nematic liquid crystal and a micro-electrode structure, forms gradients in the index of refraction as a function of voltage. We have developed a fringe skeletonizing application in order to extract the 3D wavefront from an interference pattern. This software tool obtains the optical aberrations using Chebyshev polynomials. By using phase shifted electrical signals the aberrations can be controlled independently. A complete independent control over the spherical and coma aberration has been demonstrated. Also, an independent control over the astigmatism aberration has been demonstrated in a broad range. This device has promising applications where aberration compensation is required. The independent compensation achieved for some coefficients, such as astigmatism for example, is more than 2.4 waves.

  20. Effects of Turbulent Aberrations on Probability Distribution of Orbital Angular Momentum for Optical Communication

    Institute of Scientific and Technical Information of China (English)

    ZHANG Yi-Xin; CANG Ji

    2009-01-01

    Effects of atmospheric turbulence tilt, defocus, astigmatism and coma aberrations on the orbital angular mo-mentum measurement probability of photons propagating in weak turbulent regime are modeled with Rytov approximation. By considering the resulting wave as a superposition of angular momentum eigenstates, the or-bital angular momentum measurement probabilities of the transmitted digit axe presented. Our results show that the effect of turbulent tilt aberration on the orbital angular momentum measurement probabilities of photons is the maximum among these four kinds of aberrations. As the aberration order increases, the effects of turbulence aberrations on the measurement probabilities of orbital angular momentum generally decrease, whereas the effect of turbulence defoens can be ignored. For tilt aberration, as the difference between the measured orbital angular momentum and the original orbital angular momentum increases, the orbital angular momentum measurement probabifity decreases.

  1. Ray and Wave Aberrations Revisited: A Huygens Construction yields Exact Relations

    CERN Document Server

    Restrepo, John; Ihrke, Ivo

    2015-01-01

    The optical aberrations of a system can be described in terms of the wave aberrations, defined as the departure from the ideal spherical wavefront; or the ray aberrations, which are in turn the deviations from the paraxial ray intersection measured in the image plane. The classical connection between the two descriptions is an approximation, the error of which has, so far, not been quantified analytically. We derive exact analytical equations for computing the wavefront surface, the aberrated ray directions, and the transverse ray aberrations in terms of the wave aberrations (OPD) and the reference sphere. We introduce precise conditions for a function to be an OPD function, show that every such function has an associated wavefront, and study the error arising from the classical approximation. We establish strict conditions for the error to be small. We illustrate our results with numerical simulations. Our results show that large numerical apertures and high-frequency OPD functions yield larger approximation...

  2. Ray and wave aberrations revisited: a Huygens-like construction yields exact relations.

    Science.gov (United States)

    Restrepo, John; Stoerck, Pawel J; Ihrke, Ivo

    2016-02-01

    The aberrations of an optical system can be described in terms of the wave aberrations, defined as the departure from the ideal spherical wavefront; or the ray aberrations, which are in turn the deviations from the paraxial ray intersections measured in the image plane. The classical connection between the two descriptions is an approximation, the error of which has, to our knowledge, so far not been quantified analytically. We derive exact analytical equations for computing the wavefront surface, the aberrated ray directions, and the transverse ray aberrations in terms of the wave aberrations (OPD) and the reference sphere. We introduce precise conditions for a function to be an OPD function, show that every such function has an associated wavefront, and study the error arising from the classical approximation. We establish strict conditions for the error to be small. We illustrate our results with numerical simulations. Our results show that large numerical apertures and OPD functions with strong gradients yield larger approximation errors.

  3. Chromosome aberrations in workers of ignalina nuclear power plant

    Energy Technology Data Exchange (ETDEWEB)

    Griciene, B.; Januskeviciute, I.; Mierauskiene, J.; Slapsyte, G. [Vilnius Univ. (Lithuania)

    2006-07-01

    Full text of publication follows: The Ignalina Nuclear Power Plant (I.N.P.P.) workers and outside workers including visitors constitute the largest occupational group exposed to low doses of ionizing radiation in Lithuania. In 2004, the annual collective dose to these workers (4392 persons) was 6,83 man Sv. The maximum annual individual dose of I.N.P.P. workers was 19,16 mSv, and of outside workers was 29,41 mSv. However, according to calculations performed by the Lithuanian Radiation Protection Centre, the decommissioning of I.N.P.P. (the I.N.P.P. is to be shut down by 2009) will result in collective dose of 35 man Sv. Therefore, a special attention should be given to implementation of radiation protection programme. The importance of cytogenetic studies in the medical surveillance of radiation-exposed persons is generally acknowledged. The aim of the present study was to analyse chromosome aberration frequencies in lymphocytes of I.N.P.P. workers. The blood sampling of 27 male workers was performed in October 2004, after planned outage of I.N.P.P.. It was estimated that outages of I.N.P.P. Units contributed 84% to all annual occupational collective dose. Average cumulative dose of 18 workers was 290,7 mSv (group A), and of 9 workers - 71,7 mSv (group B). The mean annual doses averaged over the three-year-period were 15,2 mSv and 0,76 mSv, respectively. None of the exposed workers had ever exceeded the permissible dose limit. The average age of group A workers was 45,2 years, and group B 48,2 years. A questionnaire form with details on age, occupational history, smoking habit and alcohol intake, medication, history of recent illness was completed for each person at the time of blood collection. 64 non-exposed male donors approximately matched by age were used as controls (group C). Heparinized venous blood samples were taken and cultures were initiated within 24 h according to the standard procedures. At least 500 first cycle metaphases were analysed from each

  4. Hypermethylation and aberrant expression of SRY-box 17 gene in esophageal squamous cell cancer%SRY-box 17基因在食管鳞状细胞癌中异常甲基化及表达的研究

    Institute of Scientific and Technical Information of China (English)

    郭艳丽; 郭炜; 邝钢; 杨植彬; 董稚明

    2012-01-01

    methylation of SRY-box] 7 gene and its mRNA expression in ESCC cell lines TE1 and TE13 as well as ESCC tissues and their adjacent tissues from 109 patients were detected by methylation specific-PCR (MSP) and RT-PCR, respectively. The association of SRY-box17 gene with β-catenin in Wnt signaling pathway was analyzed. Results: The expression of SRY-box 17 mRNA was undetected or at extremely low level in ESCC cell lines TE1 and TE13. The expression level of SRY-box 17 mRNA was obviously increased after treatment with a demethylation agent 5-aza-2'-deoxycytidine (5-Aza-dC). The result of MSP indicated that the SRY-box] 7 gene exerted a hypermethylation status in ESCC cell lines TE1 and TE1 3. The methylation rate of SRY-box 17 gene was 89.0% (97/109) in the ESCC tissues, which was significantly higher than that in the adjacent tissues [53.2% (58/109); P 0.05). Furthermore, the positive rate of SRY-box 17 mRNA expression [28.4% (31 /109)] in the ESCC tissues was significantly lower than that in the adjacent tissues. The hypermethylation status of SRY-box 17 gene was associated with the loss of SRY-box 17 mRNA expression and the ectopic expression of p-catenin (P < 0.05). Conclusion: The hypermethylation of SRY-box 17 gene is a frequent event in ESCC cell lines and the ESCC tissues, and it may play an important role in the downregulation of SRY-box17 mRNA expression and the pathogenesis and development of ESCC through the activation of Wnt/p-catenin signaling pathway. Analysis of methylation status of SRY-box17 gene may have definite value in predicting the prognosis of ESCC.

  5. Hepatic aberrant glycosylation by N-acetylglucosaminyltransferase V accelerates HDL assembly.

    Science.gov (United States)

    Kamada, Yoshihiro; Kida, Sachiho; Hirano, Ken-Ichi; Yamaguchi, Satoshi; Suzuki, Akira; Hashimoto, Chikako; Kimura, Akihiro; Sato, Motoya; Fujii, Hironobu; Sobajima, Tomoaki; Yamamoto, Akiko; Ebisutani, Yusuke; Takamatsu, Shinji; Shinzaki, Shinichiro; Yoshida, Yuichi; Yamada, Makoto; Nagasaka, Hironori; Takehara, Tetsuo; Miyoshi, Eiji

    2016-11-01

    Glycosylation is involved in various pathophysiological conditions. N-Acetylglucosaminyltransferase V (GnT-V), catalyzing β1-6 branching in asparagine-linked oligosaccharides, is one of the most important glycosyltransferases involved in cancer and the immune system. Recent findings indicate that aberrant N-glycan structure can modify lipid metabolism. In this study, we investigated the effects of aberrant glycosylation by GnT-V on high-density lipoprotein cholesterol (HDL) assembly. We used GnT-V transgenic (Tg) mice and GnT-V Hep3B cell (human hepatoma cell line) transfectants. The study also included 96 patients who underwent medical health check-ups. Total serum cholesterol levels, particularly HDL-cholesterol (HDL-C) levels, were significantly increased in Tg vs. wild-type (WT) mice. Hepatic expression of apolipoprotein AI (ApoAI) and ATP-binding cassette subfamily A member 1 (ABCA1), two important factors in HDL assembly, were higher in Tg mice compared with WT mice. ApoAI and ABCA1 were also significantly elevated in GnT-V transfectants compared with mock-transfected cells. Moreover, ApoAI protein in the cultured media of GnT-V transfectants was significantly increased. Finally, we found a strong correlation between serum GnT-V activity and HDL-C concentration in human subjects. Multivariate logistic analyses demonstrated that GnT-V activity was an independent and significant determinant for serum HDL-C levels even adjusted with age and gender differences. Further analyses represented that serum GnT-V activity had strong correlation especially with the large-size HDL particle concentration. These findings indicate that enhanced hepatic GnT-V activity accelerated HDL assembly and could be a novel mechanism for HDL synthesis. Copyright © 2016 the American Physiological Society.

  6. Misalignment Induced Aberrations of JWST: Isolating Low Order Primary Figure Residuals from Misalignment

    Science.gov (United States)

    2010-06-07

    7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Iris AO, Inc. 2680 Bancroft Way Berkeley, CA 04704 8...aberration theory. 15. SUBJECT TERMS Nodal Aberration Theory, James Webb Space Telescope, Misalignment, Segmented , Mirror, Adaptive Optics, Coma...NOT field quadratic K. P. Thompson, “Description of the third-order optical aberrations of near-circular pupil optical systems without symmetry,” J

  7. A method of dynamic chromatic aberration correction in low-voltage scanning electron microscopes.

    Science.gov (United States)

    Khursheed, Anjam

    2005-07-01

    A time-of-flight concept that dynamically corrects for chromatic aberration effects in scanning electron microscopes (SEMs) is presented. The method is predicted to reduce the microscope's chromatic aberration by an order of magnitude. The scheme should significantly improve the spatial resolution of low-voltage scanning electron microscopes (LVSEMs). The dynamic means of correcting for chromatic aberration also allows for the possibility of obtaining high image resolution from electron guns that have relatively large energy spreads.

  8. Fourth-order-dispersion limitations of aberration-free chirped-pulse amplification systems

    Energy Technology Data Exchange (ETDEWEB)

    Kane, S. [Center for Ultrafast Optical Science, University of Michigan, 2200 Bonisteel Boulevard, Room 1006, Institute for Science and Technology Building, Ann Arbor, Michigan 48109-2099 (United States); Squier, J. [Institute for Nonlinear Science, University of California, San Diego, Urey Hall, Mail Code 0339, La Jolla, California 92093-0339 (United States)

    1997-05-01

    To obtain shorter pulses in chirped-pulse-amplification lasers, researchers have recently proposed several designs for aberration-free pulse stretchers. We examine the limitations of two aberration-free chirped-pulse-amplification systems and show that comparable results can be obtained with simpler, conventional pulse stretchers. In addition, we present a simple, quintic-phase-limited, aberration-free chirped-pulse-amplification system that can support ultrashort, high-contrast pulses. {copyright} 1997 Optical Society of America

  9. ANALYSES OF CHROMOSOME ABERRATIONS IN LYMPHOCYTES AND BONE MARROW CELLS INDUCED BY RADIATION OR BENZENE

    Institute of Scientific and Technical Information of China (English)

    张鸿源; 王兰金; 等

    1995-01-01

    The chromosomoe and chromatid type aberration can be induced by benzene and the dicentric and ring ones were not observed in vitro experiment but observed in vivo one.In vitro experiment a good linear reression can be given between benzene concentrations and total aberration cells while power regression for radiation dose.The chromosome aberrations induced by benzene combined with radiation in rabbit blood lymphocytes are higher than in bone marryow cells.

  10. ABERRATIONS MINIMIZATION FOR IMPROVING CHARACTERISTICS OF COMPACT HIGH-APERTURE DISPERSIVE SPECTROMETERS

    Directory of Open Access Journals (Sweden)

    E. S. Voropay

    2010-01-01

    Full Text Available Schemes of high-aperture and compact optical spectrometers and giperspectrometer with minimized aberrations are presented. In the first scheme usage of inclined plane-parallel plate allows decreasing of astigmatism. In the second scheme off-axis aberrations are practically removed due to axial propagation of light. For giperspectrometer narrowing of light propagation angle through the object lens and turning the light out of dispersion plane lead to minimizing of picture aberrations.

  11. Spherical aberration from trajectories in real and hard-edge solenoid fields

    Indian Academy of Sciences (India)

    BISWAS B

    2016-06-01

    For analytical, real and hard-edge solenoidal axial magnetic fields, the low-energy electron trajectories are obtained using the third-order paraxial ray equation. Using the particle trajectories, it is shown that the spherical aberration in the hard-edge model is high and it increases monotonously with hard edginess, although the focal length converges, in agreement with a recentfield and spherical aberration model. The model paved the way for a hard-edge approximation that gives correct focal length and spherical aberration, which is verified here by the trajectory method. In essence, we show that exact hard-edge fields give infinite spherical aberrations.

  12. Influence of ocular longitudinal chromatic aberration on the selection of aspheric intraocular lenses.

    Science.gov (United States)

    Hong, Xin; Choi, Myoung

    2010-12-06

    Polychromatic defocus could affect the optimal residual spherical aberration that could yield the best image quality for patients with intraocular lenses (IOLs). Modulation transfer functions (MTFs) were generated using a model that included polychromatic defocus. The maximum MTF volume occurred at + 0.05 μm of overall ocular spherical aberration. For 3 case studies, the optimal overall ocular spherical aberration was ~0.05 μm more positive with the contribution of polychromatic defocus than without it. Overall, the model indicated that image quality was usually best when IOLs allowed overall ocular spherical aberration that was slightly positive, rather than strongly positive, zero, or negative.

  13. Theoretical estimates of spherical and chromatic aberration in photoemission electron microscopy.

    Science.gov (United States)

    Fitzgerald, J P S; Word, R C; Könenkamp, R

    2016-01-01

    We present theoretical estimates of the mean coefficients of spherical and chromatic aberration for low energy photoemission electron microscopy (PEEM). Using simple analytic models, we find that the aberration coefficients depend primarily on the difference between the photon energy and the photoemission threshold, as expected. However, the shape of the photoelectron spectral distribution impacts the coefficients by up to 30%. These estimates should allow more precise correction of aberration in PEEM in experimental situations where the aberration coefficients and precise electron energy distribution cannot be readily measured.

  14. Measurement of chromatic aberration in STEM and SCEM by coherent convergent beam electron diffraction.

    Science.gov (United States)

    Zheng, C L; Etheridge, J

    2013-02-01

    A simple method is described for the accurate and precise measurement of chromatic aberration under electron-optical conditions pertinent to scanning transmission electron microscopy (STEM) and scanning confocal electron microscopy (SCEM). The method requires only the measurement of distances in a coherent CBED pattern and knowledge of the electron wavelength and the lattice spacing of a calibration specimen. The chromatic aberration of a spherical-aberration corrected 300 kV thermal field emission TEM is measured in STEM and SCEM operating modes and under different condenser lens settings. The effect of the measured chromatic aberrations on the 3 dimensional intensity distribution of the electron probe is also considered.

  15. Higher order aberration comparison between two aspherical intraocular lenses: MC6125AS and Akreos advanced optics

    Institute of Scientific and Technical Information of China (English)

    Mohammad; Taher; Rajabi; Sara; Korouji; Mahgol; Farjadnia; Mohammad; Naderan; Mohammad; Bagher; Rajabi; Bahram; Khosravi; Seyed; Mehdi; Tabatabaie

    2015-01-01

    AIM: To compare higher order aberrations in two aspherical intraocular lenses(IOLs): Akreos advanced optics(AO) and Dr. Schmidt Microcrystalline 6125 aspheric anterior surface(MC6125AS) with each other. METHODS: Forty eyes of 39 patients underwent phacoemulsification and Akreos AO and MC6125 AS were implanted in their eyes in a random manner. Three months post-operatively, higher order aberrations including spherical aberration, coma aberration, and total aberrations were measured and compared.RESULTS: The total aberration was 0.24±0.17 in eyes with Dr. Schmidt and 0.20 ±0.01 in eyes with Akreos AO(P =0.361). The mean of coma aberration was 0.17 ±0.21 and 0.09 ±0.86 in Dr. Schmidt and Akreos lenses,respectively(P =0.825). Total spherical aberration was almost the same in both groups(mean: 0.05, P =0.933).Best corrected visual acuity in Akreos AO(0.10±0.68) and Dr. Schmidt(0.09±0.67) did not differ significantly(P =0.700). CONCLUSION: There is no statistically significant difference in the higher order aberrations between these two aspherical lenses.

  16. Identification of Unbalanced Aberrations in the Genome of Equine Sarcoid Cells Using CGH Technique

    National Research Council Canada - National Science Library

    Monika Bugno-Poniewierska; Beata Staroń; Leszek Potocki; Artur Gurgul; Maciej Wnuk

    2016-01-01

    ...) technique identifying the unbalanced chromosome aberrations was used to analyze the genome of equine sarcoid cells and to diagnose the chromosome rearrangements involving large deletions or amplification...

  17. Sodium channel cleavage is associated with aberrant neuronal activity and cognitive deficits in a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Corbett, Brian F; Leiser, Steven C; Ling, Huai-Ping; Nagy, Reka; Breysse, Nathalie; Zhang, Xiaohong; Hazra, Anupam; Brown, Jon T; Randall, Andrew D; Wood, Andrew; Pangalos, Menelas N; Reinhart, Peter H; Chin, Jeannie

    2013-04-17

    BACE1 is the rate-limiting enzyme that cleaves amyloid precursor protein (APP) to produce the amyloid β peptides that accumulate in Alzheimer's disease (AD). BACE1, which is elevated in AD patients and APP transgenic mice, also cleaves the β2-subunit of voltage-gated sodium channels (Navβ2). Although increased BACE1 levels are associated with Navβ2 cleavage in AD patients, whether Navβ2 cleavage occurs in APP mice had not yet been examined. Such a finding would be of interest because of its potential impact on neuronal activity: previous studies demonstrated that BACE1-overexpressing mice exhibit excessive cleavage of Navβ2 and reduced sodium current density, but the phenotype associated with loss of function mutations in either Navβ-subunits or pore-forming α-subunits is epilepsy. Because mounting evidence suggests that epileptiform activity may play an important role in the development of AD-related cognitive deficits, we examined whether enhanced cleavage of Navβ2 occurs in APP transgenic mice, and whether it is associated with aberrant neuronal activity and cognitive deficits. We found increased levels of BACE1 expression and Navβ2 cleavage fragments in cortical lysates from APP transgenic mice, as well as associated alterations in Nav1.1α expression and localization. Both pyramidal neurons and inhibitory interneurons exhibited evidence of increased Navβ2 cleavage. Moreover, the magnitude of alterations in sodium channel subunits was associated with aberrant EEG activity and impairments in the Morris water maze. Together, these results suggest that altered processing of voltage-gated sodium channels may contribute to aberrant neuronal activity and cognitive deficits in AD.

  18. Aberrant expression of soluble B and T lymphocyte attenuator and its ligand in murine herpetic stromal keratitis%可溶性B、T淋巴细胞衰减因子及其配体在单纯疱疹性角膜基质炎小鼠体内的异常表达

    Institute of Scientific and Technical Information of China (English)

    夏丽坤; 李琰; 张胜男; 曹哲瑶; 陆岩; 杨宏伟

    2011-01-01

    膜上皮层和内皮层也有表达.结论 在HSK小鼠模型中,BTLA及其配体HVEM蛋白在角膜组织中及外周血CD4+T细胞上表达明显增强,共抑制信号BTLA-HVEM参与了CD4+T细胞介导的HSK的免疫病理过程.%Objective To investigate the role of negative costimulatory signals lymphocyte attenuator (BTLA) and herpes virus entry mediator (HVEM) in murine herpetic stromal keratitis (HSK) mediated by CD4+ T cells by testing the expression of BTLA and HVEM in corneal tissues and CD4+ T cells of peripheral blood. Methods Corneas of BALB/c mice were infected with 106 plague forming unit( PFU) of herpes simplex virus type 1 (HSV-1) KOS strain for establishing HSK animal models. About 1 Ml orbital venous sinus blood was collected from left eyes of rats before corneal inoculation and on the 3rd,7th, 10th, 14th,21st day after corneal inoculation with HSV-1. Lymphocytes were segregated and taken fluorescent antibody staining. By flow cytometry,the expression of CD4+ BTLA+ T cells and CD3+ CD4+ HVEM in murine peripheral blood was evaluated. The clinical evaluation of infected eyes was taken under the slit lamp microscope, and the characteristic expression of BTLA and HVEM surface protein on corneas was evaluated by immunohistochemistry. Results Replication of HSV-1 was found in corneal clean and polish liquid at 1 to 5 days after corneal inoculation with HSV-1, which indicated that rats had infected herpes virus. Slit lamp microscope had shown that all rats had infected with acute epithelial keratitis on the 3rd day after corneal inoculation with HSV-1 ,and cured at 1 week after infection;There were changes of corneal interstitial keratitis on the 8th day after inoculation with HSV-1 .showing gray opacity of corneal stroma,went to peak at the 10th day and gradually decreased at the 14th day after corneal inoculation. Flow cytome-try detection had shown that positive rates of CD3+ CD4+ BTLA+ T cells and CD3 + CD4 + HVEM+ T cells were(3.15 ±0.60)% and(9. 84 ± 1.06)% at the day

  19. Chromosomal aberrations related to metastasis of human solid tumors

    Institute of Scientific and Technical Information of China (English)

    Lun-Xiu Qin

    2002-01-01

    The central role of sequential accumulation of genetic alterations during the development of cancer has been firmly established since the pioneering cytogenetic studies successfully defined recurrent chromosome changes in spedfic types of tumor. In the course of carcinogenesis, cells experience several genetic alterations that are associated with the transition from a preneoplastic lesion to an invasive tumor and finally to the metastatic state. Tumor progression is characterized by stepwise accumulation of genetic alterations.So does the dominant metastatic clone. Modern molecular genetic analyses have clarified that genomic changes accumulate during the development and progression of cancers. In comparison with the corresponding primary tumor,additional events of chromosomal aberrations (including gains or allelic losses) are frequently found in metastases, and the incidence of combined chromosomal alterations in the primary tumor, plus the occurrence of additional aberrations inthe distant metastases, correlated significantly with decreased postmetastatic survival. The deletions at 3p, 4p, 6q, 8p, 10q,11p, 11q, 12p, 13q, 16q, 17p, 18q, 21q, and 22q, as well as the over-representations at 1q, 8q, 9q, 14q and 15q, have been found to associate preferentially with the metastatic phenotype of human cancers. Among of them, the deletions on chromosomes 8p, 17p, 11p and 13p seem to be more significant, and more detail fine regions of them, including 8p11, 8p21-12, 8p22, 8p23, 17p13.3, 11p15.5, and 13q12-13 have been suggested harboring metastasis-suppressor genes.During the past decade, several human chromosomes have been functionally tested through the use of microcell-mediated chromosome transfer (MMCT), and metastasis-suppressor activities have been reported on chromosomes 1, 6, 7, 8, 10,11, 12, 16, and 17. However, it is not actually known at what stage of the metastatic cascade these alterations have occurred.There is still controversial with the association

  20. Focal chromosomal copy number aberrations identify CMTM8 and GPR177 as new candidate driver genes in osteosarcoma.

    Directory of Open Access Journals (Sweden)

    Joeri Both

    Full Text Available Osteosarcoma is an aggressive bone tumor that preferentially develops in adolescents. The tumor is characterized by an abundance of genomic aberrations, which hampers the identification of the driver genes involved in osteosarcoma tumorigenesis. Our study aims to identify these genes by the investigation of focal copy number aberrations (CNAs, <3 Mb. For this purpose, we subjected 26 primary tumors of osteosarcoma patients to high-resolution single nucleotide polymorphism array analyses and identified 139 somatic focal CNAs. Of these, 72 had at least one gene located within or overlapping the focal CNA, with a total of 94 genes. For 84 of these genes, the expression status in 31 osteosarcoma samples was determined by expression microarray analysis. This enabled us to identify the genes of which the over- or underexpression was in more than 35% of cases in accordance to their copy number status (gain or loss. These candidate genes were subsequently validated in an independent set and furthermore corroborated as driver genes by verifying their role in other tumor types. We identified CMTM8 as a new candidate tumor suppressor gene and GPR177 as a new candidate oncogene in osteosarcoma. In osteosarcoma, CMTM8 has been shown to suppress EGFR signaling. In other tumor types, CMTM8 is known to suppress the activity of the oncogenic protein c-Met and GPR177 is known as an overexpressed upstream regulator of the Wnt-pathway. Further studies are needed to determine whether these proteins also exert the latter functions in osteosarcoma tumorigenesis.